Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

PubMed

Chang, Wei-Chin; Lin, Chun-Shu; Yang, Cheng-Yu; Lin, Chih-Kung; Chen, Yuan-Wu

2018-04-01

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study.

PubMed

Duruisseaux, Michaël; Besse, Benjamin; Cadranel, Jacques; Pérol, Maurice; Mennecier, Bertrand; Bigay-Game, Laurence; Descourt, Renaud; Dansin, Eric; Audigier-Valette, Clarisse; Moreau, Lionel; Hureaux, José; Veillon, Remi; Otto, Josiane; Madroszyk-Flandin, Anne; Cortot, Alexis; Guichard, François; Boudou-Rouquette, Pascaline; Langlais, Alexandra; Missy, Pascale; Morin, Franck; Moro-Sibilot, Denis

2017-03-28

Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, James X.; Rose, Steven; White, Sarah B.

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Coxmore » proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.« less

Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Percy, E-mail: percylee@mednet.ucla.edu; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California; Eppinga, Wietse

Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships betweenmore » high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.« less

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis.

PubMed

Abrams, Matthew J; Koffer, Paul P; Wazer, David E; Hepel, Jaroslaw T

2017-06-01

Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor-positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrams, Matthew J., E-mail: mabrams@tuftsmedicalcenter.org; Koffer, Paul P.; Wazer, David E.

Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods and Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overallmore » survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor–positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). Conclusions: There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease.« less

Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-12-01

Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.

PubMed

Zhang, Na; Ouyang, Taohui; Kang, Huicong; Long, Wang; Thomas, Benjamin; Zhu, Suiqiang

2015-09-01

To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes.

Primary tumor sidedness is an independent prognostic marker for survival in metastatic colorectal cancer: Results from a large retrospective cohort with mutational analysis.

PubMed

Kamran, Sophia C; Clark, Jeffrey W; Zheng, Hui; Borger, Darrell R; Blaszkowsky, Lawrence S; Allen, Jill N; Kwak, Eunice L; Wo, Jennifer Y; Parikh, Aparna R; Nipp, Ryan D; Murphy, Janet E; Goyal, Lipika; Zhu, Andrew X; Iafrate, A John; Corcoran, Ryan B; Ryan, David P; Hong, Theodore S

2018-05-17

Recent reports demonstrate inferior outcomes associated with primary right-sided vs left-sided colorectal tumors in patients with metastatic colorectal cancer (mCRC). We sought to describe our experience with mCRC patients on whom we have molecular data to determine whether primary tumor sidedness was an independent prognostic marker for overall survival (OS). mCRC patients with documented primary tumor sidedness who received mutational profiling between 2009 and 2014 were identified (n = 367, median follow-up 30.4 months). Mutational profiling for >150 mutations across commonly mutated cancer genes including RAS, PIK3CA, BRAF, and PTEN as well as treatment data, including receipt of a biologic agent, were collected. Univariable/multivariable models were used to analyze relationships between collected data and OS. Among 367 patients, sidedness breakdown was as follows: 234 left (64%), 133 right (36%). 56% were male, with a median age at diagnosis of 57 (range 24-89). A total of 143 patients had RAS mutations. Five-year OS was 41%, median OS was 54 months (range 1-149). Five-year OS for left- vs right-sided tumors was 46% vs 24% (P < .0001). On univariable analysis, among both RAS wildtype and mutant tumors, left-sided tumors continued to have improved OS vs right-sided tumors (HR: 0.49, 95% CI: 0.34-0.69 RAS wildtype; HR: 0.61, 95% CI: 0.40-0.95 RAS mutant). Left-sidedness was an important prognostic factor for OS among RAS wildtype patients despite treatment with or without a biologic agent (P < .05). Left-sidedness remained significant for improved OS on multivariable analysis (P < .0001). Left-sided primary tumor remained most important prognostic factor for OS, even when adjusting for mutational status and receipt of biologic agent. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Adjuvant chemotherapy and overall survival in adult medulloblastoma.

PubMed

Kann, Benjamin H; Lester-Coll, Nataniel H; Park, Henry S; Yeboa, Debra N; Kelly, Jacqueline R; Baehring, Joachim M; Becker, Kevin P; Yu, James B; Bindra, Ranjit S; Roberts, Kenneth B

2017-02-01

Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Predictors of clinical outcome in pediatric oligodendroglioma: meta-analysis of individual patient data and multiple imputation.

PubMed

Wang, Kevin Yuqi; Vankov, Emilian R; Lin, Doris Da May

2018-02-01

OBJECTIVE Oligodendroglioma is a rare primary CNS neoplasm in the pediatric population, and only a limited number of studies in the literature have characterized this entity. Existing studies are limited by small sample sizes and discrepant interstudy findings in identified prognostic factors. In the present study, the authors aimed to increase the statistical power in evaluating for potential prognostic factors of pediatric oligodendrogliomas and sought to reconcile the discrepant findings present among existing studies by performing an individual-patient-data (IPD) meta-analysis and using multiple imputation to address data not directly available from existing studies. METHODS A systematic search was performed, and all studies found to be related to pediatric oligodendrogliomas and associated outcomes were screened for inclusion. Each study was searched for specific demographic and clinical characteristics of each patient and the duration of event-free survival (EFS) and overall survival (OS). Given that certain demographic and clinical information of each patient was not available within all studies, a multivariable imputation via chained equations model was used to impute missing data after the mechanism of missing data was determined. The primary end points of interest were hazard ratios for EFS and OS, as calculated by the Cox proportional-hazards model. Both univariate and multivariate analyses were performed. The multivariate model was adjusted for age, sex, tumor grade, mixed pathologies, extent of resection, chemotherapy, radiation therapy, tumor location, and initial presentation. A p value of less than 0.05 was considered statistically significant. RESULTS A systematic search identified 24 studies with both time-to-event and IPD characteristics available, and a total of 237 individual cases were available for analysis. A median of 19.4% of the values among clinical, demographic, and outcome variables in the compiled 237 cases were missing. Multivariate Cox regression analysis revealed subtotal resection (p = 0.007 [EFS] and 0.043 [OS]), initial presentation of headache (p = 0.006 [EFS] and 0.004 [OS]), mixed pathologies (p = 0.005 [EFS] and 0.049 [OS]), and location of the tumor in the parietal lobe (p = 0.044 [EFS] and 0.030 [OS]) to be significant predictors of tumor progression or recurrence and death. CONCLUSIONS The use of IPD meta-analysis provides a valuable means for increasing statistical power in investigations of disease entities with a very low incidence. Missing data are common in research, and multiple imputation is a flexible and valid approach for addressing this issue, when it is used conscientiously. Undergoing subtotal resection, having a parietal tumor, having tumors with mixed pathologies, and suffering headaches at the time of diagnosis portended a poorer prognosis in pediatric patients with oligodendroglioma.

Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a new orleans sarcoidosis population

PubMed Central

Janot, Adam C.; Huscher, Dörte; Walker, McCall; Grewal, Harmanjot K.; Yu, Mary; Lammi, Matthew R.; Saketkoo, Lesley Ann

2016-01-01

Introduction Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1–40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25–50% of patients with sarcoidosis and can lead to blindness. Methods A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. Results Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58–17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15–26.01), and age (OR=1.114, p=0.002, 95% CI 1.04–1.19) as concomitant risk factors for the development of OS. Conclusion To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis. PMID:26278693

Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy.

PubMed

Yamashita, Shimpei; Kohjimoto, Yasuo; Iguchi, Takashi; Koike, Hiroyuki; Kusumoto, Hiroki; Iba, Akinori; Kikkawa, Kazuro; Kodama, Yoshiki; Matsumura, Nagahide; Hara, Isao

2016-03-22

While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. PSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

Role of adjuvant chemoradiotherapy in T4N0 stage IV head and neck cancer: A National Cancer Database analysis.

PubMed

Kirke, Diana N; Qureshi, Muhammad M; Kamran, Sophia C; Ezzat, Waleed; Jalisi, Scharukh; Salama, Andrew; Everett, Peter C; Truong, Minh Tam

2018-06-01

The purpose of this study was to evaluate the role of postoperative adjuvant radiotherapy (surgery + adjuvant RT) versus adjuvant chemoradiotherapy (surgery + adjuvant CRT) in patients with T4N0M0, stage IV head and neck squamous cell carcinoma (HNSCC). Between 1998 and 2011, 3518 and 885 patients were treated with surgery + adjuvant RT and surgery + adjuvant CRT, respectively. Three-year overall survival (OS) rates were determined and crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed. Median follow-up was 41.8 months with 2193 reported deaths. The 3-year OS was 67.5% for surgery + adjuvant RT and 70.5% for surgery + adjuvant CRT (P = .013). For negative margins, the corresponding 3-year OS was 70.1% and 74.9% (P = .005). For positive margins, the corresponding 3-year OS was 56.0% and 60.6% (P = .079). On multivariate analysis, the beneficial effect for adjuvant CRT over adjuvant RT was not significant (HR 0.90; CI 0.79-1.03; P = .124). In this cohort of patients with T4N0 HNSCC treated with surgery, there was no observed survival benefit of adjuvant CRT over adjuvant RT on multivariate analysis. © 2018 Wiley Periodicals, Inc.

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil; Rana, Vishal; Evans, Douglas B.

2008-03-01

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies weremore » used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.« less

The role of whole brain radiation therapy in the management of melanoma brain metastases

PubMed Central

2014-01-01

Background Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials. PMID:24954062

Osteoporosis in Cervical Spine Surgery.

PubMed

Guzman, Javier Z; Feldman, Zachary M; McAnany, Steven; Hecht, Andrew C; Qureshi, Sheeraz A; Cho, Samuel K

2016-04-01

Retrospective administrative database analysis. To investigate the effect of osteoporosis (OS) on complications and outcomes in patients undergoing cervical spine surgery. OS is the most prevalent degenerative human bone disease, and spine surgeons will inevitably perform procedures on patients with OS. These patients might present a difficult patient cohort because many fixation techniques depend on bone quality and adequate bone healing--both of which are compromised in OS. The nationwide inpatient sample was queried using the Ninth Revision, Clinical Modification procedural codes for cervical spine procedures and diagnosis codes for degenerative conditions of cervical spine from 2002 to 2011. Patients were separated into two cohorts, those patients with OS and those without OS. Demographics, hospital characteristics, and adjusted complication likelihood were analyzed. Multivariate regression analysis was performed to determine odds of revision surgery in patients with OS. Of all patients undergoing degenerative cervical spine surgery, 2% were identified as having OS (32,557 of a sample of 1,602,129 patients). Osteoporotic patients were more likely to undergo posterior cervical spine fusion when compared with those patients without OS (11.3% vs. 5.4%, P < 0.0001). Moreover, circumferential fusion was performed 3 times more frequently in the osteoporotic cohort. Adjusted complications showed increased odds for postoperative hemorrhage (odds ratio = 1.70, 95% confidence interval = 1.46-1.98, P < 0.0001). Patients with OS stayed in the hospital longer (3.5 vs. 2.5 days, P < 0.0001) and had 30% costlier hospitalizations. Multivariate for revision surgery indicated that osteoporotic patients had significantly increased odds of revision surgery (odds ratio = 1.54, P ≤ 0.0001) when referenced to non-osteoporotic patients undergoing cervical spine surgery. Osteoporotic patients were more likely to undergo revision surgery, have longer hospitalizations, and have higher hospitalization costs, than their non-osteoporotic counterparts. 3.

Radical Surgery Improves Survival in Patients with Stage 4 Neuroblastoma.

PubMed

Vollmer, Katherin; Gfroerer, Stefan; Theilen, Till-Martin; Bochennek, Konrad; Klingebiel, Thomas; Rolle, Udo; Fiegel, Henning

2018-06-01

Neuroblastoma (NBL) is the most common extracranial solid tumor in children. Despite a good overall prognosis in NBL patients, the outcome of children with stage 4 disease, even with multimodal intensive therapy, remains poor. The role of extended surgical resection of the primary tumor is in numerous studies controversial. The aim of this study was to retrospectively analyze the impact of radical surgical resection on the overall- and event-free survival of stage 4 NBL patients. We retrospectively analyzed patient charts of 40 patients with stage 4 NBL treated in our institution between January 1990 and May 2012. All clinical and pathological findings of stage 4 NBL patients were included. Extent of surgery was assessed from the operation records and was classified as non-radical (tumor biopsy, partial 50-90% resection) or radical (near-complete >90% resection, complete resection). Overall- (OS) and event-free (EFS) survival was assessed using the Kaplan-Meier analysis and log-rank test. A multivariate Cox regression analysis was used to demonstrate independency. In total, 29/40 patients were operated radically (>90% resection), whereas 11 patients received subtotal resection or biopsy only. OS and EFS were significantly increased in patients with radical operation compared with non-radical resection (p = 0.0003 for OS, p = 0.004 for EFS; log-rank test). A multivariate Cox regression analysis revealed radical operation as a significant and independent parameter for OS and EFS. Our data indicate that radical (over 90% resection) surgery improves OS and EFS in stage 4 NBL patients.

Comparison of Adjuvant Radiation Therapy Alone and Chemotherapy Alone in Surgically Resected Low-Grade Gliomas: Survival Analyses of 2253 Cases from the National Cancer Data Base.

PubMed

Wu, Jing; Neale, Natalie; Huang, Yuqian; Bai, Harrison X; Li, Xuejun; Zhang, Zishu; Karakousis, Giorgos; Huang, Raymond; Zhang, Paul J; Tang, Lei; Xiao, Bo; Yang, Li

2018-04-01

It is becoming increasingly common to incorporate chemotherapy (CT) with radiotherapy (RT) in the treatment of low-grade gliomas (LGGs) after surgical resection. However, there is a lack of literature comparing survival of patients who underwent RT or CT alone. The U.S. National Cancer Data Base was used to identify patients with histologically confirmed, World Health Organization grade 2 gliomas who received either RT alone or CT alone after surgery from 2004 to 2013. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity-score-matched analysis. In total, 2253 patients with World Health Organization grade 2 gliomas were included, of whom 1466 (65.1%) received RT alone and 787 (34.9%) CT alone. The median OS was 98.9 months for the RT alone group and 125.8 months for the CT alone group. On multivariable analysis, CT alone was associated with a significant OS benefit compared with RT alone (hazard ratio [HR], 0.405; 95% confidence interval, 0.277-0.592; P < 0.001). On subgroup analyses, the survival advantage of CT alone over RT alone persisted across all age groups, and for the subtotal resection and biopsy groups, but not in the gross total resection group. In propensity-score-matched analysis, CT alone still showed significantly improved OS compared with RT alone (HR, 0.612; 95% confidence interval, 0.506-0.741; P < 0.001). Our results suggest that CT alone was independently associated with longer OS compared with RT alone in patients with LGGs who underwent surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

PubMed

Wei, Shenhai; Tian, Jintao; Song, Xiaoping; Wu, Bingqun; Liu, Limin

2018-01-01

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Differences in open versus laparoscopic gastric bypass mortality risk using the Obesity Surgery Mortality Risk Score (OS-MRS).

PubMed

Brolin, Robert E; Cody, Ronald P; Marcella, Stephen W

2015-01-01

The Obesity Surgery Mortality Risk Score (OS-MRS) was developed to ascertain preoperative mortality risk of patients having bariatric surgery. To date there has not been a comparison between open and laparoscopic operations using the OS-MRS. To determine whether there are differences in mortality risk between open and laparoscopic Roux-en-Y Gastric Bypass (RYGB) using the OS-MRS. Three university-affiliated hospitals. The 90-day mortality of 2467 consecutive patients who had primary open (1574) or laparoscopic (893) RYGB performed by one surgeon was determined. Univariate and multivariate analysis using 5 OS-MRS risk factors including body mass index (BMI) gender, age>45, presence of hypertension and preoperative deep vein thrombosis (DVT) risk was performed in each group. Each patient was placed in 1 of 3 OS-MRS risk classes based on the number of risks: A (0-1), B (2-3), and C (4-5). Preoperative BMI and DVT risk factors were significantly greater in the open group (OG). Preoperative age was significantly greater in the laparoscopic group (LG). There were significantly more class B and C patients in LG. Ninety-day mortality rates for OG and LG patients were 1.0% and .9%, respectively. Pulmonary embolism was the most common cause of death. All deaths in LG occurred during first 4 years of that experience. Mortality rate by class was A = .1%; B = 1.5%; C = 2.3%. The difference in mortality between class B and C patients was not significant. Univariate analysis in the OG indicated that BMI, age, gender, and DVT risk were significant predictors of mortality. In the LG only BMI and DVT were significant predictors of death. Presence of hypertension was not a significant predictor in either group. Multivariate analysis excluding hypertension found that age was predictive of mortality in the OG while BMI (P = .057) and gender (P = .065) approached statistical significance. Conversely, only BMI was predictive of mortality in the LG with age approaching significance (P = .058). In multivariate analysis DVT risk was not predictive of mortality in either group. There are significant differences in the predictive value of the OS-MRS between open and laparoscopic RYGB. Although laparoscopic patients were significantly older versus the open patients, age was not predictive of mortality after laparoscopic RYGB. BMI trended toward increased mortality risk in both groups. Changes in technique and protocol likely contributed toward no mortality during the last 6 years of our laparoscopic experience. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

PubMed

Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

2017-03-01

The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

PubMed Central

McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

2016-01-01

Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

Outcome and prognostic factors in single brain metastases from small-cell lung cancer.

PubMed

Bernhardt, Denise; Adeberg, Sebastian; Bozorgmehr, Farastuk; Opfermann, Nils; Hörner-Rieber, Juliane; König, Laila; Kappes, Jutta; Thomas, Michael; Unterberg, Andreas; Herth, Felix; Heußel, Claus Peter; Warth, Arne; Debus, Jürgen; Steins, Martin; Rieken, Stefan

2018-02-01

Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.

Men and women show similar survival outcome in stage IV breast cancer.

PubMed

Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib.

PubMed

Diaz-Beveridge, R; Bruixola, G; Lorente, D; Caballero, J; Rodrigo, E; Segura, Á; Akhoundova, D; Giménez, A; Aparicio, J

2018-03-01

Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC). The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Heart Dose Is an Independent Dosimetric Predictor of Overall Survival in Locally Advanced Non-Small Cell Lung Cancer.

PubMed

Speirs, Christina K; DeWees, Todd A; Rehman, Sana; Molotievschi, Alerson; Velez, Maria A; Mullen, Daniel; Fergus, Sandra; Trovo, Marco; Bradley, Jeffrey D; Robinson, Cliff G

2017-02-01

In the randomized trial of standard- versus high-dose chemoradiotherapy for locally advanced (LA) NSCLC (Radiation Therapy Oncology Group 0617), overall survival (OS) was worse in the high-dose arm. Although heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters affecting OS in this patient population, focusing on heart dose. Clinical data were collected on 416 patients with LA NSCLC treated at a single institution, with a subset of 333 available treatment plans recontoured using Radiation Therapy Oncology Group 0617 normal tissue guidelines. Toxicity and dosimetry data were analyzed for 322 patients; multivariate analysis was performed on 251 patients. Dosimetric parameters of radiation to tumor and organs at risk were analyzed with clinical data pertaining to OS, disease-free survival, and toxicity. Patients were treated with radiation therapy to prescribed doses of 50.0 to 84.9 Gy (median 66.0 Gy). Median follow-up was 14.5 months. Median OS was 16.8 months. The 1- and 2-year OS rates were 61.4% and 38.8%, respectively. On multivariate analysis, factors independently associated with worse OS were increasing heart V 50 (volume receiving ≥50 Gy), heart volume, lung V 5 (proportion of the lung structure [excluding the target volume]) receiving at least 5 Gy), bilateral mediastinal lymph node involvement, and lack of concurrent chemotherapy. When stratified by heart V 50 less than 25% versus 25% or greater, the 1-year OS rates were 70.2% versus 46.8% and the 2-year OS rates were 45.9% versus 26.7% (p < 0.0001). Median heart V 50 was significantly higher (20.8% versus 13.9%, p < 0.0001) for patients with cardiac toxicity with a Common Terminology Criteria for Adverse Events grade of 1 or higher. Heart dose is associated with OS and cardiac toxicity for patients with LA NSCLC treated with chemoradiotherapy. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes—A 10-year Experience at a Single Center

PubMed Central

Shady, Waleed; Petre, Elena N.; Gonen, Mithat; Erinjeri, Joseph P.; Brown, Karen T.; Covey, Anne M.; Alago, William; Durack, Jeremy C.; Maybody, Majid; Brody, Lynn A.; Siegelbaum, Robert H.; D’Angelica, Michael I.; Jarnagin, William R.; Solomon, Stephen B.; Kemeny, Nancy E.

2016-01-01

Purpose To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. Materials and Methods This study consisted of a HIPAA-compliant institutional review board–approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material–enhanced CT was used to assess technique effectiveness 4–8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2–4 months. Overall survival (OS) and local tumor progression–free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. Results Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. Conclusion Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS. © RSNA, 2015 PMID:26267832

Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.

PubMed

Papadia, Andrea; Bellati, Filippo; Ditto, Antonino; Bogani, Giorgio; Gasparri, Maria Luisa; Di Donato, Violante; Martinelli, Fabio; Lorusso, Domenica; Benedetti-Panici, Pierluigi; Raspagliesi, Francesco

2015-12-01

Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

Surgical Management of Metastatic Colorectal Cancer: A Single-Centre Experience on Oncological Outcomes of Pulmonary Resection vs Cytoreductive Surgery and HIPEC.

PubMed

Wong, Evelyn Yi Ting; Tan, Grace Hwei Ching; Ng, Deanna Wan Jie; Koh, Tina Puay Theng; Kumar, Mrinal; Teo, Melissa Ching Ching

2017-12-01

Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS). A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed. The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that recurrent lung metastasis after metastasectomy was an independent prognostic factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003-0.622, p = 0.021). There were no independent prognostic factors for OS in CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients. OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.

Gastric cancer, nutritional status, and outcome.

PubMed

Liu, Xuechao; Qiu, Haibo; Kong, Pengfei; Zhou, Zhiwei; Sun, Xiaowei

2017-01-01

We aim to investigate the prognostic value of several nutrition-based indices, including the prognostic nutritional index (PNI), performance status, body mass index, serum albumin, and preoperative body weight loss in patients with gastric cancer (GC). We retrospectively analyzed the records of 1,330 consecutive patients with GC undergoing curative surgery between October 2000 and September 2012. The relationship between nutrition-based indices and overall survival (OS) was examined using Kaplan-Meier analysis and Cox regression model. Following multivariate analysis, the PNI and preoperative body weight loss were the only nutritional-based indices independently associated with OS (hazard ratio [HR]: 1.356, 95% confidence interval [CI]: 1.051-1.748, P =0.019; HR: 1.152, 95% CI: 1.014-1.310, P =0.030, retrospectively). In stage-stratified analysis, multivariate analysis revealed that preoperative body weight loss was identified as an independent prognostic factor only in patients with stage III GC (HR: 1.223, 95% CI: 1.065-1.405, P =0.004), while the prognostic significance of PNI was not significant (all P >0.05). In patients with stage III GC, preoperative body weight loss stratified 5-year OS from 41.1% to 26.5%. When stratified by adjuvant chemotherapy, the prognostic significance of preoperative body weight loss was maintained in patients treated with surgery plus adjuvant chemotherapy and in patients treated with surgery alone ( P <0.001; P =0.003). Preoperative body weight loss is an independent prognostic factor for OS in patients with GC, especially in stage III disease. Preoperative body weight loss appears to be a superior predictor of outcome compared with other established nutrition-based indices.

Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with Cholangiocarcinoma.

PubMed

Saito, Nobuhiro; Shirai, Yoshihiro; Horiuchi, Takashi; Sugano, Hiroshi; Shiba, Hiroaki; Sakamoto, Taro; Uwagawa, Tadashi; Yanaga, Katsuhiko

2018-02-01

The purpose of this study was to evaluate the prognostic index of the preoperative platelet to albumin ratio (PAR) in patients who underwent primary resection for cholangiocarcinoma. A total of 59 patients were divided into two groups: those with PAR ≥72.6×10 3 or <72.6×10 3 according to the area under the receiver operating characteristics curve. PAR was significantly inversely associated with overall (OS) and disease-free (DFS) survival on univariate analysis. PAR showed significance on multivariate analysis for OS (hazard ratio=6.232, 95% confidence interval=1.283-30.279, p=0.023), along with tumor differentiation (p=0.009), nodal involvement (p=0.001), intraoperative blood loss (p=0.001), and serum carcinoembryonic antigen (CEA) (p=0.012). High PAR was also significantly associated poor DFS on multivariate analysis (hazard ratio(HR)=4.422, 95% confidence interval(CI)=1.168-16.732, p=0.029), along with tumor differentiation (p=0.009). PAR is a useful prognostic index for OS and DFS in patients with cholangiocarcinoma after primary resection. By accumulating cases prospectively, this new index may be a reference for use before neoadjuvant chemotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

PubMed

Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

2017-07-01

An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

[Value of Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio for Prognostic Evaluation of Diffuse Large B-cell Lymphoma].

PubMed

Ni, Jing; Wang, Yong-Qing; Zhang, Ying-Ping; Wu, Wei; Zeng, Qing-Shu; Yang, Ming-Zhen; Xia, Rui-Xiang

2016-04-01

To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) for the patients with diffuse large B-cell lymphoma (DLBCL). The clinical data of 57 DLBCL patients admitted in the First Affiliated hospital of Anhui Medical University were analyzed retrospectively. According to ROC curve, the cut-off value for NLR and PLR was deterimined, and the patients were divided into high and low NLR/PLR groups before first chamotherapy. Then the relation of NLR and PLR with overall survival (OS) and progression-free survival (PFS) was analyzed by univariate and multivariate COX regression. The optimal cut-off value for NLR and PLR was 2.915 and 270.27, respectively. NLR at the diagnosis was found to be an independent predictor for OS and PFS by univariate and multivariate analysis, while the PLR was an independent predictor for PFS, but did not affect the OS. NLR and PLR may provide additional prognostic information for DLBCL patients.

Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

PubMed Central

Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

2015-01-01

Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

Difference in Postsurgical Prognostic Factors between Lung Adenocarcinoma and Squamous Cell Carcinoma

PubMed Central

Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

2017-01-01

Purpose: The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma (SQ). Methods: A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors. Results: A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1–3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis. Conclusion: Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study. PMID:28966230

Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd

2015-11-01

Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Coxmore » proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.« less

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PubMed

Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

2016-01-01

The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Body weight changes in patients undergoing chemotherapy for ovarian cancer influence progression-free and overall survival.

PubMed

Mardas, Marcin; Stelmach-Mardas, Marta; Madry, Radosław

2017-03-01

The aim of this study was to evaluate whether body weight changes in patients undergoing chemotherapy for epithelial ovarian cancer (EOC) influence progression-free survival (PFS) and overall survival (OS). An analysis of 190 patients diagnosed with ovarian cancer after first-line chemotherapy was conducted. Changes in body weight were assessed by comparing measurements at baseline to those of the third and sixth cycles of chemotherapy. PFS and OS were calculated with the Kaplan-Meier method and multivariate Cox model. Significant reduction in body weight in advanced EOC was observed with no changes in early EOC. Significant differences in PFS were observed in advanced EOC patients that lost more than 5 % of their body weight (6 months), maintained weight (13 months), or gained more than 5 % of their body weight (15 months). Similarly, significant differences in OS were noted in advanced EOC at the following time points: 24.3, 42.4, and 66.2 months. No effect was reported for early EOC patients. The multivariate Cox analysis showed significant body weight changes from the first to the sixth chemotherapy cycle for PFS (HR = 0.97; 95 % CI 0.95-0.99) and OS (HR = 0.94; 95 % CI 0.91-0.97) as well as from the first to the third chemotherapy cycle for OS (HR = 0.93; 95 % CI 0.88-0.98). Body weight changes can be recognized as a prognostic factor for PFS and OS in advanced EOC patients undergoing chemotherapy. Weight loss is associated with poorer survival while weight gain improved outcomes.

A high proportion of cells carrying trisomy 12 is associated with a worse outcome in patients with chronic lymphocytic leukemia.

PubMed

González-Gascón Y Marín, Isabel; Hernández-Sánchez, María; Rodríguez-Vicente, Ana-Eugenia; Sanzo, Carmen; Aventín, Anna; Puiggros, Anna; Collado, Rosa; Heras, Cecilia; Muñoz, Carolina; Delgado, Julio; Ortega, Margarita; González, María-Teresa; Marugán, Isabel; de la Fuente, Ignacio; Recio, Isabel; Bosch, Francesc; Espinet, Blanca; González, Marcos; Hernández-Rivas, Jesús-María; Hernández, José-Ángel

2016-06-01

The prognosis of chronic lymphocytic leukemia (CLL) patients displaying trisomy 12 (+12) remains unclear. In this study, we analyzed the influence of the proportion of cells with +12, and other clinical and biologic factors, in time to first therapy (TTFT) and overall survival (OS), in 289 patients diagnosed with CLL carrying +12. Median OS was 129 months. One hundred seventy-four patients (60.2%) presented +12 in <60% of cells. TTFT and OS for this subgroup were longer than for the subgroup with +12 in ≥60% of cells, with a median TTFT of 49 months (CI95%, 39-58) vs 30 months (CI95%, 22-38) (P = 0.001); and a median OS of 159 months (CI95%, 119-182), vs 96 months (CI95%, 58-134) (P = 0.015). Other factors associated with a shorter TTFT were: Binet stage, B symptoms, lymphadenopathy, splenomegaly, high lymphocyte count, 11q-, high β2 microglobulin, and high LDH. In the multivariate analysis, clinical stage, +12 in ≥60% of cells, high lymphocyte count, B symptoms, and 11q- in addition, resulted of significance in predicting shorter TTFT. Significant variables for OS were: Binet stage, lymphadenopathy, splenomegaly, high LDH, high β2 microglobulin, 11q-, and CD38. In the multivariate analysis, only Binet stage, 11q-, and high β2microglobulin significantly predicted shorter OS. CLL with +12 entails a heterogeneous group with intermediate prognosis. However, a high proportion of cells carrying +12 separates a subgroup of patients with poor outcome. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Prediction of survival with multi-scale radiomic analysis in glioblastoma patients.

PubMed

Chaddad, Ahmad; Sabri, Siham; Niazi, Tamim; Abdulkarim, Bassam

2018-06-19

We propose a multiscale texture features based on Laplacian-of Gaussian (LoG) filter to predict progression free (PFS) and overall survival (OS) in patients newly diagnosed with glioblastoma (GBM). Experiments use the extracted features derived from 40 patients of GBM with T1-weighted imaging (T1-WI) and Fluid-attenuated inversion recovery (FLAIR) images that were segmented manually into areas of active tumor, necrosis, and edema. Multiscale texture features were extracted locally from each of these areas of interest using a LoG filter and the relation between features to OS and PFS was investigated using univariate (i.e., Spearman's rank correlation coefficient, log-rank test and Kaplan-Meier estimator) and multivariate analyses (i.e., Random Forest classifier). Three and seven features were statistically correlated with PFS and OS, respectively, with absolute correlation values between 0.32 and 0.36 and p < 0.05. Three features derived from active tumor regions only were associated with OS (p < 0.05) with hazard ratios (HR) of 2.9, 3, and 3.24, respectively. Combined features showed an AUC value of 85.37 and 85.54% for predicting the PFS and OS of GBM patients, respectively, using the random forest (RF) classifier. We presented a multiscale texture features to characterize the GBM regions and predict he PFS and OS. The efficiency achievable suggests that this technique can be developed into a GBM MR analysis system suitable for clinical use after a thorough validation involving more patients. Graphical abstract Scheme of the proposed model for characterizing the heterogeneity of GBM regions and predicting the overall survival and progression free survival of GBM patients. (1) Acquisition of pretreatment MRI images; (2) Affine registration of T1-WI image with its corresponding FLAIR images, and GBM subtype (phenotypes) labelling; (3) Extraction of nine texture features from the three texture scales fine, medium, and coarse derived from each of GBM regions; (4) Comparing heterogeneity between GBM regions by ANOVA test; Survival analysis using Univariate (Spearman rank correlation between features and survival (i.e., PFS and OS) based on each of the GBM regions, Kaplan-Meier estimator and log-rank test to predict the PFS and OS of patient groups that grouped based on median of feature), and multivariate (random forest model) for predicting the PFS and OS of patients groups that grouped based on median of PFS and OS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Bhavana V.; Gill, Beant S.; Viswanathan, Akila N.

Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. Results: We identified 3075 patients withmore » a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy.« less

Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

PubMed

Li, Xiaoxia; Yuan, Ying; Ren, Jiliang; Shi, Yiqian; Tao, Xiaofeng

2018-03-26

We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC 10 , ADC 50 , and ADC 90 ); mean ADC values (ADC mean ); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC 10  > 0.958 × 10 -3 mm 2 /s, ADC 50  > 1.089 × 10 -3 mm 2 /s, ADC 90  > 1.152 × 10 -3 mm 2 /s, ADC mean  > 1.047 × 10 -3 mm 2 /s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC 90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement. ADC histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Prognostic implications of adhesion molecule expression in colorectal cancer.

PubMed

Seo, Kyung-Jin; Kim, Maru; Kim, Jeana

2015-01-01

Research on the expression of adhesion molecules, E-cadherin (ECAD), CD24, CD44 and osteopontin (OPN) in colorectal cancer (CRC) has been limited, even though CRC is one of the leading causes of cancer-related deaths. This study was conducted to evaluate the expression of adhesion molecules in CRC and to determine their relationships with clinicopathologic variables, and the prognostic significance. The expression of ECAD, CD24, CD44 and OPN was examined in 174 stage II and III CRC specimens by immunohistochemistry of TMA. Negative ECAD expression was significantly correlated with advanced nodal stage and poor tumor differentiation. Multivariate analysis showed that both negative expression of ECAD and positive expression of CD24 were independent prognostic factors for disease-free survival (DFS) in CRC patients (P<0.001, relative risk [RR] = 5.596, 95% CI = 2.712-11.549; P = 0.038, RR = 3.768, 95% CI = 1.077-13.185, respectively). However, for overall survival (OS), only ECAD negativity showed statistically significant results in multivariate analysis (P<0.001, RR = 4.819, 95% CI = 2.515-9.234). Positive expression of CD24 was associated with poor OS in univariate analysis but was of no prognostic value in multivariate analysis. In conclusion, our study suggests that among these four adhesion molecules, ECAD and CD24 expression can be considered independent prognostic factors. The role of CD44 and OPN may need further evaluation.

Prognostic implications of adhesion molecule expression in colorectal cancer

PubMed Central

Seo, Kyung-Jin; Kim, Maru; Kim, Jeana

2015-01-01

Research on the expression of adhesion molecules, E-cadherin (ECAD), CD24, CD44 and osteopontin (OPN) in colorectal cancer (CRC) has been limited, even though CRC is one of the leading causes of cancer-related deaths. This study was conducted to evaluate the expression of adhesion molecules in CRC and to determine their relationships with clinicopathologic variables, and the prognostic significance. The expression of ECAD, CD24, CD44 and OPN was examined in 174 stage II and III CRC specimens by immunohistochemistry of TMA. Negative ECAD expression was significantly correlated with advanced nodal stage and poor tumor differentiation. Multivariate analysis showed that both negative expression of ECAD and positive expression of CD24 were independent prognostic factors for disease-free survival (DFS) in CRC patients (P<0.001, relative risk [RR] = 5.596, 95% CI = 2.712-11.549; P = 0.038, RR = 3.768, 95% CI = 1.077-13.185, respectively). However, for overall survival (OS), only ECAD negativity showed statistically significant results in multivariate analysis (P<0.001, RR = 4.819, 95% CI = 2.515-9.234). Positive expression of CD24 was associated with poor OS in univariate analysis but was of no prognostic value in multivariate analysis. In conclusion, our study suggests that among these four adhesion molecules, ECAD and CD24 expression can be considered independent prognostic factors. The role of CD44 and OPN may need further evaluation. PMID:26097606

Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children.

PubMed

Kann, Benjamin H; Park, Henry S; Lester-Coll, Nataniel H; Yeboa, Debra N; Benitez, Viviana; Khan, Atif J; Bindra, Ranjit S; Marks, Asher M; Roberts, Kenneth B

2016-12-01

Postoperative radiotherapy to the craniospinal axis is standard-of-care for pediatric medulloblastoma but is associated with long-term morbidity, particularly in young children. With the advent of modern adjuvant chemotherapy strategies, postoperative radiotherapy deferral has gained acceptance in children younger than 3 years, although it remains controversial in older children. To analyze recent postoperative radiotherapy national treatment patterns and implications for overall survival in patients with medulloblastoma ages 3 to 8 years. Using the National Cancer Data Base, patients ages 3 to 8 years diagnosed as having histologically confirmed medulloblastoma in 2004 to 2012, without distant metastases, who underwent surgery and adjuvant chemotherapy with or without postoperative radiotherapy at facilities nationwide accredited by the Commission on Cancer were identified. Patients were designated as having "postoperative radiotherapy upfront" if they received radiotherapy within 90 days of surgery or "postoperative radiotherapy deferred" otherwise. Factors associated with postoperative radiotherapy deferral were identified using multivariable logistic regression. Overall survival (OS) was compared using Kaplan-Meier analysis with log-rank tests and multivariable Cox regression. Statistical tests were 2-sided. Postoperative radiotherapy utilization and overall survival. Among 816 patients, 123 (15.1%) had postoperative radiotherapy deferred, and 693 (84.9%) had postoperative radiotherapy upfront; 36.8% of 3-year-olds and 4.1% of 8-year-olds had postoperative radiotherapy deferred (P < .001). On multivariable logistic regression, variables associated with postoperative radiotherapy deferral were age (odds ratio [OR], 0.57 per year; 95% CI, 0.49-0.67 per year) and year of diagnosis (OR, 1.18 per year; 95% CI, 1.08-1.29 per year). On survival analysis, with median follow-up of 4.8 years, OS was improved for those receiving postoperative radiotherapy upfront vs postoperative radiotherapy deferred (5-year OS: 82.0% vs 63.4%; P < .001). On multivariable analysis, variables associated with poorer OS were postoperative radiotherapy deferral (hazards ratio [HR], 1.95; 95% CI, 1.15-3.31); stage M1-3 disease (HR, 1.86; 95% CI, 1.10-3.16), and low facility volume (HR, 1.75; 95% CI, 1.04-2.94). Our national database analysis reveals a higher-than-expected and increasing rate of postoperative radiotherapy deferral in children with medulloblastoma ages 3 to 8 years. The analysis suggests that postoperative radiotherapy deferral is associated with worse survival in this age group, even in the modern era of chemotherapy.

The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas.

PubMed

Patel, Mausam; Hans, Harliv S; Pan, Kelsey; Khan, Humza; Donath, Elie; Caldera, Humberto

2018-04-18

Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P<0.05). On multivariable analysis; radiation improved OS and DSS (adjusted hazard ratio [aHR], 0.592 and 0.589, respectively), pancreatectomy improved OS and DSS (aHR, 0.360 and 0.355, respectively), and combination therapy improved OS and DSS (aHR, 0.295 and 0.286, respectively). Age, site, and stage were also independent predictors of OS and DSS. Subgroup analysis demonstrated treatment to be an independent predictor of OS and DSS in localized/regional disease, in distant disease, and in patients diagnosed between 2000 and 2013. Age, site, stage, and treatment independently predict OS and DSS in pancreatic SRCC.

Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

PubMed

Sher, David J; Posner, Marshall R; Tishler, Roy B; Sarlis, Nicholas J; Haddad, Robert I; Holupka, Edward J; Devlin, Phillip M

2011-12-01

To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. Copyright © 2011 Elsevier Inc. All rights reserved.

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sher, David J., E-mail: dsher@partners.org; Posner, Marshall R.; Tishler, Roy B.

2011-12-01

Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8more » weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.« less

The prognostic significance of nonsentinel lymph node metastasis in melanoma.

PubMed

Brown, Russell E; Ross, Merrick I; Edwards, Michael J; Noyes, R Dirk; Reintgen, Douglas S; Hagendoorn, Lee J; Stromberg, Arnold J; Martin, Robert C G; McMasters, Kelly M; Scoggins, Charles R

2010-12-01

We hypothesized that metastasis beyond the sentinel lymph nodes (SLN) to the nonsentinel nodes (NSN) is an important predictor of survival. Analysis was performed of a prospective multi-institutional study that included patients with melanoma ≥ 1.0 mm in Breslow thickness. All patients underwent SLN biopsy; completion lymphadenectomy was performed for all SLN metastases. Disease-free survival (DFS) and overall survival (OS) were computed by Kaplan-Meier analysis; univariate and multivariate analyses were performed to identify factors associated with differences in survival among groups. A total of 2335 patients were analyzed over a median follow-up of 68 months. We compared 3 groups: SLN negative (n = 1988), SLN-only positive (n = 296), and both SLN and NSN positive (n = 51). The 5-year DFS rates were 85.5, 64.8, and 42.6% for groups 1, 2, and 3, respectively (P < 0.001). The 5-year OS rates were 85.5, 64.9, and 49.4%, respectively (P < 0.001). On univariate analysis, predictors of decreased OS included: SLN metastasis, NSN metastasis, increased total number of positive LN, increased ratio of positive LN to total LN, increased age, male gender, increased Breslow thickness, presence of ulceration, Clark level ≥ IV, and axial primary site (in all cases, P < 0.01). When the total number of positive LN and NSN status were evaluated using multivariate analysis, NSN status remained statistically significant (P < 0.01), while the total number of positive LN and LN ratio did not. NSN melanoma metastasis is an independent prognostic factor for DFS and OS, which is distinct from the number of positive lymph nodes or the lymph node ratio.

A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

PubMed

Rades, Dirk; Janssen, Stefan; Dziggel, Liesa; Blanck, Oliver; Bajrovic, Amira; Veninga, Theo; Schild, Steven E

2017-01-06

This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

LKB1/STK11 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value.

PubMed

Facchinetti, Francesco; Bluthgen, Maria Virginia; Tergemina-Clain, Gabrielle; Faivre, Laura; Pignon, Jean-Pierre; Planchard, David; Remon, Jordi; Soria, Jean-Charles; Lacroix, Ludovic; Besse, Benjamin

2017-10-01

LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet. This retrospective analysis included consecutive NSCLC patients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features. Kaplan-Meier and Cox models were used for survival curves and multivariate analyses, respectively. Among the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and 25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were observed between STK11 status and clinico-pathological variables. We detected a significant correlation between STK11 and KRAS status (p=0.008); among the 25 STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild-type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085). STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non-significant results were observed for progression-free survival. The co-occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect in OS (p=0.12). In our cohort enriched for advanced NSCLC patients who received platinum-based chemotherapy, STK11 mutations were not specifically associated with clinico-pathological features and they did not impact upon survival. We confirm the positive correlation between STK11 and KRAS mutations. The co-occurrence of KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

PubMed

Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

2017-04-01

Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Marital status and survival in patients with renal cell carcinoma.

PubMed

Li, Yan; Zhu, Ming-Xi; Qi, Si-Hua

2018-04-01

Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients.We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS).We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370-1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144-1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS.In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS.

Marital status and survival in patients with renal cell carcinoma

PubMed Central

Li, Yan; Zhu, Ming-xi; Qi, Si-hua

2018-01-01

Abstract Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients. We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan–Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS). We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370–1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144–1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS. In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS. PMID:29668592

The prognostic impact of tumor volume on stage I non-small cell lung cancer.

PubMed

Su, Xiao-Dong; Xie, Hao-Jun; Liu, Qian-Wen; Mo, Yun-Xian; Long, Hao; Rong, Tie-Hua

2017-02-01

The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection. We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program. The optimal cutoff values of TV were determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify risk factors for DFS and OS. By using 3.046cm 3 and 8.078cm 3 as two optimal cutoff values of TV, the patients were separated into three groups. The 5-year DFS and OS for patients with TV≤3.046cm 3 , 3.046-8.078cm 3 , and>8.078cm 3 were 88.0%, 73.6%, and 62.1%, respectively (P<0.001), and 91.4%, 84.5%, and 73.3%, respectively (p<0.001). Multivariate analysis showed that age and TV were independent factors associated with DFS. Sex, age, histology, visceral pleural invasion, and TV were independent factors associated with OS. Stage Ia patients might be separated into three groups on the basis of TV with significantly different DFS and OS. Patients with tumor diameter≤2cm and 2-3cm were also stratified into two groups with significantly different DFS and OS on the basis of TV, respectively. TV is an independent risk factor for DFS and OS for stage I NSCLC after complete resection. TV might provide additional prognostic information over tumor diameter in patients with stage I NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study.

PubMed

Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

2017-01-01

Male breast cancer (MaBC) is an understudied disease; information about locoregional treatment and outcomes in patients with early stage is unknown. We aimed to analyse patient characteristics, locoregional treatment and overall survival (OS) of T1a,b,cN0M0 male breast cancer. We evaluated men with T1a,b,cN0M0 breast cancer reported to Surveillance, Epidemiology, and End Results program from 1988 to 2012. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. We included 1263 patients. Median age was 66 years (range 27-103). Median follow-up was 62 months (range 1-294). OS at 5 and 10 years were 85.1% and 66.5%, respectively. Distribution according to tumour sub-stage was: T1a 6.5%, T1b 20.7% and T1c 72.8%. Mastectomy was performed in >74% of patients of each tumour size group and overall 44.1% had >5 lymph nodes examined (LNE). Univariate analysis showed that patients with T1c, no surgery and 0 LNE had worse prognosis. In multivariate analysis, older age (hazard ratio [HR] 11.09), grade 3/4 tumours (HR 1.7), no surgery (HR 3.3), 0 LNE (HR 5.1) and unmarried patients (HR 1.7) had significantly shorter OS. There were no differences in OS between breast conservation versus mastectomy and 1-5 LNE versus > 5 LNE. Men with early breast cancer have a favourable OS. However, older age, higher grade, no breast surgery, no LNE and unmarried status emerged as poor prognostic characteristics. Efforts to decrease the high rates of mastectomy and extensive LNE should be taken given similar OS observed with breast conservation and 1-5 LNE, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of the Charlson comorbidity index and hypertension with survival in men with metastatic castration-resistant prostate cancer.

PubMed

Goyal, Jatinder; Pond, Gregory R; Galsky, Matthew D; Hendricks, Ryan; Small, Alexander; Tsao, Che-Kai; Sonpavde, Guru

2014-01-01

The independent prognostic effect of comorbidities on outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) is unclear. We sought to determine whether the Charlson comorbidity index (CCI) and hypertension (HTN) are associated with overall survival (OS) independent of known clinical prognostic factors in mCRPC. A retrospective analysis was conducted on 221 patients with mCRPC treated with docetaxel plus prednisone combined with AT-101 (bcl-2 antagonist) or placebo on a prospective randomized phase II trial. The Cox regression analysis was performed to identify whether the CCI or HTN or both (by medical history) independently predicted OS after adjusting for baseline variables known to be associated with OS. The Wilcoxon rank sum test and the Fisher exact test were used to compare data by comorbidity groups (CCI as a continuous variable, CCI = 6 vs. CCI ≥ 7 and HTN vs. no HTN). The CCI was 6 in 116 patients (52.7%), 7 in 70 (31.8%), 8 in 23 (10.5%), 9 in 4 (1.8%), and 10 in 7 patients (3.2%). HTN was present in 107 (48.6%) patients. Patients with CCI of ≥ 7 were older and exhibited worse performance status and anemia than patients with CCI of 6 (P<0.05). The CCI was not independently predictive of OS on univariable and multivariable analyses. HTN alone or in combination with the CCI was borderline significantly associated with OS (P ~ 0.09) on both univariable and multivariable analyses. The CCI did not predict OS independent of known prognostic factors in mCRPC. Age, performance status, and anemia may adequately capture comorbidities in the context of mCRPC, given their association with higher CCI. Further prospective study of comorbidities in a larger data set may be warranted. The study of HTN in a larger data set may also be warranted given its borderline-independent association with OS. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeLaney, Thomas F.; Kepka, Lucyna; Goldberg, Saveli I.

Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%,more » respectively. LC was highest with extremity lesions (p < 0.01), radiation dose >64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving >64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if {<=}64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (>50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p < 0.01 and dose (>64 vs. {<=}64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. Conclusion: Local control is achieved in most PM STS patients undergoing RT. Doses >64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure.« less

Can the new RCP R0/R1 classification predict the clinical outcome in ductal adenocarcinoma of the pancreatic head?

PubMed

Janot, M S; Kersting, S; Belyaev, O; Matuschek, A; Chromik, A M; Suelberg, D; Uhl, W; Tannapfel, A; Bergmann, U

2012-08-01

According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1 mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. Following the UICC criteria, a positive RM was detected in 8 %. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26 % resulting in no significant impact on OS in univariate analysis. Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.

The complexity of interpreting genomic data in patients with acute myeloid leukemia

PubMed Central

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-01-01

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML. PMID:27983727

The complexity of interpreting genomic data in patients with acute myeloid leukemia.

PubMed

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-12-16

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML.

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

PubMed

Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

2016-07-15

To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

Significant Prognostic Factors for Completely Resected pN2 Non-small Cell Lung Cancer without Neoadjuvant Therapy

PubMed Central

Nakao, Masayuki; Mun, Mingyon; Nakagawa, Ken; Nishio, Makoto; Ishikawa, Yuichi; Okumura, Sakae

2015-01-01

Purpose: To identify prognostic factors for pathologic N2 (pN2) non-small cell lung cancer (NSCLC) treated by surgical resection. Methods: Between 1990 and 2009, 287 patients with pN2 NSCLC underwent curative resection at the Cancer Institute Hospital without preoperative treatment. Results: The 5-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) rates were 46%, 55% and 24%, respectively. The median follow-up time was 80 months. Multivariate analysis identified four independent predictors for poor OS: multiple-zone mediastinal lymph node metastasis (hazard ratio [HR], 1.616; p = 0.003); ipsilateral intrapulmonary metastasis (HR, 1.042; p = 0.002); tumor size >30 mm (HR, 1.013; p = 0.002); and clinical stage N1 or N2 (HR, 1.051; p = 0.030). Multivariate analysis identified three independent predictors for poor RFS: multiple-zone mediastinal lymph node metastasis (HR, 1.457; p = 0.011); ipsilateral intrapulmonary metastasis (HR, 1.040; p = 0.002); and tumor size >30 mm (HR, 1.008; p = 0.032). Conclusion: Multiple-zone mediastinal lymph node metastasis, ipsilateral intrapulmonary metastasis, and tumor size >30 mm were common independent prognostic factors of OS, CSS, and RFS in pN2 NSCLC. PMID:25740454

Hypofractionated Whole-Brain Radiotherapy for Multiple Brain Metastases From Transitional Cell Carcinoma of the Bladder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk, E-mail: Rades.Dirk@gmx.ne; Department of Radiation Oncology, University of Hamburg; Meyners, Thekla

2010-10-01

Purpose: Brain metastases in bladder cancer patients are extremely rare. Most patients with multiple lesions receive longer-course whole-brain radiotherapy (WBRT) with 10 x 3 Gy/2 weeks or 20 x 2 Gy/4 weeks. Because its radiosensitivity is relatively low, metastases from bladder cancer may be treated better with hypofractionated radiotherapy. This study compared short-course hypofractionated WBRT (5 x 4 Gy/1 week) to longer-course WBRT. Methods and Materials: Data for 33 patients receiving WBRT alone for multiple brain metastases from transitional cell bladder carcinoma were retrospectively analyzed. Short-course WBRT with 5 x 4 Gy (n = 12 patients) was compared to longer-coursemore » WBRT with 10 x 3 Gy/20 x 2 Gy (n = 21 patients) for overall survival (OS) and local (intracerebral) control (LC). Five additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, and extracranial metastases. The Bonferroni correction for multiple tests was used to adjust the p values derived from the multivariate analysis. p values of <0.025 were considered significant. Results: At 6 months, OS was 42% after 5 x 4 Gy and 24% after 10 x 3/20 x 2 Gy (p = 0.31). On univariate analysis, improved OS was associated with less than four brain metastases (p = 0.021) and almost associated with a lack of extracranial metastases (p = 0.057). On multivariate analysis, both factors were not significant. At 6 months, LC was 83% after 5 x 4 Gy and 27% after 10 x 3/20 x 2 Gy (p = 0.035). Improved LC was almost associated with a KPS of {>=}70 (p = 0.051). On multivariate analysis, WBRT regimen was almost significant (p = 0.036). KPS showed a trend (p = 0.07). Conclusions: Short-course WBRT with 5 x 4 Gy should be seriously considered for most patients with multiple brain metastases from bladder cancer, as it resulted in improved LC.« less

Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients.

PubMed

Yue, Yong; Osipov, Arsen; Fraass, Benedick; Sandler, Howard; Zhang, Xiao; Nissen, Nicholas; Hendifar, Andrew; Tuli, Richard

2017-02-01

To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Twenty-six PA patients treated with RT from 2011-2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Median age was 69 y (range, 46-86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation (<15%). Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response-driven adaptive RT.

Classification and regression tree (CART) analysis of endometrial carcinoma: Seeing the forest for the trees.

PubMed

Barlin, Joyce N; Zhou, Qin; St Clair, Caryn M; Iasonos, Alexia; Soslow, Robert A; Alektiar, Kaled M; Hensley, Martee L; Leitao, Mario M; Barakat, Richard R; Abu-Rustum, Nadeem R

2013-09-01

The objectives of the study are to evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS. All patients diagnosed with endometrial cancer from 1/1993-12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy. The cohort included 1920 patients, with a median age of 62 years. The median number of LNs removed was 16 (range, 1-99). The removal of PALNs was not associated with OS (P=0.450). Using the CART hierarchically, stage I vs. stages II-IV and grades 1-2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS. This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation of the ICON-S staging for HPV-associated oropharyngeal carcinoma using a pre-defined treatment policy.

PubMed

Porceddu, Sandro V; Milne, Rob; Brown, Elizabeth; Bernard, Anne; Rahbari, Reza; Cartmill, Bena; Foote, Matthew; McGrath, Margaret; Coward, Jermaine; Panizza, Benedict

2017-03-01

To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV+OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6-100%), Stage III 93.8% (95% CI; 85.9-100%), Stage IVa 86.4% (95% CI; 81.6-91.5%) and Stage IVb 62.3% (95% CI; 46.8-82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p=0.98, HR=0.97, 95% CI; 0.11-8.64), IVa (p=0.67, HR=1.56, 95% CI; 0.2-11.94) and IVb (p=0.11, HR=5.54, 95% CI; 0.69-44.52), respectively. The 5-year OS with ICON-S staging were Stage I 93.6% (95% CI; 89.4-98.0%), Stage II 81.9% (95% CI; 73.7-91.1%) and Stage III 69.1% (95%; 57.9-82.6%). There was a consistent decrease of OS with increasing stage. On multivariate Cox regression analysis, when compared to Stage I, OS was significantly lower for stage II (p=0.007, HR=2.84, 95% CI; 1.33-6.05) and stage III (p<0.001, HR=3.78, 95% CI; 1.81-7.92), respectively. The ICON-S staging provides better OS stratification for HPV+OPC following RT compared with the 7th Ed TNM staging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.

PubMed

Balermpas, P; Michel, Y; Wagenblast, J; Seitz, O; Weiss, C; Rödel, F; Rödel, C; Fokas, E

2014-01-21

We aimed to investigate the prognostic value of tumour-infiltrating lymphocytes' (TILs) expression in pretreatment specimens from patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT). The prevalence of CD3+, CD8+, CD4+ and FOXP3+ TILs was assessed using immunohistochemistry in tumour tissue obtained from 101 patients before CRT and was correlated with clinicopathological characteristics as well as local failure-free- (LFFS), distant metastases free- (DMFS), progression-free (PFS) and overall survival (OS). Survival curves were measured using the Kaplan-Meier method, and differences in survival between the groups were estimated using the log-rank test. Prognostic effects of TIL subset density were determined using the Cox regression analysis. With a mean follow-up of 25 months (range, 2.3-63 months), OS at 2 years was 57.4% for the entire cohort. Patients with high immunohistochemical CD3 and CD8 expression had significantly increased OS (P=0.024 and P=0.028), PFS (P=0.044 and P=0.047) and DMFS (P=0.021 and P=0.026) but not LFFS (P=0.90 and P=0.104) in multivariate analysis that included predictive clinicopathologic factors, such as age, sex, T-stage, N-stage, tumour grading and localisation. Neither CD4 nor FOXP3 expression showed significance for the clinical outcome. The lower N-stage was associated with improved OS in the multivariate analysis (P=0.049). The positive correlation between a high number of infiltrating CD3+ and CD8+ cells and clinical outcome indicates that TILs may have a beneficial role in HNSCC patients and may serve as a biomarker to identify patients likely to benefit from definitive CRT.

Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk, E-mail: Rades.Dirk@gmx.ne; Heisterkamp, Christine; Huttenlocher, Stefan

2010-06-01

Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) controlmore » (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.« less

Prognostic Significance of the Number of Positive Lymph Nodes in Women With T1-2N1 Breast Cancer Treated With Mastectomy: Should Patients With 1, 2, and 3 Positive Lymph Nodes Be Grouped Together?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai Kubicky, Charlotte, E-mail: charlottedai@gmail.com; Mongoue-Tchokote, Solange

2013-04-01

Purpose: To determine whether patients with 1, 2, or 3 positive lymph nodes (LNs) have similar survival outcomes. Methods and Materials: We analyzed the Surveillance, Epidemiology, and End Results registry of breast cancer patients diagnosed between 1990 and 2003. We identified 10,415 women with T1-2N1M0 breast cancer who were treated with mastectomy with no adjuvant radiation, with at least 10 LNs examined and 6 months of follow-up. The Kaplan-Meier method and log–rank test were used for survival analysis. Multivariate analysis was performed using the Cox proportional hazard model. Results: Median follow-up was 92 months. Ten-year overall survival (OS) and cause-specificmore » survival (CSS) were progressively worse with increasing number of positive LNs. Survival rates were 70%, 64%, and 60% (OS), and 82%, 76%, and 72% (CSS) for 1, 2, and 3 positive LNs, respectively. Pairwise log–rank test P values were <.001 (1 vs 2 positive LNs), <.001 (1 vs 3 positive LNs), and .002 (2 vs 3 positive LNs). Multivariate analysis showed that number of positive LNs was a significant predictor of OS and CSS. Hazard ratios increased with the number of positive LNs. In addition, age, primary tumor size, grade, estrogen receptor and progesterone receptor status, race, and year of diagnosis were significant prognostic factors. Conclusions: Our study suggests that patients with 1, 2, and 3 positive LNs have distinct survival outcomes, with increasing number of positive LNs associated with worse OS and CSS. The conventional grouping of 1-3 positive LNs needs to be reconsidered.« less

Survival of Subcutaneous Panniculitis-Like T-Cell Lymphoma and Peripheral T-Cell Lymphoma Not Otherwise Specified: A Propensity-Matched Analysis of the Surveillance, Epidemiology, and End Results Database.

PubMed

Bhatt, Vijaya Raj; Giri, Smith; Verma, Vivek; Manandhar, Samyak; Pathak, Ranjan; Bociek, R Gregory; Vose, Julie M; Armitage, James O

2016-07-01

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare entity with no previous population-based study. We used the Surveillance, Epidemiology, and End Results 18 database to identify adult patients with SPTCL and peripheral T-cell lymphoma not otherwise specified (PTCL NOS) diagnosed between 1973 and 2011. The actuarial survival of SPTCL was compared with a propensity-matched cohort of PTCL NOS. Multivariate analysis was conducted using weighted Cox proportional hazard regression model. Patients with SPTCL (n = 118), compared with PTCL NOS (n = 3296), were more likely to be younger (median age of 47 vs. 62 years; P < .01), women (67% vs. 40%, P < .01), and diagnosed with stage I/II disease (46% vs. 36%; P = .01). The 5-year actuarial, relative, and cause-specific survival for SPTCL was 40%, 57%, and 64%, respectively. After propensity-matching, the 5-year overall survival (OS) of SPTCL was better than that of PTCL NOS (57% vs. 40%; P < .01). In a multivariate analysis, mortality was significantly lower among SPTCL versus PTCL NOS (hazard ratio, 0.54; 95% confidence interval, 0.39-0.75; P < .01). Among patients with SPTCL, advanced age (P < .01) and diagnosis before the year 2008 (P = .02) were predictors of worse OS. Our study provides characteristics and OS of a large cohort of SPTCL. Compared with PTCL NOS, SPTCL patients were more likely to be younger, female, and diagnosed at an early stage. The OS of SPTCL was better than PTCL NOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Value of Different Comorbidity Indices for Predicting Outcome in Patients with Acute Myeloid Leukemia.

PubMed

Wass, Maxi; Hitz, Friederike; Schaffrath, Judith; Müller-Tidow, Carsten; Müller, Lutz P

2016-01-01

Age is a dominant predictor of outcome in acute myeloid leukemia (AML). However, it is not clear to which extent comorbidities contribute to this effect. The objective of this study was to determine the impact of pretreatment comorbidities on survival of AML patients. In a single-center retrospective study 194 adult AML patients were included. The Hematopoietic cell transplantation comorbidity index (HCT-CI), the Adult Comorbidity Evaluation-27 (ACE-27) score and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) as well as data on demographics, cytogenetics, treatment and outcome were evaluated at the time of initial diagnosis by univariate and multivariate analysis. The study included 102 male and 92 female (median age 60.9 years) of which 173 (89.2%) received intensive chemotherapy. Median overall survival (OS) was 17 months. In univariate analysis, cardiovascular disease (26 vs 12 months, p = .005), severe hepatic disease (19 vs 4 months, p = .013) and renal impairment (17 vs 7 months, p = .016) was associated with inferior OS. For each index, the highest comorbidity burden was associated with reduced OS. However, in multivariate analysis only the ACE-27 score was associated with outcome. Besides ECOG ≥ 2 and poor cytogenetics only the ACE-27 score but not higher age was associated with OS in the group of patients receiving intensive therapy. Adjusted hazard ratios were 3.1, 3.5 and 4.0 for mild, moderate and severe ACE-27-assessed comorbidities, respectively (p = .012). Our study confirms that comorbidities significantly impact survival of AML patients and a pretreatment assessment of comorbidities may help to identify patients with poor outcome.

Value of Different Comorbidity Indices for Predicting Outcome in Patients with Acute Myeloid Leukemia

PubMed Central

Wass, Maxi; Hitz, Friederike; Schaffrath, Judith; Müller-Tidow, Carsten; Müller, Lutz P.

2016-01-01

Age is a dominant predictor of outcome in acute myeloid leukemia (AML). However, it is not clear to which extent comorbidities contribute to this effect. The objective of this study was to determine the impact of pretreatment comorbidities on survival of AML patients. In a single-center retrospective study 194 adult AML patients were included. The Hematopoietic cell transplantation comorbidity index (HCT-CI), the Adult Comorbidity Evaluation-27 (ACE-27) score and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) as well as data on demographics, cytogenetics, treatment and outcome were evaluated at the time of initial diagnosis by univariate and multivariate analysis. The study included 102 male and 92 female (median age 60.9 years) of which 173 (89.2%) received intensive chemotherapy. Median overall survival (OS) was 17 months. In univariate analysis, cardiovascular disease (26 vs 12 months, p = .005), severe hepatic disease (19 vs 4 months, p = .013) and renal impairment (17 vs 7 months, p = .016) was associated with inferior OS. For each index, the highest comorbidity burden was associated with reduced OS. However, in multivariate analysis only the ACE-27 score was associated with outcome. Besides ECOG ≥ 2 and poor cytogenetics only the ACE-27 score but not higher age was associated with OS in the group of patients receiving intensive therapy. Adjusted hazard ratios were 3.1, 3.5 and 4.0 for mild, moderate and severe ACE-27-assessed comorbidities, respectively (p = .012). Our study confirms that comorbidities significantly impact survival of AML patients and a pretreatment assessment of comorbidities may help to identify patients with poor outcome. PMID:27732646

Procarbazine, CCNU, vincristine combination in the treatment of brain tumors.

PubMed

Güllü, I H; Celik, I; Tekuzman, G; Altunbaş, M; Güler, N; Barişta, I; Alkiş, N; Yalçin, S; Kars, A; Baltali, E; Kansu, E; Firat, D

1996-01-01

Forty patients with primary malignant brain tumor were treated by combination chemotherapy after prior treatment with surgery and radiotherapy. The chemotherapy schedule consisted of PCV: procarbazine per os, 100 mg/m2, during 14 consecutive days; CCNU, per os, 80 mg/m2 on day 1 and vincristine, intravenously, 1.4 mg/m2 on days 1 and 14. This protocol was planned to be repeated every 45 days for 6 courses. Median 5 courses (range, 2-6) of chemotherapy was administered to patients. The median relapse free (RFS) and overall survival (OS) rates were found to be 28 and 79+ months, respectively. According to univariate analysis, performance status (PS) of patients was an important prognostic factor on RFS and OS where extent of surgery was an additional significant determinant of OS. Multivariate analysis of pretreatment factors revealed the influence of sex, type of histopathology and PS on RFS and that of PS on OS rates (P < 0.05). The toxicity of this regimen was mild to moderate. The major toxicity noted was myelosuppression. Severe (grade III-IV) neutropenia and thrombocytopenia has been observed in 13 (7%) and 6 courses (3.5%), respectively. In general, PCV is well tolerated and the median RFS and OS times elucidated are comparable with particular trials utilizing combination chemotherapy and longer than using radiotherapy alone.

The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doll, Corinne M., E-mail: Corinne.Doll@albertahealthservices.ca; Aquino-Parsons, Christina; Pintilie, Melania

2013-03-01

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens weremore » retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.« less

Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome

PubMed Central

Greaves, Paul; Clear, Andrew; Coutinho, Rita; Wilson, Andrew; Matthews, Janet; Owen, Andrew; Shanyinde, Milensu; Lister, T. Andrew; Calaminici, Maria; Gribben, John G.

2013-01-01

Purpose The immune microenvironment is key to the pathophysiology of classical Hodgkin lymphoma (CHL). Twenty percent of patients experience failure of their initial treatment, and others receive excessively toxic treatment. Prognostic scores and biomarkers have yet to influence outcomes significantly. Previous biomarker studies have been limited by the extent of tissue analyzed, statistical inconsistencies, and failure to validate findings. We aimed to overcome these limitations by validating recently identified microenvironment biomarkers (CD68, FOXP3, and CD20) in a new patient cohort with a greater extent of tissue and by using rigorous statistical methodology. Patients and Methods Diagnostic tissue from 122 patients with CHL was microarrayed and stained, and positive cells were counted across 10 to 20 high-powered fields per patient by using an automated system. Two statistical analyses were performed: a categorical analysis with test/validation set-defined cut points and Kaplan-Meier estimated outcome measures of 5-year overall survival (OS), disease-specific survival (DSS), and freedom from first-line treatment failure (FFTF) and an independent multivariate analysis of absolute uncategorized counts. Results Increased CD20 expression confers superior OS. Increased FOXP3 expression confers superior OS, and increased CD68 confers inferior FFTF and OS. FOXP3 varies independently of CD68 expression and retains significance when analyzed as a continuous variable in multivariate analysis. A simple score combining FOXP3 and CD68 discriminates three groups: FFTF 93%, 62%, and 47% (P < .001), DSS 93%, 82%, and 63% (P = .03), and OS 93%, 82%, and 59% (P = .002). Conclusion We have independently validated CD68, FOXP3, and CD20 as prognostic biomarkers in CHL, and we demonstrate, to the best of our knowledge for the first time, that combining FOXP3 and CD68 may further improve prognostic stratification. PMID:23045593

Do Patients Receiving Whole-Brain Radiotherapy for Brain Metastases From Renal Cell Carcinoma Benefit From Escalation of the Radiation Dose?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk, E-mail: Rades.Dirk@gmx.ne; Department of Radiation Oncology, University Hospital Hamburg-Eppendorf, Hamburg; Heisterkamp, Christine

2010-10-01

Purpose: Whole-brain radiotherapy (WBRT) is the most common treatment for brain metastases from renal cell carcinoma (RCC). Most patients cannot receive more aggressive therapies including surgery or radiosurgery. The standard WBRT regimen, 30 Gy/10 fractions (10 x 3 Gy), has resulted in poor survival (OS). This study investigates whether escalation of the WBRT dose improves treatment outcomes. Methods and Materials: Data from 60 patients receiving WBRT for brain metastases from RCC were retrospectively analyzed. A dose of 10 x 3 Gy (n = 31) was compared with higher doses (40 Gy/20 fractions or 45 Gy/15 fractions; n = 29) formore » OS and local control (LC). Additional factors evaluated were patient age, sex, performance status, number of metastases, interval from diagnosis of RCC to WBRT, extracerebral metastases, recursive partitioning analysis (RPA) class, and year of WBRT. Results: The OS at 6 months was 29% after 10 x 3 Gy and 52% after higher doses (p = 0.003). The OS at 12 months was 13% and 47%, respectively. On multivariate analysis, higher WBRT doses (p = 0.022), Karnofsky performance status score {>=}70 (p = 0.017), fewer than four brain metastases (p = 0.035), and RPA Class 1 (p = 0.003) resulted in better OS. The LC at 6 months was 21% after 10 x 3 Gy and 57% after higher doses (p = 0.013). The LC at 12 months was 7% and 35%, respectively. On multivariate analysis, fewer than four brain metastases (p < 0.001) were associated with LC. A trend was found for WBRT regimen (p = 0.06) and RPA class (p = 0.06). Conclusions: The findings suggest that escalation of the WBRT dose beyond 10 x 3 Gy improves outcomes in patients with brain metastases from RCC. The results should be confirmed in a randomized trial stratifying for significant prognostic factors.« less

Propensity score analysis of recurrence for neutrophil-to-lymphocyte ratio in colorectal cancer.

PubMed

Balde, Alpha I; Fang, Suzhen; He, Linyun; Cai, Zhai; Han, Shuai; Wang, Weiwei; Li, Zhou; Kang, Liang

2017-11-01

The perioperative serum neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict adverse prognosis in colorectal cancer (CRC). However, its interpretation remains unclear. The present study aimed to clarify the prognostic value of NLR in predicting survival among CRC patients. A single-centre, retrospective, propensity score-matched study of adenocarcinoma patients who underwent D3 lymphadenectomy via laparoscopic or open surgery between 2010 and 2016 was conducted. A cutoff of 3.5 was used based on the receiver operating characteristic curve. To overcome selection biases, we performed a 1:1 match using six covariates. The high-preoperative NLR group had a higher recurrence rate than the low group (P < 0.001). Univariate analysis showed that increased NLR (P < 0.001), N1 (P = 0.016), and N2 (P < 0.001) were associated with worse recurrence-free survival (RFS). Multivariate analysis showed that N2 (hazard ratio [HR], 2.492; P = 0.008) was an adverse prognostic factor for RFS. Univariate analysis for overall survival (OS) revealed that high perioperative NLR (P = 0.001), N1 (P = 0.01), N2 (P < 0.001), and distant metastasis (P < 0.001) were adverse prognostic factors. Subsequent multivariate analysis showed that M1 (HR, 3.973; P < 0.001) and N2 (HR, 2.381; P = 0.013) were highly adverse factors for OS. Clinical assessments performed during a 21.14 (±16.20)-mo follow-up revealed that OS (P = 0.001) and RFS (P < 0.001) were worse in the high-perioperative group than in the low group between the matched groups. An elevated preoperative NLR is a strong predictor of worse RFS and OS in CRC patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartford, Alan C., E-mail: Alan.C.Hartford@Hitchcock.org; Paravati, Anthony J.; Spire, William J.

2013-03-01

Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, formore » time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.« less

Excellent real-world outcomes of adults with Burkitt lymphoma treated with CODOX-M/IVAC plus or minus rituximab.

PubMed

Zhu, Katie Y; Song, Kevin W; Connors, Joseph M; Leitch, Heather; Barnett, Michael J; Ramadan, Khaled; Slack, Graham W; Abou Mourad, Yasser; Forrest, Donna L; Hogge, Donna E; Nantel, Stephen H; Narayanan, Sujaatha; Nevill, Thomas J; Power, Maryse M; Sanford, David S; Sutherland, Heather J; Tucker, Tracy; Toze, Cynthia L; Sehn, Laurie H; Broady, Raewyn; Gerrie, Alina S

2018-06-01

Treatment of Burkitt lymphoma (BL) with intensive, multi-agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population-based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high-dose methotrexate (MTX) (CODOX-M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX-M/IVAC) ± rituximab over a 15-year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus-associated BL), 5-year progression-free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63-83%] and 77% (95% CI: 66-85%), respectively, with no treatment-related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5-year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5-year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high-dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real-world analysis of BL patients treated with CODOX-M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice. © 2018 John Wiley & Sons Ltd.

Prognostic factors, patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy.

PubMed

Haefner, Matthias F; Lang, Kristin; Krug, David; Koerber, Stefan A; Uhlmann, Lorenz; Kieser, Meinhard; Debus, Juergen; Sterzing, Florian

2015-07-01

The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients recieved either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Thermal decomposition of ammonium hexachloroosmate.

PubMed

Asanova, T I; Kantor, I; Asanov, I P; Korenev, S V; Yusenko, K V

2016-12-07

Structural changes of (NH 4 ) 2 [OsCl 6 ] occurring during thermal decomposition in a reduction atmosphere have been studied in situ using combined energy-dispersive X-ray absorption spectroscopy (ED-XAFS) and powder X-ray diffraction (PXRD). According to PXRD, (NH 4 ) 2 [OsCl 6 ] transforms directly to metallic Os without the formation of any crystalline intermediates but through a plateau where no reactions occur. XANES and EXAFS data by means of Multivariate Curve Resolution (MCR) analysis show that thermal decomposition occurs with the formation of an amorphous intermediate {OsCl 4 } x with a possible polymeric structure. Being revealed for the first time the intermediate was subjected to determine the local atomic structure around osmium. The thermal decomposition of hexachloroosmate is much more complex and occurs within a minimum two-step process, which has never been observed before.

Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rutter, Charles E., E-mail: charles.rutter@yale.edu; Chagpar, Anees B.; Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut

2014-10-01

Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed formore » noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does not appear to increase the risk of death in this national database relative to right-sided tumors. Consequently, radiation therapy–induced cardiac disease may be less prominent than previously demonstrated.« less

Short-course whole-brain radiotherapy (WBRT) for brain metastases due to small-cell lung cancer (SCLC).

PubMed

Bohlen, Guenther; Meyners, Thekla; Kieckebusch, Susanne; Lohynska, Radka; Veninga, Theo; Stalpers, Lukas J A; Schild, Steven E; Rades, Dirk

2010-04-01

Many patients with brain metastases due to SCLC have a poor survival prognosis. The most common treatment is whole-brain radiotherapy (WBRT). This retrospective study compares short-course WBRT with 5x4Gy in 1 week to standard WBRT with 10x3Gy in 2 weeks. Forty-four SCLC patients receiving WBRT with 5x4Gy were compared to 102 patients receiving 10x3Gy for survival (OS) and local (intracerebral) control (LC). Seven further potential prognostic factors were investigated: age, gender, Karnofsky Performance Score (KPS), number of brain metastases, extracerebral metastases, interval from tumor diagnosis to WBRT, RPA (Recursive Partitioning Analysis) class. After 5x4Gy, 12-month OS was 15%, versus 22% after 10x3Gy (p=0.69). On multivariate analysis, improved OS was associated with age or=70 (p<0.001), <4 brain metastases (p=0.011), and RPA class 1 (p<0.001). 12-month LC was 34% after 5x4Gy versus 25% after 10x3Gy (p=0.32). On multivariate analysis, improved LC was associated with KPS >or=70 (p<0.001), <4 brain metastases (p=0.027), and RPA class 1 (p<0.001). In patients with brain metastases due to SCLC, short-course WBRT with 5x4Gy provided similar outcomes as 10x3Gy and appears preferable, particularly for patients with poor estimated survival.

Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases.

PubMed

Shindoh, Junichi; Loyer, Evelyne M; Kopetz, Scott; Boonsirikamchai, Piyaporn; Maru, Dipen M; Chun, Yun Shin; Zimmitti, Giuseppe; Curley, Steven A; Charnsangavej, Chusilp; Aloia, Thomas A; Vauthey, Jean-Nicolas

2012-12-20

The purposes of this study were to confirm the prognostic value of an optimal morphologic response to preoperative chemotherapy in patients undergoing chemotherapy with or without bevacizumab before resection of colorectal liver metastases (CLM) and to identify predictors of the optimal morphologic response. The study included 209 patients who underwent resection of CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based regimens with or without bevacizumab. Radiologic responses were classified as optimal or suboptimal according to the morphologic response criteria. Overall survival (OS) was determined, and prognostic factors associated with an optimal response were identified in multivariate analysis. An optimal morphologic response was observed in 47% of patients treated with bevacizumab and 12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS rates were higher in the optimal response group (82% and 74%, respectively) compared with the suboptimal response group (60% and 45%, respectively; P < .001). On multivariate analysis, suboptimal morphologic response was an independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before chemotherapy of ≤ 3 cm (odds ratio, 2.12; P = .025) were significantly associated with optimal morphologic response. The morphologic response showed no specific correlation with conventional size-based RECIST criteria, and it was superior to RECIST in predicting major pathologic response. Independent of preoperative chemotherapy regimen, optimal morphologic response is sufficiently correlated with OS to be considered a surrogate therapeutic end point for patients with CLM.

Optimal Morphologic Response to Preoperative Chemotherapy: An Alternate Outcome End Point Before Resection of Hepatic Colorectal Metastases

PubMed Central

Shindoh, Junichi; Loyer, Evelyne M.; Kopetz, Scott; Boonsirikamchai, Piyaporn; Maru, Dipen M.; Chun, Yun Shin; Zimmitti, Giuseppe; Curley, Steven A.; Charnsangavej, Chusilp; Aloia, Thomas A.; Vauthey, Jean-Nicolas

2012-01-01

Purpose The purposes of this study were to confirm the prognostic value of an optimal morphologic response to preoperative chemotherapy in patients undergoing chemotherapy with or without bevacizumab before resection of colorectal liver metastases (CLM) and to identify predictors of the optimal morphologic response. Patients and Methods The study included 209 patients who underwent resection of CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based regimens with or without bevacizumab. Radiologic responses were classified as optimal or suboptimal according to the morphologic response criteria. Overall survival (OS) was determined, and prognostic factors associated with an optimal response were identified in multivariate analysis. Results An optimal morphologic response was observed in 47% of patients treated with bevacizumab and 12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS rates were higher in the optimal response group (82% and 74%, respectively) compared with the suboptimal response group (60% and 45%, respectively; P < .001). On multivariate analysis, suboptimal morphologic response was an independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before chemotherapy of ≤ 3 cm (odds ratio, 2.12; P = .025) were significantly associated with optimal morphologic response. The morphologic response showed no specific correlation with conventional size-based RECIST criteria, and it was superior to RECIST in predicting major pathologic response. Conclusion Independent of preoperative chemotherapy regimen, optimal morphologic response is sufficiently correlated with OS to be considered a surrogate therapeutic end point for patients with CLM. PMID:23150701

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Marital status is an independent prognostic factor for tracheal cancer patients: an analysis of the SEER database.

PubMed

Li, Mu; Dai, Chen-Yang; Wang, Yu-Ning; Chen, Tao; Wang, Long; Yang, Ping; Xie, Dong; Mao, Rui; Chen, Chang

2016-11-22

Although marital status is an independent prognostic factor in many cancers, its prognostic impact on tracheal cancer has not yet been determined. The goal of this study was to examine the relationship between marital status and survival in patients with tracheal cancer. Compared with unmarried patients (42.67%), married patients (57.33%) had better 5-year OS (25.64% vs. 35.89%, p = 0.009) and 5-year TCSS (44.58% vs. 58.75%, p = 0.004). Results of multivariate analysis indicated that marital status is an independent prognostic factor, with married patients showing better OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95, p = 0.015) and TCSS (HR = 0.70, 95% CI 0.54-0.91, p = 0.008). In addition, subgroup analysis suggested that marital status plays a more important role in the TCSS of patients with non-low-grade malignant tumors (HR = 0.71, 95% CI 0.53-0.93, p = 0.015). We extracted 600 cases from the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Pearson chi-squared test, t-test, log-rank test, and multivariate Cox regression analysis. Overall survival (OS) and tracheal cancer-specific survival (TCSS) were compared between subgroups with different pathologic features and tumor stages. Marital status is an independent prognostic factor for survival in patients with tracheal cancer. For that reason, additional social support may be needed for unmarried patients, especially those with non-low-grade malignant tumors.

Prognostic value of combined preoperative fibrinogen and neutrophil–lymphocyte ratio in patients with hepatocellular carcinoma after liver transplantation

PubMed Central

Chen, Mao-Gen; Wang, Xiao-Ping; Ju, Wei-Qiang; Zhao, Qiang; Wu, Lin-Wei; Ren, Qing-Qi; Guo, Zhi-Yong; Wang, Dong-Ping; Zhu, Xiao-Feng; Ma, Yi; He, Xiao-Shun

2017-01-01

Objectives Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil–lymphocyte ratio (NLR). Results Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. Materials and Methods Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. Conclusions Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing. PMID:27935864

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

PubMed

Salah, Samer; Ardissone, Francesco; Gonzalez, Michel; Gervaz, Pascal; Riquet, Marc; Watanabe, Kazuhiro; Zabaleta, Jon; Al-Rimawi, Dalia; Toubasi, Samar; Massad, Ehab; Lisi, Elena; Hamed, Osama H

2015-01-01

Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Identification of the compositional changes in Orthosiphon stamineus leaves triggered by different drying techniques using 1 H NMR metabolomics.

PubMed

Pariyani, Raghunath; Ismail, Intan Safinar; Ahmad Azam, Amalina; Abas, Faridah; Shaari, Khozirah

2017-09-01

Java tea is a well-known herbal infusion prepared from the leaves of Orthosiphon stamineus (OS). The biological properties of tea are in direct correlation with the primary and secondary metabolite composition, which in turn largely depends on the choice of drying method. Herein, the impact of three commonly used drying methods, i.e. shade, microwave and freeze drying, on the metabolite composition and antioxidant activity of OS leaves was investigated using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy combined with multivariate classification and regression analysis tools. A total of 31 constituents comprising primary and secondary metabolites belonging to the chemical classes of fatty acids, amino acids, sugars, terpenoids and phenolic compounds were identified. Shade-dried leaves were identified to possess the highest concentrations of bioactive secondary metabolites such as chlorogenic acid, caffeic acid, luteolin, orthosiphol and apigenin, followed by microwave-dried samples. Freeze-dried leaves had higher concentrations of choline, amino acids leucine, alanine and glutamine and sugars such as fructose and α-glucose, but contained the lowest levels of secondary metabolites. Metabolite profiling coupled with multivariate analysis identified shade drying as the best method to prepare OS leaves as Java tea or to include in traditional medicine preparation. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Expression of miR-146a-5p in patients with intracranial aneurysms and its association with prognosis.

PubMed

Zhang, H-L; Li, L; Cheng, C-J; Sun, X-C

2018-02-01

The study aims to detect the association of miR-146a-5p with intracranial aneurysms (IAs). The expression of miR-146a-5p was compared from plasma samples between 72 patients with intracranial aneurysms (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed to analyze the relationship between miR-146a-5p expression and clinical data and overall survival (OS) time of IAs patients. Univariate and multivariate Cox proportional hazards have also been performed. Notably, higher miR-146a-5p expression was found in plasma samples from 72 patients with intracranial aneurysms (IAs) compared with 40 healthy controls. Higher miR-146a-5p expression was significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan-Meier survival analysis verified that higher miR-146a-5p expression predicted a shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs patients. Univariate and multivariate Cox proportional hazards demonstrated that higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk factors of OS in patients with intracranial aneurysms (IAs). MiR-146a-5p expression may serve as a biomarker for predicting prognosis in patients with IAs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morganti, Alessio G.; Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso; Falconi, Massimo

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462more » patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.« less

Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer.

PubMed

Carbognin, Luisa; Sperduti, Isabella; Brunelli, Matteo; Marcolini, Lisa; Nortilli, Rolando; Pilotto, Sara; Zampiva, Ilaria; Merler, Sara; Fiorio, Elena; Filippi, Elisa; Manfrin, Erminia; Pellini, Francesca; Bonetti, Franco; Pollini, Giovanni Paolo; Tortora, Giampaolo; Bria, Emilio

2016-03-22

The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67. At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8%, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21%); 10-years DFS and OS were 75.1, 66.5, and 30.2% (p = 0.01) and 84.3, 76.4 and 59% (p = 0.003), for patients with a Ki67 < 6%, between 6 and 21%, and >21%, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85%, OS 100%). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology. Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sole, Claudio V., E-mail: csole@iram.cl; School of Medicine, Complutense University, Madrid; Calvo, Felipe A.

Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-freemore » survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.« less

Time from Prior Chemotherapy Enhances Prognostic Risk Grouping in the Second-line Setting of Advanced Urothelial Carcinoma: A Retrospective Analysis of Pooled, Prospective Phase 2 Trials

PubMed Central

Sonpavde, Guru; Pond, Gregory R.; Fougeray, Ronan; Choueiri, Toni K.; Qu, Angela Q.; Vaughn, David J.; Niegisch, Guenter; Albers, Peter; James, Nicholas D.; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Khan, Awais; Vogelzang, Nicholas J.; Beer, Tomasz M.; Stadler, Walter M.; O’Donnell, Peter H.; Sternberg, Cora N.; Rosenberg, Jonathan E.; Bellmunt, Joaquim

2014-01-01

Background Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). Objectives The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352). Outcome measurements and statistical analysis Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. Results and limitations ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Conclusions Shorter TFPC enhances prognostic classification independent of ECOG-PS>0, Hb<10 g/ dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. PMID:23206856

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kishi, Takahiro; Matsuo, Yukinori, E-mail: ymatsuo@kuhp.kyoto-u.ac.jp; Ueki, Nami

Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on causemore » of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.« less

Initial FDG-PET/CT predicts survival in adults Ewing sarcoma family of tumors

PubMed Central

Jamet, Bastien; Carlier, Thomas; Campion, Loic; Bompas, Emmanuelle; Girault, Sylvie; Borrely, Fanny; Ferrer, Ludovic; Rousseau, Maxime; Venel, Yann; Kraeber-Bodéré, Françoise; Rousseau, Caroline

2017-01-01

Purpose The aim of this retrospective study was to determine, at baseline, the prognostic value of different FDG-PET/CT quantitative parameters in a homogenous Ewing Sarcoma Family of Tumors (ESFT) adult population, compared with clinically relevant prognostic factors. Methods Adult patients from 3 oncological centers, all with proved ESFT, were retrospectively included. Quantitative FDG-PET/CT parameters (SUV (maximum, peak and mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion of each patient were recorded before treatment, as well as usual clinical prognostic factors (stage of disease, location, tumor size, gender and age). Then, their relation with progression free survival (PFS) and overall survival (OS) was evaluated. Results 32 patients were included. Median age was 21 years (range, 15 to 61). Nineteen patients (59%) were initially metastatic. On multivariate analysis, high SUVmax remained independent predictor of worst OS (p=0.02) and PFS (p=0.019), metastatic disease of worst PFS (p=0.01) and high SUVpeak of worst OS (p=0.01). Optimal prognostic cut-off of SUVpeak was found at 12.5 in multivariate analyses for PFS and OS (p=0.0001). Conclusions FDG-PET/CT, recommended at ESFT diagnosis for initial staging, can be a useful tool for predicting long-term adult patients outcome through semi-quantitative parameters. PMID:29100369

VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma.

PubMed

Park, Seongyeol; Nam, Soo Jeong; Keam, Bhumsuk; Kim, Tae Min; Jeon, Yoon Kyung; Lee, Se-Hoon; Hah, J Hun; Kwon, Tack-Kyun; Kim, Dong-Wan; Sung, Myung-Whun; Heo, Dae Seog; Bang, Yung-Jue

2016-04-01

The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS). In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.

DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

PubMed

Dong, Xiaoqun; Li, Yanan; Hess, Kenneth R; Abbruzzese, James L; Li, Donghui

2011-01-01

DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

Prognostic Value of Pretherapeutic Tumor-to-Blood Standardized Uptake Ratio in Patients with Esophageal Carcinoma.

PubMed

Bütof, Rebecca; Hofheinz, Frank; Zöphel, Klaus; Stadelmann, Tobias; Schmollack, Julia; Jentsch, Christina; Löck, Steffen; Kotzerke, Jörg; Baumann, Michael; van den Hoff, Jörg

2015-08-01

Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Role of rituximab in treatment of patients with primary central nervous system lymphoma: a retrospective analysis of the Czech lymphoma study group registry.

PubMed

Mocikova, Heidi; Pytlik, Robert; Sykorova, Alice; Janikova, Andrea; Prochazka, Vit; Vokurka, Samuel; Berkova, Adela; Belada, David; Campr, Vit; Buresova, Lucie; Trneny, Marek

2016-12-01

We have investigated whether the addition of rituximab to methotrexate, procarbazine, vincristine, radiotherapy and cytarabine was associated with improved outcome of primary central nervous system lymphomas (PCNSL). Of 164 patients, 49 received rituximab. Median age was 63 years, median Karnofsky performance score (KPS) was 60 and median follow-up of living patients was 59.5 months. 1- and 2-year PFS were 49.7 and 37.9%, 1- and 2-year OS were 57.0 and 45.3%. Median progression-free survival (PFS), but not overall survival (OS) was significantly better for patients treated with rituximab (22.9 vs. 10.9 months, p = 0.037). In multivariate analysis, age ≤70 years and KPS ≥90 were predictive for PFS and OS, rituximab was an independent prognostic factor for PFS only. In landmark analyses, rituximab was not found beneficial for long-term survivors and no group particularly benefited from rituximab. In conclusion, addition of rituximab was associated with improved PFS, but not OS in this unselected cohort of PCNSL patients.

Localized sinonasal mucosal melanoma: Outcomes and associations with stage, radiotherapy, and positron emission tomography response.

PubMed

Samstein, Robert M; Carvajal, Richard D; Postow, Michael A; Callahan, Margaret K; Shoushtari, Alexander N; Patel, Snehal G; Lee, Nancy Y; Barker, Christopher A

2016-09-01

Sinonasal mucosal melanoma is a rare neoplasm with a poor prognosis. Retrospective analysis was conducted on 78 patients with localized sinonasal mucosal melanoma treated at Memorial Sloan Kettering Cancer Center (MSKCC from 1998-2013). Demographic, tumor, imaging, and treatment factors were recorded and survival and disease-control outcomes were analyzed. Median overall survival (OS) and disease-specific survival (DSS) were 32 and 50 months, respectively. Median locoregional recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were 43 and 12 months, respectively. Multivariate analysis demonstrated greater OS in nasal cavity tumors and earlier T classification. Radiotherapy (RT) was associated with significantly greater LRFS (5-years; 35% vs 59%; p = .01), but no difference in OS. Post-RT positron emission tomography (PET) response was associated with greater OS. Distant metastasis is the predominant mode of recurrence in sinonasal mucosal melanoma, but local recurrence remains common. RT is associated with improved local control, but no survival benefit. The prognostic value of post-RT PET imaging warrants further investigation. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1310-1317, 2016. © 2016 Wiley Periodicals, Inc.

Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

PubMed

White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

2014-05-01

The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer

PubMed Central

Chu, Michael P.; Hecht, J. Randolph; Slamon, Dennis; Wainberg, Zev A.; Bang, Yung-Jue; Hoff, Paulo M.; Sobrero, Alberto; Qin, Shukui; Afenjar, Karen; Houe, Vincent; King, Karen; Koski, Sheryl; Mulder, Karen; Hiller, Julie Price; Scarfe, Andrew; Spratlin, Jennifer; Huang, Yingjie J.; Khan-Wasti, Saba; Chua, Neil

2016-01-01

Importance Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib. Proton pump inhibitor use was identified by medication records. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with PPIs vs patients who were not. Specific subgroups were accounted for, such as younger age (<60 years), Asian ethnicity, female sex, and disease stage (metastatic/advanced) in multivariate Cox proportional hazards modeling. The TRIO-013 trial accrued and randomized patients between June 2008 and January 2012; this analysis took place in January 2014. Interventions Patients were divided based on PPI exposure. Main Outcomes and Measures Primary study outcome was PFS and OS between patients treated with PPIs vs patients who were not. Secondary outcomes included disease response rates and toxicities. Results Of the 545 patients with GEC (median age, 60 years; 406 men [74%]) included in the study, 229 received PPIs (42.0%) and were evenly distributed between arms. In the placebo arm, PPI-treated patients had poorer median PFS, 4.2 vs 5.7 months (hazard ratio [HR], 1.55; 95% CI, 1.29-1.81, P < .001); OS, 9.2 vs 11.3 months (HR, 1.34; 95% CI, 1.06-1.62; P = .04); and disease control rate (72% vs 83%; P = .02) vs patients not treated with PPIs. In multivariate analysis considering age, race, disease stage, and sex, PPI-treated patients had poorer PFS (HR, 1.68; 95% CI, 1.42-1.94; P < .001) and OS (HR, 1.41; 95% CI, 1.11-1.71; P = .001). In patients treated with CapeOx and lapatinib, PPIs had less effect on PFS (HR, 1.08; P = .54) and OS (HR, 1.26; P = .10); however, multivariate analysis in this group demonstrated a significant difference in OS (HR, 1.38; 95% CI, 1.06-1.66; P = .03). Conclusions and Relevance Proton pump inhibitors negatively effected capecitabine efficacy by possibly raising gastric pH levels, leading to altered dissolution and absorption. These results are consistent with previous erlotinib and sunitinib studies. Whether PPIs affected lapatinib is unclear given concurrent capecitabine. Given capecitabine’s prevalence in treatment breast cancer and colon cancer, further studies are under way. Trial Registration clinicaltrials.gov Identifier: NCT00680901 PMID:27737436

Impact of the Bim Deletion Polymorphism on Survival Among Patients With Completely Resected Non-Small-Cell Lung Carcinoma.

PubMed

Atsumi, Jun; Shimizu, Kimihiro; Ohtaki, Yoichi; Kaira, Kyoichi; Kakegawa, Seiichi; Nagashima, Toshiteru; Enokida, Yasuaki; Nakazawa, Seshiru; Obayashi, Kai; Takase, Yoshiaki; Kawashima, Osamu; Kamiyoshihara, Mitsuhiro; Sugano, Masayuki; Ibe, Takashi; Igai, Hitoshi; Takeyoshi, Izumi

2016-02-01

A deletion polymorphism of the Bim gene has been reported to be a prognostic factor for patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors in the Asian population. We investigated the impact of the Bim deletion polymorphism on survival among patients with completely resected NSCLC. The Bim polymorphism was detected by polymerase chain reaction analysis. We measured overall survival (OS) and recurrence-free survival rates in 411 patients and postrecurrence survival (PRS) in 94 patients who experienced recurrence and received additional anticancer therapy. The Bim deletion polymorphism was detected in 61 patients (14.8%). OS rates were significantly lower for patients with the Bim deletion polymorphism than for those with the wild-type sequence. On multivariable analysis, the Bim deletion polymorphism was identified as an independent prognostic factor for OS (hazard ratio, 1.98; 95% CI, 1.17 to 3.36; P = .011). Among the 94 patients who experienced recurrence and were treated with anticancer therapy, patients with the Bim deletion polymorphism showed significantly poorer PRS than those with the wild-type sequence (median, 9.8 months v 26.9 months, respectively; P < .001). Multivariable analysis revealed that the Bim deletion polymorphism was an independent predictor of PRS (hazard ratio, 3.36; 95% CI, 1.75 to 6.47; P < .001). This trend remained apparent in subgroup analyses stratified by EGFR status, histology, and therapeutic modality. The Bim deletion polymorphism is a novel indicator of shortened PRS among patients with recurrent NSCLC treated with anticancer therapy in the Asian population.

Factors predicting survival following complete surgical remission of pulmonary metastasis in osteosarcoma

PubMed Central

SALAH, SAMER; TOUBASI, SAMAR

2015-01-01

Pulmonary metastasectomy (PM) is associated with improved survival of patients with metastatic osteosarcoma; however, the factors affecting survival following achievement of complete surgical remission remain controversial. The main objective of this study was to report the outcomes and prognostic factors of osteosarcoma patients who achieved complete remission (CR) following PM. We analyzed the effect of demographic and disease-related characteristics on the overall survival (OS) of consecutive patients with metastatic osteosarcoma who were treated at a single institution and achieved CR following PM, through univariate and multivariate analyses. Between January, 2000 and August, 2013, 62 patients with metastatic osteosarcoma were treated and followed up at our institution. A total of 25 patients achieved CR following PM and were included in this analysis. The 5-year OS and disease-free survival following PM were 30 and 21%, respectively. The factors correlated with inferior OS in the univariate analysis included chondroblastic subtype, post-chemotherapy necrosis <90% in the primary tumor, metastasis detected during neoadjuvant or adjuvant chemotherapy and pathological identification of tumor cells reaching the visceral pleural surface of any of the resected nodules. In the multivariate analysis, the chondroblastic subtype was the sole independent adverse prognostic factor (HR=4.6, 95% CI: 1.0–21.3, P=0.044). Therefore, factors associated with tumor biology, including poor tumor necrosis in the primary tumor and detection of metastasis during primary chemotherapy, are associated with poor post-metastasectomy survival. In addition, chondroblastic subtype and visceral pleural involvement predicted poor prognosis in our series. PMID:25469287

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

PubMed

Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours.

PubMed

Zandee, Wouter T; van Adrichem, Roxanne C; Kamp, Kimberly; Feelders, Richard A; van Velthuysen, Marie-Louise F; de Herder, Wouter W

2017-08-01

Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden. © 2017 John Wiley & Sons Ltd.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in males, smokers, and non-adenocarcinoma lung cancer in patients with EGFR mutations.

PubMed

Zeng, Zhu; Chen, Hua-Jun; Yan, Hong-Hong; Yang, Jin-Ji; Zhang, Xu-Chao; Wu, Yi-Long

2013-09-27

The demographical/clinical characteristics of being Asian, having an adenocarcinoma, being female, and being a "never-smoker" are regarded as favorable predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy in non-small cell lung cancer (NSCLC) with unknown EGFR gene status. In this study, we examined the effects of the supposedly unfavorable clinical variables in EGFR-mutant patients. In total, 159 EGFR-mutant NSCLC patients' clinical features were correlated with progression-free survival (PFS), response rate (RR), and overall survival (OS). Multivariate analysis of clinical characteristics was performed using the Cox and logistic regression methods. There were 90 females (56.6%), 112 never-smokers (70.4%), and 153 patients with adenocarcinomas (96.2%). All patients were treated with EGFR-TKI, and 52.8% received TKI in a first-line setting. The median PFS of patients receiving first-line TKI was similar, regardless of gender (males vs females: 9.1 vs 9.7 months, p=0.793), smoking status (never-smokers vs smokers: 9.9 vs 9.1 months, p=0.570), or histology (adenocarcinoma vs non-adenocarcinoma: 9.7 vs 9.2 months, p=0.644). OS curves of first-line TKI-treated patients were also not associated with gender (p=0.722), smoking status (p=0.579), or histology (p=0.480). Similar results of PFS and OS were obtained for patients who received TKI beyond first-line. Multivariate analysis indicated that none of these clinical factors was an independent predictor of survival. The supposedly 'favorable' clinical factors of female gender, non-smoking status, and adenocarcinoma were not independent predictive factors for PFS or OS in this population of EGFR-mutant NSCLC patients.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

PubMed

de la Motte Rouge, Thibault; Pautier, Patricia; Genestie, Catherine; Rey, Annie; Gouy, Sébastien; Leary, Alexandra; Haie-Meder, Christine; Kerbrat, Pierre; Culine, Stéphane; Fizazi, Karim; Lhommé, Catherine

2016-09-01

The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. No conflict of interest. Copyright © 2016. Published by Elsevier Inc.

Infused autograft lymphocyte-to-monocyte ratio and survival in T-cell lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

PubMed

Porrata, Luis F; Inwards, David J; Ansell, Stephen M; Micallef, Ivana N; Johnston, Patrick B; Hogan, William J; Markovic, Svetomir N

2015-07-03

The infused autograft lymphocyte-to-monocyte ratio (A-LMR) is a prognostic factor for survival in B-cell lymphomas post-autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if the A-LMR is also a prognostic factor for survival post-APHSCT in T-cell lymphomas. From 1998 to 2014, 109 T-cell lymphoma patients that underwent APHSCT were studied. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to identify the optimal cut-off value of A-LMR for survival analysis and k-fold cross-validation model to validate the A-LMR cut-off value. Univariate and multivariate Cox proportional hazard models were used to assess the prognostic discriminator power of A-LMR. ROC and AUC identified an A-LMR ≥ 1 as the best cut-off value and was validated by k-fold cross-validation. Multivariate analysis showed A-LMR to be an independent prognostic factor for overall survival (OS) and progression-free survival (PFS). Patients with an A-LMR ≥ 1.0 experienced a superior OS and PFS versus patients with an A-LMR < 1.0 [median OS was not reached vs 17.9 months, 5-year OS rates of 87% (95% confidence interval (CI), 75-94%) vs 26% (95% CI, 13-42%), p < 0.0001; median PFS was not reached vs 11.9 months, 5-year PFS rates of 72% (95% CI, 58-83%) vs 16% (95% CI, 6-32%), p < 0.0001]. A-LMR is also a prognostic factor for clinical outcomes in patients with T-cell lymphomas undergoing APHSCT.

Conformal Therapy Improves the Therapeutic Index of Patients with Anal Canal Cancer Treated with Combined Chemotherapy and External Beam Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vuong, Te; Kopek, Neil; Ducruet, Thierry

2007-04-01

Purpose: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. Methods and Materials: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinummore » given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. Results: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). Conclusion: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS.« less

Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.

PubMed

Epperla, Narendranath; Hamadani, Mehdi; Cashen, Amanda F; Ahn, Kwang W; Oak, Eunhye; Kanate, Abraham S; Calzada, Oscar; Cohen, Jonathon B; Farmer, Luke; Ghosh, Nilanjan; Tallarico, Michael; Nabhan, Chadi; Costa, Luciano J; Kenkre, Vaishalee P; Hari, Parameswaran N; Fenske, Timothy S

2017-12-01

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses. Copyright © 2017 John Wiley & Sons, Ltd.

Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis.

PubMed

McConechy, Melissa K; Talhouk, Aline; Leung, Samuel; Chiu, Derek; Yang, Winnie; Senz, Janine; Reha-Krantz, Linda J; Lee, Cheng-Han; Huntsman, David G; Gilks, C Blake; McAlpine, Jessica N

2016-06-15

The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on POLE-mutated tumors was assessed. A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled HR for PFS, DSS, and OS. POLE EDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with POLE-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, POLE-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE-mutated cases could not be determined conclusively; however, both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15-0.73] and 0.35 (95% CI, 0.13-0.92), respectively. POLE EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. Clin Cancer Res; 22(12); 2865-73. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial

PubMed Central

Smyth, Elizabeth C.; Fassan, Matteo; Cunningham, David; Allum, William H.; Okines, Alicia F.C.; Lampis, Andrea; Hahne, Jens C.; Rugge, Massimo; Peckitt, Clare; Nankivell, Matthew; Langley, Ruth; Ghidini, Michele; Braconi, Chiara; Wotherspoon, Andrew; Grabsch, Heike I.

2016-01-01

Purpose The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate. PMID:27298411

Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non-Small Cell Lung Cancer.

PubMed

Sepesi, Boris; Cuentas, Edwin Parra; Canales, Jaime Rodriguez; Behrens, Carmen; Correa, Arlene M; Vaporciyan, Ara; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar; Swisher, Stephen; Wistuba, Ignacio

2017-01-01

Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis. Statistics included recursive partitioning, univariable, multivariable, and Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87) experienced significantly better overall survival (OS) (P = 0.001) than patients with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N = 24) also experienced significantly better (P = 0.005) OS than patients with >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1 expression in both tumor and macrophages with 5-year OS of 94% (N = 17). Contrarily, patients with high PD-L1 expression in both tumor and macrophages experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in the TIMs was independently associated with survival in multivariable analysis (P = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and in the TIMs seems to be associated with significantly better OS in surgically resected stage I lung cancer. Additional studies are needed to validate PD-L1 as a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

[Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy].

PubMed

Wang, J B; Jiang, W; Ji, Z; Cao, J Z; Liu, L P; Men, Y; Xu, C; Wang, X Z; Hui, Z G; Liang, J; Lyu, J M; Zhou, Z M; Xiao, Z F; Feng, Q F; Chen, D F; Zhang, H X; Yin, W B; Wang, L H

2016-08-01

This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. Radiation therapy technique is a factor affecting prognosis of LA-NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation-induced lung toxicity.

Impact of postmastectomy radiotherapy in T3N0 invasive carcinoma of the breast: a Surveillance, Epidemiology, and End Results database analysis.

PubMed

McCammon, Robert; Finlayson, Christina; Schwer, Amanda; Rabinovitch, Rachel

2008-08-15

Randomized trials provide evidence for improved outcomes with postmastectomy radiotherapy (PMRT) in high-risk patients. It has been suggested that patients with T3N0 breast cancer represent a favorable subgroup for which PMRT renders little benefit. In the current study, the authors used a United States population database to evaluate PMRT in this subgroup. The cause-specific survival (CSS) and overall survival (OS) of women with T3N0M0 breast cancer in the Surveillance, Epidemiology, and End Results database after mastectomy and axillary staging from 1988 to 2002 were analyzed. Univariate analysis was performed to relate CSS with PMRT (yes vs no), tumor size (< or =7 cm vs >7 cm), grade (1 vs 2 or 3), patient age (< or =50 years vs >50 years), the number of lymph nodes dissected (< or =13 vs >13), and the era treated (1988-1997 vs 1998-2002). Multivariate analyses for CSS and OS were also performed. In total, 1865 women met the analysis criteria for OS; CSS data were available for 98.8% of those women. Of the women who were diagnosed during the era from 1988 to 1997, 22% received PMRT, and that rate increased to 41% during the era from 1998 to 2002. The actuarial 10-year CSS for those who received PMRT versus those who did not receive PMRT was 81.6% versus 79.8%, respectively (P = .38). PMRT was not associated with a CSS benefit in any subgroup, a finding that persisted in multivariate analyses. Women who received PMRT had an increased 10-year OS rate (70.7% vs 58.4%; P < .001) that was confined to women aged >50 years in a subgroup analysis. This retrospective, population-based analysis demonstrated no increase in CSS with PMRT for women with T3N0 breast cancer, lending further support to the hypothesis that T3N0 disease postmastectomy represents a favorable subset of locally advanced breast cancer. The increased OS associated with PMRT in the absence of improved CSS likely reflects patient selection in this nonrandomized dataset. Prospective evaluation of PMRT in this population subset is warranted. 2008 American Cancer Society

Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy.

PubMed

Bernhardt, Denise; Adeberg, Sebastian; Bozorgmehr, Farastuk; Opfermann, Nils; Hoerner-Rieber, Juliane; König, Laila; Kappes, Jutta; Thomas, Michael; Herth, Felix; Heußel, Claus Peter; Warth, Arne; Debus, Jürgen; Steins, Martin; Rieken, Stefan

2017-08-01

The purpose of this study was to evaluate prognostic factors associated with overall survival (OS) and neurological progression free survival (nPFS) in small-cell lung cancer (SCLC) patients with brain metastases who received whole-brain radiotherapy (WBRT). From 2003 to 2015, 229 SCLC patients diagnosed with brain metastases who received WBRT were analyzed retrospectively. In this cohort 219 patients (95%) received a total photon dose of 30 Gy in 10 fractions. The prognostic factors evaluated for OS and nPFS were: age, Karnofsky Performance Status (KPS), number of brain metastases, synchronous versus metachronous disease, initial response to chemotherapy, the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class and thoracic radiation. Median OS after WBRT was 6 months and the median nPFS after WBRT was 11 months. Patients with synchronous cerebral metastases had a significantly better median OS with 8 months compared to patients with metachronous metastases with a median survival of 3 months (p < 0.0001; HR 0.46; 95% CI 0.31-0.67). Based on RPA classification median survival after WBRT was 17 months in RPA class I, 7 months in class II and 3 months in class III (p < 0.0001). Karnofsky performance status scale (KPS < 70%) was significantly associated with OS in both univariate (HR 2.84; p < 0.001) and multivariate analyses (HR 2.56; p = 0.011). Further, metachronous brain metastases (HR 1.8; p < 0.001), initial response to first-line chemotherapy (HR 0.51, p < 0.001) and RPA class III (HR 2.74; p < 0.001) were significantly associated with OS in univariate analysis. In multivariate analysis metachronous disease (HR 1.89; p < 0.001) and initial response to chemotherapy (HR 0.61; p < 0.001) were further identified as significant prognostic factors. NPFS was negatively significantly influenced by poor KPS (HR 2.56; p = 0.011), higher number of brain metastases (HR 1.97; p = 0.02), and higher RPA class (HR 2.26; p = 0.03) in univariate analysis. In this series, the main prognostic factors associated with OS were performance status, time of appearance of intracranial disease (synchronous vs. metachronous), initial response to chemotherapy and higher RPA class. NPFS was negatively influenced by poor KPS, multiplicity of brain metastases, and higher RPA class in univariate analysis. For patients with low performance status, metachronous disease or RPA class III, WBRT should be weighed against supportive therapy with steroids alone or palliative chemotherapy.

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial.

PubMed

Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E; Phillips, Heidi S; Bais, Carlos

2015-09-01

The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. © 2015 by American Society of Clinical Oncology.

Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.

PubMed

Villablanca, Judith G; Ji, Lingyun; Shapira-Lewinson, Adi; Marachelian, Araz; Shimada, Hiroyuki; Hawkins, Randall A; Pampaloni, Miguel; Lai, Hollie; Goodarzian, Fariba; Sposto, Richard; Park, Julie R; Matthay, Katherine K

2018-05-01

The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing. © 2018 Wiley Periodicals, Inc.

Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation.

PubMed

Fenske, Timothy S; Ahn, Kwang W; Graff, Tara M; DiGilio, Alyssa; Bashir, Qaiser; Kamble, Rammurti T; Ayala, Ernesto; Bacher, Ulrike; Brammer, Jonathan E; Cairo, Mitchell; Chen, Andy; Chen, Yi-Bin; Chhabra, Saurabh; D'Souza, Anita; Farooq, Umar; Freytes, Cesar; Ganguly, Siddhartha; Hertzberg, Mark; Inwards, David; Jaglowski, Samantha; Kharfan-Dabaja, Mohamed A; Lazarus, Hillard M; Nathan, Sunita; Pawarode, Attaphol; Perales, Miguel-Angel; Reddy, Nishitha; Seo, Sachiko; Sureda, Anna; Smith, Sonali M; Hamadani, Mehdi

2016-07-01

For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT. © 2016 John Wiley & Sons Ltd.

Pretreatment TG/HDL-C Ratio Is Superior to Triacylglycerol Level as an Independent Prognostic Factor for the Survival of Triple Negative Breast Cancer Patients.

PubMed

Dai, Danian; Chen, Bo; Wang, Bin; Tang, Hailin; Li, Xing; Zhao, Zhiping; Li, Xuan; Xie, Xiaoming; Wei, Weidong

2016-01-01

Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR. Univariate and multivariate logistic regression analyses were used to assess the effect of the TG level and the THR on overall survival (OS) and disease-free survival (DFS). The optimal cutoff values of the TG level and the THR were determined to be 0.935 mmol/L and 0.600, respectively. As shown in a Kaplan-Meier analysis, TNBC patients with a high TG level and THR had shorter OS and DFS than patients in the low-level groups ( p < 0.05). The multivariate analysis suggested that the pretreatment THR level is an independent prognostic factor of OS (HR: 1.935; 95%CI: 1.032-3.629; p = 0.040) in TNBC patients. In conclusion, our data indicate that a high THR is an independent predictor and is superior to the TG level for predicting poor clinical outcomes in TNBC patients.

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAleer, Mary Frances, E-mail: mfmcalee@mdanderson.or; Moughan, Jennifer M.S.; Byhardt, Roger W.

2010-03-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk)more » on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.« less

Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials.

PubMed

Sonpavde, Guru; Pond, Gregory R; Fougeray, Ronan; Choueiri, Toni K; Qu, Angela Q; Vaughn, David J; Niegisch, Guenter; Albers, Peter; James, Nicholas D; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S; Galsky, Matthew D; Petrylak, Daniel P; Vaishampayan, Ulka N; Khan, Awais; Vogelzang, Nicholas J; Beer, Tomasz M; Stadler, Walter M; O'Donnell, Peter H; Sternberg, Cora N; Rosenberg, Jonathan E; Bellmunt, Joaquim

2013-04-01

Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n=570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n=352). Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic=0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Predictors of survival of natural killer/T-cell lymphoma, nasal type, in a non-Asian population: a single cancer centre experience

PubMed Central

Vásquez, Jule; Serrano, Mariana; Lopez, Lourdes; Pacheco, Cristian; Quintana, Shirley

2016-01-01

Background Natural killer/T-cell lymphoma (NKTCL), part of T-cell and NK-cell neoplasms in the World Health Organisation (WHO) classification, is an aggressive lymphoma with poor prognosis more predominantly seen in Asian and South American countries. This study evaluates the factors associated with survival among patients with newly diagnosed NKTCL in Peru. Methods Information was abstracted from medical records (MR) for all NKTCL patients >13 years of age at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2002 and 2011. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. Results Around 226 MR were reviewed, 153 met the selection criteria, the median age was 40 years (14–84). The median progression-free survival (PFS) was 20 months, five year PFS was 42.6%, univariable analysis (UA) showed statistical significance (p < 0.05) for male sex, non-nasal primary site, advanced clinical stages, B symptoms, poor performance status, regional nodal involvement (RNI). In the multivariate analysis the only poor prognostic factors was primary non-nasal (Hazard ratio (HR) = 2.40, 95% confidence interval (CI) = 1.43– 4.02, P = 0.01). The median overall survival (OS) was 49 months, five year OS was 48.9%, UA showed statistical significance for non-nasal primary site, advanced clinical stages, B symptoms, lactate dehydrogenase (LDH) > normal, RNI and local tumour invasion. In the multivariate analysis, primary non-nasal was the only poor prognostic factor with HR = 2.57, 95% CI = 1.37–4.83, P = 0.03. Conclusions In Peru, OS of NKTCL is similar to other countries. This result suggests that non-nasal NKTCL is the only poor prognostic factor of OS and PFS. PMID:27994644

Similar Survival With Breast Conservation Therapy or Mastectomy in the Management of Young Women With Early-Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahmood, Usama, E-mail: usama.mahmood@gmail.com; Morris, Christopher; Neuner, Geoffrey

2012-08-01

Purpose: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. Results: A total of 14,764 women weremore » identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5-, 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). Conclusions: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival.« less

Hematopoietic lineage cell-specific protein 1 immunoreactivity indicates an increased risk of poor overall survival in patients with ovarian carcinoma.

PubMed

Liu, Wenting; Kajiyama, Hiroaki; Shibata, Kiyosumi; Koya, Yoshihiro; Senga, Takeshi; Kikkawa, Fumitaka

2018-06-01

Hematopoietic lineage cell-specific protein 1 (HS1) is a 75-kDa intracellular protein that is expressed primarily in hematopoietic cells. Several previous studies have demonstrated the association between HS1 expression and a poor prognosis in hematopoietic malignancies; however, in solid tumors, no studies not been reported. The present study examined the distribution and expression of HS1 in human epithelial ovarian carcinoma (EOC) to determine its clinical significance. Paraffin sections were obtained from EOC tissues and immunostained with HS1 antibody, and then the staining intensities were evaluated. Overall survival (OS) was determined using the Kaplan-Meier estimator method, and multivariate analysis was performed using the Cox proportional hazards analysis. In total, 195 patients with EOC (median age, 56 years) were enrolled into the present study. HS1 immunoreactivity was categorized based on expression levels: Low (89/195; 45.6%) and high (106/195; 54.4%). Results demonstrated no association between expression level(s) and any clinicopathological parameter including age, International Federation of Gynecology and Obstetrics (FIGO) staging, type of chemotherapy or type of surgery received. The 5-year OS rates of patients who demonstrated low (n=89) and high (n=106) HS1 expression were 90.4 and 66.7%, respectively. The OS times for patients with high HS1 expression were significantly shorter compared with those for patients exhibiting low HS1 expression (P=0.0065). Results obtained from the multivariate analysis demonstrated that the FIGO stage and the amount of HS1 expressed were significant independent prognostic markers for poorer OS (hazard ratio, 3.539; 95% confidence interval, 1.221-12.811; P=0.0187). High HS1 expression levels may serve as a useful biomarker in patients with EOC who are likely to exhibit an unfavorable clinical outcome.

Prognostic significance of interventricular septal thickness in patients with AL amyloidosis.

PubMed

Cho, Hyunsoo; Kim, Soo-Jeong; Shim, Chi Young; Hong, Geu-Ru; Ha, Jong-Won; Kim, Yu Ri; Yang, Woo Ick; Chung, Haerim; Jang, Ji Eun; Cheong, June-Won; Min, Yoo Hong; Kim, Jin Seok

2017-09-01

The major prognostic determinant of immunoglobulin light chain (AL) amyloidosis is cardiac involvement. However, the role of interventricular septal thickness (IVST), which reflects the extent of cardiac involvement, remains unclear. Therefore, we analyzed 77 patients with newly diagnosed AL amyloidosis and evaluated the prognostic role of IVST. Fifty patients (64.9%) had cardiac involvement and 17 patients (22.1%) showed IVST >15mm. Among all patients, the revised Mayo Clinic Stage III-IV and IVST >15mm were independently associated with inferior overall survival (OS) in a multivariable analysis. IVST >15mm was also adversely prognostic for OS in a subgroup of advanced-stage (revised Mayo Clinic stage III-IV) patients in a multivariable analysis (P<0.001). Furthermore, advanced-stage patients with IVST >15mm did not show survival benefit from treatment with bortezomib-based regimens and/or autologous stem-cell transplantation (ASCT). Our study demonstrated that IVST >15mm is adversely prognostic independent of the revised Mayo Clinic staging system in patients with AL amyloidosis. In addition, the degree of IVST might be used as a useful prognostic indicator that can guide the management of patients with AL amyloidosis especially at an advanced stage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Favorable versus unfavorable prognostic groups by post-chemoradiation FDG-PET imaging in node-positive esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PubMed

Yap, Wing-Keen; Chang, Yu-Chuan; Hsieh, Chia-Hsun; Chao, Yin-Kai; Chen, Chien-Cheng; Shih, Ming-Chieh; Hung, Tsung-Min

2018-05-01

Our purpose was to examine the prognostic value of post-CRT PET based on the presence or absence of FDG-avid metastatic lymph node(s) and metabolic response of the primary tumor in patients with clinically node-positive ESCC treated with definitive chemoradiotherapy (dCRT). We identified 108 eligible patients treated by chemoradiotherapy (CRT) with or without resection from our prospectively collected database. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after initial CRT was defined as the Post-CRT PET favorable group (yPET-F), and otherwise as unfavorable group (yPET-U). The Kaplan-Meier method and Cox regression were performed for survival analyses and multivariable analysis, respectively. The study cohort was comprised of 59 patients receiving dCRT. Forty-five patients receiving trimodality therapy (TMT) comprised the comparative group and four patients were excluded from further analyses for developing interval distant metastasis detected on post-CRT PET scan. The median follow-up for the study cohort was 41 months. On K-M analysis of the study cohort, yPET-F was found to have significantly better OS (2-year: 72.5% vs 13.7%, p < 0.01) and DMFS (2-year: 71.6% vs 36.6%, p = 0.01) than yPET-U. In multivariable analysis, yPET-F remained as a strong independent favorable prognosticator on both OS (HR 0.08, p < 0.01) and DMFS (HR 0.14, p = 0.02) for the dCRT cohort. Compared with TMT cohort, for yPET-U patients, TMT had better OS (p = 0.03) than dCRT-Operable and dCRT-Operable had superior OS (p = 0.04) than dCRT-Unresectable. For yPET-F patients, there was no difference in both OS (p > 0.99) and DMFS (p = 0.92) between these three groups. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after CRT (i.e., yPET-F status) prognosticate for excellent OS and DMFS in cN+ ESCC patients treated with dCRT, and might be comparable to TMT.

Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia.

PubMed

Hansson, Lotta; Asklid, Anna; Diels, Joris; Eketorp-Sylvan, Sandra; Repits, Johanna; Søltoft, Frans; Jäger, Ulrich; Österborg, Anders

2017-10-01

This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial. A multivariate Cox proportional hazards regression model was used which estimated the hazard ratio (HR) of ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus the previous standard-of-care cohort was 0.15 (p < 0.0001) for progression-free survival (PFS) and 0.36 (p < 0.0001) for overall survival (OS). A similar difference was observed also when patients treated late in the period (2012-) were compared separately. Multivariate analysis showed that later line of therapy, male gender, older age and poor performance status were significant independent risk factors for worse PFS and OS. Our results suggest that PFS and OS with ibrutinib in the RESONATE study were significantly longer than with previous standard-of-care regimens used in second or later lines in routine healthcare. The approach used, which must be interpreted with caution, compares patient-level data from a clinical trial with outcomes observed in a daily clinical practice and may complement results from randomised trials or provide preliminary wider comparative information until phase 3 data exist.

Prognostic Relevance of the Peritoneal Surface Disease Severity Score Compared to the Peritoneal Cancer Index for Colorectal Peritoneal Carcinomatosis

PubMed Central

Ng, Jia Lin; Ong, Whee Sze; Chia, Claramae Shulyn; Tan, Grace Hwei Ching; Soo, Khee-Chee; Teo, Melissa Ching Ching

2016-01-01

Background. Peritoneal Carcinomatosis Index (PCI) is a widely established scoring system that describes disease burden in isolated colorectal peritoneal carcinomatosis (CPC). Its significance may be diminished with complete cytoreduction. We explore the utility of the recently described Peritoneal Surface Disease Severity Score (PSDSS) and compare its prognostic value against PCI. Methods. The endpoints were overall survival (OS), progression-free survival (PFS), and survival less than 18 months (18 MS). Results. Fifty patients underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for CPC from 2003 to 2014, with 98% achieving complete cytoreduction. Median OS was 28.8 months (95% CI, 18.0–39.1); median PFS was 9.4 months (95% CI, 7.7–13.9). Univariate analysis showed that higher PCI was significantly associated with poorer OS (HR 1.11; 95% CI, 1.03–1.20) and PFS (HR 1.09; 95% CI, 1.03–1.14). Conversely, PSDSS was not associated with either endpoint. Multivariate analysis showed that PCI, but not PSDSS, was predictive of OS and PFS. PCI was also able to discriminate survival outcomes better than PSDSS for both OS and PFS. There was no association between 18 MS and either score. Conclusion. PCI is superior to PSDSS in predicting OS and PFS and remains the prognostic score of choice in CPC patients undergoing CRS/HIPEC. PMID:27006828

PD-L1 expression as poor prognostic factor in patients with non-squamous non-small cell lung cancer.

PubMed

Zhou, Cuiling; Tang, Jianjun; Sun, Huanhuan; Zheng, Xiaobin; Li, Zhanyu; Sun, Tiantian; Li, Jie; Wang, Shuncong; Zhou, Xiuling; Sun, Hongliu; Cheng, Zhibin; Zhang, Hongyu; Ma, Haiqing

2017-08-29

The role of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), especially according to histologic type, remains controversial. The purpose of this study was to assess PD-L1 expression and its association with overall survival (OS) and clinicopathologic characteristics in NSCLC. Formalin-fixed paraffin-embedded specimens were obtained from 108 patients with surgically resected primary NSCLC. PD-L1 expression was assessed via immunohistochemistry using a histochemistry score system. The relationship between OS or clinicopathologic characteristics and PD-L1 expression was evaluated via the Kaplan-Meier method and Cox proportional hazards model, respectively. Of 108 NSCLC specimens, 44 had high PD-L1 expression, which was highly associated with histologic type ( p = 0.003). Patients without PD-L1 expression had remarkably longer OS than those with PD-L1 expression (median OS: 96 months vs. 33 months, p < 0.001). In the subgroup analysis of non-squamous cell carcinoma, OS was more favorable in those without PD-L1 expression than in those with PD-L1 expression (median OS: 113 months vs. 37 months, p < 0.001). Multivariate analysis revealed that PD-L1 expression (95% confidence interval 1.459-4.520, p < 0.001), male sex and higher tumor-node-metastasis stage were significantly correlated with shorter OS. This study demonstrated that PD-L1 expression is an independent prognostic factor for poor survival in NSCLC patients, especially those with non-squamous NSCLC.

Heterogeneity of Glucose Metabolism in Esophageal Cancer Measured by Fractal Analysis of Fluorodeoxyglucose Positron Emission Tomography Image: Correlation between Metabolic Heterogeneity and Survival.

PubMed

Tochigi, Toru; Shuto, Kiyohiko; Kono, Tsuguaki; Ohira, Gaku; Tohma, Takayuki; Gunji, Hisashi; Hayano, Koichi; Narushima, Kazuo; Fujishiro, Takeshi; Hanaoka, Toshiharu; Akutsu, Yasunori; Okazumi, Shinichi; Matsubara, Hisahiro

2017-01-01

Intratumoral heterogeneity is a well-recognized characteristic feature of cancer. The purpose of this study is to assess the heterogeneity of the intratumoral glucose metabolism using fractal analysis, and evaluate its prognostic value in patients with esophageal squamous cell carcinoma (ESCC). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies of 79 patients who received curative surgery were evaluated. FDG-PET images were analyzed using fractal analysis software, where differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor lesion. Maximum standardized uptake value (SUVmax) and FD were compared with overall survival (OS). The median SUVmax and FD of ESCCs in this cohort were 13.8 and 1.95, respectively. In univariate analysis performed using Cox's proportional hazard model, T stage and FD showed significant associations with OS (p = 0.04, p < 0.0001, respectively), while SUVmax did not (p = 0.1). In Kaplan-Meier analysis, the low FD tumor (<1.95) showed a significant association with favorable OS (p < 0.0001). In wthe multivariate analysis among TNM staging, serum tumor markers, FD, and SUVmax, the FD was identified as the only independent prognostic factor for OS (p = 0.0006; hazards ratio 0.251, 95% CI 0.104-0.562). Metabolic heterogeneity measured by fractal analysis can be a novel imaging biomarker for survival in patients with ESCC. © 2016 S. Karger AG, Basel.

[Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

PubMed

Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

2016-09-01

Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.

2006-10-01

Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis includedmore » lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.« less

Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging.

PubMed

Coburger, Jan; Wirtz, Christian R; König, Ralph W

2017-06-01

In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un-methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications.

Primary site and regional lymph node involvement are independent prognostic factors for early-stage extranodal nasal-type natural killer/T cell lymphoma.

PubMed

Niu, Shao-Qing; Yang, Yong; Li, Yi-Yang; Wen, Ge; Wang, Liang; Li, Zhi-Ming; Wang, Han-Yu; Zhang, Lu-Lu; Xia, Yun-Fei; Zhang, Yu-Jing

2016-04-04

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL. To develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index) and calibration curve. The 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010). The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysis showed that age >60 years, ECOG performance status score ≥2, elevated lactate dehydrogenase (LDH) level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year OS rate; age >60 years, elevated LDH level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year PFS rate. The nomogram included the primary site and regional lymph node involvement based on multivariate analysis. The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates, and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634, respectively. The primary site and regional lymph node involvement are independent prognostic factors for early-stage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

Oncologic outcomes following robot-assisted radical cystectomy with minimum 5-year follow-up: the Roswell Park cancer institute experience.

PubMed

Raza, Syed Johar; Al-Daghmin, Ali; Zhuo, Sharon; Mehboob, Zayn; Wang, Katy; Wilding, Gregory; Kauffman, Eric; Guru, Khurshid A

2014-11-01

Long-term oncologic outcomes following robot-assisted radical cystectomy (RARC) remain scarce. To report long-term oncologic outcomes following RARC at a single institution. Retrospective review of 99 patients who underwent RARC for urothelial carcinoma of bladder between 2005 and 2009. RARC was performed. Primary outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS), measured by the Kaplan-Meier method. The association between primary outcomes and perioperative and pathologic factors was assessed using a multivariable Cox proportional hazards model. Fifty-one (52%) patients had stage pT3 or higher disease. Eight (8%) patients had positive margins and 30 (30%) had positive lymph nodes (LNs), with a median of 21 LNs removed. Median follow-up for patients alive was 74 mo. The 5-yr RFS, CSS, and OS rates were 52.5%, 67.8%, and 42.4%, respectively. Tumor stage, LN stage, and margin status were each significantly associated with RFS, CSS, and OS. On multivariable analysis, tumor and LN stage were independent predictors of RFS, CSS, and OS, while positive margin status and Charlson comorbidity index predicted worse OS and CSS. Adjuvant chemotherapy predicted RFS only. Retrospective design and lack of open comparison are main limitations of this study. Long-term oncologic outcomes following RARC demonstrate RFS and CSS estimates similar to those reported in literature for open radical cystectomy. Randomized controlled trials can better define outcomes of any alternative technique. Survival data 5 yr after RARC for bladder cancer demonstrate that survival outcomes are dependent on the same oncologic parameters as previously reported for open surgery. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Does autologous blood transfusion during liver transplantation for hepatocellular carcinoma increase risk of recurrence?

PubMed Central

Araujo, Raphael LC; Pantanali, Carlos Andrés; Haddad, Luciana; Rocha Filho, Joel Avancini; D’Albuquerque, Luiz Augusto Carneiro; Andraus, Wellington

2016-01-01

AIM: To analyze outcomes in patients who underwent liver transplantation (LT) for hepatocellular carcinoma (HCC) and received autologous intraoperative blood salvage (IBS). METHODS: Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fisher’s exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death, and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Between 2002 and 2012, 158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients, 122 (77.2%) were in the IBS group and 36 (22.8%) in the non-IBS group. The overall survival (OS) and recurrence free survival (RFS) at 5 years were 59.7% and 83.3%, respectively. No differences in OS (P = 0.51) or RFS (P = 0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS, degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS, no differences were detected in OS or RFS (P = 0.055 and P = 0.512, respectively) according to the volume infused, even when outcomes at 90 d or longer were analyzed separately (P = 0.518 for both outcomes). CONCLUSION: No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes. PMID:26981190

Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

PubMed Central

Wu, San-Gang; Wang, Yan; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; He, Zhen-Yu

2015-01-01

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer. PMID:25973321

Academic Facility Utilization and Survival Outcomes in Adult Head and Neck Sarcomas: An NCDB Analysis.

PubMed

Cannon, Richard B; Carpenter, Patrick S; Boothe, Dustin; Buchmann, Luke O; Hunt, Jason P; Lloyd, Shane; Hitchcock, Ying J; Houlton, Jeffrey J; Weis, John R; Shepherd, Hailey M; Monroe, Marcus M

2018-04-01

Objectives To investigate clinicopathologic and treatment factors associated with survival in adult head and neck sarcomas in the National Cancer Database (NCDB). To analyze whether treatment settings and therapies received influence survival outcomes and to compare trends in utilization via an aggregated national data set. Study Design Prospectively gathered data. Setting NCDB. Subjects and Methods The study comprised a total of 6944 adult patients treated for a head and neck sarcoma from January 2004 to December 2013. Overall survival (OS) was the primary outcome. Results Increased age and tumor size, nodal involvement, and poorly differentiated histology had significantly reduced OS ( P < .001). Angiosarcoma, malignant nerve sheath tumor, malignant fibrous histiocytoma, osteosarcoma, and rhabdomyosarcoma histologic subtypes had significantly reduced OS, while liposarcoma, chondrosarcoma, and chordoma had improved OS ( P < .001). Utilization of surgical therapy was associated with improved OS, while positive surgical margins were associated with treatment at a community-based cancer program and had reduced OS ( P < .001). On multivariate analysis, treatment with radiation and/or chemotherapy was not significantly associated with OS; however, primary treatment with definitive chemoradiotherapy had significantly reduced OS. Patients treated at academic/research cancer programs (n = 3874) had significantly improved 5- and 10-year OS (65% and 54%, respectively) when compared with patients treated at community-based cancer programs (n = 3027; 49% and 29%; P < .001). The percentage utilization of these programs (56% vs 44%) did not change over the study period. Conclusion For adult head and neck sarcomas, treatment at an academic/research cancer program was associated with improved survival; however, despite increasing medical specialization, the percentage utilization of these programs for this rare tumor remains constant.

Incidence and long-term survival of patients with de novo head and neck carcinoma after liver transplantation.

PubMed

Coordes, Annekatrin; Albers, Andreas E; Lenarz, Minoo; Seehofer, Daniel; Puhl, Gero; Pascher, Andreas; Neuhaus, Ruth; Neuhaus, Peter; Pratschke, Johann; Andreou, Andreas

2016-05-01

Liver transplant recipients have an increased risk of developing de novo malignancies. We conducted a prospective evaluation of clinicopathological data and predictors for overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) after liver transplantation (1988 to 2010). Thirty-three of 2040 patients who underwent liver transplantation (1.6%) developed de novo HNSCC. The incidence of HNSCC in liver transplant recipients with end-stage alcoholic liver disease (26) was 5%. After a median follow-up of 9 years, 1-year, 3-year, and 5-year OS rates were 74%, 47%, and 34%, respectively. Tumor size, cervical lymph node metastases, tumor site, and therapy (surgery only vs surgery and adjuvant radiotherapy [RT]/chemoradiotherapy [CRT] vs RT/CRT only; p < .0001) were significantly associated with OS in univariate analysis. However, surgery only predicted OS independently in multivariate analysis. Early diagnosis and surgical treatment of de novo HNSCC are crucial to the outcome. HNSCC risk should be taken into close consideration during posttransplantation follow-up examinations, especially among patients with a positive history of smoking and alcohol consumption. © 2015 Wiley Periodicals, Inc.

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma

PubMed Central

Nerich, Virginie; Hugues, Marion; Paillard, Marie Justine; Borowski, Laëtitia; Nai, Thierry; Stein, Ulrich; Nguyen Tan Hon, Thierry; Montcuquet, Philippe; Maurina, Tristan; Mouillet, Guillaume; Kleinclauss, François; Pivot, Xavier; Limat, Samuel; Thiery-Vuillemin, Antoine

2014-01-01

Introduction The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. Patients and methods All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. Results For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13–22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22–0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31–0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22–0.82], P=0.002). Median OS was 21 months [14–29 months] for patients who received at least one targeted therapy compared with 12 months [7–15 months] for patients who were treated only by immunotherapy agents (P=0.003). Conclusion Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications. PMID:24600236

Observation versus adjuvant radiation or chemotherapy in the management of stage I seminoma: clinical outcomes and prognostic factors for relapse in a large US cohort.

PubMed

Soper, Margaret S; Hastings, Joseph R; Cosmatos, Harry A; Slezak, Jeffrey M; Wang, Ricardo; Lodin, Kenneth

2014-08-01

The management of stage I seminoma has evolved over the past 20 years. Contemporary management options after orchiectomy include adjuvant radiation, adjuvant chemotherapy, and observation. This analysis defines the experience at Kaiser Permanente Southern California from 1990 to 2010. We examined outcomes for stage I seminoma patients and reviewed prognostic factors for recurrence in those managed with observation. This is a retrospective study of 502 stage I seminoma patients who underwent orchiectomy from 1990 to 2010. Outcomes examined were relapse-free survival (RFS), overall survival (OS), and cause-specific survival (CSS). Risk factors for recurrence evaluated were age, preoperative hCG elevation, preoperative LDH elevation, tumor size, lymphovascular invasion, rete testis invasion, epididymis invasion, and invasion through the tunica albuginea. Among radiation patients, 5-year RFS was 97.2%, OS was 98.0%, and CSS was 99.3%. Among chemotherapy patients, 2-year RFS was 98.3% and OS and CSS were 100%. Among observation patients, 5-year RFS was 89.2%, OS was 98.8%, and CSS was 100%. There was no difference in OS or CSS among the groups. RFS was significantly lower for observation patients. Among observation patients, univariate analysis identified tumor size, lymphovascular invasion, and rete testis invasion as risk factors for relapse. No factors were significant on multivariate analysis. Our data show that adjuvant radiation and chemotherapy yield similar outcomes in the management of stage I seminoma. Observation results in a lower RFS, but patients who relapse can be salvaged; OS and CSS are not affected.

Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

PubMed Central

Ren, Yong; Yao, Yu; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhou, Liang-Fu; Zhong, Ping

2014-01-01

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. PMID:24932704

Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity.

PubMed

Hoffmann, M; Saleh-Ebrahimi, L; Zwicker, F; Haering, P; Schwahofer, A; Debus, J; Huber, P E; Roeder, F

2015-12-04

To report our long-term results with postoperative intensity-modulated radiation therapy (IMRT) in patients suffering from squamous-cell carcinoma (SCC) of the oral cavity or oropharynx. Seventy five patients were retrospectively analyzed. Median age was 58 years and 84 % were male. 76 % of the primaries were located in the oropharynx. Surgery resulted in negative margins (R0) in 64 % of the patients while 36 % suffered from positive margins (R1). Postoperative stages were as follows: stage 1:4 %, stage 2:9 %, stage 3:17 %, stage 4a:69 % with positive nodes in 84 %. Perineural invasion (Pn+) and extracapsular extension (ECE) were present in 7 % and 29 %, respectively. All patients received IMRT using the step-and-shoot approach with a simultaneously integrated boost (SIB) in 84 %. Concurrent systemic therapy was applied to 53 patients, mainly cisplatin weekly. Median follow-up was 55 months (5-150). 13 patients showed locoregional failures (4 isolated local, 4 isolated neck, 5 combined) transferring into 5-year-LRC rates of 85 %. Number of positive lymph nodes (n > 2) and presence of ECE were significantly associated with decreased LRC in univariate analysis, but only the number of nodes remained significant in multivariate analysis. Overall treatment failures occurred in 20 patients (9 locoregional only, 7 distant only, 4 combined), transferring into 3-and 5-year-FFTF rates of 77 % and 75 %, respectively. The 3-and 5-year-OS rates were 80 % and 72 %, respectively. High clinical stage, high N stage, number of positive nodes (n > 2), ECE and Pn1 were significantly associated with worse FFTF and OS in univariate analysis, but only number of nodes remained significant for FFTF in multivariate analysis. Maximum acute toxicity was grade 3 in 64 % and grade 4 in 1 %, mainly hematological or mucositis/dysphagia. Maximum late toxicity was grade 3 in 23 % of the patients, mainly long-term tube feeding dependency. Postoperative IMRT achieved excellent LRC and good OS with acceptable acute and low late toxicity rates. The number of positive nodes (n > 2) was a strong prognostic factor for all endpoints in univariate and the only significant factor for LRC and FFTF in multivariate analysis. Patients with feeding tubes due to postoperative complications had an increased risk for long-term feeding tube dependency.

Impact of involved field radiotherapy in partial response after doxorubicin-based chemotherapy for advanced aggressive non-Hodgkin's lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moser, Elizabeth C.; Kluin-Nelemans, Hanneke C.; Carde, Patrice

2006-11-15

Purpose: Whether salvage therapy in patients with advanced aggressive non-Hodgkin's lymphoma (NHL) in partial remission (PR) should consist of radiotherapy or autologous stem-cell transplantation (ASCT) is debatable. We evaluated the impact of radiotherapy on outcome in PR patients treated in four successive European Organization for Research and Treatment of Cancer trials for aggressive NHL. Patients and Methods: Records of 974 patients (1980-1999) were reviewed regarding initial response, final outcome, and type and timing of salvage treatment. After 8 cycles of doxorubicin-based chemotherapy, 227 NHL patients were in PR and treated: 114 received involved field radiotherapy, 16 ASCT, 93 second-line chemotherapy,more » and 4 were operated. Overall survival (OS) and progression-free survival (PFS) after radiotherapy were estimated (Kaplan-Meier method) and compared with other treatments (log-rank). Impact on survival was evaluated by multivariate analysis (Cox proportional hazards model). Results: The median PFS in PR patients was 4.2 years and 48% remained progression-free at 5 years. Half of the PR patients converted to a complete remission. After conversion, survival was comparable to patients directly in complete remission. Radiotherapy resulted in better OS and PFS compared with other treatments, especially in patients with low to intermediate International Prognostic Index score, bulky disease, or nodal disease only. Correction by multivariate analysis for prognostic factors such as stage, bulky disease, and number of extranodal locations showed that radiotherapy was clearly the most significant factor affecting both OS and PFS. Conclusion: This retrospective analysis demonstrates that radiotherapy can be effective for patients in PR after fully dosed chemotherapy; assessment in a randomized trial (radiotherapy vs. ASCT) is justified.« less

Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

PubMed

Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

2015-07-10

Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001). The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

PubMed

Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Survival outcomes of radical prostatectomy and external beam radiotherapy in clinically localized high-risk prostate cancer: a population-based, propensity score matched study

PubMed Central

Gu, Xiaobin; Gao, Xianshu; Cui, Ming; Xie, Mu; Ma, Mingwei; Qin, Shangbin; Li, Xiaoying; Qi, Xin; Bai, Yun; Wang, Dian

2018-01-01

Objective This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7 months for RP and EBRT groups, respectively (P<0.001). The subgroup analyses showed that CSS of the RP group was better than that of the EBRT group for patients aged <65 years (P<0.001), White race (P<0.001), and married status (P<0.001). However, there was no significant difference in CSS for patients aged ≥65 years, Black race, other race, and unmarried status. Similar trends were observed for OS. Multivariate analysis showed that EBRT treatment modality, T3–T4 stage, Gleason score 8–10, and prostate-specific antigen >20 ng/mL were significant risk factors for both CSS and OS. Conclusion This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged <65 years; however, RP and EBRT provided equivalent survival outcomes in older patients, which argues for primary radiotherapy in this older cohort.

Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

PubMed

Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

2018-04-23

Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

Chondrosarcoma of the Osseous Spine: An Analysis of Epidemiology, Patient Outcomes, and Prognostic Factors Using the SEER Registry From 1973 to 2012.

PubMed

Arshi, Armin; Sharim, Justin; Park, Don Y; Park, Howard Y; Bernthal, Nicholas M; Yazdanshenas, Hamed; Shamie, Arya N

2017-05-01

Retrospective analysis. To determine the epidemiology and prognostic indicators in patients with chondrosarcoma of the osseous spine. Chondrosarcoma of the spine is rare, with limited data on its epidemiology, clinicopathologic features, and treatment outcomes. Therapy centers on complete en bloc resection with radiotherapy reserved for subtotal resection or advanced disease. The Surveillance, Epidemiology, and End Results Registry was queried for patients with chondrosarcoma of the osseous spine from 1973 to 2012. Study variables included age, sex, race, year of diagnosis, size, grade, extent of disease, and treatment modality. The search identified 973 cases of spinal chondrosarcoma. Mean age at diagnosis was 51.6 years, and 627% of patients were males. Surgical resection and radiotherapy were performed in 75.2% and 21.3% of cases, respectively. Kaplan-Meier analysis demonstrated overall survival (OS) and disease-specific survival (DSS) of 53% and 64%, respectively, at 5 years. Multivariate Cox regression analysis showed that age (OS, P < 0.001; DSS, P = 0.007), grade (OS, P < 0.001; DSS, P < 0.001), surgical resection (OS, P < 0.001; DSS, P < 0.001), and extent of disease (OS, P < 0.001; DSS, P < 0.001) were independent survival determinants; tumor size was an independent predictor of OS (P = 0.006). For confined disease, age (P = 0.013), decade of diagnosis (P = 0.023), and surgery (P = 0.017) were independent determinants of OS. For locally invasive disease, grade (OS, P < 0.001; DSS, P = 0.003), surgery (OS, P = 0.013; DSS, P = 0.046), and size (OS, P = 0.001, DSS, P = 0.002) were independent determinants of OS and DSS. Radiotherapy was an independent indicator of worse OS for both confined (P = 0.004) and locally invasive disease (P = 0.002). For metastatic disease, grade (OS, P = 0.021; DSS, P = 0.012) and surgery (OS, P = 0.007; DSS, P = 0.004) were survival determinants for both OS and DSS, whereas radiotherapy predicted improved OS (P = 0.039). Surgical resection confers survival benefit in patients with chondrosarcoma of the spine independent of extent of disease. Radiotherapy improves survival in patients with metastatic disease and worsens outcomes in patients with confined and locally invasive disease. 4.

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

PubMed

Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

2018-01-02

Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p < 0.001) and OS (p < 0.001). The 3-year OS for patients with ICPS =0, ICPS =1, ICPS =2 and ICPS =3 were 95.6, 88.2, 76.0 and 62.2%, respectively (p < 0.001). The 3-year PFS for patients with ICPS = 0-1, ICPS = 2 and ICPS = 3 were 84.8, 71.6 and 54.5%, respectively (p < 0.001). The prognostic value of the ICPS model indicated that the degree of systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases.

PubMed

Wang, Jane; Margonis, Georgios Antonios; Amini, Neda; Andreatos, Nikolaos; Yuan, Chunhui; Damaskos, Christos; Antoniou, Efstathios; Garmpis, Nikolaos; Buettner, Stefan; Barbon, Carlotta; Deshwar, Amar; He, Jin; Burkhart, Richard; Pawlik, Timothy M; Wolfgang, Christopher L; Weiss, Matthew J

2018-04-09

Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.

Meta-analysis of prognostic value of inflammation parameter in breast cancer.

PubMed

Chen, Jie; Pan, Yuqin; He, Bangshun; Ying, Houqun; Sun, Huiling; Deng, Qiwen; Liu, Xian; Wang, Shukui

2018-01-01

Recently, increasing studies investigated the association between inflammation parameter such as neutrophil to lymphocyte ratio (NLR) and the prognosis of cancers. However, the clinical and prognostic significance of NLR in breast cancer remains controversial. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted using PubMed and Web of Science. Six studies dating up to July 2014 with 2267 patients were enrolled in the present study. STATA 11.0 software (STATA Corporation, College Station, TX, USA) was selected for data analysis. In order to evaluate the association between NLR and overall survival (OS), disease-free survival (DFS), recurrence-free survival or cancer-specific survival, the hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Subgroup analyses showed that NLR was a strong prognostic factor for OS in multivariate analysis (HR = 2.81, 95% CI = 2.13-3.71, P H = 0.992) and without metastasis (HR = 1.45, 95% CI = 0.37-5.66, P H < 0.001). Elevated NLR was associated with a high risk for DFS in subgroups of multivariate analysis (HR = 2.16, 95% CI = 1.67-2.80, P H = 0.977) and mixed metastasis (HR = 2.13, 95% CI = 1.38-3.30, P H = 0.84). In summary, NLR may be considered as a predictive factor for patients with breast cancer.

Primary Squamous Cell Carcinoma of the Thyroid: A Population-Based Analysis.

PubMed

Au, Joshua K; Alonso, Jose; Kuan, Edward C; Arshi, Armin; St John, Maie A

2017-07-01

Objectives To analyze the epidemiology and describe the prognostic indicators of patients with primary squamous cell carcinoma of the thyroid. Study Design and Setting Retrospective cohort study based on a national database. Methods The US National Cancer Institute's SEER registry (Surveillance, Epidemiology, and End Results) was reviewed for patients with primary squamous cell carcinoma of the thyroid from 1973 to 2012. Study variables included age, sex, race, tumor size, tumor grade, regional and distant metastases, and treatment modality. Survival measures included overall survival (OS) and disease-specific survival (DSS). Results A total of 199 cases of primary squamous cell carcinoma of the thyroid were identified. Mean age at diagnosis was 68.1 years; 58.3% were female; and 79.4% were white. Following diagnosis, 46.3% of patients underwent surgery; 55.7%, radiation therapy; and 45.8%, surgery with radiation therapy. Kaplan-Meier analysis demonstrated OS and DSS of 16% and 21% at 5 years, respectively. Median survival after diagnosis was 9.1 months. Multivariate Cox regression analysis showed that predictors of OS and DSS included age ( P < .001, P < .001, respectively), tumor grade ( P < .001, P = .001), and tumor size ( P < .001, P = .001). Surgical management was a predictor of OS but not DSS. Conclusion Squamous cell carcinoma of the thyroid is a rare malignancy with a very poor prognosis. Surgical resection confers an overall survival benefit. Age, tumor grade, and tumor size are predictors of OS and DSS.

Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, T. Jonathan; Oh, Jung Hun; Folkert, Michael R.

2014-11-01

Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system wasmore » used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.« less

Phenotype of osteosarcopenia in older individuals with a history of falling.

PubMed

Huo, Ya Ruth; Suriyaarachchi, Pushpa; Gomez, Fernando; Curcio, Carmen L; Boersma, Derek; Muir, Susan W; Montero-Odasso, Manuel; Gunawardene, Piumali; Demontiero, Oddom; Duque, Gustavo

2015-04-01

In older persons, the combination of osteopenia/osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of institutionalization, falls, and fractures. However, the particular clinical, biochemical, and functional characteristics of the osteosarcopenic (OS) patients remain unknown. In this study, we used a clinical definition of osteosarcopenia aiming to determine the clinical, functional, and biochemical features that are unique to these patients within a population of older people who fall. Cross-sectional study. Falls and Fractures Clinic, Nepean Hospital (Penrith, NSW, Australia). A total of 680 people (mean age = 79, 65% women) assessed between 2009 and 2013. Assessment included medical history, physical examination, bone densitometry and body composition by dual-energy X-ray absorptiometry, posturography, grip strength, gait parameters (GaitRITE), and blood tests for nutrition and secondary causes of sarcopenia and osteoporosis. Patients were divided into 4 groups: (1) osteopenic (BMD <-1.0 SD), (2) sarcopenic, (3) OS, and (4) nonsarcopenic/nonosteopenic. Difference between groups was assessed with 1-way ANOVA and χ(2) analysis. Multivariable linear regression evaluated the association between the groups and measures of physical function. Multivariable logistic regression evaluated risk factors for being in the OS group. Mean age of the OS patients was 80.4 ± 7.0 years. Our analyses showed that OS patients are older, mostly women, are at high risk for depression and malnutrition, have body mass index lower than 25, and showed a higher prevalence of peptic disease, inflammatory arthritis, maternal hip fracture, history of atraumatic fracture, and impaired mobility. We have reported a set of characteristics that are highly prevalent in OS patients. This study could be used to inform the design of future trials and to develop interventions to prevent institutionalization and poor outcomes in this particular set of high-risk patients. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louie, Alexander V., E-mail: Dr.alexlouie@gmail.com; Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario; Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts

Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogrammore » for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.« less

Metformin Use and Endometrial Cancer Survival

PubMed Central

Nevadunsky, Nicole S.; Van Arsdale, Anne; Strickler, Howard D.; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L.; Einstein, Mark H.

2013-01-01

Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. PMID:24189334

Predictors and Patterns of Local, Regional, and Distant Failure in Squamous Cell Carcinoma of the Vulva.

PubMed

Bogani, Giorgio; Cromi, Antonella; Serati, Maurizio; Uccella, Stefano; Donato, Violante Di; Casarin, Jvan; Naro, Edoardo Di; Ghezzi, Fabio

2017-06-01

To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

Metformin use and endometrial cancer survival.

PubMed

Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L; Einstein, Mark H

2014-01-01

Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio=0.54, 95% CI: 0.30-0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. © 2013. Published by Elsevier Inc. All rights reserved.

Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas

PubMed Central

Kai, Keita; Komukai, Sho; Koga, Hiroki; Yamaji, Koutaro; Ide, Takao; Kawaguchi, Atsushi; Aishima, Shinichi; Noshiro, Hirokazu

2018-01-01

AIM To investigate the association between smoking habits and surgical outcomes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients. METHODS We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups’ clinicopathological features and surgical outcomes, i.e., disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients. RESULTS The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS (P = 0.0039) and DSS (P = 0.0416). In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS, or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status. CONCLUSION A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes. PMID:29358882

Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas.

PubMed

Kai, Keita; Komukai, Sho; Koga, Hiroki; Yamaji, Koutaro; Ide, Takao; Kawaguchi, Atsushi; Aishima, Shinichi; Noshiro, Hirokazu

2018-01-07

To investigate the association between smoking habits and surgical outcomes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients. We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups' clinicopathological features and surgical outcomes, i.e ., disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients. The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS ( P = 0.0039) and DSS ( P = 0.0416). In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS, or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status. A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes.

PD-L1 expression as poor prognostic factor in patients with non-squamous non-small cell lung cancer

PubMed Central

Zheng, Xiaobin; Li, Zhanyu; Sun, Tiantian; Li, Jie; Wang, Shuncong; Zhou, Xiuling; Sun, Hongliu; Cheng, Zhibin; Zhang, Hongyu; Ma, Haiqing

2017-01-01

Objectives The role of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), especially according to histologic type, remains controversial. The purpose of this study was to assess PD-L1 expression and its association with overall survival (OS) and clinicopathologic characteristics in NSCLC. Materials and methods Formalin-fixed paraffin-embedded specimens were obtained from 108 patients with surgically resected primary NSCLC. PD-L1 expression was assessed via immunohistochemistry using a histochemistry score system. The relationship between OS or clinicopathologic characteristics and PD-L1 expression was evaluated via the Kaplan-Meier method and Cox proportional hazards model, respectively. Results Of 108 NSCLC specimens, 44 had high PD-L1 expression, which was highly associated with histologic type (p = 0.003). Patients without PD-L1 expression had remarkably longer OS than those with PD-L1 expression (median OS: 96 months vs. 33 months, p < 0.001). In the subgroup analysis of non-squamous cell carcinoma, OS was more favorable in those without PD-L1 expression than in those with PD-L1 expression (median OS: 113 months vs. 37 months, p < 0.001). Multivariate analysis revealed that PD-L1 expression (95% confidence interval 1.459-4.520, p < 0.001), male sex and higher tumor-node-metastasis stage were significantly correlated with shorter OS. Conclusions This study demonstrated that PD-L1 expression is an independent prognostic factor for poor survival in NSCLC patients, especially those with non-squamous NSCLC. PMID:28938570

Patterns of Care for Locally Advanced Pancreatic Adenocarcinoma Using the National Cancer Database.

PubMed

Amini, Arya; Jones, Bernard L; Stumpf, Priscilla; Leong, Stephen; Lieu, Christopher H; Weekes, Colin; Davis, S Lindsey; Messersmith, Wells A; Purcell, William T; Ghosh, Debashis; Schefter, Tracey; Goodman, Karyn A

2017-08-01

The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT). The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT. Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT declined from 2003 to 2011 (73%-53%), whereas chemotherapy alone increased. Of those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased (27%-72%), whereas 3-dimensional (3D) RT decreased (73%-28%). Unadjusted 1-year overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was 2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85-0.91; P < 0.001). Under multivariate analysis, C + RT was associated with improved OS (hazard ratio, 0.84; 0.81-0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT, and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was 13.1%, 11.6%, and 11.9% accordingly. Utilization of RT in LAPC is decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT, rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with improved OS compared with chemotherapy alone, 3D RT was not.

Leukocytosis and neutrophilia predict outcome in locally advanced esophageal cancer treated with definitive chemoradiation

PubMed Central

Schernberg, Antoine; Moureau-Zabotto, Laurence; Del Campo, Eleonor Rivin; Escande, Alexandre; Ducreux, Michel; Nguyen, France; Goere, Diane; Chargari, Cyrus; Deutsch, Eric

2017-01-01

Purpose To investigate the prognostic value of leukocyte and neutrophil count as biomarkers in patients with locally advanced esophageal squamous cell carcinoma (SCC) undergoing exclusive chemoradiation. Results A total of 126 patients were identified. Respectively, 33% and 35% displayed baseline leukocytosis and neutrophilia. Estimated 3-year OS and PFS from chemoradiation completion were 31% and 25%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS, and LRC (p < 0.01). In multivariate analysis, leukocytosis remained an independent risk factor associated with poorer OS, PFS and LRC (p < 0.05), independently from tumor stage and length, with higher prognostic value for OS compared with patients’ performance status (PS). Materials and Methods Bi-institutional clinical records from consecutive non-operable patients treated between 2003 and 2015 with definitive chemoradiation for locally advanced esophageal carcinoma were reviewed. Leukocytosis and neutrophilia were defined as a leukocyte or neutrophil count over 10 G/L and 7 G/L, respectively. These parameters were studied for their potential correlation with overall survival (OS), progression free survival (PFS), locoregional control (LRC) and distant metastases control (DMC). Conclusions Leukocytosis and neutrophilia were independent prognostic factors of poor OS, PFS, and LRC in this bi-institutional series of locally advanced esophageal SCC treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters might be clinically relevant biomarkers to be considered for further clinical investigations. PMID:28086222

Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

PubMed

Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

2017-04-01

The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma.

PubMed

Cho, Hyunsoo; Kim, Se Hoon; Kim, Soo-Jeong; Chang, Jong Hee; Yang, Woo Ick; Suh, Chang-Ok; Cheong, June-Won; Kim, Yu Ri; Lee, Jung Yeon; Jang, Ji Eun; Kim, Yundeok; Min, Yoo Hong; Kim, Jin Seok

2017-07-01

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

PubMed

Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

2016-01-15

The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Pre-treatment inflammatory indexes as predictors of survival and cetuximab efficacy in metastatic colorectal cancer patients with wild-type RAS.

PubMed

Yang, Jing; Guo, Xinli; Wang, Manni; Ma, Xuelei; Ye, Xiaoyang; Lin, Panpan

2017-12-07

This study aims at evaluating the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) in metastatic colorectal cancer (mCRC) patients treated with cetuximab. Ninety-five patients receiving cetuximab for mCRC were categorized into the high or low NLR, PLR, LMR, and SII groups based on their median index values. Univariate and multivariate survival analysis were performed to identify the indexes' correlation with progression-free survival (PFS) and overall survival (OS). In the univariate analysis, ECOG performance status, neutrphil counts, lymphocyte counts, monocyte counts, NLR, PLR, and LDH were associated with survival. Multivariate analysis showed that ECOG performance status of 0 (hazard ratio [HR] 3.608, p < 0.001; HR 5.030, p < 0.001, respectively), high absolute neutrophil counts (HR 2.837, p < 0.001; HR 1.922, p = 0.026, respectively), low lymphocyte counts (HR 0.352, p < 0.001; HR 0.440, p = 0.001, respectively), elevated NLR (HR 3.837, p < 0.001; HR 2.467, p = 0.006) were independent predictors of shorter PFS and OS. In conclusion, pre-treatment inflammatory indexes, especially NLR were potential biomarkers to predict the survival of mCRC patients with cetuximab therapy.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

PubMed

Fridman, Eran; Na'ara, Shorook; Agarwal, Jaiprakash; Amit, Moran; Bachar, Gideon; Villaret, Andrea Bolzoni; Brandao, Jose; Cernea, Claudio R; Chaturvedi, Pankaj; Clark, Jonathan; Ebrahimi, Ardalan; Fliss, Dan M; Jonnalagadda, Sashikanth; Kohler, Hugo F; Kowalski, Luiz P; Kreppel, Matthias; Liao, Chun-Ta; Patel, Snehal G; Patel, Raj P; Robbins, K Thomas; Shah, Jatin P; Shpitzer, Thomas; Yen, Tzu-Chen; Zöller, Joachim E; Gil, Ziv

2018-05-14

Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrelli, Fausto, E-mail: faupe@libero.it; Comito, Tiziana; Ghidini, Antonio

Purpose: Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. Methods and Materials: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regardingmore » SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. Results: A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. Conclusions: The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.« less

What is the role of impression management in adolescent cigarette smoking?

PubMed

O'Callaghan, F; Doyle, J

2001-01-01

This study examined the role of impression management in cigarette smoking by linking the constructs of self-monitoring, perceived success in impression management, self-esteem and social anxiety among nonsmokers (NS), occasional smokers (OS), and frequent smokers (FS). High school students (N=243) in years 8-12 completed a questionnaire assessing the above-mentioned variables. Multivariate discriminant function analysis and a priori contrasts were used to analyze the data. In comparison to OS, FS and NS had the lowest levels of self-monitoring, perceived success in impression management and self-esteem, while having the highest levels of social anxiety. Cigarette use may serve an impression management function during adolescence and subsequently influences OS' level of smoking. Intervention programs need to give greater consideration to providing adolescents with alternative strategies for both social acceptance and the acquisition and maintenance of self-esteem.

Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: A Review of the National Cancer Data Base

PubMed Central

Robinson, Cliff G.; Patel, Aalok P.; Bradley, Jeffrey D.; DeWees, Todd; Waqar, Saiama N.; Morgensztern, Daniel; Baggstrom, Maria Q.; Govindan, Ramaswamy; Bell, Jennifer M.; Guthrie, Tracey J.; Colditz, Graham A.; Crabtree, Traves D.; Kreisel, Daniel; Krupnick, Alexander S.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

2015-01-01

Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. PMID:25667283

Merkel Cell Carcinoma: A Population Analysis on Survival.

PubMed

Sridharan, Vishwajith; Muralidhar, Vinayak; Margalit, Danielle N; Tishler, Roy B; DeCaprio, James A; Thakuria, Manisha; Rabinowits, Guilherme; Schoenfeld, Jonathan D

2016-10-01

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy. However, factors associated with disease presentation and outcomes remain uncertain, especially in light of recent changes in workup, such as sentinel lymph node biopsy. Therefore, this study used the SEER database to examine factors that could affect stage at presentation and treatment. We identified 4,543 patients and evaluated associations between sex, race, age, primary disease site, disease presentation, and treatment. We also used univariate and multivariate analyses to examine the effect of these factors on disease-specific survival (DSS) and overall survival (OS). We specifically conducted subgroup analyses on a more modern cohort of patients with MCC treated between 2006 and 2012. Male sex, older age, larger tumor size, and primary tumors of the scalp, neck, or trunk were associated with a higher burden of nodal disease. Multivariate predictors of worse DSS/OS in both the recent and overall cohort included age older than 75 years, number of lymph nodes involved, tumors greater than 5 cm, metastatic disease, or lack of radiation therapy. The number of involved nodes was the best predictor of DSS/OS. Associations with radiation therapy were most pronounced in patients with nodal disease and those not undergoing surgery. Sex, age, tumor size, and primary site of disease correlated with burden of nodal disease in MCC. Associations between disease presentation and treatment strategies such as radiation and DSS and OS have remained relatively constant in the modern era from 2006 to 2012 compared with findings from prior studies. Copyright © 2016 by the National Comprehensive Cancer Network.

Positive Impact of Epidural Analgesia on Oncologic Outcomes in Patients Undergoing Resection of Colorectal Liver Metastases.

PubMed

Zimmitti, Giuseppe; Soliz, Jose; Aloia, Thomas A; Gottumukkala, Vijaya; Cata, Juan P; Tzeng, Ching-Wei D; Vauthey, Jean-Nicolas

2016-03-01

Previous studies have suggested that the use of regional anesthesia can reduce recurrence risk after oncologic surgery. The purpose of this study was to assess the effect of epidural anesthesia on recurrence-free (RFS) and overall survival (OS) after hepatic resection for colorectal liver metastases (CLM). After approval of the institutional review board, the records of all adult patients who underwent elective hepatic resection between January 2006 and October 2011 were retrospectively reviewed. Patients were categorized according to use of perioperative epidural analgesia versus intravenous analgesia. Univariate and multivariate analyses were performed to identify factors influencing RFS and OS. Of 510 total patients, 390 received epidural analgesia (EA group) and 120 patients received intravenous analgesia (IVA group). Compared with the IVA group, more patients in the EA group underwent associated surgical procedures with consequently longer operative times (p < 0.001). In addition, the EA group received more intraoperative fluids and had higher urine output volumes (p ≤ 0.001). Five-year RFS was longer in the EA group (34.7%) compared with the IVA group (21.1%). On multivariate analysis, the receipt of epidural analgesia was an independent predictor of improved RFS (p = 0.036, hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.56-0.95), but not OS (p = 0.102, HR 0.72; 95% CI 0.49-1.07). This study suggests an association between epidural analgesia and improved RFS, but not OS, after CLM resection. These results warrant further prospective, randomized studies on the benefits of regional anesthesia on oncologic outcomes after hepatic resection for CLM.

Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study.

PubMed

Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Bouadballah, R; Radford, J; Bargetzi, M; Ribrag, V; Dührsen, U; Ma, D; Briere, J; Thieblemont, C; Bachy, E; Moskowitz, C H; Glass, B; Gisselbrecht, C

2017-02-01

In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.

Leukocytosis and neutrophilia predicts outcome in anal cancer.

PubMed

Schernberg, Antoine; Escande, Alexandre; Rivin Del Campo, Eleonor; Ducreux, Michel; Nguyen, France; Goere, Diane; Chargari, Cyrus; Deutsch, Eric

2017-01-01

Leukocytosis and neutrophilia could be the tip of the iceberg in the inflammatory tumor microenvironment. We aimed to validate their prognostic significance in a cohort of patients treated with definitive chemoradiation for anal squamous cell carcinoma (SCC). Clinical records from all consecutive patients treated in a single institution between 2006 and 2016 with curative-intent radiotherapy were retrospectively analyzed. Leukocytosis and neutrophilia, defined as leukocyte or neutrophil count over 10,000 and 7500/mm 3 , respectively, were studied in terms of overall survival (OS), progression (PFS), locoregional (LFS) and distant (DFS)-free survival. We identified 103 non-metastatic HIV-negative patients, with concurrent chemotherapy use in 78%. Twelve and 8% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year OS and PFS were 88% and 67%, respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with inferior OS, PFS, LFS and DFS (p<0.01). In multivariate analysis, leukocytosis and neutrophilia remained strongly associated with patient outcome (p<0.01), independently from tumor T and N-stage. Anemia was an independent predictor of worse OS and PFS, while chemoradiation overall treatment time below 50days improved PFS. Leukocytosis and neutrophilia are strong prognostic factors for OS, PFS, LFS and DFS in anal cancer treated with chemoradiation. These biomarkers could help identify patients with higher risk of tumor relapse that require treatment intensification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Recommendation for incorporation of a different lymph node scoring system in future AJCC N category for oral cancer.

PubMed

Lee, Ching-Chih; Su, Yu-Chieh; Hung, Shih-Kai; Chen, Po-Chun; Huang, Chung-I; Huang, Wei-Lun; Lin, Yu-Wei; Yang, Ching-Chieh

2017-10-26

To compare the prognostic value of 3 different lymph node scoring systems " log odds of positive nodes (LODDS), lymph node ratio (rN), and lymph node yield " in an effort to improve the staging of oral cancer. We identified 3958 oral cancer patients from Surveillance, Epidemiology, and End Results database from 2007 to 2013. In univariate analysis, LODDS, pN, rN, and lymph node yield were prognostic factors for 5-year disease-specific survival (DSS) and overall survival (OS). Multivariate analysis indicated that patients with LODDS 4 had worst 5-year DSS and OS. Stage migration occurred in pN1 and pN2 patients with LODDS 4. In pN1 patients, those with LODDS 4 had the worst 5-year DSS (41.2%) and OS (31.6%) than patients with pN1 and LODDS 2-3. In pN2 patients, those with LODDS4 had the worst 5-year DSS (34.5%) and OS (27.4%) than patients with pN2 and LODDS 2-3. The proposed staging system, which incorporates LODDS with AJCC pN, had better discriminability and prediction accuracy for predicting survival. We also noted that patients with LODDS 4 given adjuvant radiotherapy had better 5-year DSS and OS. The LODDS should be considered as a future candidate measurement for N category in oral cancer.

Medullary Thyroid Carcinoma in MEN2A: ATA Moderate- or High-Risk RET Mutations Do Not Predict Disease Aggressiveness.

PubMed

Voss, Rachel K; Feng, Lei; Lee, Jeffrey E; Perrier, Nancy D; Graham, Paul H; Hyde, Samuel M; Nieves-Munoz, Frances; Cabanillas, Maria E; Waguespack, Steven G; Cote, Gilbert J; Gagel, Robert F; Grubbs, Elizabeth G

2017-08-01

High-risk RET mutations (codon 634) are associated with earlier development of medullary thyroid carcinoma (MTC) and presumed increased aggressiveness compared with moderate-risk RET mutations. To determine whether high-risk RET mutations are more aggressive. Retrospective cohort study using institutional multiple endocrine neoplasia type 2 registry. Tertiary cancer care center. Patients with MTC and moderate- or high-risk germline RET mutation. None (observational study). Proxies for aggressiveness were overall survival (OS) and time to distant metastatic disease (DMD). A total of 127 moderate-risk and 135 high-risk patients were included (n = 262). Median age at diagnosis was 42.3 years (range, 6.4 to 86.4 years; mean, 41.6 years) for moderate-risk mutations and 23.0 years (range, 3.7 to 66.8 years; mean, 25.6 years) for high-risk mutations (P < 0.0001). Moderate-risk patients had more T3/T4 tumors at diagnosis (P = 0.03), but there was no significant difference for N or M stage and no significant difference in OS (P = 0.40). From multivariable analysis for OS, increasing age [hazard ratio (HR), 1.05/y; 95% confidence interval (CI), 1.03 to 1.08], T3/T4 tumor (HR, 2.73; 95% CI, 1.22 to 6.11), and M1 status at diagnosis (HR, 3.93; 95% CI, 1.61 to 9.59) were significantly associated with worse OS but high-risk mutation was not (P = 0.40). No significant difference was observed for development of DMD (P = 0.33). From multivariable analysis for DMD, only N1 status at diagnosis was significant (HR, 2.10; 95% CI, 1.03 to 4.27). Patients with high- and moderate-risk RET mutations had similar OS and development of DMD after MTC diagnosis and therefore similarly aggressive clinical courses. High-risk connotes increased disease aggressiveness; thus, future guidelines should consider RET mutation classification by disease onset (early vs late) rather than by risk (high vs moderate). Copyright © 2017 Endocrine Society

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base.

PubMed

Haque, Waqar; Verma, Vivek; Butler, E Brian; Teh, Bin S

2018-02-01

Neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal cancer (EC) may utilize a wide variety of RT doses, without clear consensus to date. This study evaluated national practice patterns between lower dose (LD) (40-41.4 Gy) or higher dose (HD) (50-50.4 Gy) therapy, in addition to differences in survival and postoperative events. The National Cancer Data Base (NCDB) was queried [2004-2013] for patients with newly-diagnosed cT1a-T4aN0/N+M0 EC that received neoadjuvant CRT followed by esophagectomy. Multivariable logistic regression determined factors predictive of receiving LD RT. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. Altogether, 5,025 patients met inclusion criteria; 257 (5%) received LD RT, while 4,768 (95%) received HD RT. LD RT was more likely delivered at academic centers (P=0.038), in more recent years (2009-2013, P=0.011), and to squamous cell carcinomas (P=0.001). HD RT tended to be administered with higher T stage as well as node-positive disease (P<0.05). The median OS in the LD and HD cohorts was 39.0 vs. 35.6 months (P=0.072), and 39.0 vs. 42.7 months after propensity matching (P=0.812). Dose did not independently correlate with OS on multivariate analysis (P=0.069), but treatment at academic centers correlated with improved OS (P=0.028). There were no differences between groups in the rates of 30-day readmission (P=0.182), 30-day mortality (P=0.314), or length of postoperative hospital stay (P=0.665), but the LD group experienced lower 90-day mortality (P=0.007). Although neoadjuvant LD CRT has been underutilized for EC in the United States, it is rising in more recent years. Dose did not significantly impact survival before or after propensity matching, nor did it independently predict for survival. Treatment at academic facilities independently correlated with higher survival, which has implications for patient counseling.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

PubMed

Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

2016-01-01

Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P < 0.001) and positively with health utility (HR 0.56, P < 0.001) and hopefulness (HR 0.75, P = 0.013). In multivariable analysis, OS was also associated negatively with depression (HR 1.72, P < 0.001) and positively with health utility (HR 0.73, P = 0.014), but not with optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tao, Randa; Allen, Pamela K.; Rodriguez, Alma

Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate andmore » multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.« less

Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study.

PubMed

Robak, Tadeusz; Huang, Huiqiang; Jin, Jie; Zhu, Jun; Liu, Ting; Samoilova, Olga; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Osmanov, Evgenii; Pereira, Juliana; Mayer, Jiri; Hong, Xiaonan; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; van de Velde, Helgi; Cavalli, Franco

2017-06-05

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m 2 /cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m 2 /cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

Repeated Radiofrequency Ablation Combined With Ablated Lesion Elimination and Transarterial Chemoembolization Improves the Outcome of Solitary Huge Hepatocellular Carcinomas 10 cm or Larger

PubMed Central

Ke, Shan; Gao, Jun; Kong, Jian; Ding, Xue-Mei; Niu, Hai-Gang; Xin, Zong-Hai; Ning, Chun-Min; Guo, Shi-Gang; Li, Xiao-Long; Zhang, Long; Dong, Yong-Hong; Sun, Wen-Bing

2016-01-01

Abstract This study investigated the effectiveness of a new strategy, repeated radiofrequency (RF) ablation combined with ablated lesion elimination following transarterial chemoembolization (TACE)/transarterial embolization (TAE), for solitary huge hepatocellular carcinoma (SHHCC) 10 cm or larger. From July 2008 to October 2015, 39 consecutive patients with SHHCC were screened. Of these, 12 were treated with TACE/TAE and repeated RF ablation (TACE/TAE + RF ablation group) and the remaining 27 patients were treated with the aforementioned new strategy (new strategy group). Local tumor progression (LTP)-free survival, intrahepatic distant recurrence (IDR)-free survival, and overall survival (OS) rates were obtained using the Kaplan–Meier method. Univariate and multivariate analyses were performed on several clinicopathological variables to identify factors affecting long-term outcome and intrahepatic recurrence. Correlation analysis was also performed. The 1-, 2-, and 3-year LTP-free survival rates and OS rates were significantly higher in the new strategy group than in the TACE/TAE + RF ablation group (82.9% vs 58.3%, 73.9% vs 29.2%, 18.5% vs 9.7%, P = 0.002; 92.0% vs 75.0%, 84.0% vs 33.3%, 32.7% vs 16.7%, P = 0.025). However, there was no significant difference between the 2 groups in the 1-, 2-, and 3-year IDR-free survival rates (P = 0.108). Using univariate analysis, alpha-fetoprotein (AFP > 200 ng/mL), ablative margin (AM > 1.0 cm), and well-differentiated cells were found to be significant factors for predicting LTP, IDR, and OS. Surgical elimination was found to be a significant factor only for predicting OS. In multivariate analyses, AFP (>200 ng/mL), AM (>1.0 cm), and well-differentiated cells were found to be significant independent factors linked to LTP, IDR, and OS. Correlation analysis indicated that AM > 1.0 cm was strongly associated with surgical elimination (P < 0.001, correlation coefficient = 0.877). For patients with SHHCC who were initially excluded from surgery, the new strategy including repeated RF ablation combined with ablated lesion elimination following TACE/TAE should now be considered as an alternative treatment. PMID:27100425

Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.

PubMed

Taylor, Fiona G M; Quirke, Philip; Heald, Richard J; Moran, Brendan J; Blomqvist, Lennart; Swift, Ian R; Sebag-Montefiore, David; Tekkis, Paris; Brown, Gina

2014-01-01

The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

Survival Effect of Neoadjuvant Radiotherapy Before Esophagectomy for Patients With Esophageal Cancer: A Surveillance, Epidemiology, and End-Results Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwer, Amanda L.; Ballonoff, Ari; McCammon, Robert

2009-02-01

Purpose: The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. Methods and Materials: The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed withmore » NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. {<=}10), histologic type (adenocarcinoma vs. squamous cell carcinoma), age (<65 vs. {>=}65 years), and gender as covariates. Results: A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. Conclusion: These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.« less

Prognostic factors in patients with hepatitis B virus-related hepatocellular carcinoma undergoing nucleoside analog antiviral therapy

PubMed Central

NISHIKAWA, HIROKI; NISHIJIMA, NORIHIRO; ARIMOTO, AKIRA; INUZUKA, TADASHI; KITA, RYUICHI; KIMURA, TORU; OSAKI, YUKIO

2013-01-01

In the present era of entecavir (ETV) use for chronic hepatitis B (CHB), the prognostic factors in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. The aims of the present study were to investigate the prognostic factors in patients with HBV-related HCC treated with ETV who underwent curative therapy. A total of 74 HBV-related HCC patients treated with ETV who underwent curative therapy were analyzed. Predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) were examined using univariate and multivariate analysis. Our study population included 49 males and 25 females with a median age of 62 years. The median observation period was 3.4 years (range, 0.2–11.5 years). The 1-, 3- and 5-year cumulative OS rates were 100, 89.8 and 89.8%, respectively. The corresponding RFS rates were 82.8, 52.1 and 25.6%, respectively. In this study, 73 patients (98.6%) achieved an HBV DNA level of <400 copies/ml during the follow-up period. No viral breakthrough hepatitis, as defined by 1 log increase from nadir, was observed during ETV therapy. According to multivariate analysis, only hepatitis B e antigen (HBeAg) positivity was significantly associated with OS [hazard ratio (HR), 0.058; 95% confidence interval (CI), 0.005–0.645; P=0.020)], whereas HCC stage (HR, 0.359; 95% CI, 0.150–0.859; P=0.021), HBeAg positivity (HR, 0.202; 95% CI, 0.088–0.463; P<0.001) and γ-glutamyl transpeptidase ≥50 IU/l (HR, 0.340; 95% CI, 0.152–0.760; P=0.009) were significant predictive factors linked to RFS. In conclusion, HBeAg positivity was significantly associated with OS and RFS in HBV-related HCC patients treated with ETV who underwent curative therapy. In such patients, close observation is required, even after curative therapy for HCC. PMID:24179497

Percutaneous Lung Thermal Ablation of Non-surgical Clinical N0 Non-small Cell Lung Cancer: Results of Eight Years’ Experience in 87 Patients from Two Centers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palussiere, Jean, E-mail: J.Palussiere@bordeaux.unicancer.fr; Lagarde, Philippe, E-mail: P.Lagarde@bordeaux.unicancer.fr; Aupérin, Anne, E-mail: auperin@igr.fr

2015-02-15

PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % atmore » 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.« less

The Prognostic Significance of Sentinel Lymph Node Status for Patients with Thick Melanoma.

PubMed

Bello, Danielle M; Han, Gang; Jackson, Laura; Bulloch, Kaleigh; Ariyan, Stephan; Narayan, Deepak; Rothberg, Bonnie Gould; Han, Dale

2016-12-01

Sentinel lymph node biopsy (SLNB) is recommended for patients with intermediate-thickness melanoma, but the use of SLNB for patients with thick melanoma is debated. This report presents a single-institution study investigating factors predictive of sentinel lymph node (SLN) metastasis and outcome for thick-melanoma patients . A retrospective review of a single-institution database from 1997 to 2012 identified 147 patients with thick primary cutaneous melanoma (≥4 mm) who had an SLNB. Clinicopathologic characteristics were correlated with nodal status and outcome. The median age of the patients was 67 years, and 61.9 % of the patients were men. The median tumor thickness was 5.5 mm, and 54 patients (36.7 %) had a positive SLN. Multivariable analysis showed that only tumor thickness significantly predicted SLN metastasis (odds ratio 1.14; 95 % confidence interval (CI) 1.02-1.28; P = 0.02). The overall median follow-up period was 34.6 months. Overall survival (OS) and melanoma-specific survival (MSS) were significantly worse for the positive versus negative-SLN patients. Multivariable analysis showed that age [hazard ratio (HR) 1.04; 95 % CI 1.01-1.07; P = 0.02] and SLN status (HR 2.24; 95 % CI 1.03-4.88; P = 0.04) significantly predicted OS, whereas only SLN status (HR 3.85; 95 % CI 2.13-6.97; P < 0.01) significantly predicted MSS. Tumor thickness predicts SLN status in thick melanomas. Furthermore, SLN status is prognostic for OS and MSS in thick-melanoma patients, with positive-SLN patients having significantly worse OS and MSS. These findings show that SLNB should be recommended for thick-melanoma patients, particularly because detection of SLN metastasis can identify patients for potential systemic therapy and treatment of nodal disease at a microscopic stage.

Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

PubMed

Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

2013-01-01

This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P < 0.04). In metastatic disease, multivariate analysis found VB, K(1), and k(3) to be significant variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic factors for OS in the entire group of patients that were significant at multivariate analysis were stage of disease, VB, K(1), and (18)F-FDG INF (P < 0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients with a high (18)F-FDG INF, low VB, and high K(1) was 3 mo, as opposed to 14 mo in patients with a low (18)F-FDG INF, high VB, and low K(1) (P < 0.021), irrespective of stage and resectability. Quantitative (18)F-FDG kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy.

PubMed

Langsenlehner, Tanja; Pichler, Martin; Thurner, Eva-Maria; Krenn-Pilko, Sabine; Stojakovic, Tatjana; Gerger, Armin; Langsenlehner, Uwe

2015-05-01

Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study. Data from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease-free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates. Using receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease-free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). Our findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Felix Y., E-mail: ffeng@med.umich.edu; Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan; Blas, Kevin

2013-05-01

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64more » months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.« less

Prognostic impact of C-reactive protein/albumin ratio on the overall survival of patients with advanced nonsmall cell lung cancers receiving palliative chemotherapy

PubMed Central

Koh, Young W.; Lee, Hyun W.

2017-01-01

Abstract Recent studies have indicated that the C-reactive protein (CRP)/albumin (CRP/Alb) ratio is associated with clinical outcomes in patients with various carcinomas. However, no studies have explored the association between the ratio of CRP/Alb and clinical outcome of inoperable patients with nonsmall cell lung cancers (NSCLCs). We examined the prognostic impact of CRP/Alb ratio on 165 stage IV NSCLC receiving palliative chemotherapy. The optimal cutoff level of CRP/Alb ratio was set at 0.195. The median follow-up time was 9 months (range, 1–74 months). On univariate analysis, high CRP/Alb ratio (≥0.195) was correlated (P < .001) with poorer overall survival (OS). Subgroup analysis of adenocarcinoma showed that CRP/Alb ratio was significantly (P < .001) associated with OS. Multivariate analysis showed that CRP/Alb ratio was an independent prognostic factor for OS (hazard ratio: 2.227, P = .001). Subgroup analysis revealed that the CRP/Alb ratio had a significant (P = .001) prognostic impact on adenocarcinoma patients receiving platinum chemotherapy. Elevated CRP/Alb ratio was significantly associated with male gender (P = .002) and smoking history (P = .009). The results of this study suggest that the CRP/Alb ratio might be used as a simple, inexpensive, and independent prognostic factor for OS of patients with advanced lung adenocarcinomas receiving platinum chemotherapy. PMID:28489774

Comparative composition, diversity, and abundance of oligosaccharides in early lactation milk from commercial dairy and beef cows

PubMed Central

Sischo, William M.; Short, Diana M.; Geissler, Mareen; Bunyatratchata, Apichaya; Barile, Daniela

2017-01-01

Prebiotics are nondigestible dietary ingredients, usually oligosaccharides (OS), that provide a health benefit to the host by directly modulating the gut microbiota. Although there is some information describing OS content in dairy-source milk, no information is available to describe the OS content of beef-source milk. Given the different trait emphasis between dairy and beef for milk production and calf survivability, it is plausible that OS composition, diversity, and abundance differ between production types. The goal of this study was to compare OS in milk from commercial dairy and beef cows in early lactation. Early-lactation multiparous cows (5–12 d in milk) from 5 commercial Holstein dairy herds and 5 Angus or Angus hybrid beef herds were sampled once. Milk was obtained from each enrolled cow and frozen on the farm. Subsequently, each milk sample was assessed for total solids, pH, and OS content and relative abundance. Oligosaccharide diversity and abundance within and between samples was transformed through principal component analysis to reduce data complexity. Factors from principal component analysis were used to create similarity clusters, which were subsequently used in a multivariate logistic regression. In total, 30 OS were identified in early-lactation cow milk, including 21 distinct OS and 9 isomers with unique retention times. The majority of OS detected in the milk samples were present in all individual samples regardless of production type. Two clusters described distribution patterns of OS for the study sample; when median OS abundance was compared between the 2 clusters, we found that overall OS relative abundance was consistently greater in the cluster dominated by beef cows. For several of the structures, including those with known prebiotic effect, the difference in abundance was 2- to 4-fold greater in the beef-dominated cluster. Assuming that beef OS content in milk is the gold standard for cattle, it is likely that preweaning dairy calves are deprived of dietary-source OS. Although supplementing rations with OS is an approach to rectify this deficiency, understanding the health and productivity effects of improving OS abundance being fed to preweaning calves is a necessary next step before recommending supplementation. These studies should account for the observation that OS products are variable for both OS diversity and structural complexity, and some products may not be suitable as prebiotics. PMID:28318588

Outcome of Patients With Therapy-Related Acute Myeloid Leukemia With or Without a History of Myelodysplasia.

PubMed

Sasaki, Koji; Jabbour, Elias; Cortes, Jorge; Kadia, Tapan; Garcia-Manero, Guillermo; Borthakur, Gautam; Jain, Preetesh; Pierce, Sherry; Daver, Naval; Takahashi, Koichi; O'Brien, Susan; Kantarjian, Hagop; Ravandi, Farhad

2016-11-01

To learn whether an antecedent hematologic disorder (AHD) is associated with additional risk in patients with therapy-related acute myeloid leukemia (t-AML). We reviewed data of 301 patients with newly diagnosed t-AML who sought care from January 2000 to January 2014 (183 t-AML without AHD, 118 t-AML with AHD). Overall, median follow-up was 44 months. The primary malignancy was non-Hodgkin lymphoma in 92 (31%), breast cancer in 80 (27%), and prostate cancer in 49 (16%). Median relapse-free survival (RFS) in t-AML without or with AHD was 10 months and 29 months, respectively (P = .032); median overall survival (OS) was 8 months and 8 months, respectively (P = .53). Multivariate analysis for OS identified older age, poor performance status, thrombocytopenia, nonfavorable cytogenetics, and lack of response as adverse factors. The favorable-risk cohort had better RFS and OS compared to the outcomes of patients in the intermediate- and adverse-risk cohorts; the RFS and OS did not differ between intermediate- and adverse-risk cohorts. The presence of AHD did not affect OS. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study.

PubMed

Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Milpied, N; Radford, J; Ketterer, N; Shpilberg, O; Dührsen, U; Ma, D; Brière, J; Thieblemont, C; Salles, G; Moskowitz, C H; Glass, B; Gisselbrecht, C

2016-01-01

Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.

Bone marrow T-cell percentage: A novel prognostic indicator in acute myeloid leukemia.

PubMed

Ismail, Manar M; Abdulateef, Nahla A B

2017-04-01

Acute myeloid leukemia (AML) is an aggressive malignancy for which overall disease-free survival is less than 50%. Manipulation of the immune system is an interesting and promising therapy for AML patients. We aimed to characterize the immune system of AML patients, highlighting the clinical relevance of total bone marrow (BM) lymphocytes and subpopulations. Sixty-six new AML cases diagnosed according to WHO criteria from King Abdullah Medical City, KSA, from October 2012 to February 2015. Analysis of BM lymphocytes and subpopulations was done by flowcytometry. Significantly, high percentages of BM lymphocytes, T cells, and natural killer (NK) cells were detected in the group that achieved complete remission (P values = 0.004, <0.001, and <0.001, respectively). Overall survival (OS) was significantly prolonged in patients with high BM lymphocytes and T cells (P values = 0.047 and P 0.002, respectively). Multivariate analysis indicated that BM T-cell percentage and cytogenetics were independent prognostic factors predictive of OS (HR 4.7, P value = 0.011). BM T-cell percentage constitutes a novel host factor that can be used in combination with cytogenetics to better predict OS. Large-scale multicenter studies are recommended to clarify its role as a predictor of OS and leukemia-free survival.

A new prognostic score for elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts is absent.

PubMed

Procházka, Vít; Pytlík, Robert; Janíková, Andrea; Belada, David; Sálek, David; Papajík, Tomáš; Campr, Vít; Fürst, Tomáš; Furstova, Jana; Trněný, Marek

2014-01-01

Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

Impact of marital status at diagnosis on survival and its change over time between 1973 and 2012 in patients with nasopharyngeal carcinoma: a propensity score-matched analysis.

PubMed

Xu, Cheng; Liu, Xu; Chen, Yu-Pei; Mao, Yan-Ping; Guo, Rui; Zhou, Guan-Qun; Tang, Ling-Long; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2017-12-01

The impact of marital status at diagnosis on survival outcomes and its change over time in patients with nasopharyngeal carcinoma (NPC) are unclear. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with NPC in the United States from 1973 to 2012. A primary comparison (married vs. unmarried) was implemented with 1:1 propensity score matching. Secondary comparisons were performed individually between three unmarried subgroups (single, separated/divorced, widowed) and married group. The effect of marital status on cause-specific survival (CSS) and overall survival (OS) were evaluated using univariate/multivariate analysis. Moreover, we investigated the change over time (1973-2012) in the effect of marital status on NPC survival. Married patients had better 5-year CSS/OS than unmarried patients (61.1% vs. 52.6%, P < 0.001; 55.6% vs. 45.3%, P < 0.001, respectively). In multivariate analysis, unmarried patients had significantly poorer CSS/OS than married patients (adjusted hazard ratio [aHR] = 1.35, P < 0.001; aHR = 1.40, P < 0.001, respectively). The survival benefit of being married was only detected in non-Hispanic white and Chinese American patients. Single, separated/divorced, and widowed patients had significantly poorer CSS/OS than married patients (aHR = 1.37 and 1.37; 1.46 and 1.42; 1.43 and 1.48, respectively; all P < 0.001). The change over time in the effect of marital status on survival was more stable in male than female. The strength of the negative effect of separated/divorced and widowed status showed a downward and upward trend, respectively. Gender difference in the adverse effect of single status on NPC survival became smaller over time. Only non-Hispanic white and Chinese American patients with NPC obtain survival benefits from married status. Single and widowed patients are regarded as high-risk population. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Bim may be a poor prognostic biomarker in breast cancer patients especially in those with luminal A tumors.

PubMed

Maimaiti, Yusufu; Dong, Lingling; Aili, Aikebaier; Maimaitiaili, Maimaitiaili; Huang, Tao; Abudureyimu, Kelimu

2017-07-04

Bcl-2 interacting mediator of cell death (Bim) appears to have contradictory roles in cancer. It is uncertain whether Bim show prognostic significance in patients with breast cancer. To investigate the correlation between Bim expression and clinicopathological characteristics of breast cancer and to evaluate Bim's effect on overall survival (OS). We used immunohistochemistry (IHC) technique to detect the expression of Bim via tissue microarray in 275 breast cancer samples, Kaplan-Meier analysis to perform survival analysis, and Cox proportional hazards regression model to explore the risk factors of breast cancer. The results revealed that Bim expression was significantly correlated with age, estrogen receptor (ER) and/or progesterone receptor (PR), human epidermal growth factor receptor (HER2) and Ki67 expression (P< 0.05). Bim expression was significantly different in the four molecular subtypes (P= 0.000). Survival analysis showed that Bim positive expression contributed to a shorter OS (P= 0.034), especially in patients with luminal A tumors (P= 0.039). Univariate and multivariate regression analysis showed that Bim was an independent prognostic factor for breast cancer (P< 0.05). Bim may serve as an effective predictive factor for lower OS in breast cancer patients, especially in those with luminal A tumors.

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brower, Jeffrey V.; Chen, Shuai; Bassetti, Michael F.

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received dosesmore » >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.« less

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012.

PubMed

Brower, Jeffrey V; Chen, Shuai; Bassetti, Michael F; Yu, Menggang; Harari, Paul M; Ritter, Mark A; Baschnagel, Andrew M

2016-12-01

To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Samir; Portelance, Lorraine; Gilbert, Lucy

2007-08-01

Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less

Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis.

PubMed

Zhang, Yunyuan; Zhou, Jun; Sun, Meiling; Sun, Guirong; Cao, Yongxian; Zhang, Haiping; Tian, Runhua; Zhou, Lan; Duan, Liang; Chen, Xian; Lun, Limin

2017-07-01

Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR = 2.23, 95 % CI: 1.56-3.17, P < 0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR = 2.08, 95 % CI: 1.33-3.27, P < 0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PubMed

Mannelli, Giuditta; Cecconi, Lorenzo; Fasolati, Martina; Santoro, Roberto; Franchi, Alessandro; Gallo, Oreste

Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival

PubMed Central

Ramjeesingh, R.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.

2016-01-01

Background Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. Methods After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan–Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. Results We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). Conclusions Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses. PMID:27122979

Intra- and interspecies gene expression models for predicting drug response in canine osteosarcoma.

PubMed

Fowles, Jared S; Brown, Kristen C; Hess, Ann M; Duval, Dawn L; Gustafson, Daniel L

2016-02-19

Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or interspecies manner to predict chemosensitivity and treatment outcome in canine OS. Models were built and evaluated using microarray gene expression and drug sensitivity data from human and canine cancer cell lines, and canine OS tumor datasets. The "COXEN" method was utilized to filter gene signatures between human and dog datasets based on strong co-expression patterns. Models were built using linear discriminant analysis via the misclassification penalized posterior algorithm. The best doxorubicin model involved genes identified in human lines that were co-expressed and trained on canine OS tumor data, which accurately predicted clinical outcome in 73 % of dogs (p = 0.0262, binomial). The best carboplatin model utilized canine lines for gene identification and model training, with canine OS tumor data for co-expression. Dogs whose treatment matched our predictions had significantly better clinical outcomes than those that didn't (p = 0.0006, Log Rank), and this predictor significantly associated with longer disease free intervals in a Cox multivariate analysis (hazard ratio = 0.3102, p = 0.0124). Our data show that intra- and interspecies gene expression models can successfully predict response in canine OS, which may improve outcome in dogs and serve as pre-clinical validation for similar methods in human cancer research.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stauder, Michael C., E-mail: mstauder@mdanderson.org; Caudle, Abigail S.; Allen, Pamela K.

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologicmore » stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.« less

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy: A Multicenter Experience.

PubMed

Ferro, Matteo; De Cobelli, Ottavio; Buonerba, Carlo; Di Lorenzo, Giuseppe; Capece, Marco; Bruzzese, Dario; Autorino, Riccardo; Bottero, Danilo; Cioffi, Antonio; Matei, Deliu Victor; Caraglia, Michele; Borghesi, Marco; De Berardinis, Ettore; Busetto, Gian Maria; Giovannone, Riccardo; Lucarelli, Giuseppe; Ditonno, Pasquale; Perdonà, Sisto; Bove, Pierluigi; Castaldo, Luigi; Hurle, Rodolfo; Musi, Gennaro; Brescia, Antonio; Olivieri, Michele; Cimmino, Amelia; Altieri, Vincenzo; Damiano, Rocco; Cantiello, Francesco; Serretta, Vincenzo; De Placido, Sabino; Mirone, Vincenzo; Sonpavde, Guru; Terracciano, Daniela

2015-10-01

Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients.A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3-60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%).In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31-1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86-3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS.In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients.

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy

PubMed Central

Ferro, Matteo; De Cobelli, Ottavio; Buonerba, Carlo; Di Lorenzo, Giuseppe; Capece, Marco; Bruzzese, Dario; Autorino, Riccardo; Bottero, Danilo; Cioffi, Antonio; Matei, Deliu Victor; Caraglia, Michele; Borghesi, Marco; De Berardinis, Ettore; Busetto, Gian Maria; Giovannone, Riccardo; Lucarelli, Giuseppe; Ditonno, Pasquale; Perdonà, Sisto; Bove, Pierluigi; Castaldo, Luigi; Hurle, Rodolfo; Musi, Gennaro; Brescia, Antonio; Olivieri, Michele; Cimmino, Amelia; Altieri, Vincenzo; Damiano, Rocco; Cantiello, Francesco; Serretta, Vincenzo; De Placido, Sabino; Mirone, Vincenzo; Sonpavde, Guru; Terracciano, Daniela

2015-01-01

Abstract Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients. A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3–60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%). In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31–1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86–3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS. In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients. PMID:26496339

RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer.

PubMed

Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy

2015-04-15

RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.

Chemotherapy Versus Chemoradiation for Node-Positive Bladder Cancer: Practice Patterns and Outcomes from the National Cancer Data Base

PubMed Central

Haque, Waqar; Verma, Vivek; Butler, E. Brian; Teh, Bin S.

2017-01-01

Background: Management of clinically node-positive bladder cancer (cN+ BC) is poorly defined; national guidelines recommend chemotherapy (CT) alone or chemoradiation (CRT). Objective: Using a large, contemporary dataset, we evaluated national practice patterns and outcomes of CT versus CRT to elucidate the optimal therapy for this patient population. Methods: The National Cancer Data Base (NCDB) was queried (2004–2013) for patients diagnosed with cTanyN1-3M0 BC. Patients were divided into two groups: CT alone or CRT. Statistics included multivariable logistic regression to determine factors predictive of receiving additional radiotherapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Propensity score matching was performed to assess groups in a balanced manner while reducing indication biases. Results: Of 1,783 total patients, 1,388 (77.8%) underwent CT alone, and 395 (22.2%) CRT. Although patients receiving CRT tended to be of higher socioeconomic status, they were more likely older (p = 0.053), higher T stage, N1 (versus N2) disease, squamous histology, and treated at a non-academic center (p < 0.05). Median overall survival (OS) was 19.0 months and 13.8 months (p < 0.001) for patients receiving CRT or CT, respectively. On Cox multivariate analysis, receipt of CRT was independently associated with improved survival (p < 0.001). Outcome improvements with CRT persisted on evaluation of propensity-matched populations (p < 0.001). Conclusions: CRT is underutilized in the United States for cN+ BC but is independently associated with improved survival despite being preferentially administered to a somewhat higher-risk population. PMID:29152552

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

PubMed

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Correlation of degree of hypothyroidism with survival outcomes in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.

PubMed

Bailey, Erin B; Tantravahi, Srinivas K; Poole, Austin; Agarwal, Archana M; Straubhar, Alli M; Batten, Julia A; Patel, Shiven B; Wells, Chesley E; Stenehjem, David D; Agarwal, Neeraj

2015-06-01

Hypothyroidism is a common adverse effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in patients with metastatic renal cell carcinoma (mRCC). Some studies have shown an association with improved survival. However, hypothyroidism severity has not been correlated with survival outcomes. We report the incidence and severity of VEGFR-TKI therapy-associated hypothyroidism in correlation with the survival outcomes of patients with mRCC. A retrospective analysis of patients with mRCC who received VEGFR-TKIs (2004 through 2013) was conducted from a single institutional database. Hypothyroidism, progression-free survival (PFS), and overall survival (OS) were assessed. Univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazard models. Of 125 patients with mRCC, 65 were eligible. Their median age was 59 years (range, 45-79 years), and 46 (70.8%) were male. Hypothyroidism occurred in 25 patients (38.5%), of whom 13 had a peak thyroid-stimulating hormone (TSH) level > 10 mIU/L during treatment. The median OS was significantly longer in patients with a peak TSH > 10 mIU/L than in patients with a peak TSH of ≤ 10 mIU/L (not reached vs. 21.4 months, P = .005). On multivariate analysis, risk criteria, number of previous therapies, and severe hypothyroidism (TSH > 10 mIU/L) during VEGFR-TKI therapy remained significant for improvements in PFS and OS. The severity of VEGFR-TKI therapy-associated hypothyroidism (TSH > 10 mIU/L) was associated with improved survival outcomes in patients with mRCC and should not necessitate a dose reduction or therapy discontinuation. Copyright © 2015 Elsevier Inc. All rights reserved.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study.

PubMed

Shi, Xiao; Zhang, Ting-Ting; Hu, Wei-Ping; Ji, Qing-Hai

2017-04-25

The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study

PubMed Central

Shi, Xiao; Zhang, Ting-ting; Hu, Wei-ping; Ji, Qing-hai

2017-01-01

Background The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Results Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187–1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266–1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). Materials and Methods 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Conclusions Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role. PMID:28415710

Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

PubMed Central

Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

2010-01-01

Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan.

PubMed

Shida, Dai; Ahiko, Yuka; Tanabe, Taro; Yoshida, Takefumi; Tsukamoto, Shunsuke; Ochiai, Hiroki; Takashima, Atsuo; Boku, Narikazu; Kanemitsu, Yukihide

2018-03-27

The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear. This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance. Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033). Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.

Baseline peripheral blood leukocytosis: Biological marker predicts outcome in oropharyngeal cancer, regardless of HPV-status.

PubMed

Gouw, Zeno A R; Paul de Boer, Jan; Navran, Arash; van den Brekel, Michiel W M; Sonke, Jan-Jakob; Al-Mamgani, Abrahim

2018-03-01

To study the prognostic value of abnormalities in baseline complete blood count in patients with oropharyngeal cancer (OPC) treated with (chemo) radiation. The prognostic value of baseline complete blood count on outcome in 234 patients with OPC treated between 2010 and 2015 was examined in multivariate analysis together with other conventional prognostic variables including HPV-status, tumor stage, tumor and nodal size. The 3-year overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant control (DC) of the whole group were 74%, 64%, 79%, and 88%, respectively. Leukocytosis and HPV-status were the only significant prognosticators for OS and DFS at the multivariate analysis. Patients without leukocytosis had a significantly better DC compared to those with leukocytosis (92% and 70%, respectively, p < 0.001). Patients with HPV-negative OPC had significantly worse LRC compared to HPV-positive patients (67% and 90%, respectively, p < 0.001). The 3-year OS in HPV-positive group with leukocytosis compared to those without leukocytosis were 69% and 95%, respectively (p < 0.001). The figures for HPV-negative patients were 41% vs. 61%, respectively (p = 0.010). This is the first study to date reporting the independent impact of leukocytosis and HPV-status on outcome of patients with OPC. The poor outcome of patients with leukocytosis is mainly caused by the worse DC. The significant impact of leukocytosis on outcome was even more pronounced in HPV-positive patients. These biomarkers could help identifying patients with poor prognosis at baseline requiring intensification of local and/or systemic treatment while treatment de-intensification might be offered to the low-risk group. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of risk grouping on therapeutic decisions in patients with anaplastic thyroid carcinoma.

PubMed

Sun, Chuanzheng; Li, Chao; Hu, Zedong; Li, Xiaojiang; He, Jiehua; Song, Ming; Li, Guojun; Zhang, Fenghua; Li, Qiuli

2015-04-01

We investigated prognostic factors in 42 anaplastic thyroid carcinoma (ATC) patients from a single institution over a 30-year period and explored the use of risk grouping to guide therapeutic decisions. Univariable and multivariable differences in overall survival (OS) were evaluated using the Kaplan-Meier method and the log-rank test as well as Cox proportional hazards model. Risk grouping in making therapeutic decisions for ATC patients was explored. The 1- and 3-year OS rates were 28.6 % and 18.5 %, respectively. Univariate analysis indicated that 4 pre-therapeutic factors of patients were related to poorer prognoses: age ≥ 55 years, white blood cell count ≥ 10.0 × 10(9)/L, blood platelet count ≥ 300.0 × 10(9)/L and advanced clinical tumor-node-metastasis stage. These factors were used to calculate the risk indices. Patients with total risk index scores of no more than 1 were considered to be in the low-risk group, and patients with scores ≥ 2 were considered to be in the high-risk group. The patients in the low-risk group had significantly better 1- and 3-year OS rates (90.9 % and 63.6 %, respectively) than those in the high-risk group (6.5 % and 3.2 %, respectively). Risk group and therapeutic regimen were the 2 factors that independently influenced survival according to multivariable analysis. Surgery that was combined with postoperative radiotherapy significantly benefited the patients in the low-risk group rather than the patients in the high-risk group. Risk grouping was a helpful tool of evaluating the prognoses and guiding the treatment of ATC patients.

Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older.

PubMed

Gardin, Claude; Chevret, Sylvie; Pautas, Cécile; Turlure, Pascal; Raffoux, Emmanuel; Thomas, Xavier; Quesnel, Bruno; de Revel, Thierry; de Botton, Stéphane; Gachard, Nathalie; Renneville, Aline; Boissel, Nicolas; Preudhomme, Claude; Terré, Christine; Fenaux, Pierre; Bordessoule, Dominique; Celli-Lebras, Karine; Castaigne, Sylvie; Dombret, Hervé

2013-01-20

Although standard chemotherapy remains associated with a poor outcome in older patients with acute myeloid leukemia (AML), it is unclear which patients can survive long enough to be considered as cured. This study aimed to identify factors influencing the long-term outcome in these patients. The study included 727 older patients with AML (median age, 67 years) treated in two idarubicin (IDA) versus daunorubicin (DNR) Acute Leukemia French Association trials. Prognostic analysis was based on standard univariate and multivariate models and also included a cure fraction model to focus on long-term outcome. Age, WBC count, secondary AML, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adverse-risk and favorable-risk AML subsets (European LeukemiaNet classification) all influenced complete remission (CR) rate and overall survival (OS). IDA random assignment was associated with higher CR rate, but not with longer OS (P = .13). The overall cure rate was 13.3%. Older age and ECOG-PS more than 1 negatively influenced cure rate, which was higher in patients with favorable-risk AML (39.1% v 8.0% in adverse-risk AML; P < .001) and those treated with IDA (16.6% v 9.8% with DNR; P = .018). The long-term impact of IDA was still observed in patients younger than age 65 years, although all of the younger patients in the DNR control arm received high DNR doses (cure rate, 27.4% for IDA v 15.9% for DNR; P = .049). In multivariate analysis, IDA random assignment remained associated with a higher cure rate (P = .04), together with younger age and favorable-risk AML, despite not influencing OS (P = .11). In older patients with AML, younger age, favorable-risk AML, and IDA treatment predict a better long-term outcome.

Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

PubMed

Peters, Solange; Weder, Walter; Dafni, Urania; Kerr, Keith M; Bubendorf, Lukas; Meldgaard, Peter; O'Byrne, Kenneth J; Wrona, Anna; Vansteenkiste, Johan; Felip, Enriqueta; Marchetti, Antonio; Savic, Spasenija; Lu, Shun; Smit, Egbert; Dingemans, Anne-Marie; Blackhall, Fiona H; Baas, Paul; Camps, Carlos; Rosell, Rafael; Stahel, Rolf A

2014-11-01

The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.

Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger Patients Who Participated in US National Cancer Institute Cooperative Group Studies.

PubMed

Stinchcombe, Thomas E; Zhang, Ying; Vokes, Everett E; Schiller, Joan H; Bradley, Jeffrey D; Kelly, Karen; Curran, Walter J; Schild, Steven E; Movsas, Benjamin; Clamon, Gerald; Govindan, Ramaswamy; Blumenschein, George R; Socinski, Mark A; Ready, Neal E; Akerley, Wallace L; Cohen, Harvey J; Pang, Herbert H; Wang, Xiaofei

2017-09-01

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non-small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute-supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients.

Prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy: validation of Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score and impacts of pre-existing obesity and diabetes mellitus.

PubMed

Hu, Meng-Bo; Yang, Tian; Hu, Ji-Meng; Zhu, Wen-Hui; Jiang, Hao-Wen; Ding, Qiang

2018-06-01

Our aim was to determine the prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy (PADT), validate the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, and investigate the impacts of pre-existing obesity and diabetes mellitus (DM). The study enrolled Chinese patients diagnosed with prostatic adenocarcinoma and treated with bilateral orchiectomy as PADT at Huashan Hospital, Fudan University (Shanghai, China), from January 2003 to December 2015. The overall survival (OS) and prognostic value of J-CAPRA score, pre-existing obesity, DM, and various clinicopathological variables were analyzed. Of the 435 patients enrolled, 174 (40.0%) deaths occurred during follow-up; 3- and 5-year OS were 74.0 and 58.9%, respectively. Multivariate analysis identified that higher Gleason score and metastasis were both correlated with worse OS and that higher J-CAPRA score was correlated with worse OS [hazard ratio (HR) 1.110, 95% confidence interval (CI) 1.035-1.190, P = 0.003). Different risk categories based on J-CAPRA score showed good stratification in OS (log-rank P = 0.015). In subgroup analysis, pre-existing obesity as a protective factor in younger patients (age ≤ 65, HR 0.271, 95% CI 0.075-0.980, P = 0.046) and pre-existing DM as a risk factor in older patients (> 75, HR 1.854, 95% CI 1.026-3.351, P = 0.041) for OS were recognized, and the prediction accuracy of J-CAPRA was elevated after incorporating pre-existing obesity and DM. The J-CAPRA score presented with good OS differentiation among Chinese patients under PADT. Younger patients (age ≤ 65) had better OS with pre-existing obesity, while older patients (age > 75) had worse OS with pre-existing DM.

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base.

PubMed

Sumner, Whitney A; Amini, Arya; Hankinson, Todd C; Foreman, Nicholas K; Gaspar, Laurie E; Kavanagh, Brian D; Karam, Sana D; Rusthoven, Chad G; Liu, Arthur K

2017-01-01

Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p  = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p  = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years ( n  = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p  = 0.032) and for patients >18 years ( n  = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p  = 0.049), respectively. In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

Early Stage Hepatocellular Carcinomas Not Feasible for Ultrasound-Guided Radiofrequency Ablation: Comparison of Transarterial Chemoembolization Alone and Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyun, Dongho; Cho, Sung Ki, E-mail: chosk@skku.edu; Shin, Sung Wook

2016-03-15

PurposeTo report the results of combined therapy with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early stage hepatocellular carcinoma (HCC) considered infeasible for ultrasound (US)-guided RFA in comparison with those of TACE monotherapy.MethodsFrom January 2007 through December 2010, 91 patients with early or very early stage HCC infeasible for US-guided RFA received either TACE alone (TACE group; n = 54) or TACE immediately followed by RFA (TACE–RFA group; n = 37) as a first-line treatment. 1-month tumor response, time to progression (TTP), and overall survival (OS) rates were calculated. Univariate and multivariate analyses were performed to identify prognostic factors.ResultsTACE–RFA group showed a bettermore » 1-month tumor response than TACE group (P < .001). The mean TTP was 29.7 ± 3.4 months (95 % confidence intervals [CIs] 23.0–36.5) in TACE group and 34.9 ± 2.8 months (95 % CIs 29.4–40.4) in TACE–RFA group. TACE–RFA group had a significantly longer TTP (P = .014). Cumulative 1-, 2-, and 3-year OS rates in the TACE and TACE–RFA groups were 91, 79, and 71 % and 100, 97, and 93 %, respectively (P = .008). Initial treatment of TACE was found to be the only significant risk factor for tumor progression and OS in multivariate analysis.ConclusionTACE–RFA combination therapy appears superior to TACE monotherapy in terms of 1-month tumor response, TTP, and OS when performed for early stage HCC infeasible for US-guided RFA.« less

The impact of treatment on quality of life of patients with head and neck cancer and its association with prognosis.

PubMed

Carrillo, J F; Carrillo, L C; Ramirez-Ortega, M C; Ochoa-Carrillo, F J; Oñate-Ocaña, L F

2016-10-01

Information is scarce regarding the impact of treatment on Health-Related Quality of Life (HRQL) of patients with Head and Neck (H&N) cancers. We assessed the effect of treatment on HRQL and its association with prognosis in H&N cancer. Patients with H&N cancer in whom HRQL was assessed before and after treatment. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 instruments were used. Association of changes in patients' HRQL after treatment with Loco-Regional Recurrence (LRR) and Overall Survival (OS) was investigated. One hundred sixty patients were included; scales of the baseline assessment of HRQL were moderately associated with LRR and OS, but the impact of treatment on most HRQL scales was strongly associated with OS. By multivariate analysis, baseline assessment of Global Health, Physical, HN Teeth, HN Dry mouth, and HN Cough scales, and impact of treatment on the Physical and Pain scales comprised independent variables associated with LRR. Male gender, positive lymph nodes, baseline assessment of Role, HN Pain, HN Cough, and impact of treatment on Emotion, Pain, Financial, HN Swallowing, HN Social contact, and the interaction of HN Pain-change in Pain scales were associated with OS. Both multivariate models were adjusted by the neoplasm's site of origin. Aside from well-known clinical-pathologic prognostic factors in H&N cancers, HRQL assessment, both prior to and after treatment, provides significant prognostic information and should be measured. Design of therapeutic clinical trials in patients with H&N cancers should consider these novel prognostic factors. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.

PubMed

He, Sha-Sha; Chen, Yong; Shen, Xiao-Ming; Wang, Hong-Zhi; Sun, Peng; Dong, Jun; Guo, Gui-Fang; Chen, Ju-Gao; Xia, Liang-Ping; Hu, Pei-Li; Qiu, Hui-Juan; Liu, Shou-Sheng; Zhou, Yi-Xin; Wang, Wei; Hu, Wei-Han; Cai, Xiu-Yu

2017-01-01

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes ( P = 0.016) and distant metastasis ( P = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression ( P = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup ( P = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients ( P = 0.039 and 0.037, respectively). Conclusions : Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

PubMed Central

Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Stotz, Michael; Samonigg, Hellmut; Ploner, Ferdinand; Stojakovic, Tatjana; Leithner, Andreas; Pichler, Martin

2014-01-01

Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models. Results Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001). Conclusion The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality. PMID:25207808

Impact of academic facility type and volume on post-surgical outcomes following diagnosis of glioblastoma.

PubMed

Hauser, Alan; Dutta, Sunil W; Showalter, Timothy N; Sheehan, Jason P; Grover, Surbhi; Trifiletti, Daniel M

2018-01-01

To identify if facility type and/or facility volume impact overall survival (OS) following diagnosis of glioblastoma (GBM). We also sought to compare early post-surgical outcomes based on these factors. The National Cancer Database was queried for patients with GBM diagnosed from 2004 to 2013 with known survival. Patients were grouped based on facility type and facility volume. Multivariable analyses were performed to investigate factors associated OS following diagnosis and Chi-square tests were used to compare early post-surgical outcomes. 89,839 patients met inclusion criteria. Factors associated with improved OS on multivariable analysis included younger patient age, female gender, race, lower comorbidity score, higher performance score, smaller tumor size, unifocal tumors, MGMT hypermethylation, fully resected tumors, radiotherapy, and chemotherapy (each p < .001). Also, OS was improved among patients treated at centers averaging at least 30.2 cases per year (HR 0.948, compared to <7.4 cases/year, p < .001), and patients treated at Academic/Research programs had improved survival compared to those treated at Comprehensive Community Cancer programs (HR 1.069, p < .001) and Integrated Network Cancer programs (HR 1.126, p < .001). Similarly, Academic/Research programs and high volume centers demonstrated improved 30- and 90-day morality as well as 30-day readmission rates (p < .001). This study suggests that patients treated in Academic/Research programs and high patient-volume centers have increased survival and more favorable early-postsurgical outcomes. The extent to which differences in patient populations, socioeconomic factors, and/or provider expertise play into this cause will be areas of future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma

PubMed Central

Wang, Wenjia; Ma, Xiao-Pin; Shi, Zhuqing; Zhang, Pengyin; Ding, Dong-Lin; Huang, Hui-Xing; Saiyin, Hexi Ge; Chen, Tao-Yang; Lu, Pei-Xin; Wang, Neng-Jin; Yu, Hongjie; Sun, Jielin; Zheng, S Lilly; Yu, Long; Xu, Jianfeng; Jiang, De-Ke

2015-01-01

The EGFR signaling pathway is important in the control of vital processes in the carcinogenesis of hepatocellular carcinoma (HCC), including cell survival, cell cycle progression, tumor invasion and angiogenesis. In the current study, we aim to assess if genetic variants in the genes of the EGFR signaling pathway are associated with the prognosis of HCC. We genotyped 36 single nucleotide polymorphisms (SNP) in four core genes (EGF, EGFR, VEGF, and VEGFR2) by using DNA from blood samples of 363 HCC patients with surgical resection. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confident intervals (CIs) were estimated for the multivariate survival analyses by Cox proportional hazards regression models, adjusting for age, gender, family history, HBsAg and AFP. We found that five SNPs in the VEGFR2 gene were significantly associated with clinical outcomes of HCC patients. Among them, four SNPs (rs7692791, rs2305948, rs13109660, rs6838752) were associated with OS (p=0.035, 0.038, 0.029 and 0.028, respectively), and two SNPs (rs7692791 and rs2034965) were associated with DFS (p=0.039 and 0.017, respectively). Particularly, rs7692791 TT genotype was associated with both reduced OS (p=0.037) and DFS (p=0.043). However, only one SNP rs2034965 with the AA genotype was shown to be an independent effect on DFS (p=0.009) in the multivariate analysis. None of the other 31 polymorphisms or 9 haplotypes attained from the four genes was significantly associated with OS or DFS. Our results illustrated the potential use of VEGFR2 polymorphisms as prognostic markers for HCC patients. PMID:25628948

Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.

PubMed

Sonnenblick, Amir; Agbor-Tarh, Dominique; Bradbury, Ian; Di Cosimo, Serena; Azim, Hatem A; Fumagalli, Debora; Sarp, Severine; Wolff, Antonio C; Andersson, Michael; Kroep, Judith; Cufer, Tanja; Simon, Sergio D; Salman, Pamela; Toi, Masakazu; Harris, Lyndsay; Gralow, Julie; Keane, Maccon; Moreno-Aspitia, Alvaro; Piccart-Gebhart, Martine; de Azambuja, Evandro

2017-05-01

Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry-with or without metformin treatment-were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor-positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.

The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies.

PubMed

Beer, Tomasz M; Miller, Kurt; Tombal, Bertrand; Cella, David; Phung, De; Holmstrom, Stefan; Ivanescu, Cristina; Skaltsa, Konstantina; Naidoo, Shevani

2017-12-01

Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78-0.84]) and 21% in PREVAIL (HR 0.79 [0.76-0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84-0.93]) and 10% (HR 0.90 [0.86-0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

PubMed

Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.

PubMed

Zekri, Jamal; Ahmad, Imran; Fawzy, Ehab; Elkhodary, Tawfik R; Al-Gahmi, Aboelkhair; Hassouna, Ashraf; El Sayed, Mohamed E; Ur Rehman, Jalil; Karim, Syed M; Bin Sadiq, Bakr

2015-01-01

Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC. We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis. On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02). LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

PubMed Central

Pantano, Francesco; Santoni, Matteo; Procopio, Giuseppe; Rizzo, Mimma; Iacovelli, Roberto; Porta, Camillo; Conti, Alessandro; Lugini, Antonio; Milella, Michele; Galli, Luca; Ortega, Cinzia; Guida, Francesco Maria; Silletta, Marianna; Schinzari, Giovanni; Verzoni, Elena; Modica, Daniela; Crucitti, Pierfilippo; Rauco, Annamaria; Felici, Alessandra; Ballatore, Valentina; Cascinu, Stefano; Tonini, Giuseppe; Carteni, Giacomo; Russo, Antonio; Santini, Daniele

2015-01-01

Background Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC. Methods 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated. Results Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis. Conclusion C+T raise is an early predictor for everolimus efficacy for patients with mRCC. PMID:25885920

Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chadha, Awalpreet S.; Liu, Guan; Chen, Hsiang-Chun

2017-02-01

Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gymore » (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.« less

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

PubMed

Stocker, Gertraud; Hacker, Ulrich T; Fiteni, Frédéric; John Mahachie, Jestinah; Roth, Arnaud D; Van Cutsem, Eric; Peeters, Marc; Lordick, Florian; Mauer, Murielle

2018-06-12

Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m 2 ), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model. 13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m 2 , and 5.3% had both a BMI ≥ 30 kg/m 2 and a body surface area (BSA) ≥2 m 2 . Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m 2 and 32.4% with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , respectively. In patients with BMI ≥ 30 kg/m 2 , multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men. Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dose escalation of definitive radiation is not associated with improved survival for cervical esophageal cancer: a National Cancer Data Base (NCDB) analysis.

PubMed

De, B; Rhome, R; Doucette, J; Buckstein, M

2017-04-01

For cervical esophageal cancer (CEC), National Comprehensive Cancer Network guidelines support RT to 50-50.4 Gy with chemotherapy but acknowledge higher doses may be appropriate. This study uses the National Cancer Database (NCDB) to characterize RT practices and identify if a dose-response relationship exists for overall survival (OS) for definitive treatment of CEC. We queried the NCDB for patients diagnosed with Stage I-III CEC from 2004 to 2013, and selected patients receiving definitive RT with doses between 50 and 74 Gy. Using multivariate logistic regression, the database was analyzed to determine factors associated with use of RT > 50.4 Gy. Patients were then stratified into three dose categories. Predictors of OS were analyzed with univariate and multivariate methods using the Kaplan-Meier curves, the log-rank test, and the Cox proportional hazards analysis. We stratified 789 patients with CEC who were treated with definitive radiation ± chemotherapy: 50-50.4 Gy ('standard'), >50.4 and <66 Gy ('medium'), and 66-74 Gy ('high'). Of these patients, 215 (27%) received standard doses, 375 (48%) received medium doses, and 199 (25%) received high doses. Patients with Medicaid insurance and those with Stage II disease were less likely (P < 0.05) to receive >50.4 Gy. Sex, histology, distance to treatment facility, and academic/community facility type were not significantly associated with receipt of >50.4 Gy. There was no association between dose and OS for the medium or high groups when using univariate analysis or analysis adjusted for demographic, facility, and clinical attributes. Stage III disease and the Charlson-Deyo scores of 1 or 2 were associated with higher mortality (P < 0.05), while female sex and use of chemotherapy were associated with lower mortality (P < 0.01). Nearly three-fourths of CEC patients in the United States are treated with RT > 50.4 Gy. Higher radiation doses were not associated with increased OS in CEC patients in the NCDB. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Outcome predictors in the management of intramedullary classic ependymoma: An integrative survival analysis.

PubMed

Wang, Yinqing; Cai, Ranze; Wang, Rui; Wang, Chunhua; Chen, Chunmei

2018-06-01

This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan-Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P < .05.A total of 35 studies were identified, including 169 cases of CE. The mean follow-up time across cases was 64.2 ± 51.5 months. Univariate analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000-0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000-0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management. 4.

Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies.

PubMed

Bruix, Jordi; Cheng, Ann-Lii; Meinhardt, Gerold; Nakajima, Keiko; De Sanctis, Yoriko; Llovet, Josep

2017-11-01

Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) vs. placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase III studies. To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model. Hazard ratios (HRs) and median OS were evaluated across pooled subgroups. To assess factors predictive of sorafenib benefit, the interaction term between treatment for each subgroup was evaluated by Cox proportional hazard model. In 827 patients (448 sorafenib; 379 placebo) analyzed, strong prognostic factors for poorer OS identified from MV analysis in both treatment arms were presence of macroscopic vascular invasion (MVI), high alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ⩽ vs. >median [3.1]). Sorafenib OS benefit was consistently observed across all subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). In this exploratory analysis, presence of MVI, high AFP, and high NLR were prognostic factors of poorer OS. Sorafenib benefit was consistently observed irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were predictive of a greater OS benefit with sorafenib. This exploratory pooled analysis showed that treatment with sorafenib provides a survival benefit in all subgroups of patients with HCC; however, the magnitude of benefit is greater in patients with disease confined to the liver (without extrahepatic spread), or in those with hepatitis C virus, or a lower neutrophil-to-lymphocyte ratio, an indicator of inflammation status. These results help inform the prognosis of patients receiving sorafenib therapy and provide further refinements for the design of trials testing new agents vs. sorafenib. Clinical Trial Numbers: NCT00105443 and NCT00492752. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Association of tumor growth on nude mice and poor clinical outcome in soft tissue sarcoma patients.

PubMed

Budach, W; Budach, V

2001-09-01

Permanent growth in nude mice (PGNM) may be associated with poor clinical outcome. We tested this hypothesis in a group of soft tissue sarcoma (STS) patients. Small chunks from fresh tumor biopsies of 81 patients with STS were transplanted subcutaneously into NMRI-nu/nu nude mice. Tumor cell lines exhibiting growth in nude mice for more than three tumor passages were considered as permanently established. Clinical outcome of all patients was monitored with a median follow-up of 38 months. 39/81 (48%) STSs exhibited PGNM. High grade, high S-phase proportion, and aneuploidy were significant predictors of PGNM. Overall survival (OS) at 3 years was 21% (+7% standard error of median) for STS patients with PGNM and 53% (+/-8%) for patients without PGNM (P<0.01). Considering only patients without distant metastasis at the time of biopsy (n = 49), 3-year-OS was 25% (+/-10%) and 71% (+/-9%) for STS with PGNM and without PGNM, respectively (P<0.01). In the univariate analysis, PGNM, aneuploidy high S-phase proportion, tumor location at the trunk, high tumor grade, and non-liposarcoma histology were associated with reduced survival time. In the multivariate analysis, aneuploidy and tumor location at the trunk were the only independent predictors of overall survival. Permanent growth of STS on nude mice is associated with poor clinical outcome in the univariate analysis, but is not an independent predictor of survival in the multivariate analysis due to a strong co-correlation to other known adverse prognostic factors.

Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change.

PubMed

Christopeit, Maximilian; Kuss, Oliver; Finke, Jürgen; Bacher, Ulrike; Beelen, Dietrich Wilhelm; Bornhäuser, Martin; Schwerdtfeger, Rainer; Bethge, Wolfgang Andreas; Basara, Nadezda; Gramatzki, Martin; Tischer, Johanna; Kolb, Hans-Jochem; Uharek, Lutz; Meyer, Ralf G; Bunjes, Donald; Scheid, Christof; Martin, Hans; Niederwieser, Dietger; Kröger, Nicolaus; Bertz, Hartmut; Schrezenmeier, Hubert; Schmid, Christoph

2013-09-10

To evaluate the role of a second allogeneic hematopoietic stem-cell transplantation (HSCT2) given for relapsed acute leukemia (AL) after related or unrelated first hematopoietic stem-cell transplantation (HSCT1) and to analyze the role of donor change for HSCT2 in both settings. We performed a retrospective registry study on 179 HSCT2s given for relapse after HSCT1 from matched related donors (n = 75) or unrelated donors (n = 104), using identical or alternative donors for HSCT2. Separate analyses were performed according to donor at HSCT1. Independent of donor, 74% of patients achieved complete remission after HSCT2, and half of these patients experienced relapse again. Overall survival (OS) at 2 years was 25% ± 4% (39% ± 7% after related HSCT2; 19% ± 4% after unrelated HSCT2). Long-term survivors were observed even after two unrelated HSCT2s. Multivariate analysis for OS from HSCT2 confirmed established risk factors (remission duration after HSCT1: hazard ratio [HR], 2.37; 95% CI, 1.61 to 3.46; P < .001; stage at HSCT2: HR, 0.53; 95% CI, 0.34 to 0.83; P = .006). Outcome of HSCT2 was better after related HSCT1 than after unrelated HSCT1 (2-year OS: 37% ± 6% v 16% ± 4%, respectively; HR, 0.68; 95% CI, 0.47 to 0.98; P = .042, multivariate Cox regression). After both related and unrelated HSCT1, selecting a new donor for HSCT2 did not result in a relevant improvement in OS compared with HSCT2 from the original donor; however, donor change was not detrimental either. After relapse from allogeneic HSCT1, HSCT2 can induce 2-year OS in approximately 25% of patients. Unrelated HSCT2 is feasible after related and unrelated HSCT1. Donor change for HSCT2 is a valid option. However, a clear advantage in terms of OS could not be demonstrated.

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

PubMed Central

Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

2015-01-01

Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593

Complete Placenta Previa: Ultrasound Biometry and Surgical Outcomes

PubMed Central

Wortman, Alison C.; Schaefer, Stephanie L.; McIntire, Donald D.; Sheffield, Jeanne S.; Twickler, Diane M.

2018-01-01

Objective  To evaluate the relationship between surgical outcomes and ultrasound measurement of placental extension beyond the cervical os in women with placenta previa. Study Design  This is a retrospective cohort study of singleton pregnancies with placenta previa undergoing third-trimester ultrasound and delivering at our institution from 2002 through 2011. For study purposes, an investigator measured placental extension, defined as the placental distance from the internal os across the placenta continuing out to the lowest placental edge. If morbidly adherent placentation was suspected, women were excluded. Receiver operating characteristic (ROC) curves were developed for pertinent surgical outcomes, and multivariate analysis was performed to determine the placental extension with the best predictive discriminatory zone. Results  In total, 157 women had placenta previa, ultrasound, and delivery data: 86 (55%) had a placental extension of <40 mm, and 71 (45%) had a placental extension of ≥40 mm. Women with placental extension of ≥40 mm had increased surgical time, blood loss > 2,000 mL, blood transfusion, and rate of peripartum hysterectomy. After multivariate analysis, only peripartum hysterectomy and surgical time > 90 minutes remained significant, p ≤ 0.05 and p ≤ 0.01, respectively. Conclusion  In women with placenta previa, the placental extension ultrasound measurement of ≥40 mm is a predictor of adverse surgical outcomes. PMID:29686936

Complete Placenta Previa: Ultrasound Biometry and Surgical Outcomes.

PubMed

Wortman, Alison C; Schaefer, Stephanie L; McIntire, Donald D; Sheffield, Jeanne S; Twickler, Diane M

2018-04-01

Objective  To evaluate the relationship between surgical outcomes and ultrasound measurement of placental extension beyond the cervical os in women with placenta previa. Study Design  This is a retrospective cohort study of singleton pregnancies with placenta previa undergoing third-trimester ultrasound and delivering at our institution from 2002 through 2011. For study purposes, an investigator measured placental extension, defined as the placental distance from the internal os across the placenta continuing out to the lowest placental edge. If morbidly adherent placentation was suspected, women were excluded. Receiver operating characteristic (ROC) curves were developed for pertinent surgical outcomes, and multivariate analysis was performed to determine the placental extension with the best predictive discriminatory zone. Results  In total, 157 women had placenta previa, ultrasound, and delivery data: 86 (55%) had a placental extension of <40 mm, and 71 (45%) had a placental extension of ≥40 mm. Women with placental extension of ≥40 mm had increased surgical time, blood loss > 2,000 mL, blood transfusion, and rate of peripartum hysterectomy. After multivariate analysis, only peripartum hysterectomy and surgical time > 90 minutes remained significant, p ≤ 0.05 and p ≤ 0.01, respectively. Conclusion  In women with placenta previa, the placental extension ultrasound measurement of ≥40 mm is a predictor of adverse surgical outcomes.

Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients.

PubMed

Kilburn, Jeremy M; Soike, Michael H; Lucas, John T; Ayala-Peacock, Diandra; Blackstock, William; Isom, Scott; Kearns, William T; Hinson, William H; Miller, Antonius A; Petty, William J; Munley, Michael T; Urbanic, James J

2016-01-01

Image guided radiation therapy (IGRT) is designed to ensure accurate and precise targeting, but whether improved clinical outcomes result is unknown. A retrospective comparison of locally advanced lung cancer patients treated with and without IGRT from 2001 to 2012 was conducted. Median local failure-free survival (LFFS), regional, locoregional failure-free survival (LRFFS), distant failure-free survival, progression-free survival, and overall survival (OS) were estimated. Univariate and multivariate models assessed the association between patient- and treatment-related covariates and local failure. A total of 169 patients were treated with definitive radiation therapy and concurrent chemotherapy with a median follow-up of 48 months in the IGRT cohort and 96 months in the non-IGRT cohort. IGRT was used in 36% (62 patients) of patients. OS was similar between cohorts (2-year OS, 47% vs 49%, P = .63). The IGRT cohort had improved 2-year LFFS (80% vs 64%, P = .013) and LRFFS (75% and 62%, P = .04). Univariate analysis revealed IGRT and treatment year improved LFFS, whereas group stage, dose, and positron emission tomography/computed tomography planning had no impact. IGRT remained significant in the multivariate model with an adjusted hazard ratio of 0.40 (P = .01). Distant failure-free survival (58% vs 59%, P = .67) did not differ significantly. IGRT with daily cone beam computed tomography confers an improvement in the therapeutic ratio relative to patients treated without this technology. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients.

PubMed

Wang, Yinyan; Wang, Kai; Wang, Jiangfei; Li, Shaowu; Ma, Jun; Dai, Jianping; Jiang, Tao

2016-04-01

Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients.

Prognostic significance of pre-resection albumin/fibrinogen ratio in patients with non-small cell lung cancer: A propensity score matching analysis.

PubMed

Chen, Shuaishuai; Yan, Haixi; Du, Juping; Li, Jun; Shen, Bo; Ying, Haijian; Zhang, Ying; Chen, Shiyong

2018-07-01

Nutrition and coagulation play important roles in cancer progression. This study was aimed to investigate the value of the albumin/fibrinogen ratio (AFR) in non-small cell lung cancer (NSCLC) patients, through a propensity score matching (PSM) method. We retrospectively analyzed 529 NSCLC patients underwent surgical resection from 2010 to 2015. PSM was used to eliminate possible biases. A Cox proportional hazards regression model was performed to evaluate the prognostic value of AFR in NSCLC. The optimal value was 9.67 for the AFR by ROC (receiver operating characteristic) curve. The AFR was statistically significantly associated with age, sex, smoking history, histological subtype, tumor size, pathological stage and adjuvant therapy (p < 0.05). Multivariate analysis indicated that the pathological stage and pre-resection AFR were independent prognostic factors for patients with NSCLC. Additionally, elevated AFR indicated a better outcome, and patients with higher AFR had lower risk for overall death (OS) (HR 0.512, 95% CI 0.316-0.829, p = 0.006) as well as disease-free death (DFS) (HR 0.561, 95% CI 0.399-0.787, p = 0.001). The propensity score model identified 120 patients from each group that were balanced for age, sex, smoking history, histological subtype, tumor size, stage distribution and adjuvant therapy. In multivariable regression analysis of PSM groups, the result indicated that the AFR was predictive for OS (HR 0.392, 95% CI 0.225-0.683, p < 0.001) and DFS (HR 0.526, 95% CI 0.344-0.805, p = 0.003). Pre-resection AFR can be considered as an independent prognostic factor in NSCLC patients, and higher AFR may enhance OS and DFS of NSCLC patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Forkhead-box series expression network is associated with outcome of clear-cell renal cell carcinoma.

PubMed

Jia, Zhongwei; Wan, Fangning; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Dai, Bo; Ye, Dingwei

2018-06-01

Previous studies have demonstrated that several members of the Forkhead-box (FOX) family of genes are associated with tumor progression and metastasis. The objective of the current study was to screen candidate FOX family genes identified from analysis of molecular networks in clear cell renal cell carcinoma (ccRCC). The expression of FOX family genes as well as FOX family-associated genes was examined, and Kaplan-Meier survival analysis was performed in The Cancer Genome Atlas (TCGA) cohort (n=525). Patient characteristics, including sex, age, tumor diameter, laterality, tumor-node-metastasis, tumor grade, stage, white blood cell count, platelet count, the levels of hemoglobin, overall survival (OS) and disease-free survival (DFS), were collected for univariate and multivariate Cox proportional hazards ratio analyses. A total of seven candidate FOX family genes were selected from the TCGA database subsequent to univariate and multivariate Cox proportional hazards ratio analyses. FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 were associated with poor OS time, while FOXA1, FOXA2, FOXD1 and FOXK2 were associated with poor DFS time (P<0.05). FOXN2 was associated with favorable outcomes for overall and disease-free survival (P<0.05). In the gene cluster network analysis, the expression of FOX family-associated genes, including nuclear receptor coactivator ( NCOA ) 1 , NADH-ubiquinone oxidoreductase flavoprotein 3 ( NDUFV3 ), phosphatidylserine decarboxylase ( PISD ) and pyruvate kinase liver and red blood cell ( PKLR ), were independent prognostic factors for OS in patients with ccRCC. Results of the present study revealed that the expression of FOX family genes, including FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 , and FOX family-associated genes, including NCOA1, NDUFV3, PISD and PKLR , are independent prognostic factors for patients with ccRCC.

Comparison between early and late onset breast cancer in Pakistani women undergoing breast conservative therapy: is there any difference?

PubMed

Bhatti, Abu Bakar Hafeez; Jamshed, Aarif; Khan, Amina; Siddiqui, Neelam; Muzaffar, Nargis; Shah, Mazhar Ali

2014-01-01

Early onset breast cancer is associated with poor outcomes but variable results have been reported. It is a significant problem in Pakistani women but remains under reported. Breast conservation plays an important role in surgical management of this younger patient group. The objective of this study was to determine the outcome of breast conservative therapy in patients with early onset breast cancer in our population and compare it with their older counterparts. A review of patients with invasive breast cancer who underwent breast conservation surgery at Shaukat Khanum Cancer Hospital from 1997 to 2009 was performed. Patients were divided into two groups i.e. Group I age ≤ 40 and Group II >40 years. A total of 401 patients with breast cancer were identified in Group I and 405 patients in Group II. Demographics, histopathological findings and receptor status of the two groups were compared. The Chi square test was used for categorical variables. Outcome was assessed on basis of 10 year locoregional recurrence free survival (LRRFS), disease free survival (DFS) and overall survival (OS) . For survival analysis Kaplan Meier curves were used and significance was determined using the Log rank test. Cox regression was applied for multivariate analysis. Median follow up was 4.31 (0.1-15.5) years. Median age at presentation was 34.6 years (17-40) and 51.9 years (41-82) for the two groups. Groups were significantly different from each other with respect to grade, receptor status, tumor stage and use of neoadjuvant therapy. No significant difference was present between the two groups for estimated 10 year LRRFS (86% vs 95%) (p=0.1), DFS (70% vs 70%) (p=0.5) and OS (75% vs 63%) (p=0.1). On multivariate analysis, tumor stage was an independent predictor of LRRFS, DFS and OS. Early onset breast cancer is associated with a distinct biology but does not lead to poorer outcomes in our population.

Significance of sarcopenia as a prognostic factor for metastatic urothelial carcinoma patients treated with systemic chemotherapy.

PubMed

Abe, Hideyuki; Takei, Kohei; Uematsu, Toshitaka; Tokura, Yuumi; Suzuki, Issei; Sakamoto, Kazumasa; Nishihara, Daisaku; Yamaguchi, Yoshiyuki; Mizuno, Tomoya; Nukui, Akinori; Kobayashi, Minoru; Kamai, Takao

2018-04-01

Recently, numerous studies have reported an association between sarcopenia and poor outcomes in various kinds of malignancies. We investigated whether sarcopenia predicts the survival of patients with metastatic urothelial carcinoma who underwent systemic chemotherapy. We reviewed 87 metastatic urothelial carcinoma patients who underwent chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin for cisplatin-unfit patients) between 2007 and 2015. A computed tomography scan prior to chemotherapy was used for evaluating sarcopenia, and we measured three cross-sectional areas of skeletal muscle at the third lumbar vertebra and calculated the skeletal muscle index (SMI), the paraspinal muscle index (PSMI), and the total psoas area (TPA) of each patient. Predictive values of survival were assessed using Cox regression analysis. The median overall survival (OS) was 16 months (95% CI 13.5-18). Although SMI alone was not a significant predictor of shorter OS (P = 0.117) in univariate analysis, SMI stratified by the value of the body mass index (BMI) was a significant predictor of shorter OS in univariate analysis (P = 0.037) and was also an independent predictor of shorter OS in multivariate analysis (P = 0.026). PSMI and TPA were not significant prognostic factors even when stratified by BMI (P = 0.294 and 0.448), respectively. Neither PSMI nor TPA could substitute SMI as a predictor for poor outcomes in metastatic urothelial carcinoma patients treated with systemic chemotherapy in our study. SMI stratified by BMI is a useful predictor of prognosis in these patients.

Impact of Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression on Prognosis After Surgical Resection for Biliary Carcinoma.

PubMed

Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

2017-06-01

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that influences chemotherapy effectiveness and prognosis. The aim of this study was to investigate whether SPARC expression correlates with the postoperative survival of patients treated with surgical resection for biliary carcinoma. SPARC expression in resected biliary carcinoma specimens was investigated immunohistochemically in 175 patients. The relationship between SPARC expression and prognosis after surgery was evaluated using univariate and multivariate analyses. High SPARC expression in peritumoral stroma was found in 61 (35%) patients. In all patients, stromal SPARC expression was significantly associated with overall survival (OS) (P = 0.006). Multivariate analysis revealed that high stromal SPARC expression was an independent risk factor for poor OS (HR 1.81, P = 0.006). Moreover, high stromal SPARC expression was independently associated with poor prognosis in a subset of 118 patients treated with gemcitabine-based adjuvant chemotherapy (HR 2.04, P = 0.010) but not in the 57 patients who did not receive adjuvant chemotherapy (P = 0.21). Stromal SPARC expression correlated with the prognosis of patients with resectable biliary carcinoma, and its significance was enhanced in patients treated with adjuvant gemcitabine-based chemotherapy.

The impact of hyperglycemia on survival in glioblastoma: A systematic review and meta-analysis.

PubMed

Lu, Victor M; Goyal, Anshit; Vaughan, Lachlin S; McDonald, Kerrie L

2018-07-01

In the management of glioblastoma (GBM), there is a considerable predisposition to hyperglycemia due to significant integration of corticosteroid therapy to treat predictable clinical sequelae following diagnosis and treatment. The aim of this study was to quantify effect of hyperglycemia during the management of GBM on overall survival (OS). Searches of seven electronic databases from inception to January 2018 were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. There were 1475 articles identified for screening. Prognostic hazard ratios (HRs) derived from multivariate regression analysis were extracted, and analyzed using meta-analysis of proportions and linear regression. Six observational studies reporting prognostic HRs in 10 cohorts were included. They described 1481 GBM diagnoses, all surveyed for hyperglycemia during management. Hyperglycemia was found to confer a statistically significant poorer OS outcome (HR, 1.671; p < 0.001). This trend and its significance was not modified by study year, size or proportion of pre-diagnostic diabetes mellitus. Hyperglycemia in GBM is an independent poor prognostic factor for OS. Heterogeneity in clinical course limits inter-study comparability. Future, prospective, randomized studies will validate the findings of this study, and ascertain the potential benefit of more rigorous monitoring for hyperglycemia and glycemic control. Copyright © 2018 Elsevier B.V. All rights reserved.

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

PubMed

Tam, Samantha; Sandulache, Vlad C; Metwalli, Kareem A; Rock, Crosby D; Eraj, Salman A; Sheu, Tommy; El-Naggar, Adel K; Fuller, Clifton D; Weber, Randal S; Lai, Stephen Y

2018-05-07

Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HR adjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HR adjusted 9.53; 95% CI 3.04-27.06). Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival. © 2018 Wiley Periodicals, Inc.

Quantitative Analysis of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Yi; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo; Song, Jie

Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). Conclusion: Quantitative analysis identified novel {sup 18}F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.« less

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

PubMed

Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

2015-01-01

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Impact of oligodendroglial component in glioblastoma (GBM-O): Is the outcome favourable than glioblastoma?

PubMed

Goda, Jayant S; Lewis, Shirley; Agarwal, Aditi; Epari, Sridhar; Churi, Shraddha; Padmavati, A; Gupta, Tejpal; Shetty, Prakash; Moiyadi, Aliasgar; Jalali, Rakesh

2015-08-01

Prognosis of patients with glioblastoma with oligodendroglial component (GBM-O) is not well defined. We report our experience of patients of GBM-O treated at our center. Between January 2007 and August 2013, out of 817 consecutive patients with glioblastoma (GBM), 74 patients with GBM-O were identified in our prospectively maintained database. An experienced neuropathologist revaluated the histopathology of all these 74 patients and the diagnosis of GBM-O was eventually confirmed in 57 patients. Patients were uniformly treated with maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolamide (TMZ). At a median follow up of 16 months, median overall survival (OS) and progression free survival (PFS) of the entire cohort was 23 months and 13 months respectively. Near total excision was performed in 30/57 (52.6%). On univariate analysis, age < 50 years was a significant favourable prognostic factor for OS (p = 0.009) and PFS (p = 0.017), while patients with near total resection had a significantly better PFS (p = 0.017), patients who completed a minimum of 6 cycles of adjuvant TMZ had significantly better OS (p = 0.000) and PFS (p = 0.003). On multivariate analysis, none of the above factors were significant except for patient who had completed a minimum of 6 cycles of TMZ (OS; p = 0.000 & PFS; p = 0.015). A comparative analysis of GBM-O patients with a similarly treated cohort of 105 GBM patients during the same period revealed significantly better median OS in favour of GBM-O (p = 0.01). Our experience suggests patients with GBM-O have a more favourable clinical outcome as compared to GBM. Copyright © 2015 Elsevier B.V. All rights reserved.

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

PubMed

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Jeanny; Kim, Il Han, E-mail: ihkim@snu.ac.kr; Cancer Research Institute, Seoul National University College of Medicine, Seoul

Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8%more » had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.« less

CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers

PubMed Central

Vedeld, Hege Marie; Merok, Marianne; Jeanmougin, Marine; Danielsen, Stine A.; Honne, Hilde; Presthus, Gro Kummeneje; Svindland, Aud; Sjo, Ole H.; Hektoen, Merete; Eknæs, Mette; Nesbakken, Arild; Lothe, Ragnhild A.

2017-01-01

The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5‐markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni‐ and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (<60, 60‐74, ≥75 years). Patients with CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31‐2.63] and 1.89 [1.34‐2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P < 0.001), and MSS BRAF mutated tumors (P < 0.001), a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis (P < 0.01). Consistent results were found for all three age groups. To conclude, CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors. PMID:28542846

A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors.

PubMed

Andersen, N S; Jensen, M K; de Nully Brown, P; Geisler, C H

2002-02-01

This study presents the first large clinical analysis of 105 unselected mantle cell lymphoma (MCL) patients diagnosed from 1992 to 2000 in a well-defined Danish population. The annual incidences were 0.7/100000 for men and 0.2/100000 for women, with no significant change during the study period. Of 97 evaluable cases, 43% achieved a complete response (CR) after initial therapy. The median disease-free (DFS) and overall survival (OS) rates were 15 and 30 months, respectively. In multivariate analysis, splenomegaly (P=0.002), anaemia (P=0.0001) and age (P=0.002), but not the international prognostic index (IPI) and the Ann Arbor staging system, had an independent impact on survival. Moreover, in a sub-analysis of 45 younger MCL patients (<65 years), a trend towards an OS plateau of 58% was observed in cases without splenomegaly and anaemia (n=29). Thus, in contrast to previously suggested prognostic factors, these variables may prove useful for clinical decisions in a significant subset of MCL patients.

Enhanced expressions of FHL2 and iASPP predict poor prognosis in acute myeloid leukemia.

PubMed

Cheng, Zhiheng; Dai, Yifeng; Pang, Yifan; Jiao, Yang; Zhao, Hongmian; Zhang, Zhihui; Qin, Tong; Hu, Ning; Zhang, Yijie; Ke, Xiaoyan; Chen, Yang; Wu, Depei; Shi, Jinlong; Fu, Lin

2018-06-18

iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study. Patients with high expressions of FHL2 and iASPP had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expressions (P = 0.005, P = 0.003, respectively). Univariate analysis indicated that high expressions of FHL2 or iASPP were unfavorable for EFS and OS (all P < 0.05), while multivariate analysis confirmed that high FHL2 expression was an independent risk factor for EFS and OS (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, EFS and OS were not significantly different between FHL2 or iASPP high- and low-expression groups. Our results suggested that high expressions of FHL2 and iASPP were poor prognostic factors for AML, but the prognostic effect might be overcome by allo-HSCT.

Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

PubMed Central

Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

2015-01-01

Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

PubMed

Petrich, Adam M; Gandhi, Mitul; Jovanovic, Borko; Castillo, Jorge J; Rajguru, Saurabh; Yang, David T; Shah, Khushboo A; Whyman, Jeremy D; Lansigan, Frederick; Hernandez-Ilizaliturri, Francisco J; Lee, Lisa X; Barta, Stefan K; Melinamani, Shruthi; Karmali, Reem; Adeimy, Camille; Smith, Scott; Dalal, Neil; Nabhan, Chadi; Peace, David; Vose, Julie; Evens, Andrew M; Shah, Namrata; Fenske, Timothy S; Zelenetz, Andrew D; Landsburg, Daniel J; Howlett, Christina; Mato, Anthony; Jaglal, Michael; Chavez, Julio C; Tsai, Judy P; Reddy, Nishitha; Li, Shaoying; Handler, Caitlin; Flowers, Christopher R; Cohen, Jonathon B; Blum, Kristie A; Song, Kevin; Sun, Haowei Linda; Press, Oliver; Cassaday, Ryan; Jaso, Jesse; Medeiros, L Jeffrey; Sohani, Aliyah R; Abramson, Jeremy S

2014-10-09

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed. © 2014 by The American Society of Hematology.

Statin and Metformin Use Prolongs Survival in Patients With Resectable Pancreatic Cancer.

PubMed

Kozak, Margaret M; Anderson, Eric M; von Eyben, Rie; Pai, Jonathan S; Poultsides, George A; Visser, Brendan C; Norton, Jeffrey A; Koong, Albert C; Chang, Daniel T

2016-01-01

The aim of this study was to investigate the impact of statin and metformin therapy on disease outcome for patients with pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 171 PDAC patients who underwent surgical resection at the Stanford Cancer Institute between 1998 and 2013. No patients received neoadjuvant therapy. Statin and metformin use was defined as use during initial consult and continuing upon discharge from the hospital after surgery. Dose of each medication was recorded, as was the type of statin taken. The median follow-up for all patients was 11.23 months (range, 0.2-105.0 months). Among the 171 patients included in our analysis, 18 patients (10.5%) took metformin and 34 patients (19.9%) took statins. Statin use was associated with better overall survival (OS) in patients with PDAC (P = 0.011). Metformin use was also associated with better OS (P = 0.035). The use of statins remained significant on multivariate analysis for OS (P = 0.014; hazards ratio, 0.33; 95% confidence interval, 0.139-0.799), but metformin use did not (P = 0.33; hazards ratio 0.60, 95% confidence interval, 0.211-1.675). Statin and metformin use is associated with improved OS in patients with resectable PDAC. These medications should be further investigated for possible long-term use in the general population.

National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

PubMed

Post, Carl M; Lin, Chi; Adeberg, Sebastian; Gupta, Mrigank; Zhen, Weining; Verma, Vivek

2018-03-01

The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prognostic Significance of Nodal Location and Ratio in Stage IIIC Endometrial Carcinoma Among a Multi-Institutional Academic Collaboration.

PubMed

Mayadev, Jyoti; Elshaikh, Mohamed A; Christie, Alana; Nagel, Christa; Kennedy, Vanessa; Khan, Nadia; Lea, Jayanthi; Ghanem, Ahmad; Miller, David; Xie, Xian-Jin; Folkert, Michael; Albuquerque, Kevin

2018-04-20

Stage IIIC endometrial carcinoma (EC) represents pathologically heterogenous patients with single/multiple pelvic (stage IIIC1) or paraaortic (stage IIIC2) lymph nodes (LNs). There is an increasing trend to offer adjuvant chemotherapy (CT) +/- radiation (RT) uniformly to these patients, regardless of substage. We investigate the prognostic significance of positive LN (pLN) number, ratio (%pLN), location (IIC1 vs. IIC2), and adjuvant treatment on patterns of failure and survival in a large collaborative multi-institutional series. Clinical data for stage III EC patients such as patient characteristics, surgery/pathologic details, adjuvant therapies (including CT, RT, and chemotherapy and radiation), and outcomes (including pelvic control [PC], disease-free survival [DFS], distant DFS, and overall survival [OS]) were collected from 3 academic institutions. Log-rank analyses, Cox regression univariate and multivariate analyses were performed. Of the 264 patients queried for stage III disease, 237 (73%) had pLN, and complete LN sampling for analysis. The mean number of pLN in the combined data were 3.9, with 26.1% of all LN sampled positive; 121 patients (51%) staged IIIC1, and 116 patients (49%) staged IIIC2. There was a significant difference in number of pLN (P=0.0006) and total LN sampled by institution (range, 13 to 35; P=0.0004), without a difference in %pLN (P=0.35). Ninety-seven of 220 (44.1%) have ≥20% pLN. While controlling for substage and institution, a decrease in DFS (hazard ratio [HR], 1.1; P=0.007), and OS (HR, 1.1; P=0.01) was observed with every increase of 10% in the pLN ratio. There was a significant difference in DFS (HR, 1.8; P=0.003), PC (HR, 1.9; P=0.004), and distant DFS (HR, 1.6; P=0.03), as well as a trend for decreased OS (HR, 1.6; P=0.08) for substage IIIC2 versus IIIC1 disease; 5 years DFS 40% versus 45%, OS 50% versus 57%. Patients received no adjuvant therapy (10%), CT alone (27%), RT alone (16%), or chemotherapy and radiation (47%). There was no significant difference in PC, DFS, or OS between the various treatment regimens. On univariate analysis, while pLN was significant, treatment type did not impact DFS or OS. On multivariate analysis for DFS, patient age, race, and IIIC1 versus IIIC2 substage retained significance (HR, 0.56; P=0.01). Stage III EC patients with substage IIIC2 disease have a significantly increased risk of local and distant disease recurrence and death from EC. A decrease in DFS and OS was observed with every increase of 10% in the pLN ratio. Stage IIIC2 patients represent a high-risk subpopulation for whom clinical trials, or targeted regimens should be explored to achieve improved oncologic outcomes.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, Lachlan J.; Huang, Shao Hui; Xu, Wei

Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodalmore » irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.« less

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.

2009-09-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. Onmore » univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.« less

Combination of Pre-Treatment DWI-Signal Intensity and S-1 Treatment: A Predictor of Survival in Patients with Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy and Sequential S-1.

PubMed

Zhang, Yu; Zhu, Xiaofei; Liu, Ri; Wang, Xianglian; Sun, Gaofeng; Song, Jiaqi; Lu, Jianping; Zhang, Huojun

2018-04-01

To identify whether the combination of pre-treatment radiological and clinical factors can predict the overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation and sequential S-1 (a prodrug of 5-FU combined with two modulators) therapy with improved accuracy compared with that of established clinical and radiologic risk models. Patients admitted with LAPC underwent diffusion weighted imaging (DWI) scan at 3.0-T (b = 600 s/mm 2 ). The mean signal intensity (SI b = 600) of region-of-interest (ROI) was measured. The Log-rank test was done for tumor location, biliary stent, S-1, and other treatments and the Cox regression analysis was done to identify independent prognostic factors for OS. Prediction error curves (PEC) were used to assess potential errors in prediction of survival. The accuracy of prediction was evaluated by Integrated Brier Score (IBS) and C index. 41 patients were included in this study. The median OS was 11.7 months (2.8-23.23 months). The 1-year OS was 46%. Multivariate analysis showed that pre-treatment SI b = 600 value and administration of S-1 were independent predictors for OS. The performance of pre-treatment SI b = 600 and S-1 treatment in combination was better than that of SI b = 600 or S-1 treatment alone. The combination of pre-treatment SI b = 600 and S-1 treatment could predict the OS in patients with LAPC undergoing SBRT and sequential S-1 therapy with improved accuracy compared with that of established clinical and radiologic risk models. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Outcome and Prognostic Factors in Endometrial Stromal Tumors: A Rare Cancer Network Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schick, Ulrike, E-mail: Ulrike.schick@icr.ac.uk; Bolukbasi, Yasmin; Thariat, Juliette

2012-04-01

Purpose: To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). Methods and Materials: A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. Results: Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administeredmore » to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age ({<=}60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I-II vs. III-IV). Positive lymph node staging had an impact on OS (p < 0.001). Conclusion: The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines.« less

Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

PubMed

Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

2018-01-01

We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Efficacy of Pemetrexed-based Chemotherapy in Comparison to Non-Pemetrexed-based Chemotherapy in Advanced, ALK+ Non-Small Cell Lung Cancer.

PubMed

Jo, Jaemin; Kim, Se Hyun; Kim, Yu Jung; Lee, Juhyun; Kim, Miso; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong Wan; Heo, Dae Seog; Chung, Jin Haeng; Jeon, Yoon Kyung; Lee, Jong Seok

2018-03-01

Previous retrospective studies suggest that anaplastic lymphoma kinase (ALK) mutation-positive (ALK+) non-small cell lung cancer (NSCLC) patients are sensitive to pemetrexed. To determine its efficacy, we retrospectively evaluated clinical outcomes of pemetrexed-based chemotherapy in patients with ALK+ NSCLC. We identified 126 patients with advanced, ALK+ NSCLC who received first-line cytotoxic chemotherapy. We compared response, progression-free survival (PFS), and overall survival (OS) rates according to chemotherapy regimens. Furthermore, we evaluated intracranial time to tumor progression (TTP) and proportion of ALK+ cells as prognostic factors. Forty-eight patients received pemetrexed-based chemotherapy, while 78 received other regimens as first-line treatment. The pemetrexed-based chemotherapy group showed superior overall response (44.7% vs. 14.3%, p<0.001) and disease control (85.1% vs. 62.3%, p=0.008) rates. The pemetrexed-based chemotherapy group also exhibited longer PFS (6.6 months vs. 3.8 months, p<0.001); OS rates were not significantly different. The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS. Intracranial TTP was similar between the treatment groups (32.7 months vs. 35.7 months, p=0.733). Patients who harbored a greater number of ALK+ tumor cells (≥70%) showed prolonged OS on univariate analysis (not reached vs. 44.8 months, p=0.041), but not on multivariate analysis (hazard ratio: 0.19, 95% confidence interval: 0.03-1.42; p=0.106). Pemetrexed-based regimens may prolong PFS in patients with ALK+ NSCLC as a first-line treatment, but are not associated with prolonged OS. Exposure to second-generation ALK inhibitors may improve OS rates in patients with ALK+ NSCLC. © Copyright: Yonsei University College of Medicine 2018

Prognostic value of PAX9 in patients with esophageal squamous cell carcinoma and its prediction value to radiation sensitivity.

PubMed

Tan, Bingxu; Wang, Jianbo; Song, Qingxu; Wang, Nana; Jia, Yibin; Wang, Cong; Yao, Bin; Liu, Zhulong; Zhang, Xiaomei; Cheng, Yufeng

2017-07-01

Abnormal paired box 9 (PAX9) expression is associated with tumorigenesis, cancer development, invasion and metastasis. The present study investigated the prognostic significance of PAX9 in esophageal squamous cell carcinoma (ESCC) and its role in predicting radiation sensitivity. A total of 52.8% (121/229) ESCC tissues were positive for PAX9. The 1‑, 3‑ and 5‑year disease‑free survival (DFS) rates were 72.2, 35.2 and 5.6%, respectively, and the overall survival (OS) rates were and 86.1, 44.4, and 23.1%, respectively, in PAX9‑positive tumors. In PAX9‑negative tumors, the one‑, three‑ and five‑year DFS rates were 76.9, 47.9 and 24.0%, and the OS rates were 90.9, 57.9 and 38.8%, respectively. Univariate analysis revealed that PAX9, differentiation, T stage, lymph node metastasis, and tumor‑node‑metastasis stage were associated with OS. Multivariate analysis of DFS and OS revealed that the hazard ratios for PAX9 were 0.624 (95% CI: 0.472‑0.869, P=0.004) and 0.673 (95% CI: 0.491‑0.922, P=0.014), respectively. Patients that received adjuvant therapy exhibited significant differences in the 5‑year DFS (P<0.001) and OS (P<0.001). PAX9‑positive ESCC patients who received post‑surgery radiotherapy had a significantly greater 5‑year DFS (P=0.011) and OS (P=0.009) than patients who received surgery only. Thus, PAX9 may be an independent prognostic factor for the surgical treatment of ESCC and a possible predictor of radiation sensitivity.

A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab.

PubMed

Berger, Martin D; Stintzing, Sebastian; Heinemann, Volker; Cao, Shu; Yang, Dongyun; Sunakawa, Yu; Matsusaka, Satoshi; Ning, Yan; Okazaki, Satoshi; Miyamoto, Yuji; Suenaga, Mitsukuni; Schirripa, Marta; Hanna, Diana L; Soni, Shivani; Puccini, Alberto; Zhang, Wu; Cremolini, Chiara; Falcone, Alfredo; Loupakis, Fotios; Lenz, Heinz-Josef

2018-02-15

Purpose: Vitamin D exerts its inhibitory influence on colon cancer growth by inhibiting Wnt signaling and angiogenesis. We hypothesized that SNPs in genes involved in vitamin D transport, metabolism, and signaling are associated with outcome in metastatic colorectal cancer (mCRC) patients treated with first-line FOLFIRI and bevacizumab. Experimental Design: 522 mCRC patients enrolled in the FIRE-3 (discovery cohort) and TRIBE (validation set) trials treated with FOLFIRI/bevacizumab were included in this study. 278 patients receiving FOLFIRI and cetuximab (FIRE-3) served as a control cohort. Six SNPs in 6 genes ( GC, CYP24A1, CYP27B1, VDR, DKK1, CST5 ) were analyzed. Results: In the discovery cohort, AA carriers of the GC rs4588 SNP encoding for the vitamin D-binding protein, and treated with FOLFIRI/bevacizumab had a shorter overall survival (OS) than those harboring any C allele (15.9 vs. 25.1 months) in both univariable ( P = 0.001) and multivariable analyses ( P = 0.047). This association was confirmed in the validation cohort in multivariable analysis (OS 18.1 vs. 26.2 months, HR, 1.83; P = 0.037). Interestingly, AA carriers in the control set exhibited a longer OS (48.0 vs. 25.2 months, HR, 0.50; P = 0.021). This association was further confirmed in a second validation cohort comprising refractory mCRC patients treated with cetuximab ± irinotecan (PFS 8.7 vs. 3.7 months) in univariable ( P = 0.033) and multivariable analyses ( P = 0.046). Conclusions: GC rs4588 SNP might serve as a predictive marker in mCRC patients treated with FOLFIRI/bevacizumab or FOLFIRI/cetuximab. Whereas AA carriers derive a survival benefit with FOLFIRI/cetuximab, treatment with FOLFIRI/bevacizumab is associated with a worse outcome. Clin Cancer Res; 24(4); 784-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors: an international tamoxifen exemestane adjuvant multinational trial analysis.

PubMed

Fontein, Duveken B Y; Seynaeve, Caroline; Hadji, Peyman; Hille, Elysée T M; van de Water, Willemien; Putter, Hein; Kranenbarg, Elma Meershoek-Klein; Hasenburg, Annette; Paridaens, Robert J; Vannetzel, Jean-Michel; Markopoulos, Christos; Hozumi, Yasuo; Bartlett, John M S; Jones, Stephen E; Rea, Daniel William; Nortier, Johan W R; van de Velde, Cornelis J H

2013-06-20

Specific adverse events (AEs) associated with endocrine therapy and related to depletion or blocking of circulating estrogens may be related to treatment efficacy. We investigated the relationship between survival outcomes and specific AEs including vasomotor symptoms (VMSs), musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with breast cancer participating in the international Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Primary efficacy end points were disease-free survival (DFS), overall survival (OS), and distant metastases (DM). VMSs, MSAEs, and VVSs arising in the first year of endocrine treatment were considered. Patients who did not start or who discontinued their allocated therapy and/or had an event (recurrence/death) within 1 year after randomization were excluded. Landmark analyses and time-dependent multivariate Cox proportional hazards models assessed survival differences up to 5 years from the start of treatment. A total of 9,325 patients were included. Patients with specific AEs (v nonspecific or no AEs) had better DFS and OS (multivariate hazard ratio [HR] for DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866]; MSAEs, 0.826 [95% CI, 0.694 to 0.982]; VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for OS: VMSs, 0.583 [95% CI, 0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570 [95% CI, 0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749 [95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not reporting these symptoms. Increasing numbers of specific AEs were also associated with better survival outcomes. Outcomes were unrelated to treatment allocation. Certain specific AEs are associated with superior survival outcomes and may therefore be useful in predicting treatment responses in patients with breast cancer treated with endocrine therapy.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base

PubMed Central

Haque, Waqar; Verma, Vivek; Butler, E. Brian

2018-01-01

Background Neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal cancer (EC) may utilize a wide variety of RT doses, without clear consensus to date. This study evaluated national practice patterns between lower dose (LD) (40–41.4 Gy) or higher dose (HD) (50–50.4 Gy) therapy, in addition to differences in survival and postoperative events. Methods The National Cancer Data Base (NCDB) was queried [2004–2013] for patients with newly-diagnosed cT1a-T4aN0/N+M0 EC that received neoadjuvant CRT followed by esophagectomy. Multivariable logistic regression determined factors predictive of receiving LD RT. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. Results Altogether, 5,025 patients met inclusion criteria; 257 (5%) received LD RT, while 4,768 (95%) received HD RT. LD RT was more likely delivered at academic centers (P=0.038), in more recent years (2009–2013, P=0.011), and to squamous cell carcinomas (P=0.001). HD RT tended to be administered with higher T stage as well as node-positive disease (P<0.05). The median OS in the LD and HD cohorts was 39.0 vs. 35.6 months (P=0.072), and 39.0 vs. 42.7 months after propensity matching (P=0.812). Dose did not independently correlate with OS on multivariate analysis (P=0.069), but treatment at academic centers correlated with improved OS (P=0.028). There were no differences between groups in the rates of 30-day readmission (P=0.182), 30-day mortality (P=0.314), or length of postoperative hospital stay (P=0.665), but the LD group experienced lower 90-day mortality (P=0.007). Conclusions Although neoadjuvant LD CRT has been underutilized for EC in the United States, it is rising in more recent years. Dose did not significantly impact survival before or after propensity matching, nor did it independently predict for survival. Treatment at academic facilities independently correlated with higher survival, which has implications for patient counseling. PMID:29564174

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma.

PubMed

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-06-27

Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients' overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.

Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, David H.A., E-mail: dhanguyen@yahoo.com; Departement de Radio-Oncologie, Hopital Maisonneuve-Rosemont, Montreal, Quebec; Truong, Pauline T.

2012-09-01

Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRTmore » consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease, clear margins, and distant disease limited to one subsite, bone-only involvement, or fewer than five metastatic lesions.« less

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.

2012-08-01

Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADTmore » and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.« less

Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merrell, Kenneth W.; Haddock, Michael G.; Quevedo, J. Fernando

Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gymore » in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection.« less

Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.

PubMed

Cella, D; Traina, S; Li, T; Johnson, K; Ho, K F; Molina, A; Shore, N D

2018-02-01

Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression. In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P < 0.0001). In multivariate models, all except pain intensity remained associated with OS. Pain intensity, PWB and FWB improvements remained associated with rPFS. In COU-AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results. PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The prognostic value of preoperative inflammation-based prognostic scores and nutritional status for overall survival in resected patients with nonmetastatic Siewert type II/III adenocarcinoma of esophagogastric junction.

PubMed

Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman

2017-07-01

Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.

The modified glasgow prognostic score is an independent prognostic indicator in neoadjuvantly treated adenocarcinoma of the esophagogastric junction

PubMed Central

Jomrich, Gerd; Hollenstein, Marlene; John, Maximilian; Baierl, Andreas; Paireder, Matthias; Kristo, Ivan; Ilhan-Mutlu, Aysegül; Asari, Reza; Preusser, Matthias; Schoppmann, Sebastian F.

2018-01-01

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients’ characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.3–89.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS. PMID:29467943

An association between preoperative anemia and decreased survival in early-stage non-small-cell lung cancer patients treated with surgery alone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yovino, Susannah; Kwok, Young; Krasna, Mark

2005-08-01

Purpose: Surgical resection is the mainstay of therapy for patients presenting with Stage I and II non-small-cell lung cancer (NSCLC). Despite optimal staging and surgery, these patients are still at significant risk for failure. The purpose of this study is to report a retrospective analysis of the outcome of patients treated with surgery alone, as well as to analyze prognostic factors associated with survival. Materials and Methods: From May 2000 to November 2002, there was a total of 125 patients who were treated with surgery for NSCLC at University of Maryland Medical Center. Of these, 82 Stage I and IImore » patients who received surgery alone as the definitive therapy were identified. The median age of the entire cohort was 68 years (range, 43-88 years). There were 48 males and 34 females. Sixty-three patients (76.8%) underwent lobectomies whereas 19 patients (23.2%) underwent nonlobectomy (wedge resection or segmentectomy) procedures. Patients who received neoadjuvant or adjuvant radiation therapy or chemotherapy were excluded from the study. Factors included in univariate and multivariate analyses were age, sex, tumor histology, pathologic stage, p53 status, preoperative hemoglobin (Hgb), and type of surgery performed. Endpoints of the study were relapse-free survival (RFS) and overall survival (OS). Results: Median follow-up was 20.8 months (range, 0.4-43.2 months). For the entire cohort, the 2-year RFS was 66.0% and 2-year OS was 76.3%. Median survival for the entire cohort has not been achieved. In univariate analysis, the only factor that achieved statistical significance was preoperative Hgb level. Patients who had preoperative Hgb <12 mg/dL experienced significantly worse RFS (mean RFS: 26.6 months vs. 34.9 months, p = 0.043) and OS (median OS: 27 months vs. 42.5 months, p = 0.011). For Stage I patients (n = 72), the 2-year RFS and OS were 66.4% and 77.1%, respectively. In the subgroup of stage IA patients (n = 37), there was a trend toward decreased overall survival in the anemic patients (2-year OS of 65.6% vs. 90.9%, p = 0.07). For Stage II patients (n = 10), the 2-year RFS and OS were 60.0% and 66.7%. In the Cox multivariate regression analysis, the only factor that achieved statistical significance was preoperative Hgb, with patients with Hgb <12 mg/dL having decreased RFS (RR 4.1, p = 0.020) and OS (RR 2.9, p = 0.026). There was a trend toward worse RFS (p = 0.056) and OS (p = 0.068) in p53-negative patients (n = 39). Stage, histologic type, type of surgery performed, age, and sex did not affect outcome. Conclusions: In our cohort of mostly Stage I NSCLC patients treated with surgery only, preoperative Hgb <12 mg/dL predicted for worse outcome. This effect was observed even in the traditionally low-risk subgroup of completely resected stage IA patients. Much has been written in the literature about anemia causing possible worsening of tumor hypoxia within solid tumors, thereby increasing radio-resistance. This has been a popular argument to explain poorer outcomes of anemic patients with solid tumors who undergo radiotherapy. However, our data suggest that anemia may be a sign of a more aggressive tumor that is at an increased risk of failure independent of the treatment modality.« less

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

Analysis of fracture healing in osteopenic bone caused by disuse: experimental study.

PubMed

Paiva, A G; Yanagihara, G R; Macedo, A P; Ramos, J; Issa, J P M; Shimano, A C

2016-03-01

Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2), suspended and immobilized for 2 weeks after osteotomy (OS2), unrestricted and immobilized for 6 weeks after osteotomy (OU6), and suspended and immobilized for 6 weeks after osteotomy (OS6). Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, P<0.000). Similarly, the mechanical properties showed that animals had stronger bones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, P<0.000). Histomorphometry indicated gradual bone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension.

Prospective evaluation of Ki-67 system in histological grading of soft tissue sarcomas in the Japan Clinical Oncology Group Study JCOG0304.

PubMed

Tanaka, Kazuhiro; Hasegawa, Tadashi; Nojima, Takayuki; Oda, Yoshinao; Mizusawa, Junki; Fukuda, Haruhiko; Iwamoto, Yukihide

2016-04-18

The correct clinical staging of soft tissue sarcomas (STS) is critical for the selection of treatments. The staging system consists of histological grade of the tumors and French Federation of Cancer Center (FNCLCC) system based on mitotic count is widely used for the grading. In this study, we compared the validity and usefulness of Ki-67 grading system with FNCLCC system in JCOG0304 trial which investigated the efficacy and safety of perioperative chemotherapy with doxorubicin and ifosfamide for STS. All 70 eligible patients with STS in the extremities treated by perioperative chemotherapy in JCOG0304 were analyzed. Univariate and multivariate Cox regression analyses were conducted to investigate an influence on overall survival. The reproducibility of Ki-67 grading system in the histological grading of STS was higher than FNCLCC system (κ = 0.54 [95 % CI 0.39-0.71], and 0.46 [0.32-0.62], respectively). Although FNCLCC grade was not associated with overall survival (OS) in univariate analysis (HR 2.80 [0.74-10.55], p = 0.13), Ki-67 grading system had a tendency to associate with OS in univariate analysis (HR 4.12 [0.89-19.09], p = 0.07) and multivariate analysis with backward elimination (HR 3.51 [0.75-16.36], p = 0.11). This is the first report demonstrating the efficacy of Ki-67 grading system for the patients with STS in the prospective trial. The results indicate that Ki-67 grading system might be useful for the evaluation of histological grade of STS.

Glycolytic activity in breast cancer using 18F-FDG PET/CT as prognostic predictor: A molecular phenotype approach.

PubMed

Garcia Vicente, A M; Soriano Castrejón, A; Amo-Salas, M; Lopez Fidalgo, J F; Muñoz Sanchez, M M; Alvarez Cabellos, R; Espinosa Aunion, R; Muñoz Madero, V

2016-01-01

To explore the relationship between basal (18)F-FDG uptake in breast tumors and survival in patients with breast cancer (BC) using a molecular phenotype approach. This prospective and multicentre study included 193 women diagnosed with BC. All patients underwent an (18)F-FDG PET/CT prior to treatment. Maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N), and the N/T index was obtained in all the cases. Metabolic stage was established. As regards biological prognostic parameters, tumors were classified into molecular sub-types and risk categories. Overall survival (OS) and disease free survival (DFS) were obtained. An analysis was performed on the relationship between semi-quantitative metabolic parameters with molecular phenotypes and risk categories. The effect of molecular sub-type and risk categories in prognosis was analyzed using Kaplan-Meier and univariate and multivariate tests. Statistical differences were found in both SUVT and SUVN, according to the molecular sub-types and risk classifications, with higher semi-quantitative values in more biologically aggressive tumors. No statistical differences were observed with respect to the N/T index. Kaplan-Meier analysis revealed that risk categories were significantly related to DFS and OS. In the multivariate analysis, metabolic stage and risk phenotype showed a significant association with DFS. High-risk phenotype category showed a worst prognosis with respect to the other categories with higher SUVmax in primary tumor and lymph nodes. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naïve Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis.

PubMed

Magnuson, William J; Lester-Coll, Nataniel H; Wu, Abraham J; Yang, T Jonathan; Lockney, Natalie A; Gerber, Naamit K; Beal, Kathryn; Amini, Arya; Patil, Tejas; Kavanagh, Brian D; Camidge, D Ross; Braunstein, Steven E; Boreta, Lauren C; Balasubramanian, Suresh K; Ahluwalia, Manmeet S; Rana, Niteshkumar G; Attia, Albert; Gettinger, Scott N; Contessa, Joseph N; Yu, James B; Chiang, Veronica L

2017-04-01

Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

Analysis of failure in patients with adenoid cystic carcinoma of the head and neck. An international collaborative study.

PubMed

Amit, Moran; Binenbaum, Yoav; Sharma, Kanika; Ramer, Naomi; Ramer, Ilana; Agbetoba, Abib; Miles, Brett; Yang, Xinjie; Lei, Delin; Bjøerndal, Kristine; Godballe, Christian; Mücke, Thomas; Wolff, Klaus-Dietrich; Fliss, Dan; Eckardt, André M; Copelli, Chiara; Sesenna, Enrico; Palmer, Frank; Patel, Snehal; Gil, Ziv

2014-07-01

Adenoid cystic carcinoma (ACC) is a locally aggressive tumor with a high prevalence of distant metastases. The purpose of this study was to identify independent predictors of outcome and to characterize the patterns of failure. An international retrospective review was conducted of 489 patients with ACC treated between 1985 and 2011 in 9 cancer centers worldwide. Five-year overall-survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 76%, 80%, and 68%, respectively. Independent predictors of OS and DSS were: age, site, N classification, and presence of distant metastases. N classification, age, and bone invasion were associated with DFS on multivariate analysis. Age, tumor site, orbital invasion, and N classification were independent predictors of distant metastases. The clinical course of ACC is slow but persistent. Paranasal sinus origin is associated with the lowest distant metastases rate but with the poorest outcome. These prognostic estimates should be considered when tailoring treatment for patients with ACC. Copyright © 2013 Wiley Periodicals, Inc.

Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy.

PubMed

Saito, Yuki; Omura, Go; Yasuhara, Kazuo; Rikitake, Ryoko; Akashi, Ken; Fukuoka, Osamu; Yoshida, Masafumi; Ando, Mizuo; Asakage, Takahiro; Yamasoba, Tatsuya

2017-08-01

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma. Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases. We reviewed 135 records (120 men and 15 women; age range, 36-84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS. Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1535-1543, 2017. © 2017 Wiley Periodicals, Inc.

[Neutrophil to lymphocyte ratio in peripheral blood: a novel independent prognostic factor in patients with head and neck squamous cell carcinoma].

PubMed

Wu, F; Wu, L L; Zhu, L X

2017-01-23

Objective: To investigate whether neutrophil to lymphocyte ratio (NLR) in peripheral blood can be an independent prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Clinical data of 97 HNSCC patients who received surgical treatment in our department between January 2008 and January 2012 were analyzed retrospectively. The 97 patients were divided into low NLR group (NLR≤5, n =69) and high NLR group (NLR>5, n =28) according to the NLR in preoperative peripheral blood. The relationships of NLR and clinicopathological features were analyzed. Kaplan-Meier method was used for univariate survival analysis and Cox proportional hazard model for multivariate survival analysis. Results: The clinical stages were significantly different between high NLR group and low NLR group ( P <0.05), however, the age, gender, location, lymph node metastasis, smoking and alcohol of the two groups showed no significant differences ( P > 0.05 of all). Univariate survival analysis showed that smoking, lymph node metastasis, clinical stage and NLR value were risk factors for 3-year overall survival (OS) rate and relapse-free survival (RFS) rate of HNSCC patients ( P <0.05). The OS rate of high NLR and low NLR groups was 42.9% and 91.3%, and the RFS rate was 44.2% and 80.1%, respectively, with a statistically significant difference ( P <0.05 for both). Cox multivariate survival analysis showed that clinical stage and NLR were independent factors for prognostic evaluation of HNSCC patients ( P <0.05 for both). Conclusions: NLR level is significantly associated with clinical stage of HNSCC. High NLR is an independent prognostic rick factor and plays an important role in prognostic evaluation of HNSCC patients.

A preliminary investigation into textural features of intratumoral metabolic heterogeneity in 18F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy

PubMed Central

Ho, Kung-Chu; Fang, Yu-Hua Dean; Chung, Hsiao-Wen; Yen, Tzu-Chen; Ho, Tsung-Ying; Chou, Hung-Hsueh; Hong, Ji-Hong; Huang, Yi-Ting; Wang, Chun-Chieh; Lai, Chyong-Huey

2016-01-01

We examined the role of intratumoral metabolic heterogeneity on 18F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial 18F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity < 55% and the decline of TLG (∆TLG) < 60% were associated with significantly worse OS. In multivariate analysis, only ∆TLG was significant (P = 0.009). Combining pretreatment with intra-treatment factors, we defined the patients with a initial GLNU > 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course. PMID:27508103

Racial differences in advanced colorectal cancer outcomes and pharmacogenetics: a subgroup analysis of a large randomized clinical trial.

PubMed

Sanoff, Hanna K; Sargent, Daniel J; Green, Erin M; McLeod, Howard L; Goldberg, Richard M

2009-09-01

Racial disparities in colorectal cancer (CRC) survival are documented, but there are few data on comparative response to chemotherapy. A subgroup analysis of a multisite National Cancer Institute-sponsored trial (N9741) was performed comparing outcomes of black and white patients with metastatic CRC receiving uniform treatment. Adverse events (AEs), response rate (RR), time to progression (TTP), overall survival (OS), and dose-intensity were examined as a function of self-reported race in 1,412 patients treated with irinotecan/fluorouracil, fluorouracil/oxaliplatin, or irinotecan/oxaliplatin. Pharmacogenetic analysis was performed on 486 patients with blood available for germline DNA analysis. OS was 1.5 months shorter and TTP was 0.6 months shorter in black than white patients (OS: hazard ratio [HR] = 1.13; 95% CI, 0.90 to 1.42; TTP: HR = 0.91, 95% CI, 0.73 to 1.13); neither difference was statistically significant. RR was significantly higher in whites (41%) than blacks (28%; P = .008). Grade 3 or greater AEs were also higher in whites (48%) than blacks (34%; P = .004). These relationships were maintained in multivariate models adjusting for arm, age, sex, and performance status. There was no difference in dose-intensity of delivered therapy. Significant racial differences in prevalence of pharmacogenetic variants were observed, although small sample size precluded investigating the relationship between treatment, race, and genotype. OS and TTP are similar in black and white patients treated per protocol with standardized therapy for metastatic CRC. However, RR and AEs vary considerably by race. The marked racial differences in relevant pharmacogenetics, a potential explanation for differing RR and AEs, are worthy of future study.

A preliminary investigation into textural features of intratumoral metabolic heterogeneity in (18)F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy.

PubMed

Ho, Kung-Chu; Fang, Yu-Hua Dean; Chung, Hsiao-Wen; Yen, Tzu-Chen; Ho, Tsung-Ying; Chou, Hung-Hsueh; Hong, Ji-Hong; Huang, Yi-Ting; Wang, Chun-Chieh; Lai, Chyong-Huey

2016-01-01

We examined the role of intratumoral metabolic heterogeneity on (18)F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial (18)F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity < 55% and the decline of TLG (∆TLG) < 60% were associated with significantly worse OS. In multivariate analysis, only ∆TLG was significant (P = 0.009). Combining pretreatment with intra-treatment factors, we defined the patients with a initial GLNU > 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course.

Prognostic factors in patients with advanced renal cell carcinoma.

PubMed

Muriel López, Carolina; Esteban, Emilio; Berros, Jose Pablo; Pardo, Pablo; Astudillo, Aurora; Izquierdo, Marta; Crespo, Guillermo; Sanmamed, Miguel; Fonseca, Paula J; Martínez-Camblor, Pablo

2012-12-01

The purpose of this study was to evaluate prognostic factors in patients with RCC. The expression of several biomarkers were measured by immunohistochemistry (IHC), together with 2 analytic factors (thrombocytosis and neutrophilia), in 135 patients with advanced RCC treated with new targeted drugs (NTDs) (n = 67) and/or cytokines (CKs) (n = 68)-with 23 of the patients who received CKs also receiving NTDs-between July 1996 and February 2010. Relationships with overall survival (OS) and progression-free survival (PFS) were searched for. Univariate statistical analysis revealed that high expression of hypoxia-inducible factor-1α (HIF-1α) correlated with poor prognosis in NTD treatment (PFS, 5.4 vs. 13.5, low expression months; P = .033) and CK treatment (PFS, 3.3 vs. 5.7, low expression; P = .003). Overexpression of carbonic anhydrase IX (CAIX) was associated with better prognosis with NTD treatment (OS, 32.1 vs. 7.8 months; P < .001) and CK treatment (OS, 32.9 vs. 5.9 months; P = .001). Positive PTEN was related to good prognosis with sunitinib (PFS, 15.1 vs. 6.5 months; P = .003) and CKs (OS, 13.7 vs. 7.9 months; P = .039). Increased expression of p21 was related to poor prognosis with NTD treatment (PFS, 5.9 vs. 16.8 months; P = .024) and CK treatment (PFS, 3.9 vs. 7.5 months; P < .001) Thrombocytosis was related to poor prognosis with NTDs (OS, 15.9 vs. 26.7 months; P = .007) and CKs (OS, 5.9 vs. 14.3 months; P = .010). Neutrophilia was related to poor prognosis with NTDs (OS, 17.6 vs. 25.4 months; P = .063) and CKs (OS, 5.9 vs. 12.8 months; P = .035). Multivariate analysis revealed that overexpression of CAIX was a favorable prognostic factor independent of PFS (hazard ratio [HR], 0.107; P < .001) and OS (HR, 0.055; P < .001). HIF-1α, PTEN, p21, thrombocytosis, neutrophilia, and CAIX in particular are useful prognostic factors in patients with advanced RCC. Copyright © 2012 Elsevier Inc. All rights reserved.

Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741.

PubMed

Sanoff, Hanna K; Sargent, Daniel J; Campbell, Megan E; Morton, Roscoe F; Fuchs, Charles S; Ramanathan, Ramesh K; Williamson, Stephen K; Findlay, Brian P; Pitot, Henry C; Goldberg, Richard M

2008-12-10

In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups. A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase). Multivariate prognostic factor analysis was used to assess clinical factors for their relationships to OS, TTP, response, and toxicity by using Cox and logistic regression models. The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128). OS and TTP were significantly longer for FOLFOX (20.2 months and 8.9 months, respectively) than for IFL (14.6 months and 6.1 months, respectively; P < .001 for both) or for IROX (17.3 months and 6.7 months, respectively; P < .001 for both). OS differed by risk group: 20.7 months for low risk, 17.4 months for intermediate risk, and 9.4 months for high risk (P < .001). FOLFOX treatment was superior in all risk groups and was the most powerful prognostic factor for OS, TTP, response rate, and toxicity. The 9.8% 5-year OS in patients with metastatic colorectal cancer who were treated with first-line FOLFOX sets a new benchmark. Neither baseline risk group nor any prognostic factor examined was predictive of treatment-specific outcome. However, treatment efficacy and patient longevity varied as a function of risk group.

Five-Year Data and Prognostic Factor Analysis of Oxaliplatin and Irinotecan Combinations for Advanced Colorectal Cancer: N9741

PubMed Central

Sanoff, Hanna K.; Sargent, Daniel J.; Campbell, Megan E.; Morton, Roscoe F.; Fuchs, Charles S.; Ramanathan, Ramesh K.; Williamson, Stephen K.; Findlay, Brian P.; Pitot, Henry C.; Goldberg, Richard M.

2008-01-01

Purpose In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups. Patients and Methods A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase). Multivariate prognostic factor analysis was used to assess clinical factors for their relationships to OS, TTP, response, and toxicity by using Cox and logistic regression models. Results The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128). OS and TTP were significantly longer for FOLFOX (20.2 months and 8.9 months, respectively) than for IFL (14.6 months and 6.1 months, respectively; P < .001 for both) or for IROX (17.3 months and 6.7 months, respectively; P < .001 for both). OS differed by risk group: 20.7 months for low risk, 17.4 months for intermediate risk, and 9.4 months for high risk (P < .001). FOLFOX treatment was superior in all risk groups and was the most powerful prognostic factor for OS, TTP, response rate, and toxicity. Conclusion The 9.8% 5-year OS in patients with metastatic colorectal cancer who were treated with first-line FOLFOX sets a new benchmark. Neither baseline risk group nor any prognostic factor examined was predictive of treatment-specific outcome. However, treatment efficacy and patient longevity varied as a function of risk group. PMID:19001325

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

Tumor deposits counted as positive lymph nodes in TNM staging for advanced colorectal cancer: a retrospective multicenter study.

PubMed

Li, Jun; Yang, Shengke; Hu, Junjie; Liu, Hao; Du, Feng; Yin, Jie; Liu, Sai; Li, Ci; Xing, Shasha; Yuan, Jiatian; Lv, Bo; Fan, Jun; Leng, Shusheng; Zhang, Xin; Wang, Bing

2016-04-05

We investigated the possibility of counting tumor deposits (TDs) as positive lymph nodes (pLNs) in the pN category and evaluated its prognostic value for colorectal cancer (CRC) patients. A new pN category (npN category) was calculated using the numbers of pLNs plus TDs. The npN category included 4 tiers: npN1a (1 tumor node), npN1b (2-3 tumor nodes), npN2a (4-6 tumor nodes), and npN2b (≥7 tumor nodes). We identified 4,121 locally advanced CRC patients, including 717 (11.02%) cases with TDs. Univariate and multivariate analyses were performed to evaluate the disease-free and overall survival (DFS and OS) for npN and pN categories. Multivariate analysis showed that the npN and pN categories were both independent prognostic factors for DFS (HR 1.614, 95% CI 1.541 to 1.673; HR 1.604, 95% CI 1.533 to 1.679) and OS (HR 1.633, 95% CI 1.550 to 1.720; HR 1.470, 95% CI 1.410 to 1.532). However, the npN category was superior to the pN category by Harrell's C statistic. We conclude that it is thus feasible to consider TDs as positive lymph nodes in the pN category when evaluating the prognoses of CRC patients, and the npN category is potentially superior to the TNM (7th edition) pN category for predicting DFS and OS among advanced CRC patients.

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

PubMed

Perez, Marco V; Hoffmann, Thomas J; Tang, Hua; Thornton, Timothy; Stefanick, Marcia L; Larson, Joseph C; Kooperberg, Charles; Reiner, Alex P; Caan, Bette; Iribarren, Carlos; Risch, Neil

2013-09-01

Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans. © 2013.

Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma.

PubMed

Sohn, Bo Hwa; Shim, Jae-Jun; Kim, Sang-Bae; Jang, Kyu Yun; Kim, Soo Mi; Kim, Ji Hoon; Hwang, Jun Eul; Jang, Hee-Jin; Lee, Hyun-Sung; Kim, Sang-Cheol; Jeong, Woojin; Kim, Sung Soo; Park, Eun Sung; Heo, Jeonghoon; Kim, Yoon Jun; Kim, Dae-Ghon; Leem, Sun-Hee; Kaseb, Ahmed; Hassan, Manal M; Cha, Minse; Chu, In-Sun; Johnson, Randy L; Park, Yun-Yong; Lee, Ju-Seog

2016-03-01

The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. We analyzed gene expression data from Mst1/2(-/-) and Sav1(-/-) mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P < 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. ©2015 American Association for Cancer Research.

Costs associated with Eribulin treatment for patients with metastatic breast cancer in a comprehensive cancer center in France.

PubMed

Hurtaud, Aline; Donnadieu, Anne; Escalup, Laurence; Cottu, Paul H; Baffert, Sandrine

2016-12-01

There is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven ® ) has shown a significant improvement in overall survival (OS) in this setting. Its use may however be hampered by its cost, which is up to three times the cost of other standard drugs. We report the clinical outcomes and health care costs of a large series of consecutive MBC patients treated with Eribulin. A monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model. We included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0-13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028-21,360], and €2581 [CI 95%: 2226-3038] per month. Eribulin administration contributed to 79% of per-patient costs. Innovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diffuse myogenin expression by immunohistochemistry is an independent marker of poor survival in pediatric rhabdomyosarcoma: a tissue microarray study of 71 primary tumors including correlation with molecular phenotype.

PubMed

Heerema-McKenney, Amy; Wijnaendts, Liliane C D; Pulliam, Joseph F; Lopez-Terrada, Dolores; McKenney, Jesse K; Zhu, Shirley; Montgomery, Kelli; Mitchell, Janet; Marinelli, Robert J; Hart, Augustinus A M; van de Rijn, Matt; Linn, Sabine C

2008-10-01

The pathologic classification of rhabdomyosarcoma (RMS) into embryonal or alveolar subtype is an important prognostic factor guiding the therapeutic protocol chosen for an individual patient. Unfortunately, this classification is not always straightforward, and the diagnostic criteria are controversial in a subset of cases. Ancillary studies are used to aid in the classification, but their potential use as independent prognostic factors is rarely studied. The aim of this study is to identify immunohistochemical markers of potential prognostic significance in pediatric RMS and to correlate their expression with PAX-3/FKHR and PAX-7/FKHR fusion status. A single tissue microarray containing 71 paraffin-embedded pediatric RMSs was immunostained with antibodies against p53, bcl-2, Ki-67, CD44, myogenin, and MyoD1. The tissue microarray and whole paraffin blocks were studied for PAX-3/FKHR and PAX-7/FKHR gene fusions by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction. Clinical follow-up data were available for each patient. Immunohistochemical staining results and translocation status were correlated with recurrence-free interval (RFI) and overall survival (OS) using the Kaplan-Meier method, the log-rank test, and Cox proportional hazard regression. The minimum clinical follow-up interval was 24 months (median follow-up=57 mo). On univariable analysis, immunohistochemical expression of myogenin, bcl-2, and identification of a gene fusion were associated with decreased 5-year RFI and 10-year OS (myogenin RFI P=0.0028, OS P=0.0021; bcl-2 RFI P=0.037, OS P=0.032; gene fusion RFI P=0.0001, OS P=0.0058). After adjustment for Intergroup Rhabdomyosarcoma Study-TNM stage, tumor site, age, tumor histology, and translocation status by multivariable analysis, only myogenin retained an independent association with RFI (P=0.034) and OS (P=0.0069). In this retrospective analysis, diffuse immunohistochemical reactivity for myogenin in RMS correlates with decreased RFI and OS, independent of histologic subtype, translocation status, tumor site, or stage.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV.

PubMed

Saussele, Susanne; Krauss, Marie-Paloma; Hehlmann, Rüdiger; Lauseker, Michael; Proetel, Ulrike; Kalmanti, Lida; Hanfstein, Benjamin; Fabarius, Alice; Kraemer, Doris; Berdel, Wolfgang E; Bentz, Martin; Staib, Peter; de Wit, Maike; Wernli, Martin; Zettl, Florian; Hebart, Holger F; Hahn, Markus; Heymanns, Jochen; Schmidt-Wolf, Ingo; Schmitz, Norbert; Eckart, Michael J; Gassmann, Winfried; Bartholomäus, Andrea; Pezzutto, Antonio; Leibundgut, Elisabeth Oppliger; Heim, Dominik; Krause, Stefan W; Burchert, Andreas; Hofmann, Wolf-Karsten; Hasford, Joerg; Hochhaus, Andreas; Pfirrmann, Markus; Müller, Martin C

2015-07-02

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874. © 2015 by The American Society of Hematology.

Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML Study IV

PubMed Central

Krauß, Marie-Paloma; Hehlmann, Rüdiger; Lauseker, Michael; Proetel, Ulrike; Kalmanti, Lida; Hanfstein, Benjamin; Fabarius, Alice; Kraemer, Doris; Berdel, Wolfgang E.; Bentz, Martin; Staib, Peter; de Wit, Maike; Wernli, Martin; Zettl, Florian; Hebart, Holger F.; Hahn, Markus; Heymanns, Jochen; Schmidt-Wolf, Ingo; Schmitz, Norbert; Eckart, Michael J.; Gassmann, Winfried; Bartholomäus, Andrea; Pezzutto, Antonio; Leibundgut, Elisabeth Oppliger; Heim, Dominik; Krause, Stefan W.; Burchert, Andreas; Hofmann, Wolf-Karsten; Hasford, Joerg; Hochhaus, Andreas; Pfirrmann, Markus; Müller, Martin C.

2015-01-01

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874. PMID:25918346

T-cell subsets in lymph nodes identify a subgroup of follicular lymphoma patients with favorable outcome.

PubMed

Magnano, Laura; Martínez, Antonio; Carreras, Joaquim; Martínez-Trillos, Alejandra; Giné, Eva; Rovira, Jordina; Dlouhy, Ivan; Baumann, Tycho; Balagué, Olga; Campo, Elías; López-Guillermo, Armando; Villamor, Neus

2017-04-01

We have analyzed in lymph nodes at diagnosis of 75 patients with follicular lymphoma (FL) the relationship between different T-cell subpopulations, assessed by immunohistochemistry (IHC) and flow cytometry (FC), with the outcome. CD4 + cells were the most abundant T-cells in tumor tissue sections, whilst CD57 + cells were the less frequent. In addition to nonambulatory performance status, advanced stage and FLIPI, low CD4 + CD57 + /CD4 + ratio (p = .041), and low CD4 + /CD8 + ratio (p = .008) predicted poor overall survival (OS). Multivariate analysis showed that CD4 + CD57 + /CD4 + ratio was the most important variable for OS. In conclusion, T-cell subpopulations, including CD4 + CD57 + /CD4 + ratio analyzed by FC, could identify FL patients with favorable outcome.

Comparative composition, diversity, and abundance of oligosaccharides in early lactation milk from commercial dairy and beef cows.

PubMed

Sischo, William M; Short, Diana M; Geissler, Mareen; Bunyatratchata, Apichaya; Barile, Daniela

2017-05-01

Prebiotics are nondigestible dietary ingredients, usually oligosaccharides (OS), that provide a health benefit to the host by directly modulating the gut microbiota. Although there is some information describing OS content in dairy-source milk, no information is available to describe the OS content of beef-source milk. Given the different trait emphasis between dairy and beef for milk production and calf survivability, it is plausible that OS composition, diversity, and abundance differ between production types. The goal of this study was to compare OS in milk from commercial dairy and beef cows in early lactation. Early-lactation multiparous cows (5-12 d in milk) from 5 commercial Holstein dairy herds and 5 Angus or Angus hybrid beef herds were sampled once. Milk was obtained from each enrolled cow and frozen on the farm. Subsequently, each milk sample was assessed for total solids, pH, and OS content and relative abundance. Oligosaccharide diversity and abundance within and between samples was transformed through principal component analysis to reduce data complexity. Factors from principal component analysis were used to create similarity clusters, which were subsequently used in a multivariate logistic regression. In total, 30 OS were identified in early-lactation cow milk, including 21 distinct OS and 9 isomers with unique retention times. The majority of OS detected in the milk samples were present in all individual samples regardless of production type. Two clusters described distribution patterns of OS for the study sample; when median OS abundance was compared between the 2 clusters, we found that overall OS relative abundance was consistently greater in the cluster dominated by beef cows. For several of the structures, including those with known prebiotic effect, the difference in abundance was 2- to 4-fold greater in the beef-dominated cluster. Assuming that beef OS content in milk is the gold standard for cattle, it is likely that preweaning dairy calves are deprived of dietary-source OS. Although supplementing rations with OS is an approach to rectify this deficiency, understanding the health and productivity effects of improving OS abundance being fed to preweaning calves is a necessary next step before recommending supplementation. These studies should account for the observation that OS products are variable for both OS diversity and structural complexity, and some products may not be suitable as prebiotics. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Clinicopathological characteristics and prognostic factors of primary gastrointestinal lymphoma: a 22-year experience from South China.

PubMed

Li, Minrui; Zhang, Shenghong; Gu, Fang; Xiao, Weiwei; Yao, Jiayan; Chao, Kang; Chen, Minhu; Li, Juan; Zhong, Bihui

2014-01-01

Primary gastrointestinal lymphoma (PGIL) is a kind of relatively rare cancer and easily misdiagnosed due to its unspecific signs in digestive tract. Data including 216 patients histologically diagnosed as PGIL between January 1991 and October 2012 from The First Affiliated Hospital of Sun Yat-sen University were reviewed. This study was to investigate the clinicopathological features and prognosis, and make the comparison between the different sites of PGIL. Abdominal pain (75.9%) was the most frequent symptom and intermediate-grade lymphoma (53.7%) presented as the most common histological type. Intestine (55.1%) was the most common site involved, followed by stomach (38.5%), both intestine and stomach (6.4%). PGIL of different original site showed distinguished clinicopathological characteristics that patients in Stomach and GI group were older than Intestine group (Mean age: 54 and 53 vs. 43 years, p<0.001); diarrhea, B symptom, abdominal mass and complication occurred more in intestine group. Histologically, high-grade lymphoma (especially T-cell type) almost located in Intestine group (82.5%). Five-year overall survival (OS) and event-free survival (EFS) for all PGIL patients were 56.4% and 49.3%, respectively. Stomach group had better OS (72.3%) and EFS (48.4%) than Intestine group (43.1% and 23.6% respectively), but it lost the significance in the multivariate analysis. Univariate and multivariate analysis revealed that performance status, lactate dehydrogenase (LDH) level and histological type were independent prognostic factors for PGIL.

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer.

PubMed

Vyfhuis, Melissa A L; Burrows, Whitney M; Bhooshan, Neha; Suntharalingam, Mohan; Donahue, James M; Feliciano, Josephine; Badiyan, Shahed; Nichols, Elizabeth M; Edelman, Martin J; Carr, Shamus R; Friedberg, Joseph; Henry, Gavin; Stewart, Shelby; Sachdeva, Ashutosh; Pickering, Edward M; Simone, Charles B; Feigenberg, Steven J; Mohindra, Pranshu

2018-06-01

To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P = .004; FFR: HR 0.426, 95% CI 0.250-0.726, P = .002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P = .001; FFR: HR 0.455, 95% CI 0.266-0.778, P = .004). However, pCR did not independently impact OS (P = .918) or FFR (P = .474). Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Survival Analyses and Prognosis of Plasma Cell Myeloma and Plasmacytoma-Like Post-Transplant Lymphoproliferative Disorders

PubMed Central

Rosenberg, Aaron S.; Ruthazer, Robin; Paulus, Jessica K.; Kent, David M.; Evens, Andrew M.; Klein, Andreas K.

2016-01-01

Background Multiple myeloma/plasmacytoma-like post-transplant lymphoproliferative disorder (PTLD-MM) is a rare complication of solid organ transplant. Case series have shown variable outcomes and survival data in the modern era are lacking. Methods A cohort of 212 PTLD-MM patients was identified in the Scientific Registry of Transplant Recipients between 1999-2011. Overall survival (OS) was estimated using the Kaplan-Meier method and the effects of treatment and patient characteristics on OS evaluated with Cox proportional hazards models. OS in 185 PTLD-MM patients was compared with 4048 matched controls with multiple myeloma (SEER-MM) derived from SEER. Results Men comprised 71% of patients; extramedullary disease was noted in 58%. Novel therapeutic agents were used in 19% of patients (more commonly 2007-2011 versus 1999-2006 (P=0.01)), reduced immunosuppression in 55%, and chemotherapy in 32%. Median OS was 2.4 years, and improved in the later time period (aHR 0.64, P=0.05). Advanced age, creatinine>2, Caucasian race and use of OKT3 were associated with inferior OS in multivariable analysis. OS of PTLD-MM is significantly inferior to SEER-MM patients (aHR 1.6, p<0.001). Improvements in OS over time differed between PTLD-MM and SEER-MM. Median OS of patients diagnosed 2000-2005 was shorter for PTLD-MM than SEER-MM patients (18 vs 47 months P<0.001). There was no difference among those diagnosed 2006-2010 (44 mo vs median not reached P=0.5) (interaction P=0.08). Conclusions Age at diagnosis, elevated creatinine, Caucasian race and OKT3 were associated with inferior survival in patients with PTLD-MM. Survival of PTLD-MM is inferior to SEER-MM, though significant improvements in survival have been documented. PMID:27771291

A scoring system to guide the decision for a new systemic treatment after at least two lines of palliative chemotherapy for metastatic cancers: a prospective study.

PubMed

Chanez, Brice; Bertucci, François; Gilabert, Marine; Madroszyk, Anne; Rousseau, Frédérique; Perrot, Delphine; Viens, Patrice; Raoul, Jean-Luc

2017-09-01

A four-parameter score has been identified as associated with overall survival (OS) in patients with advanced cancer with an estimated survival inferior to 6 months. Here, we tested its prognostic value for OS in patients who had received more than two lines of systemic therapy. We prospectively enrolled patients with advanced cancer who were going to receive a third or more therapeutic line outside classical clinical guidelines. The four parameters (Eastern Cooperative Oncology Group performance status, number of metastatic sites, serum LDH, and serum albumin) were collected at baseline, allowing to calculate the score, which sorted the patients in three groups, A, B, and C (low, intermediate, and high score, respectively). We then searched for correlations between this grouping and clinicopathological features particularly OS. From August 2013 to March 2014, 65 patients were enrolled and corresponded after determining their score to 26 patients in group A, 30 in B, and 9 in C. The median OS of the cohort was 4.4 months, and the 6-month OS was 42%. Overall survival was different between the three groups, with respective 6-month OS equal to 80% in group A, 17% in group B, and 0% in group C and respective median OS of 9, 2.3, and 1.6 months. Such prognostic value persisted in multivariate analysis. Similar OS differences were observed in patients with PS ≤2. This simple scoring should help oncologists identify which patients, after at least two lines of systemic therapy, might benefit from best supportive care alone.

Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies.

PubMed

Rule, Simon; Dreyling, Martin; Goy, Andre; Hess, Georg; Auer, Rebecca; Kahl, Brad; Cavazos, Nora; Liu, Black; Yang, Shiyi; Clow, Fong; Goldberg, Jenna D; Beaupre, Darrin; Vermeulen, Jessica; Wildgust, Mark; Wang, Michael

2017-11-01

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease. © 2017 John Wiley & Sons Ltd.

CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers.

PubMed

Vedeld, Hege Marie; Merok, Marianne; Jeanmougin, Marine; Danielsen, Stine A; Honne, Hilde; Presthus, Gro Kummeneje; Svindland, Aud; Sjo, Ole H; Hektoen, Merete; Eknaes, Mette; Nesbakken, Arild; Lothe, Ragnhild A; Lind, Guro E

2017-09-01

The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5-markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni- and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (<60, 60-74, ≥75 years). Patients with CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31-2.63] and 1.89 [1.34-2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P < 0.001), and MSS BRAF mutated tumors (P < 0.001), a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis (P < 0.01). Consistent results were found for all three age groups. To conclude, CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Defining the surgical margins of adenoid cystic carcinoma and their impact on outcome: An international collaborative study.

PubMed

Amit, Moran; Na'ara, Shorook; Trejo-Leider, Leonor; Ramer, Naomi; Burstein, David; Yue, Ma; Miles, Brett; Yang, Xinjie; Lei, Delin; Bjoerndal, Kristine; Godballe, Christian; Mücke, Thomas; Wolff, Klaus-Dietrich; Eckardt, André M; Copelli, Chiara; Sesenna, Enrico; Patel, Snehal; Ganly, Ian; Gil, Ziv

2017-05-01

The mainstay of treatment in adenoid cystic carcinoma (ACC) of the head and neck is surgical resection with negative margins. The purpose of this study was to define the margin status that associates with survival outcomes of ACC of the head and neck. We conducted univariate and multivariate analyses of international data. Data of 507 patients with ACC of the head and neck were analyzed; negative margins defined as ≥5 mm were detected in 253 patients (50%). On multivariate analysis, the hazard ratios (HRs) of positive margin status were 2.68 (95% confidence interval [CI], 1.2-6.2; p = .04) and 2.63 (95% CI, 1.1-6.3; p = .03) for overall survival (OS) and disease-specific survival (DSS), respectively. Close margins had no significant impact on outcome, with HRs of 1.1 (95% CI, 0.4-3.0; p = .12) and 1.07 (95% CI, 0.3-3.4; p = .23) for OS and DSS, respectively, relative with negative margins. In head and neck ACC, positive margins are associated with the worst outcome. Negative or close margins are associated with improved outcome, regardless of the distance from the tumor. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1008-1014, 2017. © 2017 Wiley Periodicals, Inc.

Layer-oriented total pelvic exenteration for locally advanced primary colorectal cancer.

PubMed

Koda, Keiji; Shuto, Kiyohiko; Matsuo, Kenichi; Kosugi, Chihiro; Mori, Mikito; Hirano, Atsushi; Hiroshima, Yukihiko; Tanaka, Kuniya

2016-01-01

The clinical outcomes of patients who have undergone total pelvic exenteration (TPE) for locally advanced primary colorectal cancer have not been satisfactory. For the last 13 years, we have performed layer-oriented, en bloc resection of tumor for which TPE is indicated, in the hope of improving postoperative outcomes. The clinical outcomes of these cases were retrospectively analyzed. A total of 54 patients who underwent TPE from 1986 to 2013 were retrospectively analyzed. Since 2002, a layer-oriented removal for clinical T4 colorectal cancer, as in T3 or less invasive tumors removed by total mesorectal excision, was applied to 23 cases for which TPE was indicated. Postoperative mortality, morbidity, overall survival (OS), and disease-free survival (DFS) were evaluated. On univariate analysis, good postoperative OS and DFS were associated with the layer-oriented operative maneuver, blood loss less than 2000 mL, negative nodal metastasis, and no preoperative radiation therapy. Male sex was the marginal determinant correlated with good OS and DFS. Depth of invasion to T3 was the marginal determinant correlated with good DFS. On multivariate analysis using the 4 factors identified on univariate analyses, the layer-oriented operative procedure was a significant determinant for both good OS and DFS, together with negative nodal metastases. Postoperative mortality and morbidity in the layer-oriented excision were acceptable. For primary colorectal cancers for which TPE is indicated, layer-oriented excision was a safe and effective procedure, and it may be recommended as one of the standard surgical approaches in TPE.

Allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia who had central nervous system involvement: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation.

PubMed

Shigematsu, Akio; Kako, Shinichi; Mitsuhashi, Kenjiro; Iwato, Koji; Uchida, Naoyuki; Kanda, Yoshinobu; Fukuda, Takahiro; Sawa, Masashi; Senoo, Yasushi; Ogawa, Hiroyasu; Miyamura, Koichi; Takada, Satoru; Nagamura-Inoue, Tokiko; Morishima, Yasuo; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mizuta, Shuichi; Tanaka, Junji

2017-06-01

The prognosis for adult acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement (CNS+) who received allogeneic hematopoietic stem cell transplantation (allo-SCT) remains unclear. We retrospectively compared the outcomes of allo-SCT for patients with CNS involvement and for patients without CNS involvement (CNS-) using a database in Japan. The eligibility criteria for this study were as follows: diagnosis of ALL, aged more than 16 years, allo-SCT between 2005 and 2012, and first SCT. Data for 2582 patients including 136 CNS+ patients and 2446 CNS- patients were used for analyses. As compared with CNS- patients, CNS+ patients were younger, had worse disease status at SCT and had poorer performance status (PS) at SCT (P < 0.01). Incidence of relapse was higher in CNS+ patients (P = 0.02), and incidence of CNS relapse was also higher (P < 0.01). The probability of 3-year overall survival (OS) was better in CNS- patients (P < 0.01) by univariate analysis. However, in patients who received SCT in CR, there was no difference in the probability of OS between CNS+ and CNS- patients (P = 0.38) and CNS involvement did not have an unfavorable effect on OS by multivariate analysis. CNS+ patients who achieved CR showed OS comparable to that of CNS- patients.

The Effect of Bridging Locoregional Therapy and Sociodemographics on Survival in Hepatocellular Carcinoma Patients Undergoing Orthotopic Liver Transplantation: A United Network for Organ Sharing Population Study.

PubMed

Magnetta, Michael J; Xing, Minzhi; Zhang, Di; Kim, Hyun S

2016-12-01

To investigate socioeconomic and demographic factors associated with transplantation outcomes in patients with hepatocellular carcinoma (HCC) treated with bridging locoregional therapy (LRT) before orthotopic liver transplantation (OLT). The United Network for Organ Sharing (UNOS) database was used to identify all patients in the United States with HCC who were listed for OLT between 2002 and 2013. Mean overall survival (OS) after OLT was stratified based on age, sex, ethnicity, transplant year, region, and insurance status. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazards model to assess independent prognostic factors for OS. Of the 17,291 listed patients with HCC, 14,511 underwent OLT. Mean age was 57.4 years (76.8% male). Favorable sociodemographic factors were associated with increased rates of bridging LRT before OLT and longer wait time on the transplant list and were shown to be independent prognostic factors for prolonged OS after OLT using multivariate analysis. Favorable demographic factors included patient age < 60 years, donor age < 45 years, year of diagnosis between 2008 and 2013, UNOS regions 4 and 5, Asian ethnicity, high functional status, postgraduate education, private payer insurance, and employment at the time of OLT. Patients with favorable sociodemographics had higher rates of LRT before OLT performed for HCC cure. These patients had longer transplant wait times and longer OS after OLT. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

The Impact of Race in Male Breast Cancer Treatment and Outcome in the United States: A Population-Based Analysis of 4,279 Patients

PubMed Central

Shin, Jacob Y.; Kachnic, Lisa A.; Hirsch, Ariel E.

2014-01-01

The purpose of this study is to compare the racial differences in treatment and overall survival (OS) of male breast cancer (MBC) patients. Data were extracted from the NCI SEER database that included population-based registries from 1988 to 2010 and analyzed using SPSS 20.0. 4,279 MBC patients were identified. 3,266 (76.3%) patients were White, 552 (12.9%) Black, 246 (5.7%) Hispanic, and 215 (5.0%) Asian. Black patients were more likely to be diagnosed at younger age (P < 0.001), have advanced stage disease (P = 0.001), and be unmarried (P < 0.001) and less likely to undergo lymph node dissection (P = 0.006). When stratified by stage, there was no difference in receipt of primary treatment by race. The 5-year OS for White, Black, Hispanic, and Asian races was 73.8%, 66.3%, 74.0%, and 85.3% (P < 0.001). This significant worse 5-year OS for Blacks persisted regardless of age, stage II or III disease, and grade 2 or 3 disease. On multivariate analysis, Black race was a significant independent prognostic factor for worse OS. Blacks were less likely to receive lymph node dissection of which patients may derive benefit, though we did not observe receipt of primary treatment, after stratifying for disease stage, to be an underlying factor contributing to racial outcome differences. PMID:25349739

Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients

PubMed Central

Li, Jingjie; Yan, Mengdan; Xie, Zhilan; Zhu, Yuanyuan; Chen, Chao; Jin, Tianbo

2016-01-01

Previous studies suggested that single nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) are associated with risk of glioma. However, the associations between these SNPs and glioma patient prognosis have not yet been fully investigated. Therefore, the present study was aimed to evaluate the effects of EGFR polymorphisms on the glioma patient prognosis. We retrospectively evaluated 269 glioma patients and investigated associations between EGFR SNPs and patient prognosis using Cox proportional hazard models and Kaplan-Meier curves. Univariate analysis revealed that age, gross-total resection and chemotherapy were associated with the prognosis of glioma patients (p < 0.05). In addition, four EGFR SNPs (rs11506105, rs3752651, rs1468727 and rs845552) correlated with overall survival (OS) (Log-rank p = 0.011, 0.020, 0.008, and 0.009, respectively) and progression-free survival PFS (Log-rank p = 0.026, 0.024, 0.019 and 0.009, respectively). Multivariate analysis indicated that the rs11506105 G/G genotype, the rs3752651 and rs1468727 C/C genotype and the rs845552 A/A genotype correlated inversely with OS and PFS. In addition, OS among patients with the rs730437 C/C genotype (p = 0.030) was significantly lower OS than among patients with A/A genotype. These data suggest that five EGFR SNPs (rs11506105, rs3752651, rs1468727, rs845552 and rs730437) correlated with glioma patient prognosis, and should be furthered validated in studies of ethnically diverse patients. PMID:27437777

Treatment of adult ALL with central nervous system involvement at diagnosis using autologous and allogeneic transplantation: a study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Chantepie, S P; Mohty, M; Tabrizi, R; Robin, M; Deconinck, E; Buzyn, A; Contentin, N; Raus, N; Lhéritier, V; Reman, O

2013-05-01

To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central nervous system involvement at diagnosis, we retrospectively analyzed 90 patients who underwent autologous HSCT (auto-HSCT group; n=27) or allogeneic HSCT (allo-HSCT group; n=63) and reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between 1994 and 2008. At the time of transplantation, 67 patients (74%) were in first CR, 15 (17%) in CR2 and 8 (9%) with progressive disease. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33% for the auto-HSCT groups, respectively (P=NS). The TRM at 5 years was 29.8% for the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis, a time for transplantation of <12 months, the remission status at transplantation, the use of high-dose TBI and the number of the transplant were all determined to be prognostic factors for improved DFS and OS probabilities. Using multivariate analysis, we demonstrated that both the use of high-dose TBI and the remission status had a favorable impact on OS. Although the DFS and OS were better in the allo-HSCT group, the differences were not statistically significant.

Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy

PubMed Central

Wang, H. M.; Liao, Z. X.; Komaki, R.; Welsh, J. W.; O'Reilly, M. S.; Chang, J. Y.; Zhuang, Y.; Levy, L. B.; Lu, C.; Gomez, D. R.

2013-01-01

Background Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. Patients and methods We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Results In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). Conclusion Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes. PMID:23300016

ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR CHEMOTHERAPY-UNRESPONSIVE MANTLE CELL LYMPHOMA: A COHORT ANALYSIS FROM THE CIBMTR

PubMed Central

Hamadani, Mehdi; Saber, Wael; Ahn, Kwang Woo; Carreras, Jeanette; Cairo, Mitchell S.; Fenske, Timothy S.; Gale, Robert Peter; Gibson, John; Hale, Gregory A.; Hari, Parameswaran N.; Hsu, Jack W.; Inwards, David J.; Kamble, Rammurti T.; Klein, Anderas; Maharaj, Dipnarine; Marks, David I.; Rizzieri, David A.; Savani, Bipin N.; Schouten, Harry C.; Waller, Edmund K.; Wirk, Baldeep; Lazarus, Hillard M.

2013-01-01

Patients with chemorefractory mantle cell lymphoma (MCL) have poor prognosis. We used the CIBMTR database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced intensity/non-myeloablative conditioning (RIC/NST), during 1998–2010. We analyzed non-relapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients received MA, and 128 underwent RIC/NST. Median ages are 54 and 59 years for MA and RIC/NST allo-HCT recipients, respectively. Median follow-up after MA and RIC/NST allo-HCT is 35 months and 43 months, respectively. At 3 years, comparing MA with RIC/NST allo-HCT, no significant differences were found in terms of NRM (47% vs. 43%; p-value=0.68), relapse/progression (33% vs. 32%; p-value=0.89), PFS (20% vs. 25%; p=0.53), and OS (25% vs. 30%; p-value=0.45). On multivariate analysis no significant differences were observed in NRM, relapse, PFS and OS between MA and RIC/NST allo-HCT; however, receiving a bone marrow or T-cell depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Despite a refractory disease state, approximately a fourth of MCL patients can attain durable remissions after allo-HCT. Conditioning regimen intensity did not influence the outcomes of patients after allo HCT. PMID:23333532

Treatment and survival of second primary early-stage lung cancer, following treatment of head and neck cancer in the Netherlands.

PubMed

Louie, Alexander V; Damhuis, Ronald A; Haasbeek, Cornelis J; Warner, Andrew; Rodin, Danielle; Slotman, Ben J; Leemans, C Rene; Senan, Suresh

2016-04-01

The goal of this study was to evaluate treatment patterns and outcomes in early stage (ES) second primary lung cancer (SPLC) after head and neck squamous cell cancer (HNSCC), in the Netherlands. Details of patients diagnosed between 1997 and 2011 with either an ES primary, or a SPLC after HNSCC, were obtained from the Netherlands Cancer Registry. Survival outcomes were compared between treatment groups before, and after, 2005. Univariable and multivariable Cox regression modeling were performed to determine factors prognostic for OS in ES-SPLC. In total, 21,648 patients were diagnosed with ES primary (n=21,032) or SPLC (n=616). Use of surgery for ES-SPLC decreased significantly over time (range 71-44%, p<0.001), while the proportion of such patients receiving radiotherapy increased (range 17-41%, p<0.001). Prior to 2005, OS after surgery in ES-SPLC was significantly better than when compared to radiation, but no difference in OS was noted between surgery and radiotherapy after 2005 (p=0.116). There were no significant differences in OS between treatment eras for surgery (p=0.751) and with palliative care (p=0.306), but a significant improvement in OS was noted for radiotherapy (p=0.049). Multivariable modeling revealed that age, T-stage, HNSCC location and treatment type were associated with worse OS in the later era. Changes in the treatment patterns in HNSCC survivors presenting with ES-SPLC were observed in the Netherlands, with less surgery and increased utilization of radiotherapy. No differences in OS were observed between patients undergoing either surgery or radiotherapy after 2005, suggesting that both local modalities were equally effective. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Expression of CD105 cancer stem cell marker in three subtypes of renal cell carcinoma.

PubMed

Saeednejad Zanjani, Leili; Madjd, Zahra; Abolhasani, Maryam; Shariftabrizi, Ahmad; Rasti, Arezoo; Asgari, Mojgan

2018-01-01

CD105 is recently described as a cancer stem cell (CSC) marker. The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes.

Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan: results from a prospective multicenter registry.

PubMed

Kawabata, Hiroshi; Tohyama, Kaoru; Matsuda, Akira; Araseki, Kayano; Hata, Tomoko; Suzuki, Takahiro; Kayano, Hidekazu; Shimbo, Kei; Zaike, Yuji; Usuki, Kensuke; Chiba, Shigeru; Ishikawa, Takayuki; Arima, Nobuyoshi; Nogawa, Masaharu; Ohta, Akiko; Miyazaki, Yasushi; Mitani, Kinuko; Ozawa, Keiya; Arai, Shunya; Kurokawa, Mineo; Takaori-Kondo, Akifumi

2017-09-01

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan-Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols.

TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes

PubMed Central

Sallman, David A.; Basiorka, Ashley A.; Irvine, Brittany A.; Zhang, Ling; Epling-Burnette, P.K.; Rollison, Dana E.; Mallo, Mar; Sokol, Lubomir; Solé, Francesc; Maciejewski, Jaroslaw; List, Alan F.

2015-01-01

P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to −2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome. PMID:26416416

A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients

PubMed Central

Shoji, Koichi; Teishima, Jun; Hayashi, Tetsutaro; Shinmei, Shunsuke; Akita, Tomoyuki; Sentani, Kazuhiro; Takeshima, Yukio; Arihiro, Koji; Tanaka, Junko; Yasui, Wataru; Matsubara, Akio

2017-01-01

An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa. PMID:28693168

Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer.

PubMed

Shah, Manasi S; Fogelman, David R; Raghav, Kanwal Pratap Singh; Heymach, John V; Tran, Hai T; Jiang, Zhi-Qin; Kopetz, Scott; Daniel, Carrie R

2015-09-01

Obesity is strongly linked with chronic systemic inflammation, and each has been linked with disease progression and survival in patients with colorectal cancer (CRC). The authors investigated the joint prognostic effects of obesity and circulating cytokines in patients with metastatic CRC (mCRC), an understudied patient group. In 242 chemotherapy-naive patients with mCRC, the authors measured a multiplex cytokine panel and abstracted clinicopathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of mCRC diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression. In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha, and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS (hazard ratio [HR] and 95% confidence interval [95% CI] for above vs below the (referent) knot point: 2.5 [95% CI, 1.7-3.7], 1.9 [95% CI, 1.3-2.7], and 2.2 [95% CI, 1.6-3.1], respectively; all P<.001). Obesity (body mass index ≥30 kg/m(2) ) was not found to be associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4-fold and 5-fold risk of death, respectively, in obese patients compared with a 2-fold risk of death in nonobese patients (P for interaction of .06 and .04, respectively). Similar results emerged from joint effects analysis, in which obese patients with high IL-8 (or LDH) experienced the highest risk of death. Although obesity itself was not found to be independently associated with survival in patients with mCRC, the adverse prognostic significance of LDH and IL-8 was found to be enhanced in obese patients. © 2015 American Cancer Society.

A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients.

PubMed

Shoji, Koichi; Teishima, Jun; Hayashi, Tetsutaro; Shinmei, Shunsuke; Akita, Tomoyuki; Sentani, Kazuhiro; Takeshima, Yukio; Arihiro, Koji; Tanaka, Junko; Yasui, Wataru; Matsubara, Akio

2017-07-01

An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa.

Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation.

PubMed

Facciorusso, Antonio; Del Prete, Valentina; Antonino, Matteo; Neve, Viviana; Crucinio, Nicola; Di Leo, Alfredo; Carr, Brian I; Barone, Michele

2014-11-01

Hepatic iron accumulation is considered to be a cofactor that influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation (RFA). We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and their influence on OS and TTR was evaluated in univariate and multivariate analyses. SF did not correlate with α-fetoprotein (rho: -0.12, P = 0.22), neutrophil/lymphocyte ratio (rho: -0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18, P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage (P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off point for SF. Median OS was 62 months (54-78) and survival rate was 97%, 65%, and 52% at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS at multivariate analysis. Median TTR was 38 months (34-49) with a recurrence-free survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and age were the only predictors of TTR. SF level, possibly reflecting the degree of hepatic inflammation and fibrosis, is a negative risk factor for survival and recurrence after percutaneous RFA in HCC patients. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Chad G., E-mail: chad.rusthoven@ucdenver.edu; Carlson, Julie A.; Waxweiler, Timothy V.

2014-04-01

Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated,more » with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.« less

Hepatitis B Virus Infection Predicts Better Survival In Patients With Colorectal Liver-only Metastases Undergoing Liver Resection

PubMed Central

Zhao, Yujie; Lin, Junzhong; Peng, Jianhong; Deng, Yuxiang; Zhao, Ruixia; Sui, Qiaoqi; Lu, Zhenhai; Wan, Desen; Pan, Zhizhong

2018-01-01

Objective: Hepatitis B virus (HBV) infection has been shown to decrease the risk of liver metastasis in patients with non-metastatic colorectal cancer (CRC). However, the prognostic value of HBV infection in long-term survival of patients with colorectal liver-only metastases (CRLM) after liver resection has not yet been evaluated. This study aims to explore the association between HBV infection and survival in CRLM patients. Methods: A total of 289 CRLM patients undergoing liver resection were recruited at our center from September 1999 to August 2015. Patients were divided into an HBV infection group and a non-HBV infection group. Progression-free survival (PFS) and overall survival (OS) related to HBV infection were analyzed using both Kaplan-Meier and multivariate Cox regression methods. Results: HBV infection was found in 12.1 %(35/289) of patients. Of these patients, 31.4 %(11/35) had chronic hepatitis B (CHB), 42.9 % (15/35) were inactive hepatitis B surface antigen (HBsAg) carriers (IC) and 25.7 % (9/35) did not undergo HBV DNA detection. HBV infection was associated with more liver metastases (P = 0.025) and larger-sized liver metastases (P = 0.049). The 3-year OS and PFS rates in the HBV infection group were higher than those in the HBV non-infected group (OS: 75.0 % vs 64.8 %, P = 0.031; PFS: 55.9 % vs 39.6 %, P = 0.034). In multivariate Cox analysis, HBV infection was identified as an independent factor for better 3-year OS (hazard ratio (HR), 0.446; 95 %confidence interval (CI), 0.206-0.966; P = 0.041) but not an independent factor for 3-year PFS. Conclusions: HBV-infected CRLM patients survived longer than non-infected patients. In clinical work, therapeutic regimens and follow-up for HBsAg-positive patients may be different from that for HBsAg-negative patients, even though objective prospective studies are still needed. PMID:29760793

Outcome of proximal esophageal cancer after definitive combined chemo-radiation: a Swiss multicenter retrospective study.

PubMed

Herrmann, Evelyn; Mertineit, Nando; De Bari, Berardino; Hoeng, Laura; Caparotti, Francesca; Leiser, Dominic; Jumeau, Raphael; Cihoric, Nikola; Jensen, Alexandra D; Aebersold, Daniel M; Ozsahin, Mahmut

2017-06-14

To report oncological outcomes and toxicity rates, of definitive platin-based chemoradiadiationtherapy (CRT) in the management of proximal esophageal cancer. We retrospectively reviewed the medical records of patients with cT1-4 cN0-3 cM0 cervical esophageal cancer (CEC) (defined as tumors located below the inferior border of the cricoid cartilage, down to 22 cm from the incisors) treated between 2004 and 2013 with platin-based definitive CRT in four Swiss institutions. Acute and chronic toxicities were retrospectively scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE-NCI v.4.0). Primary endpoint was loco-regional control (LRC). We also evaluated overall survival (OS) and disease-free survival (DFS) rates. The influence of patient- and treatment related features have been calculated using the Log-rank test and multivariate Cox proportional hazards model. We enrolled a total of 55 patients. Median time interval from diagnosis to CRT was 78 days (6-178 days). Median radiation dose was 56Gy (28-72Gy). Induction chemotherapy (ICHT) was delivered in 58% of patients. With a median follow up of 34 months (6-110months), actuarial 3-year LRC, DFS and OS were 52% (95% CI: 37-67%), 35% (95% CI: 22-50%) and 52% (95% CI: 37-67%), respectively. Acute toxicities (dysphagia, pain, skin-toxicity) ranged from grade 0 - 4 without significant dose-dependent differences. On univariable analyses, the only significant prognostic factor for LRC was the time interval > 78 days from diagnosis to CRT. On multivariable analysis, total radiation dose >56Gy (p <0.006) and ICHT (p < 0.004) were statistically significant positive predictive factors influencing DFS and OS. Definitive CRT is a reliable therapeutic option for proximal esophageal cancer, with acceptable treatment related toxicities. Higher doses and ICHT may improve OS and DFS and. These findings need to be confirmed in further prospective studies.

Impact of timing of radiotherapy in patients with newly diagnosed glioblastoma.

PubMed

Randolph, David M; McTyre, Emory R; Paulsson, Anna K; Holmes, Jordan A; Hinson, William H; Lesser, Glenn J; Strowd, Roy; Lo, Hui-Wen; Laxton, Adrian W; Tatter, Stephen B; Debinski, Waldemar; Chan, Michael D

2016-12-01

To further evaluate if a delay in the start of radiation therapy (RT) affects patient outcomes for glioblastoma (GBM). From May 1999 to May 2010, a total of 161 patients underwent surgery followed by RT for GBM. We assessed overall survival (OS) and progression free survival (PFS), stratified by extent of surgical resection. Included in the analysis were genomic predictors of progression. Median time from surgery to start of RT was 20days for biopsy alone, 28days for subtotal resection (STR) and 28days for gross total resection (GTR). For all patients, a delay >28days did not result in a difference in PFS when compared to no delay (6.7 vs. 6.9 months, p=0.07). PFS was improved in biopsy or STR patients with a >28day delay to start of RT (4.2 vs. 6.7 months, p=0.006). OS was also improved in patients receiving biopsy or STR with a >28day delay to start of RT (12.3 vs. 7.8 months, p=0.005). Multivariable analysis (MVA) demonstrated an improvement in OS and PFS with time to RT >28days for biopsy or STR patients (HR 0.52 p=0.008 and HR 0.48 p=0.02, respectively). In this retrospective review of GBM patients treated at a single institution, OS and PFS were not different between time to RT >28days compared to <28 days. There was a modest improvement in both PFS and OS in patients who received biopsy or STR with time to RT >28 days. Copyright © 2016 Elsevier B.V. All rights reserved.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

PubMed

Di Cataldo, A; Agodi, A; Balaguer, J; Garaventa, A; Barchitta, M; Segura, V; Bianchi, M; Castel, V; Castellano, A; Cesaro, S; Couselo, J M; Cruz, O; D'Angelo, P; De Bernardi, B; Donat, J; de Andoin, N G; Hernandez, M I; La Spina, M; Lillo, M; Lopez-Almaraz, R; Luksch, R; Mastrangelo, S; Mateos, E; Molina, J; Moscheo, C; Mura, R; Porta, F; Russo, G; Tondo, A; Torrent, M; Vetrella, S; Villegas, J A; Viscardi, E; Zanazzo, G A; Cañete, A

2017-01-01

SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

Facility Volume and Survival in Nasopharyngeal Carcinoma.

PubMed

Yoshida, Emi J; Luu, Michael; David, John M; Kim, Sungjin; Mita, Alain; Scher, Kevin; Shiao, Stephen L; Tighiouart, Mourad; Lee, Nancy Y; Ho, Allen S; Zumsteg, Zachary S

2018-02-01

Definitive treatment of nasopharyngeal carcinoma (NPC) is challenging owing to its rarity, complicated regional anatomy, and the intensity of therapy. In contrast to other head and neck cancers, the effect of facility volume has not been well described for NPC. The National Cancer Database was queried for patients with stage II-IVB NPC diagnosed from 2004 to 2014 and treated with definitive radiation. Patients with incomplete staging, unknown receipt or timing of treatment, unknown follow-up duration, incomplete socioeconomic information, or treatment outside the reporting facility were excluded. High-volume facilities (HVFs) were defined as the top 5% of facilities according to the annual facility volume. The present analysis included 3941 NPC patients treated at 804 facilities with a median follow-up duration of 59.4 months, including 1025 patients (26.0%) treated at HVFs. Treatment at HVFs was associated with significantly improved overall survival (OS) on multivariable analysis (hazard ratio 0.79, 95% confidence interval 0.69-0.90; P=.001). In propensity score-matched cohorts, 5-year OS was 69.1% versus 63.3% at HVFs versus lower volume facilities (LVFs), respectively (P=.003). Similar results were seen when facility volume was analyzed as a continuous variable. The effect of facility volume on survival varied by academic status (P=.002 for interaction). At academic centers, the propensity score-matched cohorts had 5-year OS of 71.4% compared with 62.4% (P<.001) at HVFs and LVFs, respectively. In contrast, the 5-year OS was 63.5% versus 67.9% (P=.68) in propensity score-matched patients at nonacademic HVFs and LVFs. Treatment at HVFs was associated with improved OS for patients with NPC, with the effect exclusively seen at academic centers. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-Wide Identification of the Alba Gene Family in Plants and Stress-Responsive Expression of the Rice Alba Genes.

PubMed

Verma, Jitendra Kumar; Wardhan, Vijay; Singh, Deepali; Chakraborty, Subhra; Chakraborty, Niranjan

2018-03-28

Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa , Zea mays , Sorghum bicolor , Cicer arietinum , and Vitis vinifera , and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii , Physcomitrella patens , and Amborella trichopoda , revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A phylogenetic analysis of the genes and of their counterparts in other plant species indicated evolutionary conservation and diversification. In each group, the structural components of the genes and motifs showed significant conservation. The chromosomal location of the Alba genes of rice ( OsAlba ), showed an unequal distribution on 8 of its 12 chromosomes. The expression profiles of the OsAlba genes indicated a distinct tissue-specific expression in the seedling, vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR) analysis of the OsAlba genes confirmed their stress-inducible expression under multivariate environmental conditions and phytohormone treatments. The evaluation of the regulatory elements in 68 Alba genes from the 9 species studied led to the identification of conserved motifs and overlapping microRNA (miRNA) target sites, suggesting the conservation of their function in related proteins and a divergence in their biological roles across species. The 3D structure and the prediction of putative ligands and their binding sites for OsAlba proteins offered a key insight into the structure-function relationship. These results provide a comprehensive overview of the subtle genetic diversification of the OsAlba genes, which will help in elucidating their functional role in plants.

Clinical outcomes in patients with metastatic renal cell carcinoma receiving everolimus or temsirolimus after sunitinib

PubMed Central

Iacovelli, Roberto; Cartenì, Giacomo; Milella, Michele; Berardi, Rossana; Di Lorenzo, Giuseppe; Verzoni, Elena; Rizzo, Mimma; Santoni, Matteo; Procopio, Giuseppe

2014-01-01

Introduction: There are little data on the clinical activity of temsirolimus (TM) and everolimus (EV) when used as second-line therapy after sunitinib (SU) in patients with metastatic renal cell carcinoma (mRCC). Methods: Patients with mRCC treated with EV or TM after SU were included in this retrospective analysis. Progression-free survival (PFS), time to sequence failure (TTSF) from the start of SU to disease progression with EV/TM and overall survival (OS) were estimated using Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional hazards models were applied to investigate predictors of TTSF and OS. Results: In total, 89 patients (median age 60.0 years) were included. At baseline 43% were classified as MSKCC good-risk, 43% as intermediate-risk and 14% as poor-risk. Median OS was 36.3 months and median TTSF was 17.2 months. Sixty-five patients received SU-EV and 24 patients SU-TM. Median PFS after the second-line treatment was 4.3 months in the EV group and 3.5 months in the TM group (p = 0.63). Median TTSF was 17.0 and 18.9 months (p = 0.32) and the OS was 35.8 and 38.3 months (p = 0.73) with SU-EV and SU-TM, respectively. The prognostic role of initial MSKCC was confirmed by multivariable analysis (hazard ratio 1.76, 95% confidence interval 1.08–2.85. p = 0.023). Conclusions: This study did not show significant differences in terms of disease control and OS between EV and TM in the second-line setting. EV remains the preferred mTOR inhibitor for the treatment of mRCC patients resistant to prior tyrosine kinase inhibitor treatment. PMID:24678349

The impact of primary tumour location in patients undergoing hepatic resection for colorectal liver metastasis.

PubMed

Wang, Kun; Xu, Da; Yan, Xiao-Luan; Poston, Graeme; Xing, Bao-Cai

2018-06-01

Primary tumour location has long been debated as a prognostic factor in colorectal cancer patients with liver metastases (CRLM) undergoing liver resection. This retrospective study was conducted to clarify the prognostic value of tumour location after radical hepatectomy for CRLM and its underlying causes. We retrospectively analysed clinical data from 420 patients with CRLM whom underwent liver resection between January 2002 and December 2015. Right-sided (RS) tumours include tumours located in the cecum, ascending colon, and transverse colon, and left-sided (LS) tumours include those located in the splenic flexure, descending colon, sigmoid colon, and rectum. Both overall survival (OS) and disease-free survival (DFS) were similar between patients with RS and LS primary tumours (5-year OS: 46.5% vs 38.3%, P = 0.699; 5-year DFS: 29.1% vs 22.4%, P = 0.536). Specifically, RAS mutation rate was significantly higher in patients with RS tumours (P = 0.007). Subgroup analysis showed that the RAS mutation on the LS and RS tumours have different prognostic impact for CRLM patients on long-term survival after hepatic resection (RS, OS: P = 0.437, DFS: P = 0.471; LS, OS: P < 0.001, DFS: P = 0.002). The multivariable analysis showed that RAS mutant is an independent factor influencing OS in patients with LS primary tumour only. The site of the primary tumour has no significant impact on the long-term survival in patients with CRLM undergoing radical surgery. However, prognostic value of RAS status differs depending on the site of the primary tumour. Copyright © 2018. Published by Elsevier Ltd.

Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu; Mehta, Par; Khan, Atif

Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlationmore » with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.« less

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.

PubMed

Arias-Pulido, Hugo; Royce, Melanie; Gong, Yun; Joste, Nancy; Lomo, Lesley; Lee, Sang-Joon; Chaher, Nabila; Verschraegen, Claire; Lara, Juanita; Prossnitz, Eric R; Cristofanilli, Massimo

2010-08-01

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.

The Impact of Radiation Treatment Time on Survival in Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaikh, Talha; Handorf, Elizabeth A.; Murphy, Colin T.

Purpose: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation. Methods and Materials: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT wasmore » defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ{sup 2} tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status. Results: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01). Conclusion: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies.« less

Early PET/CT scan is more effective than RECIST in predicting outcome of patients with liver metastases from colorectal cancer treated with preoperative chemotherapy plus bevacizumab.

PubMed

Lastoria, Secondo; Piccirillo, Maria Carmela; Caracò, Corradina; Nasti, Guglielmo; Aloj, Luigi; Arrichiello, Cecilia; de Lutio di Castelguidone, Elisabetta; Tatangelo, Fabiana; Ottaiano, Alessandro; Iaffaioli, Rosario Vincenzo; Izzo, Francesco; Romano, Giovanni; Giordano, Pasqualina; Signoriello, Simona; Gallo, Ciro; Perrone, Francesco

2013-12-01

Markers predictive of treatment effect might be useful to improve the treatment of patients with metastatic solid tumors. Particularly, early changes in tumor metabolism measured by PET/CT with (18)F-FDG could predict the efficacy of treatment better than standard dimensional Response Evaluation Criteria In Solid Tumors (RECIST) response. We performed PET/CT evaluation before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase 2 trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum standardized uptake value (SUV) and the total lesion glycolysis (TLG) were determined. On the basis of previous studies, a ≤ -50% change from baseline was used as a threshold for significant metabolic response for maximum SUV and, exploratively, for TLG. Standard RECIST response was assessed with CT after 3 mo of treatment. Pathologic response was assessed in patients undergoing resection. The association between metabolic and CT/RECIST and pathologic response was tested with the McNemar test; the ability to predict progression-free survival (PFS) and overall survival (OS) was tested with the Log-rank test and a multivariable Cox model. Thirty-three patients were analyzed. After treatment, there was a notable decrease of all the parameters measured by PET/CT. Early metabolic PET/CT response (either SUV- or TLG-based) had a stronger, independent and statistically significant predictive value for PFS and OS than both CT/RECIST and pathologic response at multivariate analysis, although with different degrees of statistical significance. The predictive value of CT/RECIST response was not significant at multivariate analysis. PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer, and its predictive ability was higher than that of CT/RECIST response after 3 mo of treatment. Such findings need to be confirmed by larger prospective trials.

Comparison of milk oligosaccharides between goats with and without the genetic ability to synthesize αs1-casein

PubMed Central

Meyrand, M.; Dallas, D.C.; Caillat, H.; Bouvier, F.; Martin, P.; Barile, D.

2014-01-01

Milk oligosaccharides (OS)—free complex carbohydrates—confer unique health benefits to the nursing neonate. Though human digestive enzymes cannot degrade these sugars, they provide nourishment to specific commensal microbes and act as decoys to prevent the adhesion of pathogenic micro-organisms to gastrointestinal cells. At present, the limited quantities of human milk oligosaccharides (HMO) impede research on these molecules and their potential applications in functional food formulations. Considerable progress has been made in the study of OS structures; however, the synthetic pathways leading to their synthesis in the mammary gland are poorly understood. Recent studies show that complex OS with fucose and N-acetyl neuraminic acid (key structural elements of HMO bioactivity) exist in goat milk. Polymorphisms in the CSN1S1 locus, which is responsible for synthesis of αs1-casein, affect lipid and casein micelle structure in goat milk. The present study sought to determine whether CSN1S1 polymorphisms also influence goat milk oligosaccharide (GMO) production and secretion. The GMO compositions of thirty-two goat milk samples, half of which were from genotype A/A (αs1-casein producers) and half from genotype O/O (αs1-casein non-producers), were determined with nanoflow liquid chromatography high-accuracy mass spectrometry. This study represents the most exhaustive characterization of GMO to date. A systematic and comprehensive GMO library was created, consolidating information available in the literature with the new findings. Nearly 30 GMO, 11 of which were novel, were confirmed via tandem mass spectrometric analyses. Six fucosylated OS were identified; 4 of these matched HMO compositions and three were identified for the first time in goat milk. Importantly, multivariate statistical analysis demonstrated that the OS profiles of the A/A and O/O genotype milks could be discriminated by the fucosylated OS. Quantitative analysis revealed that the goat milk samples contained 1.17 g/L of OS; however, their concentration in milks from A/A and O/O genotypes was not different. This study provides evidence of a genetic influence on specific OS biosynthesis but not total OS production. The presence of fucosylated GMO suggests that goat milk represents a potential source of bioactive milk OS suitable as a functional food ingredient. PMID:24587592

Revisiting a dogma: similar survival of patients with small bowel and gastric GIST. A population-based propensity score SEER analysis.

PubMed

Guller, Ulrich; Tarantino, Ignazio; Cerny, Thomas; Ulrich, Alexis; Schmied, Bruno M; Warschkow, Rene

2017-01-01

The objective of the present analysis was to assess whether small bowel gastrointestinal stromal tumor (GIST) is associated with worse cancer-specific survival (CSS) and overall survival (OS) compared with gastric GIST on a population-based level. Data on patients aged 18 years or older with histologically proven GIST was extracted from the SEER database from 1998 to 2011. OS and CSS for small bowel GIST were compared with OS and CSS for gastric GIST by application of adjusted and unadjusted Cox regression analyses and propensity score analyses. GIST were located in the stomach (n = 3011, 59 %), duodenum (n = 313, 6 %), jejunum/ileum (n = 1288, 25 %), colon (n = 139, 3 %), rectum (n = 172, 3 %), and extraviscerally (n = 173, 3 %). OS and CSS of patients with GIST in the duodenum [OS, HR 0.95, 95 % confidence interval (CI) 0.76-1.19; CSS, HR 0.99, 95 % CI 0.76-1.29] and in the jejunum/ileum (OS, HR 0.97, 95 % CI 0.85-1.10; CSS, HR = 0.95, 95 % CI 0.81-1.10) were similar to those of patients with gastric GIST in multivariate analyses. Conversely, OS and CSS of patients with GIST in the colon (OS, HR 1.40; 95 % CI 1.07-1.83; CSS, HR 1.89, 95 % CI 1.41-2.54) and in an extravisceral location (OS, HR 1.42, 95 % CI 1.14-1.77; CSS, HR = 1.43, 95 % CI 1.11-1.84) were significantly worse than those of patients with gastric GIST. Contrary to common belief, OS and CSS of patients with small bowel GIST are not statistically different from those of patients with gastric GIST when adjustment is made for confounding variables on a population-based level. The prognosis of patients with nongastric GIST is worse because of a colonic and extravisceral GIST location. These findings have implications regarding adjuvant treatment of GIST patients. Hence, the dogma that small bowel GIST patients have worse prognosis than gastric GIST patients and therefore should receive adjuvant treatment to a greater extent must be revisited.

Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT.

PubMed

Battipaglia, G; Labopin, M; Candoni, A; Fanin, R; El Cheikh, J; Blaise, D; Michallet, M; Ruggeri, A; Contentin, N; Ribera, J M; Stadler, M; Sierra, J; von dem Borne, P A; Bloor, A; Socié, G; Nagler, A; Mohty, M

2017-04-01

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

Tolerability and efficacy of gamma knife radiosurgery on hepatocellular carcinoma with portal vein tumor thrombosis

PubMed Central

Lu, Xiao-Jie; Dong, Jing; Ji, Li-Juan; Xiao, Li-Xin; Ling, Chang-Quan; Zhou, Jun

2016-01-01

This is a retrospective study on the safety and efficacy of gamma knife radiosurgery (GKR) in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Patients with confirmed HCC and PVTT were allocated into two groups based on the treatments they received (palliative or GKR). A total of 138 patients were included (74 in the palliative group, 64 in GKR group). No significant differences in baseline characteristics existed between the two groups. Treatment-related adverse events (AEs) were recorded and compared between groups. The majority of AEs were mild to moderate and subsided naturally or after medication. There was no AE-induced death. The influences of baseline characteristics and treatment options on patients' OS were analyzed. The median OS of patients in the palliative and GKR group were 3.0 months (95% CI: 2.719-3.281) and 6.1 months (95% CI: 4.706-7.494) respectively (p = 0.003). Multivariate analysis revealed that GKR treatment, performance status 0-1, Child A, smaller tumor diameter and monolobar distribution were significant favorable prognosticators. Subgroup analyses showed OS benefit of GKR regardless of PVTT location (main or branch of PVTT). In conclusion, GKR is well tolerated in selected HCC-PVTT patients and can confer OS benefit, which needs validation in future prospective studies. PMID:26473291

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma

PubMed Central

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-01-01

Background Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients’ overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. Results The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Conclusions Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment. PMID:28118615

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis.

PubMed

Buglione, Michela; Pedretti, Sara; Gipponi, Stefano; Buttolo, Luciano; Panciani, Paolo; Poliani, Pietro Luigi; Liserre, Roberto; Borghetti, Paolo; Pegurri, Ludovica; Costa, Loredana; Triggiani, Luca; Pasinetti, Nadia; Ghirardelli, Paolo; Pandini, Sara; Padovani, Alessandro; Magrini, Stefano Maria

2015-12-01

To evaluate the efficacy of whole brain radiotherapy (WBRT) with or without other treatments in patients (pts) with 1-3 brain metastases (BM). Toxicities and survival of 134 pts treated between 2009 and 2013 with WBRT alone (58 pts), WBRT plus surgery (SUR-WBRT: 42 pts) or WBRT followed by stereotactic or integrated boost radiotherapy (SRT-WBRT: 34 pts) were analyzed. Differences in toxicity (acute and late) incidence and in overall (OS), disease-free (DFS) and disease-specific survival (DSS) were evaluated (χ(2)-test, uni- and multivariate analysis). Pts given intensified treatments (SUR- and SBRT-WBRT) had better 3-month local response compared to WBRT alone group (p < 0.045). Better 1-year local control was evident only in SRT-WBRT pts (p < 0.035). Univariate OS analysis confirmed, as favorable prognostic factors, RPA class I (p < 0.001), GPA class III and IV (p < 0.001), single metastasis (p = 0.045), stable primary disease (p = 0.03), intensified treatment (p = 0.000), systemic therapy after radiotherapy (p = 0.04) and response of metastatic lesions (p = 0.002). At multivariate analysis, OS was better in RPA class I pts (p = 0.002), who had more aggressive radiotherapy treatments (p = 0.001), chemotherapy after radiotherapy (p < 0.001) and response to RT (p = 0.003). Response to radiotherapy (p = 0.002) and BM number (p < 0.001) resulted independently prognostic for DFS. About 60 % of patients had mild acute toxicity (G1), especially headache (51 %) and fatigue (34 %); only 2 patients (2 %) had severe (G3) headache and 5 patients (4 %) severe fatigue (G3) reversible with oral steroids. No differences were evident between the different treatment groups. Among 80 pts followed up with MRI, 12 (15 %) had leukoencephalopathy (equally distributed across subgroups) and 5 (6 %) radionecroses, 4/5 asymptomatic, 5/5 in pts given intensified treatments. This analysis confirms the known prognostic factors for BM, emphasizing the importance of intensified treatments in a population with favorable features.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

PubMed

Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

2016-11-01

Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

PubMed Central

Ajani, Jaffer A.; Winter, Kathryn A.; Gunderson, Leonard L.; Pedersen, John; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2009-01-01

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. PMID:19139424

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Outcomes and Effect of Radiotherapy in Patients With Stage I or II Diffuse Large B-Cell Lymphoma: A Surveillance, Epidemiology, and End Results Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballonoff, Ari; Rusthoven, Kyle E.; Schwer, Amanda

2008-12-01

Purpose: To assess disease-specific survival (DSS), overall survival (OS), and the effect of radiotherapy (RT) in patients with localized diffuse large B-cell lymphoma (DLBCL). Patients and Methods: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with Stage I, IE, II, or IIE DLBCL between 1988 and 2004. The analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Patients who had died or were lost to follow-up within 6 months of diagnosis were excluded. Results: A total of 13,420 patients met the search criteria. Of these, 5,547 (41%) had received RTmore » and 7,873 (59%) had not. RT was associated with a significant DSS (hazard ratio, 0.82, p <0.0001) and OS benefit that persisted during the 15 years of follow-up. Elderly patients, defined either as those >60 or >70 years old, had significantly improved DSS and OS associated with RT. On multivariate analysis, RT was significantly associated with increased DSS and OS. The 5-year DSS outcomes were highly variable among patient subsets, defined by age, stage, and extranodal disease (range for RT-treated patients, 70% for Stage II, age >60 years to 87% for Stage I, age {<=}60 years). Conclusion: This analysis presents the largest detailed data set of Stage I-II DLBCL patients. The results of our study have demonstrated that RT is associated with a survival advantage in patients with localized DLBCL, a benefit that extends to elderly patients. Outcomes for discrete patient subsets varied greatly. The development of tailored therapy according to the relapse risk is warranted, rather than uniform treatment of all early-stage DLBCL.« less

Systemic treatment in advanced biliary cancers: A multicenter Australian analysis and review.

PubMed

Brungs, Daniel; Aghmesheh, Morteza; Sjoquist, Katrin; Goldstein, David

2017-10-01

While first-line palliative chemotherapy (CT1) improves survival and quality of life in advanced biliary cancer (ABC), there is no randomized evidence to support second-line chemotherapy (CT2) in ABC. We aim to explore to role of CT2 in ABC. We performed a retrospective review of all patients who received one or more lines of chemotherapy for ABC at four Australian cancer centers between 2008 and 2011. A Cox proportional hazard model was developed to determine the impact of clinicopathologic variables on overall survival (OS) from time of progression on CT1. We identified 73 patients who received palliative chemotherapy for ABC. Twenty-five patients (34%) received two or more lines of chemotherapy. Patients with a preserved performance status on progression on first-line chemotherapy (CT1) were more likely to receive second-line chemotherapy (CT2) (P < 0.001). Disease control rate with CT2 was 36%, and mean progression-free survival was 3.2 months (95% confidence interval 1.5-4.9 months). The following variables were significant in the univariate analysis of OS from time of progression on CT1: lines of chemotherapy (P = 0.0001), Eastern Cooperative Oncology Group performance status at progression on CT1 (P < 0.0001) and disease control with CT1 (P = 0.027). Lines of chemotherapy received and performance status remained significant in the multivariate analysis for OS from progression on CT1. Second-line chemotherapy is feasible in a subset of patients with ABC. Even after accounting for confounding variables, CT2 appears to increase OS in ABC, although we are unable to exclude other unmeasured factors such as tumor biology. These findings warrant further evaluation with prospective trials. © 2016 John Wiley & Sons Australia, Ltd.

Improved survival of patients with hepatocellular carcinoma and compensated hepatitis C virus-related cirrhosis who attained sustained virological response.

PubMed

Bruno, Savino; Di Marco, Vito; Iavarone, Massimo; Roffi, Luigi; Boccaccio, Vincenzo; Crosignani, Andrea; Cabibbo, Giuseppe; Rossi, Sonia; Calvaruso, Vincenza; Aghemo, Alessio; Giacomelli, Luca; Craxì, Antonio; Colombo, Massimo; Maisonneuve, Patrick

2017-10-01

Few studies examined the outcome of patients with hepatitis C virus (HCV)-related cirrhosis who developed hepatocellular carcinoma (HCC). The relative weight as determinant of death for cancer vs end-stage liver disease (ESLD) and the benefit of HCV eradication remain undefined. This multicentre, retrospective analysis evaluates overall survival (OS), rate of decompensation and tumour recurrence in compensated HCC patients treated with interferon (IFN) according to HCV status since HCC diagnosis. Two groups of patients with HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated cirrhotics with prior sustained virological response (SVR) on IFN-based regimens (N=19); (ii) compensated cirrhotics without SVR (viraemic) (N=156). Over a median follow-up of 3.0 years since the onset of HCC, OS was longer for HCC patients with SVR than for viraemic patients (log-rank P=.004). The 5-year OS rate was 65.9% in patients with SVR vs 31.9% in viraemic patients. Similar trends were reported for hepatic decompensation (log-rank P=.01) and tumour recurrence (log-rank P=.01). These findings were confirmed at multivariable and propensity score analysis. At propensity analysis, 0/19 compensated patients with SVR died for ESLD vs 7/19 (37%) viraemic patients (P=.004). HCC mortality was similar in the two groups. Hepatocellular carcinoma patients with prior SVR and compensated cirrhosis at the time of tumour diagnosis have prolonged OS than viraemic patients. Given the lack of cirrhosis progression, no SVR patient ultimately died for ESLD while this condition appears the main cause of death among viraemic patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

KPS/LDH index: a simple tool for identifying patients with metastatic melanoma who are unlikely to benefit from palliative whole brain radiotherapy.

PubMed

Partl, Richard; Fastner, Gerd; Kaiser, Julia; Kronhuber, Elisabeth; Cetin-Strohmer, Klaudia; Steffal, Claudia; Böhmer-Breitfelder, Barbara; Mayer, Johannes; Avian, Alexander; Berghold, Andrea

2016-02-01

Low Karnofsky performance status (KPS) and elevated lactate dehydrogenases (LDHs) as a surrogate marker for tumor load and cell turnover may depict patients with a very short life expectancy. To validate this finding and compare it to other indices, namely, the recursive partitioning analysis (RPA) and diagnosis-specific graded prognostic assessment (DS-GPA), a multicenter analysis was undertaken. A retrospective analysis of 234 metastatic melanoma patients uniformly treated with palliative whole brain radiotherapy (WBRT) was done. Univariate and multivariate analyses were used to determine the impact of patient-, tumor-, and treatment-related parameters on overall survival (OS). KPS and LDH emerged as independent factors predicting OS. By combining KPS and LDH values (KPS/LDH index), groups of patients with statistically significant differences in median OS (days; 95 % CI) after onset of WBRT were identified: group 1 (KPS ≥ 70/normal LDH) 234 (96-372), group 2 (KPS ≥ 70/elevated LDH) 112 (69-155), group 3 (KPS <70/normal LDH) 43 (12-74), and group 4 (KPS <70/elevated LDH) 29 (17-41). Between all four groups, statistically significant differences were observed. The RPA and DS-GPA indices failed to distinguish significantly between good and moderate prognosis and were inferior in predicting a very unfavorable prognosis. The parameters KPS and LDH independently impacted on OS. The combination of both (KPS/LDH index) identified patients with a very short life expectancy, who might be better served by recommending best supportive care instead of WBRT. The KPS/LDH index is simple and effective in terms of time and cost as compared to other prognostic indices.

Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy.

PubMed

Tokito, Takaaki; Azuma, Koichi; Kawahara, Akihiko; Ishii, Hidenobu; Yamada, Kazuhiko; Matsuo, Norikazu; Kinoshita, Takashi; Mizukami, Naohisa; Ono, Hirofumi; Kage, Masayoshi; Hoshino, Tomoaki

2016-03-01

Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups. Among stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer.

PubMed

Rubovszky, Gábor; Budai, Barna; Ganofszky, Erna; Horváth, Zsolt; Juhos, Éva; Madaras, Balázs; Nagy, Tünde; Szabó, Eszter; Pintér, Tamás; Tóth, Erika; Nagy, Péter; Láng, István; Hitre, Erika

2018-04-01

Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m 2 /week, loading dose: 400 mg/m 2 ), gemcitabine (1000 mg/m 2 on day 1 and 8), and capecitabine (1300 mg/m 2 /day on days 1-14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24-40) and 54 (43-67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.

Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis.

PubMed

Bowen, Randy C; Little, Nancy Ann B; Harmer, Joshua R; Ma, Junjie; Mirabelli, Luke G; Roller, Kyle D; Breivik, Andrew Mackay; Signor, Emily; Miller, Alec B; Khong, Hung T

2017-05-09

An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS).We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively.Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR.

Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis

PubMed Central

Bowen, Randy C.; Little, Nancy Ann B.; Harmer, Joshua R.; Ma, Junjie; Mirabelli, Luke G.; Roller, Kyle D.; Breivik, Andrew Mackay; Signor, Emily; Miller, Alec B.; Khong, Hung T.

2017-01-01

An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS). We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively. Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR. PMID:28418870

A new prognostic model identifies patients aged 80 years and older with diffuse large B-cell lymphoma who may benefit from curative treatment: A multicenter, retrospective analysis by the Spanish GELTAMO group.

PubMed

Pardal, Emilia; Díez Baeza, Eva; Salas, Queralt; García, Tomás; Sancho, Juan M; Monzón, Encarna; Moraleda, José M; Córdoba, Raúl; de la Cruz, Fátima; Queizán, José A; Rodríguez, María J; Navarro, Belén; Hernández, José A; Díez, Rosana; Vahi, María; Viguria, María C; Canales, Miguel; Peñarrubia, María J; González-López, Tomás J; Montes-Moreno, Santiago; González-Barca, Eva; Caballero, Dolores; Martín, Alejandro

2018-04-15

The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1-2) R-IPI, and treatment with R-CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R-CHOP-like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0-1 vs. 2-3 risk factors (age > 85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series. © 2018 Wiley Periodicals, Inc.

Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials

PubMed Central

Schwaederle, Maria; Zhao, Melissa; Lee, J. Jack; Eggermont, Alexander M.; Schilsky, Richard L.; Mendelsohn, John; Lazar, Vladimir; Kurzrock, Razelle

2015-01-01

Purpose The impact of a personalized cancer treatment strategy (ie, matching patients with drugs based on specific biomarkers) is still a matter of debate. Methods We reviewed phase II single-agent studies (570 studies; 32,149 patients) published between January 1, 2010, and December 31, 2012 (PubMed search). Response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared for arms that used a personalized strategy versus those that did not. Results Multivariable analysis (both weighted multiple linear regression and random effects meta-regression) demonstrated that the personalized approach, compared with a nonpersonalized approach, consistently and independently correlated with higher median RR (31% v 10.5%, respectively; P < .001) and prolonged median PFS (5.9 v 2.7 months, respectively; P < .001) and OS (13.7 v 8.9 months, respectively; P < .001). Nonpersonalized targeted arms had poorer outcomes compared with either personalized targeted therapy or cytotoxics, with median RR of 4%, 30%, and 11.9%, respectively; median PFS of 2.6, 6.9, and 3.3 months, respectively (all P < .001); and median OS of 8.7, 15.9, and 9.4 months, respectively (all P < .05). Personalized arms using a genomic biomarker had higher median RR and prolonged median PFS and OS (all P ≤ .05) compared with personalized arms using a protein biomarker. A personalized strategy was associated with a lower treatment-related death rate than a nonpersonalized strategy (median, 1.5% v 2.3%, respectively; P < .001). Conclusion Comprehensive analysis of phase II, single-agent arms revealed that, across malignancies, a personalized strategy was an independent predictor of better outcomes and fewer toxic deaths. In addition, nonpersonalized targeted therapies were associated with significantly poorer outcomes than cytotoxic agents, which in turn were worse than personalized targeted therapy. PMID:26304871

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

PubMed

Soh, Sheila X; Siddiqui, Fahad J; Allen, John C; Kim, Go Woon; Lee, Jae Cheol; Yatabe, Yasushi; Soda, Manabu; Mano, Hiroyuki; Soo, Ross A; Chin, Tan-Min; Ebi, Hiromichi; Yano, Seiji; Matsuo, Keitaro; Niu, Xiaomin; Lu, Shun; Isobe, Kazutoshi; Lee, Jih-Hsiang; Yang, James C; Zhao, Mingchuan; Zhou, Caicun; Lee, June-Koo; Lee, Se-Hoon; Lee, Ji Yun; Ahn, Myung-Ju; Tan, Tira J; Tan, Daniel S; Tan, Eng-Huat; Ong, S Tiong; Lim, Wan-Teck

2017-06-20

A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.

Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy.

PubMed

Rossi, Valentina; Nolè, Franco; Redana, Stefania; Adamoli, Laura; Martinello, Rossella; Aurilio, Gaetano; Verri, Elena; Sapino, Anna; Viale, Giuseppe; Aglietta, Massimo; Montemurro, Filippo

2014-02-01

Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation. Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation. Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary ("de novo/surgery"). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", "de novo/surgery" and "de novo" without surgery ("de novo/no surgery) stage IV breast cancer. However, women with "de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with "de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings. Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of Body Mass Index and Albumin on Perioperative Morbidity and Clinical Outcomes in Resected Pancreatic Adenocarcinoma

PubMed Central

Hendifar, Andrew; Osipov, Arsen; Khanuja, Jasleen; Nissen, Nicholas; Naziri, Jason; Yang, Wensha; Li, Quanlin; Tuli, Richard

2016-01-01

Obesity is a known risk factor for PDA and recent reports suggest obesity has a negative impact on clinical outcomes in patients with PDA. Pretreatment body mass index (BMI) and serum albumin (SA) have been shown to be associated with worse overall survival in patients with advanced and metastatic PDA. However, minimal data exists on the impact of BMI and SA on perioperative and long-term clinical outcomes in patients with early-stage resected PDA. Herein, we report on the impact of these variables on perioperative clinical outcomes, overall survival (OS) and disease free survival (DFS) in patients with resected PDA. With IRB approval, we evaluated 1,545 patients with PDA treated at a single institution from 2007–2013 and identified 106 patients who underwent upfront resection with curative intent. BMI and SA were calculated preoperatively and at the time of last clinical evaluation. Influence of preoperative BMI, SA, change in either variable, and influence of other clinical and pathologic variables on perioperative morbidity and mortality was assessed. The impact of these variables on DFS and OS was assessed with cox regression modeling and ANOVA. Actuarial estimates for DFS and OS were calculated using Kaplan-Meier methods. Median follow up time was 16 months (3–89). Mean age was 68 years. Median survival was 14 months (3–65) and median time to recurrence was 11 months (1–79). Length of hospital stay was associated with BMI (p = .023), change in BMI (p = .003) and SA (p = .004). Post-operative transfusion rate was associated with SA (p = .021). There was a strong correlation between BMI change and positive margin (p = .04) and lymph node status (p = .01). On multivariate analysis, change in SA (p = .03) and node positivity (p = .008) were associated with decreased DFS. Additionally, preoperative SA (p = .023), node positivity (p = .026) and poor differentiation (p = .045) were associated with worse OS on multivariate analysis. Low preoperative SA was associated with worse DFS and OS in patients with resected PDA. Lower BMI and SA were associated with longer post-operative hospital stay. Our study is one of the first to describe how pre-operative BMI and SA and post-operative changes in these variables impact clinical and perioperative outcomes. This data supports nutritional status and weight loss as predictors of outcome in resected pancreatic cancer patients and warrants further prospective investigation. PMID:27015568

Influence of Body Mass Index and Albumin on Perioperative Morbidity and Clinical Outcomes in Resected Pancreatic Adenocarcinoma.

PubMed

Hendifar, Andrew; Osipov, Arsen; Khanuja, Jasleen; Nissen, Nicholas; Naziri, Jason; Yang, Wensha; Li, Quanlin; Tuli, Richard

2016-01-01

Obesity is a known risk factor for PDA and recent reports suggest obesity has a negative impact on clinical outcomes in patients with PDA. Pretreatment body mass index (BMI) and serum albumin (SA) have been shown to be associated with worse overall survival in patients with advanced and metastatic PDA. However, minimal data exists on the impact of BMI and SA on perioperative and long-term clinical outcomes in patients with early-stage resected PDA. Herein, we report on the impact of these variables on perioperative clinical outcomes, overall survival (OS) and disease free survival (DFS) in patients with resected PDA. With IRB approval, we evaluated 1,545 patients with PDA treated at a single institution from 2007-2013 and identified 106 patients who underwent upfront resection with curative intent. BMI and SA were calculated preoperatively and at the time of last clinical evaluation. Influence of preoperative BMI, SA, change in either variable, and influence of other clinical and pathologic variables on perioperative morbidity and mortality was assessed. The impact of these variables on DFS and OS was assessed with cox regression modeling and ANOVA. Actuarial estimates for DFS and OS were calculated using Kaplan-Meier methods. Median follow up time was 16 months (3-89). Mean age was 68 years. Median survival was 14 months (3-65) and median time to recurrence was 11 months (1-79). Length of hospital stay was associated with BMI (p = .023), change in BMI (p = .003) and SA (p = .004). Post-operative transfusion rate was associated with SA (p = .021). There was a strong correlation between BMI change and positive margin (p = .04) and lymph node status (p = .01). On multivariate analysis, change in SA (p = .03) and node positivity (p = .008) were associated with decreased DFS. Additionally, preoperative SA (p = .023), node positivity (p = .026) and poor differentiation (p = .045) were associated with worse OS on multivariate analysis. Low preoperative SA was associated with worse DFS and OS in patients with resected PDA. Lower BMI and SA were associated with longer post-operative hospital stay. Our study is one of the first to describe how pre-operative BMI and SA and post-operative changes in these variables impact clinical and perioperative outcomes. This data supports nutritional status and weight loss as predictors of outcome in resected pancreatic cancer patients and warrants further prospective investigation.

Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H).

PubMed

Goldstein, J; Tran, B; Ensor, J; Gibbs, P; Wong, H L; Wong, S F; Vilar, E; Tie, J; Broaddus, R; Kopetz, S; Desai, J; Overman, M J

2014-05-01

The microsatellite instability-high (MSI-H) phenotype, present in 15% of early colorectal cancer (CRC), confers good prognosis. MSI-H metastatic CRC is rare and its impact on outcomes is unknown. We describe survival outcomes and the impact of chemotherapy, metastatectomy, and BRAF V600E mutation status in the largest reported cohort of MSI-H metastatic colorectal cancer (CRC). A retrospective review of 55 MSI-H metastatic CRC patients from two institutions, Royal Melbourne Hospital (Australia) and The University of Texas MD Anderson Cancer Center (United States), was conducted. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Median age was 67 years (20-90), 58% had poor differentiation, and 45% had stage IV disease at presentation. Median overall survival (OS) from metastatic disease was 15.4 months. Thirteen patients underwent R0/R1 metastatectomies, with median OS from metastatectomy 33.8 months. Thirty-one patients received first-line systemic chemotherapy for metastatic disease with median OS from the start of chemotherapy 11.5 months. No statistically significant difference in progression-free survival or OS was seen between fluoropyrimidine, oxaliplatin, or irinotecan based chemotherapy. BRAF V600E mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate analyses, BRAF V600E mutants had worse OS (HR 4.04; P = 0.005), while patients undergoing metastatectomy (HR 0.11; P = <0.001) and patients who initially presented as stage IV disease had improved OS (HR 0.27; P = 0.003). Patients with MSI-H metastatic CRC do not appear to have improved outcomes. BRAF V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.

Inflammation scores predict survival for hepatitis B virus-related hepatocellular carcinoma patients after transarterial chemoembolization

PubMed Central

Zhou, Dong-Sheng; Xu, Li; Luo, Yao-Ling; He, Feng-Ying; Huang, Jun-Ting; Zhang, Yao-Jun; Chen, Min-Shan

2015-01-01

AIM: To compare the prognostic ability of inflammation scores for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: Data of 224 consecutive patients who underwent TACE for unresectable HBV-related HCC from September 2009 to November 2011 were retrieved from a prospective database. The association of inflammation scores with clinicopathologic variables and overall survival (OS) were analyzed, and receiver operating characteristic curves were generated, and the area under the curve (AUC) was calculated to evaluate the discriminatory ability of each inflammation score and staging system, including tumor-node-metastasis, Barcelona Clinic Liver Cancer, and Cancer of the Liver Italian Program (CLIP) scores. RESULTS: The median follow-up period was 390 d, the one-, two-, and three-year OS were 38.4%, 18.3%, and 11.1%, respectively, and the median OS was 390 d. The Glasgow Prognostic Score (GPS), modifed GPS, neutrophil-lymphocyte ratio, and Prognostic Index were associated with OS. The GPS consistently had a higher AUC value at 6 mo (0.702), 12 mo (0.676), and 24 mo (0.687) in comparison with other inflammation scores. CLIP consistently had a higher AUC value at 6 mo (0.656), 12 mo (0.711), and 24 mo (0.721) in comparison with tumor-node-metastasis and Barcelona Clinic Liver Cancer staging systems. Multivariate analysis revealed that alanine aminotransferase, GPS, and CLIP were independent prognostic factors for OS. The combination of GPS and CLIP (AUC = 0.777) was superior to CLIP or GPS alone in prognostic ability for OS. CONCLUSION: The prognostic ability of GPS is superior to other inflammation scores for HCC patients undergoing TACE. Combining GPS and CLIP improved the prognostic power for OS. PMID:25987783

Margin Status Remains an Important Determinant of Survival after Surgical Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy

PubMed Central

Andreou, Andreas; Aloia, Thomas A.; Brouquet, Antoine; Dickson, Paxton V.; Zimmitti, Giuseppe; Maru, Dipen M.; Kopetz, Scott; Loyer, Evelyne M.; Curley, Steven A.; Abdalla, Eddie K.; Vauthey, Jean-Nicolas

2013-01-01

Objective To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases (CLM) after modern preoperative chemotherapy. Summary Background Data In the era of effective chemotherapy for CLM, the association between surgical margin status and survival has become controversial. Methods Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Results Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin < 1 mm). The 5-year OS rates for patients with R0 resection (margin ≥ 1 mm) and R1 resection were 55% and 26%, respectively (P=0.017). Multivariate analysis identified R1 resection (P=0.03) and minor pathologic response to chemotherapy (P=0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs. R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs. 11%, P=0.007) than in patients with optimal response (3-year OS rate: 92% vs. 88%, P=0.917) and greater in patients with minor pathologic response (5-year OS rate: 46% vs. 0%, P=0.002) than in patients with major response (5-year OS rate: 63% vs. 67%, P=0.587). Conclusions In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy. PMID:23426338

Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy.

PubMed

Andreou, Andreas; Aloia, Thomas A; Brouquet, Antoine; Dickson, Paxton V; Zimmitti, Giuseppe; Maru, Dipen M; Kopetz, Scott; Loyer, Evelyne M; Curley, Steven A; Abdalla, Eddie K; Vauthey, Jean-Nicolas

2013-06-01

To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome.

PubMed

Trédan, Olivier; Manuel, Manuarii; Clapisson, Gilles; Bachelot, Thomas; Chabaud, Sylvie; Bardin-dit-Courageot, Christine; Rigal, Chantal; Biota, Cathy; Bajard, Agathe; Pasqual, Nicolas; Blay, Jean-Yves; Caux, Christophe; Ménétrier-Caux, Christine

2013-05-01

Low lymphocyte count is a prognostic factor in cancer patients including metastatic breast cancer patients (MBC) but the relative role of each lymphocyte subtype is unclear in MBC. The impact of lymphocyte subsets was analysed in two prospective MBC patients' cohorts. Cohort A patients (n=103) were included before the first line of chemotherapy and cohort B patients (n=101) were included after at least one line of chemotherapy. Extensive phenotypic analyses were performed on fresh whole blood. Plasma cytokines levels were measured using commercially available Luminex-based multiplex kits. Prognostic value of lymphocyte subsets and circulating cytokines was analysed. In both cohorts, severe lymphopaenia (<0.7 Giga/L) correlated with poor overall survival (OS) (median OS: 6.6 months versus 21.7 months in cohort A and 4.5 versus 9 months in cohort B). CD8(+), CD19(+) and CD56(+) T cell counts had no significant prognostic value for OS. After stratification (≤0.2, [0.20-0.45], >0.45 Giga/L), CD4 lymphopaenia appeared to be correlated with poor OS in both cohorts. Furthermore, severe CD4(+) lymphopaenia (≤0.2 Giga/L) was strongly correlated with poor OS in both cohorts (1.2 months versus 24.9 months in cohort A and 5.7 versus 13.1 months in cohort B). In multivariate analysis, after stratification CD4(+) lymphopaenia appeared to be an independent prognostic factor for OS in both cohorts. CD4(+) lymphopaenia correlated with low plasmatic levels of CCL22 that might directly contribute to CD4(+) lymphopaenia. CD4(+) lymphopaenia was associated with reduced OS in MBC patients regardless of the chemotherapy line. Decreased levels of plasmatic CCL22 may contribute to CD4(+) lymphopaenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lymphopenia Association With Gross Tumor Volume and Lung V5 and Its Effects on Non-Small Cell Lung Cancer Patient Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Chad; Liao, Zhongxing, E-mail: zliao@mdanderson.org; Gomez, Daniel

2014-08-01

Purpose: Radiation therapy (RT) can both suppress and stimulate the immune system. We sought to investigate the mechanisms underlying radiation-induced lymphopenia and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Methods and Materials: Subjects consisted of 711 patients who had received definitive RT for NSCLC. A lymphocyte nadir was calculated as the minimum lymphocyte value measured during definitive RT. Associations between gross tumor volumes (GTVs) and lung dose-volume histogram (DVH) parameters with lymphocyte nadirs were assessed with Spearman correlation coefficients. Relationships between lymphocyte nadirs with overall survival (OS) and event free survival (EFS) were evaluated with Kaplan-Meiermore » analysis and compared with log-rank test results. Multivariate regressions were conducted with linear and Cox regression analyses. All variables were analyzed as continuous if possible. Results: Larger GTVs were correlated with lower lymphocyte nadirs regardless of concurrent chemotherapy receipt (with concurrent: r = −0.26, P<.0001; without: r = −0.48, P<.0001). Analyses of lung DVH parameters revealed significant correlations at lower doses (lung V5-V10: P<.0001) that incrementally decreased and became nonsignificant at higher doses (lung V60-V70: P>.05). Of note, no significant associations were detected between GTV and lung DVH parameters with total leukocyte, neutrophil, or monocyte nadirs during RT or with lymphocyte count prior to RT. Multivariate analysis revealed larger GTV (P<.0001), receipt of concurrent chemotherapy (P<.0001), twice-daily radiation fractionation (P=.02), and stage III disease (P=.05) to be associated with lower lymphocyte nadirs. On univariate analysis, patients with higher lymphocyte nadirs exhibited significantly improved OS (hazard ratio [HR] = 0.51 per 10{sup 3} lymphocytes/μL, P=.01) and EFS (HR = 0.46 per 10{sup 3} lymphocytes/μL, P<.0001). These differences held on multivariate analyses, controlling for common disease and treatment characteristics including GTV. Conclusions: Lower lymphocyte nadirs during definitive RT were associated with larger GTVs and worse patient outcomes.« less

Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.

PubMed

Wang, Tso-Fu; Chu, Sung-Chao; Lee, Jen-Jyh; Yang, Gee-Gwo; Huang, Wei-Han; Chang, En-Ting; Low, Tissot; Wu, Yi-Feng; Kao, Ruey-Ho; Lin, Chih-Bin

2017-08-01

This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients. © 2017 John Wiley & Sons Australia, Ltd.

The impact of colorectal screening program on the detection of right-sided colorectal cancer. A 5-year cohort study in the Mantua District.

PubMed

Asteria, Corrado R; Pucciarelli, Salvatore; Gerard, Leonardo; Mantovani, Nicola; Pagani, Mauro; Boccia, Luigi; Ricci, Paolo; Troiano, Luigi; Lucchini, Giuseppe; Pulica, Coriolano

2015-12-01

High rates of advanced colorectal cancer (CRC) are still diagnosed in the right side of the colon. This study aimed to investigate whether screening programs increase CRC detection and whether tumor location is associated with survival outcome. Patients affected by CRC, aged from 50 to 69 years and operated on from 2005 to 2009 were reviewed. Other than patient-, disease-, and treatment-related factors, detection mode and tumor location were recorded. Overall (OS) and disease-free survival (DFS) were investigated, using univariate and multivariate analyses. Mean age of 386 patients included was 62.0 years, 59 % were males. CRC was detected by screening in 17 % of cases, and diagnosis was made from symptoms in 67 % and emergency surgery for 16 %. Screen-detected CRCs were located in the left colon (59 %), then in rectum (25 %) and in proximal colon (16 %) (p = 0.02). Most of CRC patients urgently operated on had cancer located in proximal colon (45 %), then in the left colon (36 %) and in rectum (18 %) (p = 0.001). Right-sided CRC demonstrated higher pTNM stage (p = 0.001), adequate harvest count nodes (p = 0.0001), metastatic nodes (p = 0.02), and poor differentiation grading (p = 0.0001). With multivariate analysis, poor differentiation grade was independently associated with both worse OS (HR 3.6, p = 0.05) and worse DFS (HR 8.1, p = 0.0001), while distant recurrence was associated with worse OS (HR 20.1, p = 0.0001). Low rates of right-sided CRC are diagnosed following screening program. Proximal CRC demonstrates aggressive behavior without impact on outcome. These findings prompt concern about population awareness for CRC screening.

Clinically Non-Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation: Natural History and Outcomes after Surgical Resection with Curative Intent

PubMed Central

Merrill, Megan M.; Wood, Christopher G.; Tannir, Nizar M.; Slack, Rebecca S.; Babaian, Kara N.; Jonasch, Eric; Pagliaro, Lance C.; Compton, Zachary; Tamboli, Pheroze; Sircar, Kanishka; Pisters, Louis L.; Matin, Surena F.; Karam, Jose A.

2015-01-01

Purpose Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. While existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate post-nephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. Patients and Methods An IRB-approved review from 1986–2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. Results OS for the entire cohort (N=77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who were NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and RFS. Limitations include the retrospective nature of this study and relatively small sample size. Conclusions Long-term survival for patients with sRCC, even in clinically localized disease is poor. Aggressive surveillance of those who are NED following nephrectomy is essential and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted. PMID:25700975

Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery.

PubMed

Keung, Emily Z; Hornick, Jason L; Bertagnolli, Monica M; Baldini, Elizabeth H; Raut, Chandrajit P

2014-02-01

Although sarcoma histology is recognized as a prognostic factor, most studies of retroperitoneal sarcomas report results combining multiple histologies and are inadequately powered to identify prognostic factors specific to a particular histology. We reviewed our experience with retroperitoneal dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of outcomes. All patients with RP DDLPS treated at our institution between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were performed to identify factors predictive of progression-free survival (PFS), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). We identified 119 patients with primary DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in 72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1 months. One hundred patients (84%) experienced recurrence or progression, with 92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1, 21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2 resection. On multivariate analysis, tumor integrity (intact vs fragmented) was predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1 vs R2), grade, and tumor integrity predicted OS. In this cohort of primary RP DDLPS, factors under surgeon control (tumor integrity, extent of resection) and reflective of tumor biology (grade, multifocality) impact patient outcomes. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.

PubMed

Umemoto, Yuichiroh; Okano, Shinji; Matsumoto, Yoshihiro; Nakagawara, Hidekazu; Matono, Rumi; Yoshiya, Shohei; Yamashita, Yo-Ichi; Yoshizumi, Tomoharu; Ikegami, Toru; Soejima, Yuji; Harada, Mamoru; Aishima, Shinichi; Oda, Yoshinao; Shirabe, Ken; Maehara, Yoshihiko

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined. We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis. High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS. PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma.

PubMed

Nadal, Ernest; Chen, Guoan; Prensner, John R; Shiratsuchi, Hiroe; Sam, Christine; Zhao, Lili; Kalemkerian, Gregory P; Brenner, Dean; Lin, Jules; Reddy, Rishindra M; Chang, Andrew C; Capellà, Gabriel; Cardenal, Felipe; Beer, David G; Ramnath, Nithya

2014-10-01

The aim of this study was to examine the effects of KRAS mutant subtypes on the outcome of patients with resected lung adenocarcinoma (AC). Using clinical and sequencing data, we identified 179 patients with resected lung AC for whom KRAS mutational status was determined. A multivariate Cox model was used to identify factors associated with disease-free survival (DFS) and overall survival (OS). Publicly available mutation and gene-expression data from lung cancer cell lines and lung AC were used to assess whether distinct KRAS mutant variants have a different profile. Patients with KRAS mutation had a significantly shorter DFS compared with those with KRAS wild-type (p = 0.009). Patients with KRAS-G12C mutant tumors had significantly shorter DFS compared with other KRAS mutants and KRAS wild-type tumors (p < 0.001). In the multivariate Cox model, KRAS-G12C remained as an independent prognostic marker for DFS (Hazard ratio = 2.46, 95% confidence interval 1.51-4.00, p < 0.001) and for OS (Hazard ratio = 2.35, 95% confidence interval 1.35-4.10, p = 0.003). No genes were statistically significant when comparing the mutational or transcriptional profile of lung cancer cell lines and lung AC harboring KRAS-G12C with other KRAS mutant subtypes. Gene set enrichment analysis revealed that KRAS-G12C mutants overexpressed epithelial to mesenchymal transition genes and expressed lower levels of genes predicting KRAS dependency. KRAS-G12C mutation is associated with worse DFS and OS in resected lung AC. Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRAS-G12C mutants had an epithelial to mesenchymal transition and a KRAS-independent phenotype.

Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study.

PubMed

Desjonquères, A; Chevallier, P; Thomas, X; Huguet, F; Leguay, T; Bernard, M; Bay, J-O; Tavernier, E; Charbonnier, A; Isnard, F; Hunault, M; Turlure, P; Renaud, M; Bastié, J-N; Himberlin, C; Lepretre, S; Lioure, B; Lhéritier, V; Asnafi, V; Beldjord, K; Lafage-Pochitaloff, M; Béné, M C; Ifrah, N; Dombret, H

2016-12-09

The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.

Applying quantitative adiposity feature analysis models to predict benefit of bevacizumab-based chemotherapy in ovarian cancer patients

NASA Astrophysics Data System (ADS)

Wang, Yunzhi; Qiu, Yuchen; Thai, Theresa; More, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

2016-03-01

How to rationally identify epithelial ovarian cancer (EOC) patients who will benefit from bevacizumab or other antiangiogenic therapies is a critical issue in EOC treatments. The motivation of this study is to quantitatively measure adiposity features from CT images and investigate the feasibility of predicting potential benefit of EOC patients with or without receiving bevacizumab-based chemotherapy treatment using multivariate statistical models built based on quantitative adiposity image features. A dataset involving CT images from 59 advanced EOC patients were included. Among them, 32 patients received maintenance bevacizumab after primary chemotherapy and the remaining 27 patients did not. We developed a computer-aided detection (CAD) scheme to automatically segment subcutaneous fat areas (VFA) and visceral fat areas (SFA) and then extracted 7 adiposity-related quantitative features. Three multivariate data analysis models (linear regression, logistic regression and Cox proportional hazards regression) were performed respectively to investigate the potential association between the model-generated prediction results and the patients' progression-free survival (PFS) and overall survival (OS). The results show that using all 3 statistical models, a statistically significant association was detected between the model-generated results and both of the two clinical outcomes in the group of patients receiving maintenance bevacizumab (p<0.01), while there were no significant association for both PFS and OS in the group of patients without receiving maintenance bevacizumab. Therefore, this study demonstrated the feasibility of using quantitative adiposity-related CT image features based statistical prediction models to generate a new clinical marker and predict the clinical outcome of EOC patients receiving maintenance bevacizumab-based chemotherapy.

Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez Guerra, Jose Luis; Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid; Gomez, Daniel, E-mail: dgomez@mdanderson.org

2012-09-01

Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed bettermore » overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.« less

Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach.

PubMed

Wang, Hong-Mei; Huang, Chang-Ming; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Lu, Jun

2012-10-14

To explore the impact of tumor size on outcomes in patients with advanced gastric cancer in the lower third of the stomach. We retrospectively analyzed the clinical records of 430 patients with advanced gastric cancer in the lower third of the stomach who underwent distal subtotal gastrectomy and D2 lymphadenectomy in our hospital from January 1998 to June 2004. Receiver-operating characteristic (ROC) curve analysis was used to determine the appropriate cutoff value for tumor size, which was measured as maximum tumor diameter. Based on this cutoff value, patients were divided into two groups: those with large-sized tumors (LSTs) and those with small-sized tumors (SSTs). The correlations between other clinicopathologic factors and tumor size were investigated, and the 5-year overall survival (OS) rate was compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox's proportional hazard model analysis. The 5-year OS rates in the two groups were compared according to pT stage and pN stage. The 5-year OS rate in the 430 patients with advanced gastric cancer in the lower third of the stomach was 53.7%. The mean ± SD tumor size was 4.9 ± 1.9 cm, and the median tumor size was 5.0 cm. ROC analysis indicated that the sensitivity and specificity results for the appropriate tumor size cutoff value of 4.8 cm were 80.0% and 68.2%, respectively (AUC = 0.795, 95%CI: 0.751-0.839, P = 0.000). Using this cutoff value, 222 patients (51.6%) had LSTs (tumor size ≥ 4.8 cm) and 208 (48.4%) had SSTs (tumor size < 4.8 cm). Tumor size was significantly correlated with histological type (P = 0.039), Borrmann type (P = 0.000), depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.000), tumor-nodes metastasis stage (P = 0.000), mean number of metastatic lymph nodes (P = 0.000) and metastatic lymph node ratio (P = 0.000). Patients with LSTs had a significantly lower 5-year OS rate than those with SSTs (37.1% vs 63.3%, P = 0.000). Univariate analysis showed that depth of tumor invasion (χ² = 69.581, P = 0.000), lymph node metastasis (χ² = 138.815, P = 0.000), tumor size (χ² = 78.184, P = 0.000) and metastatic lymph node ratio (χ² = 139.034, P = 0.000) were significantly associated with 5-year OS rate. Multivariate analysis revealed that depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.019) and tumor size (P = 0.000) were independent prognostic factors. Gastric cancers were divided into 12 subgroups: pT2N0; pT2N1; pT2N2; pT2N3; pT3N0; pT3N1; pT3N2; pT3N3; pT4aN0; pT4aN1; pT4aN2; and pT4aN3. In patients with pT2-3N3 stage tumors and patients with pT4a stage tumors, 5-year OS rates were significantly lower for LSTs than for SSTs (P < 0.05 each), but there were no significant differences in the 5-year OS rates in LST and SST patients with pT2-3N0-2 stage tumors (P > 0.05). Using a tumor size cutoff value of 4.8 cm, tumor size is a prognostic factor in patients with pN3 stage or pT4a stage advanced gastric cancer located in the lower third of the stomach.

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

PubMed

Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

2018-01-01

The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR < 2.95 compared to 20% in the group with NLR ⩾ 2.95 (P= 0.094). NLR was lower in CR patients in comparison to Non-CR subjects (P= 0.044). Patients with a NLR ⩾ 2.95 experienced inferior median survival compared to those with NLR < 2.95 (4-year OS rates were 30.9% and 64.8%, respectively, P= 0.029). In multivariate analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

Survival of patients with head and neck cancer. Impact of physical status and comorbidities.

PubMed

Sadat, F; Wienke, A; Dunst, J; Kuhnt, T

2012-01-01

Prognostic factors (e.g., gender, tumor stage, and hypoxia) have an impact on survival in patients with head and neck cancer. Thus, the impact of physical status and comorbidities on treatment decision and survival were evaluated. A total of 169 primary, inoperable patients with squamous cell cancer of the head and neck were retrospectively investigated. Patients were treated with hyperfractionated accelerated radio(chemo)therapy (HARcT) or hypofractionated radio(chemo)therapy (HypoRcT). Depending on the individual patient's situation (Karnofsky Performance Index, KPI), treatment for patients with a KPI of 80-100% was generally radiochemotherapy and for patients with a KPI ≤ 70% treatment was radiotherapy alone. In addition, all comorbidities were evaluated. Uni- and multivariate proportional hazards model were used, and overall survival (OS) was estimated by the Kaplan-Meier method. Treatment consisted of HARcT for 76 patients (45%), HART for 28 patients (17%), HypoRcT for 14 patients(8%), and HypoRT for 51 patients (30%). Of the patients, 107 patients (63%) presented with a KPI of 80-100%. OS (20%) was significantly better for patients with a KPI of 80-100%, while the OS for patients with a KPI ≤ 70% was 8% (p < 0.001). Good KPI, total irradiation dose (> 70 Gy), and chemotherapy were significant prognostic factors for better OS. Our retrospective analysis shows that performance status with dependency on comorbidities was an independent risk factor for OS.

Does tumor size have its prognostic role in colorectal cancer? Re-evaluating its value in colorectal adenocarcinoma with different macroscopic growth pattern.

PubMed

Dai, Weixing; Li, Yaqi; Meng, Xianke; Cai, Sanjun; Li, Qingguo; Cai, Guoxiang

2017-09-01

Few previous studies have taken the growth pattern into consideration when analyzing the prognostic value of tumor size in colorectal cancer (CRC). We sought to reveal the prognostic role of tumor size in different macroscopic growth patterns of CRC. Using Cancer Center datasets, we identified 4057 cases with colorectal adenocarcinoma treated with curative resection. Macroscopic growth patterns of tumors were classified into three types: infiltrative, ulcerative and expansive types based on tumor gross appearance. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic factors for overall survival (OS) and disease-free survival (DFS). In whole cohort, tumor size was an independent factor for OS (HR 1.10, 95%CI 1.04-1.16, p < 0.001). Subgroup analysis based on macroscopic growth pattern suggested that tumor size was an independent factor for OS both in the infiltrative (HR 1.37, 95%CI 1.12-1.66, p = 0.002) group and ulcerative group (HR 1.08, 95%CI 1.00-1.16, p = 0.044) and tumor size (HR 1.22, 95%CI 1.06-1.40, p = 0.004) was found as an independent factor for DFS only in infiltrative group. Tumor size is an independent factor for OS and DFS in patients with colorectal adenocarcinoma of infiltrative type, while only for OS in patients of ulcerative type. Copyright © 2017. Published by Elsevier Ltd.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

PubMed

Kozman, Mathew A; Fisher, Oliver M; Rebolledo, Bree-Anne J; Parikh, Roneil; Valle, Sarah J; Arrowaili, Arief; Alzahrani, Nayef; Liauw, Winston; Morris, David L

2018-03-01

Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior. © 2017 Wiley Periodicals, Inc.

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer

PubMed Central

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-01-01

Purpose This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). Materials and Methods We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). Results In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Conclusion Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID:27669704

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer.

PubMed

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-07-01

This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus.

PubMed

Miyake, Hideaki; Sugiyama, Takayuki; Aki, Ryota; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Otsuka, Atsushi

2018-06-01

To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy. This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy. Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27 (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted therapy alone and both therapies, respectively, as management for metastatic diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No significant differences in OS were noted according to the level of the IVC tumor thrombus. There were no significant differences in OS among groups A, B and C; however, OS in groups B and C was significantly superior to that in group A. Furthermore, multivariate analysis of several parameters identified the following independent predictors of poor OS-elevated C-reactive protein, liver metastasis and postoperative treatment with cytokine therapy alone. The prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy may be significantly affected by the type of postoperative systemic therapy rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive nephrectomy should be considered as a major therapeutic option for patients with mRCC involving the IVC, particularly in the era of targeted therapy.

Glypican-3 mRNA expression level in Wilms tumor: correlation with histological type, stage, and outcome.

PubMed

Wari, Md Nahidul; Vallonthaiel, Archana George; Ahmed, Aijaz; Saxena, Deepali; Iyer, Venkateswaran K; Mathur, Sandeep R; Agarwala, Sandeep; Bakhshi, Sameer; Srinivas, V; Chattopadhyaya, P; Sharma, Arundhati; Gupta, S Datta; Dinda, Amit

2017-06-01

To correlate expression of Glypican-3 in Wilms tumor with histopathology, stage, and outcome. Glypican-3 mRNA expression by real-time PCR on tumor and normal germline samples from 75 fresh nephrectomies for Wilms tumor with fold change after normalization against GAPDH was compared. Survival analysis for event-free and overall survival (EFS, OS) with 2-year follow-up for Glypican-3 overexpression (>1.5 times) and clinicopathological parameters was performed. Glypican-3 was overexpressed in 37/75 (49.3%). It was overexpressed in 77% (10/13) cases with blastema predominance or anaplastic histology, as compared to 44% of other histologies (27/62) (p = 0.03). OS was 73 and 93%, respectively (p = 0.016), for those with and without GPC-3 overexpression. EFS was not significantly different with Glypican-3 overexpression (p = 0.11). All 5 deaths among blastema predominant tumors and 4/5 deaths among triphasic tumors had overexpressed Glypican-3. Most deaths in Stage IV, Stage III, and Stage I + II (5/7, 3/3, 1/1) had GPC-3 overexpression. On multivariate analysis, only histology and stage were found to have independent prognostic value. Glypican-3 overexpression in Wilms tumor correlates with poor OS on univariate analysis. However, only histology and stage have independent prognostic value. Glypican-3 levels may help to stratify intermediate outcome histology (triphasic) and Stage III Wilms tumors.

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma: A single-institution experience in China

PubMed Central

Hu, Hai-Jie; Mao, Hui; Shrestha, Anuj; Tan, Yong-Qiong; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

2016-01-01

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution. METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated by univariate and multivariate analyses. RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio (HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease (HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation (HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion (HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins (HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease (HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation (HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion (HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins (HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio (OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter (OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures (OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage (OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion (OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumor-free margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin. PMID:26937148

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

PubMed

Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

Surgery in adrenocortical carcinoma: Importance of national cooperation and centralized surgery.

PubMed

Hermsen, Ilse G C; Kerkhofs, Thomas M A; den Butter, Gijsbert; Kievit, Job; van Eijck, Casper H J; Nieveen van Dijkum, Els J M; Haak, Harm R

2012-07-01

The low incidence rate of adrenocortical carcinoma (ACC) requires a multidisciplinary approach in which surgery plays an essential role because complete resection of the primary tumor is the only chance of cure. To improve patient care, insight into operative results within the ACC population is essential. In 2007, a Dutch Adrenal Network Registry was created covering care and outcome of patients treated for ACC in the Netherlands since 1965. Using this database, we performed a study (1) to gain insight into surgical performance in the Netherlands and (2) to compare operative data with international literature. Data on patients treated from 1965 until January 2008 were studied. The following data were collected: age, gender, functionality of the tumor, stage at diagnosis, operative procedure, completeness of surgery, disease recurrence, adjuvant mitotane therapy, and recurrence-free and overall survival (OS). A total of 175 patients were studied, of whom 149 underwent surgery. Patients with complete resection had significantly longer OS times than patients with incomplete resection (P = .010). Patients operated on in a Dutch Adrenal Network center had significantly longer duration of OS in both univariate (P = .011) and multivariate analysis (P = .014). A significantly greater OS was observed for operated stage IV patients compared with nonoperated patients (P = .002). Our data suggest the relevance of national cooperation and centralized surgery in ACC. For selected patients with stage IV disease, surgery can be beneficial in extending survival. On the basis of the retrospective analysis, operative ACC in the Netherlands can and will be improved. Copyright © 2012. Published by Mosby, Inc.

The diagnostic and prognostic value of SALL4 in hepatoblastoma.

PubMed

Zhou, Shengmei; Venkatramani, Rajkumar; Gomulia, Ellen; Shillingford, Nick; Wang, Larry

2016-11-01

To investigate the expression of spalt-like transcription factor 4 (SALL4), a regulator of embryonal development, in three epithelial components of hepatoblastoma (HB) and the relationship between SALL4 expression levels and patients' clinicopathological features. A total of 115 specimens from 79 patients with HB were selected for immunostaining of SALL4. Nuclear staining was semi-quantified using the immunoreactive score (IS; range: 0-12). SALL4 expression was seen in all embryonal components (mean IS = 8.58) and in 41% of fetal components (mean IS = 0.78). No SALL4 expression was seen in either small cell undifferentiated or mesenchymal components of HB. Neither chemotherapy nor metastasis altered SALL4 expression significantly. High SALL4 expression levels were associated significantly with decreased overall survival (OS) (P = 0.004), event-free survival (EFS) (P = 0.003) and the presence of metastasis (P = 0.049) on univariate analysis. Multivariate analysis identified SALL4 as an independent prognostic predictor for OS (P = 0.029). SALL4 is useful for subtyping HB, and high SALL4 expression is associated with decreased survival in HB. © 2016 John Wiley & Sons Ltd.

Associations Between PET Textural Features and GLUT1 Expression, and the Prognostic Significance of Textural Features in Lung Adenocarcinoma.

PubMed

Koh, Young Wha; Park, Seong Yong; Hyun, Seung Hyup; Lee, Su Jin

2018-02-01

We evaluated the association between positron emission tomography (PET) textural features and glucose transporter 1 (GLUT1) expression level and further investigated the prognostic significance of textural features in lung adenocarcinoma. We evaluated 105 adenocarcinoma patients. We extracted texture-based PET parameters of primary tumors. Conventional PET parameters were also measured. The relationships between PET parameters and GLUT1 expression levels were evaluated. The association between PET parameters and overall survival (OS) was assessed using Cox's proportional hazard regression models. In terms of PET textural features, tumors expressing high levels of GLUT1 exhibited significantly lower coarseness, contrast, complexity, and strength, but significantly higher busyness. On univariate analysis, the metabolic tumor volume, total lesion glycolysis, contrast, busyness, complexity, and strength were significant predictors of OS. Multivariate analysis showed that lower complexity (HR=2.017, 95%CI=1.032-3.942, p=0.040) was independently associated with poorer survival. PET textural features may aid risk stratification in lung adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Modeling and simulation of maintenance treatment in first-line non-small cell lung cancer with external validation.

PubMed

Han, Kelong; Claret, Laurent; Sandler, Alan; Das, Asha; Jin, Jin; Bruno, Rene

2016-07-13

Maintenance treatment (MTx) in responders following first-line treatment has been investigated and practiced for many cancers. Modeling and simulation may support interpretation of interim data and development decisions. We aimed to develop a modeling framework to simulate overall survival (OS) for MTx in NSCLC using tumor growth inhibition (TGI) data. TGI metrics were estimated using longitudinal tumor size data from two Phase III first-line NSCLC studies evaluating bevacizumab and erlotinib as MTx in 1632 patients. Baseline prognostic factors and TGI metric estimates were assessed in multivariate parametric models to predict OS. The OS model was externally validated by simulating a third independent NSCLC study (n = 253) based on interim TGI data (up to progression-free survival database lock). The third study evaluated pemetrexed + bevacizumab vs. bevacizumab alone as MTx. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, baseline tumor size, ECOG score, Asian ethnicity, age, and gender were significant covariates in the final OS model. The OS model was qualified by simulating OS distributions and hazard ratios (HR) in the two studies used for model-building. Simulations of the third independent study based on interim TGI data showed that pemetrexed + bevacizumab MTx was unlikely to significantly prolong OS vs. bevacizumab alone given the current sample size (predicted HR: 0.81; 95 % prediction interval: 0.59-1.09). Predicted median OS was 17.3 months and 14.7 months in both arms, respectively. These simulations are consistent with the results of the final OS analysis published 2 years later (observed HR: 0.87; 95 % confidence interval: 0.63-1.21). Final observed median OS was 17.1 months and 13.2 months in both arms, respectively, consistent with our predictions. A robust TGI-OS model was developed for MTx in NSCLC. TTG captures treatment effect. The model successfully predicted the OS outcomes of an independent study based on interim TGI data and thus may facilitate trial simulation and interpretation of interim data. The model was built based on erlotinib data and externally validated using pemetrexed data, suggesting that TGI-OS models may be treatment-independent. The results supported the use of longitudinal tumor size and TTG as endpoints in early clinical oncology studies.

Assessment of the Spatial Distribution of Metal(Oid)s in Soils Around an Abandoned Pb-Smelter Plant

NASA Astrophysics Data System (ADS)

dos Santos, Nielson Machado; do Nascimento, Clístenes Williams Araújo; Matschullat, Jörg; de Olinda, Ricardo Alves

2017-03-01

Todos os Santos (All Saints) Bay area, NE-Brazil, is known for one of the most important cases of urban lead (Pb) contamination in the world. The main objective of this work was to assess and interpret the spatial distribution of As, Cd, Hg, Pb, and Zn in "background" soils of this environmentally impacted bay area, using a combination of geostatistical and multivariate analytical methods to distinguish between natural and anthropogenic sources of those metal(oid)s in soils. We collected 114 topsoil samples (0.0-0.2 m depth) from 38 sites. The median values for trace metal concentrations in soils (mg kg-1) followed the order Pb (33.9) > Zn (8.8) > As (1.2) > Cd (0.2) > Hg (0.07), clearly reflecting a Pb-contamination issue. Principal component analysis linked Cd, Pb, and Zn to the same factor (F1), chiefly corroborating their anthropogenic origin; yet, both Pb and Zn are also influenced by natural lithogenic sources. Arsenic and Hg concentrations (F2) are likely related to the natural component alone; their parent material (igneous-metamorphic rocks) seemingly confirm this hypothesis. The heterogeneity of sources and the complexity of the spatial distribution of metals in large areas such as the Todos os Santos Bay warrant, the importance of multivariate and geostatistical analyses in the interpretation of environmental data.

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

PubMed

Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

PubMed

Silva, Jack P; Gorman, Richard A; Berger, Nicholas G; Tsai, Susan; Christians, Kathleen K; Clarke, Callisia N; Mogal, Harveshp; Gamblin, T Clark

2017-12-01

Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients. © 2017 Wiley Periodicals, Inc.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

PubMed

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

2018-02-01

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m 2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m 2 ), 262 (64.5%); overweight (≥25 to <30 kg/m 2 ), 75 (18.5%); and obese (≥30.0 kg/m 2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m 2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m 2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age. Copyright © 2017 John Wiley & Sons, Ltd.

Expression Levels of DNA Damage Repair Proteins Are Associated With Overall Survival in Platinum-Treated Advanced Urothelial Carcinoma.

PubMed

Mullane, Stephanie A; Werner, Lillian; Guancial, Elizabeth A; Lis, Rosina T; Stack, Edward C; Loda, Massimo; Kantoff, Philip W; Choueiri, Toni K; Rosenberg, Jonathan; Bellmunt, Joaquim

2016-08-01

Combination platinum chemotherapy is standard first-line therapy for metastatic urothelial carcinoma (mUC). Defining the platinum response biomarkers for patients with mUC could establish personalize medicine and provide insights into mUC biology. Although DNA repair mechanisms have been hypothesized to mediate the platinum response, we sought to analyze whether increased expression of DNA damage genes would correlate with worse overall survival (OS) in patients with mUC. We retrospectively identified a clinically annotated cohort of patients with mUC, who had been treated with first-line platinum combination chemotherapy. A tissue microarray was constructed from formalin-fixed paraffin-embedded tissue from the primary tumor before treatment. Immunohistochemical analysis of the following DNA repair proteins was performed: ERCC1, RAD51, BRCA1/2, PAR, and PARP-1. Nuclear and cytoplasmic expression was analyzed using multispectral imaging. Nuclear staining was used for the survival analysis. Cox regression analysis was used to evaluate the associations between the percentage of positive nuclear staining and OS in multivariable analysis, controlling for known prognostic variables. In a cohort of 104 patients with mUC, a greater percentage of nuclear staining of ERCC1 (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .0007), RAD51 (HR, 5.6; 95% CI, 1.7-18.3; P = .005), and PAR (HR, 2.2; 95% CI, 1.1-4.4; P = .026) was associated with worse OS. BRCA1, BRCA2, and PARP-1 expression was not associated with OS (P = .76, P = .38, and P = .09, respectively). A greater percentage of combined ERCC1 and RAD51 nuclear staining was strongly associated with worse OS (P = .005). A high percentage of nuclear staining of ERCC1, RAD51, and PAR, assessed by immunohistochemistry, correlated with worse OS for patients with mUC treated with first-line platinum combination chemotherapy, supporting the evidence of the DNA repair pathways' role in the prognosis of mUC. We also report new evidence that RAD51 and PAR might play a role in the platinum response. Additional prospective studies are required to determine the prognostic or predictive nature of these biomarkers in mUC. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical characteristics and outcomes of Castleman disease: A multicenter study of 185 Chinese patients.

PubMed

Zhang, Xuanye; Rao, Huilan; Xu, Xiaolu; Li, Zhihua; Liao, Bing; Wu, Hongmei; Li, Mei; Tong, Xiuzhen; Li, Juan; Cai, Qingqing

2018-01-01

Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. One hundred and twenty-one patients (65.4%) were classified as unicentric CD (UCD) and 64 patients (34.6%) were classified as multicentric CD (MCD). The histology subtype was hyaline-vascular for 132 patients (71.4%), plasma cell for 50 patients (27%), and mixed type for 3 patients (1.6%). The 5-year overall survival (OS) of 185 CD cases was 80.3%. All UCD patients underwent surgical excision, whereas the treatment strategies of MCD patients were heterogeneous. The outcome for UCD patients was better than MCD patients, with 5-year OS rates of 93.6% and 51.2%, respectively. In further analysis of the MCD subgroup, a multivariate analysis using a Cox regression model revealed that age, splenomegaly and pretreatment serum albumin level were independent prognostic factors for OS. This multicenter study comprising the largest sample size to date suggested that MCD is a distinct entity from UCD with a significantly worse outcome. Older age (≥40 years), splenomegaly, and hypoalbuminemia were risk factors for poorer MCD prognosis. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Membrane localization of insulin receptor substrate-2 (IRS-2) is associated with decreased overall survival in breast cancer

PubMed Central

Clark, Jennifer L.; Dresser, Karen; Hsieh, Chung-Cheng; Sabel, Michael; Kleer, Celina G.; Khan, Ashraf

2011-01-01

Recent studies have identified a role for insulin receptor substrate-2 (IRS-2) in promoting motility and metastasis in breast cancer. However, no published studies to date have examined IRS-2 expression in human breast tumors. We examined IRS-2 expression by immunohistochemistry (IHC) in normal breast tissue, benign breast lesions, and malignant breast tumors from the institutional pathology archives and a tumor microarray from a separate institution. Three distinct IRS-2 staining patterns were noted: diffusely cytoplasmic, punctate cytoplasmic, and localized to the cell membrane. The individual and pooled datasets were analyzed for associations of IRS-2 staining pattern with core clinical parameters and clinical outcomes. Univariate analysis revealed a trend toward decreased overall survival (OS) with IRS-2 membrane staining, and this association became significant upon multivariate analysis (P = 0.01). In progesterone receptor negative (PR−) tumors, in particular, IRS-2 staining at the membrane correlated with significantly worse OS than other IRS-2 staining patterns (P < 0.001). When PR status and IRS-2 staining pattern were evaluated in combination, PR− tumors with IRS-2 at the membrane were associated with a significantly decreased OS when compared with all other combinations (P = 0.002). Evaluation of IRS-2 staining patterns could potentially be used to identify patients with PR− tumors who would most benefit from aggressive treatment. PMID:21258861

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

PubMed

Schernberg, Antoine; Huguet, Florence; Moureau-Zabotto, Laurence; Chargari, Cyrus; Rivin Del Campo, Eleonor; Schlienger, Michel; Escande, Alexandre; Touboul, Emmanuel; Deutsch, Eric

2017-07-01

To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Jeremy P.; Murphy, James D.; Hanlon, Alexandra L.

2014-03-15

Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC frommore » 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.« less

Combined use of susceptibility weighted magnetic resonance imaging sequences and dynamic susceptibility contrast perfusion weighted imaging to improve the accuracy of the differential diagnosis of recurrence and radionecrosis in high-grade glioma patients.

PubMed

Kim, Tae-Hyung; Yun, Tae Jin; Park, Chul-Kee; Kim, Tae Min; Kim, Ji-Hoon; Sohn, Chul-Ho; Won, Jae Kyung; Park, Sung-Hye; Kim, Il Han; Choi, Seung Hong

2017-03-21

Purpose was to assess predictive power for overall survival (OS) and diagnostic performance of combination of susceptibility-weighted MRI sequences (SWMRI) and dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) for differentiation of recurrence and radionecrosis in high-grade glioma (HGG). We enrolled 51 patients who underwent radiation therapy or gamma knife surgeryfollowed by resection for HGG and who developed new measurable enhancement more than six months after complete response. The lesions were confirmed as recurrence (n = 32) or radionecrosis (n = 19). The mean and each percentile value from cumulative histograms of normalized CBV (nCBV) and proportion of dark signal intensity on SWMRI (proSWMRI, %) within enhancement were compared. Multivariate regression was performed for the best differentiator. The cutoff value of best predictor from ROC analysis was evaluated. OS was determined with Kaplan-Meier method and log-rank test. Recurrence showed significantly lower proSWMRI and higher mean nCBV and 90th percentile nCBV (nCBV90) than radionecrosis. Regression analysis revealed both nCBV90 and proSWMRI were independent differentiators. Combination of nCBV90 and proSWMRI achieved 71.9% sensitivity (23/32), 100% specificity (19/19) and 82.3% accuracy (42/51) using best cut-off values (nCBV90 > 2.07 and proSWMRI≤15.76%) from ROC analysis. In subgroup analysis, radionecrosis with nCBV > 2.07 (n = 5) showed obvious hemorrhage (proSWMRI > 32.9%). Patients with nCBV90 > 2.07 and proSWMRI≤15.76% had significantly shorter OS. In conclusion, compared with DSC PWI alone, combination of SWMRI and DSC PWI have potential to be prognosticator for OS and lower false positive rate in differentiation of recurrence and radionecrosis in HGG who develop new measurable enhancement more than six months after complete response.

Studying a Rare Disease Using Multi-Institutional Research Collaborations vs Big Data: Where Lies the Truth?

PubMed

Johnson, Aileen C; Ethun, Cecilia G; Liu, Yuan; Lopez-Aguiar, Alexandra G; Tran, Thuy B; Poultsides, George; Grignol, Valerie; Howard, J Harrison; Bedi, Meena; Gamblin, T Clark; Tseng, Jennifer; Roggin, Kevin K; Chouliaras, Konstantinos; Votanopoulos, Konstantinos; Cullinan, Darren; Fields, Ryan C; Delman, Keith A; Wood, William C; Cardona, Kenneth; Maithel, Shishir K

2018-06-12

Multi-institutional collaborations provide granularity lacking in epidemiologic datasets to enable in-depth study of rare diseases. For pts with superficial, high-grade soft tissue sarcomas (STS) of the trunk/extremity, the value of radiation therapy (RT) is not clear. We aimed to utilize the 7-institution US-Sarcoma-Collaborative (USSC) and the National Cancer Database (NCDB) to investigate this issue. All adult pts with superficial truncal/extremity high-grade STS who underwent primary curative-intent resection from 2000-2016 at USSC institutions or were included in the NCDB from 2004-2013 were analyzed. Propensity-score matching was performed. Endpoints were locoregional recurrence-free survival(LRFS), overall-survival(OS), and disease-specific survival(DSS). Of 4,153pts in the USSC, 169pts with superficial high-grade tumors underwent primary curative-intent resection, of whom 38% received RT. On multivariable Cox-regression analysis, RT was not associated with improved LRFS(p=0.56), OS(p=0.31), or DSS(p=0.20). On analysis of 51 propensity-score matched-pairs, RT was still not associated with increased LRFS, OS, or DSS. Analysis of 631 propensity-score matched-pairs in the NCDB demonstrated improved 5-yr OS associated with RT (80%vs70%;p=0.02). LRFS and DSS were not evaluable. Granular data afforded by collaborative research enables in-depth analysis of patient outcomes. The NCDB, although powered with large numbers, cannot assess many relevant outcomes (recurrence, DSS, or complications). In this study, the approaches yielded conflicting results. USSC data suggested no value of radiation while the NCDB demonstrated improved overall survival, contradicting all randomized-controlled trials in sarcoma. The pros/cons of either approach must be considered when applying results to clinical practice, and underscore the importance of randomized-controlled trials. Copyright © 2018. Published by Elsevier Inc.

Racial and economic disparities in the treatment of penile squamous cell carcinoma: Results from the National Cancer Database.

PubMed

Sharma, Pranav; Ashouri, Kenan; Zargar-Shoshtari, Kamran; Luchey, Adam M; Spiess, Philippe E

2016-03-01

We evaluated sociodemographic and economic differences in overall survival (OS) of patients with penile SCC using the National Cancer Data Base (NCDB). We identified 5,412 patients with a diagnosis of penile squamous cell carcinoma from 1998 to 2011 with clinically nonmetastatic disease and available pathologic tumor and nodal staging. OS was estimated using the Kaplan-Meier method, and differences were determined using the log-rank test. Cox proportional hazard regression was performed to identify independent predictors of OS. Estimated median OS was 91.9 months (interquartile range: 25.8-not reached) at median follow-up of 44.7 months (interquartile range: 17.2-81.0). Survival did not change over the study period (P = 0.28). Black patients presented with a higher stage of disease (pT3/T4: 16.6 vs. 13.2%, P = 0.027) and had worse median OS (68.6 vs. 93.7 months, P<0.01). Patients with private insurance and median income≥$63,000 based on zip code presented with a lower stage of disease (pT3/T4: 11.6 vs. 14.7%, P = 0.002 and 12.0 vs. 14.0%, P = 0.042, respectively) and had better median OS (163.2 vs. 70.8 months, P<0.01 and 105.3 vs. 86.4 months, p = 0.001, respectively). On multivariate analysis, black race (hazard ratio [HR]: 1.39, 95% confidence interval [CI]: 1.21-1.58; P<0.01) was independently associated with worse OS, whereas private insurance (HR = 0.79, 95% CI: 0.63-0.98; P = 0.028) and higher median income≥$63,000 (HR = 0.82; 95% CI: 0.72-0.93; P = 0.001) were independently associated with better OS. Racial and economic differences in the survival of patients with penile cancer exist. An understanding of these differences may help minimize disparities in cancer care. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytoreductive Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma in the Targeted Therapy Era.

PubMed

Uprety, Dipesh; Bista, Amir; Smith, Angela L; Vallatharasu, Yazhini; Marinier, David E

2018-05-01

The role of cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) is not clearly understood after the approval of targeted therapies, particularly in the elderly population. The aim of this study was to compare survivals between patients who did and did not receive CN. The SEER-18 database was utilized in order to identify elderly patients with mRCC to compare overall survival (OS) and cancer-specific survival (CSS) between patients who did or did not receive CN between February 2006 and 2012. Kaplan-Meier curve and log rank test were used to compare OS and CSS between these two arms. Cox proportional hazard model was used for multivariate analysis and statistical significance was defined as p≤0.05. There was a significant survival benefit for those who received CN compared to those who did not receive CN (median OS: 18 months vs. 4 months, p<0.001; median CSS: 21 months vs. 5 months, p<0.001). CN offered significant survival benefit, even in elderly patients with metastatic renal cell cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors.

PubMed

Roy, Laurent-Olivier; Poirier, Marie-Belle; Fortin, David

2018-04-08

Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β). We hypothesized that TGF-β gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-β₁ and -β₂ expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-β₁ and -β₂ levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-β₁ significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β₁ is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β₂. We believe our study is the first to unveil a significant relationship between TGF-β₁ expression and OS or PFS in newly diagnosed GBM. TGF-β₁ could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

Age distribution and age-related outcomes of olfactory neuroblastoma: a population-based analysis.

PubMed

Yin, Zhenzhen; Wang, Youyou; Wu, Yuemei; Zhang, Ximei; Wang, Fengming; Wang, Peiguo; Tao, Zhen; Yuan, Zhiyong

2018-01-01

The objective of the study was to describe the age distribution and to evaluate the role of prognostic value of age on survival in patients diagnosed with olfactory neuroblastoma (ONB). A population-based retrospective analysis was conducted. The population-based study of patients in the Surveillance, Epidemiology, and End Results (SEER) tumor registry, who were diagnosed with ONB from 1973 to 2014, were retrospectively analyzed. The cohort included 876 patients with a median age of 54 years. There was a unimodal distribution of age and ONBs most frequently occurred in the fifth to sixth decades of life. Kaplan-Meier analysis demonstrated overall survival (OS) and cancer-specific survival (CSS) rates of 69% and 78% at 5 years. Multivariable Cox regression analysis showed that age, SEER stage, and surgery were independent prognostic factors for CSS. The risk of overall death and cancer-specific death increased 3.1% and 1.6% per year, respectively. Patients aged >60 years presented significantly poor OS and CSS compared with patients aged ≤60 years, even in patients with loco-regional disease or in those treated with surgery. This study highlights the growing evidence that there is a unimodal age distribution of ONB and that age is an important adverse prognostic factor.

Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study.

PubMed

de Morrée, Ellen S; Vogelzang, Nicholas J; Petrylak, Daniel P; Budnik, Nikolay; Wiechno, Pawel J; Sternberg, Cora N; Doner, Kevin; Bellmunt, Joaquim; Burke, John M; Ochoa de Olza, Maria; Choudhury, Ananya; Gschwend, Juergen E; Kopyltsov, Evgeny; Flechon, Aude; van As, Nicolas; Houede, Nadine; Barton, Debora; Fandi, Abderrahim; Jungnelius, Ulf; Li, Shaoyi; Li, Jack Shiansong; de Wit, Ronald

2017-01-01

The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles. To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial. The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors. Total number of docetaxel cycles delivered as an independent factor for OS. Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001). These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted.

Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients.

PubMed

Johnbeck, Camilla B; Knigge, Ulrich; Langer, Seppo W; Loft, Annika; Berthelsen, Anne Kiil; Federspiel, Birgitte; Binderup, Tina; Kjaer, Andreas

2016-12-01

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18 F-FLT PET as a prognostic marker for NENs in comparison with 18 F-FDG PET and Ki-67 index. One hundred patients were PET-scanned with both 18 F-FLT and 18 F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18 F-FLT uptake was also investigated. Thirty-seven percent of patients had a positive 18 F-FLT PET scan, and 49% had 18 F-FDG PET-positive foci. Patients with a high 18 F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18 F-FLT uptake. No correlation was found between Ki-67 index and 18 F-FLT uptake. In a multivariate analysis 18 F-FLT, 18 F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18 F-FDG and Ki-67 remained significant. 18 F-FLT PET has prognostic value in NEN patients but when 18 F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18 F-FLT PET only adds information regarding PFS but not OS, whereas 18 F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18 F-FLT in addition to 18 F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18 F-FLT PET in NENs remains to be established. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Impact of novel histopathological factors on the outcomes of liver surgery for colorectal cancer metastases.

PubMed

Serrablo, A; Paliogiannis, P; Pulighe, F; Moro, S Saudi-Moro; Borrego-Estella, V; Attene, F; Scognamillo, F; Hörndler, C

2016-09-01

We evaluated the impacts of a series of novel histopathological factors on clinical-surgical outcomes and survival of patients who underwent surgery for colorectal cancer liver metastasis, with and without neoadjuvant chemotherapy. A prospective database including 150 consecutive patients who underwent 183 hepatic resections for metastatic colorectal cancer was evaluated. Among them, 74 (49.3%) received neoadjuvant chemotherapy before surgery. The histopathological factors studied were: a) microsatellitosis, b) type and pattern of tumour growth, c) nuclear grade and the number of mitoses/mm(2), d) perilesional pseudocapsule, e) intratumoural fibrosis, f) lesion cellularity, g) hypoxic-angiogenic perilesional growth pattern, and h) the tumour normal interface. Three or more metastatic lesions, R1 resection margins, and <50% tumour necrosis were prognostic factors for a worse OS, but only the former was confirmed to be an independent prognostic factor in the multivariate analysis. Furthermore, tumour fibrosis <40% and cellularity >10% were predictive of a worse neoadjuvant therapy response, but these findings were not confirmed in the multivariate analysis. Finally, tumour necrosis <50%, cellularity >10%, and TNI >0.5 mm were prognostic factors for a worse DFS and AS in the univariate but not in the multivariate analysis. Several factors seem to influence the outcomes of surgery for colorectal cancer liver metastasis, especially the number of the lesions, the margins of resection, the percentage of necrosis and fibrosis, as well as the cellularity and the TNI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Concordance of Results from Randomized and Observational Analyses within the Same Study: A Re-Analysis of the Women's Health Initiative Limited-Access Dataset.

PubMed

Bolland, Mark J; Grey, Andrew; Gamble, Greg D; Reid, Ian R

2015-01-01

Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women's Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study. WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population. In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints. Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS.

Concordance of Results from Randomized and Observational Analyses within the Same Study: A Re-Analysis of the Women’s Health Initiative Limited-Access Dataset

PubMed Central

Bolland, Mark J.; Grey, Andrew; Gamble, Greg D.; Reid, Ian R.

2015-01-01

Background Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women’s Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study. Methods WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population. Results In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints. Conclusions Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS. PMID:26440516

Adjuvant radiation therapy and survival for adenoid cystic carcinoma of the breast.

PubMed

Sun, Jia-Yuan; Wu, San-Gang; Chen, Shan-Yu; Li, Feng-Yan; Lin, Huan-Xin; Chen, Yong-Xiong; He, Zhen-Yu

2017-02-01

The assess the clinical value of different types of surgical procedures and further analyze the effect of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast. Patients with ACC of the breast were identified using a population-based national registration database (Surveillance, Epidemiology, and End Results, SEER). The Kaplan-Meier method and Cox regression models were performed to determine the impact of the surgical procedures and adjuvant RT associated with cause-specific survival (CSS) and overall survival (OS). A total of 478 patients with ACC of the breast were identified. The median follow-up was 59 months. The 10-year CSS and OS were 87.5% and 75.3%, respectively. For the Kaplan-Meier analysis, the 5-year CSS were 96.1%, 91.8%, 90.2%, and 94.1% in patients that received lumpectomy + adjuvant RT, lumpectomy alone, mastectomy alone, and mastectomy + adjuvant RT, respectively (p = 0.026). In the multivariate Cox analyses, lumpectomy + adjuvant RT was an independent prognostic factor for CSS and OS. Patients that received lumpectomy + adjuvant RT had better survival rates than patients that underwent lumpectomy only (CSS, p = 0.018; OS, p = 0.031) and mastectomy only (CSS, p = 0.010; OS, p = 0.004). ACC of the breast has an excellent prognosis. Breast-conserving surgery is a reasonable alternative for patients with ACC of the breast, and adjuvant RT after lumpectomy improved survival rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Percent of Positive Biopsy Cores Improves Prediction of Prostate Cancer-Specific Death in Patients Treated With Dose-Escalated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian Yushen; Feng, Felix Y.; Veterans Administration Medical Center, Ann Arbor, MI

2011-11-01

Purpose: To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy. Methods and Materials: We performed a retrospective analysis of patients treated at University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification.more » Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy. Results: PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence interval (CI), 1.4-3.0]) and FFM (p = 0.05; HR, 1.7 [95% CI, 1.1-2.9]) and marginally increased the risk for CSS (p = 0.057; HR, 2.1 [95% CI, 1.0-4.6]). Conclusion: PPC at the time of biopsy adds prognostic value for clinically meaningful endpoints for patients treated with dose-escalated radiation therapy. This was particularly true for NCCN-defined intermediate- and high-risk patients.« less

Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival in Patients Diagnosed with Hepatocellular Carcinoma (HCC).

PubMed

Lamarca, Angela; Mendiola, Marta; Bernal, Elsa; Heredia, Victoria; Díaz, Esther; Miguel, María; Pastrian, Laura G; Burgos, Emilio; Feliu, Jaime; Barriuso, Jorge

2015-01-01

Hepatocellular carcinoma (HCC) tends to develop in the liver when there is a high level of background inflammation (cirrhosis). Treatment options are limited and mainly based on systemic therapies such as anti-angiogenic drugs (e.g. sorafenib). Connective tissue growth factor (CTGF) is a matricellular protein involved in inflammation, tumour growth and angiogenesis. The aim of this study is to determine the expression of CTGF and hypoxia inducible factors (HIF) in HCC and to clarify its impact on relapse and survival. Eligibility criteria for the study consisted of patients with a diagnosis of HCC, formalin-fixed and paraffin-embedded (FFPE) biopsy tissue, as well as relapse and available survival data. A tissue microarray was constructed from ≥ 70% tumoural sections. The expressions of CTGF, HIF1α and HIF2α were analysed by immunohistochemistry. The relationship between expression of CTGF/HIF1α and CTGF/HIF2α were analysed. Univariate and multivariate analyses were performed. Fifty-three patients were screened; 39 patients were eligible for this study. Patients were treated with radical intent. At the end of follow up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and 7.7% distant metastases). Estimated median disease-free survival (DFS) and overall survival (OS) were 23.4 (95%CI 7.18-39.66) and 38.6 months (95%CI 30.7-46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and diffuse 23.1%. A non-statistically significant relationship between expression of CTGF and HIF was shown supporting an alternative pathway for CTGF expression in HCC. In multivariate analysis CTGF expression was an independent factor related to OS, with shorter survival in those patients with focal/diffuse CTGF expression (HR 2.46; 95%CI 1.18-5.15). Our results support that expression of CTGF is an independent factor associated with shorter OS in HCC. Further analysis of CTGF expression in a larger series of HCC patients is required to confirm CTGF as a prognostic biomarker in HCC.

Association of High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) bone microarchitectural parameters with previous clinical fracture in older men: The Osteoporotic Fractures in Men (MrOS) study.

PubMed

Fink, Howard A; Langsetmo, Lisa; Vo, Tien N; Orwoll, Eric S; Schousboe, John T; Ensrud, Kristine E

2018-05-08

High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture. However, studies of the association of HR-pQCT parameters with fracture history have been small, predominantly limited to postmenopausal women, often performed limited adjustment for potential confounders including for BMD, and infrequently assessed strength or failure measures. We used data from the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of distal radius, proximal (diaphyseal) tibia and distal tibia HR-pQCT parameters measured at the Year 14 (Y14) study visit with prior clinical fracture. The primary HR-pQCT exposure variables were finite element analysis estimated failure loads (EFL) for each skeletal site; secondary exposure variables were total vBMD, total bone area, trabecular vBMD, trabecular bone area, trabecular thickness, trabecular number, cortical vBMD, cortical bone area, cortical thickness, and cortical porosity. Clinical fractures were ascertained from questionnaires administered every 4 months between MrOS study baseline and the Y14 visit and centrally adjudicated by masked review of radiographic reports. We used multivariate-adjusted logistic regression to estimate the odds of prior clinical fracture per 1 SD decrement for each Y14 HR-pQCT parameter. Three hundred forty-four (19.2%) of the 1794 men with available HR-pQCT measures had a confirmed clinical fracture between baseline and Y14. After multivariable adjustment, including for total hip areal BMD, decreased HR-pQCT finite element analysis EFL for each site was associated with significantly greater odds of prior confirmed clinical fracture and major osteoporotic fracture. Among other HR-pQCT parameters, decreased cortical area appeared to have the strongest independent association with prior clinical fracture. Future studies should explore associations of HR-pQCT parameters with specific fracture types and risk of incident fractures and the impact of age and sex on these relationships. Published by Elsevier Inc.

Clinical significance of isolated biliary candidiasis in patients with unresectable cholangiocarcinoma.

PubMed

Kim, In-Ho; Choi, Jae-Ki; Lee, Dong-Gun; Lee, In Seok; Hong, Tae Ho; You, Young Kyoung; Chun, Ho Jong; Lee, Myung Ah

2016-10-01

The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was significantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without [median overall survival (OS): 32 vs 62 days, P=0.011]. Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candidiasis (median OS: 30 vs 49 days, P=0.046). Biliary candidiasis was identified as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated candidiasis (4/19, 21%) showed Candida species in consecutive blood culture until the end of the study, but others showed no candidemia. Isolated biliary candidiasis may be associated with poor prognosis in patients with unresectable cholangiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.

Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy.

PubMed

Li, Changyou; Xu, Jing; Wang, Qi; Geng, Shaoqing; Yan, Zheng; You, Jin; Li, Zhenfeng; Zou, Xiao

2018-05-01

The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.

The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

PubMed

Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

2017-02-01

The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; p<0.0001) were independent prognostic factors. In Kaplan-Meier analysis of recurrence-free survival (RFS), cancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study.

PubMed

Zhang, Jieyun; Gan, Lu; Wu, Zhenhua; Yan, Shican; Liu, Xiyu; Guo, Weijian

2017-04-04

Marital status was reported as a prognostic factor in many cancers. However, its role in gastric cancer (GC) hasn't been thoroughly explored. In this study, we aimed to investigate the effect of marital status on survival, stage, treatment, and survival in subgroups. We used the Surveillance, Epidemiology and End Results (SEER) database and identified 16910 GC patients. These patients were categorized into married (58.44%) and unmarred (41.56%) groups. Pearson chi-square, Wilcoxon-Mann-Whitney, Log-rank, multivariate Cox regression, univariate and multivariate binomial or multinomial logistic regression analysis were used in our analysis. Subgroup analyses of married versus unmarried patients were summarized in a forest plot. Married patients had better 5-year overall survival (OS) (32.09% VS 24.61%, P<0.001) and 5-year cancer-caused special survival (CSS) (37.74% VS 32.79%, P<0.001) than unmarried ones. Then we studied several underlying mechanisms. Firstly, married patients weren't in earlier stage at diagnosis (P=0.159). Secondly, married patients were more likely to receive surgery (P < 0.001) or radiotherapy (P < 0.001) compared with the unmarried. Thirdly, in subgroup analyses, married patients still had survival advantage in subgroups with stage II-IV and no radiotherapy. These results showed that marital status was an independently prognostic factor for both OS and CSS in GC patients. Undertreatment and lack of social support in unmarried patients were potential explanations. With the knowledge of heterogeneous effects of marriage in subgroups, we can target unmarried patients with better social support, especially who are diagnosed at late stage and undergo no treatment.

The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study

PubMed Central

Yan, Shican; Liu, Xiyu; Guo, Weijian

2017-01-01

Background & Aims Marital status was reported as a prognostic factor in many cancers. However, its role in gastric cancer (GC) hasn't been thoroughly explored. In this study, we aimed to investigate the effect of marital status on survival, stage, treatment, and survival in subgroups. Methods We used the Surveillance, Epidemiology and End Results (SEER) database and identified 16910 GC patients. These patients were categorized into married (58.44%) and unmarred (41.56%) groups. Pearson chi-square, Wilcoxon-Mann-Whitney, Log-rank, multivariate Cox regression, univariate and multivariate binomial or multinomial logistic regression analysis were used in our analysis. Subgroup analyses of married versus unmarried patients were summarized in a forest plot. Results Married patients had better 5-year overall survival (OS) (32.09% VS 24.61%, P<0.001) and 5-year cancer-caused special survival (CSS) (37.74% VS 32.79%, P<0.001) than unmarried ones. Then we studied several underlying mechanisms. Firstly, married patients weren't in earlier stage at diagnosis (P=0.159). Secondly, married patients were more likely to receive surgery (P < 0.001) or radiotherapy (P < 0.001) compared with the unmarried. Thirdly, in subgroup analyses, married patients still had survival advantage in subgroups with stage II-IV and no radiotherapy. Conclusions These results showed that marital status was an independently prognostic factor for both OS and CSS in GC patients. Undertreatment and lack of social support in unmarried patients were potential explanations. With the knowledge of heterogeneous effects of marriage in subgroups, we can target unmarried patients with better social support, especially who are diagnosed at late stage and undergo no treatment. PMID:26894860

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

PubMed

Jimenez-Zepeda, V H; Reece, D E; Trudel, S; Chen, C; Tiedemann, R; Kukreti, V

2015-02-01

The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (<12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small cell lung cancer patients treated with definitive concurrent chemo-radiotherapy.

PubMed

Oh, Dongryul; Ahn, Yong Chan; Park, Hee Chul; Lim, Do Hoon; Noh, Jae Myoung; Cho, Won Kyung; Pyo, Hongryull

2017-05-30

This study aimed to investigate the prognostic impact of supraclavicular lymph node (SCN) metastasis in patients who were treated with definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer (NSCLC). The 2- and 5-year overall survival (OS) rates were 57.3% and 35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN metastasis, respectively. The median OS was 34 months in both groups. There was no significant difference in OS between the two groups (p = 0.679). The 2- and 5-year progression-free survival (PFS) rates were 24.1% and 12.6% in patients without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis, respectively. Patients without SCN metastasis had slightly longer median PFS (10 months vs. 8 months), but the difference was not statistically significant (p = 0.223). In multivariate analysis, SCN metastasis was not a significant factor for OS (p = 0.391) and PFS (p = 0.149). This retrospective analysis included 204 consecutive patients who were treated with chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients (58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease: mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one (1.2%). The patients were divided into two groups according to SCN metastasis. SCN metastasis does not compromise treatment outcomes compared to other mediastinal metastasis in the setting of definitive chemoradiotherapy.

LDH is an adverse prognostic factor independent of ISS in transplant-eligible myeloma patients receiving bortezomib-based induction regimens.

PubMed

Chim, Chor Sang; Sim, Joycelyn; Tam, Sidney; Tse, Eric; Lie, Albert Kwok Wai; Kwong, Yok Lam

2015-04-01

Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum β2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high β2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008). In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Glasgow Prognostic Score is superior to ECOG PS as a prognostic factor in patients with gastric cancer with peritoneal seeding.

PubMed

Yuan, Shu-Qiang; Nie, Run-Cong; Chen, Yong-Ming; Qiu, Hai-Bo; Li, Xiao-Ping; Chen, Xiao-Jiang; Xu, Li-Pu; Yang, Li-Fang; Sun, Xiao-Wei; Li, Yuan-Fang; Zhou, Zhi-Wei; Chen, Shi; Chen, Ying-Bo

2018-04-01

The Glasgow Prognostic Score (GPS) has been shown to be associated with survival rates in patients with advanced cancer. The present study aimed to compare the GPS with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in patients with gastric cancer with peritoneal seeding. For the investigation, a total of 384 gastric patients with peritoneal metastasis were retrospectively analyzed. Patients with elevated C-reactive protein (CRP; >10 mg/l) and hypoalbuminemia (<35 mg/l) were assigned a score of 2. Patients were assigned a score of 1 if presenting with only one of these abnormalities, and a score of 0 if neither of these abnormalities were present. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal seeding were analyzed. The results showed that the median overall survival (OS) of patients in the GPS 0 group was longer, compared with that in the GPS 1 and GPS 2 groups (15.50, vs. 10.07 and 7.97 months, respectively; P<0.001). No significant difference was found between the median OS of patients with a good performance status (ECOG <2) and those with a poor (ECOG ≥2) performance status (13.67, vs. 11.80 months; P=0.076). In the subgroup analysis, the median OS in the GPS 0 group was significantly longer, compared with that in the GPS 1 and GPS 2 groups, for the patients receiving palliative chemotherapy and patients without palliative chemotherapy. Multivariate survival analysis demonstrated that CA19-9, palliative gastrectomy, first-line chemotherapy and GPS were the prognostic factors predicting OS. In conclusion, the GPS was superior to the subjective assessment of ECOG PS as a prognostic factor in predicting the outcome of gastric cancer with peritoneal seeding.

The use of spine stereotactic radiosurgery for oligometastatic disease.

PubMed

Ho, Jennifer C; Tang, Chad; Deegan, Brian J; Allen, Pamela K; Jonasch, Eric; Amini, Behrang; Wang, Xin A; Li, Jing; Tatsui, Claudio E; Rhines, Laurence D; Brown, Paul D; Ghia, Amol J

2016-08-01

OBJECTIVE The authors investigated the outcomes following spine stereotactic radiosurgery (SSRS) for patients with oligometastatic disease of the spine. METHODS The study was a secondary analysis of 38 of 209 patients enrolled in 2 separate institutional Phase I/II prospective protocols and treated with SSRS between 2002 and 2011. Of these 38 patients, 33 (87%) were treated for a solitary spine metastasis, with no other history of metastatic disease. SSRS was prescribed to 24 Gy in 1 fraction (8%), 18 Gy in 1 fraction (18%), 16 Gy in 1 fraction (11%), 27 Gy in 3 fractions (53%), 30 Gy in 5 fractions (8%), or 20 Gy in 5 fractions (3%). Seventeen patients (45%) received prior conventional external beam radiation therapy. RESULTS The median overall survival (OS) was 75.7 months, and the 2- and 5-year OS rates were 84% and 60%, respectively. In multivariate analysis, patients who had prior spine surgery and a better Karnofsky Performance Scale score had an improved OS (HR 0.16, 95% CI 0.05-0.52, p < 0.01, and HR 0.33, 95% CI 0.13%-0.84%, p = 0.02, respectively), and those who had undergone prior radiation therapy had a worse OS (HR 3.6, 95% CI 1.2%-10%, p = 0.02). The 1-, 2-, and 5-year local progression-free survival rates were 85%, 82%, and 78%, respectively. The median time to systemic therapy modification was 41 months. Two patients (5%) experienced late Grade 3-4 toxicity. CONCLUSIONS Patients with oligometastatic disease of the spine treated with SSRS can experience long-term survival and a long time before needing a modification in systemic therapy. In addition, SSRS leads to excellent local control and minimal late toxicity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muijs, Christina, E-mail: c.t.muijs@umcg.nl; Smit, Justin; Karrenbeld, Arend

Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis wasmore » performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.« less

Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xing, Minzhi; Sakaria, Sonali; Dhanasekaran, Renumathy

Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B).more » Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.« less

Pediatric Hodgkin Lymphoma Treated at Cancer Institute, Chennai, India: Long-Term Outcome

PubMed Central

Dhanushkodi, Manikandan; Ganesan, Trivadi S.; Ganesan, Prasanth; Sundersingh, Shirley; Selvaluxmy, Ganesarajah; Swaminathan, Rajaraman; Rama, Ranganathan; Sagar, Tenali Gnana

2017-01-01

Purpose Pediatric Hodgkin lymphoma (HL) is a highly curable malignancy. Outcomes for pediatric HL may vary between developed and developing countries for multiple reasons. This study was conducted to ascertain the outcomes of children with HL at our center and to identify risk factors for recurrent disease. Methods We analyzed the outcomes of 172 consecutive, previously untreated patients with pediatric HL presenting at our center from 2001 to 2010. Patients were treated with either adriamycin, bleomycin, vinblastine, and dacarbazine or adriamycin, bleomycin, vinblastine, cyclophosphamide, vincristine, prednisone, and procarbazine chemotherapy initially, and radiation to bulky sites or a single site of residual disease when appropriate. Results The median duration of follow-up was 77 months. The median age of the patients was 10 years; 127 (74%) of the 172 patients were male. The extent of disease was stage I and II in 59% of the patients. B symptoms were present in 32% of the patients, and 27% had bulky disease. The most common histologic subtype was mixed cellularity (45%). The 5-year overall survival (OS) and progression-free survival (PFS) of the entire cohort were 92.9% and 83.1%, respectively. The 5-year OS rates for patients with stage I, II, III, and IV were 96%, 94.7%, 84%, and 69.8%, respectively. On univariate analysis, advanced stage, response on interim radiologic assessment, and presence of B symptoms significantly predicted inferior PFS and OS. On multivariate analysis, only interim radiologic response significantly predicted PFS (P < .001) and OS (P < .001). Conclusion Overall, the outcomes of patients treated at our center are comparable to those observed in other centers in India and globally. PMID:29094094

Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection.

PubMed

Kuroda, Daisuke; Sawayama, Hiroshi; Kurashige, Junji; Iwatsuki, Masaaki; Eto, Tsugio; Tokunaga, Ryuma; Kitano, Yuki; Yamamura, Kensuke; Ouchi, Mayuko; Nakamura, Kenichi; Baba, Yoshifumi; Sakamoto, Yasuo; Yamashita, Yoichi; Yoshida, Naoya; Chikamoto, Akira; Baba, Hideo

2018-03-01

Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection. Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. CONUT-high patients were significantly older (p < 0.001) and had a lower body mass index (p = 0.019), deeper invasion (p < 0.001), higher serum carcinoembryonic antigen (p = 0.037), and higher serum carbohydrate antigen 19-9 (p = 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12-8.30, p < 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested. CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.

Pretreatment of liver grafts in vivo by γ-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat

PubMed Central

Hori, Tomohide; Gardner, Lindsay B.; Hata, Toshiyuki; Chen, Feng; Baine, Ann-Marie T.; Uemoto, Shinji; Nguyen, Justin H.

2014-01-01

Summary Background: Gamma-aminobutyric acid (GABA) is found throughout the body. The regulation of GABA receptor (GABAR) reduces oxidative stress (OS). Ischemia/reperfusion injury after orthotopic liver transplantation (OLT) causes OS-induced graft damage. The effects of GABAR regulation in donors in vivo were investigated. Material/Methods: Donor rats received saline, a GABAR agonist or GABAR antagonist 4 h before surgery. Recipient rats were divided into four groups according to the donor treatments: laparotomy, OLT with saline, OLT with GABAR agonist and OLT with GABAR antagonist. Histopathological, biochemical and immunohistological examinations were performed at 6, 12 and 24 h after OLT. Protein assays were performed at 6 h after OLT. The 4-hydroxynonenal (4-HNE), ataxia-telangiectasia mutated kinase (ATM), phosphorylated histone H2AX (γH2AX), phosphatidylinositol-3 kinase (PI3K), Akt and superoxide dismutase (SOD) were assessed by western blot analysis. Results: In the univariate analysis, histopathological and biochemical profiles verified that the GABAR agonist reduced graft damage. Immunohistology revealed that the GABAR agonist prevented the induction of apoptosis. Measurement of 4-4-HNE levels confirmed OS-induced damage after OLT, and the GABAR agonist improved this damage. In the γH2AX, PI3K, Akt and antioxidant enzymes (SODs), ATM and H2AX were greatly increased after OLT, and were reduced by the GABAR agonist. In the multivariate analyses between multiple groups, histopathological assessment, aspartate aminotransferase level, immunohistological examinations for apoptotic induction and γH2AX showed statistical differences. Conclusions: A specific agonist demonstrated regulation of GABAR in vivo in the liver. This activation in vivo reduced OS after OLT via the ATM/H2AX pathway. PMID:23792534

Pretreatment Serum Lactate Dehydrogenase and N Classification Predict Long-Term Survival and Distant Metastasis in Patients With Nasopharyngeal Carcinoma Who Have A Positive Family History of Cancer

PubMed Central

Zhang, Wenna; Chen, Yupei; Zhou, Guanqun; Liu, Xu; Chen, Lei; Tang, Linglong; Mao, Yanping; Sun, Ying; Ma, Jun

2015-01-01

Abstract The purpose of the present study was to evaluate prognostic factors in patients with nasopharyngeal carcinoma (NPC) from the endemic area of southern China who have a positive family history (FH) of cancer. Retrospective analysis of 600 patients with nondisseminated NPC and a positive FH was conducted. The prognostic value of different factors for overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local relapse-free survival (LRFS) were assessed using Cox regression models. The 3-year OS, DMFS, DFS, and LRFS rates were 93.8%, 91.3%, 86.3%, and 93.8%, respectively. The FH tumor type was NPC for 226/600 (37.7%) patients and other cancers for 374/600 (62.3%) patients. The 3-year OS and DMFS rates for patients with an FH of NPC were 91.2% and 89.8%, respectively. Thirty of 600 (5.0%) patients had elevated pretreatment serum lactate dehydrogenase (LDH >245.0 IU/L). In multivariate analysis, N classification (HR 4.56, 95% CI 2.13–9.74, P < 0.0001) and elevated pretreatment serum LDH (HR 2.87, 95% CI 1.08–7.62, P = 0.034) were independent prognosticators for OS. Female patients (HR 0.42, 95% CI 0.19–0.95, P = 0.037) and patients with normal pretreatment serum LDH (HR 2.42, 95% CI 1.02–5.78, P = 0.046) had better DMFS. Elevated pretreatment serum LDH and N classification are independent prognostic factors for poorer survival in patients with NPC who have a positive FH of cancer. PMID:26376394

Patterns of care and treatment outcomes of patients with Craniopharyngioma in the national cancer database.

PubMed

Rao, Yuan J; Hassanzadeh, Comron; Fischer-Valuck, Benjamin; Chicoine, Michael R; Kim, Albert H; Perkins, Stephanie M; Huang, Jiayi

2017-03-01

To investigate the patterns of care and outcomes in patients with craniopharyngioma in the National Cancer Data Base (NCDB). This study included 697 patients (166 pediatric and 531 adult cases) treated for craniopharyngioma between 2004 and 2012 in the NCDB. Adjuvant radiotherapy (RT) was defined if within 6 months of surgery. Limited surgery (LS) was defined as biopsy or subtotal resection. Proportional-hazards models were used to evaluate associations between covariates and overall survival (OS). A time-dependent analysis of RT was performed to account for early deaths after surgery. Median follow-up was 46 months. Overall, 21% of patients received adjuvant RT. Of patients with known surgical extent (n = 195), 71% had LS. Utilization of adjuvant RT increased from 18% in 2004-2007 to 24% in 2008-2012. Patterns of care regarding adjuvant RT or LS were not significantly different between adult and pediatric patients. Tumor size, low comorbidity, and LS were associated with increased utilization of adjuvant RT. The 5-year OS among patients treated with LS, LS+RT, and gross total resection were 75, 85, and 82% (p = 0.02). On multivariate analysis of the 195 patients with known surgical extent, LS+RT was associated with improved OS compared to LS (HR 0.22, 95% CI 0.05-0.99, p = 0.04), but was not significant when early deaths (<2 months from surgery) were removed to adjust for immortal-time bias. Medical practice regarding surgical approach and adjuvant RT are similar for pediatric and adult craniopharyngiomas. Immortal-time bias may confound assessment of OS for adjuvant RT. Prospective studies comparing adjuvant RT versus observation after LS are warranted.

Stereotactic Body Radiation Therapy in Recurrent Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Wen-Yen; Jen, Yee-Min, E-mail: yeeminjen@yahoo.com.tw; Lee, Meei-Shyuan

2012-10-01

Purpose: To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC). Methods and Materials: This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4-5 fractions over 4-5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses. Results: The median follow-up time was 14 months formore » all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size ({<=}4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable. Conclusion: SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.« less

Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial

PubMed Central

Tabouret, Emeline; Houillier, Caroline; Martin-Duverneuil, Nadine; Blonski, Marie; Soussain, Carole; Ghesquières, Herve; Houot, Roch; Larrieu, Delphine; Soubeyran, Pierre; Gressin, Remy; Gyan, Emmanuel; Chinot, Olivier; Taillandier, Luc; Choquet, Sylvain; Alentorn, Agusti; Leclercq, Delphine; Omuro, Antonio; Tanguy, Marie-Laure

2017-01-01

Abstract Background. Our aim was to review MRI characteristics of patients with primary CNS lymphoma (PCNSL) enrolled in a randomized phase II trial and to evaluate their potential prognostic value and patterns of relapse, including T2 fluid attenuated inversion recovery (FLAIR) MRI abnormalities. Methods. Neuroimaging findings in 85 patients with PCNSL enrolled in a prospective trial were reviewed blinded to outcomes. MRI characteristics and responses according to International PCNSL Collaborative Group (IPCG) criteria were correlated with progression-free survival (PFS) and overall survival (OS). Results. Multivariate analysis showed that objective response at 2 months (P < .001) and at end of treatment (P = .015) were predictors of prolonged OS. Infratentorial location (P = .008) and large (>11.4 cm3) enhancing tumor volume (P = .006) were associated with poor OS and PFS, respectively. Ratio of change in product of largest diameters at early MRI evaluation but not timing of complete response achievement (early vs delayed) was prognostic for OS. Sixty-nine patients relapsed. Relapse in the brain (n = 52) involved an initial enhancing site, a different site, or both in 46%, 40%, and 14% of patients, respectively. At baseline, non-enhancing T2-FLAIR hypersignal lesions distant from the enhancing tumor site were detected in 18 patients. These lesions markedly decreased (>50%) in 16 patients after chemotherapy, supporting their neoplastic nature. Of these patients, 10/18 relapsed, half (n = 5) in the initially non-enhancing T2-FLAIR lesions. Conclusions. Baseline tumor size and infratentorial localization are of prognostic value in PCNSL. Our findings provide evidence that non-enhancing FLAIR abnormalities may add to overall tumor burden, suggesting that response criteria should be refined to incorporate evaluation of T2-weighted/FLAIR sequences. PMID:27994065

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, Andrew J.; Greenfield, Brad; Mahajan, Anita

2014-10-01

Purpose: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity. Methods and Materials: We reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity. Results: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742;more » nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction. Conclusions: Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function.« less

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

PubMed Central

MIYAZAKI, AKIRA; MIYAKE, HIDEAKI; HARADA, KEN-ICHI; INOUE, TAKA-AKI; FUJISAWA, MASATO

2015-01-01

The aim of this study was to evaluate the oncological efficacy of tyrosine kinase inhibitors (TKIs) as first-line molecular-targeted therapy for Japanese patients with metastatic renal cell carcinoma (mRCC) in a routine clinical setting. This study included a total of 271 consecutive Japanese patients with TKI-naive mRCC, including 172 patients who received sorafenib and 99 who received sunitinib for ≥2 months as a first-line molecular-targeted agent. The prognostic outcomes of these patients were retrospectively assessed. During the observation period (median, 19 months), 126 patients (46.5%) succumbed to the disease and the median overall survival (OS) for the entire cohort was 33.1 months. The univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, histological subtype and sarcomatoid characteristics as significant predictors of OS. Of these factors, only the MSKCC classification, CRP level and liver metastasis were found to be independently associated with OS in the multivariate analysis. Furthermore, there were significant differences in OS according to the positivity for these 3 independent risk factors (i.e., negative for all factors vs. positive for a single factor vs. positive for 2 or 3 factors). These findings suggest that the introduction of TKIs as first-line molecular-targeted agents resulted in favorable cancer control outcomes in Japanese mRCC patients and that the prognosis of these patients may be stratified by 3 potential parameters, including the MSKCC classification, CRP level and liver metastasis. PMID:26137274

No significant impact of response to prior androgen receptor-axis-targeted agents on the efficacy of subsequent docetaxel in patients with metastatic castration-resistant prostate cancer.

PubMed

Miyake, Hideaki; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Sugiyama, Takayuki; Otsuka, Atsushi

2018-06-01

To investigate whether the response to an androgen receptor-axis-targeted (ARAT) agent is associated with the efficacy of subsequent docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients. This study included 114 consecutive mCRPC patients, comprising 54 and 60 patients who progressed with abiraterone acetate (AA) and enzalutamide (Enz), respectively, before the introduction of docetaxel. The impact of the response to either ARAT agent on the activity of docetaxel was assessed. Following ARAT therapy, a prostate-specific antigen (PSA) response was observed in 73 of the 114 patients, of whom 33 and 40 received AA and Enz, respectively. In the 114 patients, PSA response to docetaxel was achieved in 48 (42.1%) patients, and median PSA progression-free survival (PFS) and overall survival (OS) with docetaxel were 7.2 and 17.5 months, respectively. No significant difference was noted in PSA response rate, PSA PFS or OS with docetaxel between responders and non-responders to a prior ARAT agent in the overall 114 patients, 54 receiving AA and 60 receiving Enz. Despite the absence of a significant impact of the response to a prior ARAT agent on PSA PFS or OS by univariate analysis, independent prognostic predictors were identified by multivariate analysis, as performance status (PS) for PSA PFS, and PS and visceral metastasis for OS. Disease control by docetaxel may not be affected by the response to a prior ARAT agent. Therefore, a prior response to an ARAT agent should not influence the decision on the subsequent introduction of docetaxel for mCRPC patients.

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rimner, Andreas; Lovie, Shona; Hsu, Meier

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followedmore » by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.« less

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma

PubMed Central

He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-01-01

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P=0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P=0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS (P=0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL. PMID:29190934

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma.

PubMed

Luo, Huaichao; Quan, Xiaoying; Song, Xiao-Yu; Zhang, Li; Yin, Yilin; He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-11-03

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P =0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P =0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS ( P =0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL.

Multicenter Prospective Study of Angiogenesis Polymorphism Validation in HCC Patients Treated with Sorafenib. An INNOVATE Study Protocol.

PubMed

Casadei Gardini, Andrea; Faloppi, Luca; Aprile, Giuseppe; Brunetti, Oronzo; Caparello, Chiara; Corbelli, Jody; Chessa, Luchino; Bruno, Daniele; Ercolani, Giorgio; Leonetti, Alessandro; de Stefano, Giorgio; Farella, Nunzia; Foschi, Francesco Giuseppe; Lanzi, Arianna; Dadduzio, Vincenzo; Marisi, Giorgia; Masi, Gianluca; Negri, Francesca V; Pagan, Flavia; Santini, Daniele; Scarpi, Emanuela; Silletta, Marianna; Silvestris, Nicola; Tamburini, Emiliano; Tassinari, Davide; Vivaldi, Caterina; Gentilucci, Umberto Vespasiani; Zagonel, Vittorina; Calvetti, Lorenzo; Cascinu, Stefano; Frassineti, Giovanni Luca; Scartozzi, Mario

2017-12-01

Introduction Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set. Methods This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib. Conclusions Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.

Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma.

PubMed

Hao, S; Chen, S; Yang, X; Wan, C

2017-01-01

Introduction To evaluate the impact of intermittent portal clamping (IPC) on long-term postoperative outcomes in patients with hepatocellular carcinoma (HCC). Methods Clinical records of 355 patients underwent curative liver resection for HCC in January 2007 to December 2010 were retrospectively reviewed. According to how portal clamping was performed, patients were grouped as: IPC, n=113; other portal clamping (OPC), n=190; and no portal clamping (NPC), n=52. Results Median recurrence-free survival (RFS) was statistically significantly shorter in the IPC (39.4 months) than OPC (47.3 months, p=0.010) and NPC groups (51.4 months, p=0.008). Median overall survival (OS) was also significantly shorter with IPC (46.3 months), versus 52.9 months with OPC (p=0.022) and 56.2 months with NPC (p=0.015). Kaplan-Meier survival analysis revealed that 5-year cumulative RFS was much lower in the IPC (42.5%) than OPC (50.9%, p=0.014) and NPC groups (49.6%, p=0.013). Five-year cumulative OS was also much lower in the IPC (44.9%) than OPC (58.0%, p=0.020) and NPC groups (57.7%, p=0.025). On univariate analysis, tumour grade, size and number, TNM stage, blood transfusion, vascular invasion and IPC were significantly inversely correlated with RFS and OS. On multivariate analysis, tumour size and number, blood transfusion, vascular invasion and IPC remained significant. Conclusions Our study suggests that IPC is an independent risk factor for poor long-term postoperative outcomes in patients with HCC.

Clinical prognostic value of metastasis-associated lung adenocarcinoma transcript 1 in various human cancers: an updated meta-analysis.

PubMed

Li, Yang; Yang, Ze; Wan, Xiaoya; Zhou, Jianguo; Zhang, Yu; Ma, Hu; Bai, Yuju

2016-05-28

Many studies have investigated the prognostic value of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human cancers. However, these studies were often limited by small sample sizes. Therefore, we performed this updated meta-analysis to summarize the potential value of MALAT1 as a biomarker for early treatment and to predict survival in various human malignant neoplasms, through the inclusion of the latest literature and improved methodology. Twelve eligible articles were systematically obtained from PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure and the Cochrane Library, from inception up to June 30, 2015. Survival was assessed using pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs). By combining the results of 12 studies, we found elevated MALAT1 expression was associated with poor survival in most cancers, with a pooled HR of 1.90 (95% CI, 1.56-2.30) for overall survival (OS) and 3.06 (95% CI, 2.06-4.56) for recurrence-free survival/disease-free survival. Subgroup analyses according to ethnicity, tumor type, assay method, sample size, HR-calculation method and analysis type did not affect the predictive role of MALAT1 for OS in various cancer types. Further, by combining results from studies that used multivariate analyses, we found elevated MALAT1 was an independent prognostic factor for OS (HR = 1.98; 95% CI, 1.58-2.48). MALAT1 could serve as a potential prognostic biomarker in various cancers and may be a potential therapeutic target for the treatment and early detection of recurrence.

VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PubMed

Lastraioli, E; Boni, L; Romoli, M R; Crescioli, S; Taddei, A; Beghelli, S; Tomezzoli, A; Vindigni, C; Saragoni, L; Messerini, L; Bernini, M; Bencini, L; Giommoni, E; Freschi, G; Di Costanzo, F; Scarpa, A; Morgagni, P; Farsi, M; Roviello, F; De Manzoni, G; Bechi, P; Arcangeli, A

2014-10-01

The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nuclear magnetic resonance (NMR) study of the effect of cisplatin on the metabolic profile of MG-63 osteosarcoma cells.

PubMed

Duarte, Iola F; Lamego, Ines; Marques, Joana; Marques, M Paula M; Blaise, Benjamin J; Gil, Ana M

2010-11-05

In the present study, (1)H HRMAS NMR spectroscopy was used to assess the changes in the intracellular metabolic profile of MG-63 human osteosarcoma (OS) cells induced by the chemotherapy agent cisplatin (CDDP) at different times of exposure. Multivariate analysis was applied to the cells spectra, enabling consistent variation patterns to be detected and drug-specific metabolic effects to be identified. Statistical recoupling of variables (SRV) analysis and spectral integration enabled the most relevant spectral changes to be evaluated, revealing significant time-dependent alterations in lipids, choline-containing compounds, some amino acids, polyalcohols, and nitrogenated bases. The metabolic relevance of these compounds in the response of MG-63 cells to CDDP treatment is discussed.

The impact of comorbidity on overall survival in elderly nasopharyngeal carcinoma patients: a National Cancer Data Base analysis.

PubMed

Huang, Ying; Chen, Wei; Haque, Waqar; Verma, Vivek; Xing, Yan; Teh, Bin S; Brian Butler, Edward

2018-04-01

The number of elderly patients with cancer is increasing. Medical comorbidities are more common in this population. Little is known regarding the prognostic relevance of comorbidities in elderly patients with nasopharyngeal carcinoma (NPC). Using the National Cancer Data Base (NCDB), we queried patients age >65 years diagnosed with NPC and treated with definitive radiation between 2004 and 2012 to examine the association between comorbidity and survival outcomes. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). The influence of comorbidity on overall survival (OS) was evaluated. Cox proportional hazards model was used to study the impact of comorbidity on OS. A total of 1137 patients met the specified criteria. Median follow-up was 61.2 months. Five-year OS was 50.4%. Comorbidities were present in 22.4% of patients, with 17.6% of patients having a CCI score of 1% and 4.8% having a CCI score of ≥2. Patients with a CCI score of 0 had significantly higher 5-year OS than patients with a CCI score of 1 or ≥2 (53.1% vs. 42.2% vs. 32.9%, P < 0.001). In multivariate analysis, CCI was a statistically significant independent prognostic factor for the risk of death of all causes for patients with a CCI score of 1 (hazard ratio [HR]: 1.242; 95% confidence interval [CI]: 1.002-1.539) or CCI score of ≥2 (HR: 1.625; 95% CI: 1.157-2.283) when compared to patients with a CCI score of 0. Comorbidity as measured by CCI is a strong independent prognostic factor for OS in elderly patients with NPC and lends support to the inclusion of comorbidity assessment due to its prognostic value when treating elderly patients with NPC. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heumann, Thatcher R.; Esiashvili, Natia; Winship Cancer Institute

2015-05-01

Purpose: To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. Methods and Materials: We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log–rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Results: Median age at diagnosis and at time of radiation was 52 and 56 years, respectively.more » Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. Conclusions: These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.« less

The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective Analysis.

PubMed

Zhou, Bin; Xu, Ling; Ye, Jingming; Xin, Ling; Duan, Xuening; Liu, Yinhua

2017-08-01

The American Joint Committee on Cancer (AJCC) released its 8th edition of tumor staging which is to be implemented in early 2018. The present study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging System in HER2-enriched breast cancer, on a retrospective cohort. This study was a retrospective single-center study of HER2-enriched breast cancer cases diagnosed from January 2008 to December 2014. Clinicopathological features and follow up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore prognostic factors for disease outcome. We restaged patients based on the 8th edition of the AJCC cancer staging system and analyzed prognostic value of the Anatomic Stage Group and the Prognostic Stage Group. The study enrolled 170 HER2-enriched subtype breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5-year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%) changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged case. The Anatomic Stage Groups had a significant prognostic impact on DFS (χ 2 =16.752, p<0.001) and OS (χ 2 =25.038, p<0.001). The Prognostic Staging Groups had a significant prognostic impact on DFS (χ 2 =6.577, p=0.037) and OS (χ 2 =21.762, p<0.001). In the multivariate analysis, both stage groups were independent predictors of OS. Both Anatomic and Prognostic Stage Groups in the 8th edition of the AJCC breast cancer staging system had prognostic value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a breakthrough on the basis of anatomic staging system. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Evaluation of a prognostic scoring system based on the systemic inflammatory and nutritional status of patients with locally advanced non-small-cell lung cancer treated with chemoradiotherapy.

PubMed

Mitsuyoshi, Takamasa; Matsuo, Yukinori; Itou, Hitoshi; Shintani, Takashi; Iizuka, Yusuke; Kim, Young Hak; Mizowaki, Takashi

2018-01-01

Systemic inflammation and poor nutritional status have a negative effect on the outcomes of cancer. Here, we analyzed the effects of the pretreatment inflammatory and nutritional status on clinical outcomes of locally advanced non-small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. We retrospectively reviewed 89 patients with locally advanced NSCLC treated with chemoradiotherapy between July 2006 and June 2013. Serum C-reactive protein (CRP) was assessed as an inflammatory marker, and serum albumin, body mass index (BMI) and skeletal mass index were assessed as nutritional status markers. The relationships between these markers and overall survival (OS) were assessed. The median OS was 24.6 months [95% confidence interval (CI): 19.4-39.3 months]. During follow-up, 58 patients (65%) had disease recurrence and 52 patients (58%) died. In multivariate Cox hazard analysis, CRP levels and BMI approached but did not achieve a significant association with OS (P = 0.062 and 0.094, respectively). Recursive partitioning analysis identified three prognostic groups based on hazard similarity (CRP-BMI scores): 0 = CRP < 0.3 mg/dl, 1 = CRP ≥ 0.3 mg/dl and BMI ≥ 18.5 kg/m2, and 2 = CRP ≥ 0.3 mg/dl and BMI < 18.5 kg/m2. The CRP-BMI score was significantly associated with OS (P = 0.023). Patients with scores of 0, 1 and 2 had median OS of 39.3, 24.5 and 14.5 months, respectively, and the scores also predicted the probability of receiving salvage treatment after recurrence. The CRP-BMI score is thus a simple and useful prognostic marker of clinical outcome for patients with locally advanced NSCLC treated with chemoradiotherapy. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Genome-Wide Identification of the Alba Gene Family in Plants and Stress-Responsive Expression of the Rice Alba Genes

PubMed Central

Verma, Jitendra Kumar; Wardhan, Vijay; Singh, Deepali; Chakraborty, Subhra; Chakraborty, Niranjan

2018-01-01

Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa, Zea mays, Sorghum bicolor, Cicer arietinum, and Vitis vinifera, and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii, Physcomitrella patens, and Amborella trichopoda, revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A phylogenetic analysis of the genes and of their counterparts in other plant species indicated evolutionary conservation and diversification. In each group, the structural components of the genes and motifs showed significant conservation. The chromosomal location of the Alba genes of rice (OsAlba), showed an unequal distribution on 8 of its 12 chromosomes. The expression profiles of the OsAlba genes indicated a distinct tissue-specific expression in the seedling, vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR) analysis of the OsAlba genes confirmed their stress-inducible expression under multivariate environmental conditions and phytohormone treatments. The evaluation of the regulatory elements in 68 Alba genes from the 9 species studied led to the identification of conserved motifs and overlapping microRNA (miRNA) target sites, suggesting the conservation of their function in related proteins and a divergence in their biological roles across species. The 3D structure and the prediction of putative ligands and their binding sites for OsAlba proteins offered a key insight into the structure–function relationship. These results provide a comprehensive overview of the subtle genetic diversification of the OsAlba genes, which will help in elucidating their functional role in plants. PMID:29597290

The impact of thyroid hormones on patients with hepatocellular carcinoma.

PubMed

Pinter, Matthias; Haupt, Lukas; Hucke, Florian; Bota, Simona; Bucsics, Theresa; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

2017-01-01

Hypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients. Of 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated. Thyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9-15.7 months) vs. 7.3 months (5.4-9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5-13.6 months) vs. 3.3 months (2.2-4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3-3.3); p = 0.002) in multivariate analysis. TSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

PubMed

Palmerini, Emanuela; Agostinelli, Claudio; Picci, Piero; Pileri, Stefano; Marafioti, Teresa; Lollini, Pier-Luigi; Scotlandi, Katia; Longhi, Alessandra; Benassi, Maria Serena; Ferrari, Stefano

2017-12-19

We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome. Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases. Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.

Adenoid cystic carcinoma of the skull base: results with an aggressive multidisciplinary approach.

PubMed

Ramakrishna, Rohan; Raza, Shaan M; Kupferman, Michael; Hanna, Ehab; DeMonte, Franco

2016-01-01

OBJECT Adenoid cystic carcinoma (ACC) is a locally aggressive tumor of salivary gland origin. Little data exist to guide treatment when this tumor extends to involve the structures of the skull base. METHODS Fifty-one patients with a diagnosis of ACC affecting the skull base were identified from a prospective database at MD Anderson Cancer Center (from 1992 to 2010). RESULTS Median follow-up for study patients was 6.75 years. The 5- and 10-year overall survival (OS) rates were 78% and 50%, respectively. Sixty-six percent of patients had progression of their disease. The 5- and 10-year progression-free survival (PFS) rates were 46.7% and 21.0%, respectively. Gross-total resection was achieved in 75% of patients, with 49% having microscopically negative margins at the time of first operation. On univariate analysis, resections with microscopically negative margins were associated with a significant OS advantage (20.1 ± 3.3 years) compared with resections that left residual disease, even if microscopic (10.3 ± 1.6 years, p = 0.035). In patients who underwent reoperation, the effect persisted, with improved OS in those with negative margins (21.4 ± 0.0 vs 16.7 ± 4.0 years, p = 0.06). The use of adjuvant radiotherapy was associated with an OS advantage (16.2 ± 2.5 vs 5.5 ± 2.2 years, p = 0.03) at initial diagnosis and improved PFS (7.8 ± 1.0 vs 2.1 ± 0.62 years, p = 0.005), whereas repeat irradiation provided no benefit. The use of adjuvant chemotherapy at diagnosis or at recurrence was not associated with any significant advantage. Multivariate analysis revealed margin-negative resection at initial operation and at recurrence retained OS significance, even after controlling for age, radiation therapy, and T stage. CONCLUSIONS ACC of the skull base is best treated with a multidisciplinary approach aimed at maximal, safe resection. Adjuvant radiotherapy should be offered, whereas chemotherapy does not confer benefit.

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern

PubMed Central

2013-01-01

Background To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Methods Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1–3 months after CCRT. Results With a median follow-up of 34 months (range, 2–116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). Conclusions 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors. PMID:24139225

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern.

PubMed

Bao, Yong; Liu, ShiLiang; Zhou, QiChao; Cai, PeiQiang; Anfossi, Simone; Li, QiaoQiao; Hu, YongHong; Liu, MengZhong; Fu, JianHua; Rong, TieHua; Li, Qun; Liu, Hui

2013-10-18

To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1-3 months after CCRT. With a median follow-up of 34 months (range, 2-116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors.

Long-term outcomes in patients with early stage nodular lymphocyte-predominant Hodgkin's lymphoma treated with radiotherapy.

PubMed

Solanki, Abhishek A; LeMieux, Melissa Horoschak; Chiu, Brian C-H; Mahmood, Usama; Hasan, Yasmin; Koshy, Matthew

2013-01-01

Radiation therapy (RT) is commonly used as definitive treatment for early-stage nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). We evaluated the cause-specific survival (CSS), overall survival (OS), and second malignancy (SM) rates in patients with early-stage NLPHL treated with RT. Patients with stage I-II NLPHL between 1988 and 2009 who underwent RT were selected from the Surveillance, Epidemiology and End Results database. Univariate analysis (UVA) for CSS and Os was performed using the Kaplan-Meier method and included age, gender, involved site, year of diagnosis, presence of B-symptoms, and extranodal involvement (ENI). Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling and included the above clinical variables. SM were classified as RT-related or non-RT-related. Freedom from SM and freedom from RT-related SM were determined using the Kaplan-Meier method. The study cohort included 469 patients. Median age was 37 years. The most common involved sites were the head and neck (36%), axilla/arm (26%), and multiple lymph node regions (18%). Sixty-eight percent had stage I disease, 70% were male, 4% had ENI, and 7% had B-symptoms. Median follow-up was 6 years. Ten-year CSS and Os were 98% and 88%, respectively. On UVA, none of the covariates was associated with CSS. Increasing age (p<0.01) and female gender (p<0.01) were associated with worse Os. On MVA, older age (p<0.01), female gender (p=0.04), multiple regions of involvement (p=0.03), stage I disease (p=0.02), and presence of B-symptoms (p=0.02) were associated with worse Os. Ten-year freedom from SM and freedom from RT-related SM were 89% and 99%, respectively. This is the largest series to evaluate the outcomes of stage I-II NLPHL patients treated with RT and found that this patient population has an excellent long-term prognosis and a low rate of RT-related second malignancies.

A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival

PubMed Central

Graham, C.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.; Ramjeesingh, R.

2016-01-01

Background Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. Methods We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan–Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). Results We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). Conclusions Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses. PMID:28050148