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Sample records for local recurrence-free survival

  1. Exclusive intraoperative radiotherapy for invasive breast cancer in elderly patients (>70 years): proportion of eligible patients and local recurrence-free survival.

    PubMed

    Lambaudie, Eric; Houvenaeghel, Gilles; Ziouèche, Amira; Knight, Sophie; Dravet, François; Garbay, Jean Remy; Giard, Sylvie; Charitansky, Hélène; Cohen, Monique; Faure, Christelle; Hudry, Delphine; Azuar, Paul; Villet, Richard; Gimbergues, Pierre; de Lara, Christine Tunon; Tallet, Agnès; Bannier, Marie; Minsat, Mathieu; Resbeut, Michel

    2016-11-15

    To estimate the proportion of elderly patients (>70 years) with breast cancer eligible for an Exclusive IntraOperative RadioTherapy (E-IORT) and to evaluate their local recurrence-free survival rate. This retrospective study examining two cohorts focuses on patients over 70 years old: a multi-centric cohort of 1411 elderly patients and a mono-centric cohort of 592 elderly patients. All patients underwent conservative surgery followed by external radiotherapy for T0-T3 N0-N1 invasive breast cancer, between 1980 and 2008. Within each cohort two groups were identified according to the inclusion criteria of the RIOP trial (R group) and TARGIT E study (T group). Each group was divided into two sub-groups, patients eligible (E) or non-eligible (nE) for IORT. The population of patients that were eligible in the TARGIT E study but not in the RIOP trial were also studied in both cohorts. The proportion of patients eligible for IORT was calculated, according to the eligibility criteria of each study. A comparison of the 5-year local or locoregional recurrence-free survival rate between eligible vs non-eligible patients was made. In both cohorts, the proportion of patients eligible according to the RIOP trial's eligibility criteria was 35.4 and 19.3%, and according to the TARGIT E study criteria was 60.9 and 45.3%. The 5-year locoregional recurrence-free survival rate was not significantly different between RE and RnE groups, TE and TnE groups. In both cohorts RE and (TE-RE) groups were not significantly different. Our results encourage further necessary studies to define and to extend the eligibility criteria for per operative exclusive radiotherapy.

  2. DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer

    PubMed Central

    Lott, Steven T.; Chen, Nanyue; Chandler, Dawn S.; Yang, Qifeng; Wang, Luo; Rodriguez, Marivonne; Xie, Hongyan; Balasenthil, Seetharaman; Buchholz, Thomas A.; Sahin, Aysegul A.; Chaung, Katrina; Zhang, Baili; Olufemi, Shodimu-Emmanu; Chen, Jinyun; Adams, Henry; Band, Vimla; El-Naggar, Adel K.; Frazier, Marsha L.; Keyomarsi, Khandan; Hunt, Kelly K.; Sen, Subrata; Haffty, Bruce; Hewitt, Stephen M.; Krahe, Ralf; Killary, Ann McNeill

    2009-01-01

    Background Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium–associated RING Chromosome 1), a novel gene encoding a member of the TRIM (tripartite motif) subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer. Methods and Findings Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH) in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS), an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD) were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D) basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs) recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a

  3. Effects of postoperative epidural analgesia on recurrence-free and overall survival in patients with nonsmall cell lung cancer.

    PubMed

    Cata, Juan P; Gottumukkala, Vijaya; Thakar, Dilip; Keerty, Dinesh; Gebhardt, Rodolfo; Liu, Diane D

    2014-02-01

    To determine whether postoperative epidural analgesia is associated with better recurrence-free survival and overall survival after lung cancer surgery. Retrospective study. Academic hospital. Data of patients with stage 1, stage 2, and stage 3 nonsmall cell lung cancer, who underwent tumor resection surgery, were studied. Patient data were grouped into three different postoperative pain management interventions: intravenous patient-controlled analgesia, patient-controlled epidural analgesia, and their combination. Univariate and multicovariate Cox proportional hazards models were applied to assess the effects of covariates of interest on overall survival and recurrence-free survival. The type of postoperative analgesia used for patients who underwent surgery for nonsmall cell lung cancer did not affect recurrence-free survival or overall survival. However, certain variables, including age ≥ 65 years, male gender, body mass index ≥ 25 kg/m(2), ASA physical status 4, and the need for preoperative blood transfusions, pneumonectomy, and postoperative radiation, were associated with decreased recurrence-free survival and overall survival. The type of postoperative analgesia used after surgery for nonsmall cell lung cancer is not associated with better 2-year or 5-year recurrence-free survival or overall survival rates. © 2013 Elsevier Inc. All rights reserved.

  4. Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma.

    PubMed

    Olar, Adriana; Wani, Khalida M; Wilson, Charmaine D; Zadeh, Gelareh; DeMonte, Franco; Jones, David T W; Pfister, Stefan M; Sulman, Erik P; Aldape, Kenneth D

    2017-03-01

    Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNAs)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p = 0.0793). The methylation predictor, however, was significantly associated with tumor recurrence (p < 0.0001). CNAs were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence

  5. Recurrence-free survival in breast cancer is associated with MRI tumor enhancement dynamics quantified using computer algorithms.

    PubMed

    Mazurowski, Maciej A; Grimm, Lars J; Zhang, Jing; Marcom, P Kelly; Yoon, Sora C; Kim, Connie; Ghate, Sujata V; Johnson, Karen S

    2015-11-01

    The purpose of this study is to investigate the association between breast cancer recurrence-free survival and breast magnetic resonance imaging (MRI) tumor enhancement dynamics which are quantified semi-automatically using computer algorithms. In this retrospective IRB-approved study, we analyzed data from 275 breast cancer patients at a single institution. Recurrence-free survival data were obtained from the medical record. Routine clinical pre-operative breast MRIs were performed in all patients. The tumors were marked on the MRIs by fellowship-trained breast radiologists. A previously developed computer algorithm was applied to the marked tumors to quantify the enhancement dynamics relative to the automatically assessed background parenchymal enhancement. To establish whether the contrast enhancement feature quantified by the algorithm was associated with recurrence-free survival, we constructed a Cox proportional hazards regression model with the computer-extracted feature as a covariate. We controlled for tumor grade and size (major axis length), patient age, patient race/ethnicity, and menopausal status. The analysis showed that the semi-automatically obtained feature quantifying MRI tumor enhancement dynamics was independently predictive of recurrence-free survival (p=0.024). Semi-automatically quantified tumor enhancement dynamics on MRI are predictive of recurrence-free survival in breast cancer patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer

    PubMed Central

    Rock, Cheryl L.; Flatt, Shirley W.; Laughlin, Gail A.; Gold, Ellen B.; Thomson, Cynthia A.; Natarajan, Loki; Jones, Lovell A.; Caan, Bette J.; Stefanick, Marcia L.; Hajek, Richard A.; Al-Delaimy, Wael K.; Stanczyk, Frank Z.; Pierce, John P.

    2008-01-01

    Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01−1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03−1.53), and free estradiol (HR, 1.31; 95% CI, 1.03−1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer. PMID:18323413

  7. Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer.

    PubMed

    Rock, Cheryl L; Flatt, Shirley W; Laughlin, Gail A; Gold, Ellen B; Thomson, Cynthia A; Natarajan, Loki; Jones, Lovell A; Caan, Bette J; Stefanick, Marcia L; Hajek, Richard A; Al-Delaimy, Wael K; Stanczyk, Frank Z; Pierce, John P

    2008-03-01

    Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.

  8. MITOTIC INDEX IS AN INDEPENDENT PREDICTOR OF RECURRENCE-FREE SURVIVAL IN MENINGIOMA

    PubMed Central

    Olar, Adriana; Wani, Khalida M; Sulman, Erik P; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine D; DeMonte, Franco; Fuller, Gregory N; Aldape, Kenneth D

    2014-01-01

    While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within-grade heterogeneity with respect to recurrence-free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on H&E sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment we evaluated 363 meningiomas with phospho-histoneH3(Ser10), and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grades I (n=268), II (n=84), and III (n=11) tumors were 1, 4, and 12, Classification and regression tree analysis to categorize cutoffs identified 3 subgroups defined by mitotic indices of 0–2, 3–4, and ≥5, which on univariate analysis were associated with RFS (p<0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (p<0.01) after adjustment for Simpson grade, WHO grade, and MIB-1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification. PMID:25040885

  9. Mitotic Index is an Independent Predictor of Recurrence-Free Survival in Meningioma.

    PubMed

    Olar, Adriana; Wani, Khalida M; Sulman, Erik P; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine D; DeMonte, Franco; Fuller, Gregory N; Aldape, Kenneth D

    2015-05-01

    While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within-grade heterogeneity with respect to recurrence-free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho-histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut-offs identified three subgroups defined by mitotic indices of 0-2, 3-4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB-1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.

  10. Plasma carotenoids and recurrence-free survival in women with a history of breast cancer.

    PubMed

    Rock, Cheryl L; Flatt, Shirley W; Natarajan, Loki; Thomson, Cynthia A; Bardwell, Wayne A; Newman, Vicky A; Hollenbach, Kathy A; Jones, Lovell; Caan, Bette J; Pierce, John P

    2005-09-20

    Previous studies suggest that diet may affect recurrence or survival rates in women who have been diagnosed with breast cancer. The purpose of this study was to examine the relationship between plasma carotenoid concentration, as a biomarker of vegetable and fruit intake, and risk for a new breast cancer event in a cohort of women with a history of early-stage breast cancer. Participants were 1,551 women previously treated for breast cancer who were randomly assigned to the control arm of a diet intervention trial between March 1995 and November 2000. Outcome events were probed during semiannual interviews and verified by medical record review. During the period under study, 205 women had a recurrence or new primary breast cancer. Plasma carotenoid concentrations were measured in baseline blood samples. Hazard ratios (HR) and 95% CIs by quartiles of plasma carotenoids were computed, controlling for tumor stage, grade, and hormone receptor status; chemotherapy and tamoxifen therapy; clinical site; age at diagnosis; body mass index; and plasma cholesterol concentration. Women in the highest quartile of plasma total carotenoid concentration had significantly reduced risk for a new breast cancer event (HR, 0.57; 95% CI, 0.37 to 0.89), controlled for covariates influencing breast cancer prognosis. Plasma carotenoids are a biologic marker of intake of vegetables and fruit, so this observation supports findings from previous studies that have linked increased vegetable and fruit intake with greater likelihood of recurrence-free survival in women who have been diagnosed with early-stage breast cancer.

  11. Pancreatic neuroendocrine tumour: Correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival.

    PubMed

    Kim, Mimi; Kang, Tae Wook; Kim, Young Kon; Kim, Seong Hyun; Kwon, Wooil; Ha, Sang Yun; Ji, Sang A

    2016-03-01

    To evaluate the correlation between grade of pancreatic neuroendocrine tumours (pNETs) based on the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC), and to assess whether the ADC value and WHO classification can predict recurrence-free survival (RFS) after surgery for pNETs. This retrospective study was approved by the Institutional Review Board. The requirement for informed consent was waived. Between March 2009 and November 2014, forty-nine patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for single pNETs were included. Correlations among qualitative MR imaging findings, quantitative ADC values, and WHO classifications were assessed. An ordered logistic regression test was used to control for tumour size as a confounding factor. The association between ADC value (or WHO classification) and RFS was analysed. All tumors (n=49) were classified as low- (n=29, grade 1), intermediate- (n=17, grade 2), and high-grade (n=3, grade 3), respectively. The mean ADC of pNETs was moderately negatively correlated with WHO classification before and after adjustment for tumour size (ρ=-0.64, p<0.001 and ρ=-0.55, p=0.001 respectively). RFS was significantly associated with WHO classification (p=0.007), but not with the ADC value (p=0.569). The ADC value of pNETs is moderately correlated with WHO tumour grade, regardless of tumour size. However, the WHO tumour classification of pNET may be more suitable for predicting RFS than the ADC value. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

    PubMed Central

    Kim, Yuhree; Margonis, Georgios A.; Prescott, Jason D.; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Evans, Douglas B.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed I.; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.; Pawlik, Timothy M.

    2016-01-01

    IMPORTANCE Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63–5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47–15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95–3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27–4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02–3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00–3.17; P = .05), positive

  13. The Effect of Hospital and Surgeon Volume on Racial Differences in Recurrence-Free Survival After Radical Prostatectomy

    PubMed Central

    Gooden, Kyna M.; Howard, Daniel L.; Carpenter, William R.; Carson, April P.; Taylor, Yhenneko J.; Peacock, Sharon; Godley, Paul A.

    2010-01-01

    Objective This study investigates associations between hospital and surgeon volume, and racial differences in recurrence after surgery for prostate cancer. Methods Data from the 1991 to 2002 Surveillance, Epidemiology, and End-Results-Medicare database were examined for 962 black and 7387 white men who received surgery for prostate cancer within 6 months of diagnosis during 1993–1999. Cox regression models were used to estimate the relationships between volume (grouped in tertiles), recurrence or death, and race, controlling for age, Gleason grade, and comorbidity score. Results Prostate cancer recurrence-free survival rates improved with hospital and surgical volume. Black men were more likely to experience recurrence than white men [hazard ratio (HR) = 1.34; 95% confidence interval (CI): 1.20 –1.50]. Stratification by hospital volume revealed that racial differences persisted for medium and high volume hospitals, even after covariate adjustments (medium HR = 1.30, 95% CI: 1.04 –1.61; high HR = 1.36, 95% CI: 1.07–1.73). Racial differences persisted within medium and high levels of surgeon volume as well (medium HR = 1.43, 95% CI: 1.10 –1.85; high HR = 1.57, 95% CI: 1.14 –2.16). Conclusions High hospital and physician volumes were not associated with reduced racial differences in recurrence-free survival after prostate cancer surgery, contrary to expectation. This study suggests that social and behavioral characteristics, and some aspects of access, may play a larger role than organizational or systemic characteristics with regard to recurrence-free survival for this population. PMID:18953228

  14. Effect of positive surgical margins on biochemical failure, biochemical recurrence-free survival, and overall survival after radical prostatectomy: median long-term results.

    PubMed

    Huri, Emre; Aydogmus, Yasin; Doluoglu, Omer Gokhan; Dadali, Mumtaz; Karakan, Tolga; Emir, Levent; Germiyanoglu, Cankon

    2014-10-01

    The aim of this study was to investigate the median long-term effects of positive surgical margin (PSM) and other prognostic factors on biochemical recurrence-free survival, overall survival, and biochemical failure in patients who underwent radical prostatectomy. Our study included 121 patients with pT2-3N0 disease treated between March 2006 and August 2012. The patients were divided into two groups: those with PSM and those with negative surgical margin (NSM). We analyzed the age, clinical and pathological stages, preoperative and postoperative Gleason scores, duration of the follow-up, adjuvant chemo-/radiotherapy, biochemical failure, biochemical recurrence-free survival, and overall survival in these patients. PSM was found in 25 (20%) patients, whereas 96 patients had NSM. The median follow-up time was 46.6 months (range 12-72 months) for the PSM group and 48.3 months (range 7-149 months) for the NSM group. The biochemical failure rate was 24% in the PSM group and 8.3% in the NSM group (p = 0.029). The biochemical recurrence-free survival was found as 76% in the PSM group and 91.7% in the NSM group. The difference between the groups was not statistically significant (p = 0.06). The overall survival was 100% in both groups. The surgical margins of the radical prostatectomy material is an important pathological indicator for biochemical failure at mid long-term follow-up. We did not find any effect of PSM on overall survival or biochemical recurrence-free survival.

  15. BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

    PubMed Central

    Lee, Y-K; Choi, E; Kim, M A; Park, P-G; Park, N-H; Lee, H

    2009-01-01

    Background: Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A. Methods: We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment. Results: The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (P<0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed. Conclusion: BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. PMID:19603021

  16. Computer-assisted measurement of primary tumor area is prognostic of recurrence-free survival in stage IB melanoma patients.

    PubMed

    Rosenbaum, Brooke E; Schafer, Christine N; Han, Sung Won; Osman, Iman; Zhong, Hua; Brinster, Nooshin

    2017-10-01

    Current staging guidelines are insufficient to predict which patients with thin primary melanoma are at high risk of recurrence. Computer-assisted image analysis may allow for more practical and objective histopathological analysis of primary tumors than traditional light microscopy. We studied a prospective cohort of stage IB melanoma patients treated at NYU Langone Medical Center from 2002 to 2014. Primary tumor width, manual area, digital area, and conformation were evaluated in a patient subset via computer-assisted image analysis. The associations between histologic variables and survival were evaluated using Cox proportional hazards model. Logistic regressions were used to build a classifier with clinicopathological characteristics to predict recurrence status. Of the 655 patients with stage IB melanoma studied, a subset of 149 patient tumors (63 recurred, 86 did not recur) underwent computer-assisted histopathological analysis. Increasing tumor width (hazard ratios (HR): 1.17, P=0.01) and digital area (HR: 1.08, P<0.01) were significantly associated with worse recurrence-free survival, whereas non-contiguous conformation (HR: 0.57, P=0.05) was significantly associated with better recurrence-free survival. The novel histopathological classifier composed of digital area, conformation, and baseline variables effectively distinguished recurrent cases from non-recurrent cases (AUC: 0.733, 95% confidence interval (CI): 0.647-0.818), compared to the baseline classifier alone (AUC: 0.635, 95% CI: 0.545-0.724). Primary tumor cross-sectional area, width, and conformation measured via computer-assisted analysis may help identify high-risk patients with stage IB melanoma.

  17. Combined overexpression of HIVEP3 and SOX9 predicts unfavorable biochemical recurrence-free survival in patients with prostate cancer

    PubMed Central

    Qin, Guo-qiang; He, Hui-chan; Han, Zhao-dong; Liang, Yu-xiang; Yang, Sheng-bang; Huang, Ya-qiang; Zhou, Liang; Fu, Hao; Li, Jie-xian; Jiang, Fu-neng; Zhong, Wei-de

    2014-01-01

    Background To clarify the involvement of HIVEP3 and SOX9 coexpression in prostate cancer (PCa). Methods A small interfering RNA was used to knockdown SOX9 expression in a PCa cell line and to analyze the effects of SOX9 inhibition on the expression of HIVEP3 in vitro. Then, HIVEP3 and SOX9 expression patterns in the human PCa tissues were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry. Results We found that the downregulation of SOX9 could inhibit the expression of HIVEP3 in the PCa cells in vitro. In addition, both HIVEP3 and SOX9 messenger RNA expression levels in the PCa tissues were significantly higher than those in the noncancerous prostate tissues (P=0.006 and P<0.001, respectively). Moreover, the immunohistochemical staining scores of HIVEP3 in the PCa tissues with PSA failure were significantly higher than those without (P=0.042); the increased SOX9 protein expression was more frequently found in the PCa tissues with a high Gleason score (P=0.045) and a high clinical stage (P=0.012). The tumors showing the HIVEP3-high/SOX9-high expression more frequently had PSA failure (P=0.024). When the patients with an HIVEP3 overexpression combined with the SOX9 overexpression, this group had a worse biochemical recurrence-free survival (P<0.001). Furthermore, the multivariate analysis showed that the HIVEP3/SOX9 coexpression was an independent predictor of an unfavorable biochemical recurrence-free survival. Conclusion Our data offer the convincing evidence for the first time that a combined analysis of HIVEP3 and SOX9 may help to predict the tumor progression and prognosis of PCa patients. In particular, the overexpression of HIVEP3 in PCa might partly explain the poor prognosis of patients with an upregulation of SOX9. PMID:24493929

  18. Reduced Connexin 43 expression is associated with tumor malignant behaviors and biochemical recurrence-free survival of prostate cancer

    PubMed Central

    Xu, Ning; Chen, Hui-Jun; Chen, Shao-Hao; Xue, Xue-Yi; Chen, Hong; Zheng, Qing-Shui; Wei, Yong; Li, Xiao-Dong; Huang, Jin-Bei; Cai, Hai; Sun, Xiong-Lin

    2016-01-01

    Connexin 43, a gap junction protein, coordinates cell-to-cell communication and adhesion. Altered Connexin 43 expression associated with cancer development and progression. In this study, we assessed Connexin 43 expression for association with clinicopathological features and biochemical recurrence of prostate cancer after radical prostatectomy. Pathological specimens were collected from 243 patients who underwent radical prostatectomy and from 60 benign prostatic hyperplasia (BPH) patients to construct tissue microarrays and immunohistochemical analysis of Connexin 43 expression. Kaplan-Meier curves and multivariable Cox proportion hazard model were performed to associate Connexin 43 expression with postoperative biochemical recurrence-free survival (BFS). Connexin 43 expression was significantly reduced or lost in tumor tissues compared to that of BPHs (39.1% vs. 96.7%, P<0.001). Reduced Connexin 43 expression was associated with high levels of preoperative PSA, high Gleason score, advanced pT stage, positive surgical margin, extracapsular extension, and seminal vesicle invasion (P < 0.05, for all). Kaplan–Meier curves showed that reduced Connexin 43 expression was associated with shortened postoperative BFS (P < 0.001). Multivariate analysis showed that reduced Connexin 43 expression, high Gleason score and advanced pT stage were independent predictors for BFS of patients (P < 0.05). Connexin 43 expression was significantly reduced or lost in prostate cancer tissues, which was associated with advanced clinicopathological features and poor BFS of patients after radical prostatectomy. PMID:27623212

  19. Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival.

    PubMed

    Kuba, Sayaka; Ohtani, Hiroshi; Yamaguchi, Junzo; Hayashi, Hiroko; Uga, Tatsuya; Kanematsu, Takashi; Shimokawa, Isao

    2011-02-01

    Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.

  20. Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

    PubMed

    Wang, Baohua; Song, Ning; Yu, Tong; Zhou, Lianya; Zhang, Helin; Duan, Lin; He, Wenshu; Zhu, Yihua; Bai, Yunfei; Zhu, Miao

    2014-01-01

    In this study, we conducted a meta-analysis on high-throughput gene expression data to identify TNF-α-mediated genes implicated in lung cancer. We first investigated the gene expression profiles of two independent TNF-α/TNFR KO murine models. The EGF receptor signaling pathway was the top pathway associated with genes mediated by TNF-α. After matching the TNF-α-mediated mouse genes to their human orthologs, we compared the expression patterns of the TNF-α-mediated genes in normal and tumor lung tissues obtained from humans. Based on the TNF-α-mediated genes that were dysregulated in lung tumors, we developed a prognostic gene signature that effectively predicted recurrence-free survival in lung cancer in two validation cohorts. Resampling tests suggested that the prognostic power of the gene signature was not by chance, and multivariate analysis suggested that this gene signature was independent of the traditional clinical factors and enhanced the identification of lung cancer patients at greater risk for recurrence.

  1. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

    PubMed

    Brennan, Donal J; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin

    2010-04-01

    Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  2. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    PubMed Central

    2010-01-01

    Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens. PMID:20359358

  3. Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization Grade I meningioma.

    PubMed

    Nanda, Anil; Bir, Shyamal C; Maiti, Tanmoy K; Konar, Subhas K; Missios, Symeon; Guthikonda, Bharat

    2017-01-01

    OBJECTIVE The clinical significance of the Simpson system for grading the extent of meningioma resection and its role as a predictor of the recurrence of World Health Organization (WHO) Grade I meningiomas have been questioned in the past, echoing changes in meningioma surgery over the years. The authors reviewed their experience in resecting WHO Grade I meningiomas and assessed the association between extent of resection, as evaluated using the Simpson classification, and recurrence-free survival (RFS) of patients after meningioma surgery. METHODS Clinical and radiological information for patients with WHO Grade I meningiomas who had undergone resective surgery over the past 20 years was retrospectively reviewed. Simpson and Shinshu grading scales were used to evaluate the extent of resection. Statistical analysis was conducted using Kaplan-Meier curves and Cox proportional-hazards regression. RESULTS Four hundred fifty-eight patients were eligible for analysis. Overall tumor recurrence rates for Simpson resection Grades I, II, III, and IV were 5%, 22%, 31%, and 35%, respectively. After Cox regression analysis, Simpson Grade I (extensive resection) was revealed as a significant predictor of RFS (p = 0.003). Patients undergoing Simpson Grade I and II resections showed significant improvement in RFS compared with patients undergoing Grade III and IV resections (p = 0.005). Extent of resection had a significant effect on recurrence rates for both skull base (p = 0.047) and convexity (p = 0.012) meningiomas. Female sex and a Karnofsky Performance Scale score > 70 were also identified as independent predictors of RFS after resection of WHO Grade I meningioma. CONCLUSIONS In this patient cohort, a significant association was noted between extent of resection and rates of tumor recurrence. In the authors' experience the Simpson grading system maintains its relevance and prognostic value and can serve an important role for patient education. Even though complete tumor

  4. Expression Profiling of Mitochondrial Voltage-Dependent Anion Channel-1 Associated Genes Predicts Recurrence-Free Survival in Human Carcinomas

    PubMed Central

    Lim, Inja; Zhou, Tong; Bang, Hyoweon

    2014-01-01

    Background Mitochondrial voltage-dependent anion channels (VDACs) play a key role in mitochondria-mediated apoptosis. Both in vivo and in vitro evidences indicate that VDACs are actively involved in tumor progression. Specifically, VDAC-1, one member of the VDAC family, was thought to be a potential anti-cancer therapeutic target. Our previous study demonstrated that the human gene VDAC1 (encoding the VDAC-1 isoform) was significantly up-regulated in lung tumor tissue compared with normal tissue. Also, we found a significant positive correlation between the gene expression of VDAC1 and histological grade in breast cancer. However, the prognostic power of VDAC1 and its associated genes in human cancers is largely unknown. Methods We systematically analyzed the expression pattern of VDAC1 and its interacting genes in breast, colon, liver, lung, pancreatic, and thyroid cancers. The genes differentially expressed between normal and tumor tissues in human carcinomas were identified. Results The expression level of VDAC1 was uniformly up-regulated in tumor tissue compared with normal tissue in breast, colon, liver, lung, pancreatic, and thyroid cancers. Forty-four VDAC1 interacting genes were identified as being commonly differentially expressed between normal and tumor tissues in human carcinomas. We designated VDAC1 and the 44 dysregulated interacting genes as the VDAC1 associated gene signature (VAG). We demonstrate that the VAG signature is a robust prognostic biomarker to predict recurrence-free survival in breast, colon, and lung cancers, and is independent of standard clinical and pathological prognostic factors. Conclusions VAG represents a promising prognostic biomarker in human cancers, which may enhance prediction accuracy in identifying patients at higher risk for recurrence. Future therapies aimed specifically at VDAC1 associated genes may lead to novel agents in the treatment of cancer. PMID:25333947

  5. Can pre- and postoperative magnetic resonance imaging predict recurrence-free survival after whole-gland high-intensity focused ablation for prostate cancer?

    PubMed

    Rosset, Rémy; Bratan, Flavie; Crouzet, Sébastien; Tonoli-Catez, Hélène; Mège-Lechevallier, Florence; Gelet, Albert; Rouvière, Olivier

    2017-04-01

    Our aim was to assess whether magnetic resonance imaging (MRI) features predict recurrence-free survival (RFS) after prostate cancer high-intensity focused ultrasound (HIFU) ablation. We retrospectively selected 81 patients who underwent (i) whole-gland HIFU ablation between 2007 and 2011 as first-line therapy or salvage treatment after radiotherapy or brachytherapy, and (ii) pre- and postoperative MRI. On preoperative imaging, two senior (R1, R2) and one junior (R3) readers assessed the number of sectors invaded by the lesion with the highest Likert score (dominant lesion) using a 27-sector diagram. On postoperative imaging, readers assessed destruction of the dominant lesion using a three-level score. Multivariate analysis included the number of sectors invaded by the dominant lesion, its Likert and destruction scores, the pre-HIFU prostate-specific antigen (PSA) level, Gleason score, and the clinical setting (primary/salvage). The most significant predictor was the number of prostate sectors invaded by the dominant lesion for R2 and R3 (p≤0.001) and the destruction score of the dominant lesion for R1 (p = 0.011). The pre-HIFU PSA level was an independent predictor for R2 (p = 0.014), but with only marginal significance for R1 (p = 0.059) and R3 (p = 0.053). The dominant lesion's size and destruction assessed by MRI provide independent prognostic information compared with usual predictors. • The size of the MR-dominant lesion significantly influences post-HIFU recurrence-free survival. • The destruction score of the MR-dominant lesion predicts post-HIFU recurrence-free survival. • Patients with a completely devascularized MR-dominant lesion show better recurrence-free survival • Pre- and post-HIFU MRI provide prognostic information independent of usual predictors.

  6. Pretreatment MR Imaging Features of Triple-Negative Breast Cancer: Association with Response to Neoadjuvant Chemotherapy and Recurrence-Free Survival.

    PubMed

    Bae, Min Sun; Shin, Sung Ui; Ryu, Han Suk; Han, Wonshik; Im, Seock-Ah; Park, In-Ae; Noh, Dong-Young; Moon, Woo Kyung

    2016-11-01

    Purpose To investigate whether pretreatment breast magnetic resonance (MR) imaging features are associated with pathologic complete response (PCR) and recurrence-free survival after neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer. Materials and Methods Identified were 132 patients with primary triple-negative breast cancers who underwent NAC and pretreatment MR imaging between 2004 and 2010. Three breast radiologists independently reviewed the MR images based on the 2013 Breast Imaging Reporting and Data System lexicon. Presence of intratumoral high signal intensity and peritumoral edema on T2-weighted images was also evaluated. Association of PCR and recurrence-free survival with MR imaging features was assessed by using logistic regression and Cox regression. Bonferroni correction was applied to the P values. Results Among 132 patients, 18 (14%) underwent PCR. Round or oval masses (odds ratio, 3.5 [95% confidence interval: 1.3, 9.7]; P = .02), the absence of intratumoral T2 high signal intensity (odds ratio, 3.8 [95% confidence interval: 1.3, 11.0]; P = .01), and the absence of peritumoral edema (odds ratio, 3.4 [95% confidence interval: 1.2, 9.5]; P = .02) were associated with PCR, but not significantly. After 54 months of median follow-up, there were 41 (31% [41 of 132]) breast cancer recurrences. Peritumoral edema was the only significant variable associated with worse recurrence-free survival (hazard ratio, 4.9 [95% confidence interval: 1.9, 12.6]; P = .001). Conclusion Pretreatment MR imaging features may be associated with PCR and recurrence-free survival in patients with triple-negative breast cancer. (©) RSNA, 2016 Online supplemental material is available for this article.

  7. Recurrence-free survival as a putative surrogate for overall survival in phase III trials of curative-intent treatment of colorectal liver metastases: Systematic review.

    PubMed

    Araujo, Raphael L C; Herman, Paulo; Riechelmann, Rachel P

    2017-06-10

    To verify whether recurrence-free survival (RFS) surrogates overall survival (OS) in phase III trials for resectable colorectal liver metastases (CRLM). MEDLINE, EMBASE, and Scopus databases were consulted. Eligible studies were phase III trials testing any type of systemic therapy (neoadjuvant, adjuvant or perioperative) added to surgery in patients with resectable CRLM. A linear regression model based on hazard ratios (HR) of OS and RFS was performed. Of 3059 studies, 5 phase III trials (1162 patients) were included for analyses. A linear regression weighted by each trial was used to estimate the association between each HR and RFS. The originated formula was: OS HR = (0.93 × RFS HR) + 0.14; with RFS 95%CI (0.48-1.38), with P = 0.007. This association suggests that RFS could work as a putative surrogate endpoint of OS in this population, avoiding bigger, longer and more resource-consuming trials. The OS could be assumed based on RFS and our model could be useful to better estimate sample size calculations of phase III trials of CRLM aiming for OS.

  8. Preoperative Gamma-Glutamyltransferase Is Associated with Cancer-Specific Survival and Recurrence-Free Survival of Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus

    PubMed Central

    Luo, Cheng; Xu, Ben; Fan, Yu; Yu, Wei

    2017-01-01

    Introduction. To evaluate the prognostic significance of preoperative gamma-glutamyltransferase (GGT) on the subgroup of nonmetastatic renal cell carcinoma (RCC) with venous tumor thrombus. Materials and Methods. We retrospectively reviewed the institutional database and collected the medical data of 156 patients with nonmetastatic RCC with venous tumor thrombus between March 2004 and December 2014. Kaplan-Meier and Cox regression analyses were applied to determine the prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS). Results. The median value and optimal cutoff point of preoperative GGT were 23.0 and 37.5 IU/L, respectively. In the entire cohort, 67 (42.9%) patients experienced disease recurrence, and 46 (29.5%) patients died. Kaplan-Meier analysis revealed that the CSS and RFS rates were lower in patients with preoperative GGT ≥ 37.5 IU/L than in those with preoperative GGT < 37.5 IU/L. Multivariate Cox proportional hazard analysis demonstrated that high preoperative GGT was significantly associated with shorter CSS (hazard ratio [HR]: 2.115; 95% CI: 1.164–3.843; p = 0.014) and RFS (HR: 1.955; 95% CI: 1.166–3.276; p = 0.011), after adjusting other covariates. Conclusions. Preoperative GGT can serve as an independent prognostic biomarker of nonmetastatic RCC patients with venous tumor thrombus. Further prospective study is warranted to confirm our results. PMID:28168196

  9. Vascular invasion is an independent prognostic factor for distant recurrence-free survival in papillary thyroid carcinoma: a matched-case comparative study.

    PubMed

    Cao, Jun; Hu, Jin-Lin; Chen, Can; Wang, Qing-Liang; Fang, Xian-Hua; Zhang, Yan; Ge, Ming-Hua

    2016-10-01

    It is still unclear whether the clinicopathological and outcome characteristics of vascular invasion (VI) (+) papillary thyroid carcinoma (PTC) differ from VI (-) PTC. This study aims to establish distinguishing features of patients with VI (+) and VI (-) PTC and to investigate the biological and clinical aggressiveness of the disease in these patient groups. A matched-case comparative study. 412 patients (VI (+) PTC study group n=103, and VI (-) PTC control group n=309). These two patient groups were matched 1:3 for variables of age, gender, histological variants, tumour/node/metastasis (TNM) staging and approximate duration of follow-up. Clinicopathological factors and prognosis were compared across the two patient groups. The median age at the time of diagnosis was 42.0 years, and 68.9% were females. Across the patient groups, the incidence of tumour multifocality in patients with VI (+) PTC was slightly higher than in those with VI (-) PTC (p=0.049). In addition, when undergoing more aggressive therapy regimens patients with VI (+) PTC showed decreased distant recurrence-free survival (DRFS), but not regional recurrence-free survival (RRFS) and disease-specific survival (DSS) compared with patients who were VI (-). VI was found to be an independent predictor of DRFS, combined with tumour size >3 cm and total thyroidectomy. VI was an independent risk factor for DRFS, necessitating the need for appropriate postoperative treatment and careful follow-up. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Image-based computer-aided prognosis of lung cancer: predicting patient recurrent-free survival via a variational Bayesian mixture modeling framework for cluster analysis of CT histograms

    NASA Astrophysics Data System (ADS)

    Kawata, Y.; Niki, N.; Ohamatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

    2012-03-01

    In this paper, we present a computer-aided prognosis (CAP) scheme that utilizes quantitatively derived image information to predict patient recurrent-free survival for lung cancers. Our scheme involves analyzing CT histograms to evaluate the volumetric distribution of CT values within pulmonary nodules. A variational Bayesian mixture modeling framework translates the image-derived features into an image-based risk score for predicting the patient recurrence-free survival. Using our dataset of 454 patients with NSCLC, we demonstrate the potential usefulness of the CAP scheme which can provide a quantitative risk score that is strongly correlated with prognostic factors.

  11. Video-assisted thoracoscopic lobectomy is associated with greater recurrence-free survival than stereotactic body radiotherapy for clinical stage I lung cancer.

    PubMed

    Cornwell, Lorraine D; Echeverria, Alfredo E; Samuelian, Jason; Mayor, Jessica; Casal, Roberto F; Bakaeen, Faisal G; Omer, Shuab; Preventza, Ourania; Mai, Weiyuan; Chen, George; Simpson, Katherine H; Moghanaki, Drew; Zhu, Angela W

    2017-08-16

    Stereotactic body radiotherapy is the standard treatment for medically inoperable early-stage non-small cell lung cancer. Recent data suggest that in operable patients, stereotactic body radiotherapy produces outcomes comparable to those of surgical resection. In veterans with early non-small cell lung cancer, we compared the outcomes of stereotactic body radiotherapy and video-assisted thoracoscopic lobectomy. We retrospectively reviewed data from 183 patients (94.0% male) with clinical stage I non-small cell lung cancer who underwent stereotactic body radiotherapy (n = 56) or video-assisted thoracoscopic lobectomy (n = 127) from 2009 to 2014. Propensity matching was used to produce more comparable groups. Primary end points were tumor control and overall, recurrence-free, and lung-cancer-specific survival, as estimated by Kaplan-Meier actuarial analysis. Multivariable analysis was used to identify independent predictors. In the overall cohort, the patients who received stereotactic body radiotherapy were older than the patients who received video-assisted thoracoscopic lobectomy (median age, 79.5 vs 64 years) and had more comorbidities. In the 37 propensity-matched pairs, the 3-year actuarial tumor control rate was 54.3% after stereotactic body radiotherapy and 90.6% after video-assisted thoracoscopic lobectomy (P = .0038). Actuarial lung cancer-specific 3-year survival was 78.1% (stereotactic body radiotherapy) versus 93.6% (video-assisted thoracoscopic lobectomy) (P = .055). One-year overall, 3-year overall, and 3-year recurrence-free survivals were 89.2%, 52.9%, and 38.5% after stereotactic body radiotherapy and 94.6%, 85.7%, and 82.8% after video-assisted thoracoscopic lobectomy (P < .005 for all), respectively. In multivariable analysis, stereotactic body radiotherapy independently predicted recurrence and poorer survival. In veteran patients with early-stage non-small cell lung cancer, video-assisted thoracoscopic lobectomy resulted in better

  12. Selective small molecule Stat3 inhibitor reduces breast cancer tumor-initiating cells and improves recurrence free survival in a human-xenograft model.

    PubMed

    Dave, Bhuvanesh; Landis, Melissa D; Tweardy, David J; Chang, Jenny C; Dobrolecki, Lacey E; Wu, Meng-Fen; Zhang, Xiaomei; Westbrook, Thomas F; Hilsenbeck, Susan G; Liu, Dan; Lewis, Michael T

    2012-01-01

    Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24-/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the percentage of cells expressing TIC markers (CD44+/CD24-/low and ALDH+) and mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day recurrence-free survival relative to docetaxel alone with the addition of the Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a strong impetus for the development of selective Stat3 inhibitors in order to improve survival in patients with p-Stat3 overexpressing tumors.

  13. Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model

    PubMed Central

    Dave, Bhuvanesh; Landis, Melissa D.; Dobrolecki, Lacey E.; Wu, Meng-Fen; Zhang, Xiaomei; Westbrook, Thomas F.; Hilsenbeck, Susan G.; Liu, Dan; Lewis, Michael T.; Tweardy, David J.; Chang, Jenny C.

    2012-01-01

    Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24−/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the percentage of cells expressing TIC markers (CD44+/CD24−/low and ALDH+) and mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day recurrence-free survival relative to docetaxel alone with the addition of the Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a strong impetus for the development of selective Stat3 inhibitors in order to improve survival in patients with p-Stat3 overexpressing tumors. PMID:22879872

  14. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

    PubMed

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-08-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. Distribution of the 729 women with EC according to BMI was BMI < 30 (n = 442; 60.6 %), 30 ≤ BMI < 35 (n = 146; 20 %) and BMI ≥ 35 (n = 141; 19.4 %). Nodal staging was less likely to be performed in women with a BMI ≥ 35 (72 %) than for those with a BMI < 30 (90 %) (p < 0.0001). With a median follow-up of 27 months (interquartile range 13-52), the 3-year RFS was 84.5 %. BMI had no impact on RFS in obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

  15. Reduced expression of cyclin D2 is associated with poor recurrence-free survival independent of cyclin D1 in stage III non-small cell lung cancer.

    PubMed

    Ko, Eunkyung; Kim, Yujin; Park, Seong-Eun; Cho, Eun Yoon; Han, Jungho; Shim, Young Mog; Park, Joobae; Kim, Duk-Hwan

    2012-08-01

    Compared to well-known function of cyclin D1 in lung cancer, the role of cyclin D2 is not clear. This study was aimed at understanding the clinicopathological significance of cyclin D2 in primary non-small cell lung cancer (NSCLC). We retrospectively analyzed expression statuses of cyclin D1, cyclin D2, p16, p21, p27, Ki-67, and phospho-pRb (Ser-807/811) using immunohistochemistry in 626 NSCLCs. Cyclin D2 was expressed in normal lung tissue, and its expression was reduced in 170 (27%) of 626 NSCLCs with a median duration of follow-up of 64 months. Mean phospho-pRb (Ser-807/811) levels were not associated with expression levels of cyclin D2 (P=0.15). The relationship between recurrence and the reduced expression of cyclin D2 was not homogenous by stage (Breslow-Day test for homogeneity, P=0.04). Reduced expression of cyclin D2 was not associated with patient's prognosis in 370 stage I, 112 stage II, and 18 stage IV NSCLCs. However, for 126 stage III NSCLCs, reduced expression of cyclin D2 was adversely associated with recurrence-free survival (RFS) (hazard ratio [HR]=3.71, 95% CI=1.54-13.17; P=0.01), independent of histology and expression of cyclin D1. The reduced expression of cyclin D2 was not associated with the overexpression of cyclin D1 (P=0.65). The present study suggests that reduced expression of cyclin D2 in stage III NSCLC may be associated with poor RFS. And, cyclin D2 may have a distinct role from cyclin D1 in NSCLC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Comparison of Biochemical Recurrence-Free Survival after Radical Prostatectomy Triggered by Grade Reclassification during Active Surveillance and in Men Newly Diagnosed with Similar Grade Disease.

    PubMed

    Diniz, Clarissa P; Landis, Patricia; Carter, H Ballentine; Epstein, Jonathan I; Mamawala, Mufaddal

    2017-09-01

    We compared biochemical recurrence between men on active surveillance who underwent radical prostatectomy triggered by grade reclassification and men diagnosed with similar grade disease treated with immediate radical prostatectomy. We retrospectively analyzed the records of men who underwent surgery from 1995 to 2015 at our institution. We identified 4 groups, including 94 and 56 men on active surveillance who underwent radical prostatectomy following reclassification to Gleason 7 (3 + 4) or greater (grade groups 2 or greater) and Gleason 7 (3 + 4) (grade group 2), and 3,504 and 1,979 in the immediate prostatectomy group diagnosed with grade group 2 or greater and 2, respectively. Biochemical recurrence was assessed by Kaplan-Meir analysis and a multivariable Cox model. Men on active surveillance had a lower incidence of biochemical recurrence than men in the immediate radical prostatectomy groups for biopsy grade groups 2 or greater and 2 (each p <0.05). One, 5 and 10-year biochemical recurrence-free survival for men in the active surveillance group vs the immediate radical prostatectomy group was 97.9% vs 85.5%, 76.6% vs 65.1% and 69.0% vs 54.2% in biopsy grade groups 2 or greater (p = 0.009) and 96.4% vs 91.2%, 89.6% vs 74.0% and 89.6% vs 63.9%, respectively, in biopsy grade group 2 (p = 0.071). For biopsy grade groups 2 or greater there was no significant difference in the risk of biochemical recurrence between the groups after adjusting for age, biopsy extent of cancer and prostate specific antigen density. Patients on active surveillance reclassified to grade groups 2 or greater are at no greater risk for treatment failure than men newly diagnosed with similar grades. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  17. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657.

    PubMed

    Esserman, Laura J; Berry, Donald A; DeMichele, Angela; Carey, Lisa; Davis, Sarah E; Buxton, Meredith; Hudis, Cliff; Gray, Joe W; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C; Olopade, Olufunmilayo I; Rugo, Hope S; Carpenter, John T; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn-Yi; Giri, Dilip; van 't Veer, Laura; Hylton, Nola

    2012-09-10

    Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage

  18. Association of global levels of histone modifications with recurrence-free survival in stage IIB and III esophageal squamous cell carcinomas.

    PubMed

    I, Hoseok; Ko, Eunkyung; Kim, Yujin; Cho, Eun Yoon; Han, Joungho; Park, Joobae; Kim, Kwhanmien; Kim, Duk-Hwan; Shim, Young Mog

    2010-02-01

    This study was aimed at understanding the effects of histone modifications on recurrence-free survival (RFS) after esophagectomy in esophageal squamous cell carcinoma (ESCC). The acetylation of histone H3 lysine (H3K9Ac), histone H3 lysine 18 (H3K18Ac), and histone H4 lysine 12 (H4K12Ac), and the dimethylation of histone H3 lysine 9 (H3K9diMe) and histone H4 arginine 3 (H4R3diMe) were analyzed by immunohistochemistry in 237 ESCCs. The K-means clustering algorithm was used to identify unique patterns of histone modifications. At a median follow-up of 5.1 years, 109 (46%) of 237 patients had developed recurrence of disease. Mean global levels of H3K9Ac, H3K18Ac, H3K9diMe, H4K12Ac, and H4R3diMe were 81.5%, 65.1%, 80.3%, 45.9%, and 27.4%, respectively. In the analysis of individual histones, a 1% increase in the global level of H3K18Ac in pathologic stage III worsened RFS at 1.009 times [95% confidence interval (CI), 1.001-1.016; P = 0.03], after adjusting for age, sex, and operative method. Cluster analysis also showed significant effects of histone modifications on RFS. For stage IIB cancers, Cox proportional hazards analysis showed that RFS of cluster 1, with high global levels of H3K18Ac and H4R3diMe, was 2.79 times poorer (95% CI, 1.14-6.27; P = 0.008) than that of cluster 2, with low levels. RFS for stage III cancers was also poorer in cluster 1 than cluster 2 (adjusted hazard ratio, 2.42; 95% CI, 1.10-5.34; P = 0.02). In conclusion, the present study suggests that global levels of histone modifications in ESCC may be an independent prognostic factor of RFS.

  19. Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

    PubMed Central

    Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela; Carey, Lisa; Davis, Sarah E.; Buxton, Meredith; Hudis, Cliff; Gray, Joe W.; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C.; Olopade, Olufunmilayo I.; Rugo, Hope S.; Carpenter, John T.; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn-Yi; Giri, Dilip; van 't Veer, Laura; Hylton, Nola

    2012-01-01

    Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall

  20. Pre- and post-operative nomograms to predict recurrence-free probability in korean men with clinically localized prostate cancer.

    PubMed

    Kang, Minyong; Jeong, Chang Wook; Choi, Woo Suk; Park, Yong Hyun; Cho, Sung Yong; Lee, Sangchul; Lee, Seung Bae; Ku, Ja Hyeon; Hong, Sung Kyu; Byun, Seok-Soo; Jeong, Hyeon; Kwak, Cheol; Kim, Hyeon Hoe; Lee, Eunsik; Lee, Sang Eun

    2014-01-01

    Although the incidence of prostate cancer (PCa) is rapidly increasing in Korea, there are few suitable prediction models for disease recurrence after radical prostatectomy (RP). We established pre- and post-operative nomograms estimating biochemical recurrence (BCR)-free probability after RP in Korean men with clinically localized PCa. Our sampling frame included 3,034 consecutive men with clinically localized PCa who underwent RP at our tertiary centers from June 2004 through July 2011. After inappropriate data exclusion, we evaluated 2,867 patients for the development of nomograms. The Cox proportional hazards regression model was used to develop pre- and post-operative nomograms that predict BCR-free probability. Finally, we resampled from our study cohort 200 times to determine the accuracy of our nomograms on internal validation, which were designated with concordance index (c-index) and further represented by calibration plots. Over a median of 47 months of follow-up, the estimated BCR-free rate was 87.8% (1 year), 83.8% (2 year), and 72.5% (5 year). In the pre-operative model, Prostate-Specific Antigen (PSA), the proportion of positive biopsy cores, clinical T3a and biopsy Gleason score (GS) were independent predictive factors for BCR, while all relevant predictive factors (PSA, extra-prostatic extension, seminal vesicle invasion, lymph node metastasis, surgical margin, and pathologic GS) were associated with BCR in the post-operative model. The c-index representing predictive accuracy was 0.792 (pre-) and 0.821 (post-operative), showing good fit in the calibration plots. In summary, we developed pre- and post-operative nomograms predicting BCR-free probability after RP in a large Korean cohort with clinically localized PCa. These nomograms will be provided as the mobile application-based SNUH Prostate Cancer Calculator. Our nomograms can determine patients at high risk of disease recurrence after RP who will benefit from adjuvant therapy.

  1. Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients.

    PubMed

    Rades, Dirk; Veninga, Theo; Stalpers, Lukas J A; Schulte, Rainer; Hoskin, Peter J; Poortmans, Philip; Schild, Steven E; Rudat, Volker

    2006-01-01

    To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and being ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.

  2. Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Veninga, Theo; Stalpers, Lukas J.A.; Schulte, Rainer; Hoskin, Peter J.; Poortmans, Philip; Schild, Steven E.; Rudat, Volker

    2006-01-01

    Purpose: To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. Methods and Materials: The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. Results: On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and being ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Conclusion: Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.

  3. Additional androgen deprivation makes the difference: Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy.

    PubMed

    Schiffmann, Jonas; Lesmana, Hans; Tennstedt, Pierre; Beyer, Burkhard; Boehm, Katharina; Platz, Volker; Tilki, Derya; Salomon, Georg; Petersen, Cordula; Krüll, Andreas; Graefen, Markus; Schwarz, Rudolf

    2015-04-01

    The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process.

  4. Nonlinear dimensionality reduction of CT histogram based feature space for predicting recurrence-free survival in non-small-cell lung cancer

    NASA Astrophysics Data System (ADS)

    Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

    2015-03-01

    Advantages of CT scanners with high resolution have allowed the improved detection of lung cancers. In the recent release of positive results from the National Lung Screening Trial (NLST) in the US showing that CT screening does in fact have a positive impact on the reduction of lung cancer related mortality. While this study does show the efficacy of CT based screening, physicians often face the problems of deciding appropriate management strategies for maximizing patient survival and for preserving lung function. Several key manifold-learning approaches efficiently reveal intrinsic low-dimensional structures latent in high-dimensional data spaces. This study was performed to investigate whether the dimensionality reduction can identify embedded structures from the CT histogram feature of non-small-cell lung cancer (NSCLC) space to improve the performance in predicting the likelihood of RFS for patients with NSCLC.

  5. Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.

    PubMed

    Foukakis, Theodoros; von Minckwitz, Gunter; Bengtsson, Nils-Olof; Brandberg, Yvonne; Wallberg, Birgitta; Fornander, Tommy; Mlineritsch, Brigitte; Schmatloch, Sabine; Singer, Christian F; Steger, Günther; Egle, Daniel; Karlsson, Eva; Carlsson, Lena; Loibl, Sibylle; Untch, Michael; Hellström, Mats; Johansson, Hemming; Anderson, Harald; Malmström, Per; Gnant, Michael; Greil, Richard; Möbus, Volker; Bergh, Jonas

    2016-11-08

    Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0

  6. Nuclear T-STAR protein expression correlates with HER2 status, hormone receptor negativity and prolonged recurrence free survival in primary breast cancer and decreased cancer cell growth in vitro.

    PubMed

    Sernbo, Sandra; Borrebaeck, Carl A K; Uhlén, Mathias; Jirström, Karin; Ek, Sara

    2013-01-01

    T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.

  7. MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals

    PubMed Central

    Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

    2016-01-01

    Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology. PMID:27713147

  8. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657).

    PubMed

    Esserman, Laura J; Berry, Donald A; Cheang, Maggie C U; Yau, Christina; Perou, Charles M; Carey, Lisa; DeMichele, Angela; Gray, Joe W; Conway-Dorsey, Kathleen; Lenburg, Marc E; Buxton, Meredith B; Davis, Sarah E; van't Veer, Laura J; Hudis, Clifford; Chin, Koei; Wolf, Denise; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debu; Lehman, Constance; Liu, Minetta C; Olopade, Olufunmilayo I; Rugo, Hope S; Carpenter, John T; Livasy, Chad; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunni-Yi; Giri, Dilip; Au, Alfred; Hylton, Nola

    2012-04-01

    Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥ 3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.

  9. Survivable Local Area Network.

    DTIC Science & Technology

    Enhanced availability and survivability of communications between geographically remote locations with a minimum of redundancy of transmission...isolate bus segements on either side of a connection so that if a fault occurs only the segment containing the fault will be affected. The first type

  10. Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL.

    PubMed

    Hylton, Nola M; Gatsonis, Constantine A; Rosen, Mark A; Lehman, Constance D; Newitt, David C; Partridge, Savannah C; Bernreuter, Wanda K; Pisano, Etta D; Morris, Elizabeth A; Weatherall, Paul T; Polin, Sandra M; Newstead, Gillian M; Marques, Helga S; Esserman, Laura J; Schnall, Mitchell D

    2016-04-01

    To evaluate volumetric magnetic resonance (MR) imaging for predicting recurrence-free survival (RFS) after neoadjuvant chemotherapy (NACT) of breast cancer and to consider its predictive performance relative to pathologic complete response (PCR). This HIPAA-compliant prospective multicenter study was approved by institutional review boards with written informed consent. Women with breast tumors 3 cm or larger scheduled for NACT underwent dynamic contrast-enhanced MR imaging before treatment (examination 1), after one cycle (examination 2), midtherapy (examination 3), and before surgery (examination 4). Functional tumor volume (FTV), computed from MR images by using enhancement thresholds, and change from baseline (ΔFTV) were measured after one cycle and before surgery. Association of RFS with FTV was assessed by Cox regression and compared with association of RFS with PCR and residual cancer burden (RCB), while controlling for age, race, and hormone receptor (HR)/ human epidermal growth factor receptor type 2 (HER2) status. Predictive performance of models was evaluated by C statistics. Female patients (n = 162) with FTV and RFS were included. At univariate analysis, FTV2, FTV4, and ΔFTV4 had significant association with RFS, as did HR/HER2 status and RCB class. PCR approached significance at univariate analysis and was not significant at multivariate analysis. At univariate analysis, FTV2 and RCB class had the strongest predictive performance (C statistic = 0.67; 95% confidence interval [CI]: 0.58, 0.76), greater than for FTV4 (0.64; 95% CI: 0.53, 0.74) and PCR (0.57; 95% CI: 0.39, 0.74). At multivariate analysis, a model with FTV2, ΔFTV2, RCB class, HR/HER2 status, age, and race had the highest C statistic (0.72; 95% CI: 0.60, 0.84). Breast tumor FTV measured by MR imaging is a strong predictor of RFS, even in the presence of PCR and RCB class. Models combining MR imaging, histopathology, and breast cancer subtype demonstrated the strongest predictive

  11. Radiation, hormonotherapy, survival and local control in prostatic carcinoma.

    PubMed

    Cellini, N; Luzi, S; Morganti, A G; Smaniotto, D; Niespolo, R M; Valentini, V

    1998-01-01

    The combination of concomitant external beam radiotherapy (ERT) and neoadjuvant hormonotherapy was shown to be able to significantly improve local control and disease-free survival in locally advanced prostatic carcinoma. (RTOG study 8610). Aim of this analysis was to assess the clinical results observed in a population of patients undergoing this combined treatment and, more particularly, to examine the prognostic impact of local control. 84 patients (T2: 47%, T3: 49.4%, T4: 3.6%) underwent concomitant ERT (dose to pelvic volume: 45 Gy; mean dose to prostatic volume: 65 Gy) and neoadjuvant hormonotherapy (flutamide: 250 mg three times/daily for 30 days; LH-RH analogue: 1 oral dose every 28 days starting 2 months prior to radiotherapy and for its whole duration). With a median follow-up of 36 months, 3.6% of patients were deceased; hematogenous metastases and local disease progression were recorded in 16.7% and 4.8% of patients, respectively. Local disease progression was shown to be significantly correlated with the incidence of metastases. In fact, the actuarial incidence of metastases at 5 years was 100% and 27% in patients with and without local recurrence (p = 0.0043) respectively. Overall, metastases-free local and biochemical recurrence-free survival was 89.2%, 66.5%, 85.0% and 41.9% respectively. At univariate analysis (logrank) the clinical stage (T) was shown to be significantly correlated with the incidence of metastases (p = .0004) and local progression (p < .0001). In conclusion, this study has confirmed the low rate of local progression with the combination of hormonotherapy and radiotherapy and the significant correlation of local control with the incidence of hematogenous metastases.

  12. Local survival of Dunlin wintering in California

    USGS Publications Warehouse

    Warnock, N.; Page, G.W.; Sandercock, B.K.

    1997-01-01

    We estimated local annual survival of 1,051 individually color-banded Dunlin (Calidris alpina) at Bolinas Lagoon, California from 1979 to 1992. Resighting rates for birds banded as adults varied significantly among years, and resighting rates for first-year birds varied by sex and year. No significant differences in local survival rates were found between males and females in any age classes. First-year birds had lower local survival rates than adults. We suspect that raptor predation accounted for much of this difference and other variation in survival rates. Adult Dunlin had lower local survival rates in the year of capture than in subsequent years. Variation in resighting of some groups of individuals including transient Dunlin may account for some differences. However, capture and release of Dunlin may induce short-term behavioral changes that increase the risk of depredation by avian predators within the first few days after capture.

  13. Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

    PubMed

    Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

    2016-01-01

    Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = -0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35-4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16-3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.

  14. Conditional Survival Analysis of Patients With Locally Advanced Laryngeal Cancer: Construction of a Dynamic Risk Model and Clinical Nomogram

    PubMed Central

    Sheu, Tommy; Vock, David M.; Mohamed, Abdallah S. R.; Gross, Neil; Mulcahy, Collin; Zafereo, Mark; Gunn, G. Brandon; Garden, Adam S.; Sevak, Parag; Phan, Jack; Lewin, Jan S.; Frank, Steven J.; Beadle, Beth M.; Morrison, William H.; Lai, Stephen Y.; Hutcheson, Katherine; Marai, G. Elisabeta; Canahuate, Guadalupe M.; Kies, Merrill; El-Naggar, Adel; Weber, Randal S.; Rosenthal, David I.; Fuller, Clifton D.

    2017-01-01

    Conditional survival (CS), the survival beyond a pre-defined time interval, can identify periods of higher mortality risk for patients with locally advanced laryngeal cancer who face treatment-related toxicity and comorbidities related to alcohol and smoking in the survivorship setting. Using Weibull regression modeling, we analyzed retrospectively abstracted data from 638 records of patients who received radiation to identify prognostic factors for overall survival (OS) and recurrence free survival (RFS) for the first 3 years of survival and for OS conditional upon 3 years of survival. The CS was iteratively calculated, stratifying on variables that were statistically significant on multivariate regression. Predictive nomograms were generated. The median total follow up time was 175 months. The 3- and 6- year actuarial overall survival (OS) was 68% (95% confidence interval [CI] 65–72%) and 49% (CI 45–53%). The 3-year conditional overall survival (COS) at 3 years was 72% (CI 65–74%). Black patients had worse COS over time. Nodal disease was significantly associated with recurrence, but after 3 years, the 3-year conditional RFS converged for all nodal groups. In conclusion, the CS analysis in this patient cohort identified subgroups and time intervals that may represent opportunities for intervention. PMID:28276466

  15. Local Response and Impact on Survival After Local Ablation of Liver Metastases From Colorectal Carcinoma by Computed Tomography-Guided High-Dose-Rate Brachytherapy

    SciTech Connect

    Ricke, Jens; Mohnike, Konrad; Pech, Maciej; Seidensticker, Max; Ruehl, Ricarda; Wieners, Gero; Gaffke, Gunnar; Kropf, Siegfried; Felix, Roland; Wust, Peter

    2010-10-01

    Purpose: To determine local tumor control after CT-guided brachytherapy at various dose levels and the prognostic impact of extensive cytoreduction in colorectal liver metastases. Methods and Materials: Seventy-three patients were treated on a single-center prospective trial that was initially designed to be randomized to three dose levels of 15 Gy, 20 Gy, or 25 Gy per lesion, delivered in a single fraction. However, because there was a high rate of cross-over of subjects from higher to lower dose levels, this study is better understood as a prospective trial with three dose levels. No upper size limit for the metastases was applied. We assessed time to local progression, progression-free survival, and overall survival. Results: According to safety constraints cross-over was performed. The final assignment was n = 98, n = 68, and n = 33 in the 15-Gy, 20-Gy, and 25-Gy groups, respectively. Median diameter of the largest tumor lesion in each patient was 5 cm (range, 1-13.5 cm). Estimated mean local recurrence-free survival for all lesions was 34 months (median not reached). The group assigned to 15 Gy after cross-over displayed 34 local recurrences out of 98 lesions; 20 Gy, 15 out of 68 lesions; 25 Gy, 1 out of 33 lesions. The difference between the 25-Gy and the 20-Gy or 15-Gy group was significant (p < 0.05). Repeated local tumor ablations were the most prominent factor for increased survival and dominated additional systemic antitumor treatments. Conclusions: Local tumor control after CT-guided brachytherapy of colorectal liver metastases demonstrated a strong dose dependency. The role of extensive minimally invasive tumor ablation in metastatic colorectal cancer needs to be further established.

  16. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

    PubMed Central

    Krishnan, Sunil; Chadha, Awalpreet S.; Suh, Yelin; Chen, Hsiang-Chun; Rao, Arvind; Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E.; Sawakuchi, Gabriel O.; Beddar, Sam; Katz, Matthew H.; Fleming, Jason B.; Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A.; Crane, Christopher H.

    2016-01-01

    Purpose To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P = .03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P = .05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS. PMID:26972648

  17. Benefit of Adjuvant Radiotherapy for Local Control, Distant Metastasis, and Survival Outcomes in Patients with Localized Soft Tissue Sarcoma: Comparative Effectiveness Analysis of an Observational Cohort Study.

    PubMed

    Posch, Florian; Partl, Richard; Döller, Carmen; Riedl, Jakob M; Smolle, Maria; Leitner, Lukas; Bergovec, Marko; Liegl-Atzwanger, Bernadette; Stotz, Michael; Bezan, Angelika; Gerger, Armin; Pichler, Martin; Kapp, Karin S; Stöger, Herbert; Leithner, Andreas; Szkandera, Joanna

    2017-09-11

    This study aimed to quantify the benefit of adjuvant radiotherapy (AXRT) for local control, distant metastasis, and long-term survival outcomes in patients with localized soft tissue sarcoma (STS). This single-center retrospective observational study enrolled 433 STS patients who underwent surgery with curative intent. An inverse probability of treatment-weighted (IPTW) analysis was implemented to account rigorously for imbalances in prognostic variables between the adjuvant treatment groups. During a median follow-up period of 5.5 years, the study observed 38 local recurrences (9%), 73 occurrences of distant metastasis (17%), 63 STS-related deaths (15%), and 57 deaths from other causes (13%). As expected, patients receiving AXRT (n = 258, 60%) were more likely to have high-grade G3 tumors (p < 0.0001) than patients not receiving AXRT. A crude analysis showed that AXRT was not associated with improved recurrence-free survival [hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.72-1.38; p = 0.98]. However, after IPTW, AXRT was associated with a 38% relative reduction in the risk of recurrence or death (HR 0.62; 95% CI 0.39-1.00; p = 0.05). This benefit was driven by a strong reduction in the risk of local recurrence (HR 0.42; 95% CI 0.19-0.91; p = 0.03), whereas the relative risk of distant metastasis (HR 0.69; 95% CI 0.39-1.25; p = 0.22) and overall survival (HR 0.76; 95% CI 0.44-1.30; p = 0.32) were only nonsignificantly in favor of AXRT. An exploratory analysis showed an overall survival benefit of AXRT for patients with high-grade G3 tumors (HR 0.51; 95% CI 0.33-0.78; p = 0.002). However, this finding may have been attributable to residual confounding. In this observational cohort, AXRT was associated with a 58% reduction in the relative risk of local recurrence. No consistent association between AXRT and lower risks of distant metastasis or death was observed.

  18. Local recurrence risk after previous salvage mastectomy.

    PubMed

    Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

    2016-07-01

    Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p < 0.001). Multivariate analysis showed that the lymph node status of the primary tumor was a significantly independent predictive factor of local recurrence-free survival (p = 0.02). The lymph node status of the primary tumor might be a predictive factor of local recurrence-free survival after salvage mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

    PubMed

    Genin, A S; De Rycke, Y; Stevens, D; Donnadieu, A; Langer, A; Rouzier, R; Lerebours, F

    2016-12-01

    Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  1. Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival.

    PubMed

    Bettegowda, Chetan; Yip, Stephen; Lo, Sheng-Fu Larry; Fisher, Charles G; Boriani, Stefano; Rhines, Laurence D; Wang, Joanna Y; Lazary, Aron; Gambarotti, Marco; Wang, Wei-Lien; Luzzati, Alessandro; Dekutoski, Mark B; Bilsky, Mark H; Chou, Dean; Fehlings, Michael G; McCarthy, Edward F; Quraishi, Nasir A; Reynolds, Jeremy J; Sciubba, Daniel M; Williams, Richard P; Wolinsky, Jean-Paul; Zadnik, Patricia L; Zhang, Ming; Germscheid, Niccole M; Kalampoki, Vasiliki; Varga, Peter Pal; Gokaslan, Ziya L

    2017-03-01

    Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.

  2. Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting.

    PubMed

    Villaverde, Marcela S; Combe, Kristell; Duchene, Adriana G; Wei, Ming X; Glikin, Gerardo C; Finocchiaro, Liliana M E

    2014-09-01

    In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed of B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG + Vx treatments, significantly prevented (in 50% of mice) or delayed (in the remaining 50%) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG + Vx) and overall median survival (SG + Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of the SG + Vx group suggested the development of an effective systemic immunostimulation that enhanced (18)FDG accrual in the thymus, spleen and vertebral column. When combined with surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Preoperative Radiation Therapy Followed by Reexcision May Improve Local Control and Progression-Free Survival in Unplanned Excisions of Soft Tissue Sarcomas of the Extremity and Chest-Wall

    PubMed Central

    Saeed, Hina; Johnstone, Candice A.; Charlson, John A.; Hackbarth, Donald A.; Neilson, John C.

    2016-01-01

    Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS. Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used. Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p < 0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p = 0.08). Preoperative radiation (RT) (p = 0.01) and use of any RT for UE (p = 0.003) led to improved PFS. On MVA, preoperative RT (p = 0.04) and performance status (p = 0.01) led to improved PFS. Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS. PMID:27803813

  4. Abdominoperineal resection provides better local control but equivalent overall survival to local excision of anorectal malignant melanoma: a systematic review.

    PubMed

    Matsuda, Akihisa; Miyashita, Masao; Matsumoto, Satoshi; Takahashi, Goro; Matsutani, Takeshi; Yamada, Takeshi; Kishi, Taro; Uchida, Eiji

    2015-04-01

    To determine whether the extent of surgery is associated with survival in anorectal malignant melanoma (ARMM). ARMM is a rare and highly malignant neoplasm with unfavorable prognosis. The optimal surgical management, abdominoperineal resection (APR) or local excision (LE), has been long debated, but conclusive evidence has not been obtained. A comprehensive electronic literature search was performed to identify studies evaluating survival between APR and LE for ARMM. The main outcome measures were overall survival, relapse-free survival, and local recurrence. A meta-analysis was performed using the random-effects models to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Thirty-one studies, with a total of 1006 patients [544 (54.1%) APR and 462 (45.9%) LE], were included. Meta-analyses showed that overall survival (OR, 1.14; 95% CI, 0.74-1.76; P = 0.54) and relapse-free survival (OR, 0.95; 95% CI, 0.43-2.09; P = 0.89) did not differ significantly between the APR and LE groups. APR significantly reduced local recurrence compared with LE (OR, 0.18; 95% CI, 0.09-0.36; P < 0.00001). Although several limitations, such as inclusion of only retrospective studies with relatively small sample size and selection biases for surgical procedure, are involved, this meta-analysis suggested that APR has no survival benefit; however, APR confers better local control than LE. Given that local failures after LE could be managed by salvage surgery, minimizing morbidity and maximizing quality of life should be the focus in surgical treatment of ARMM.

  5. Embryo Localization Enhances the Survival of Acidovorax citrulli in Watermelon Seeds.

    PubMed

    Dutta, Bhabesh; Schneider, Raymond W; Robertson, Clark L; Walcott, Ronald R

    2016-04-01

    Acidovorax citrulli, the causal agent of bacterial fruit blotch (BFB) of cucurbits has been observed to survive for >34 years in stored melon and watermelon seeds. To better understand this remarkable longevity, we investigated the bacterium's tolerance to desiccation and the effect of bacterial localization in different watermelon seed tissues on its survival. We compared the ability of A. citrulli to tolerate desiccation on filter paper discs and on host (watermelon) and nonhost (cabbage, corn and tomato) seeds to two seedborne (Xanthomonas campestris pv. campestris and Pantoea stewartii subsp. stewartii) and one soilborne (Ralstonia solanacearum) plant-pathogenic bacteria. A. citrulli survival on dry filter paper (>12 weeks) was similar to that of X. campestris pv. campestris but longer than P. stewartii subsp. stewartii. Ralstonia solanacearum survived longer than all other bacteria tested. On all seeds tested, A. citrulli and X. campestris pv. campestris populations declined by 5 orders of magnitude after 12 weeks of incubation at 4°C and 50% relative humidity, while R. solanacearum populations declined by 3 orders. P. stewartii subsp. stewartii was not recovered after 12 weeks of incubation. To determine the effect of tissue localization on bacterial survival, watermelon seeds infested with A. citrulli by flower stigma inoculation (resulting in bacterial localization in the embryo/endosperm) or by ovary pericarp inoculations (resulting in bacterial localization under the testa) were treated with peroxyacetic acid or chlorine (Cl2) gas. Following these treatments, a significantly higher reduction in BFB seed-to-seedling transmission was observed for seeds generated by ovary pericarp inoculation (≥89.5%) than for those generated by stigma inoculation (≤76.5%) (P<0.05). Additionally, higher populations of A. citrulli survived when the bacteria were localized to the embryo/endosperm versus the seed coat, suggesting that tissue localization is important for

  6. Factors that influence survival in unresectable metastatic or locally advanced colorectal cancer.

    PubMed

    Hsu, Chao-Wen; King, Tai-Ming; Wang, Hsin-Tai; Wang, Jui-Ho

    2011-12-01

    Half of patients with colorectal cancer (CRC) have metastasis during the whole course of the disease. Fewer than 10% of those are still alive at 5 years. Locally advanced CRC accounts for 7% to 33% of CRC relapses. Of these, only a small number of patients are resectable with a curative intent. Management of unresectable metastatic or locally advanced CRC is a significant challenge. In this study, we focus on patients with unresectable locally advanced or metastatic CRC and analyze survival rate and prognostic factors influencing the survival. There were 277 patients identified. Several clinicopathologic parameters were evaluated. To determine the prognostic impact of the factors in survival, all parameters were tested from their relationship in Cox-regression model and Cox proportional hazards model. Survival curves were generated according to Kaplan-Meier method and the differences in survival were determined by employing the log-rank test. Three factors that influence the survival were identified: one or more than two organs involved (p = 0.041), higher carcinoembryonic antigen (CEA) level (p = 0.001), and different salvage treatment (p < 0.001). In Kaplan-Meier survival analysis, there were significant differences between patients with one and more than two organs involved (p = 0.027), different ranges of CEA level (p = 0.004), and different salvage treatment (p < 0.001). We clearly demonstrated three factors that influence the survival, including more than two organs involved, higher CEA level, and different salvage treatment. The higher the CEA level and the more organs (≥2) involved, the worse the survival. Even in patients with unresectable metastatic or locally advanced, aggressive treatment with target therapy seems to have survival benefit.

  7. Tumor Wide Horizontal Invasion Predicts Local Recurrence for Scrotal Extramammary Paget’s Disease

    PubMed Central

    Wang, Lujia; Feng, Chenchen; Zhou, Minwei; Zhou, Zhongwen; Ding, Guanxiong; Gao, Peng; Ding, Qiang; Wu, Zhong

    2017-01-01

    Extramammary Paget’s disease (EMPD) is a rare malignancy, and little was known about its prognostic factors and optimal treatment. In the current study, we aimed to discuss clinical and pathological features of scrotal EMPD and determine the prognostic factors for cancer-specific survival and local recurrence. A total of 206 patients with scrotal EMPD lesions surgically treated at our institute were studied. All clinical and pathological data were reviewed. Immunohistochemical staining of TP53 and Ki67 was examined as well. At the last follow-up, 175 patients (84.95%) were alive. Twelve patients (5.83%) had died of the disease due to distant metastases. Fifteen patients (7.28%) developed local recurrences of scrotal EMPD. Ki67 expression was significantly elevated in patients with wide horizontal invasion (P = 0.003). In univariate analysis, high invasion level, presence of nodule, presence of lymphovascular invasion, adnexa invasion, lymph node metastasis and high p53 expression were significant factors for poor cancer-specific survival. In multivariate analysis, high p53 expression was significantly correlated with poor cancer-specific survival. Wide horizontal invasion was independently correlated with local recurrence-free survival of scrotal EMPD. In conclusion, wide horizontal invasion is an independent risk factor for local recurrence-free survival in the patients with scrotal EMPD. PMID:28322288

  8. Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

    SciTech Connect

    Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew; Moody, John S.

    2012-06-01

    Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued

  9. An exception that proves the rule: recurrence free survival five years after extrapleural pneumonectomy for malignant pleural mesothelioma.

    PubMed

    Treasure, Tom; Macbeth, Fergus

    2014-11-18

    Are case reports at all relevant and useful? A case report of an unusual case of mesothelioma prompts a discussion and concludes that they do have a role but that their observations and conclusions need to be treated with care.

  10. Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection.

    PubMed

    Laurence, Graham; Ahuja, Vanita; Bell, Ted; Grim, Rod; Ahuja, Nita

    2017-09-01

    Multivisceral resection (MVR) is considered a radical operation with many surgeons only using it as a last resort. However, when locally advanced colorectal cancers invade adjacent organs, MVR is an important consideration for select patients. The current study addresses the outcomes of MVR in locally advanced recto-sigmoid cancer patients subsequent to these recommendations and hypothesizes that MVR yields improved survival. SEER data (1988-2008) was used to identify all eligible patients with MVR. Patients were limited to single primary locally advanced non-metastatic colorectal cancers originating from the sigmoid and rectum. A total of 4111 locally advanced non-metastatic recto sigmoid cancer patients were included in the study. Cox regression analysis showed variables predictive of MVR were female (OR = 1.95) and late year period (OR = 1.90). Kaplan Meier analysis showed that five-year survival was highest for MVR (52.7%, 48 months), followed by standard surgery (SS; 38.9%, 32 months) and no surgery (NS; 16.6%, 12 months, P < 0.001). With radiation treatment, five year survival improved for all groups, with the highest being MVR (57%, 52 months). With no radiation treatment, five year survival decreased for all groups, with the highest being MVR (45.1%, 44 months), followed by SS (27.3%, 19 months), and NS (8.7%, 6 months, P < 0.001). The present study supports that MVR offers greater survival advantage in patients with locally advanced colorectal cancer. MVR are extensive surgical procedures with significant associated morbidity that usually require specialized training and sometimes the coordination of multiple surgical specialists. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Local-Scale Drivers of Tree Survival in a Temperate Forest

    PubMed Central

    Wang, Xugao; Comita, Liza S.; Hao, Zhanqing; Davies, Stuart J.; Ye, Ji; Lin, Fei; Yuan, Zuoqiang

    2012-01-01

    Tree survival plays a central role in forest ecosystems. Although many factors such as tree size, abiotic and biotic neighborhoods have been proposed as being important in explaining patterns of tree survival, their contributions are still subject to debate. We used generalized linear mixed models to examine the relative importance of tree size, local abiotic conditions and the density and identity of neighbors on tree survival in an old-growth temperate forest in northeastern China at three levels (community, guild and species). Tree size and both abiotic and biotic neighborhood variables influenced tree survival under current forest conditions, but their relative importance varied dramatically within and among the community, guild and species levels. Of the variables tested, tree size was typically the most important predictor of tree survival, followed by biotic and then abiotic variables. The effect of tree size on survival varied from strongly positive for small trees (1–20 cm dbh) and medium trees (20–40 cm dbh), to slightly negative for large trees (>40 cm dbh). Among the biotic factors, we found strong evidence for negative density and frequency dependence in this temperate forest, as indicated by negative effects of both total basal area of neighbors and the frequency of conspecific neighbors. Among the abiotic factors tested, soil nutrients tended to be more important in affecting tree survival than topographic variables. Abiotic factors generally influenced survival for species with relatively high abundance, for individuals in smaller size classes and for shade-tolerant species. Our study demonstrates that the relative importance of variables driving patterns of tree survival differs greatly among size classes, species guilds and abundance classes in temperate forest, which can further understanding of forest dynamics and offer important insights into forest management. PMID:22347996

  12. Local Therapy Improves Overall Survival in Patients With Newly Diagnosed Metastatic Prostate Cancer.

    PubMed

    Parikh, Rahul R; Byun, John; Goyal, Sharad; Kim, Isaac Yi

    2017-05-01

    The role of local therapy, in the form of radiation therapy (RT) or radical prostatectomy(RP), and its association on outcomes is not well established in patients with metastatic prostate cancer. Using the National Cancer Database (NCDB), we evaluated patterns of care and outcomes among patients diagnosed with metastatic prostate cancer from 2004 to 2013 treated with local therapy (RP, intensity-modulated radiation therapy [IMRT], or 2D/3D-conformal radiation therapy [CRT]). The association between local therapy, co-variates, and outcomes was assessed in a multivariable Cox proportional hazards model and Propensity score (PS) matching was performed to balance confounding factors. Survival was estimated using the Kaplan-Meier method. Among the 1,208,180 patients in the NCDB with prostate cancer, 6,051 patients met the inclusion criteria. No local therapy was used in 5,224 patients, while 622 (10.3%), 52 (0.9%), 153 (2.5%) patients received RP, IMRT, and 2D/3D-CRT, respectively. Use of local therapy was associated with younger age (≤70), lower co-morbidity score, lower T-stage, Gleason score <8, node-negative status, private, and Medicare insurance, higher income quartile, and treatment at comprehensive or academic/research programs (P < 0.05). Five-year overall survival for patients receiving local therapy was 45.7% versus 17.1% for those not receiving local therapy (P < 0.01). In multivariate analysis, RP (HR = 0.51; 95%CI, 0.45-0.59, P < 0.01) and IMRT (HR = 0.47; 95%CI, 0.31-0.72, P < 0.01) were independently associated with superior overall survival. After PS-matching, the use of local therapy (RP or IMRT) remained significantly associated with overall survival (HR = 0.35; 95%CI, 0.30-0.41, P < 0.01). The use of RP and IMRT, to treat the primary disease, was associated with improvements in overall survival for patients with metastatic prostate cancer. We have identified patient-specific variations in the use of local therapy

  13. Local Efficacy and Survival after Microwave Ablation of Lung Tumors: A Retrospective Study in 183 Patients.

    PubMed

    Zheng, Aimin; Ye, Xin; Yang, Xia; Huang, Guanghui; Gai, Yonghao

    2016-12-01

    To retrospectively evaluate local efficacy and survival after microwave (MW) ablation of lung tumors and identify predictors of prognosis. Data from 183 consecutive patients (67 women; mean age, 61.5 y ± 13.4) with lung tumors who had undergone 203 lung MW ablation sessions from January 2011 to May 2013 were assessed. The χ(2) test, independent-samples t test, Kaplan-Meier analysis, and Cox regression model analysis were used to estimate survival rates and evaluate significance of factors affecting rates of incomplete ablation, local progression, remote progression-free survival (RPFS), and cancer-specific survival (CSS). Technical success rate was 100%. Incomplete ablation rate after 183 first MW ablations was 14.2% (26 of 183); maximum diameter of target tumors (P = .00001) was associated with incomplete ablation on univariate analysis. The local progression rate was 19.1% (35 of 183); emphysema (P = .020) and maximum diameter of target tumor (P = .000003) were associated with local progression. Median and 4-year RPFS were 15.0 months (95% confidence interval [CI], 11.1-18.9 mo) and 23.8%, respectively. Tumor stage (P < .01) and incomplete ablation (P = .002) were independent predictors of RPFS. Median and 4-year CSS were 24.9 months (95% CI, 19.9-29.9 mo) and 31.1%, respectively. Median and 4-year overall survival were 23.7 months (95% CI, 20.6-26.8 mo) and 29.6%, respectively. Tumor stage (P < .01) and maximum diameter (P = .009) were independent risk factors for CSS. MW ablation is effective for lung tumors, especially small lesions of early-stage primary lung cancer and solitary lung metastasis. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  14. Local weather, regional climate, and annual survival of the northern spotted owl

    USGS Publications Warehouse

    Glenn, E.M.; Anthony, R.G.; Forsman, E.D.; Olson, G.S.

    2011-01-01

    We used an information-theoretical approach and Cormack-Jolly-Seber models for open populations in program MARK to examine relationships between survival rates of Northern Spotted Owls and a variety of local weather variables and long-term climate variables. In four of the six populations examined, survival was positively associated with wetter than normal conditions during the growing season or high summer temperatures. At the three study areas located at the highest elevations, survival was positively associated with winter temperature but also had a negative or quadratic relation with the number of storms and winter precipitation. A metaanalysis of all six areas combined indicated that annual survival was most strongly associated with phase shifts in the Southern Oscillation and Pacific Decadal Oscillation, which reflect large-scale temperature and precipitation patterns in this region. Climate accounted for a variable amount (1-41%) of the total process variation in annual survival but for more year-to-year variation (3-66%) than did spatial variation among owl territories (0-7%). Negative associations between survival and cold, wet winters and nesting seasons were similar to those found in other studies of the Spotted Owl. The relationships between survival and growing-season precipitation and regional climate patterns, however, had not been reported for this species previously. Climate-change models for the first half of the 21st century predict warmer, wetter winters and hotter, drier summers for the Pacific Northwest. Our results indicate that these conditions could decrease Spotted Owl survival in some areas. Copyright ?? The Cooper Ornithological Society 2011.

  15. Locally applied valproate enhances survival in rats after neocortical treatment with tetanus toxin and cobalt chloride.

    PubMed

    Altenmüller, Dirk-Matthias; Hebel, Jonas M; Rassner, Michael P; Volz, Silvanie; Freiman, Thomas M; Feuerstein, Thomas J; Zentner, Josef

    2013-01-01

    In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl₂). In rats, VPA (n = 5) or sodium chloride (NaCl) (n = 5) containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl₂. Video-EEG monitoring was performed with intracortical depth electrodes. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (P < 0.01). In both groups, witnessed deaths occurred in the context of seizures. At least 3/4 of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures. The novel TeT/CoCl₂ approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.

  16. The survive and thrive program: encouraging coaching, mentoring, and peer learning among new local health officials.

    PubMed

    Henry, Vonna; Sarpy, Sue Ann; Green, Rachel; Kaplan, Seth; Bonzon, Ramon

    2010-01-01

    There is a need for programs tailored to train the approximately 300 new local health officials (LHOs) who emerge each year with the knowledge and skills needed to build, maintain, and enhance public health capacity and infrastructure. The Survive and Thrive program incorporates a curriculum that is designed to address the challenges faced by a new LHO. The Survive and Thrive program seeks to address these issues by leveraging the expertise of the current generation of local public health leadership by incorporating experienced LHOs as coaches. Coaching, mentoring, and peer assistance by seasoned LHOs is critical to these new learning opportunities. This article highlights aspects of the coaching component of Survive and Thrive program. Actual examples of its relevance to the professional growth and development of new LHOs and the coaches themselves are presented. The article also describes the novel approach of including coaches in evaluating program effectiveness. The Survive and Thrive program's coaching component can serve as a template for other public health leadership programs and related workforce development initiatives as well as a model to help facilitate lifelong learning of LHOs.

  17. Pretreatment Neutrophil to Lymphocyte Ratio Is Associated with Poor Survival in Patients with Stage I-III Non-Small Cell Lung Cancer

    PubMed Central

    Wang, Jun; Kalhor, Neda; Hu, Jianhua; Wang, Baocheng; Chu, Huili; Zhang, Bicheng; Guan, Yaping; Wu, Yun

    2016-01-01

    Background Neutrophil-to-lymphocyte ratio (NLR) has been shown to be a prognostic indicator in several types of cancer. We aimed to investigate the association between NLR and survival in surgery-treated non-small cell lung cancer (NSCLC) patients. Study Design This large retrospective study included 1,245 patients who underwent initial surgery for stage I–III NSCLC at The University of Texas MD Anderson Cancer Center between December 2002 and November 2010. We analyzed the relationship of NLR with clinicopathological variables, local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) in patients with high or low NLR using Kaplan-Meier method. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the prognostic strength of NLR. Results There was a statistically significant association between the pretreatment NLR and histology type (P = 0.003) and tumor grade (P = 0.028). At a median follow-up time of 50.6 months, high NLR was associated with reduced DRFS (P = 0.011), OS (P < 0.0001) and DSS (P = 0.004); it was not associated with LRFS and RFS. Multivariable Cox analysis further revealed that NLR (P = 0.027), pathologic stage (P < 0.0001) and lymphovascular invasion (P < 0.0001) were strong independent predictors for DRFS. NLR was also an independent marker predicting poor OS (P = 0.002) and DSS (P = 0.017). Conclusion The pretreatment NLR can serve as a biomarker to predict distant recurrence and death in stage I–III NSCLC patients. Combination of NLR and pathologic stage can better predict the OS and DSS in stage I-II NSCLC patients. PMID:27695079

  18. Early-Stage Young Breast Cancer Patients: Impact of Local Treatment on Survival

    SciTech Connect

    Bantema-Joppe, Enja J.; Munck, Linda de; Willemse, Pax H.B.; Langendijk, Johannes A.; Siesling, Sabine; Maduro, John H.

    2011-11-15

    Purpose: In young women, breast-conserving therapy (BCT), i.e., lumpectomy followed by radiotherapy, has been associated with an increased risk of local recurrence. Still, there is insufficient evidence that BCT impairs survival. The aim of our study was to compare the effect of BCT with mastectomy on overall survival (OS) in young women with early-stage breast cancer. Methods and Materials: From two Dutch regional population-based cancer registries (covering 6.2 million inhabitants) 1,453 women <40 years with pathologically T1N0-1M0 breast cancer were selected. Cox regression survival analysis was used to study the effect of local treatment (BCT vs. mastectomy) stratified for nodal stage on survival and corrected for tumor size, age, period of diagnosis, and use of adjuvant systemic therapy. Results: With a median follow-up of 9.6 years, 10-year OS was 83% after BCT and 78% after mastectomy, respectively (unadjusted hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.09-1.72). In N0-patients, 10-year OS was 84% after BCT and 81% after mastectomy and local treatment was not associated with differences in OS (HR 1.19; 95% CI, 0.89-1.58; p = 0.25). Within the N1-patient group, OS was better after BCT compared with mastectomy, 79% vs. 71% at 10 years (HR 1.91; 95% CI, 1.28-2.84; p = 0.001) and in patients treated with adjuvant hormonal therapy (HR 0.34; 95% CI, 0.18-0.66; p = 0.001). Conclusions: In this large population-based cohort of early-stage young breast cancer patients, 10-year OS was not impaired after BCT compared with mastectomy. Patients with 1 to 3 positive lymph nodes had better prognosis after BCT than after mastectomy.

  19. Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma.

    PubMed

    Will, Olga Maria; Purcz, Nicolai; Chalaris, Athena; Heneweer, Carola; Boretius, Susann; Purcz, Larissa; Nikkola, Lila; Ashammakhi, Nureddin; Kalthoff, Holger; Glüer, Claus-Christian; Wiltfang, Jörg; Açil, Yahya; Tiwari, Sanjay

    Despite aggressive treatment with radiation and combination chemotherapy following tumor resection, the 5-year survival rate for patients with head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of diclofenac from electrospun nanofibers generated from poly(D,L-lactide-co-glycolide) polymer. Diclofenac was chosen since anti-inflammatory agents that inhibit cyclooxygenase have shown great potential in their ability to directly inhibit tumor growth as well as suppress inflammation-mediated tumor growth. A mouse resection model of oral carcinoma was developed by establishing tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1) no treatment, 2) implanted scaffolds without diclofenac, 3) implanted scaffolds loaded with diclofenac, and 4) diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal determination of tumor recurrence. At the end of 7 weeks following tumor resection, 33% of mice with diclofenac-loaded scaffolds had a recurrent tumor, in comparison to 90%-100% of the mice in the other three groups. At this time point, mice with diclofenac-releasing scaffolds showed 89% survival rate, while the other groups showed survival rates of 10%-25%. Immunohistochemical staining of recurrent tumors revealed a near 10-fold decrease in the proliferation marker Ki-67 in the tumors derived from mice with diclofenac-releasing scaffolds. In summary, the local application of diclofenac in an orthotopic mouse tumor resection model of oral cancer reduced tumor recurrence with significant improvement in survival over a 7-week study period following tumor resection. Local drug release of anti-inflammatory agents should be investigated as a therapeutic option in the prevention of tumor recurrence in oral squamous

  20. Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma

    PubMed Central

    Will, Olga Maria; Purcz, Nicolai; Chalaris, Athena; Heneweer, Carola; Boretius, Susann; Purcz, Larissa; Nikkola, Lila; Ashammakhi, Nureddin; Kalthoff, Holger; Glüer, Claus-Christian; Wiltfang, Jörg; Açil, Yahya; Tiwari, Sanjay

    2016-01-01

    Despite aggressive treatment with radiation and combination chemotherapy following tumor resection, the 5-year survival rate for patients with head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of diclofenac from electrospun nanofibers generated from poly(D,L-lactide-co-glycolide) polymer. Diclofenac was chosen since anti-inflammatory agents that inhibit cyclooxygenase have shown great potential in their ability to directly inhibit tumor growth as well as suppress inflammation-mediated tumor growth. A mouse resection model of oral carcinoma was developed by establishing tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1) no treatment, 2) implanted scaffolds without diclofenac, 3) implanted scaffolds loaded with diclofenac, and 4) diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal determination of tumor recurrence. At the end of 7 weeks following tumor resection, 33% of mice with diclofenac-loaded scaffolds had a recurrent tumor, in comparison to 90%–100% of the mice in the other three groups. At this time point, mice with diclofenac-releasing scaffolds showed 89% survival rate, while the other groups showed survival rates of 10%–25%. Immunohistochemical staining of recurrent tumors revealed a near 10-fold decrease in the proliferation marker Ki-67 in the tumors derived from mice with diclofenac-releasing scaffolds. In summary, the local application of diclofenac in an orthotopic mouse tumor resection model of oral cancer reduced tumor recurrence with significant improvement in survival over a 7-week study period following tumor resection. Local drug release of anti-inflammatory agents should be investigated as a therapeutic option in the prevention of tumor recurrence in oral squamous

  1. Local Competition Between Foraging Relatives: Growth and Survival of Bruchid Beetle Larvae.

    PubMed

    Smallegange, Isabel M; Tregenza, Tom

    2008-09-01

    Kin selection theory states that when resources are limited and all else is equal, individuals will direct competition away from kin. However, when competition between relatives is completely local, as is the case in granivorous insects whose larval stages spend their lives within a single seed, this can reduce or even negate the kin-selected benefits. Instead, an increase in competition may have the same detrimental effects on individuals that forage with kin as those that forage with non-kin. In a factorial experiment we assessed the effects of relatedness and competition over food on the survival and on fitness-related traits of the bruchid beetle Callosobruchus maculatus. Relatedness of competitors did not affect the survival of larvae. Larval survival substantially decreased with increasing larval density, and we found evidence that beetles maturing at a larger size were more adversely affected by competition, resulting in lower survival rates. Furthermore, females showed a reduction in their growth rate with increasing larval density, emerging smaller after the same development time. Males increased their growth rate, emerging earlier but at a similar size when food was more limited. Our results add to the growing number of studies that fail to show a relationship between relatedness and a reduction in competition between relatives in closed systems, and emphasize the importance of the scale at which competition between relatives occurs.

  2. Tumor volume as a prognostic factor for local control and overall survival in advanced larynx cancer.

    PubMed

    Timmermans, Adriana J; Lange, Charlotte A H; de Bois, Josien A; van Werkhoven, Erik; Hamming-Vrieze, Olga; Hilgers, Frans J M; van den Brekel, Michiel W M

    2016-02-01

    Tumor volume has been postulated to be an important prognostic factor for oncological outcome after radiotherapy or chemoradiotherapy. This postulate was retrospectively investigated in a consecutively treated cohort of T3-T4 larynx cancer patients. Retrospective cohort study. For 166 patients with T3-T4 larynx cancer (1999-2008), pretreatment computed tomography and magnetic resonance imaging scans were available for tumor volume delineation. Patients were treated with radiotherapy, chemoradiotherapy, or total laryngectomy with postoperative radiotherapy. Both a dedicated head and neck radiologist and the first author determined all tumor volumes. Statistical analysis was by Kaplan-Meier plots and Cox proportional hazard models. Patients with T3 larynx cancer had significantly smaller tumor volumes than patients with T4 larynx cancer (median = 8.1 cm(3) and 15.8 cm(3), respectively; P < .0001). In the group treated with total laryngectomy and postoperative radiotherapy, no association was found between tumor volume and local or locoregional control or overall survival. In the group treated with radiotherapy, a nonsignificant trend was observed between local control and tumor volume. In the chemoradiotherapy group, however, a significant impact of tumor volume was found on local control (hazard ratio = 1.07; 95% confidence interval = 1.01-1.13; P = .028). Tumor volume was not significantly associated with local control, locoregional control, or overall survival in the surgically treated group. In the group treated with radiotherapy, there was no statistically significant association, but a trend was observed between local control and tumor volume. Only in patients treated with concurrent chemoradiotherapy was a significant impact of tumor volume on local control found. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  3. The Matrix Metalloproteinase-7 Polymorphism Rs10895304 Is Associated With Increased Recurrence Risk in Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Jaboin, Jerry J.; Hwang, Misun; Lopater, Zachary; Chen Heidi; Ray, Geoffrey L.; Perez, Carmen; Cai Qiuyin; Wills, Marcia L.; Lu Bo

    2011-04-01

    Purpose: To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer. Methods and Materials: Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years. Genotyping was performed using hybridization with custom-designed allele-specific probes. Three single nucleotide polymorphisms within the matrix metalloproteinase-7 gene were assessed with respect to age at diagnosis, margin status, extracapsular extension, lymph node involvement, recurrence-free survival, and overall survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer who underwent radical prostatectomy. Results: Rs10895304 was the sole significant polymorphism. The A/G genotype of rs10895304 had a statistically significant association with recurrence-free survival in postprostatectomy patients (p = 0.0061, log-rank test). The frequency of the risk-reducing genotype (A/A) was 74%, whereas that of the risk-enhancing genotypes (A/G and G/G) were 20% and 6%, respectively. Multivariable Cox regression analyses detected a significant association between rs10895304 and recurrences after adjustment for known prognostic factors. The G allele of this polymorphism was associated with increased risk of prostate cancer recurrence (adjusted hazards ratio, 3.375; 95% confidence interval 1.567-7.269; p < 0.001). The other assayed polymorphisms were not significant, and no correlations were made to other clinical variables. Conclusions: The A/G genotype of rs10895304 is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer. Our data suggest that for this subset of patients, prostatectomy alone may not be adequate for local control. This is a novel and relevant marker that should be evaluated for improved risk stratification of patients who

  4. Early Enhanced Local Neutrophil Recruitment in Peritonitis-Induced Sepsis Improves Bacterial Clearance and Survival

    PubMed Central

    Craciun, Florin L.; Schuller, Elizabeth R.; Remick, Daniel G.

    2017-01-01

    Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis. PMID:21041722

  5. Integrative Systemic and Local Metabolomics with Impact on Survival in High-Grade Serous Ovarian Cancer.

    PubMed

    Bachmayr-Heyda, Anna; Aust, Stefanie; Auer, Katharina; Meier, Samuel M; Schmetterer, Klaus G; Dekan, Sabine; Gerner, Christopher; Pils, Dietmar

    2017-04-15

    Purpose: Cancer metabolism is characterized by alterations including aerobic glycolysis, oxidative phosphorylation, and need of fuels and building blocks.Experimental Design: Targeted metabolomics of preoperative and follow-up sera, ascites, and tumor tissues, RNA sequencing of isolated tumor cells, local and systemic chemokine, and local immune cell infiltration data from up to 65 high-grade serous ovarian cancer patients and 62 healthy controls were correlated to overall survival and integrated in a Systems Medicine manner.Results: Forty-three mainly (poly)unsaturated glycerophospholipids and four essential amino acids (citrulline) were significantly reduced in patients with short compared with long survival and healthy controls. The glycerophospholipid fingerprint is identical to the fingerprint from isolated (very) low-density lipoproteins (vLDL), indicating that the source of glycerophospholipids consumed by tumors is (v)LDL. A glycerophospholipid-score (HR, 0.46; P = 0.007) and a 100-gene signature (HR, 0.65; P = 0.004) confirmed the independent impact on survival in training (n = 65) and validation (n = 165) cohorts. High concentrations of LDLs and glycerophospholipids were independently predictors for favorable survival. Patients with low glycerophospholipids presented with more systemic inflammation (C-reactive protein and fibrinogen negatively and albumin positively correlated) but less adaptive immune cell tumor infiltration (lower tumor and immune cell PD-L1 expression), less oxygenic respiration and increased triglyceride biosynthesis in tumor cells, and lower histone expressions, correlating with higher numbers of expressed genes and more transcriptional noise, a putative neo-pluripotent tumor cell phenotype.Conclusions: Low serum phospholipids and essential amino acids are correlated with worse outcome in ovarian cancer, accompanied by a specific tumor cell phenotype. Clin Cancer Res; 23(8); 2081-92. ©2016 AACR.

  6. Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival.

    PubMed

    Craciun, Florin L; Schuller, Elizabeth R; Remick, Daniel G

    2010-12-01

    Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis.

  7. African American Race is an Independent Risk Factor in Survival from Initially Diagnosed Localized Breast Cancer

    PubMed Central

    Wieder, Robert; Shafiq, Basit; Adam, Nabil

    2016-01-01

    BACKGROUND: African American race negatively impacts survival from localized breast cancer but co-variable factors confound the impact. METHODS: Data sets were analyzed from the Surveillance, Epidemiology and End Results (SEER) directories from 1973 to 2011 consisting of patients with designated diagnosis of breast adenocarcinoma, race as White or Caucasian, Black or African American, Asian, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, age, stage I, II or III, grade 1, 2 or 3, estrogen receptor or progesterone receptor positive or negative, marital status as single, married, separated, divorced or widowed and laterality as right or left. The Cox Proportional Hazards Regression model was used to determine hazard ratios for survival. Chi square test was applied to determine the interdependence of variables found significant in the multivariable Cox Proportional Hazards Regression analysis. Cells with stratified data of patients with identical characteristics except African American or Caucasian race were compared. RESULTS: Age, stage, grade, ER and PR status and marital status significantly co-varied with race and with each other. Stratifications by single co-variables demonstrated worse hazard ratios for survival for African Americans. Stratification by three and four co-variables demonstrated worse hazard ratios for survival for African Americans in most subgroupings with sufficient numbers of values. Differences in some subgroupings containing poor prognostic co-variables did not reach significance, suggesting that race effects may be partly overcome by additional poor prognostic indicators. CONCLUSIONS: African American race is a poor prognostic indicator for survival from breast cancer independent of 6 associated co-variables with prognostic significance. PMID:27698895

  8. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    SciTech Connect

    Habr-Gama, Angelita; Gama-Rodrigues, Joaquim; São Julião, Guilherme P.; Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B.; Perez, Rodrigo O.

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

  9. Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul

    2016-01-01

    Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer. PMID:27306773

  10. Localized hypoxia within the subgranular zone determines the early survival of newborn hippocampal granule cells

    PubMed Central

    Chatzi, Christina; Schnell, Eric; Westbrook, Gary L

    2015-01-01

    The majority of adult hippocampal newborn cells die during early differentiation from intermediate progenitors (IPCs) to immature neurons. Neural stem cells in vivo are located in a relative hypoxic environment, and hypoxia enhances their survival, proliferation and stemness in vitro. Thus, we hypothesized that migration of IPCs away from hypoxic zones within the SGZ might result in oxidative damage, thus triggering cell death. Hypoxic niches were observed along the SGZ, composed of adult NSCs and early IPCs, and oxidative byproducts were present in adjacent late IPCs and neuroblasts. Stabilizing hypoxia inducible factor-1α with dimethyloxallyl glycine increased early survival, but not proliferation or differentiation, in neurospheres in vitro and in newly born SGZ cells in vivo. Rescue experiments in Baxfl/flmutants supported these results. We propose that localized hypoxia within the SGZ contributes to the neurogenic microenvironment and determines the early, activity-independent survival of adult hippocampal newborn cells. DOI: http://dx.doi.org/10.7554/eLife.08722.001 PMID:26476335

  11. Percutaneous core needle biopsy in retroperitoneal sarcomas does not influence local recurrence or overall survival.

    PubMed

    Wilkinson, M J; Martin, J L; Khan, A A; Hayes, A J; Thomas, J M; Strauss, D C

    2015-03-01

    Tumours within the retroperitoneum can cause a diagnostic dilemma. A preoperative core needle biopsy often is required to establish a histological diagnosis. Preoperative core needle biopsy for extremity soft-tissue sarcoma is oncologically safe and biopsy site recurrence is extremely rare, attributed to placing the biopsy site within the planned resection field. This study investigates whether preoperative core needle biopsy affects oncological outcomes in retroperitoneal sarcomas. Patients undergoing resection of intermediate- and high-grade primary retroperitoneal sarcoma from 1990 until 2011 were included. Primary endpoints were immediate biopsy-related complications, local recurrence, and overall survival. A total of 150 patients were included in the analysis. Of these, 90 patients underwent resection after a preoperative biopsy. Median follow-up was 48 months. One patient required hospital admission postbiopsy for an abdominal wall rectus sheath haematoma. No patient developed intra-abdominal complications that required hospitalisation or early operation related to core needle biopsy. No patient developed a biopsy site recurrence. There was no significant increase in either local recurrence (p = 0.101) or overall survival (p = 0.191) after core needle biopsy. Preoperative core needle biopsy for retroperitoneal sarcomas is safe and does not affect oncological outcome.

  12. Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

    PubMed

    Fettiplace, Michael R; McCabe, Daniel J

    2017-08-01

    The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I(2) to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

  13. Outcomes of surgery followed by local brain radiotherapy compared with surgery followed by whole brain radiotherapy for single brain metastasis.

    PubMed

    Igaki, Hiroshi; Harada, Ken; Umezawa, Rei; Miyakita, Yasuji; Ohno, Makoto; Takahashi, Masamichi; Sumi, Minako; Inaba, Koji; Murakami, Naoya; Ito, Yoshinori; Narita, Yoshitaka; Itami, Jun

    2017-07-31

    To determine the clinical efficacy of surgery followed by local brain radiotherapy (LBRT) for patients with a single brain metastasis, by comparing the results with those of postoperative whole brain radiotherapy (WBRT). We performed a retrospective analysis to compare the survival rate, recurrence-free rates, and causes of death for single brain metastasis patients who underwent surgery followed by LBRT or WBRT in the 2010-2015 period. After their surgery, 22 and 32 patients were treated by LBRT and WBRT, respectively. The median survival times for these LBRT and WBRT groups were 18.3 months and 19.2 months, respectively (p = 0.356). The local recurrence-free rates were 81.2% at 1 year and 81.2% at 2 years after LBRT, and 63.8% at 1 year and 58.9% at 2 years after WBRT (p = 0.589). The distant brain recurrence-free rates were 42.5% at 1 year and 25.5% at 2 years after LBRT, and 69.8% at 1 year and 52.4% at 2 years after WBRT (p = 0.044). Distant brain recurrences were observed significantly more frequently in the LBRT group, but the rates of salvage treatment application and survival were not significantly different between the LBRT and WBRT groups. The probability of neurologic death was not significantly higher in the LBRT group compared with the WBRT group. Surgery followed by LBRT for single brain metastasis is not inferior to postoperative WBRT, because survival and the necessity of salvage treatment after LBRT were equivalent to those after WBRT.

  14. Local annual survival and seasonal residency rates of Semipalmated Sandpipers (Calidris pusilla) in Puerto Rico

    USGS Publications Warehouse

    Rice, S.M.; Collazo, J.A.; Alldredge, M.W.; Harrington, B.A.; Lewis, A.R.

    2007-01-01

    We report seasonal residency and local annual survival rates of migratory Semipalmated Sandpipers (Calidris pusilla) at the Cabo Rojo salt flats, Puerto Rico. Residency rate (daily probability of remaining on the flats) was 0.991 ± 0.001 (x̄ ± SE), yielding a mean length of stay of 110 days. This finding supports the inclusion of the Caribbean as part of the species' winter range. Average estimated percentage of fat was low but increased throughout the season, which suggests that birds replenish some spent fat reserves and strive for energetic maintenance. Local annual survival rate was 0.62 ± 0.04, within the range of values reported for breeding populations at Manitoba and Alaska (0.53–0.76). The similarity was not unexpected because estimates were obtained annually but at opposite sites of their annual migratory movements. Birds captured at the salt flats appeared to be a mix of birds from various parts of the breeding range, judging from morphology (culmen's coefficient of variation = 9.1, n = 106). This suggested that origin (breeding area) of birds and their proportion in the data should be ascertained and accounted for in analyses to glean the full conservation implications of winter-based annual survival estimates. Those data are needed to unravel the possibility that individuals of distinct populations are affected by differential mortality factors across different migratory routes. Mean length of stay strongly suggested that habitat quality at the salt flats was high. Rainfall and tidal flow combine to increase food availability during fall. The salt flats dry up gradually toward late January, at the onset of the dry season. Semipalmated Sandpipers may move west to other Greater Antilles or south to sites such as coastal Surinam until the onset of spring migration. They are not an oversummering species at the salt flats. Conservation efforts in the Caribbean region require understanding the dynamics of this species throughout winter to protect

  15. Operative management of locally advanced, differentiated thyroid cancer

    PubMed Central

    Wang, Laura Y.; Nixon, Iain J.; Patel, Snehal G.; Palmer, Frank L.; Tuttle, R. Michael; Shaha, Ashok; Shah, Jatin P.; Ganly, Ian

    2016-01-01

    Background The majority of differentiated thyroid cancer tends to present with limited locoregional disease, leading to excellent long-term survival after operative treatment. Even patients with advanced local disease may survive for long periods with appropriate treatment. The aim of this study is to present our institutional experience of the management of locally advanced differentiated thyroid cancer and to analyze factors predictive of outcome. Methods We reviewed our institutional database of 3,664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010. A total of 153 patients had tumor extension beyond the thyroid capsule that invaded the subcutaneous soft tissues, recurrent laryngeal nerve, larynx, trachea, or esophagus. Details on extent of operation and adjuvant therapy were recorded. Disease-specific survival and locoregional recurrence-free probability were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by multivariate analysis. Results The median age of the 153 patients with tumor extension beyond the thyroid capsule was 55 years (range 11–91 years). Eighty-nine patients (58.2%) were female. Twenty-three patients (15.0%) were staged as M1 at presentation, and 122 (79.7%) had pathologically involved lymph nodes. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (51.0%) followed by the trachea (46.4%) and esophagus (39.2%). Sixty-three patients (41%) required resection of the recurrent laryngeal nerve due to tumor involvement. After surgery, 20 patients (13.0%) had gross residual disease (R2), 63 (41.2%) had a positive margin of resection (R1), and 70 (45.8%) had complete resection with negative margins (R0). With a median follow-up of 63.9 months, 5-year, disease-specific survival, when stratified by R0/R1/R2 resection, was 94.4%, 87.6%, and 67.9%, respectively (P = .030). The data do not demonstrate a statistical difference in survival

  16. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma.

    PubMed Central

    Singer, S; Corson, J M; Gonin, R; Labow, B; Eberlein, T J

    1994-01-01

    OBJECTIVE: The authors sought to identify prognostic factors in the management of extremity soft tissue sarcoma. SUMMARY BACKGROUND DATA: The surgical management of soft tissue sarcoma has evolved because of advances in therapy, resulting in increased limb preservation and quality of life. However, identifying a subset of patients most likely to benefit from adjuvant chemotherapy has been difficult to achieve. METHODS: A retrospective analysis of a prospective data base of 182 patients with extremity sarcomas from 1970 to 1992 was performed. RESULTS: A histologic diagnosis of Ewing's sarcoma, synovial sarcoma, and angiosarcoma was associated with a 13-fold increased risk of death compared with liposarcoma, fibrosarcoma, and malignant peripheral nerve sheath histologic types after having adjusted for the other prognostic factors (p < 0.001). In addition to histologic type, high-grade sarcomas (p = 0.018), sarcomas greater than 10 cm in size (p = 0.006), and age at diagnosis (p = 0.016) were found to be important prognostic factors for survival but not for local recurrence. For the first time to their knowledge, the authors showed that mean mitotic activity has prognostic value after having adjusted for other prognostic factors, such as grade (p = 0.005). The only prognostic factors predictive for local recurrence were whether the patient presented with locally recurrent disease (p = 0.0001) or had microscopically positive margins (p = 0.052). CONCLUSIONS: The use of mitotic activity along with grade, size, histologic type, and age at diagnosis is prognostic for survival in extremity soft tissue sarcoma. The use of an objective pathologic feature, such as mean mitotic activity, is also useful in selecting patients for future systemic neoadjuvant or adjuvant trials and primary therapy. PMID:8129487

  17. Monoubiquitination of survival motor neuron regulates its cellular localization and Cajal body integrity

    PubMed Central

    Han, Ke-Jun; Foster, Daniel; Harhaj, Edward W.; Dzieciatkowska, Monika; Hansen, Kirk; Liu, Chang-Wei

    2016-01-01

    Low levels of the survival motor neuron (SMN) protein cause spinal muscular atrophy, the leading genetic disorder for infant mortality. SMN is ubiquitously expressed in various cell types and localizes in both the cytoplasm and the nucleus, where it concentrates in two subnuclear structures termed Cajal body (CB) and gems. In addition, SMN can also be detected in the nucleolus of neurons. Mechanisms that control SMN sorting in the cell remain largely unknown. Here, we report that the ubiquitin (Ub) ligase Itch directly interacts with and monoubiquitinates SMN. Monoubiquitination of SMN has a mild effect on promoting proteasomal degradation of SMN. We generated two SMN mutants, SMN(K0), in which all lysines are mutated to arginines and thereby abolishing SMN ubiquitination, and Ub-SMN(K0), in which a single Ub moiety is fused at the N-terminus of SMN(K0) and thereby mimicking SMN monoubiquitination. Immunostaining assays showed that SMN(K0) mainly localizes in the nucleus, whereas Ub-SMN(K0) localizes in both the cytoplasm and the nucleolus in neuronal SH-SY5Y cells. Interestingly, canonical CB foci and coilin/small nuclear ribonucleoprotein (snRNP) co-localization are significantly impaired in SH-SY5Y cells stably expressing SMN(K0) or Ub-SMN(K0). Thus, our studies discover that Itch monoubiquitinates SMN and monoubiquitination of SMN plays an important role in regulating its cellular localization. Moreover, mislocalization of SMN disrupts CB integrity and likely impairs snRNP maturation. PMID:26908624

  18. Monoubiquitination of survival motor neuron regulates its cellular localization and Cajal body integrity.

    PubMed

    Han, Ke-Jun; Foster, Daniel; Harhaj, Edward W; Dzieciatkowska, Monika; Hansen, Kirk; Liu, Chang-Wei

    2016-04-01

    Low levels of the survival motor neuron (SMN) protein cause spinal muscular atrophy, the leading genetic disorder for infant mortality. SMN is ubiquitously expressed in various cell types and localizes in both the cytoplasm and the nucleus, where it concentrates in two subnuclear structures termed Cajal body (CB) and gems. In addition, SMN can also be detected in the nucleolus of neurons. Mechanisms that control SMN sorting in the cell remain largely unknown. Here, we report that the ubiquitin (Ub) ligase Itch directly interacts with and monoubiquitinates SMN. Monoubiquitination of SMN has a mild effect on promoting proteasomal degradation of SMN. We generated two SMN mutants, SMN(K0), in which all lysines are mutated to arginines and thereby abolishing SMN ubiquitination, and Ub-SMN(K0), in which a single Ub moiety is fused at the N-terminus of SMN(K0) and thereby mimicking SMN monoubiquitination. Immunostaining assays showed that SMN(K0) mainly localizes in the nucleus, whereas Ub-SMN(K0) localizes in both the cytoplasm and the nucleolus in neuronal SH-SY5Y cells. Interestingly, canonical CB foci and coilin/small nuclear ribonucleoprotein (snRNP) co-localization are significantly impaired in SH-SY5Y cells stably expressing SMN(K0) or Ub-SMN(K0). Thus, our studies discover that Itch monoubiquitinates SMN and monoubiquitination of SMN plays an important role in regulating its cellular localization. Moreover, mislocalization of SMN disrupts CB integrity and likely impairs snRNP maturation.

  19. Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer: An International Collaborative Review.

    PubMed

    Wallis, Christopher J D; Glaser, Adam; Hu, Jim C; Huland, Hartwig; Lawrentschuk, Nathan; Moon, Daniel; Murphy, Declan G; Nguyen, Paul L; Resnick, Matthew J; Nam, Robert K

    2017-06-10

    Evaluation of treatment options for localized prostate cancer (PCa) remains among the highest priorities for comparative effectiveness research. Surgery and radiotherapy (RT) are the two interventions most commonly used. To provide a critical narrative review of evidence of the comparative effectiveness and harms of surgery and RT in the treatment of localized PCa. A collaborative critical narrative review of the literature was conducted. Evidence to clearly guide treatment choice in PCa remains insufficient. Randomized trials are underpowered for clinically meaningful endpoints and have demonstrated no difference in overall or PCa-specific survival. Observational studies have consistently demonstrated an absolute survival benefit for men treated with radical prostatectomy, but are limited by selection bias and residual confounding errors. Surgery and RT are associated with comparable health-related quality of life following treatment in three randomized trials. Randomized data regarding urinary, erectile, and bowel function show few long-term (>5 yr) differences, although short-term continence and erectile function were worse following surgery and short-term urinary bother and bowel function were worse following RT. There has been recent recognition of other complications that may significantly affect the life trajectory of those undergoing PCa treatment. Of these, hospitalization, the need for urologic, rectoanal, and other major surgical procedures, and secondary cancers are more common among men treated with RT. Androgen deprivation therapy, frequently co-administered with RT, may additionally contribute to treatment-related morbidity. Technological innovations in surgery and RT have shown inconsistent oncologic and functional benefits. Owing to underpowered randomized control studies and the selection biases inherent in observational studies, the question of which treatment provides better PCa control cannot be definitively answered now or in the near future

  20. Prognostic Value of Ki67 in Localized Prostate Carcinoma: A Multi-Institutional Study of >1,000 Prostatectomies

    PubMed Central

    Tretiakova, Maria S.; Wei, Wei; Boyer, Hilary D.; Newcomb, Lisa F.; Hawley, Sarah; Auman, Heidi; Vakar-Lopez, Funda; McKenney, Jesse K.; Fazli, Ladan; Simko, Jeffry; Troyer, Dean A.; Hurtado-Coll, Antonio; Thompson, Ian M.; Carroll, Peter R.; Ellis, William J.; Gleave, Martin E.; Nelson, Peter S.; Lin, Daniel W.; True, Lawrence D.; Feng, Ziding; Brooks, James D.

    2017-01-01

    Background Expanding interest in and use of active surveillance for early state prostate cancer has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinico-pathologic features and validate its utility as a clinical grade test in predicting cancer-specific outcomes. Methods After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (3 cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinico-pathologic factors and recurrence free survival including biochemical recurrence, metastasis or PC death (7-year median follow-up). Results In 1004 PCs (~4,000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (p<0.0001), seminal vesicle invasion (SVI, p=0.02), extracapsular extension (ECE, p<0.0001) and Gleason Score (GS, p<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence free, overall and disease-specific survival by multivariable Cox proportional hazard model (HR=1.04–1.1, p=0.02–0.0008). High Ki67 score (defined as ≥5%) was significantly associated with worse recurrence free survival (HR=1.47, p=0.0007) and worse overall survival (HR=2.03, p=0.03). Conclusion In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE, and greater probability of recurrence. PMID:27136741

  1. Radiation-induced brachial plexopathy: Neurological follow-up in 161 recurrence-free breast cancer patients

    SciTech Connect

    Olsen, N.K.; Pfeiffer, P.; Johannsen, L.; Schroder, H.; Rose, C. )

    1993-04-30

    The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus. 24 refs., 9 tabs.

  2. Inconsistent selection and definition of local and regional endpoints in breast cancer research.

    PubMed

    Moossdorff, M; van Roozendaal, L M; Schipper, R-J; Strobbe, L J A; Voogd, A C; Tjan-Heijnen, V C G; Smidt, M L

    2014-12-01

    Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  3. A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound

    NASA Astrophysics Data System (ADS)

    Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad J.; Kim, Christina; Ghandi, Sonal; Trudeau, Maureen; Pritchard, Kathleen; Tran, William T.; Slodkowska, Elzbieta; Sadeghi-Naini, Ali; Czarnota, Gregory J.

    2017-04-01

    Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS model was constructed, which demonstrated a response prediction accuracy of 88% and ability to predict patient 5-year survival rates (p = 0.01). QUS features demonstrated superior performance in comparison to molecular markers and the combination of QUS and molecular markers did not improve response prediction. This study demonstrates, for the first time, that non-invasive QUS features in the core and margin of breast tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and predict five-year recurrence-free survival.

  4. 5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients

    PubMed Central

    Johnson, Kevin C.; Houseman, E. Andres; King, Jessica E.; von Herrmann, Katharine M.; Fadul, Camilo E.; Christensen, Brock C.

    2016-01-01

    Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and binding sites of transcription factors that drive cellular proliferation. In addition, model-based clustering results indicate that patients with low-5-hydroxymethylcytosine patterns have significantly poorer overall survival. Our results demonstrate that 5-hydroxymethylcytosine patterns are strongly related with transcription, localizes to disease-critical genes and are associated with patient prognosis. PMID:27886174

  5. Daily nest survival rates of Gunnison Sage-Grouse (Centrocercus minimus): assessing local- and landscape-scale drivers

    USGS Publications Warehouse

    Stanley, Thomas R.; Cameron Aldridge,; Joanne Saher,; Theresa Childers,

    2015-01-01

    The Gunnison Sage-Grouse (Centrocercus minimus) is a species of conservation concern and is a candidate for listing under the U.S. Endangered Species Act because of substantial declines in populations from historic levels. It is thought that loss, fragmentation, and deterioration of sagebrush (Artemisia spp.) habitat have contributed to the decline and isolation of this species into seven geographically distinct subpopulations. Nest survival is known to be a primary driver of demography of Greater Sage-Grouse (C. urophasianus), but no unbiased estimates of daily nest survival rates (hereafter nest survival) exist for Gunnison Sage-Grouse or published studies identifying factors that influence nest survival. We estimated nest survival of Gunnison Sage-Grouse for the western portion of Colorado's Gunnison Basin subpopulation, and assessed the effects and relative importance of local- and landscape-scale habitat characteristics on nest survival. Our top performing model was one that allowed variation in nest survival among areas, suggesting a larger landscape-area effect. Overall nest success during a 38-day nesting period (egg-laying plus incubation) was 50% (daily survival rate; SE  =  0.982 [0.003]), which is higher than previous estimates for Gunnison Sage-Grouse and generally higher than published for the closely related Greater Sage-Grouse. We did not find strong evidence that local-scale habitat variables were better predictors of nest survival than landscape-scale predictors, nor did we find strong evidence that any of the habitat variables we measured were good predictors of nest survival. Nest success of Gunnison Sage-Grouse in the western portion of the Gunnison Basin was higher than previously believed.

  6. Response to combined modality therapy correlates with survival in locally advanced non-small-cell lung cancer

    SciTech Connect

    Kim, Dong Wook; Shyr, Yu; Chen, Heidi; Akerley, Wallace; Johnson, David H.; Choy, Hak . E-mail: Hak.Choy@utsouthwestern.edu

    2005-11-15

    Purpose: Although concurrent chemoradiotherapy can now achieve demonstrated long-term survival in patients with locally advanced non-small-cell lung cancer (LANSCLC), it is difficult to predict which patients will benefit most from this therapeutic approach. Studies have suggested that local control, and the response to therapy, may be linked to improved survival; however, detailed analysis of the impact of tumor response to chemoradiotherapy on survival has not been thoroughly reported. Therefore, we sought to determine the impact of the response rate on survival for patients who were treated with combined modality therapy for LANSCLC. Methods and Materials: We reviewed the data from 116 patients enrolled between 1994 and 1997 in three trials investigating paclitaxel-based concurrent chemoradiotherapy for LANSCLC. Tumor size measurements were assessed immediately before and 2 months after completion of combined modality therapy to determine the response and to calculate the percentage of decrease in tumor size. Results: Patients with a response (complete or partial) had an improved 4-year overall survival rate compared with patients with no response (stable or progressive disease; 21.1% vs. 3.3%, p <0.0001) in the 109 assessable patients. Progression-free survival also improved significantly with response. An analysis of the percentage of decrease in tumor size vs. survival was performed (n = 74) using Cox proportion model analysis. After combined modality therapy, a 20%, 40%, 60%, 80%, and 100% decrease in tumor size conferred a 39%, 63%, 78%, 86%, and 92% reduction in risk of death compared with a 0% decrease in tumor size (p <0.0001). Conclusion: The response by conventional response criteria correlated strongly with improved overall survival and progression-free survival and an increasing percentage of decrease in tumor size resulted in a reduction in the risk of death. Additional investigation of the degree of response as a factor predictive of improved

  7. Radiation Treatment Time and Overall Survival in Locally Advanced Non-small Cell Lung Cancer.

    PubMed

    McMillan, Matthew T; Ojerholm, Eric; Verma, Vivek; Higgins, Kristin A; Singhal, Sunil; Predina, Jarrod D; Berman, Abigail T; Grover, Surbhi; Robinson, Cliff G; Simone, Charles B

    2017-08-01

    Prolonged radiation treatment (RT) time (RTT) has been associated with worse survival in several malignancies. The present study investigated whether delays during RT are associated with overall survival (OS) in non-small cell lung cancer (NSCLC). The National Cancer Database was queried for patients with stage III NSCLC who had received definitive concurrent chemotherapy and fractionated RT to standard doses (59.4-70.0 Gy) and fractionation from 2004 to 2013. The RTT was classified as standard or prolonged for each treatment regimen according to the radiation dose and number of fractions. Cox proportional hazards models were used to evaluate the association between the following factors and OS: RTT, RT fractionation, demographic and pathologic factors, and chemotherapeutic agents. Of 14,154 patients, the RTT was prolonged in 6262 (44.2%). Factors associated with prolonged RTT included female sex (odds ratio [OR] 1.21, P<.0001), black race (OR 1.20, P=.001), nonprivate health insurance (OR 1.30, P<.0001), and lower income (<$63,000 annually, OR 1.20, P<.0001). The median OS was significantly worse for patients with prolonged RTT than that for those with standard RTT (18.6 vs 22.7 months, P<.0001). Furthermore, the OS worsened with each cumulative interval of delay (standard RTT vs prolonged 1-2 days, 20.5 months, P=.009; prolonged 3-5 days, 17.9 months, P<.0001; prolonged 6-9 days, 17.7 months, P<.0001; prolonged >9 days, 17.1 months, P<.0001). On multivariable analysis, prolonged RTT was independently associated with inferior OS (hazard ratio 1.21, P<.0001). Prolonged RTT as a continuous variable was also significantly associated with worse OS (hazard ratio 1.001, P=.0007). Delays during RT appear to negatively affect survival for patients with locally advanced NSCLC. We have detailed the demographic and socioeconomic barriers influencing prolonged RTT as a method to address the health disparities in this regard. Cumulative interruptions of RT should be

  8. Impact of local treatment on overall survival of patients with metastatic prostate cancer: systematic review and meta-analysis

    PubMed Central

    Carneiro, Arie; Baccaglini, Willy; Glina, Felipe P.A.; Kayano, Paulo P.; Nunes, Victor M.; Smaletz, Oren; Bernardo, Wanderley Marques; de Carvalho, Icaro Thiago; Lemos, Gustavo Caserta

    2017-01-01

    ABSTRACT Context Currently, standard treatment of metastatic prostatic cancer (MPCa) is androgen-deprivation therapy (ADT). Recent studies suggested that local treatment of MPCa is related to increase of survival of those patients, as observed in other tumors. Objective To evaluate the impact of local treatment on overall survival and cancer specific survival in 3 and 5 years in patients with MPCa. Materials and Methods Systematic review and meta-analysis of population studies published at PubMed, Scielo, Lilacs, Cochrane and EMBASE databases until June 2016. Several large cohorts and Post-Roc studies were included, that evaluated patients with MPCa submitted to local treatment (LT) using radiotherapy (RDT), surgery (RP) or brachytherapy (BCT) or not submitted to local treatment (NLT). Results 34.338 patients were analyzed in six included papers, 31.653 submitted to NLT and 2.685 to LT. Overall survival in three years was significantly higher in patients submitted to LT versus NLT (64.2% vs. 44.5%; RD 0.19, 95% CI, 0.17-0.21; p<0.00001; I2=0%), as well as in five years (51.9% vs. 23.6%; RD 0.30, 95% CI, 0.11-0.49; p<0.00001; I2=97%). Sensitive analysis according to type of local treatment showed that surgery (78.2% and 45.0%; RD 0.31, 95% CI, 0.26-0.35; p<0.00001; I2=50%) and radiotherapy (60.4% and 44.5%; RD 0.17, 95% CI, 0.12-0.22; p<0.00001; I2=67%) presented better outcomes. Conclusion LT using RDT, RP or BCT seems to significantly improve overall survival and cancer-specific survival of patients with metastatic prostatic cancer. Prospective and randomized studies must be performed in order to confirm our results. PMID:27802009

  9. Survival and failure outcomes in locally advanced esthesioneuroblastoma: a single centre experience of 15 patients.

    PubMed

    Kumar, Ritesh; Ghoshal, Sushmita; Khosla, Divya; Bharti, Shreekant; Das, Ashim; Kumar, Narendra; Kapoor, Rakesh; Sharma, Suresh Chander

    2013-05-01

    Esthesioneuroblastoma (ENB) constitutes 3 % of all malignant intranasal tumors. As the tumor is very rare, the number of patients of ENB treated in individual departments is small. We present our institute's experience in combined modality management of 15 successive patients of ENB treated from 2006 to 2010. Clinical characteristics and treatment modality in form of surgery, radiotherapy and chemotherapy were noted. Kadish stage C was the most common stage (12 patients) followed by stage B (3 patients). Fourteen patients underwent primary surgery, of which nine had total excision and five had subtotal excision. One patient was treated with combination of chemotherapy (CT) and radiotherapy (RT). Median RT dose delivered was 54 Gy. Twelve patients received CT with cisplatin and etoposide. Overall, eight patients had complete response, five had partial response, while one had static disease and progressive disease each. Two patients had distant metastases. Four-year loco-regional control (LRC) was 25 % and 4-year overall survival (OS) was 45 %. Most common presentation in our series was locally advanced tumors. Most of these patients require adjuvant RT, which helps in significant LRC. Systemic CT benefits in inoperable, advanced and high risk tumors. Risk-adapted and multimodality approach is the need of hour to achieve good control rates while minimizing treatment related toxicity.

  10. Radicality of resection and survival after multimodality treatment is influenced by subsite of locally recurrent rectal cancer.

    PubMed

    Kusters, Miranda; Dresen, Raphaëla C; Martijn, Hendrik; Nieuwenhuijzen, Grard A; van de Velde, Cornelis J H; van den Berg, Hetty A; Beets-Tan, Regina G H; Rutten, Harm J T

    2009-12-01

    To analyze results of multimodality treatment in relation to subsite of locally recurrent rectal cancer (LRRC). A total of 170 patients with LRRC who underwent treatment between 1994 and 2008 were studied. The basic principle of multimodality treatment was preoperative (chemo)radiotherapy, intended radical surgery, and intraoperative radiotherapy. The subsites of LRRC were classified as presacral, posterolateral, (antero)lateral, anterior, anastomotic, or perineal. Subsites were related to radicality of the resection, local re-recurrence rate, distant metastasis rate, and cancer-specific survival. R0 resections were achieved in 54% of the patients, and 5-year cancer-specific survival was 40.5%. The worst outcomes were seen in presacral LRRC, with only 28% complete resections and 19% 5-year survival (p = 0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable outcomes, with 77% R0 resections and 60% 5-year survival (p = 0.04). Generally, if a complete resection was achieved, survival improved, except in posterolateral LRRC. Local re-recurrence and metastasis rate were lowest in anastomotic LRRC. Classification of the subsite of LRRC is a predictor of potentially resectable and consequently curable disease. Treatment of posterior LRRC imposes poor results, whereas anastomotic LRRC location shows superior results.

  11. Radicality of Resection and Survival After Multimodality Treatment is Influenced by Subsite of Locally Recurrent Rectal Cancer

    SciTech Connect

    Kusters, Miranda; Dresen, Raphaela C.; Martijn, Hendrik; Nieuwenhuijzen, Grard A.; Velde, Cornelis J.H. van de; Berg, Hetty A. van den; Beets-Tan, Regina G.H.; Rutten, Harm J.T.

    2009-12-01

    Purpose: To analyze results of multimodality treatment in relation to subsite of locally recurrent rectal cancer (LRRC). Method and Materials: A total of 170 patients with LRRC who underwent treatment between 1994 and 2008 were studied. The basic principle of multimodality treatment was preoperative (chemo)radiotherapy, intended radical surgery, and intraoperative radiotherapy. The subsites of LRRC were classified as presacral, posterolateral, (antero)lateral, anterior, anastomotic, or perineal. Subsites were related to radicality of the resection, local re-recurrence rate, distant metastasis rate, and cancer-specific survival. Results: R0 resections were achieved in 54% of the patients, and 5-year cancer-specific survival was 40.5%. The worst outcomes were seen in presacral LRRC, with only 28% complete resections and 19% 5-year survival (p = 0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable outcomes, with 77% R0 resections and 60% 5-year survival (p = 0.04). Generally, if a complete resection was achieved, survival improved, except in posterolateral LRRC. Local re-recurrence and metastasis rate were lowest in anastomotic LRRC. Conclusions: Classification of the subsite of LRRC is a predictor of potentially resectable and consequently curable disease. Treatment of posterior LRRC imposes poor results, whereas anastomotic LRRC location shows superior results.

  12. Local control of squamous cell carcinoma of the mobile tongue: an experience of different modalities

    SciTech Connect

    Kondo, M.; Hashimoto, S.; Dokiya, T.; Inuyama, Y.; Murakami, Y.; Nagai, T.; Asanami, S.; Fukutake, K.

    1986-05-01

    From 1966 through 1983, 163 patients with squamous cell carcinoma of the mobile tongue were treated. Fifty-two patients were staged as T1N0, 77 as T2N0, 14 as T2N+, 8 as T3N0, 7 as T3N+, and 5 as T4. The follow-ups were complete. Treatment modalities varied considerably during that period, because of increasing difficulty to use radioactive sources by regulations. All T3N+ and T4 patients died shortly after treatment. Five year absolute survivals for the T1N0, T2N0, T2N+, and T3N0 patients were 87%, 60%, 27% and 63%, respectively. Local recurrence free survivals at 5 years for the T1N0, T2N0, T2N+, and T3N0 patients were 72, 48, 58, and 88%, respectively. Local recurrence free survivals seemed to be better with Ra-226 needling +/- external irradiation (EXT) than other modalities. Because many patients with local recurrence were salvaged, ultimate local-disease-free survivals should also be considered. They were 96 and 70% at 5 years for the T1N0 patients treated with Ra-226 +/- EXT, and with surgery +/- EXT, respectively; the corresponding figures for the T2N0 patients were 83 and 64%. For these reasons, Ra-226 needling may be preferable to other modalities as initial treatment. Although cervical failures did not develop after 2 years of treatment, late local recurrences were rather common, even after 5 years. Long-term follow-up is mandatory for the management of the patients, and analyzing and comparing the results.

  13. Survival After Conservative Management Versus External Beam Radiation Therapy in Elderly Patients With Localized Prostate Cancer.

    PubMed

    Dell'Oglio, Paolo; Boehm, Katharina; Trudeau, Vincent; Tian, Zhe; Larcher, Alessandro; Leyh-Bannurah, Sami-Ramzi; Moschini, Marco; Capitanio, Umberto; Shariat, Shahrokh F; Briganti, Alberto; Montorsi, Francesco; Saad, Fred; Karakiewicz, Pierre I

    2016-12-01

    To compare survival in elderly men with clinically localized prostate cancer (PCa) according to treatment type, defined as radiation therapy (RT) with or without androgen deprivation therapy (ADT) versus conservative management (observation). In the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 23,790 patients aged 80 years or more with clinically localized PCa treated with either RT or observation between 1991 and 2009. Competing risks analyses focused on cancer-specific mortality and other-cause mortality, after accounting for confounders. All analyses were repeated after stratification according to grade (well-differentiated vs moderately differentiated vs poorly differentiated disease), race, and United States region, in patients with no comorbidities and in patients with at least 1 comorbidity. Analyses were repeated within most contemporary patients, namely those treated between 2001 and 2009. Radiation therapy was associated with more favorable cancer-specific mortality rates than observation in patients with moderately differentiated disease (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.66-0.94; P=.009) and in patients with poorly differentiated disease (HR 0.58; 95% CI 0.49-0.69; P<.001). Conversely, the benefit of RT was not observed in well-differentiated disease. The benefit of RT was confirmed in black men (HR 0.54; 95% CI 0.35-0.83; P=.004), across all United States regions (all P≤.004), in the subgroups of the healthiest patients (HR 0.67; 95% CI 0.57-0.78; P<.001), in patients with at least 1 comorbidity (HR 0.69; 95% CI 0.56-0.83; P<.001), and in most contemporary patients (HR 0.55; 95% CI 0.46-0.66; P<.001). Radiation therapy seems to be associated with a reduction in the risk of death from PCa relative to observation in elderly patients with clinically localized PCa, except for those with well-differentiated disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Soft tissue extension increases the risk of local recurrence after curettage with adjuvants for giant-cell tumor of the long bones.

    PubMed

    van der Heijden, L; van de Sande, M A; Dijkstra, P D

    2012-08-01

    Risk factors for local recurrence of giant-cell tumor of bone (GCTB) have mostly been studied in heterogeneous treatment groups, including resection and intralesional treatment. The aim of the study was the identification of individual risk factors after curettage with adjuvants in GCTB. Of 147 patients treated for primary GCTB between 1981 and 2009, 93 patients were included in this retrospective single-center study. All patients were treated with curettage and polymethylmethacrylate (PMMA) with (n = 75) or without (n = 18) phenol. Mean follow-up was 8 (2-24) years. Recurrence-free survival was assessed for treatment modalities. Age, sex, tumor location, soft tissue extension, and pathological fractures were scored for every patient and included in a Cox regression analysis. The recurrence rate after the first procedure was 25/93. Recurrence-free survival for PMMA and phenol and for PMMA alone was similar. Eventually, local control was achieved using 1 or multiple intralesional procedures in 85 patients. Resection was required in 8 patients. A higher risk of local recurrence was found for soft tissue extension (HR = 5, 95% CI: 2-12), but not for age below 30, sex, location (distal radius vs. other), or pathological fracture. Curettage with adjuvants is a feasible first-choice treatment option for GCTB, with good oncological outcome and joint preservation. Soft tissue extension strongly increased the risk of local recurrence, whereas age, sex, location, and pathological fractures did not.

  15. Survival outcome of salvage hepatectomy in patients with local, recurrent hepatocellular carcinoma who underwent radiofrequency ablation as their first treatment.

    PubMed

    Ueno, Masaki; Nakai, Takuya; Hayashi, Michihiro; Hirokawa, Fumitoshi; Nagano, Hiroaki; Wada, Hiroshi; Kaibori, Masaki; Matsui, Kosuke; Tanaka, Shogo; Yamaue, Hiroki; Kubo, Shoji

    2016-09-01

    Local recurrence is a specific problem after radiofrequency ablation of small hepatocellular carcinoma, and additional treatment is an important issue. We aimed to investigate the outcome of salvage hepatectomy in patients who develop local, recurrent hepatocellular carcinoma after treatment with radiofrequency ablation. From 2001-2013, we reviewed 58 patients from 6 university hospitals with local, recurrent hepatocellular carcinoma who underwent salvage hepatectomy after their initial radiofrequency ablation treatment. Pathologic characteristics and prognostic factors influencing overall survival were analyzed. Noncurative resection, des-gamma carboxy prothrombin levels >40 mAU/mL, and multiple preceding treatments before salvage hepatectomy were negative prognostic factors for overall survival. The 5-year survivals for the prognostic factors were 0%, 24%, and 30%, respectively, after salvage hepatectomy, and 0%, 54%, and 54% after initial radiofrequency ablation treatment, respectively. As for the pathologic finding of local, recurrent hepatocellular carcinoma after radiofrequency ablation, vascular invasion was observed frequently in patients with increases in des-gamma carboxy prothrombin levels and with multiple preceding treatments before salvage hepatectomy with a frequency of 59% and 53%, respectively (P < .01 and .05). Noncurative resection, increases in serum des-gamma carboxy prothrombin, and multiple preceding treatments were prognostic factors for subsequent salvage hepatectomy; nevertheless, survival outcomes were still acceptable when a curative salvage hepatectomy was performed. Increases in serum des-gamma carboxy prothrombin and multiple preceding treatments were positive predictors for pathologic vascular invasion. These factors should be taken into consideration when selecting treatment modalities for locally recurrent hepatocellular carcinoma following radiofrequency ablation. Repetition of unsuccessful, loco-regional treatment would appear

  16. Postoperative radiotherapy improves local control and survival in patients with uterine leiomyosarcoma

    PubMed Central

    2013-01-01

    Background To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT. Methods From 1998–2008, 69 patients with primary uterine LMS underwent hysterectomy with or without pelvic radiotherapy to a median dose of 45 Gy. Univariate analysis was performed using the Kaplan-Meier method and cumulative-incidence function, and multivariate analyses using Fine and Gray or Cox proportional hazard models. Results Following surgery, 32 out of 69 patients received RT. There was no evidence of any correlation between patient, disease and treatment characteristics and the use of RT. Median follow-up was 57 months. RT was associated with reduced local recurrence (3y LR 19% vs. 39%; Gray’s p = 0.019) and improved overall survival (3y OS 69% vs. 35%; log-rank p = 0.025) on univariate analysis. Multivariate analysis demonstrated that RT reduced LR (HR: 0.28, CI: 0.11-0.69, p = 0.006) and increased OS (HR: 0.44, CI: 0.23-0.85, p = 0.014) independent of other clinical and pathologic factors. Positive surgical margins increased the odds of LR (HR: 5.6, CI: 2.3-13.4, p = 0.00012). Large tumor size and advanced stage (II-IV) were associated with the development of distant metastases and inferior OS. Conclusions Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS. PMID:23705661

  17. Ecological Values amid Local Interests: Natural Resource Conservation, Social Differentiation, and Human Survival in Honduras

    ERIC Educational Resources Information Center

    Gareau, Brian J.

    2007-01-01

    Local peoples living in protected areas often have a different understanding about their natural space than do non-local groups that promote and declare such areas "protected." By designing protected areas without local involvement, or understandings of local social differentiation and power, natural resources management schemes will…

  18. Ecological Values amid Local Interests: Natural Resource Conservation, Social Differentiation, and Human Survival in Honduras

    ERIC Educational Resources Information Center

    Gareau, Brian J.

    2007-01-01

    Local peoples living in protected areas often have a different understanding about their natural space than do non-local groups that promote and declare such areas "protected." By designing protected areas without local involvement, or understandings of local social differentiation and power, natural resources management schemes will…

  19. Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence.

    PubMed

    Perez, Rodrigo Oliva; Habr-Gama, Angelita; São Julião, Guilherme Pagin; Proscurshim, Igor; Fernandez, Laura Melina; de Azevedo, Rafael Ulysses; Vailati, Bruna B; Fernandes, Felipe Alexandre; Gama-Rodrigues, Joaquim

    2016-04-01

    Transanal endoscopic microsurgery (TEM) has been considered an alternative for selected patients with rectal cancer following neoadjuvant chemoradiation (CRT). Immediate total mesorectal completion for all patients with unfavorable pathological features would result in unnecessary protectomies in a significant proportion of patients. Instead, salvage total mesorectal excision (TME) could be restricted for patients developing local recurrence. The aim of the present study is to determine oncological outcomes of salvage resection for local recurrences following CRT and TEM. Consecutive patients undergoing TEM following neoadjuvant CRT for rectal cancer were reviewed. Patients with "near" complete response to CRT (≤3 cm; ycT1-2N0) were offered TEM. Salvage surgery was attempted in the event of a local recurrence. A total of 53 patients were managed by CRT followed by TEM. Unfavorable pathological features were present in 36 patients (68 %). None of the patients underwent immediate completion TME. There were 12 patients who developed local recurrence resulting in a 2-year local recurrence-free survival of 77 % (95 % CI, 53-100 %). Of these patients, 9 developed exclusively local recurrences, and all had at least 1 unfavorable pathological feature in the specimen after TEM (100 %). Eight patients (8 of 9) underwent salvage resection (abdominoperineal resection [APR] in 87 %) with CRM+ in 7 of 8 patients (87 %). Four patients developed local re-recurrence after a median 36 months of follow-up. The 2-year local re-recurrence free survival was 60 %. Salvage resection for local recurrence following CRT and TEM is associated with high rates of R1 resection (CRM+) and local re-recurrence. Immediate completion of TME should be considered for patients with unfavorable pathological features after TEM.

  20. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    SciTech Connect

    Alberda, Wijnand J.; Verhoef, Cornelis; Nuyttens, Joost J.; Meerten, Esther van; Rothbarth, Joost; Wilt, Johannes H.W. de; Burger, Jacobus W.A.

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  1. Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

    PubMed

    Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

    2016-08-01

    Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. © 2016 UICC.

  2. Surgical and Survival Outcomes Following Pelvic Exenteration for Locally Advanced Primary Rectal Cancer: Results from an International Collaboration.

    PubMed

    2017-09-21

    The aim of the study was to analyze data from an international collaboration, and ascertain prognostic indicators that inform clinical decision-making and practices regarding the role of pelvic exenteration for locally advanced primary rectal cancer (LARC). With improved national screening programs fewer patients present with LARC. Despite this, select cohorts of patients require pelvic exenteration. To date, the majority of outcome data are from single-center series. Anonymized data from 14 countries on patients who had pelvic exenteration for LARC between 2004 and 2014 were accumulated. The primary endpoint was overall survival. The impact of resection margin, nodal status, bone resection, and use of neoadjuvant therapy (before exenteration) on survival was evaluated using multivariable analysis. Of 1291 patients, 778 (60.3%) were male with a median (range) age of 63 (18-90) years; 78.1% received neoadjuvant therapy. Bone resection en bloc was performed in 8.2% of patients (n = 106), and 22.6% (n = 292) had resection combined with flap reconstruction. Negative resection margin (R0 resection) was achieved in 79.9%. The 30-day postoperative mortality was 1.5%.The median overall survival following R0, R1, and R2 resection was 43, 21, and 10 months (P < 0.001) with a 3-year survival of 56.4%, 29.6%, and 8.1%, respectively (P < 0.001); 37.8% of patients experienced one or more major complication. Neoadjuvant therapy increased the risk of 30-day morbidity (P < 0.012). Multivariable analysis identified resection margin and nodal status as significant determinants of overall survival (other than advanced age). Attainment of negative resection margins (R0) is the key to survival. Neoadjuvant therapy may improve survival; however, it does so at the increased risk of postoperative morbidity.

  3. Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis

    PubMed Central

    Sahu, Arvind; Ramaswamy, Anant; Sirohi, Bhawna; Bose, Subhadeep; Talreja, Vikas; Goel, Mahesh; Patkar, Shraddha; Desouza, Ashwin; Shrikhande, Shailesh V.

    2017-01-01

    Purpose Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resection, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial. PMID:28337360

  4. Habitat edges have weak effects on duck nest survival at local spatial scales

    USGS Publications Warehouse

    Raquel, Amelia J; Ringelman, Kevin M.; Ackerman, Josh; Eadie, John M.

    2015-01-01

    Edge effects on nesting success have been documented in breeding birds in a variety of contexts, but there is still uncertainty in how edge type and spatial scale determine the magnitude and detectability of edge effects. Habitat edges are often viewed as predator corridors that surround or penetrate core habitat and increase the risk of predation for nearby nests. We studied the effects of three different types of potential predator corridors (main perimeter roads, field boundaries, and ATV trails within fields) on waterfowl nest survival in California. We measured the distance from duck nests to the nearest edge of each type, and used distance as a covariate in a logistic exposure analysis of nest survival. We found only weak evidence for edge effects due to predation. The best supported model of nest survival included all three distance categories, and while all coefficient estimates were positive (indicating that survival increased with distance from edge), 85% coefficient confidence intervals approached or bounded zero indicating an overall weak effect of habitat edges on nest success. We suggest that given the configuration of edges at our site, there may be few areas far enough from hard edges to be considered ‘core’ habitat, making edge effects on nest survival particularly difficult to detect.

  5. Effect of Radiotherapy Planning Complexity on Survival of Elderly Patients With Unresected Localized Lung Cancer

    SciTech Connect

    Park, Chang H.; Bonomi, Marcelo; Cesaretti, Jamie; Neugut, Alfred I.; Wisnivesky, Juan P.

    2011-11-01

    Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials.

  6. Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally advanced carcinoma of the uterine cervix.

    PubMed

    Corn, B W; Hanlon, A L; Pajak, T F; Owen, J; Hanks, G E

    1994-06-01

    The purpose of this study was to document whether the technical qualities of a brachytherapy application impacts on the outcome of patients with locally advanced cervix cancer treated by definitive irradiation. A previous report from the patterns of care study demonstrated the importance of brachytherapy in the treatment of locally advanced cervix cancer. Locally advanced disease was defined as FIGO stages Ib (if tumor diameter was < or = 4 cm), IIb (if disease was bilateral or involved the lateral aspect of either parametrium), and III. Localization films from 128 patients with locally advanced squamous cell carcinoma of the cervix were reviewed by a radiation physicist and a radiation oncologist with expertise in gynecologic radiotherapy. All patients received external beam irradiation followed by one brachytherapy application (median point A dose = 8040 cGy; range, 4083-10,020 cGy). Brachytherapy parameters assessed were (a) the distance between the right colpostat source and the distal tandem source, (b) the distance between the left colpostat source and the distal tandem source, and (c) the symmetry of colpostat placement. Implants were scored as "ideal" (n = 8) when all three parameters were deemed satisfactory, "unacceptable" (n = 17) when none of the parameters was deemed satisfactory, and "adequate" (n = 41) in all other cases. Significantly improved 5-year local control was seen when comparing ideal and adequate placements to unacceptable placements (68% vs 34%, P = 0.02). A strong trend toward improved 5-year survival was also noted among the group with ideal and adequate implants as opposed to unacceptable implants (60% vs 40%). Multivariate analysis showed that the technical adequacy of the brachytherapy implant was the most important prognostic discriminant of local control. In conclusion, these analyses demonstrate the direct influence of competent technical implant performance on tumor control and even survival. While only a small fraction of

  7. Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma.

    PubMed

    Geiger, Jessica L; Lazim, Ahmed F; Walsh, Francis J; Foote, Robert L; Moore, Eric J; Okuno, Scott H; Olsen, Kerry D; Kasperbauer, Jan L; Price, Daniel L; Garces, Yolanda I; Ma, Daniel J; Neben-Wittich, Michelle A; Molina, Julian R; Garcia, Joaquin J; Price, Katharine A R

    2014-04-01

    Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent. This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16-positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose or weekly cisplatin. Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients. 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p=0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p=0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p=0.56), and 3-year recurrence free survival of 84% and 82% (p=0.93). Extracapsular extension did not affect prognosis in either group. No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be a better treatment for patients with HPV-positive oropharynx cancer to preserve survival and minimize toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. A Population-based Model of Local Control and Survival Benefit of Radiotherapy for Lung Cancer.

    PubMed

    Shafiq, J; Hanna, T P; Vinod, S K; Delaney, G P; Barton, M B

    2016-10-01

    To estimate the population-based locoregional control and overall survival benefits of radiotherapy for lung cancer if the whole population were treated according to evidence-based guidelines. These estimates were based on a published radiotherapy utilisation (RTU) model that has been used to estimate the demand and planning of radiotherapy services nationally and internationally. The lung cancer RTU model was extended to incorporate an estimate of benefits of radiotherapy alone, and of radiotherapy in conjunction with concurrent chemotherapy (CRT). Benefits were defined as the proportional gains in locoregional control and overall survival from radiotherapy over no radiotherapy for radical indications, and from postoperative radiotherapy over surgery alone for adjuvant indications. A literature review (1990-2015) was conducted to identify benefit estimates of individual radiotherapy indications and summed to estimate the population-based gains for these outcomes. Model robustness was tested through univariate and multivariate sensitivity analyses. If evidence-based radiotherapy recommendations are followed for the whole lung cancer population, the model estimated that radiotherapy alone would result in a gain of 8.3% (95% confidence interval 7.4-9.2%) in 5 year locoregional control, 11.4% (10.8-12.0%) in 2 year overall survival and 4.0% (3.6-4.4%) in 5 year overall survival. For the use of CRT over radiotherapy alone, estimated benefits would be: locoregional control 1.7% (0.8-2.4%), 2 year overall survival 1.7% (0.5-2.8%) and 5 year overall survival 1.2% (0.7-1.9%). The model provided estimates of radiotherapy benefit that could be achieved if treatment guidelines are followed for all cancer patients. These can be used as a benchmark so that the effects of a shortfall in the utilisation of radiotherapy can be better understood and addressed. The model can be adapted to other populations with known epidemiological parameters to ensure the planning of equitable

  9. Effect of Radiotherapy Interruptions on Survival in Medicare Enrollees With Local and Regional Head-and-Neck Cancer

    SciTech Connect

    Fesinmeyer, Megan Dann; Mehta, Vivek; Blough, David; Tock, Lauri; Ramsey, Scott D.

    2010-11-01

    Purpose: To investigate whether interruptions in radiotherapy are associated with decreased survival in a population-based sample of head-and-neck cancer patients. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare linked database we identified Medicare beneficiaries aged 66 years and older diagnosed with local-regional head-and-neck cancer during the period 1997-2003. We examined claims records of 3864 patients completing radiotherapy for the presence of one or more 5-30-day interruption(s) in therapy. We then performed Cox regression analyses to estimate the association between therapy interruptions and survival. Results: Patients with laryngeal tumors who experienced an interruption in radiotherapy had a 68% (95% confidence interval, 41-200%) increased risk of death, compared with patients with no interruptions. Patients with nasal cavity, nasopharynx, oral, salivary gland, and sinus tumors had similar associations between interruptions and increased risk of death, but these did not reach statistical significance because of small sample sizes. Conclusions: Treatment interruptions seem to influence survival time among patients with laryngeal tumors completing a full course of radiotherapy. At all head-and-neck sites, the association between interruptions and survival is sensitive to confounding by stage and other treatments. Further research is needed to develop methods to identify patients most susceptible to interruption-induced mortality.

  10. Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

    PubMed

    Hassel, Alexander J; Danner, Daniel; Freier, Kolja; Hofele, Christof; Becker-Bikowski, Kirsten; Engel, Michael

    2012-06-01

    This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa.

  11. Childhood craniopharyngioma: survival, local control, endocrine and neurologic function following radiotherapy

    SciTech Connect

    Danoff, B.F.; Cowchock, F.S.; Kramer, S.

    1983-02-01

    Between 1961 and 1978, 19 patients with a diagnosis of childhood or teenage craniopharyngioma received supervoltage radiotherapy. All patients had previously undergone either partial surgical resection (10 patients), total gross resection (3 patients), or aspiration and biopsy (6 patients). Fourteen patients were treated primarily and five were treated for recurrence. The five-year survival was 73% with a 10-year survival of 64%. Sixteen percent developed a recurrence following radiotherapy. Long term effects were assesed in terms of neurologic, intellectual, psychological and endocrine function. Seventy-nine percent had none or minimal neurologic disability. The mean full scale IQ for the group was 90. There were no additional endocrine deficiencies that could be directly attributed to radiation. Behavioral disorders occurred in 50%. These results are at least comparable, if not superior, to those of surgery.

  12. Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival.

    PubMed

    Gong, N; Pleyer, U; Volk, H-D; Ritter, T

    2007-03-01

    In this study, we explored the immunomodulatory effects of viral interleukin (IL) IL-10 after ex vivo and in vivo gene transfer in experimental corneal transplantation. Wistar-Furth rats were used as donors and major histocompatibility complex class I/II-disparate Lewis rats served as recipients. For ex vivo gene therapy donor corneas were either transfected with liposome/vIL-10 plasmid DNA mixtures or transduced with a vIL-10 expressing adenovirus vector (AdvIL-10). For in vivo studies, recipients were treated with AdvIL-10 intraperitoneally 1 day before transplantation. Graft survival was analysed using the Kaplan-Meier survival method. To monitor the efficacy of the therapy messenger RNA (mRNA) cytokine expression profiles in grafts and draining lymph nodes were analysed by quantitative real-time reverse transcription-polymerase chain reaction. Moreover, anti-adenovirus immunity was also investigated. Neither ex vivo liposome-mediated vIL-10 gene transfer nor ex vivo AdvIL-10 gene transfer led to prolonged corneal allograft survival. In contrast, corneal allograft survival was significantly prolonged in animals receiving systemic AdvIL-10 gene transfer. Moreover, only systemic vIL-10 gene therapy modulated the cytokine mRNA expression profile in draining lymph nodes. Interestingly, systemic AdvIL-10 gene transfer could not inhibit the generation of anti-adenovirus antibodies. Our data indicate systemic expression of the vIL-10 gene is required to modulate the cytokine expression profile in the draining lymph nodes, which might be a pre-requisite for the success of cytokine gene therapy.

  13. Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance).

    PubMed

    Niedzwiecki, Donna; Frankel, Wendy L; Venook, Alan P; Ye, Xing; Friedman, Paula N; Goldberg, Richard M; Mayer, Robert J; Colacchio, Thomas Anthony; Mulligan, Jude Marie; Davison, Timothy S; O'Brien, Eamonn; Kerr, Peter; Johnston, Patrick G; Kennedy, Richard D; Harkin, D Paul; Schilsky, Richard L; Bertagnolli, Monica M; Warren, Robert S; Innocenti, Federico

    2016-09-01

    Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581. C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables. Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk. ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis. © 2016 by American Society of Clinical Oncology.

  14. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

    PubMed

    Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

    2011-10-01

    To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

  15. [A case of breast cancer with postoperative metastasis to the supraclavicular lymph nodes-recurrence-free survival achieved by surgical excision following chemotherapy].

    PubMed

    Tezuka, Kenji; Dan, Nobuhiro; Tendo, Masashige; Hori, Takeshi; Nishino, Hiroji

    2011-08-01

    The patient, a 58-year-old woman, underwent a partial excision of the right breast and an axillary lymph node dissection in October 2004. The histopathological findings were: solid tubular carcinoma with metastasis to 17 axillary lymph nodes; triple negative-type breast cancer. As adjuvant therapy, FEC60 was administered 6 times, followed by radiotherapy applied to the residual breast and the right supraclavicular fossa. In Novermber 2007, she noted a tumorous growth above the right clavicle. The pathological diagnosis via fine needle biopsy was adenocarcinoma. An oral antineoplastic agent was given for about 6 months, but did not alter the lymph nodes. No distant recurrence was noted during this time. In August 2008, the right supraclavicular lymph nodes were dissected. The patient has been under observation without treatment, but no signs of recurrence have been noted. It was thought that excision of the recurrent supra-clavicular lymph nodes should be considered after careful examination in some individual cases.

  16. PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy

    PubMed Central

    Dietrich, Jörn; Sailer, Verena; Ellinger, Jörg; Dietrich, Dimo; Kristiansen, Glen

    2016-01-01

    Background The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa). Results In the training cohort, normal tissue showed significantly lower levels of mPD-L1 compared to tumor tissue. High mPD-L1 in PCa was associated with biochemical recurrence (BCR) in univariate Cox proportional hazards (hazard ratio (HR)=2.60 [95%CI: 1.50-4.51], p=0.001) and Kaplan-Meier analyses (p<0.001). These results were corroborated in an independent validation cohort in univariate Cox (HR=1.24 [95%CI: 1.08-1.43], p=0.002) and Kaplan-Meier analyses (p=0.029). Although mPD-L1 and PD-L1 protein expression did not correlate in the validation cohort, both parameters added significant prognostic information in bivariate Cox analysis (HR=1.22 [95%CI: 1.05-1.42], p=0.008 for mPD-L1 and HR=2.58 [95%CI: 1.43-4.63], p=0.002 for PD-L1 protein expression). Methods mPD-L1 was analyzed in a training cohort from The Cancer Genome Atlas (n=498) and was subsequently measured in an independent validation cohort (n=299) by quantitative methylation-specific real-time PCR. All patients had undergone radical prostatectomy. Conclusions mPD-L1 is a promising biomarker for the risk stratification of PCa patients and might offer additional relevant prognostic information to the implemented clinical parameters, particularly in the setting of immune checkpoint inhibition. PMID:27835597

  17. Neutralizing Interleukin-1β (IL-1β) Induces β-Cell Survival by Maintaining PDX1 Protein Nuclear Localization*

    PubMed Central

    Ardestani, Amin; Sauter, Nadine S.; Paroni, Federico; Dharmadhikari, Gitanjali; Cho, Jae-Hyoung; Lupi, Roberto; Marchetti, Piero; Oberholzer, José; Conte, Julie Kerr; Maedler, Kathrin

    2011-01-01

    The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. Acute glucose exposure leads to translocalization of PDX1 to the nucleoplasm, whereas under conditions of oxidative stress, PDX1 shuttles from the nucleus to the cytosol. Here we show that cytosolic PDX1 expression correlated with β-cell failure in diabetes. In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. In diabetic islets, PDX1 protein was localized in the cytosol, whereas in non-diabetic controls, PDX1 was in the nucleus. In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. PMID:21393239

  18. Impact of lymph node invasion and sarcomatoid differentiation on the survival of patients with locally advanced renal cell carcinoma.

    PubMed

    Rodríguez-Covarrubias, Francisco; Castillejos-Molina, Ricardo; Sotomayor, Mariano; Méndez-Probst, Carlos E; Gómez-Alvarado, Martha Olivia; Uribe-Uribe, Norma; Gabilondo, Fernando; Feria-Bernal, Guillermo

    2010-01-01

    The application of current prognosticators in locally advanced nonmetastatic renal cell carcinoma (RCC) is controversial. We analyzed the impact of clinical and pathological variables on the survival of this subset of patients. We studied patients with RCC in stages III and IV without metastases, treated surgically between 1980 and 2009. We calculated disease-free (DFS) and cancer-specific survival (CSS), and the relation of clinical and pathological variables with these end-points. We identified 126 patients with locally advanced RCC; 8.7% had sarcomatoid differentiation. Tumor stage was pT3a in 48% and pT3b in 42%; 11.9% had lymph node invasion (N+). Patients with N- and N+ had a 10-year DFS of 49.0 and 23.4%, respectively (p = 0.0001). In multivariate analysis N+ (p = 0.0002) was the strongest predictor of DFS. The 10-year CSS of patients without sarcomatoid differentiation was 53.1% while those with sarcomatoid differentiation did not reach the median time to death (p < 0.0001). In multivariate analysis, sarcomatoid differentiation (p = 0.01) was the strongest predictor of CSS. Locally advanced RCC portends poor prognosis. Preoperatively, weight loss and Eastern Cooperative Oncology Group performance status are predictors of recurrence and mortality, respectively. However, the most powerful predictors of DFS and CSS in our cohort were lymph node status and sarcomatoid differentiation. Copyright (c) 2010 S. Karger AG, Basel.

  19. Detritus Quality and Locality Determines Survival and Mass, but Not Export, of Wood Frogs at Metamorphosis

    PubMed Central

    Milanovich, Joseph R.; Barrett, Kyle; Crawford, John A.

    2016-01-01

    Single-site experiments have demonstrated detritus quality in wetlands can have strongly negative, neutral, and even positive influences on wildlife. However, an examination of the influence of detritus quality across several regions is lacking and can provide information on whether impacts from variation in detritus quality are consistent across species with wide ranges. To address this gap in regional studies we examined effects of emergent and allochthonous detritus of different nutrient qualities on amphibians and assessed a mechanism that may contribute to potential impacts. We used aquatic mesocosms to raise wood frogs (Rana sylvatica) from two regions of the United States with whole plants from purple loosestrife (Lythrum salicaria), leaf litter from native hardwood trees, and a mixture of both. We examined several metrics of amphibian fitness and life history, including survival, number of days to metamorphosis, and size at metamorphosis. Further, we quantified whether the effects of detritus type could translate to variation in anuran biomass or standing stock of nitrogen or phosphorus export. Our results show detritus with high nutrient quality (purple loosestrife) negatively influenced survival of wood frogs, but increased size of metamorphic individuals in two different regions of the United States. Despite the decrease in survival, the increase in size of post-metamorphic anurans raised with high quality detritus resulted in anuran biomass and standing stock of N and P export being similar across treatments at both locations. These results further demonstrate the role of plant quality in shaping wetland ecosystem dynamics, and represent the first demonstration that effects are consistent within species across ecoregional boundaries. PMID:27824915

  20. Survival, growth, and localization of epiphytic fitness mutants of pseudomonas syringae on leaves

    SciTech Connect

    Beattie, G.A.; Lindow, S.E. )

    1994-10-01

    Among 82 epiphytic fitness mutants of a Pseudomonas syringae pv. syringae strain that were characterized in a previous study, 4 mutants were particularly intolerant of the stresses associated with dry leaf surfaces. These four mutants each exhibited distinctive behaviors when inoculated into and into plant leaves. For example, while non showed measurable growth on dry potato leaf surfaces, they grew to different population sizes in the intercellular space of bean leaves and on dry bean leaf surfaces, and one mutant appeared incapable of growth in both environments although it grew well on moist bean leaves. The presence of the parental strain did not influence the survival of the mutants immediately following exposure of leaves to dry, high-light incubation conditions, suggesting that the reduced survival of the mutants did not result from an inability to produce extracellular factors in planta. On moist bean leaves that were colonized by either a mutant or the wild type, the proportion of the total epiphytic population that was located in sizes protected from a surface sterilant was smaller for the mutants than for the wild type, indicating that the mutants were reduced in their ability to locate, multiply in, and/or survive in such protected sites. This reduced ability was only one of possible several factors contributing to the reduced epiphytic fitness of each mutant. Their reduced fitness was not specific to the host plant bean, since they also exhibited reduced fitness on the nonhost plant potato; the functions altered in these strains are thus of interest for their contribution to the general fitness of bacterial epiphytes. 52 refs., 6 figs., 1 tab.

  1. Detritus Quality and Locality Determines Survival and Mass, but Not Export, of Wood Frogs at Metamorphosis.

    PubMed

    Milanovich, Joseph R; Barrett, Kyle; Crawford, John A

    2016-01-01

    Single-site experiments have demonstrated detritus quality in wetlands can have strongly negative, neutral, and even positive influences on wildlife. However, an examination of the influence of detritus quality across several regions is lacking and can provide information on whether impacts from variation in detritus quality are consistent across species with wide ranges. To address this gap in regional studies we examined effects of emergent and allochthonous detritus of different nutrient qualities on amphibians and assessed a mechanism that may contribute to potential impacts. We used aquatic mesocosms to raise wood frogs (Rana sylvatica) from two regions of the United States with whole plants from purple loosestrife (Lythrum salicaria), leaf litter from native hardwood trees, and a mixture of both. We examined several metrics of amphibian fitness and life history, including survival, number of days to metamorphosis, and size at metamorphosis. Further, we quantified whether the effects of detritus type could translate to variation in anuran biomass or standing stock of nitrogen or phosphorus export. Our results show detritus with high nutrient quality (purple loosestrife) negatively influenced survival of wood frogs, but increased size of metamorphic individuals in two different regions of the United States. Despite the decrease in survival, the increase in size of post-metamorphic anurans raised with high quality detritus resulted in anuran biomass and standing stock of N and P export being similar across treatments at both locations. These results further demonstrate the role of plant quality in shaping wetland ecosystem dynamics, and represent the first demonstration that effects are consistent within species across ecoregional boundaries.

  2. Lymphopenia and its association with survival in patients with locally advanced cervical cancer

    PubMed Central

    Cobb, Lauren P.; Cholakian, Diana; Kong, Xiangrong; Fader, Amanda N.; Levinson, Kimberly L.; Tanner, Edward J.; Stone, Rebecca L.; Piotrowski, Anna; Grossman, Stuart; Roche, Kara Long

    2016-01-01

    Objective To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. Methods A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). Results Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs 45.0 months, P = 0.03) and similar 25th percentile PFS (6.3 vs 7.7 months, P = 0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05–1.03; P = 0.053) and 58% decrease in hazards of death (HR: 0.42; 95% CI 0.12–1.46; P = 0.17) respectively. Conclusion More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor. PMID:26571200

  3. Lymphopenia and its association with survival in patients with locally advanced cervical cancer.

    PubMed

    Wu, Emily S; Oduyebo, Titilope; Cobb, Lauren P; Cholakian, Diana; Kong, Xiangrong; Fader, Amanda N; Levinson, Kimberly L; Tanner, Edward J; Stone, Rebecca L; Piotrowski, Anna; Grossman, Stuart; Roche, Kara Long

    2016-01-01

    To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs. 45.0 months, P=0.03) and similar 25th percentile PFS (6.3 vs. 7.7 months, P=0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05-1.03; P=0.053) and 58% decrease in hazards of death (HR: 0.42; 95%CI 0.12-1.46; P=0.17) respectively. More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Influence of close resection margins on local recurrence and disease-specific survival in oral and oropharyngeal carcinoma.

    PubMed

    Wong, Ling Siew; McMahon, Jeremy; Devine, John; McLellan, Douglas; Thompson, Ewen; Farrow, Adrian; Moos, Khursheed; Ayoub, Ashraf

    2012-03-01

    There is a lack of consistency among published reports in the definition of what constitutes close resection margins (1-5mm) in the surgical treatment of oral and oropharyngeal squamous cell carcinoma (SCC). Our aim was to define what would constitute close resection margins in predicting local recurrence and disease-specific survival. The study comprised 192 previously untreated patients with oral and oropharyngeal SCC who were recruited at the Southern General Hospital, Glasgow, from 2001 to 2007 with a minimum follow-up of 2 years. Resection was the primary treatment and the surgical margins were recorded for all patients. Statistical analyses were aided by the Statistical Package for the Social Sciences, version 15.0, and MedCalc software. The status of the surgical margins was evaluated using a receiver operating characteristic (ROC) curve to define the cut-off point. Cox's proportional hazard model was used to establish predictive factors for local recurrence and disease-specific survival. Of 192 patients, 23 (12%) had involved margins (<1.0mm), 107 (56%) had close margins (1.0-2.0mm (16.1%); 2.1-3.0mm (12%); 3.1-4.0mm (10.4%); 4.1-5.0mm (17.2%), and 62 (32.3%) had clear margins (>5mm). No predictive cut-off point was found that related close surgical margins to local recurrence. However, there was a significant adverse association between surgical margins ≤1.6mm and disease-specific survival. In recommending postoperative adjuvant treatment for oral and oropharyngeal SCC, we suggest that surgical margins within 2mm should be considered as the cut-off. However, other clinical and pathological prognostic factors should also be taken into consideration when recommending further treatment.

  5. Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

    SciTech Connect

    Winkfield, Karen M.; Chen Minghui; Dosoretz, Daniel E.; Salenius, Sharon A.; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2011-11-15

    Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.

  6. Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

    PubMed

    Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

    2016-03-30

    Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization

  7. Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons

    PubMed Central

    Fallini, Claudia; Donlin-Asp, Paul G.; Rouanet, Jeremy P.

    2016-01-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels of GAP43 mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restores GAP43 mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. SIGNIFICANCE STATEMENT The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite

  8. Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I{sup 125} Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

    SciTech Connect

    Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

    2011-10-01

    Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I{sup 125} brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I{sup 125} monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I{sup 125} monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

  9. Surgical techniques influence local environment of injured spinal cord and cause various grafted cell survival and integration.

    PubMed

    Hou, Shaoping; Saltos, Tatiana M; Iredia, Idiata W; Tom, Veronica J

    2017-09-22

    Cellular transplantation to repair a complete spinal cord injury (SCI) is tremendously challenging due to the adverse local milieu for graft survival and growth. Results from cell transplantation studies yield great variability, which may possibly be due to the surgical techniques employed to induce an SCI. In order to delineate the influence of surgery on such inconsistency, we compared lesion morphology and graft survival as well as integration from different lesion methodologies of SCI. Surgical techniques, including a traditional approach cut+microaspiration, and two new approaches, cut alone as well as crush, were employed to produce a complete SCI, respectively. Approximately half of the rats in each group received injury only, whereas the other half received grafts of fetal brainstem cells into the lesion gap. Eight weeks after injury with or without graft, histological analysis showed that the cut+microaspiration surgery resulted in larger lesion cavities and severe fibrotic scars surrounding the cavity, and cellular transplants rarely formed a tissue bridge to penetrate the barrier. In contrast, the majority of cases treated with cut alone or crush exhibited smaller cavities and less scarring; the grafts expanded and blended extensively with the host tissue, which often built continuous tissue bridging the rostral and caudal cords. Scarring and cavitation were significantly reduced when microaspiration was avoided in SCI surgery, facilitating graft/host tissue fusion for signal transmission. The result suggests that microaspiration frequently causes severe scars and cavities, thus impeding graft survival and integration. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Outcomes of temporal bone resection for locally advanced parotid cancer.

    PubMed

    Mehra, Saral; Morris, Luc G; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H

    2011-11-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death.

  11. Outcomes of Temporal Bone Resection for Locally Advanced Parotid Cancer

    PubMed Central

    Mehra, Saral; Morris, Luc G.; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H.

    2011-01-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death. PMID:22547966

  12. Competing with giants. Survival strategies for local companies in emerging markets.

    PubMed

    Dawar, N; Frost, T

    1999-01-01

    The arrival of a multinational corporation often looks like a death sentence to local companies in an emerging market. After all, how can they compete in the face of the vast financial and technological resources, the seasoned management, and the powerful brands of, say, a Compaq or a Johnson & Johnson? But local companies often have more options than they might think, say the authors. Those options vary, depending on the strength of globalization pressures in an industry and the nature of a company's competitive assets. In the worst case, when globalization pressures are strong and a company has no competitive assets that it can transfer to other countries, it needs to retreat to a locally oriented link within the value chain. But if globalization pressures are weak, the company may be able to defend its market share by leveraging the advantages it enjoys in its home market. Many companies in emerging markets have assets that can work well in other countries. Those that operate in industries where the pressures to globalize are weak may be able to extend their success to a limited number of other markets that are similar to their home base. And those operating in global markets may be able to contend head-on with multinational rivals. By better understanding the relationship between their company's assets and the industry they operate in, executives from emerging markets can gain a clearer picture of the options they really have when multinationals come to stay.

  13. Transarterial chemoembolization for early stage hepatocellular carcinoma decrease local tumor control and overall survival compared to radiofrequency ablation

    PubMed Central

    Hocquelet, Arnaud; Seror, Olivier; Blanc, Jean-Frédéric; Frulio, Nora; Salut, Cécile; Nault, Jean-Charles; Hervé Trillaud

    2017-01-01

    Background & Aims To compare treatment failure and survival associated with ultrasound-guided radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE) for early-stage HCC in Child-Pugh A cirrhosis patients. Methods 122 cirrhotic patients (RFA: 61; TACE: 61) were well matched according to cirrhosis severity; tumor size and serum alpha-fetoprotein. TACE was performed in case of inconspicuous nodule on US or nodule with “at risk location”. Treatment failure was defined as local tumor progression (LTP) and primary treatment failure (failing to obtain complete response after two treatment session). Treatment failure and overall survival (OS) were compared after coarsened exact matching. Cox proportional model to assess independent predictive factors was performed. Results No significant difference was seen for baseline characteristics between the two groups. Mean tumor size was 3cm in both group with 41% HCC>3cm. Treatment failure rates after TACE was 42.6% (14 primary treatment failures and 12 LTP) and 9.8% after RFA (no primary treatment failure and 6 LTP) P < 0.001. TACE was the only predictive factor of treatment failure (Hazard ratio: 5.573). The 4-years OS after RFA and TACE were 54.1% and 31.5% (P = 0.042), respectively. Conclusion For Child-Pugh A patients with early-stage HCC, alternative treatment as supra-selective TACE to RFA regarded as too challenging using common US guidance decrease significantly the local tumor control and overall survival. Efforts to improve feasibility of RFA especially for inconspicuous target have to be made. PMID:27793027

  14. Prognostic Factors for Survival and Resection in Patients With Initial Nonresectable Locally Advanced Pancreatic Cancer Treated With Chemoradiotherapy

    SciTech Connect

    Bjerregaard, Jon K.; Mortensen, Michael B.; Jensen, Helle A.; Nielsen, Morten; Pfeiffer, Per

    2012-07-01

    Background and Purpose: Controversies regarding the optimal therapy for patients with locally advanced pancreatic cancer (LAPC) exist. Although the prognosis as a whole remains dismal, subgroups are known to benefit from intensive therapy, including chemoradiotherapy (CRT). We describe the results in 178 patients treated from 2001 to 2010 and have developed a prognostic model for both survival and the possibility of a subsequent resection in these patients. Methods and Materials: From 2001 until 2010, 178 consecutive patients with LAPC were treated and included in the present study, with CRT consisting of 50 Gy in 27 fractions combined with tegafur-uracil(UFT)/folinic acid(FA). Results: The median survival from diagnosis was 11.5 months. Adverse events of Grade 3 or above were seen in 36% of the patients. Ninety-three percent of the patients completed all fractions. A Cox regression model for survival demonstrated resection (hazard ratio [HR] 0.12; 95% confidence interval [CI], 0.1-0.3) and pre-CRT gemcitabine-based therapy (HR 0.57; 95% CI, 0.4-0.9) as being associated with a favorable outcome, increasing gross tumor volume (HR 1.14; 95% CI, 1.0-1.3) was associated with shorter survival. A logistic regression model showed Stage III disease (odds ratio [OR] 0.16; 95% CI, 0.0-1.1) and abnormal hemoglobin (OR 0.26; 95% CI, 0.0-1.2) as being associated with lower odds of resection. Conclusion: This study confirms the favorable prognosis for patients receiving gemcitabine therapy before CRT and the poor prognosis associated with increasing tumor volume. In addition, CRT in patients with abnormal hemoglobin and Stage III disease rarely induced tumor shrinkage allowing subsequent resection.

  15. Surviving the crisis: Adaptive wisdom, coping mechanisms and local responses to avian influenza threats in Haining, China.

    PubMed

    Zhang, Letian; Pan, Tianshu

    2008-04-01

    Based on ethnographic research conducted in the summer of 2006, this paper examines local responses to the imminent threat of avian flu in Haining County of Zhejiang Province. During our field investigation, we conducted interviews with officials from local medical institutions (including the hospitals, the animal husbandry and veterinary station, and health clinics), to bureaus of public health and agro-economy. We also visited chicken farms, restaurants and farming households. We address the following factors that commonly structured the perceptions and actions of different social actors in the area of study: The changing mode of information-sharing and communication practices in the local communities; the official drive to professionalize the emergency response management system in the county; and the coping mechanisms that helped the villagers and town residents to weather the storm of avian flu. Our field research suggests that collective survival consciousness was translated into a spirit of voluntarism during the crisis. One important practical lesson we have learned from this study is that the adaptive wisdom embedded in local memories demonstrated its operational worth as a resourceful knowledge base for ordinary farmers to deal with food shortage, famine, plague and future pandemics.

  16. Desmoid-type fibromatosis-associated Gardner fibromas: prevalence and impact on local recurrence.

    PubMed

    Cates, Justin M M; Stricker, Thomas P; Sturgeon, Duveen; Coffin, Cheryl M

    2014-10-28

    Although Gardner fibroma is a precursor lesion of desmoid tumor, the prevalence and prognostic importance of Gardner fibroma associated with desmoid tumors has not been systematically studied in adults. From 129 patients with desmoid-type fibromatosis, 170 specimens were re-examined for the presence of an associated Gardner fibroma. Clinicopathologic features of Gardner fibroma-associated desmoid-type fibromatosis were compared to desmoid tumors without associated Gardner fibroma. Recurrence-free survival was compared using multivariate Cox proportional hazard regression to account for known confounding factors. Of 104 evaluable primary desmoid tumor resections, 25 (24%) had an associated Gardner fibroma. When previous incisional biopsies and resection specimens of locally recurrent desmoid tumors were also examined, the overall prevalence of associated Gardner fibroma was 37%. Desmoid tumors arising in high risk anatomic sites (extremities or deep soft tissues of the back and chest wall) were more often associated with Gardner fibroma than tumors at other sites. Median recurrence-free survival for patients with Gardner fibroma-associated desmoid-type fibromatosis was 3.2 years, whereas median survival for patients without associated Gardner fibroma was >25 years (hazard ratio 2.8; P = 0.001). Although the presence of Gardner fibroma had no impact on the recurrence rate of desmoid tumors arising at high risk anatomic sites, associated Gardner fibroma increased the risk of recurrence 4-fold for desmoid tumors at low risk anatomic sites. Associated Gardner fibroma is under-recognized in desmoid-type fibromatosis and increases the risk of local recurrence for a subgroup of patients.

  17. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    PubMed Central

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    Objectives If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5–7 and 11–15 months, respectively. The extension of surgery did not affect the outcome. Conclusion The

  18. Incidence, Survival, and Treatment of Localized and Metastatic Neuroblastoma in Germany 1979-2015.

    PubMed

    Berthold, Frank; Spix, Claudia; Kaatsch, Peter; Lampert, Fritz

    2017-08-07

    A comprehensive clinical long-term survey over the complete spectrum of neuroblatoma disease is lacking in the literature. Our objective was to describe the incidence, risk profiles, therapies, and outcomes for the total cohort of German patients with neuroblastoma including all clinical stages and risk groups. Epidemiological, clinical, and outcome data of neuroblastoma patients who participated in one of the six consecutive national trials between 1979 and 2015 were analyzed retrospectively. Of all German neuroblastoma patients known to the national childhood cancer registry, ninety seven percent enrolled in one of the trials. The absolute neuroblastoma rate has increased slightly, whereas the median age at diagnosis has decreased. Except for the screening period (1995-2000), the risk factors lactate dehydrogenase (LDH), ferritin, chromosome 1p, and the MYCN oncogene have remained largely constant, with the exception of an increase in MYCN amplification at stage 4 for those aged ≥18 months between trials NB97 (27%) and NB2004 (35%). The 10-year overall survival increased in patients with stage 1-3 neuroblastoma from 83 to 91%, for stage 4S from 80 to 85%, and for stage 4 aged ≥18 months from 2 to 38%. The fraction of patients in stages 1-3 who never received chemotherapy (neither for frontline nor at recurrence) increased from 35 to 60%. The proportion of macroscopically complete surgical resections of the primary tumor decreased for the total population as well as for patients with stage 4 aged ≥18 months. The impact of chemotherapy response on the outcome was trial dependent. The overall proportion of toxic death during the time of the protocol therapy was 6% for stage 4 patients aged ≥18 months and 2% for low-/intermediate-risk patients. The most frequently reported late sequelae in stage 4 patients aged ≥18 months were renal dysfunctions, hypothyroidism, major hearing impairment, and second malignancies. The body of data for incidences, risk

  19. Subcellular Localization of the Intracellular Survival-Enhancing Eis Protein of Mycobacterium tuberculosis

    PubMed Central

    Dahl, John L.; Wei, Jun; Moulder, James W.; Laal, Suman; Friedman, Richard L.

    2001-01-01

    Mycobacterium tuberculosis is a facultative intracellular pathogen that has evolved the ability to survive and multiply within human macrophages. It is not clear how M. tuberculosis avoids the destructive action of macrophages, but this ability is fundamental in the pathogenicity of tuberculosis. A gene previously identified in M. tuberculosis, designated eis, was found to enhance intracellular survival of Mycobacterium smegmatis in the human macrophage-like cell line U-937 (J. Wei et al., J. Bacteriol. 182:377–384, 2000). When eis was introduced into M. smegmatis on a multicopy vector, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the appearance of a unique 42-kDa protein band corresponding to the predicted molecular weight of the eis gene product. This band was electroeluted from the gel with a purity of >90% and subjected to N-terminal amino acid sequencing, which demonstrated that the 42-kDa band was indeed the protein product of eis. The Eis protein produced by M. tuberculosis H37Ra had an identical N-terminal amino acid sequence. A synthetic polypeptide corresponding to a carboxyl-terminal region of the deduced eis protein sequence was used to generate affinity-purified rabbit polyclonal antibodies that reacted with the 42-kDa protein in Western blot analysis. Hydropathy profile analysis showed the Eis protein to be predominantly hydrophilic with a potential hydrophobic amino terminus. Phase separation of M. tuberculosis H37Ra lysates by the nonionic detergent Triton X-114 revealed the Eis protein in both the aqueous and detergent phases. After fractionation of M. tuberculosis by differential centrifugation, Eis protein appeared mainly in the cytoplasmic fraction but also in the membrane, cell wall, and culture supernatant fractions as well. Forty percent of the sera from pulmonary tuberculosis patients tested for anti-Eis antibody gave positive reactions in Western blot analysis. Although the function of Eis remains unknown, evidence

  20. Percutaneous cryoablation of metastatic lesions from non-small cell lung carcinoma: Initial survival, local control, and cost observations

    PubMed Central

    Bang, Hyun J.; Littrup, Peter J.; Currier, Brandt P.; Goodrich, Dylan J.; Aoun, Hussein D.; Klein, Lydia C.; Kuo, Jarret C.; Heilbrun, Lance K.; Gadgeel, Shirish; Goodman, Allen C.

    2013-01-01

    Purpose To assess feasibility, complications, local tumor recurrences, overall survival (OS) and estimates of cost-effectiveness for multi-site cryoablation (MCA) of oligometastatic non-small cell lung cancer (mNSCLC). Materials and Methods 49 CT and/or US-guided percutaneous MCA procedures were performed on 60 tumors in 31 oligo-mNSCLC patients. Average patient age was 65 years, including 19 females and 12 males. Tumor location was grouped according to common metastatic sites. Median OS was determined using the Kaplan-Meier method and defined life years gained (LYG). Estimates of MCA costs per LYG were compared with established values for systemic therapies. Results Total number of tumors and cryoablation procedures for each anatomical site are as follows: 20, 18 – lung; 9, 7 – liver; 12, 11 - superficial; 7, 7 – adrenal; 2, 2 – para-aortic/isolated; and 10, 7 – bone. A mean 1.6 procedures per patient were performed with a median clinical follow-up of 11 months. Major complication and local recurrence rates were 8% (4/49) and 8% (5/60), respectively. Median OS for MCA was 1.33 years with an estimated 1-year survival of ~53%. MCA appeared cost-effective even when added to the cost of BSC or systemic regimens, with an adjunctive cost-effectiveness ratio (ACER) of $49,008 – $87,074. Conclusions Multi-site cryoablation had very low morbidity and local tumor recurrence rates for all anatomic sites, and possibly increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligo-mNSCLC. PMID:22626267

  1. Impact of extraperitoneal lymphadenectomy on treatment and survival in patients with locally advanced cervical cancer.

    PubMed

    Gil-Moreno, Antonio; Díaz-Feijoo, Berta; Pérez-Benavente, Asumpció; del Campo, José M; Xercavins, Jordi; Martínez-Palones, José M

    2008-09-01

    During the last years, and coinciding with the beginning of the concomitant treatment with radio-chemotherapy, a better control of local cervical cancer has been reached, although failures in the systemic control of the illness have been more frequent. One of the main causes is not treating the illness at the level of the para-aortic lymph nodes, basically because their affectation is unknown and because imaging tests have a high percentage of false negative results. At this time, it is when laparoscopic para-aortic lymphadenectomy arises, in order to be able to know the extension of the illness better before treatment. A extraperitoneal laparoscopic approach is described in order to reduce complications derived from a possible extended irradiation. Between August 2001 and October 2007, a total of 69 patients with bulky and locally advanced cervical cancer (FIGO stages IB2, IIA > 4 cm and IIB-IVA) underwent extraperitoneal laparoscopic lymphadenectomy for surgical staging. Extraperitoneal aortic lymphadenectomy by laparoscopic approach is a technique with low morbidity. Special laparoscopic material is not required and if it is performed by a team trained in technical endoscopics it is not difficult. Radio-chemotherapy treatment began immediately after laparoscopy because of its minimal aggression.

  2. Growth and regression in bovine corpora lutea: regulation by local survival and death pathways.

    PubMed

    Skarzynski, D J; Piotrowska-Tomala, K K; Lukasik, K; Galvão, A; Farberov, S; Zalman, Y; Meidan, R

    2013-09-01

    The bovine corpus luteum (CL) is a transient gland with a life span of only 18 days in the cyclic cow. Mechanisms controlling CL development and secretory function may involve factors produced both within and outside this gland. Although luteinizing hormone (LH) surge is the main trigger of ovulation and granulosa cells luteinization, many locally produced agents such as arachidonic acid (AA) metabolites, growth factors and cytokines were shown to complement gonadotropins action in the process of CL development. Bovine CL is a highly vascular gland, where the very rapid angiogenesis rate (until Day 5 of the cycle) results in the development of a capillary network, endowing this gland with one of the highest blood flow rate per unit mass in the body. Angiogenesis in the developing CL is later followed by either controlled regression of the microvascular tree in the non-fertile cycle or maintenance and stabilization of the blood vessels, as seen during pregnancy. Different luteal cell types (both steroidogenic and accessory luteal cells: immune cells, endothelial cells, pericytes and fibroblasts) are involved in the pro- and/or anti-angiogenic responses. The balance between pro- and anti-angiogenic responses to the main luteolysin - prostaglandin F2α (PGF2α) could be decisive in whether or not PGF2α induces CL regression. Fibroblast growth factor-2 (FGF2) may be one of the factors that modulate the angiogenic response to PGF2α. Manipulation of local production and action of FGF2 will provide new tools for reproductive management of dairy cattle. Luteolysis is characterized by a rapid decrease in progesterone production, followed by structural regression. Factors like endothelin-1, cytokines (tumour necrosis factorα, interferons) and nitric oxide were all shown to play critical roles in functional and structural regression of the CL by inhibiting steroidogenesis and inducting apoptosis.

  3. [Post-recurrence survival after surgical resection of non-small cell lung cancer with local recurrence].

    PubMed

    Yokouchi, Hideoki; Miyazaki, Masaki; Miyamoto, Takeaki; Tsuji, Fumio; Ebisui, Chikara; Murata, Kohei

    2014-11-01

    We retrospectively evaluated the clinical outcomes of 192 consecutive patients with local recurrence after complete resection of non-small cell lung cancer NSCLC). The initial local recurrent site was the resection stump in 5 patients the chest wall in 3 patients, mediastinum in 1 patient, and diaphragm in 1 patient), and the hilar and/or mediastinal lymph node (HMLN) in 17 patients. The sites of distant metastasis were the lungs in 10 patients, pleura in 4 patients, brain in 7 patients, liver in 5 patients, bone in 4 patients, and other sites in 4 patients. Treatments after initial recurrence included surgery in 2 patients, radiotherapy in 5 patients, chemotherapy in 9 patients, and chemo-radiotherapy in 5 patients. Only 1 patient received supportive care. The response to radiotherapy was a complete response (R) in 1 patient, partial response (PR) in 5 patients, stable disease (SD )in 3 patients, and progressive disease (PD )in 1 patient. The best response of all lines of chemotherapy was CR in 3 patients, PR in 4 patients, SD in 3 patients, and PD in 4 patients. The median post-recurrence survival (PRS) time with local recurrence was better than that with distant metastasis (23 vs 14 months); however, the best PRS was obtained in patients with recurrence in the lungs (29 months). A CR for more than 2 years was obtained in 1 patient after surgery, in 1 patient after radiotherapy, and in 2 patients after chemotherapy. Although local recurrence of resected NSCLC can be potentially controlled by using local treatments - such as surgery and radiotherapy - or systemic chemotherapy, curative aggressive treatment should be considered when required.

  4. Percutaneous Radiofrequency Ablation and Transcatheter Arterial Chemoembolization for Hypervascular Hepatocellular Carcinoma: Rate and Risk Factors for Local Recurrence

    SciTech Connect

    Murakami, Tomonori Ishimaru, Hideki; Sakamoto, Ichiro; Uetani, Masataka; Matsuoka, Yohjiro; Daikoku, Manabu; Honda, Sumihisa; Koshiishi, Takeshi; Fujimoto, Toshifumi

    2007-07-15

    Purpose. To analyze local recurrence-free rates and risk factors for recurrence following percutaneous radiofrequency ablation (RFA) or transcatheter arterial chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC). Methods. One hundred and nine nodules treated by RFA and 173 nodules treated by TACE were included. Hypovascular nodules were excluded from this study. Overall local recurrence-free rates of each treatment group were calculated using the Kaplan-Meier method. The independent risk factors of local recurrence and the hazard ratios were analyzed using Cox's proportional-hazards regression model. Based on the results of multivariate analyses, we classified HCC nodules into four subgroups: central nodules {<=}2 cm or >2 cm and peripheral nodules {<=}2 cm or >2 cm. The local recurrence-free rates of these subgroups for each treatment were also calculated. Results. The overall local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p = 0.013). The 24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and 48.9%, respectively. In the RFA group, the only significant risk factor for recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a central location was the only significant risk factor for recurrence. In central nodules that were {<=}2 cm, the local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p < 0.001). In the remaining three groups, there was no significant difference in local recurrence-free rate between the two treatment methods. Conclusion. A tumor diameter of >2 cm was the only independent risk factor for local recurrence in RFA treatment, and a central location was the only independent risk factor in TACE treatment. Central lesions measuring {<=}2 cm should be treated by RFA.

  5. Local mitochondrial-endolysosomal microfusion cleaves voltage-dependent anion channel 1 to promote survival in hypoxia.

    PubMed

    Brahimi-Horn, M Christiane; Lacas-Gervais, Sandra; Adaixo, Ricardo; Ilc, Karine; Rouleau, Matthieu; Notte, Annick; Dieu, Marc; Michiels, Carine; Voeltzel, Thibault; Maguer-Satta, Véronique; Pelletier, Joffrey; Ilie, Marius; Hofman, Paul; Manoury, Bénédicte; Schmidt, Alexander; Hiller, Sebastian; Pouysségur, Jacques; Mazure, Nathalie M

    2015-05-01

    The oxygen-limiting (hypoxic) microenvironment of tumors induces metabolic reprogramming and cell survival, but the underlying mechanisms involving mitochondria remain poorly understood. We previously demonstrated that hypoxia-inducible factor 1 mediates the hyperfusion of mitochondria by inducing Bcl-2/adenovirus E1B 19-kDa interacting protein 3 and posttranslational truncation of the mitochondrial ATP transporter outer membrane voltage-dependent anion channel 1 in hypoxic cells. In addition, we showed that truncation is associated with increased resistance to drug-induced apoptosis and is indicative of increased patient chemoresistance. We now show that silencing of the tumor suppressor TP53 decreases truncation and increases drug-induced apoptosis. We also show that TP53 regulates truncation through induction of the mitochondrial protein Mieap. While we found that truncation was independent of mitophagy, we observed local microfusion between mitochondria and endolysosomes in hypoxic cells in culture and in patients' tumor tissues. Since we found that the endolysosomal asparagine endopeptidase was responsible for truncation, we propose that it is a readout of mitochondrial-endolysosomal microfusion in hypoxia. These novel findings provide the framework for a better understanding of hypoxic cell metabolism and cell survival through mitochondrial-endolysosomal microfusion regulated by hypoxia-inducible factor 1 and TP53.

  6. Relation between the level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A; Sturgis, Erich M; Garden, Adam S; Lee, J Jack; William, William N

    2016-02-15

    The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. This study investigated the impact of the level of lymph node metastasis (LNM) on survival. The Surveillance, Epidemiology, and End Results registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. A multivariate Cox proportional hazards model was used to evaluate whether the level of LNM was an independent prognostic factor. Site-specific recursive-partitioning analysis was performed to classify patients into different risk groups. In all, 14,499 patients, including OC (n = 2463), OP (n = 8567), LAR (n = 2332), and HP patients (n = 1137), were analyzed. Both the American Joint Committee on Cancer (AJCC) N classification and the level of LNM showed significant effects on overall survival (OS) in patients with OC, OP, or LAR HNSCC but not in patients with HP HNSCC. In patients with N2 disease, the AJCC subclassification (N2a, N2b, or N2c) was significantly associated with the OS of patients with OP and LAR HNSCC but not with the OS of patients with OC or HP HNSCC, whereas the level of LNM (primary, secondary, or tertiary) was significantly associated with the OS of patients with OC, OP, and LAR HNSCC but not HP HNSCC. With recursive-partitioning analysis, a simple, primary site-specific prognostic tool integrating the AJCC T and N classifications and the level of LNM was designed, and it could be easily used by health care providers in clinic. The level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classifications in patients with locally advanced HNSCC. © 2015 American Cancer Society.

  7. Relationship between level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A.; Sturgis, Erich M.; Garden, Adam S.; Lee, J. Jack; William, William N.

    2015-01-01

    Background The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. We sought to investigate the impact of level of lymph node metastasis (LNM) on survival Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. Multivariate Cox proportional hazards model was used to evaluate whether level of LNM is an independent prognostic factor. Site-specific recursive-partitioning analysis (RPA) was performed to classify patients into different risk groups. Results Totally, 14,499 patients including OC (N=2,463), OP (N=8,567), LAR (N=2,332) and HP (N=1,137) were analyzed. Both AJCC N classification and level of LNM showed significant effects on overall survival (OS) in patients with OC, OP or LAR, but not in HP. In patients with N2 disease, AJCC subclassification (N2a, N2b, N2c) was significantly associated with OS of patients with OP and LAR, but not OC or HP, while level of LNM (primary, secondary, and tertiary) was significantly associated with OS in patients with OC, OP and LAR, but not HP. Using RPA, we designed a simple, primary site-specific prognostic tool integrating AJCC T classification, N classification, and level of LNM that can be easily utilized by health care providers in clinic. Conclusions Level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classification in patients with locally advanced HNSCC. PMID:26554754

  8. The midregion, nuclear localization sequence, and C terminus of PTHrP regulate skeletal development, hematopoiesis, and survival in mice

    PubMed Central

    Toribio, Ramiro E.; Brown, Holly A.; Novince, Chad M.; Marlow, Brandlyn; Hernon, Krista; Lanigan, Lisa G.; Hildreth, Blake E.; Werbeck, Jillian L.; Shu, Sherry T.; Lorch, Gwendolen; Carlton, Michelle; Foley, John; Boyaka, Prosper; McCauley, Laurie K.; Rosol, Thomas J.

    2010-01-01

    The functions of parathyroid hormone-related protein (PTHrP) on morphogenesis, cell proliferation, apoptosis, and calcium homeostasis have been attributed to its N terminus. Evidence suggests that many of these effects are not mediated by the N terminus but by the midregion, a nuclear localization sequence (NLS), and C terminus of the protein. A knock-in mouse lacking the midregion, NLS, and C terminus of PTHrP (PthrpΔ/Δ) was developed. PthrpΔ/Δ mice had craniofacial dysplasia, chondrodysplasia, and kyphosis, with most mice dying by d 5 of age. In bone, there were fewer chondrocytes and osteoblasts per area, bone mass was decreased, and the marrow was less cellular, with erythroid hypoplasia. Cellular proliferation was impaired, and apoptosis was increased. Runx2, Ocn, Sox9, Crtl1, β-catenin, Runx1, ephrin B2, cyclin D1, and Gata1 were underexpressed while P16/Ink4a, P21, GSK-3β, Il-6, Ffg3, and Ihh were overexpressed. Mammary gland development was aberrant, and energy metabolism was deregulated. These results establish that the midregion, NLS, and C terminus of PTHrP are crucial for the commitment of osteogenic and hematopoietic precursors to their lineages, and for survival, and many of the effects of PTHrP on development are not mediated by its N terminus. The down-regulation of Runx1, Runx2, and Sox9 indicates that PTHrP is a modulator of transcriptional activation during stem cell commitment. Toribio, R. E., Brown, H. A., Novince, C. M., Marlow, B. Hernon, K., Lanigan, L. G., Hildreth III, B. E., Werbeck, J. L., Shu, S. T., Lorch, G., Carlton, M., Foley, J., Boyaka, P., McCauley, L. K., Rosol, T. J. The midregion, nuclear localization sequence, and C terminus of PTHrP regulate skeletal development, hematopoiesis, and survival in mice. PMID:20145205

  9. Induction chemotherapy for the treatment of non-endemic locally advanced nasopharyngeal carcinoma

    PubMed Central

    Zhao, Lina; Xu, Man; Jiang, Wen; Pan, Haitao; Zang, Jian; Luo, Shanquan; Wang, Jianhua; Zhou, Yongchun; Shi, Mei

    2017-01-01

    Background The role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC). Results With a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17.2% patients. Multivariate analyses showed that retropharyngeal and bilateral neck lymph node metastasis were significant prognostic factors for DFS and OS. Moreover, patients receiving both GP (gemcitabine+cisplatin) and TP (docetaxel+cisplatin) regimes had significantly higher DFS and OS compared with PF (cisplatin+5-FU) regime. GP regimes lead to significantly improved OS than TP/PF in some subgroup of patients. No severe toxicities were observed. Materials and Methods We retrospectively analyzed stage III-IVb NPC patients treated between Jan 2006 and Dec 2014, with induction chemotherapy followed by concurrent chemoradiation (IC-CCRT). Statistical analyses were performed on survival and failure patterns. Conclusions These results suggested IC-CCRT was safe and effective for NPCs from non-endemic region. The choice of induction regimen appeared to affect patient outcomes. PMID:28036270

  10. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations

    PubMed Central

    Fuller, Donald Blake; Naitoh, John; Mardirossian, George

    2014-01-01

    Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered “Virtual HDR” treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients. Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create “HDR-like” PTV dose distribution. Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient’s potent pre-SBRT, 65% remained so at 5 years. Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported

  11. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations.

    PubMed

    Fuller, Donald Blake; Naitoh, John; Mardirossian, George

    2014-01-01

    Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered "Virtual HDR" treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients. Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create "HDR-like" PTV dose distribution. Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient's potent pre-SBRT, 65% remained so at 5 years. Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

  12. Pregnancy Specific β-1 Glycoprotein 1 is Expressed in Pancreatic Ductal Adenocarcinoma and its Subcellular Localization Correlates with Overall Survival

    PubMed Central

    Shahinian, Jasmin H.; Fuellgraf, Hannah; Tholen, Stefan; Mastroianni, Justin; Knopf, Julia Daniela; Kuehs, Markus; Mayer, Bettina; Schlimpert, Manuel; Kulemann, Birte; Kuesters, Simon; Hoeppner, Jens; Wellner, Ulrich F.; Werner, Martin; Hopt, Ulrich T.; Zeiser, Robert; Bronsert, Peter; Schilling, Oliver

    2016-01-01

    Proteins of the pregnancy specific β-1 glycoprotein (PSG) family are renowned for their elevated expression during pregnancy. Only few reports have investigated their expression in adenocarcinomas. We studied the expression of PSG1 in pancreatic adenocarcinoma (PDAC). In a cohort of 104 patient samples, immunohistochemical analysis determined PSG1 expression in every specimen. PSG1 was found at apical and cytoplasmic localization or solely at cytoplasmic localization, with the latter case being correlated to shortened median survival (25 vs 11 months, logrank p-value < 0.001). At the same time, enzyme linked immunosorbent assay (ELISA) did not detect elevated PSG1 levels in the plasma of PDAC patients as opposed to the plasma of healthy, non-pregnant control individuals. We also probed the impact of PSG1 expression in a murine tumor model system, using subcutaneous injection of Colo-26 cells into immunocompetent BALB/c mice. Here, tumor growth was not affected by the expression of human PSG1. Our study reaffirms interest into the tumor-contextual biology of PSG proteins. PMID:27877217

  13. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma

    PubMed Central

    2013-01-01

    Background Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. Methods Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy). Results LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. Conclusions This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an

  14. Association of extent of local tumor invasion and survival in patients with malignant primary osseous spinal neoplasms from the surveillance, epidemiology, and end results (SEER) database.

    PubMed

    Mukherjee, Debraj; Chaichana, Kaisorn L; Adogwa, Owoicho; Gokaslan, Ziya; Aaronson, Oran; Cheng, Joseph S; McGirt, Matthew J

    2011-12-01

    Malignant osseous spinal neoplasms are aggressive tumors associated with poor outcomes despite aggressive multidisciplinary measures. It remains unknown whether increased local tumor invasion at time of treatment predicts worse survival. The surveillance, epidemiology, and end results (SEER) registry was reviewed to determine whether extent of local tumor invasion at presentation was independently associated with overall survival. The SEER registry (1973-2003) was queried to identify cases of histologically confirmed primary spinal chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma. Extent of local invasion was defined at time of care by histology, radiology, or intraoperative assessment and classified as confined (tumor within periosteum), local invasion (extension to surrounding tissues), or distal metastasis. The association of extent of local tumor invasion with overall survival was assessed by Cox analysis. One thousand eight hundred ninety-two patients were identified (414 chordoma, 579 chondrosarcoma, 430 osteosarcoma, 469 Ewing sarcoma). Overall median survival was histology specific (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months; chordoma, 50 months) and correlated with extent of local tissue invasion or metastasis at presentation. Presence of metastasis was associated with marked decrease in survival (P < 0.001) for all tumor types. For patients with isolated spine tumors, neoplasms confined within the periosteum were associated with improved overall survival independent of age, radiotherapy, or surgical resection for chordoma (hazard ratio [HR], 0.50; P = 0.08), chondrosarcoma (HR, 0.62; P = 0.03), and osteosarcoma (HR, 0.68; P = 0.05), but not Ewing sarcoma (HR, 0.62; P = 0.27). The preoperative radiographic recognition of local tissue invasion may identify patients with a more aggressive tumor and help guide the level of aggressiveness in subsequent treatment strategies. Copyright © 2011. Published by Elsevier Inc.

  15. A Nomogram to Predict Recurrence and Survival of High-Risk Patients Undergoing Sublobar Resection for Lung Cancer: An Analysis of a Multicenter Prospective Study (ACOSOG Z4032).

    PubMed

    Kent, Michael S; Mandrekar, Sumithra J; Landreneau, Rodney; Nichols, Francis; Foster, Nathan R; DiPetrillo, Thomas A; Meyers, Bryan; Heron, Dwight E; Jones, David R; Tan, Angelina D; Starnes, Sandra; Putnam, Joe B; Fernando, Hiran C

    2016-07-01

    Individualized prediction of outcomes may help with therapy decisions for patients with non-small cell lung cancer. We developed a nomogram by analyzing 17 clinical factors and outcomes from a randomized study of sublobar resection for non-small cell lung cancer in high-risk operable patients. The study compared sublobar resection alone with sublobar resection with brachytherapy. There were no differences in primary and secondary outcomes between the study arms, and they were therefore combined for this analysis. The clinical factors of interest (considered as continuous variables) were assessed in a univariate Cox proportional hazards model for significance at the 0.10 level for their impact on overall survival (OS), local recurrence-free survival (LRFS), and any recurrence-free survival (RFS). The final multivariable model was developed using a stepwise model selection. Of 212 patients, 173 had complete data on all 17 risk factors. Median follow-up was 4.94 years (range, 0.04 to 6.22). The 5-year OS, LRFS, and RFS were 58.4%, 53.2%, and 47.4%, respectively. Age, baseline percent diffusing capacity of lung for carbon monoxide, and maximum tumor diameter were significant predictors for OS, LRFS, and RFS in the multivariable model. Nomograms were subsequently developed for predicting 5-year OS, LRFS, and RFS. Age, baseline percent diffusing capacity of lung for carbon monoxide, and maximum tumor diameter significantly predicted outcomes after sublobar resection. Such nomograms may be helpful for treatment planning in early stage non-small cell lung cancer and to guide future studies. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma.

    PubMed

    Matsui, Daisuke; Zaidi, Ali H; Martin, Samantha A; Omstead, Ashten N; Kosovec, Juliann E; Huleihel, Luai; Saldin, Lindsey T; DiCarlo, Christina; Silverman, Jan F; Hoppo, Toshitaka; Finley, Gene G; Badylak, Stephen F; Kelly, Ronan J; Jobe, Blair A

    2016-12-06

    Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC.

  17. Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Matsui, Daisuke; Zaidi, Ali H.; Martin, Samantha A.; Omstead, Ashten N.; Kosovec, Juliann E.; Huleihel, Luai; Saldin, Lindsey T.; DiCarlo, Christina; Silverman, Jan F.; Hoppo, Toshitaka; Finley, Gene G.; Badylak, Stephen F.; Kelly, Ronan J.; Jobe, Blair A.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC. PMID:27793030

  18. Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

    SciTech Connect

    Bentzen, Anne Gry; Guren, Marianne G.; Wanderas, Eva H.; Frykholm, Gunilla; Tveit, Kjell M.; Wilsgaard, Tom; Dahl, Olav; Balteskard, Lise

    2012-06-01

    Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

  19. Chemoradiotherapy of anal carcinoma: survival and recurrence in an unselected national cohort.

    PubMed

    Bentzen, Anne Gry; Guren, Marianne G; Wanderås, Eva H; Frykholm, Gunilla; Tveit, Kjell M; Wilsgaard, Tom; Dahl, Olav; Balteskard, Lise

    2012-06-01

    To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. High expression of flotillin-2 is associated with poor clinical survival in cervical carcinoma

    PubMed Central

    Liu, Yaqiong; Lin, Li; Huang, Zijian; Ji, Bing; Mei, Shanshan; Lin, Ying; Shen, Zhuanxing

    2015-01-01

    Aims: To investigate the expression and clinical significance of flotillin-2 (FLOT2) in cervical cancer (CC). Methods: We examined FLOT2 mRNA levels in 10 pairs of cervical cancer and adjacent normal tissues. Immunohistochemistry was performed to analyze FLOT2 protein expression in 115 archived cervical cancer samples. The association between FLOT2 levels, clinicopathologic factors and prognosis was analyzed statistically as well. Results: The cancer tissues of CC patients had clearly increased expression of FLOT2 at mRNA level as compared to adjacent nontumorous tissues. Survival analysis of CC patients indicated that FLOT2 expression was significantly associated with poor overall and local recurrence-free survival (P = 0.025 and P = 0.028, respectively). Moreover, FLOT2 expression was significantly correlated with clinical stage, tumor differentiation, and lymph nodes metastasis. Multivariate analysis revealed that FLOT2 expression was an independent prognostic factor for overall survival in CC patients. Conclusion: FLOT2 may serve as an oncogene in the development of CC, and may serve as a clinicopathologic biomarker for prognosis in CC patients. PMID:25755754

  1. Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

    SciTech Connect

    Caujolle, Jean-Pierre; Paoli, Vincent; Chamorey, Emmanuel; Maschi, Celia; Baillif, Stéphanie; Herault, Joël; Gastaud, Pierre; Hannoun-Levi, Jean Michel

    2013-04-01

    Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.

  2. Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature

    PubMed Central

    González Ferreira, José A.; Jaén Olasolo, Javier; Azinovic, Ignacio; Jeremic, Branislav

    2015-01-01

    Treatment delays in completing radiotherapy (RT) for many neoplasms are a major problem affecting treatment outcome, as increasingly shown in the literature. Overall treatment time (OTT) could be a critical predictor of local tumor control and/or survival. In an attempt to establish a protocol for managing delays during RT, especially for heavily overloaded units, we have extensively reviewed the available literature on head and neck cancer. We confirmed a large deleterious effect of prolonged OTT on both local control and survival of these patients. PMID:26549990

  3. Outcomes of salvage surgery for cure in patients with locally recurrent disease after local excision of rectal cancer.

    PubMed

    Bikhchandani, Jai; Ong, Gabie K; Dozois, Eric J; Mathis, Kellie L

    2015-03-01

    Local excision for early rectal cancer has gained widespread interest. Currently available imaging modalities have low sensitivity to detect locoregional disease, which may result in understaging and a high risk of recurrence after local excision. The purpose of this work was to study the morbidity, mortality, and long-term oncologic outcomes in a select cohort of patients undergoing salvage surgery for local recurrence after local excision of early rectal cancer. A retrospective review of patient charts was used to determine patterns of disease recurrence and outcomes as a single-institution case series. The study was conducted at a tertiary care cancer center. The study cohort included patients with early rectal cancer treated by local excision who then developed local recurrence for which a multimodal salvage surgery with curative intent was performed between 1997 and 2013 at our center. Log rank tests were used to measure overall and disease-free survival. Twenty-seven patients were identified, with a mean age of 66 ± 12 years. The median time to recurrence was 54 weeks (range, 7-326 weeks). Recurrent disease was luminal in 23 patients, regional (involving both mesorectal and pelvic lymph nodes) in 6 patients, and both luminal and nodal in 2 patients. For salvage surgery, neoadjuvant chemoradiation was used in 12 patients (44%), and radiation alone was used in 1 patient. Sphincter-preserving surgery was performed in 9 patients (33%). R0 resection was achieved in 25 patients (93%). Four patients received intraoperative radiation therapy. Five-year overall survival was 50% (95% CI, 30%-74%), and re-recurrence-free survival was 47% (95% CI, 25%-68%). This study was limited by its retrospective nature, small patient cohort, referral bias, and selection bias. Even in highly selected patients who undergo surgery for local recurrence after transanal excision of early stage rectal cancer, oncologic outcomes are poor.

  4. Addition of anti-neu antibody to local irradiation can improve tumor-bearing BALB/c mouse survival through immune-mediated mechanisms.

    PubMed

    Ma, Sun Young; Song, Hyunkeun; Park, Jin-Hee; Choi, Jae-Hyeog; Kim, Jin-Ho; Kim, Ki Hyang; Park, SungJae; Park, Dong Hyen; Kang, Mi Seon; Kwak, Minjung; Fu, Yang-Xin; Choi, Inhak; Cho, Heunglae; Park, SaeGwang

    2015-03-01

    This study investigated the therapeutic effects of combined local irradiation and anti-HER2/neu antibody in a mixed tumor mouse model comprised of a nonmetastatic neu-positive tumor and a metastatic neu-negative tumor. While local irradiation alone could control the primary tumor in a dose-dependent manner, it did not improve mouse survival. Combined treatment comprised of local irradiation and anti-neu antibody of tumor-bearing BALB/c mice significantly improved mouse survival (P < 0.5), even though the tumor growth was similar to that of the irradiated-alone group. The combined treatment significantly reduced metastatic tumor masses in the lung and increased immune cell infiltration in primary tumor tissues. However, immune deficient nude mice with tumors did not exhibit prolonged survival in response to the combined treatment. Collectively, these results show that combined local irradiation and anti-neu antibody can elicit an immune-mediated abscopal effect to extend survival. Although the mechanism for abscopal effects induced by the combined treatment of radiation and anti-HER2/neu antibody was not elucidated, to our knowledge this is the first published study to describe the abscopal effect induced by the combination of local irradiation and the anti-HER2/neu antibody.

  5. HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers.

    PubMed

    Wang, Tonghui; Xu, Ye; Sheng, Shuyan; Yuan, Hua; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2017-02-06

    It is well documented that HER2 overexpression/amplification is associated with the poor survival in breast cancer patients. However, it is largely unknown whether HER2 somatic mutations are associated with the survival in HER2-negative breast cancer patients. Here, we identified HER2 somatic mutations in tumors from 1,348 unselected breast cancer patients by sequencing the entire HER2 coding region. All these mutations were tested for in corresponding blood samples to determine whether they were somatic or germline mutations. We further investigated the associations between the HER2 somatic mutations and recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) in this cohort of patients. We found that 27 of 1,348 (2.0%) of these patients carried a HER2 somatic mutation. In vitro experiments demonstrated that some of novel mutations and those with unknown functions increased HER2 activity. HER2 status was available for 1,306 patients, and the HER2 somatic mutation rates in HER2-positive (n=353) and HER2-negative breast cancers (n=953) were 1.4% and 2.3%, respectively. Among the HER2-negative patients, those with a HER2 somatic mutation had a significantly worse recurrence-free survival (unadjusted hazard ratio [HR] =2.67; 95% confidence interval [CI]: 1.25-5.72, P=0.002) and distant recurrence-free survival (unadjusted HR=2.50; 95% CI: 1.10-5.68, P=0.004) than those with wild-type HER2. Taken together, our findings suggested that HER2 somatic mutations occur at a higher frequency in HER2-negative breast cancer, and HER2-negative breast cancer patients with these mutations have poor survival. Therefore, HER2-negative patients with a HER2 somatic mutation are potentially good candidates for HER2-targeted therapy. This article is protected by copyright. All rights reserved.

  6. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis.

    PubMed

    Liu, Zhi-Gang; Zhao, Yu; Tang, Jiao; Zhou, Yu-Juan; Yang, Wen-Juan; Qiu, Yan-Fang; Wang, Hui

    2016-04-26

    Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated.

  7. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis

    PubMed Central

    Zhou, Yu-juan; Yang, Wen-juan; Qiu, Yan-fang; Wang, Hui

    2016-01-01

    Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated. PMID:27016412

  8. Clinical implications of preoperative chemoradiotherapy prior to laparoscopic surgery for locally advanced low rectal cancer

    PubMed Central

    Kondo, Keisaku; Shimbo, Taiju; Tanaka, Keitaro; Yamamoto, Masashi; Narumi, Yoshifumi; Okuda, Junji; Uchiyama, Kazuhisa

    2017-01-01

    The present study aimed to evaluate whether preoperative chemoradiotherapy (CRT) has any adverse effects on laparoscopic surgery (LS) for locally advanced low rectal cancer (LARC). The study was performed at the Osaka Medical College Hospital, and included patients who were operated on between July 2006 and December 2013. The short-term outcomes in 156 patients who underwent surgery for LARC following CRT were evaluated, of whom 152 underwent LS. Among the patients who were followed for >40 months, 77 patients (the CRT group) were compared with 39 patients who underwent LS without CRT (the surgery-alone group) for long-term outcomes. The total number of patients who received sphincter-preserving surgery was 74%. No positive longitudinal resection margins were identified, and only 1.3% had identifiable positive circumferential resection margins. The complication rate was 14%, and no serious complications occurred. There were no significant differences between the CRT and the surgery-alone groups in terms of the 5-year relapse-free survival rate (70.1 vs. 61.5%; P=0.81) or the 5-year overall survival rate (88.3 vs. 69.2%; P=0.06). However, the 5-year local recurrence-free survival rate was significantly improved in the CRT group patients (96.1 vs. 79.5%; P=0.009). In conclusion, our results have demonstrated that LS with preoperative CRT appears to be feasible and safe, and may have beneficial effects on local recurrence. PMID:28123724

  9. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  10. Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases.

    PubMed

    Yamashita, S; Odisio, B C; Huang, S Y; Kopetz, S E; Ahrar, K; Chun, Y S; Conrad, C; Aloia, T A; Gupta, S; Harmoush, S; Hicks, M E; Vauthey, J-N

    2017-06-01

    In patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear. We identified 74 patients with CLM who underwent percutaneous ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated. Recurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin (P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin (P = 0.022). Compared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  11. Is there role of additional chemotherapy after definitive local treatment for stage I/II marginal zone lymphoma?: Consortium for Improving Survival of Lymphoma (CISL) study.

    PubMed

    Koh, Myeong Seok; Kim, Won Seog; Kim, Seok Jin; Oh, Sung Yong; Yoon, Dok Hyun; Lee, Soon Il; Hong, Junshik; Song, Moo Kon; Shin, Ho-Jin; Kwon, Jung Hye; Kim, Hyo Jung; Do, Yong Rok; Suh, Cheolwon; Kim, Hyo Jin

    2015-10-01

    Even though local stage (Ann Arbor stage I/II) marginal zone lymphoma (MZL) is well controlled with local treatment-based therapy, no data exist on the role of additional chemotherapy after local treatment for stage I/II MZL. Patients with biopsy-confirmed Ann Arbor stage I/II MZL (n = 210) were included for analysis in this study. Of these, 180 patients (85.7 %) were stage I and 30 (14.3 %) were stage II. Most patients (n = 182, 86.7 %) were treated with a local modality including radiation therapy or surgery and 28 (13.3 %) received additional systemic chemotherapy after local treatment. The overall response rate was 98.3 % (95 % CI 96-100 %), with 187 complete responses and 20 partial responses. In the local treatment group, the mean progression-free survival (PFS) was 147.4 months (95 % CI 126.7-168.1 months) and the overall survival (OS) was 188.2 months (95 % CI 178.8-197.7 months). In the additional chemotherapy group, the mean PFS was 103.4 months (95 % CI 84.9-121.9 months) and the OS was 137.3 months (95 % CI 127.9-146.7 months). There was no difference between the two groups in OS (p = 0.836) and PFS (p = 0.695). Local stage MZL has a good clinical course and is well controlled with a local treatment modality without additional chemotherapy.

  12. Surgical margins and primary site resection in achieving local control in oral cancer resections.

    PubMed

    Varvares, Mark A; Poti, Shannon; Kenyon, Bianca; Christopher, Kara; Walker, Ronald J

    2015-10-01

    Evaluate effectiveness of resection of oral cavity cancer with a standardized approach for margin evaluation. Primary end points were local control and survival. Retrospective, nonrandomized, single institution. One hundred eight patients who underwent surgery for oral cancer were evaluated using specific anatomical pathology criteria. Frozen section was performed with the surgeon and pathologist agreeing where on the specimen the frozen sections should be taken in most cases. Ninety-one patients (84.3%) had frozen sections taken from the specimen, eight from the tumor bed, and nine had none taken at the time of surgery. Overall local recurrence rate was 18.5%, 25% in patients who had margins taken from the tumor bed and 17.6% when taken from the specimen. Twenty-nine patients had margins ≥5 mm, 53 <5 mm and clear, and 14 positive re-resected to negative with local recurrence rates of 3.4%, 26.4%, and 28.6%, respectively. The radial distance of the resection margin was shown to have an impact on overall survival (hazard ratio [HR] = 3.59, 95% confidence interval [CI] = 1.12-11.57), disease-free survival (HR = 7.00, 95% CI = 1.89-25.95), and local recurrence-free survival (HR = 28.80, 95% CI = 3.00-276.82). Assessing margins from the resection specimen rather than the tumor bed consistently predicts local control. There is a statistical improvement in local control, disease-free, and overall survival with increasing radial margin distance from the tumor, and 5 mm should be agreed upon as the definition of a clear resection margin. Frozen sections can be used to revise positive or close resection margins intraoperatively with improved outcomes. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Stereotactic Body Radiotherapy for Pulmonary Metastases From Soft-Tissue Sarcomas: Excellent Local Lesion Control and Improved Patient Survival

    SciTech Connect

    Dhakal, Sughosh; Corbin, Kimberly S.; Milano, Michael T.; Philip, Abraham; Sahasrabudhe, Deepak; Jones, Carolyn

    2012-02-01

    Purpose: Patients with pulmonary metastases (PM) from soft-tissue sarcomas (STS) have historically been treated with surgery and/or chemotherapy. Since 2001, we have treated PM with stereotactic body radiation therapy (SBRT). We postulated that SBRT for PM from STS would yield excellent local control (LC) and overall survival (OS). Methods and Materials: Fifty-two patients with PM from STS, diagnosed between 1990 and 2006 at University of Rochester, were retrospectively reviewed. Most patients received multimodality treatment comprising of surgery, chemotherapy, and/or radiation. SBRT used the Novalis ExacTrac patient positioning platform, vacuum bag immobilization, and relaxed end-expiratory breath hold techniques. Results: Leiomyosarcoma (23%), malignant fibrous histiocytoma (19%), and synovial sarcoma (15%) were the most common histologies. Forty-eight percent initially presented with PM, whereas 52% developed PM at a median of 0.7 (0.3-7.3) years after initial diagnosis. Median follow-up from diagnosis of PM was 0.9 (0.3-7.3) years. Fifteen patients underwent SBRT to 74 lesions. Median number of lesions treated was 4 (1-16) per patient and 3.5 (1-6) per session. Preferred dose and fractionation was 50 Gy in 5 Gy fractions. Three-year LC was 82%. No patients experienced Grade {>=}3 toxicity. Median OS was 2.1 (0.8-11.5) years for patients treated with SBRT, and 0.6 (0.1-7.8) years for those who never received SBRT (p = 0.002). Conclusions: SBRT provides excellent LC of PM and may extend OS. SBRT should be considered for all patients with PM from STS, particularly those who are not surgical candidates. Further investigation is warranted to establish criteria for the use of SBRT for STS patients with PM.

  14. Genetic profiling to determine risk of relapse-free survival in high-risk localized prostate cancer.

    PubMed

    Barnett, Christine M; Heinrich, Michael C; Lim, Jeong; Nelson, Dylan; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Higano, Celestia S; Garzotto, Mark; Qian, David; Corless, Christopher L; Thomas, George V; Beer, Tomasz M

    2014-03-01

    The characterization of actionable mutations in human tumors is a prerequisite for the development of individualized, targeted therapy. We examined the prevalence of potentially therapeutically actionable mutations in patients with high-risk clinically localized prostate cancer. Forty-eight samples of formalin-fixed paraffin-embedded prostatectomy tissue from a neoadjuvant chemotherapy trial were analyzed. DNA extracted from microdissected tumor was analyzed for 643 common solid tumor mutations in 53 genes using mass spectroscopy-based sequencing. In addition, PTEN loss and erythroblast transformation-specific-related gene (ERC) translocations were examined using immunohistochemistry (IHC) in associated tissue microarrays. Association with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations. Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 47 tumors evaluable for IHC, 36% had PTEN loss and 40% had ERG rearrangement. Individual mutations were not frequent enough to determine associations with relapse. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median relapse-free survival, 19 versus 106 months (P = 0.01). This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. Although point mutations alone did not have a statistically significant association with relapse, PTEN loss was associated with an increased relapse in high-risk prostate cancer treated with chemotherapy followed by surgery. ©2013 AACR

  15. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control

    PubMed Central

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-01-01

    Abstract Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival. This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months. Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival. TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT. PMID:27512857

  16. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control.

    PubMed

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-08-01

    Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival.This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months.Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival.TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT.

  17. Improved Survival in Patients With Stage III-IV Head and Neck Cancer Treated With Radiotherapy as Primary Local Treatment Modality

    SciTech Connect

    Rusthoven, Kyle E.; Raben, David; Chen Changhu

    2008-10-01

    Purpose: To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. Methods and Materials: The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. Results: Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. Conclusions: The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

  18. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer

    PubMed Central

    Simone, Charles B.; Cengel, Keith A.

    2016-01-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6–9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis. PMID:27594732

  19. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    PubMed

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  20. {sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

    SciTech Connect

    Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko; Graves, Edward E.; Kunz, Pamela; Ford, James M.; Fisher, George A.; Goodman, Karyn A.; Koong, Albert C.; Chang, Daniel T.

    2010-08-01

    Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

  1. WE-E-17A-03: FDG-PET-Based Radiomics to Predict Local Control and Survival Following Radiotherapy

    SciTech Connect

    Oh, J; Apte, A; Folkerts, M; Kohutek, Z; Wu, A; Rimmer, A; Lee, N; Deasy, J

    2014-06-15

    Purpose: An exploding field in cancer research is “radiomics,” based on the hypothesis that there is statistical (hidden) information in medical images that is prognostic or predictive of outcomes. Our group has developed an efficient pipeline to extract and analyze quantitative image features from medical images as related to outcomes or diagnosis. In this work, we summarize our previous studies with positron emission tomography (PET) images and show the potential of the use of radiomics for outcomes research. Methods: We analyzed two cancer datasets, each consisting of pre-radiotherapy-treatment PET scans: 163 T1-2N0M0 non-small cell lung cancer (NSCLC) patients and 174 head and neck (H and N) cancer patients with stage III–IV. The PET scans were converted to Computational Environment for Radiological Research (CERR) format, and CERR was used to generate 24 shape, texture, and intensity-histogram based image features. Data-mining and logistic regression methods were then used to model local failure (LF) and overall survival (OS). Unbiased estimates of performance were generated using leave-one-out cross-validation (LOOCV). Results: For predicting LF, the models with biologically equivalent dose (BED) and TLG (metabolic tumor volume (MTV) x SUVmean) in NSCLC, and skewness and MTV in H and N, achieved the best performance with AUC=0.818 (p<0.0001) and AUC=0.826 (p=0.0002), respectively. For predicting OS, the models with kurtosis and volume in NSCLC and SUVmax and homogeneity in H and N achieved the best performance with AUC=0.706 (p<0.0001) and AUC=0.656 (p=0.0003), respectively. On LOOCV, all these models retained significant predictive power. Interestingly, MTV was highly correlated with LF in both sites. Conclusion: PET-based imaged features are promising tools for improving treatment management decision making. Much more research is needed to identify optimal radiomics metrics and to correlate imaging phenotype with other clinical or genomic information.

  2. Preoperative controlling nutritional status (CONUT) score as a novel predictive biomarker of survival in patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy.

    PubMed

    Ishihara, Hiroki; Kondo, Tsunenori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Tanabe, Kazunari

    2017-09-01

    The purpose of this study was to investigate the correlation between the controlling nutritional status (CONUT) score and survival of patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy (RNU). We retrospectively enrolled 107 patients. CONUT score was calculated based on the serum albumin concentration, lymphocyte count, and total cholesterol concentration. Patients were classified into 2 groups based on CONUT score. Relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU were compared between the 2 groups, and predictors of survival were analyzed using Cox proportional hazards regression models. For CONUT score, the area under the curve was 0.588 and the optimal cutoff value was 3. Twenty-four patients (22.4%) had high CONUT scores. The patients with high CONUT scores had significantly shorter 5-year RFS, CSS, and OS than did those with low CONUT scores (RFS: 50.1% vs. 66.0%; CSS: 28.1% vs. 71.7%; OS: 26.4% vs. 66.8%; all P<0.05). Results of the multivariable analysis, after adjustment for factors such as pT stage, pN stage, tumor grade, presence of lymphovascular invasion, and C-reactive protein level, revealed that CONUT score was an independent predictor of CSS (hazard ratio [HR] = 5.44, P = 0.0016) and OS (HR = 2.90, P = 0.0214) and showed marginal significance for predicting RFS (HR = 2.26, P = 0.0581). Preoperative CONUT score helps predict survival in patients with localized urothelial carcinoma of the upper urinary tract treated with RNU. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

    SciTech Connect

    Yoo, Tae; Lee, Woo Jin; Woo, Sang Myung; Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae; Moon, Sung Ho; Shin, Kyung Hwan; Kim, Sang Soo; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-11-15

    Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM{sup 3m}), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, and CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM{sup 3m}, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2-31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM{sup 3m} occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level ({<=}400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM{sup 3m} (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p < 0.05 for all three parameters). Conclusion: For patients with localized and unresectable pancreatic cancer, pretreatment CA 19-9 level could be helpful in predicting tumor response, DM{sup 3m}, and overall survival and identifying patients who will benefit from CRT.

  4. Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC).

    PubMed

    Lam, Vincent K; Bentzen, Søren M; Mohindra, Pranshu; Nichols, Elizabeth M; Bhooshan, Neha; Vyfhuis, Melissa; Scilla, Katherine A; Feigenberg, Steven J; Edelman, Martin J; Feliciano, Josephine L

    2017-02-01

    To determine the prognostic effect of Body Mass Index (BMI) in definitively treated locally advanced NSCLC patients. In this single institution retrospective cohort study, we evaluated 291 patients who were treated for locally advanced NSCLC from 2000 to 2010. They were stratified into four BMI groups based on World Health Organization criteria: underweight (<18.5kg/m2), normal weight (18.5 to <25kg/m2), overweight (25 to <30kg/m2), and obese (≧30kg/m2). Overall survival was analyzed by BMI group. Baseline patient characteristics and treatment parameters were similar between obese and normal weight patients. Increasing BMI was associated with improved overall survival (P=0.011), even when underweight cases were excluded. There was a sustained 31%-58% reduction in mortality of obese relative to normal weight patients (HR 0.68±0.21, 0.61±0.19, and 0.42±0.19, for each year post-treatment respectively). Statin use after diagnosis was highly associated with increasing BMI (P<0.001) and predicted improved survival in a multivariate analysis (HR 0.60, 95% CI 0.41-0.89, P=0.011). Obese patients in this retrospective study had significantly improved survival relative to normal weight patients. Our data suggest that the protective effect of obesity in locally advanced NSCLC is not solely due to short-term treatment effects, decreased smoking exposure, or poor prognostic factors from underweight patients. Notably, statin use was also associated with improved survival. Additional studies are needed to clarify the mechanisms and possible concomitant factors underlying the obesity paradox in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Effect of the local microenvironment on survival and thermal inactivation of Salmonella in low- and intermediate-moisture multi-ingredient foods.

    PubMed

    Li, Haiping; Fu, Xiaowen; Bima, Yige; Koontz, John; Megalis, Christina; Yang, Fei; Fleischman, Gregory; Tortorello, Mary Lou

    2014-01-01

    Multi-ingredient foods having low- or intermediate-moisture characteristics may pose a special challenge to process design and validation. Ingredients of these foods can create local microenvironments that may have a distinct impact on pathogen survival and processing requirements. In this study, two model systems, each consisting of 80% commercial peanut butter (P) and 20% nonfat dry milk powder (M), were formulated to be identical in composition, but different in the source of the Salmonella contamination as originating in either the ingredient P or M. Immediately after inoculation, Salmonella showed a 2.0-log reduction when M was the contaminated ingredient compared with a 0.6-log reduction when P was the contaminated ingredient. This pattern of survival was consistent with the single-ingredient control containing only M (2.5-log reduction) or only P (0.7-log reduction), suggesting that the immediate proximity of cells is determined by the contaminated ingredient in the model system. After 5 weeks of storage, the survival rates of Salmonella in the two systems remained different, i.e.a 4- and 2-log reduction resulted in the system with M or P as the contaminated ingredient, respectively. Furthermore, thermal inactivation efficacies also differed significantly between the two systems. Fourier transform infrared spectroscopy demonstrated the nonhomogeneous distribution of water, lipid, and protein, indicating that varied local microenvironments were present and likely affected the behavior of the pathogen. The impact of the microenvironment on inactivation and survival of Salmonella was further confirmed in a butter cookie formulation in which Salmonella was inoculated via four different ingredients. This study shows that the local microenvironment in low- and intermediate-moisture foods affects Salmonella survival and thermal inactivation. The ingredient source of the contamination should be taken into account for process design and validation to ensure the

  6. Clinical Outcome and Survival of Osteosarcoma Patients in Cipto Mangunkusumo Hospital: Limb Salvage Surgery versus Amputation.

    PubMed

    Kamal, Achmad Fauzi; Widyawarman, Heru; Husodo, Kurniadi; Hutagalung, Errol Untung; Rajabto, Wulyo

    2016-07-01

    to analyze the outcome and survival rate of osteosarcoma patients in our hospital as well as the factors affecting prognosis and functional outcome. this is a retrospective cohort study of osteosarcoma patients in Cipto Mangunkusumo Hospital underwent limb salvage surgery (LSS), amputation, LSS + amputation, and refused surgery from year 1995 to 2014. The surgical decision was based on patient's age, staging, location, neurovascular involvement, Huvos type, functional demand, patient preference, and general condition. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) score with the maximum score of 30. subjects consisted of 80 male and 52 female aged 4 to 61 year-old. They underwent limb salvage surgery (LSS) (n=37), amputation (n=42), LSS + amputation (n=2), and refused surgery (n=51). Overall 5-year cumulative survival rate was 14.6%. The 5-year survival rate for each group; LSS, amputation, combined LSS and amputation, and refused surgery was 34.8%; 15.9%; 0%; and 0%, respectively. Patients with tumor size <8 cm tend to underwent LSS compared to amputations (60.7% vs 39.3%, p=0.046). Local recurrence-free survival for LSS and amputation was 96.2% and 86.5% respectively (p=0.586). MSTS score was higher in LSS than amputation group (25.0 vs 18.5, p=0.011). LSS had higher survival rate than amputation in osteosarcoma patients who were treated in Cipto Mangunkusumo Hospital. MSTS functional score in the LSS group was higher than amputation group.

  7. Distribution of lymph node metastases is an independent predictor of survival for sigmoid colon and rectal cancer.

    PubMed

    Huh, Jung Wook; Kim, Young Jin; Kim, Hyeong Rok

    2012-01-01

    This study evaluated the prognostic significance of the distribution of lymph node metastases (LND) in patients with colorectal cancer. The impact of the LND on survival in colorectal cancer is unknown. A total of 1205 consecutive patients who underwent potentially curative surgery for sigmoid colon or rectal cancer with high ligation of the inferior mesenteric artery (IMA) from January 1997 to February 2008 were assigned to 4 groups based on LND: LND0, no lymph node metastases-615 patients (51.0%); LND1, metastases in the pericolic nodes-324 patients (26.9%); LND2, metastases in the intermediate nodes-172 patients (14.3%); and LND3, node metastases at the origin of the IMA-94 patients (7.8%). The 5-year overall survival rates of patients with LND0, LND1, LND2, and LND3 were 83%, 63%, 52%, and 28%, respectively (P < 0.001). The 5-year disease-free survival rates of patients with LND0, LND1, LND2, and LND3 were 83%, 54%, 43%, and 21%, respectively (P < 0.001). On multivariate analysis, LND was an independent prognostic factor for both overall survival and disease-free survival. However, the 5-year local recurrence-free survival rate was not inversely related to the LND. On a subset analysis that compared stage III disease with stage IV disease, the 5-year overall survival and disease-free survival rates were 45% and 31% for the patients with stage IV disease compared with 40% and 32% for the patients with stage III, LND3 disease, respectively (P = 0.761 and 0.704). For the patients with pN1 tumors, the overall survival and disease-free survival did not differ significantly according to the LND (P = 0.471 and 0.347, respectively). However, for patients with pN2 tumors, the overall survival and disease-free survival curves among the LND groups significantly differed (P < 0.001 and <0.001, respectively). LND is an independent predictor of survival for colorectal cancer patients, but it does not predict local recurrence. The N categorization including LND may enhance

  8. Scoring Systems to Estimate Intracerebral Control and Survival Rates of Patients Irradiated for Brain Metastases;Brain metastases; Radiation therapy; Local control; Survival; Prognostic scores

    SciTech Connect

    Rades, Dirk; Dziggel, Liesa; Haatanen, Tiina; Veninga, Theo; Lohynska, Radka; Dunst, Juergen; Schild, Steven E.

    2011-07-15

    Purpose: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. Methods and Materials: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC. The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. Results: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). Conclusions: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores.

  9. Survival of women with clear cell and papillary serous endometrial cancer after adjuvant radiotherapy.

    PubMed

    Foerster, Robert; Kluck, Robert; Rief, Harald; Rieken, Stefan; Debus, Juergen; Lindel, Katja

    2014-06-18

    Type II (papillary serous and clear cell) endometrial carcinoma (EC) is a rare subgroup and is considered to have an unfavorable prognosis. The purpose of this retrospective analysis was to elucidate the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors in these patients (pts). From 2004-2012 forty-two pts with type II EC underwent surgery followed by adjuvant RT at our department. Median age was 72 years. The majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4 [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy (IVB) boost. Five-year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, and 64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor (p = .028). Adjuvant RT with EBRT/IVB ensures adequate local control in type II EC, but control rates remain lower than in type I EC. A benefit of additional adjuvant ChT could not be demonstrated and a general omission of EBRT cannot be recommended at this point. Lymphovascular infiltration and pT stage might be the best predictive factors for a benefit from combined local and systemic treatment.

  10. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Jolly, Shruti

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  11. Investigation of long-term survival outcomes and failure patterns of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a retrospective analysis

    PubMed Central

    Zhao, Wei; Lei, Hao; Zhu, Xiaodong; Li, Ling; Qu, Song; Liang, Xia

    2016-01-01

    Intensity-modulated radiotherapy (IMRT) has replaced the conventional radiotherapy (2D-RT) and improved clinical efficacy in Nasopharyngeal Carcinoma (NPC) patients. In the present study, we retrospectively analyzed the clinical characteristics of patients with NPC treated with IMRT to assess the long-term survival outcomes and failure patterns. Of the 527 patients, One hundred and twenty-one patients experienced treatment failure, 86 patients developed distant metastases, and 12 patients developed a second primary tumor. The local and regional recurrence rates were 31.4% and 14.0%, respectively. The 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastatic relapse-free survival (DMFS) rates were 80.9%, 75.6%, 91.7%, 96.2%, and 83.0%, respectively. The 5-year LRFS rates of Stage T1-4 patients were 100.0%, 93.1%, 92.0%, and 85.8%, respectively. The 5-year DMFS rates of Stage N0-3 patients were 95.0%, 86.1%, 79.5%, and 67.2%, respectively. Multivariate analysis showed age and T-stage were independent predictors of OS, T-stage was an independent predictor of LRFS, and age and N-stage were independent predictors of PFS and DMFS. In summary, the improved treatment results with IMRT are primarily due to the achievement of a higher local tumor control rate and OS in NPC patients. However, distant metastasis was the most commonly observed failure pattern after treatment. These results provide deep insights about the value of IMRT in the treatment and prognosis of NPC patients. PMID:27894100

  12. Assessing the Relative Importance of Local and Regional Processes on the Survival of a Threatened Salmon Population

    PubMed Central

    Miller, Jessica A.; Teel, David J.; Peterson, William T.; Baptista, Antonio M.

    2014-01-01

    Research on regulatory mechanisms in biological populations often focuses on environmental covariates. An integrated approach that combines environmental indices with organismal-level information can provide additional insight on regulatory mechanisms. Survival of spring/summer Snake River Chinook salmon (Oncorhynchus tshawytscha) is consistently low whereas some adjacent populations with similar life histories experience greater survival. It is not known if populations with differential survival respond similarly during early marine residence, a critical period in the life history. Ocean collections, genetic stock identification, and otolith analyses were combined to evaluate the growth-mortality and match-mismatch hypotheses during early marine residence of spring/summer Snake River Chinook salmon. Interannual variation in juvenile attributes, including size at marine entry and marine growth rate, was compared with estimates of survival and physical and biological metrics. Multiple linear regression and multi-model inference were used to evaluate the relative importance of biological and physical metrics in explaining interannual variation in survival. There was relatively weak support for the match-mismatch hypothesis and stronger evidence for the growth-mortality hypothesis. Marine growth and size at capture were strongly, positively related to survival, a finding similar to spring Chinook salmon from the Mid-Upper Columbia River. In hindcast models, basin-scale indices (Pacific Decadal Oscillation (PDO) and the North Pacific Gyre Oscillation (NPGO)) and biological indices (juvenile salmon catch-per-unit-effort (CPUE) and a copepod community index (CCI)) accounted for substantial and similar portions of variation in survival for juvenile emigration years 1998–2008 (R2>0.70). However, in forecast models for emigration years 2009–2011, there was an increasing discrepancy between predictions based on the PDO (50–448% of observed value) compared with those

  13. Assessing the relative importance of local and regional processes on the survival of a threatened salmon population.

    PubMed

    Miller, Jessica A; Teel, David J; Peterson, William T; Baptista, Antonio M

    2014-01-01

    Research on regulatory mechanisms in biological populations often focuses on environmental covariates. An integrated approach that combines environmental indices with organismal-level information can provide additional insight on regulatory mechanisms. Survival of spring/summer Snake River Chinook salmon (Oncorhynchus tshawytscha) is consistently low whereas some adjacent populations with similar life histories experience greater survival. It is not known if populations with differential survival respond similarly during early marine residence, a critical period in the life history. Ocean collections, genetic stock identification, and otolith analyses were combined to evaluate the growth-mortality and match-mismatch hypotheses during early marine residence of spring/summer Snake River Chinook salmon. Interannual variation in juvenile attributes, including size at marine entry and marine growth rate, was compared with estimates of survival and physical and biological metrics. Multiple linear regression and multi-model inference were used to evaluate the relative importance of biological and physical metrics in explaining interannual variation in survival. There was relatively weak support for the match-mismatch hypothesis and stronger evidence for the growth-mortality hypothesis. Marine growth and size at capture were strongly, positively related to survival, a finding similar to spring Chinook salmon from the Mid-Upper Columbia River. In hindcast models, basin-scale indices (Pacific Decadal Oscillation (PDO) and the North Pacific Gyre Oscillation (NPGO)) and biological indices (juvenile salmon catch-per-unit-effort (CPUE) and a copepod community index (CCI)) accounted for substantial and similar portions of variation in survival for juvenile emigration years 1998-2008 (R2>0.70). However, in forecast models for emigration years 2009-2011, there was an increasing discrepancy between predictions based on the PDO (50-448% of observed value) compared with those based on

  14. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    PubMed Central

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  15. North America and the Francophone: Local and Transnational Movements for the Survival of French-Speaking North America.

    ERIC Educational Resources Information Center

    St-Hilaire, Aonghas

    1997-01-01

    Notes that North American French survives as a first language of home and community in three historic Francophone strongholds: Quebec, New Brunswick, and Louisiana. It is suggested that the dynamics of cooperation between the Quebecois, Acadians, Cajuns, and the global Francophone tell of a common cultural struggle toward a community of…

  16. Cervical nodal necrosis is an independent survival predictor in nasopharyngeal carcinoma: an observational cohort study

    PubMed Central

    Luo, Yangkun; Ren, Jing; Zhou, Peng; Gao, Yang; Yang, Guangquan; Lang, Jinyi

    2016-01-01

    Purpose Most nasopharyngeal carcinoma (NPC) patients present with locoregionally advanced disease at the time of diagnosis; however, there is a lack of consensus on specific prognostic factors potentially improving overall survival, especially in late-stage disease. Herein, we conducted a retrospective study to evaluate various potential prognostic factors in order to provide useful information for clinical treatment of T3/T4-stage NPC. Patients and methods A total of 189 previously untreated NPC patients were enrolled in the current study. All patients received intensity-modulated radiotherapy. Survival, death, relapse-free survival (both local and regional), and metastasis were recorded during follow-up. Factors affecting patient survival were assessed by using univariate and multivariate analyses. Results The median follow-up time was 69 months. The 5-year local-regional recurrence-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) of the entire group were 89.8%, 71.5%, 66.3%, and 68.9%, respectively. Univariate analysis revealed significant differences in the 5-year PFS (58.5% vs 72.5%, P=0.015) and OS (59.5% vs 75.8%, P=0.033) rates of patients with and without cervical nodal necrosis (CNN). Subgroup analyses revealed that CNN was associated with poorer distant metastasis-free survival and PFS among patients with N2 stage (P=0.046 and P=0.005) and with poorer PFS among patients with T3 or III stage (all P=0.022). Multivariate analysis revealed CNN to be an independent prognostic factor for PFS and OS (PFS: adjusted hazard ratio, 1.860; 95% CI: 1.134–3.051; P=0.014; OS: adjusted hazard ratio, 1.754; 95% CI: 1.061–2.899; P=0.028). Conclusion CNN is a potential independent negative prognostic factor in NPC patients. Our results suggest that stratification of NPC patients based on their CNN status should be considered as part of NPC disease management. PMID:27843328

  17. Increased expression of MUC3A is associated with poor prognosis in localized clear-cell renal cell carcinoma

    PubMed Central

    Zhang, Yuan; Fu, Qiang; Liu, Zheng; Wang, Zewei; Fu, Hangcheng; Xu, Jiejie; Liu, Kun

    2016-01-01

    MUC3A is a membrane-associated mucin that recent evidence reveals the role of MUC3A in pathogenesis and progression of cancers. To evaluate the association between MUC3A expression with overall survival (OS) and recurrence-free survival (RFS) in patients with localized clear-cell renal cell carcinoma (ccRCC), we retrospectively detected MUC3A expression in samples of 384 postoperative localized ccRCC patients by immunohistochemistry. Median follow-up was 73 months (range: 42 – 74 mo). Overall, 41 patients died, 47 experienced recurrence. High MUC3A expression occurred in 45.8% of localized ccRCC cases, which was significantly associated with high pT-stage, high Fuhrman grade, high frequency of necrosis and LVI, and increased risk of recurrence and death (Logrank test P < 0.001 and P < 0.001, respectively). By multivariate analysis, MUC3A expression was confirmed as an adverse independent prognostic factor for OS and RFS. The prognostic accuracy of UISS, SSIGN, Leibovich models was significantly increased when MUC3A expression was integrated. Meanwhile, MUC3A was enrolled into a newly built nomogram with other factors selected by multivariate analysis. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high MUC3A expression is an adverse prognostic biomarker for OS and RFS in postoperative localized ccRCC patients. PMID:27374181

  18. Potential for local adaptation in response to an anthropogenic agent of selection: effects of road deicing salts on amphibian embryonic survival and development

    PubMed Central

    Hopkins, Gareth R; French, Susannah S; Brodie, Edmund D

    2013-01-01

    The application of millions of tons of road deicing salts every winter in North America presents significant survival challenges to amphibians inhabiting roadside habitats. While much is known of the effects of NaCl on anuran tadpoles, less is known of effects on amphibian eggs, or any caudate life stage. In addition, little is known of the effects of MgCl2, which is now the 2nd most commonly used road deicer. Most studies have considered amphibians to be helpless victims of deicing salts, and ignore the possibility of the evolution of local adaptation to this stressor. We attempt to address these knowledge gaps and explore this evolutionary potential by examining the effects of NaCl and MgCl2 on the survival and development of eggs from different female rough-skinned newts (Taricha granulosa) from the same population. We demonstrate that both salts, at environmentally relevant concentrations, severely affect the embryonic survival and development of this amphibian, but that the effects of the salt are dependent on the identity of the mother. This female × treatment interaction results in substantial variation in tolerance to road deicing salts among newt families, providing the raw material necessary for natural selection and the evolution of local adaptation in this amphibian. PMID:23467723

  19. Potential for local adaptation in response to an anthropogenic agent of selection: effects of road deicing salts on amphibian embryonic survival and development.

    PubMed

    Hopkins, Gareth R; French, Susannah S; Brodie, Edmund D

    2013-02-01

    The application of millions of tons of road deicing salts every winter in North America presents significant survival challenges to amphibians inhabiting roadside habitats. While much is known of the effects of NaCl on anuran tadpoles, less is known of effects on amphibian eggs, or any caudate life stage. In addition, little is known of the effects of MgCl2, which is now the 2nd most commonly used road deicer. Most studies have considered amphibians to be helpless victims of deicing salts, and ignore the possibility of the evolution of local adaptation to this stressor. We attempt to address these knowledge gaps and explore this evolutionary potential by examining the effects of NaCl and MgCl2 on the survival and development of eggs from different female rough-skinned newts (Taricha granulosa) from the same population. We demonstrate that both salts, at environmentally relevant concentrations, severely affect the embryonic survival and development of this amphibian, but that the effects of the salt are dependent on the identity of the mother. This female × treatment interaction results in substantial variation in tolerance to road deicing salts among newt families, providing the raw material necessary for natural selection and the evolution of local adaptation in this amphibian.

  20. An insulin-like growth factor-II intronic variant affects local DNA conformation and ovarian cancer survival.

    PubMed

    Lu, Lingeng; Risch, Evan; Deng, Qian; Biglia, Nicoletta; Picardo, Elisa; Katsaros, Dionyssios; Yu, Herbert

    2013-09-01

    Insulin-like growth factor-II (IGF-II) may be a prognostic marker in ovarian cancer, and its intronic single nucleotide polymorphism (SNP) rs4320932 has been associated with risk of the disease. We determined whether rs4320932 is associated with IGF-II expression and patient survival in ovarian cancer, and explored whether the SNP variation affects DNA conformation both in the absence of and presence of carboplatin. IGF-II genotype (rs4320932) and phenotype were analyzed in 212 primary invasive epithelial ovarian cancer tissue samples with Taqman® SNP genotyping assays, quantitative reverse transcription-polymerase chain reaction and commercial enzyme-linked immunosorbent assay. DNA conformation was evaluated by circular dichroism (CD) spectra. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to analyze the SNP associations with patient survival. The C allele of rs4320932, previously associated with decreased risk of ovarian cancer development, was here associated with significantly elevated risks of relapse (Ptrend = 0.0002) and death (Ptrend = 0.0006), remaining significant in multivariate analyses. The adjusted hazard ratios were 3.05 (95% confidence interval [CI]: 1.47-6.37) for relapse and 3.28 (95% CI: 1.64-6.57) for death, respectively. The variant was also significantly associated with chemotherapy response, but not with other clinicopathologic variables or with IGF-II expression. DNA with genotypes TT and CC had distinct CD spectra in both the absence of and presence of carboplatin. These findings suggest that the intronic SNP rs4320932 affects patient survival and chemotherapy response via alteration of DNA conformation, but not through regulation of IGF-II expression. This novel finding may have implications in individualized medicine for the design of specific molecules targeting DNA of specific conformations.

  1. Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis

    PubMed Central

    Pierorazio, Phillip M.; Johnson, Michael H.; Patel, Hiten D.; Sozio, Stephen M.; Sharma, Ritu; Iyoha, Emmanuel; Bass, Eric B.; Allaf, Mohamad E.

    2017-01-01

    Purpose Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. Materials and Methods We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. Results The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. Conclusions Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes

  2. Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis.

    PubMed

    Pierorazio, Phillip M; Johnson, Michael H; Patel, Hiten D; Sozio, Stephen M; Sharma, Ritu; Iyoha, Emmanuel; Bass, Eric B; Allaf, Mohamad E

    2016-10-01

    Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered

  3. Analysis of recurrence and survival rates in grade 3 endometrioid endometrial carcinoma

    PubMed Central

    Wang, Jieyu; Jia, Nan; Li, Qing; Wang, Chao; Tao, Xiang; Hua, Keqin; Feng, Weiwei

    2016-01-01

    The aim of the present study was to determine risk factors associated with recurrence and survival in patients with grade 3 endometrioid endometrial carcinoma (G3EEC). A retrospective analysis of 117 patients with G3EEC, who were admitted to the Obstetrics and Gynecology Hospital of Fudan University between January 2000 and December 2011, was performed. The χ2 test or Fisher's exact test were used for the comparison of categorical variables. Kaplan-Meier method was used for estimating recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) rates. Univariate and multivariate Cox proportional hazards model were used to assess the prognostic significance of various patient characteristics. In 117 patients, 16 patients (13.7%) had tumor recurrence, of which 6 (37.5%) developed local-regional recurrence and 10 (62.5%) developed distant recurrence. Out of the 16 patients with tumor recurrence, 14 (87.5%) had a recurrence within 3 years of surgery. Statistically significant characteristics affecting RFS, DSS and OS rates were outer half myometrial invasion (MI ≥50%), advanced International Federation of Gynecology and Obstetrics stage, positive lymph node metastasis (PLNM), lymph vascular space invasion, adnexal involvement and characterization as a high-risk group, according to the Gynecologic Oncology Group 99 stratification algorithm. RFS was associated with the depth of cervical mucosa (stromal) involvement. Furthermore, in the multivariate Cox proportional hazards model, significant independent adverse factors for RFS and DSS included MI ≥50% and adnexal involvement. For OS, there were no statistically significant prognostic factors. In conclusion, MI ≥50% and adnexal involvement are independent prognostic factors for RFS and DSS in G3EEC patients. PMID:27698871

  4. Adjuvant Brachytherapy Removes Survival Disadvantage of Local Disease Extension in Stage IIIC Endometrial Cancer: A SEER Registry Analysis

    SciTech Connect

    Rossi, Peter J. Jani, Ashesh B.; Horowitz, Ira R.; Johnstone, Peter A.S.

    2008-01-01

    Purpose: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. Methods and Materials: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. Results: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). Conclusion: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.

  5. 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.

  6. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate.

    PubMed

    Rocha Lima, Caio M; Green, Mark R; Rotche, Robert; Miller, Wilson H; Jeffrey, G Mark; Cisar, Laura A; Morganti, Adele; Orlando, Nicoletta; Gruia, Gabriela; Miller, Langdon L

    2004-09-15

    This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer. IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety. In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar. IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.

  7. Long-term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation.

    PubMed

    Ali, Safina; Palmer, Frank L; Katabi, Nora; Lee, Nancy; Shah, Jatin P; Patel, Snehal G; Ganly, Ian

    2017-10-01

    To report long-term local control in patients with adenoid cystic cancer (ACC) of the head and neck managed by surgery and identify factors predictive for local failure. Single-institution retrospective cohort study. Eighty-seven patients who had surgery for ACC between 1985 and 2009 were identified. Patient, tumor, and treatment characteristics were recorded. Local recurrence-free survival (LRFS) was recorded by the Kaplan-Meier method. Predictors of local control were identified. The median age was 54 years. Seventy-two (83%) patients had perineural invasion, 61 (70%) had close/positive margins, and 58 (67%) had pT 1T2. Fifty-nine (68%) patients had postoperative radiation therapy (PORT). With a median follow-up of 85 months, the 10-year LRFS was 78.7%. There were 14 local recurrences. On multivariable analysis, pathological tumor (T)3T4 stage and no PORT were independent predictors for local failure. Patients with no PORT had a 13-fold increased risk of local failure compared to patients treated with PORT (P = 0.003) after adjusting for stage. After adjusting for T stage, patients who do not get PORT are more likely to have local recurrence. 4. Laryngoscope, 127:2265-2269, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  8. Preoperative chemoradiotherapy followed by local excision in clinical T2N0 rectal cancer

    PubMed Central

    Shin, Young Seob; Yoon, Yong sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Tae Won; Chang, Heung Moon; Park, Jin-hong; Ahn, Seung Do; Lee, Sang-Wook; Choi, Eun Kyung; Kim, Jin Cheon; Kim, Jong Hoon

    2016-01-01

    Purpose To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients’ characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer. PMID:27730804

  9. Surgery for locally advanced recurrent colorectal cancer involving the aortoiliac axis: can we achieve R0 resection and long-term survival?

    PubMed

    Abdelsattar, Zaid M; Mathis, Kellie L; Colibaseanu, Dorin T; Merchea, Amit; Bower, Thomas C; Larson, David W; Dozois, Eric J

    2013-06-01

    Locally advanced, recurrent colorectal cancer involving the aortoiliac axis may be considered a contraindication for curative surgery because of the technical challenges of achieving a negative margin resection and an assumed poor prognosis. The aim of this study was to assess oncologic outcomes and the ability to achieve an R0 resection in these patients. A retrospective review of a prospectively maintained colorectal cancer database identified 406 consecutive patients who underwent surgery for locally recurrent colorectal cancer between 1997 and 2007. This study was conducted at an academic multidisciplinary tertiary center. The demographic and clinicopathological features of patients undergoing resection for locally advanced disease involving the aortoiliac axis at our institution were reviewed. Twelve patients (7 women, median age 51 years) were identified. Major vessel involvement included internal iliac artery (n = 7), common iliac artery (n = 5), external iliac artery (n = 3), aorta (n = 3), internal iliac vein (n = 2), and external iliac vein (n = 1). R0 resection was achieved in 7 patients, and R1 resection in 5. Eleven patients received intraoperative radiation therapy. Vascular reconstruction (3 aorta, 5 common iliac, 3 external iliac) included synthetic interposition grafts, femoral-femoral bypasses, or primary anastomosis. One patient underwent venous reconstruction of the external iliac vein. No graft complications were encountered, and graft patency at 4 years was 100%. Thirty-day morbidity was seen in 9 patients, 8 of whom had Clavien grade <3. Thirty-day mortality was nil. Overall and disease-free survival at 4 years was 55% and 45%. This study was limited by its sample size, retrospective design, and the number of outcome events. R0 resection of locally advanced recurrent colorectal cancer involving the aortoiliac axis was achieved in over 50% of patients. Overall and disease-free survival was comparable to outcomes seen with locally advanced

  10. Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

    SciTech Connect

    Pai Panandiker, Atmaram S.; Merchant, Thomas E.; Beltran, Chris; Wu, Shengjie; Sharma, Shelly; Boop, Frederick A.; Jenkins, Jesse J.; Helton, Kathleen J.; Wright, Karen D.; Broniscer, Alberto; Kun, Larry E.; Gajjar, Amar

    2012-04-01

    Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic

  11. Is Ki-67 Expression Prognostic for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast Conservation Therapy (BCT)?

    SciTech Connect

    Hafeez, Farhaan; Neboori, Hanmanth J.; Harigopal, Malini; Wu, Hao; Haffty, Bruce G.; Yang, Qifeng; Schiff, Devora; Moran, Meena S.

    2013-10-01

    Purpose: Ki-67 is a human nuclear protein whose expression is strongly up-regulated in proliferating cells and can be used to determine the growth fraction in clonal cell populations. Although there are some data to suggest that Ki-67 overexpression may be prognostic for endpoints such as survival or postmastectomy recurrence, further elucidation of its prognostic significance is warranted. Specifically after breast conservation therapy (BCT) (defined in this setting as breast-conserving surgery and adjuvant radiation therapy), whether Ki-67 predicts for locoregional recurrence has not been investigated. The purpose of this study was to assess Ki-67 expression in a cohort of early-stage breast cancer patients to determine whether a significant independent association between Ki-67 and locoregional relapse exists. Methods and Materials: Ki-67 staining was conducted on a tissue microarray of 438 patients previously treated with BCT, and expression was analyzed with clinicopathologic features and outcomes from our database. Results: Ki-67 expression was more prevalent in black patients (37% of black patients vs 17% of white patients, P<.01), younger patients (27% of patients aged ≤50 years vs 15% of patients aged >50 years, P<.01), estrogen receptor (ER)–negative tumors (25% of ER-negative tumors vs 17% of ER-positive tumors, P=.04), human epidermal growth factor receptor 2 (HER2)/neu–positive tumors (35% of HER2-positive tumors vs 18% of HER2-negative tumors, P=.01), and larger tumors (26% of T2 tumors vs 16% of T1 tumors, P=.03). On univariate/multivariate analysis, Ki-67 did not predict for overall survival (74.4% vs 72.6%), cause-specific survival (82.9% vs 82.1%), local relapse-free survival (83.6% vs 88.5%), distant metastasis-free survival (76.1% vs 81.4%), recurrence-free survival (65.5% vs 74.6%), and locoregional recurrence-free survival (81.6% vs 84.7%): P>.05 for all. Conclusions: Ki-67 appears to be a surrogate marker for aggressive disease and

  12. Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

    PubMed Central

    Zhang, Lu-Ning; Xiao, Wei-Wei; Xi, Shao-Yan; OuYang, Pu-Yun; You, Kai-Yun; Zeng, Zhi-Fan; Ding, Pei-Rong; Zhang, Hui-Zhong; Pan, Zhi-Zhong; Xu, Rui-Hua; Gao, Yuan-Hong

    2016-01-01

    Background Tumor deposits (TDs) were reported to be poor prognoses in colorectal carcinoma, but the significance in locally advanced rectal cancer (LARC) (T3-4/N+) following neoadjuvant chemoradiotherapy (neo-CRT) and surgery is unclear. Since adjuvant chemotherapy showed no benefit for LARC following neo-CRT, it is of great value to investigate whether TDs can identify the subgroup of patients who may benefit from adjuvant chemotherapy. Methods Between 2004 and 2012, 310 LARC patients following neo-CRT and surgery were retrospectively reviewed. Overall survival (OS), disease-free survival (DFS), distant metastasis free survival (DMFS) and local recurrence free survival (LRFS) were evaluated by Kaplan-Meier method, log-rank test and Cox models. Results TDs-positive patients showed adverse OS, DFS and DMFS (all P≤0.001), but not LRFS (P = 0.273). In multivariate analysis, TDs continued to be associated with poor OS (HR = 2.44, 95% CI 1.32-4.4, P = 0.004) and DFS (HR = 1.99, 95% CI 1.21-3.27, P = 0.007), but not DMFS (HR = 1.77, 95% CI 0.97-3.20, P = 0.061) or LRFS (HR = 1.85, 95% CI 0.58-5.85, P = 0.298). Among TDs-positive patients, adjuvant chemotherapy significantly improved OS (P = 0.045) and DMFS (P = 0.026), but not DFS (P = 0.127) or LRFS (P = 0.862). Conclusions TDs are predictive of poor survival in LARC after neo-CRT. Fortunately, TDs-positive patients appear to benefit from adjuvant chemotherapy. PMID:26695441

  13. Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?

    PubMed

    Bednar, Filip; Zenati, Mazen S; Steve, Jennifer; Winters, Sharon; Ocuin, Lee M; Bahary, Nathan; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

    2017-05-01

    Locally advanced unresectable pancreatic cancer (LAPC) historically portends a poor prognosis. FOLFIRINOX and gemcitabine/nab-paclitaxel have proven effective in the metastatic setting. We sought to evaluate the outcomes of these regimens compared with older regimens in LAPC. A retrospective, single institutional review of all consecutive LAPC treated with "new" (FOLFIRINOX and/or gemcitabine/nab-paclitaxel) and "old" (gemcitabine or 5-FU) chemotherapy from 2010 to 2014 was performed. Univariate and multivariate predictors of resection and survival were determined. A total of 92 patients (new chemotherapy = 61, old chemotherapy = 31) were analyzed, of which 19 (21%) underwent eventual resection (median overall survival [OS] = 32 vs. 14.3 months for unresected patients, P = 0.0002). For the overall cohort, resection (hazard ratio [HR] 0.261, P = 0.014), radiation therapy (HR 0.458, P = 0.004), number of lines of chemotherapy (HR 0.486, P = 0.012), and new chemotherapy (HR 0.593 vs. old regimens, P = 0.065) were independent predictors of OS on multivariate analyses (MVA). On MVA, predictors of eventual resection were head and neck tumors (OR 0.307, P = 0.033) or SMA involvement (OR 0.285, P = 0.023). In nonresected patients (73), MVA showed treatment with new chemotherapy (HR 0.452, P = 0.006), radiation (HR 0.459, P = 0.006), and number of lines of CT (HR 0.705, P = 0.013) to be predictors of survival. In LAPC, use of FOLFIRNOX and/or gemcitabine/nab-paclitaxel is associated with improved survival compared with older chemotherapy regimens, regardless of eventual resection. Tumor location and relationship to certain vasculature are important determinants of resection in this cohort.

  14. Effect of Facilitation of Local Stakeholder Groups on Equity in Neonatal Survival; Results from the NeoKIP Trial in Northern Vietnam

    PubMed Central

    Målqvist, Mats; Hoa, Dinh Phuong Thi; Persson, Lars-Åke; Ekholm Selling, Katarina

    2015-01-01

    Background To operationalize the post-MDG agenda, there is a need to evaluate the effects of health interventions on equity. The aim of this study is to evaluate the effect on equity in neonatal survival of the NeoKIP trial (ISRCTN44599712), a population-based, cluster-randomized intervention trial with facilitated local stakeholder groups for improved neonatal survival in Quang Ninh province in northern Vietnam. Methods Semi-structured interviews were conducted with all mothers experiencing neonatal mortality and a random sample of 6% of all mothers with a live birth in the study area during the study period (July 2008-June 2011). Multilevel regression analyses were performed, stratifying mothers according to household wealth, maternal education and mother’s ethnicity in order to assess impact on equity in neonatal survival. Findings In the last year of study the risk of neonatal death was reduced by 69% among poor mothers in the intervention area as compared to poor mothers in the control area (OR 0.31, 95% CI 0.15–0.66). This pattern was not evident among mothers from non-poor households. Mothers with higher education had a 50% lower risk of neonatal mortality if living in the intervention area during the same time period (OR 0.50, 95% CI 0.28–0.90), whereas no significant effect was detected among mothers with low education. Interpretation The NeoKIP intervention promoted equity in neonatal survival based on wealth but increased inequity based on maternal education. PMID:26713871

  15. Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison

    SciTech Connect

    Duttenhaver, J.R.; Shipley, W.U.; Perrone, T.; Verhey, L.J.; Goitein, M.; Munzenrider, J.E.; Prout, G.R.; Parkhurst, E.C.; Suit, H.D.

    1983-05-01

    A total of 180 patients with carcinoma of the prostate limited to the pelvis were treated with one of two external beam irradiation techniques between 1972 and 1979. One hundred and sixteen patients were treated with conventional pelvic megavoltage x-ray therapy. Sixty-four patients were treated with combined pelvic x-ray therapy plus a perineal proton beam boost to a carefully defined prostatic tumor volume. A 160 MeV proton beam has been modified to irradiate patients with localized tumors by using conventional treatment schedules. This proton beam has the physical advantage over megavoltage x-rays of reducing the dose to normal tissues adjacent to the tumor volume. By using the proton beam boost we have delivered an increased prostatic tumor dose of 500 to 700 cGy without increasing treatment morbidity at all. The two groups are actuarially analyzed for patient survival, disease-free survival and local recurrence-free survival, and thus far, no significant differences have been noted. Because of the minimal complications observed in the proton group despite a 10% increase in dose, a randomized clinical trial comparing these two treatment techniques is studied.

  16. Effect on long-term survival of psychiatric disorder, inflammation, malnutrition, and radiotherapy-related toxicity in patients with locally advanced head and neck cancer.

    PubMed

    Unal, Dilek; Eroglu, Celalettin; Ozsoy, Saliha Demirel; Besirli, Asli; Orhan, Okan; Kaplan, Bunyamin

    2015-01-01

    To evaluate the effects on the long-term survival of psychiatric disorders, inflammation, malnutrition, and radiotherapy (RT)-related toxicity in patients with locally advanced head and neck cancer. Included were 47 patients who received RT for non-metastatic locally advanced head and neck cancer. The diagnosis of psychiatric disorder was made by the Diagnostic and Statistical Manual of Mental disorders (4th edn) (DSM-IV) criteria. Malnutrition was defined as weight loss >5% of baseline during RT. Interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed by enzyme-linked immunosorbent assay (ELISA). RT-related acute toxicity was evaluated once a week using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. The mean patient age was 57.3±11.4 years (range 33-80); 42 (89.4%) patients were male. Mean disease-free (DFS) and overall survival (OS) were 53 and 55 months, respectively. Mean DFS was significantly lower in patients with psychiatric disorder compared with those without (35 vs 59 months, p=0.013) and the same applied for mean OS (41 vs 61 months, p=0.008). There was no significant difference between patients with and without malnutrition in terms of OS. Similarly, no significant difference was seen between patients with and without RT-related toxicities in terms of OS. Age, psychiatric disorder, T status, and stage differed significantly between these groups (p<0.10) in univariate analysis. The multivariate Cox regression analysis identified that the OS was significantly associated only with psychiatric disorder (odds ratio/OR: 3.22, 95% confidence interval/CI: 1.29-8.41, p=0.013). Psychiatric disorders had unfavorable effects on OS in patients with locally advanced head and neck cancer. Inflammation, malnutrition and RT-related toxicity had no significant impact on OS.

  17. Survival in gastric cancer in relation to postoperative adjuvant therapy and determinants

    PubMed Central

    Ozden, Sevgi; Ozgen, Zerrin; Ozyurt, Hazan; Gemici, Cengiz; Yaprak, Gokhan; Tepetam, Huseyin; Mayadagli, Alpaslan

    2015-01-01

    AIM: To evaluate survival data in patients with gastric cancer in relation to postoperative adjuvant therapy and survival determinants METHODS: A total of 201 patients (mean ± SD age: 56.0 ± 11.9 years, 69.7% were males) with gastric carcinoma who were operated and followed up at Lutfi Kirdar Kartal Training and Research Hospital between 1998 and 2010 were included in this retrospective study. Follow up was evaluated divided into two consecutive periods (before 2008 and 2008-2010, respectively) based on introduction of 3-D conformal technique in radiotherapy at our clinic in 2008. Data on patient demographics, clinical and histopathological characteristics of gastric carcinoma and the type of treatment applied after surgery [postoperative adjuvant treatment protocols including chemoradiotherapy (CRT) and chemotherapy (CT), supportive therapy or follow up without any treatment] were recorded. The median duration and determinants of local recurrence free (LRF) survival, distant metastasis free (DMF) survival and overall survival were evaluated in the overall population as well as with respect to follow up years [1998-2008 (n = 127) vs 2008-2010 (n = 74)]. RESULTS: Median duration for LRF survival, DMF survival and overall survival were 31.9, 24.1 and 31.9 mo, respectively in patients with postoperative adjuvant CRT. No significant difference was noted in median duration for LRF survival, DMF survival and overall survival with respect to treatment protocols in the overall population and also with respect to followed up periods. In the overall population, CT protocols FUFA [5-fluorouracil (400 mg/m2) and leucovorin-folinic acid (FA, 20 mg/m2)] (29.9 mo) and UFT® + Antrex® [a fixed combination of the oral FU prodrug tegafur (flouroprymidine, FT, 300 mg/m2 per day) with FA (Antrex®), 15 mg tablet, two times a day] (42.5 mo) was significantly associated with longer LRF survival times than other CT protocols (P = 0.036), while no difference was noted between CT

  18. The prognostic value of systemic and local inflammation in patients with laryngeal squamous cell carcinoma

    PubMed Central

    Wang, Jie; Wang, Shengzi; Song, Xinmao; Zeng, Wenjiao; Wang, Shuyi; Chen, Fu; Ding, Hao

    2016-01-01

    Background Cancer-related systemic inflammation has been demonstrated to be associated with poor outcome in multiple types of cancers. Meanwhile, the local inflammation, which is characterized by dense intratumoral immune infiltrate, is a favorable predictor of survival outcome. Purpose To evaluate the role of systemic and local inflammation in predicting outcome in patients with laryngeal squamous cell carcinoma. Patients and methods In this retrospective study, 120 patients who had undergone postoperative radiotherapy were enrolled. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as calculated from pretreatment whole blood counts, were used to indicate systemic inflammation. The optimal cutoff values of NLR and PLR were determined using receiver operating characteristic curve analysis. Tumor infiltrating lymphocytes (TILs) density, as assessed by pathologist review of hematoxylin and eosin-stained slides, was used to represent local inflammation. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis. Results The best cutoff was 2.79 for NLR and 112 for PLR. Kaplan–Meier analysis revealed that high NLR, high PLR, and low TILs density were significantly correlated with inferior OS and RFS, respectively (all P<0.05). The Cox proportional multivariate hazard model showed that a high pretreatment PLR and a low TILs density were both independently correlated with poor OS and RFS, respectively (all P<0.05). Conclusion Markers of systemic and local inflammation, especially PLR and TILs density, are reliable prognostic factors in patients with laryngeal squamous cell carcinoma. PMID:27920556

  19. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Qiu Sufang; Lin Shaojun; Tham, Ivan W.K.; Pan Jianji; Lu Jun; Lu, Jiade J.

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  20. Natural killer-like signature observed post therapy in locally advanced rectal cancer is a determinant of pathological response and improved survival.

    PubMed

    Alderdice, Matthew; Dunne, Philip D; Cole, Aidan J; O'Reilly, Paul G; McArt, Darragh G; Bingham, Vicky; Fuchs, Marc-Aurel; McQuaid, Stephen; Loughrey, Maurice B; Murray, Graeme I; Samuel, Leslie M; Lawler, Mark; Wilson, Richard H; Salto-Tellez, Manuel; Coyle, Vicky M

    2017-09-01

    Around 12-15% of patients with locally advanced rectal cancer undergo a pathologically complete response (tumor regression grade 4) to long-course preoperative chemoradiotherapy; the remainder exhibit a spectrum of tumor regression (tumor regression grade 1-3). Understanding therapy-related transcriptional alterations may enable better prediction of response as measured by progression-free and overall survival, in addition to aiding the development of improved strategies based on the underlying biology of the disease. To this end, we performed high-throughput gene expression profiling in 40 pairs of formalin-fixed paraffin-embedded rectal cancer biopsies and matched resections following long-course preoperative chemoradiotherapy (discovery cohort). Differential gene expression analysis was performed contrasting tumor regression grades in resections. Enumeration of the tumor microenvironment cell population was undertaken using in silico analysis of the transcriptional data, and real-time PCR validation of NCR1 undertaken. Immunohistochemistry and survival analysis was used to measure CD56+ cell populations in an independent cohort (n=150). Gene expression traits observed following long-course preoperative chemoradiotherapy in the discovery cohort suggested an increased abundance of natural killer cells in tumors that displayed a clinical response to CRT in a tumor regression grade-dependent manner. CD56+ natural killer-cell populations were measured by immunohistochemistry and found to be significantly higher in tumor regression grade 3 patients compared with tumor regression grade 1-2 in the validation cohort. Furthermore, it was observed that patients positive for CD56 cells after therapy had a better overall survival (HR=0.282, 95% CI=0.109-0.729, χ(2)=7.854, P=0.005). In conclusion, we have identified a novel post-therapeutic natural killer-like transcription signature in patients responding to long-course preoperative chemoradiotherapy. Furthermore, patients

  1. An analysis of the efficacy, safety, and cost-effectiveness of fulguration under local anesthesia for small-sized recurrent masses: a comparative analysis to transurethral resection of bladder tumors in a matched cohort.

    PubMed

    Park, Dong Soo; Hwang, Jin Ho; Gong, In Hyuck; Choi, Don Kyung; Kang, Moon Hyung; Oh, Jong Jin

    2013-10-01

    To investigate the efficacy, safety, and cost-effectiveness of fulguration compared with traditional transurethral resection of a bladder tumor (TURB) among patients who had recurrent lesions after an initial TURB due to bladder cancer. For the period from March 2001 to January 2012, we reviewed the records of 42 patients who underwent a fulguration procedure for a recurrent Ta small bladder mass after excluding those with ≥1-cm sized masses at recurrence and those with masses at more than three sites. The included fulguration patients were matched with 42 TURB patients who presented with similar preoperative factors. The perioperative outcomes, including complications, recurrence-free survival rate, and total medical cost during each procedure, were compared. The mean tumor size was similar between the two groups (0.54 cm in the fulguration group vs. 0.61 cm in the TURB group, p=0.161). During the follow-up periods, 12 patients (28.5%) in the fulguration group and 11 patients (26.2%) in the TURB group experienced tumor recurrence. The recurrence-free survival rate was similar for both groups (p=0.880). The mean total medical cost of fulguration was much cheaper compared with the TURB group (393.3 vs. 1164.6 US dollars, p<0.001). Fulguration under local anesthesia for a small-sized recurrent mass is safe and efficacious in properly selected patients. In addition, it also significantly reduces the medical cost and avoids unnecessary anesthesia. Although the two treatments yielded similar oncological results, this finding should be validated in a large-scale, well-designed prospective study.

  2. Dephosphorylation of survival motor neurons (SMN) by PPM1G/PP2Cγ governs Cajal body localization and stability of the SMN complex

    PubMed Central

    Petri, Sebastian; Grimmler, Matthias; Over, Sabine; Fischer, Utz; Gruss, Oliver J.

    2007-01-01

    The survival motor neuron (SMN) complex functions in maturation of uridine-rich small nuclear ribonucleoprotein (RNP) particles. SMN mediates the cytoplasmic assembly of Sm proteins onto uridine-rich small RNAs, and then participates in targeting RNPs to nuclear Cajal bodies (CBs). Recent studies have suggested that phosphorylation might control localization and function of the SMN complex. Here, we show that the nuclear phosphatase PPM1G/PP2Cγ interacts with and dephosphorylates the SMN complex. Small interfering RNA knockdown of PPM1G leads to an altered phosphorylation pattern of SMN and Gemin3, loss of SMN from CBs, and reduced stability of SMN. Accumulation in CBs is restored upon overexpression of catalytically active, but not that of inactive, PPM1G. This demonstrates that PPM1G's phosphatase activity is necessary to maintain SMN subcellular distribution. Concomitant knockdown of unr interacting protein (unrip), a component implicated in cytoplasmic retention of the SMN complex, also rescues the localization defects. Our data suggest that an interplay between PPM1G and unrip determine compartment-specific phosphorylation patterns, localization, and function of the SMN complex. PMID:17984321

  3. The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression.

    PubMed

    Smidt, Kamille; Larsen, Agnete; Brønden, Andreas; Sørensen, Karen S; Nielsen, Julie V; Praetorius, Jeppe; Martensen, Pia M; Rungby, Jørgen

    2016-04-01

    Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting (ZNTs) proteins. The role of different ZNTs in the beta cells is currently being clarified. ZNT8 transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas ZNT3 knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of ZNT3 by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of ZNT3 in a pancreatic beta cell line, INS-1E overexpressing ZNT3. In INS-1E cells, we found that ZNT3 was abundant in insulin containing granules located close to the plasma membrane. The level of ZNT8 mRNA was significantly decreased upon over-expression of ZNT3 at different glucose concentrations (5, 11 and 21 mM glucose). ZNT3 over-expression decreased insulin content and insulin secretion whereas ZNT3 over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 mM). Our data suggest that ZNT3 and ZNT8 (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since mRNA expression of ZNT3 was inversely correlated to ZNT8 and ZNT3 over-expression reduced insulin synthesis and secretion in INS-1E cells. ZNT3 over-expression improved cell survival.

  4. HER-2/Neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer.

    PubMed

    Tulbah, Asma M; Ibrahim, Ezzeldin M; Ezzat, Adnan A; Ajarim, Dahish S; Rahal, Mohammed M; El Weshi, Amr N; Sorbris, Ralph

    2002-01-01

    Data about the prognostic and predictive value of HER-2/neu overexpression in patients with locally advanced breast cancer (LABC) treated with primary chemotherapy is limited. Therefore, this retrospective study was performed to examine this issue. Fifty-four consecutive patients with LABC were prospectively managed using a uniform multimodality approach. Response to neoadjuvant chemotherapy and survival were examined against HER-2/neu overexpression as determined by an immunohistochemistry method on formalin-fixed, paraffin-embedded samples of breast cancer using the commercially available, United States Food and Drug Administration-approved kit HercepTest (Dako Corp, Carpinteria, CA). The number of patients in each HercepTest immunostaining group were as follows; 0 in 12 patients (22%), 1+ in 8 (15%), 2+ in 12 (22%), and 3+ in 22 (41%). None of the clinical variables was significantly associated with HER-2/neu expression. After primary therapy, 22% of patients attained clinical complete response and an additional 70% achieved clinical partial response with an overall response rate of 92% (95% confidence interval: 100% to 79%). There was no significant correlation between clinical response and HercepTest positivity (p = 0.85). Of 52 patients with complete pathological data, there was no significant difference in HercepTest status between those who attained complete pathological response (46%) and those who did not (38%) (p = 0.74). Moreover, there was no significant difference in disease-free survival (75% vs 84%, [p = 0.26]) or overall survival (81% vs 84% [p = 0.31]) between those who overexpressed HER-2/neu and those with negative HercepTest, respectively. In patients with LABC, HER-2/neu overexpression determined using HercepTest assay and according to the manufacturer's approved guidelines failed to demonstrate a predictive or a prognostic role.

  5. The Quality of Cervical Cancer Brachytherapy Implantation and the Impact on Local Recurrence and Disease-Free Survival in RTOG Prospective Trials 0116 and 0128

    PubMed Central

    Viswanathan, A.N.; Moughan, J.; Small, W.; Levenback, C.; Iyer, R.; Hymes, S.; Dicker, A.P.; Miller, B.; Erickson, B.; Gaffney, D.K.

    2011-01-01

    Purpose To determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on RTOG prospective trials 0116 and 0128. Materials and Methods All enrolled patients received concurrent chemo-radiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the mid-pelvis, and appropriateness of packing, were scored for each implant. Multivariate (MV) Cox proportional hazard models were constructed for each parameter for local recurrence (LR), regional recurrence (RR), distant recurrence (DR), disease-free survival (DFS) and overall survival (OS). Results Records for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (HR=2.67, 95% C.I. = [1.11, 6.45], p=0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR=2.50, 95% C.I. = [1.05, 5.93], p=0.04) and a lower DFS rate (HR=2.28, 95% C.I. = [1.18, 4.41], p=0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR=2.06, 95% C.I. = [1.08, 3.92], p=0.03). Conclusion Assessment of the quality of a brachytherapy implant is imperative, as proper placement impacts patient disease-free survival. If feasible, inappropriate placements should be corrected prior to treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners. PMID:22193645

  6. Concomitant etoposide and cisplatin provided improved survival compared with docetaxel and cisplatin in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy

    PubMed Central

    Sen, Fatma; Tambas, Makbule; Ozkaya, Kubra; Guveli, Murat Emin; Ciftci, Rumeysa; Ozkan, Berker; Oral, Ethem Nezih; Saglam, Esra Kaytan; Saip, Pinar; Toker, Alper; Demir, Adalet; Firat, Pinar; Aydiner, Adnan; Eralp, Yesim

    2016-01-01

    Abstract Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide–cisplatin (EP) or docetaxel–cisplatin (DP) in this curative setting. Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods. A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32–70 years) and 55 years (range, 37–73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1–132 months) in the EP group and 19 months (range, 1–96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25–0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3–4: 0% vs. 6%, P = 0.024). Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile. PMID:27472701

  7. Effect of Locally Administered Ciliary Neurotrophic Factor on the Survival of Transected and Repaired Adult Sheep Facial Nerve

    PubMed Central

    Al Abri, Rashid; Kolethekkat, Arif Ali; Kelleher, Michael O.; Myles, Lynn M.; Glasby, Michael A.

    2014-01-01

    Objective to determine whether the administration of Ciliary Neurotrophic Factor (CNTF) at the site of repaired facial nerve enhances regeneration in the adult sheep model. Methods Ten adult sheep were divided into 2 groups: control and study group (CNTF group). In the CNTF group, the buccal branch of the facial nerve was transected and then repaired by epineural sutures. CNTF was injected over the left depressor labii maxillaris muscle in the vicinity of the transected and repaired nerve for 28 days under local anesthesia. In the CNTF group, the sheep were again anesthetized after nine months and the site of facial nerve repair was exposed. Detailed electrophysiological, tension experiments and morphometric studies were carried out and then analyzed statistically. Results The skin CV min, refractory period, Jitter and tension parameters were marginally raised in the CNTF group than the control but the difference was statistically insignificant between the two groups. Morphometric indices also did not show any significant changes in the CNTF group. Conclusion CNTF has no profound effect on neuronal regeneration of adult sheep animal model. Keywords CNTF; Neurtrophic factors; Sheep; Facial nerve; Regeneration. PMID:24936272

  8. Effect of locally administered ciliary neurotrophic factor on the survival of transected and repaired adult sheep facial nerve.

    PubMed

    Al Abri, Rashid; Kolethekkat, Arif Ali; Kelleher, Michael O; Myles, Lynn M; Glasby, Michael A

    2014-05-01

    to determine whether the administration of Ciliary Neurotrophic Factor (CNTF) at the site of repaired facial nerve enhances regeneration in the adult sheep model. Ten adult sheep were divided into 2 groups: control and study group (CNTF group). In the CNTF group, the buccal branch of the facial nerve was transected and then repaired by epineural sutures. CNTF was injected over the left depressor labii maxillaris muscle in the vicinity of the transected and repaired nerve for 28 days under local anesthesia. In the CNTF group, the sheep were again anesthetized after nine months and the site of facial nerve repair was exposed. Detailed electrophysiological, tension experiments and morphometric studies were carried out and then analyzed statistically. The skin CV min, refractory period, Jitter and tension parameters were marginally raised in the CNTF group than the control but the difference was statistically insignificant between the two groups. Morphometric indices also did not show any significant changes in the CNTF group. CNTF has no profound effect on neuronal regeneration of adult sheep animal model. CNTF; Neurtrophic factors; Sheep; Facial nerve; Regeneration.

  9. Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

    SciTech Connect

    Vargas, Carlos; Kestin, Larry; Go, Nel; Krauss, Daniel; Chen, Peter; Goldstein, Neal; Martinez, Alvaro; Vicini, Frank A. . E-mail: fvicini@beaumont.edu

    2005-12-01

    Purpose: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. Materials and Methods: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). Results: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy {<=}9 MeV (p = 0.03, HR 1.41), final margins {<=}2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. Conclusions: After treatment for DCIS, 10-year rates of local control

  10. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    SciTech Connect

    Blackstock, A. William . E-mail: ablackst@wfubmc.edu; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

    2006-02-01

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival.

  11. Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

    PubMed Central

    Kobayashi, Mitsuyoshi; Mori, Hirohito; Ebara, Kazuo

    2014-01-01

    We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m2) and paclitaxel (60 mg/m2). After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer. PMID:25298899

  12. Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer.

    PubMed

    Hatiboglu, G; Popeneciu, I V; Deppert, M; Nyarangi-Dix, J; Hadaschik, B; Hohenfellner, M; Teber, D; Pahernik, S

    2017-01-11

    To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer. One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQ-PR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification. One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58.6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69.4%. HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not

  13. SU-F-R-27: Use Local Shape Descriptor Based On Geodesic Distance to Predict Survival in Non-Small Cell Lung Cancer After Radiotherapy

    SciTech Connect

    Zhang, H; Yan, L; Huang, K; Kong, F; Jin, J

    2016-06-15

    Purpose: The shape of the Positron Emission Tomography (PET) image represents the heterogeneity of tumor growth in various directions, and thus could be associated with tumor malignancy. We have proposed a median geodesic distance (MGD) to represent the local complexity of the shape and use a normalized MGD (NMGD) to quantify the shape, and found a potential correlation of NMGD to survival in a 20-patient pilot study. This study was to verify the finding in a larger patient cohort. Methods: Geodesic distance of two vertices on a surface is defined as the shortest path on the surface connecting the two vertices. The MGD was calculated for each vertex on the surface to display the local complexity of the shape. The NMGD was determined as: NMGD = 100*standard deviation(MGDs)/mean(MGDs). We applied the NMGD to 40 NSCLC patients who were enrolled in prospective PET image protocols and received radiotherapy. Each patient had a pre-treatment PET scan with the resolution of 4mm*4mm*5mm. Tumors were contoured by a professional radiation oncologist and triangulation meshes were built up based on the contours. Results: The mean and standard deviation of NMGD was 6.4±3.0. The OS was 33.1±16.9 months for low NMGD group, and 15.4±15.6 months for the high NMGD group. The low NMGD group had significant better OS than the high NMGD group (p=0.0013). Conclusion: NMGD could be used as a shape biomarker to predict survival and the MGD could be combined with image texture in future to increase prediction accuracy. This study was supported by Award Number 1R01CA166948 from the NIH and National Cancer Institute.

  14. PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

    PubMed Central

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Weiju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2014-01-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1–34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1–34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1–34. Furthermore, histological analyses revealed that PTH1–34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  15. PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival.

    PubMed

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R; Tseng, Wei-Ju; Zhang, Yejia; Akintoye, Sunday O; Cengel, Keith; Liu, X Sherry; Qin, Ling

    2014-10-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage.

  16. Adjuvant radiotherapy in Stage II endometrial carcinoma: Is brachytherapy alone sufficient for local control?

    PubMed

    Paydar, Ima; DeWees, Todd; Powell, Matthew; Mutch, David G; Grigsby, Perry W; Schwarz, Julie K

    2015-01-01

    To evaluate recurrence patterns and overall survival in patients treated with adjuvant radiation after surgical staging for Stage II endometrial carcinoma. Secondary goals include identification of prognostic factors for recurrence and toxicity assessment. The medical records of 41 patients treated with adjuvant radiotherapy at Washington University School of Medicine after surgical staging for endometrial cancer (total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal cytology, lymph node dissection) were reviewed. Nineteen were treated with a combination of external beam radiotherapy and vaginal brachytherapy (VB), and 22 patients were treated with postoperative VB alone. Median followup for all patients was 41 months. Median patient age was 59 years (range, 42-87 years). All tumors were of endometrioid histology. There were 20 Grade 1 tumors, 13 Grade 2 tumors, and 8 Grade 3 tumors. For all patients, the 5-year overall survival was 69.8%, and the 5-year recurrence-free survival was 89.0%. There was no statistically significant difference in overall survival (p = 0.510) or freedom from vaginal (p = 0.840), distant (p = 0.133), or any recurrence (p = 0.275) with respect to modality of treatment (external beam radiotherapy and VB vs. VB alone). There were no pelvic lymph node recurrences. In the univariate analysis, there were no risk factors influencing overall survival or recurrences. One patient experienced a toxicity requiring hospital admission. She was treated with pelvic external beam radiation plus brachytherapy. VB alone results in excellent local control for patients with Stage II endometrial cancer after surgical staging. Long-term toxicities are rare and more common in the group of patients who were treated with pelvic external beam plus brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  17. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  18. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    SciTech Connect

    Dholakia, Avani S.; Chaudhry, Muhammad; Leal, Jeffrey P.; Chang, Daniel T.; Raman, Siva P.; Hacker-Prietz, Amy; Su, Zheng; Pai, Jonathan; Oteiza, Katharine E.; Griffith, Mary E.; Wahl, Richard L.; Tryggestad, Erik; Pawlik, Timothy; Laheru, Daniel A.; Wolfgang, Christopher L.; Koong, Albert C.; and others

    2014-07-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in

  19. Salvage cryotherapy with third-generation technology for locally recurrent prostate cancer after radiation therapy.

    PubMed

    Lian, Huibo; Yang, Rong; Lin, Tingsheng; Wang, Wei; Zhang, Gutian; Guo, Hongqian

    2016-09-01

    To present the intermediate results of the use of third-generation cryotherapy as salvage treatment for locally recurrent prostate cancer after radiation therapy. From January 2006 to July 2010, 32 patients with locally recurrent prostate cancer after radiotherapy underwent salvage cryoablation using third-generation technology. Biochemical recurrence-free survival (BRFS) was defined as the time period from salvage treatment to the date of biochemical recurrence (Phoenix definition of nadir +2 ng/ml). Complications were classified as grades 1-5 according to the modified Clavien system. Multivariate logistic regression analysis was performed to identify potential risk factors associated with recurrence after salvage cryotherapy. The median follow-up was 63 months (range 38-92). Mild complications (grades 1 and 2) included mild incontinence (9.4 %), acute rectal pain (31.3 %), hematuria (6.3 %), scrotal edema (9.4 %), urinary tract infection (3.1 %), lower urinary tract symptoms (15.6 %) and erectile dysfunction (57.1 %). Severe events (grade 3) included severe incontinence (3.1 %) and urethral sloughing (3.1 %). The rate of rectourethral fistula and urinary retention was absent. The 5-year overall survival was 92.3 %. The 5-year cancer-specific survival was 100 %. The 5-year BRFS rate using the Phoenix definition was 43.5 %. A multivariate analysis disclosed that PSA at cryoablation was the only predictive factor for biochemical recurrence. Salvage cryotherapy using third-generation technology offers a safe and effective alternative for locally recurrent prostate cancer after radiation therapy. Additional studies with longer follow-up are necessary to determine the sustained efficacy of this procedure.

  20. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  1. Low p53 Binding Protein 1 (53BP1) Expression Is Associated With Increased Local Recurrence in Breast Cancer Patients Treated With Breast-Conserving Surgery and Radiotherapy

    SciTech Connect

    Neboori, Hanmanth J.R.; Haffty, Bruce G.; Wu Hao; Yang Qifeng; Aly, Amal; Goyal, Sharad; Schiff, Devora; Moran, Meena S.; Golhar, Ryan; Chen Chunxia; Moore, Dirk; and others

    2012-08-01

    Purpose: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT). Methods and Materials: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log-rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence-free survival (IBRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS). Results: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014). Conclusion: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their clinical

  2. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials.

    PubMed

    Ichinose, Y; Kato, H; Koike, T; Tsuchiya, R; Fujisawa, T; Shimizu, N; Watanabe, Y; Mitsudomi, T; Yoshimura, M

    2001-10-01

    the group of completely resected stage IIIA-N2 non-small cell lung cancer patients (NSCLC) is considered to be heterogeneous in various aspects including survival and the recurrent pattern. In the present study, we attempted to clarify the factors which separate these patients into high and low risk groups based on the survival and local recurrence. a questionnaire survey on the survival and local recurrence of non-small cell lung cancer patients with pathological stage IIIA-N2 disease who underwent a complete resection from January 1992 to December 1993 was performed by the Japan Clinical Oncology Group as of July 1999. The information on the survival of 406 patients and that of local recurrence in 332 of them was available. the 5-year survival of the 406 patients was 31.0%. In a univariate analysis, the age, clinical and pathological T status, number of N2 stations, pathological N1 disease, operative modality and postoperative radiotherapy were all found to be important prognostic factors. Clinical N2 disease marginally influenced the survival (P=0.07). In a multivariate analysis of these variables including clinical N2 disease, the survival was significantly worse in the case of multiple N2 stations (hazard ratio=1.741), the presence of pathological N1 disease (1.403), pathological T2 or 3 disease (1.399) and an age older than 65 (1.327). The rate of freedom from any local recurrence at the bronchial stump, or in the hilar, mediastinal or supraclavicular lymph nodes at 5 years was 64%. In a univariate analysis of the freedom from local recurrence, the clinical N status, pathological T status, pathological N1 disease and number of N2 stations were all found to be important prognostic factors. A multivariate analysis revealed the freedom from local recurrence to be adversely influenced by multiple N2 stations (hazard ratio=2.05), and the presence of either clinical N1 or 2 (1.733) disease. The 5-year survival and the rate of freedom from local recurrence at 5

  3. Impact of Systemic Therapy and Recurrence Pattern on Survival Outcome after Radiofrequency Ablation for Colorectal Liver Metastases

    PubMed Central

    Stang, Axel; Donati, Marcello; Weilert, Hauke; Oldhafer, Karl Jürgen

    2016-01-01

    Background: Most patients undergoing radiofrequency ablation (RFA) of colorectal liver metastasases (CLM) develop disease recurrence, but little is known about the effect of recurrence patterns and/or systemic therapy on outcome. In this study, we examined the recurrence patterns and survival after systemic therapy plus RFA in patients with unresectable CLM without extrahepatic disease. The aims were to analyze the effect of recurrence patterns on survival and to assess the relative benefit contributed by systemic therapy and local ablation to disease control and patient outcome. Methods: From January 2002 to December 2012, 113 patients underwent RFA of liver-limited CLM after systemic therapy. Univariate and multivariate analyses for associations between clinical and/or treatment-related variables, recurrence-free survival (RFS), recurrence patterns, and overall survival (OS) were carried out. Results: Of 113 patients, 105 (92.8%) had disease recurrence (median RFS: 6.1 months). Lower post-recurrence OS was observed after early (≤6 months) than after late recurrence (8.5 versus 24.0 months, p < 0.001). Recurrence sites were RFA-sites only (4.8%), liver-only (57.1%), lung-only (10.5%), or multiple (27.6%); the corresponding post-recurrence OS was 21, 19, 39, and 7 months (p < 0.001), respectively. Response to pre-RFA systemic therapy was the strongest predictor for OS (hazard ratio [HR] 5.28), RFS (HR 3.30), early (odds ratio [OR] 6.34) and multiple-site recurrence (OR 3.83) (p < 0.01), respectively; only responders achieved 5-year OS and RFS (29% and 12% versus 0% and 0% for non-responders, p < 0.001, respectively). Conclusions: Survival after RFA for liver-limited CLM is strongly linked to the timing and pattern of non-local disease recurrence. Local ablation efficacy is necessary but not sufficient to obtain long-term disease control. Effective pre-RFA systemic therapy does favourably affect the incidence, timing and patterns of recurrence and long

  4. Re-irradiation of the chest wall for local breast cancer recurrence : Results of salvage brachytherapy with hyperthermia.

    PubMed

    Auoragh, A; Strnad, V; Ott, O J; Beckmann, M W; Fietkau, R

    2016-09-01

    Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. The 5‑year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects.

  5. The effect of consolidation chemotherapy after concurrent chemoradiotherapy on the survival of patients with locally advanced non-small cell lung cancer: a meta-analysis.

    PubMed

    Wang, Xinshuai; Ding, Xuezhen; Kong, Dejiu; Zhang, Li; Guo, Yibo; Ren, Jing; Hu, Xiaochen; Yang, Junqiang; Gao, Shegan

    2017-04-01

    Whether consolidation chemotherapy (CCT) after chemoradiotherapy (CRT) helps in the treatment of locally advanced non-small cell lung cancer (LA-NSCLC) is controversial. The aim of this meta-analysis was to evaluate the impact of CCT on overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities in patients with inoperable LA-NSCLC. PubMed, Embase, The Cochrane Library, WanFang, VIP, and CNKI were searched to identify any relevant publications. After screening the literature and completing quality assessment and data extraction, the meta-analysis was performed using RevMan5.3 software. Ultimately, 5 eligible studies with a total of 1036 patients were selected for the present meta-analysis. The results of the analysis indicated that treatment of LA-NSCLC patients with CRT followed by CCT improved OS (pooled HR 0.85; 95% CI 0.73-0.99; P = 0.03), but did not improve PFS (pooled HR 0.78; 95% CI 0.60-1.02; P = 0.07) and ORR (P = 0.26). Although it could increase the risk of grade ≥3 infection (P = 0.04), it may not increase the risk of grade ≥3 radiation pneumonitis (P = 0.09) during the CCT period. CCT after concurrent CRT may provide additional benefits in the treatment of LA-NSCLC. Although this therapeutic strategy did not prolong PFS, further assessment is warranted.

  6. The lymphocyte–monocyte ratio predicts tumor response and survival in patients with locally advanced esophageal cancer who received definitive chemoradiotherapy

    PubMed Central

    Liu, Xuemei; Li, Minghuan; Zhao, Fen; Zhu, Yingming; Luo, Yijun; Kong, Li; Zhu, Hui; Zhang, Yan; Shi, Fang; Yu, Jinming

    2017-01-01

    Background The lymphocyte–monocyte ratio (LMR), a simple biomarker that can reflect the antitumor immune response of the host, has been associated with patient prognosis in several solid tumors. The aim of this study was to evaluate whether LMR can predict clinical tumor response and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received definitive chemoradiotherapy (CRT). Patients and methods A total of 162 advanced ESCC patients treated at our institution between January 2012 and December 2013 were retrospectively recruited for analysis. Patients were treated with a platinum-based bimodal cytotoxic drug chemotherapy and concurrent radiation therapy. The LMR was calculated from blood counts in samples collected prior to treatment initiation. The predictive value of LMR for clinical tumor response and prognosis was examined. Results The LMR before CRT was significantly higher in 48 patients who achieved clinical complete response (CR) compared to that in patients who did not achieve clinical CR (4.89±1.17 vs 3.87±1.29, P<0.001). Compared to their matched counterparts, patients in the high LMR group (LMR >4.02) showed a good clinical tumor response (P<0.05). A significant independent association between a high pretreatment LMR and better outcomes was identified in a multivariate analysis for progression-free survival (PFS; hazard ratio [HR]=2.17; P<0.001) and overall survival (OS; HR=2.02; P=0.002). Conclusion In ESCC patients, a high LMR before treatment, which indicates a robust host immune system, is associated with both a good clinical tumor response after definitive CRT and favorable prognosis. PMID:28243122

  7. Central versus Peripheral Tumor Location: Influence on Survival, Local Control, and Toxicity Following Stereotactic Body Radiotherapy for Primary Non-Small-Cell Lung Cancer.

    PubMed

    Park, Henry S; Harder, Eileen M; Mancini, Brandon R; Decker, Roy H

    2015-05-01

    Stereotactic body radiotherapy (SBRT) has been increasingly utilized for medically inoperable early stage non-small-cell lung cancer. However, a lower biological equivalent dose (BED) is often used for central tumors given toxicity concerns, potentially leading to decreased local control (LC). We compared survival, LC, and toxicity outcomes for SBRT patients with centrally versus peripherally located tumors. We included patients with primary cT1-2N0M0 non-small-cell lung cancer treated with SBRT at our institution from September 2007 to August 2013 with follow-up through August 2014. Central tumor location was defined as within 2 cm of the proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Kaplan-Meier analysis and multivariable Cox regression modeling were used for overall survival (OS) and LC, and the χ test and multivariable logistic regression modeling were used for toxicity. We included 251 patients (111 central, 140 peripheral) with median follow-up of 31.2 months. Patients with central tumors were more likely to be older (mean 75.8 versus 73.5 years; p = 0.04), have larger tumors (mean 2.5 cm versus 1.9 cm; p < 0.001), and be treated with a lower BED (mean 120.2 Gy versus 143.5 Gy; p < 0.001). Multivariable analysis revealed that tumor location was not associated with worse OS, LC, or toxicity. Patients with central tumors were less likely to have acute grade greater than or equal to three toxicity than those with peripheral tumors (odds ratio: 0.24; p = 0.02). Central tumor location did not predict for inferior OS, LC, or toxicity following SBRT when a lower mean BED was utilized.

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

    SciTech Connect

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

    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 ({<=} 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). 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

  9. The quality of cervical cancer brachytherapy implantation and the impact on local recurrence and disease-free survival in radiation therapy oncology group prospective trials 0116 and 0128.

    PubMed

    Viswanathan, Akila N; Moughan, Jennifer; Small, William; Levenback, Charles; Iyer, Revathy; Hymes, Sharon; Dicker, Adam P; Miller, Brigitte; Erickson, Beth; Gaffney, David K

    2012-01-01

    The objective of the study was to determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on Radiation Therapy Oncology Group prospective trials 0116 and 0128. All enrolled patients received concurrent chemoradiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the midpelvis, and appropriateness of packing, were scored for each implant. Multivariate Cox proportional hazards models were constructed for each parameter for local recurrence (LR), regional recurrence, distant recurrence, disease-free survival (DFS), and overall survival. Records for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.11-6.45; P = 0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR, 2.50; 95% CI, 1.05-5.93; P = 0.04) and a lower DFS rate (HR, 2.28; 95% CI, 1.18-4.41; P = 0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR, 2.06; 95% CI, 1.08-3.92; P = 0.03). Assessment of the quality of a brachytherapy implant is imperative, as proper placement has an impact on patient DFS. If feasible, inappropriate placements should be corrected before treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners.

  10. Nuclear Localization of DNAJB6 Is Associated With Survival of Patients With Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells.

    PubMed

    Yu, Valen Zhuoyou; Wong, Victor Chun-Lam; Dai, Wei; Ko, Josephine Mun-Yee; Lam, Alfred King-Yin; Chan, Kwok Wah; Samant, Rajeev S; Lung, Hong Lok; Shuen, Wai Ho; Law, Simon; Chan, Yuen Piu; Lee, Nikki Pui-Yue; Tong, Daniel King Hung; Law, Tsz Ting; Lee, Victor Ho-Fun; Lung, Maria Li

    2015-12-01

    The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulates chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates β-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients who underwent esophagectomy with no preoperative chemoradiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1 ± 2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs, or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2 ± 1.8 months; 95% confidence interval [CI], 15.6-22.8 mo) than patients whose tumors had low nuclear levels of DNAJB6 (12.6 ± 1.4 mo; 95% CI, 9.8-15.4 mo; P = .004, log-rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than patients with low levels (hazard ratio, 0.562; 95% CI, 0.379-0.834; P = .004). Based on log-rank analysis and Cox regression analysis, the combination of the nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or

  11. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

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

    SciTech Connect

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    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) 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

  13. Impact of local surgical treatment on survival in young women with T1 breast cancer: long-term results of a population-based cohort.

    PubMed

    Jeon, Ye Won; Choi, Jung Eun; Park, Heung Kyu; Kim, Ku Sang; Lee, Jee Yeon; Suh, Young Jin

    2013-04-01

    The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0-131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750-1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620-1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982-2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755-2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy.

  14. Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer

    PubMed Central

    Martinelli, Enrica; Pedone Anchora, Luigi; Ferrandina, Gabriella; Tropeano, Giovanna; Fagotti, Anna; Scambia, Giovanni

    2015-01-01

    Objective we investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT). Methods 84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated. Results At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis. Conclusions polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC. PMID:26335330

  15. Back to Basics: Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma.

    PubMed

    Chang, James M; McCullough, Ann E; Dueck, Amylou C; Kosiorek, Heidi E; Ocal, Idris T; Lidner, Thomas K; Gray, Richard J; Wasif, Nabil; Northfelt, Donald W; Anderson, Karen S; Pockaj, Barbara A

    2015-12-01

    Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed. Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2-) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1-3 based on observed mitoses. A total of 1292 ER+, HER2- invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0-14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009). First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.

  16. Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study.

    PubMed

    Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Magni, Giovanna; Morabito, Alessandro

    2008-09-01

    Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000-2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.

  17. Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

    PubMed Central

    Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Magni, Giovanna; Morabito, Alessandro

    2008-01-01

    Background Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. Methods The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Results Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). Conclusion This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed. PMID:18761742

  18. Local Tumor Control, Visual Acuity, and Survival After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    SciTech Connect

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    2011-09-01

    Purpose: To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. Methods and Materials: Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. Results: Median tumor height and volume decreased from 4.8 mm and 270.7 mm{sup 3} at baseline to 2.6 mm and 86.6 mm{sup 3} at the last individual follow-up, respectively (p < 0.001, p < 0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p < 0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. Conclusion: Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the

  19. [Recurrent breast cancer obtained long-term survival with local treatment(surgery and stereotactic body radiotherapy)and systemic therapy].

    PubMed

    Morioka, Emi; Ohno, Yukako; Noguchi, Miki; Nakano, Yasuharu; Noguchi, Masakuni; Kosaka, Takeo; Takanaka, Tsuyoshi

    2012-11-01

    A 52-year-old woman developed right breast cancer and underwent modified radical mastectomy in 1994. Histologically, the tumor was invasive ductal carcinoma. She was positive for estrogen receptor (ER) but negative for progesterone receptor(PgR), while her human epidermal growth factor receptor type 2(HER2) status was not examined. Although she received adjuvant hormone therapy and chemotherapy[cyclophosphamide+doxorubicin+5-fluorouraci(l CAF), 6 courses ], she underwent partial pulmonary resection on both sides with right oophorectomy in 1997. Subsequently, she was treated with weekly doses paclitaxel(12 courses). However, she developed a pulmonary metastasis in the left breast. In 2002, she underwent a partial left pulmonary resection (ER-positive and HER2 3+) and treatment with an aromatase inhibitor. Subsequently, she was treated with trastuzumab because of repeated lung metastasis. A complete response was obtained after the administration of trastuzumab. In 2008, she developed bone metastasis in the sternum and the left seventh rib, and subsequently underwent stereotactic body radiotherapy (SBRT). She was treated with trastuzumab and aromatase inhibitor. At present, she is free of pain and is still living 15 years after breast cancer recurrence. This case suggests that the interaction of local treatment(surgery and SBRT) and systemic therapy(chemotherapy, hormonal therapy, and monoclonal therapy) may improve the survival of patients with recurrent breast cancer.

  20. Local activation of coagulation factor XIII reduces systemic complications and improves the survival of mice after Streptococcus pyogenes M1 skin infection.

    PubMed

    Deicke, Christin; Chakrakodi, Bhavya; Pils, Marina C; Dickneite, Gerhard; Johansson, Linda; Medina, Eva; Loof, Torsten G

    2016-11-01

    Coagulation is a mechanism for wound healing after injury. Several recent studies delineate an additional role of the intrinsic pathway of coagulation, also known as the contact system, in the early innate immune response against bacterial infections. In this study, we investigated the role of factor XIII (FXIII), which is activated upon coagulation induction, during Streptococcus pyogenes-mediated skin and soft tissue infections. FXIII has previously been shown to be responsible for the immobilization of bacteria within a fibrin network which may prevent systemic bacterial dissemination. In order to investigate if the FXIII-mediated entrapment of S. pyogenes also influences the disease outcome we used a murine S. pyogenes M1 skin and soft tissue infection model. Here, we demonstrate that a lack of FXIII leads to prolonged clotting times, increased signs of inflammation, and elevated bacterial dissemination. Moreover, FXIII-deficient mice show an impaired survival when compared with wildtype animals. Additionally, local reconstitution of FXIII-deficient mice with a human FXIII-concentrate (Fibrogammin(®)P) could reduce the systemic complications, suggesting a protective role for FXIII during early S. pyogenes skin infection. FXIII therefore might be a possible therapeutically application to support the early innate immune response during skin infections caused by S. pyogenes. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

    PubMed

    Turner, Natalie; Wong, Hui-Li; Templeton, Arnoud; Tripathy, Sagarika; Whiti Rogers, Te; Croxford, Matthew; Jones, Ian; Sinnathamby, Mathuranthakan; Desai, Jayesh; Tie, Jeanne; Bae, Susie; Christie, Michael; Gibbs, Peter; Tran, Ben

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.

  2. Modern multidisciplinary treatment of rectal cancer based on staging with magnetic resonance imaging leads to excellent local control, but distant control remains a challenge.

    PubMed

    Engelen, S M E; Maas, M; Lahaye, M J; Leijtens, J W A; van Berlo, C L H; Jansen, R L H; Breukink, S O; Dejong, C H C; van de Velde, C J H; Beets-Tan, R G H; Beets, G L

    2013-07-01

    The purpose of this multicenter cohort study was to evaluate whether a differentiated treatment of primary rectal cancer based on magnetic resonance imaging (MRI) can reduce the number of incomplete resections and local recurrences and improve recurrence-free and overall survival. From February 2003 until January 2008, 296 patients with rectal cancer underwent preoperative MRI using a lymph node specific contrast agent to predict circumferential resection margin (CRM), T- and N-stage. Based on expert reading of the MRI, patients were stratified in: (a) low risk for local recurrence (CRM>2mm and N0 status), (b) intermediate risk and (c) high risk (close/involved CRM, N2 status or distal tumours). Mainly based on this MRI risk assessment patients were treated with (a) surgery only (TME or local excision), (b) preoperative 5 × 5 Gy+TME and (c) a long course of chemoradiation therapy followed by surgery after a 6-8 week interval. Overall 228 patients underwent treatment with curative intent: 49 with surgery only, 86 with 5 × 5 Gy and surgery and 93 with chemoradiation and surgery. The number of complete resections (margin>1mm) was 218 (95.6%). At a median follow-up of 41 months the three-year local recurrence rate, disease-free survival rate and overall survival rate is 2.2%, 80% and 84.5%, respectively. With a differentiated multimodality treatment based on dedicated preoperative MR imaging, local recurrence is no longer the main problem in rectal cancer treatment. The new challenges are early diagnosis and treatment, reducing morbidity of treatment and preferably prevention of metastatic disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Long-term survival outcome after postoperative recurrence of non-small-cell lung cancer: who is 'cured' from postoperative recurrence?

    PubMed

    Sekihara, Keigo; Hishida, Tomoyuki; Yoshida, Junji; Oki, Tomonari; Omori, Tomokazu; Katsumata, Shinya; Ueda, Takuya; Miyoshi, Tomohiro; Goto, Masaki; Nakasone, Syoko; Ichikawa, Tomohiro; Matsuzawa, Reiko; Aokage, Keiju; Goto, Koichi; Tsuboi, Masahiro

    2017-09-01

    Since survival after postoperative non-small-cell lung cancer (NSCLC) recurrence is extremely poor, the long-term post-recurrence outcomes are not well understood. The purpose of this study was to evaluate the long-term post-recurrence outcomes and clarify who are possibly 'cured' in recent clinical practice. We reviewed the medical records of 635 patients who developed postoperative recurrence until 2012 after R0 resection for pathological Stage IA-IIIA NSCLC between 1993 and 2006. Factors associated with post-recurrence survival (PRS) and the characteristics of the long-term (≥5 years) survivors were analysed retrospectively. The 5-year PRS rate of all 635 patients was 13%. Multivariable analysis revealed that female [hazard ratio (HR) = 0.78], adenocarcinoma (HR = 0.77), locoregional (only) recurrence (HR = 0.59) and longer recurrence-free survival (HR = 0.99) were favourably associated with PRS. A total of 51 patients achieved 5-year PRS; however, 32 (63%) were cancer-bearing patients in their fifth post-recurrent year who were mainly treated by epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Subsequent PRS curves for cancer-controlled and cancer-bearing groups were different (8-year PRS: 94% vs 31%, P = 0.003). Among 19 cancer-controlled patients in their fifth post-recurrent year, 17 (89%) patients initially received radical local therapy for their recurrence. Two-thirds of 5-year survivors after postoperative NSCLC recurrence had a cancer-bearing status and showed deteriorated subsequent survival. Curability of postoperative NSCLC recurrence should be evaluated in terms of the 'cancer-controlled' status, and 'cured' population is included in the patients who are 'cancer controlled' at the fifth post-recurrent year.

  4. Localized Adult Ewing Sarcoma: Favorable Outcomes with Alternating Vincristine, Doxorubicin, Cyclophosphamide, and Ifosfamide, Etoposide (VDC/IE)-Based Multimodality Therapy.

    PubMed

    Pretz, Jennifer L; Barysauskas, Constance M; George, Suzanne; Hornick, Jason L; Raut, Chandrajit P; Chen, Yen-Lin E; Marcus, Karen J; Choy, Edwin; Hornicek, Francis; Ready, John E; DeLaney, Thomas F; Baldini, Elizabeth H

    2017-05-26

    In children with localized Ewing sarcoma (ES), addition of ifosfamide and etoposide to cyclophosphamide, doxorubicin, and vincristine (VDC/IE) improved 5-year overall survival (OS) to 70%-80%. Prior to delivery of VDC/IE in adults, 5-year OS was <50%. We reviewed our institutional outcomes for adults with ES who received VDC/IE-based treatment. Between 1997-2013, 67 adults with localized ES were treated with curative intent. Local recurrence-free survival (LRFS), progression-free survival (PFS), and OS were determined using Kaplan-Meier method; comparisons were assessed with log-rank. Proportional hazard models were used to determine predictive factors. All patients received VDC/IE (median 14 cycles.) Local therapy was surgery for 33, radiation therapy for 17, or both for 17. Median follow-up for living patients was 5.2 years. Six patients had disease progression on therapy. Site of first failure was local for three, local and distant for two, and distant for ten. Five-year LRFS was 91%; 5-year LRFS was 96% for nonpelvic disease and 64% for pelvic disease (p = .003). Five-year PFS was 66%, and 5-year OS was 79%. On multivariate analysis, pelvic site had a 3.3 times increased risk of progression (p = .01). Survival for adults with localized ES treated with VDC/IE-based multimodality therapy appears to be better than historical data and similar to excellent outcomes in children. Pelvic site of disease remains a predictor of worse outcome. Given the paucity of literature for adult ES, these data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults. The Oncologist 2017;22:1-6 IMPLICATIONS FOR PRACTICE: Ewing sarcoma (ES) is rare in adults. Treatment approaches for adults have been extrapolated from the pediatric experience, and there is a sense that adults fare less well than children. We reviewed treatment outcomes in adults with localized ES treated with cyclophosphamide, doxorubicin, and vincristine in

  5. Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

    PubMed Central

    Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

    2014-01-01

    Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. PMID:25049329

  6. Circulating serum microRNA-345 correlates with unfavorable pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer

    PubMed Central

    Yu, Jing; Li, Ning; Wang, Xin; Ren, Hua; Wang, Weihu; Wang, Shulian; Song, Yongwen; Liu, Yueping; Li, Yexiong; Zhou, Xuantong; Luo, Aiping; Liu, Zhihua; Jin, Jing

    2016-01-01

    Preoperative chemoradiotherapy (pre-CRT) has been represented as the standard treatment for locally advanced rectal cancer (LARC), but large variations of tumor radiation response to CRT have been reported in the clinic. To explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC, we analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment. MiR-345 was significantly elevated in the CRT-resistant group. Therefore, miR-345 was selected as a candidate for further analysis. We assessed the correlation between the miRNA signatures and the chemoradiotherapeutic response in 20 randomly selected LARC tissue samples (Validation set) and 87 serum samples (Training set) by qRT-PCR. Further, we validated the results in 42 randomly selected LARC serum samples (Validation set). High miR-345 expression was significantly correlated with unfavorable pre-CRT pathological response in tissue and serum. Moreover, low miR-345 levels predicted superior 3-year local recurrence free survival (LRFS). Taken together, circulating serum miR-345 correlates with unfavorable pre-CRT response and poor locoregional control in LARC. It might be a promising biomarker to facilitate patient stratification for personalized treatment. PMID:27572313

  7. Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands.

    PubMed

    Qian, Xu; Kaufmann, Andreas M; Chen, Chao; Tzamalis, Georgios; Hofmann, Veit M; Keilholz, Ulrich; Hummel, Michael; Albers, Andreas E

    2016-08-01

    Adenoid cystic carcinoma (SACC) is a rare malignancy, but a frequent subtype in minor and major salivary glands. The molecular alterations or biomarkers that underlie its development and progression as well as therapy outcomes are poorly characterized. The main study goal was to investigate reliable biomarkers and patient-related factors that may have impact on recurrence and long-term survival of SACC. The prevalence of human papilloma virus (HPV) in SACC was determined by HPV-DNA genotyping and p16 immunostaining. Epithelial growth factor receptor (EGFR), p53 and Ki-67 expression were also evaluated. Twenty-eight (42%) of 67 patients were HPV-DNA positive. Kaplan-Meier analysis indicated that SACC patients with metastases (P=0.03) had a poor overall survival (OS) and a shorter recurrence-free survival (P<0.001). Positive resection margins significantly predicted shorter recurrence-free survival (P=0.01). In the multivariate analysis, non-metastatic disease (P=0.033) and p16 positivity (P=0.005) have shown their prediction value for OS while non-metastatic disease (P=0.002), HPV positivity (P=0.041) and negative resection margin predicted a better recurrence-free survival. The present study documents for the first time the positivity for HPV infection and overexpression of certain markers (p16, Ki-67, EGFR and p53) used in diagnostics in SACC as well as characterizes clinical entities. These factors might be exploited in the future as biomarkers for its prognostic value. Using the clinical and pathological basis for predicting different outcomes could significantly facilitate SACC stratification and potentially directing treatment.

  8. Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

    PubMed

    Chang, Kun; Qin, Xiao-Jian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guo-Hai; Shen, Yi-Jun; Zhu, Yi-Ying; Ye, Ding-Wei

    2016-01-01

    The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

  9. Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005

    PubMed Central

    Chang, Kun; Qin, Xiao-Jian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guo-Hai; Shen, Yi-Jun; Zhu, Yi-Ying; Ye, Ding-Wei

    2016-01-01

    The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy. PMID:26323560

  10. Ten-year Biochemical Disease-free Survival After High-intensity Focused Ultrasound (HIFU) for Localized Prostate Cancer: Comparison with Four Different Generation Devices

    SciTech Connect

    Uchida, T.; Nakano, M.; Shoji, S.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.

    2010-03-09

    HIFU has been recognized as a minimally invasive treatment option for localized prostate cancer. The purpose of the study was to assess with a long-term outcome of HIFU for prostate cancer. From January 1999, a total of 657 patients who had HIFU with at least 2 year follow-up were treated with four different types of Sonablate registered (Focus Surgery, Indianapolis, USA) devices. Thirty-three patients were treated with Sonablate registered 200 (S200) from 1999 to 2001, 406 patients with Sonablate registered 500 (S500) from 2001 to 2005, 200 patients with Sonablate registered 500 version 4 (V4) from 2005-2008 and 19 patients with Sonablate registered 500 TCM (TCM) from 2007. Biochemical disease-free survival rate (bDFS) in all patients was 59% in 8 years. bDFS in 8 years in patients with S200 and S500 groups were 55% and 56%, and bDFS in 4 and 2 years in patients with V4 and TCM group were 72% and 84%, respectively. bDFS in low, intermediate, and high risk groups were 75%, 54%, and 43% in S200/S500 and 93%, 72%, and 58% in V4/TCM group. Negative prostate biopsy rate after HIFU was 97% in S200, 79% in S500, 94% in V4 and 100% in TCM group. HIFU as primary therapy for prostate cancer is indicated in patients with low- and intermediate-risk (T1-T2b N0M0 disease, a Gleason score of <=7, a PSA level of <20 ng/mL) and a prostate volume of less than 40 mL. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

  11. Retrospective Analysis of Local Control and Cosmetic Outcome of 147 Periorificial Carcinomas of the Face Treated With Low-Dose Rate Interstitial Brachytherapy

    SciTech Connect

    Ducassou, Anne; David, Isabelle; Filleron, Thomas; Rives, Michel; Bonnet, Jacques; Delannes, Martine

    2011-11-01

    Purpose: Skin cancer is the most common malignancy in white populations. We evaluated the local cure rate and cosmetic outcome of patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the face treated with low-dose rate brachytherapy. Methods and Materials: Between February 1990 and May 2000, 147 facial carcinomas in 132 patients were treated by {sup 192}Ir wire implantation. Side effects of brachytherapy were noted. Follow-up was 2 years or more. Locoregional recurrence-free survival (LRFS) and overall survival were recorded. Group A included patients treated by primary brachytherapy, and Group B included those treated after recurrence. Results: A total of 121 carcinomas were BCCs (82.3%) and 26 were SCCs (17.7%); the median tumor size was 10 mm. Of the tumors, 86 (58.5%) were in men and 61 (41.5%) were in women; the median age was 71 years. Group A comprised 116 lesions (78.9%), and Group B, 31 (21.1%). There were 17 relapses (11.6%) after a median follow-up of 72 months: 12 local, 4 nodal, and 1 local and nodal. Locoregional-free survival was 96.6% at 2 years and 87.3% at 5 years. Five-year LRFS was 82.6% in men and 93.3% in women (p = 0.027). After adjustment for gender, LRFS was better after primary treatment than after recurrence (hasard ratio HR, 2.91; 95% confidence interval, 1.06-8.03; p = 0.039). Five-year LRFS was 90.4% for BCC and 70.8% for SCC (p = 0.03). There were no Grade 3 complications. Conclusions: Low-dose rate brachytherapy offers good local control and cosmetic outcome in patients with periorificial skin carcinomas, with no Grade 3 complications. Brchytherapy is more efficient when used as primary treatment.

  12. The proportion of signet ring cell component in patients with localized gastric adenocarcinoma correlates with the degree of response to preoperative chemoradiation

    PubMed Central

    Charalampakis, Nikolaos; Nogueras González, Graciela M.; Elimova, Elena; Wadhwa, Roopma; Shiozaki, Hironori; Shimodaira, Yusuke; Blum, Mariela A.; Rogers, Jane E.; Harada, Kazuto; Matamoros, Aurelio; Sagebiel, Tara; Das, Prajnan; Minsky, Bruce D.; Lee, Jeffrey H.; Weston, Brian; Bhutani, Manoop S.; Estrella, Jeannelyn S.; Badgwell, Brian D.; Ajani, Jaffer A.

    2016-01-01

    Background Patients with localized gastric adenocarcinoma (LGAC), who get preoperative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. Methods We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for: (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC were assessed (0%, 1–10%, 11–49%, and 50–100%) and correlated with pathologic complete response (pathCR) or survival (OS) (p=0.046 and p=0.038, respectively). Yp stage independently prognosticated OS and recurrence-free survival (p<0.001). Conclusion Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted. PMID:27046280

  13. Post-treatment PET/CT and p16 status for predicting treatment outcomes in locally advanced head and neck cancer after definitive radiation.

    PubMed

    Awan, Musaddiq J; Lavertu, Pierre; Zender, Chad; Rezaee, Rod; Fowler, Nicole; Karapetyan, Lilit; Gibson, Michael; Wasman, Jay; Faulhaber, Peter; Machtay, Mitchell; Yao, Min

    2017-06-01

    To retrospectively review post-treatment (post-tx) FDG-PET/CT scans in patients with advanced head and neck squamous cell carcinoma (HNSCC) and known p16 status, treated with definitive (chemo)radiation (RT). A total of 108 eligible patients had N2A or greater HNSCC treated with chemoRT from August 1, 2008, to February 28, 2015, with post-tx PET/CT within 6 months after RT. Kaplan-Meier curves, log-rank statistics, and Cox proportional hazards regression were used for statistical analysis. Median follow-up was 2.38 years. Sixty-eight (63.0%) patients had p16+ and 40 (37.0%) had p16- status. Two-year overall survival and recurrence-free survival were 93.4% and 77.8%, respectively. The negative predictive value (NPV) of PET/CT for local recurrence (LR) was 100%. The NPV for regional recurrence (RR) was 96.5% for all patients, 100% for p16+ patients, and 88.5% for p16- patients. The positive predictive value (PPV) of PET/CT for recurrence was 77.3% for all patients, 50.0% for p16+, and 78.6% for p16-. The PPV for LR was 72.7% for all patients, 50.0% for p16+ patients, and 72.7% for p16- patients. The PPV for RR was 50.0% for all patients, 33% for p16+, and 66.6% for p16-. Post-tx PET/CT and p16 status were independent predictors of recurrence-free survival (p < 0.01). Post-tx PET/CT predicts treatment outcomes in both p16 + and p16- patients, and does so independently of p16 status. P16- patients with negative PET have a 10% risk of nodal recurrence, and closer follow-up in these patients is warranted.

  14. Pretreatment platelet count as a predictor for survival and distant metastasis in nasopharyngeal carcinoma patients

    PubMed Central

    CHEN, YU-PEI; CHEN, CHEN; MAI, ZHUO-YAO; GAO, JIN; SHEN, LU-JUN; ZHAO, BING-CHENG; CHEN, MENG-KUN; CHEN, GANG; YAN, FANG; HUANG, TONG-YI; XIA, YUN-FEI

    2015-01-01

    The aim of the present study was to investigate the prognostic value of different pretreatment platelet (PLT) counts on the treatment outcome in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone. A total of 1,501 NPC patients, including 412 receiving CCRT and 1,089 receiving RT, were enrolled in the present study. The PLT count cut-off points for the CCRT and RT groups were 150 and 300×109/l, respectively, and the PLT counts were categorized it into three groups: Low (PLT≤150×109/l), moderate (150×109/l300×109/l). To identify independent predictors of overall survival (OS), the Cox proportional hazards model was used to determine local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates in the CCRT and RT patients. Furthermore, univariate and multivariate analysis indicated that compared with a moderate PLT count, a low PLT count was an independent unfavorable prognostic factor for OS rate in CCRT patients [hazard ratio (HR), 2.024; 95% confidence interval (CI), 1.165–3.516], and a high PLT count was an independent unfavorable prognostic factor for OS and DMFS rates in CCRT (OS: HR, 1.742; 95% CI, 1.090–2.786; DFMS: HR, 2.110; 95%CI, 1.084–4.108) and RT (OS: HR, 1.740; 95%CI, 1.283–2.362; DMFS: HR, 2.819; 95% CI, 1.766–4.497) patients. Compared with a low PLT count, a high PLT count was significantly and independently associated with a poor DMFS rate in the RT patients (P=0.025; HR, 2.454; 95% CI, 1.121–5.372). Therefore, the present study indicates that low and high PLT counts may be useful indicators of survival and distant metastasis in NPC patients who have undergone radiation treatment. PMID:25663931

  15. Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

    PubMed

    Kümmel, A; Kümmel, S; Barinoff, J; Heitz, F; Holtschmidt, J; Weikel, W; Lorenz-Salehi, F; du Bois, A; Harter, P; Traut, A; Blohmer, J U; Ataseven, B

    2015-07-01

    Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

  16. Simvastatin radiosensitizes differentiated and stem-like breast cancer cell lines and is associated with improved local control in inflammatory breast cancer patients treated with postmastectomy radiation.

    PubMed

    Lacerda, Lara; Reddy, Jay P; Liu, Diane; Larson, Richard; Li, Li; Masuda, Hiroko; Brewer, Takae; Debeb, Bisrat G; Xu, Wei; Hortobágyi, Gabriel N; Buchholz, Thomas A; Ueno, Naoto T; Woodward, Wendy A

    2014-07-01

    Reported rates of local failure after adjuvant radiation for women with inflammatory breast cancer (IBC) and triple-negative non-IBC are higher than those of women with receptor-expressing non-IBC. These high rates of locoregional recurrence are potentially influenced by the contribution of radioresistant cancer stem cells to these cancers. Statins have been shown to target stem cells and improve disease-free survival among IBC patients. We examined simvastatin radiosensitization of multiple subtypes of breast cancer cell lines in vitro in monolayer and mammosphere-based clonogenic assays and examined the therapeutic benefit of statin use on local control after postmastectomy radiation (PMRT) among IBC patients. We found that simvastatin radiosensitizes mammosphere-initiating cells (MICs) of IBC cell lines (MDA-IBC3, SUM149, SUM190) and of the metaplastic, non-IBC triple-negative receptor cell line (SUM159). However, simvastatin radioprotects MICs of non-IBC cell lines MCF-7 and SKBR3. In a retrospective clinical study of 519 IBC patients treated with PMRT, 53 patients used a statin. On univariate analysis, actuarial 3-year local recurrence-free survival (LRFS) was higher among statin users, and on multivariate analysis, triple negative breast cancer, absence of lymphatic invasion, neoadjuvant pathological tumor response to preoperative chemotherapy, and statin use were independently associated with higher LRFS. In conclusion, patients with IBC and triple-negative non-IBC breast cancer have the highest rates of local failure, and there are no available known radiosensitizers. We report significant improvement in local control after PMRT among statin users with IBC and significant radiosensitization across triple-negative and IBC cell lines of multiple subtypes using simvastatin. These data suggest that simvastatin should be justified as a radiosensitizing agent by a prospective clinical trial. ©AlphaMed Press.

  17. Hormone receptor status and survival of medullary breast cancer patients

    PubMed Central

    Aksoy, Asude; Odabas, Hatice; Kaya, Serap; Bozkurt, Oktay; Degirmenci, Mustafa; Topcu, Turkan O.; Aytekin, Aydın; Arpaci, Erkan; Avci, Nilufer; Pilanci, Kezban N.; Cinkir, Havva Y.; Bozkaya, Yakup; Cirak, Yalcin; Gumus, Mahmut

    2017-01-01

    Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p<0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p<0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p>0.05). Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates. PMID:28133688

  18. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    SciTech Connect

    Vrdoljak, Eduard . E-mail: eduard.vrdoljak@st.hinet.hr; Prskalo, Tomislav; Omrcen, Tomislav; Situm, Kristina; Boraska, Tihana; Frleta Ilic, Nives; Jankovic, Stjepan; Hamm, Wolfgang

    2005-03-01

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m{sup 2} plus cisplatin 75 mg/m{sup 2} was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.

  19. Maximum vs. Mono Androgen Blockade and the Risk of Recurrence in Men With Localized Prostate Cancer Undergoing Brachytherapy

    SciTech Connect

    Chen, Ronald C. Sadetsky, Natalia; Chen, M.-H.; Carroll, Peter R.; D'Amico, Anthony V.

    2009-09-01

    Purpose: We examined whether maximum androgen blockade (MAB) is associated with a decreased recurrence risk vs. single-agent androgen suppression (monotherapy) for men undergoing brachytherapy (BT) for localized prostate cancer. Methods and Materials: Data from 223 men in Cancer of the Prostate Strategic Urologic Research Endeavor database who received androgen deprivation therapy (ADT) concurrent with BT for intermediate- or high-risk prostatic adenocarcinoma were included; 159 (71%) received MAB, and 64 (29%) monotherapy (luteinizing hormone-releasing hormone agonist or anti-androgen alone). Cox regression analysis was performed to assess whether the choice of ADT was associated with disease recurrence adjusting for known prognostic factors. Results: Men who received MAB had similar Gleason scores, T categories, and pretreatment prostate-specific antigen as those who received monotherapy. After a median follow-up of 49 months, the use of MAB was not associated with a decrease in the risk recurrence (p = 0.72), after adjusting for known prognostic factors. A higher PSA at diagnosis (p = 0.03) and younger age at diagnosis (p < 0.01) were associated with increased recurrence risk. The 3-year recurrence free survival was 76% for patients in both monotherapy and MAB groups. Conclusions: There are varied practice patterns in physicians' choice of the extent of concurrent ADT when used with brachytherapy for men with intermediate- or high-risk prostate cancer. Given a lack of demonstrated superiority from either ADT choice, both appear to be reasonable options.

  20. Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.

    PubMed

    Kumon, Hiromi; Sasaki, Katsumi; Ariyoshi, Yuichi; Sadahira, Takuya; Araki, Motoo; Ebara, Shin; Yanai, Hiroyuki; Watanabe, Masami; Nasu, Yasutomo

    2015-12-01

    In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 10(10) , 1.0 × 10(11) , and 1.0 × 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199).

  1. Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

    PubMed Central

    Kim, Hakushi; Komiyama, Tomoyoshi; Inomoto, Chie; Kamiguchi, Hiroshi; Kajiwara, Hiroshi; Kobayashi, Hiroyuki; Nakamura, Naoya; Terachi, Toshiro

    2016-01-01

    We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients. Among 62 RCC cases for which tumor pathology was confirmed by histopathology, ND1 sequencing revealed the presence of 30 mutation sites in 19 cases. Most mutations were heteroplasmic, with 16 of 19 cases harboring one or more heteroplasmic sites. Additionally, 12 sites had amino acid mutations, which were frequent in 10 of the cases. The 5-year recurrence-free survival (RFS) rate was significantly worse in patients with tumors >40 mm in diameter (p = 0.0091), pathological T (pT) stage ≥3 (p = 0.0122), Fuhrman nuclear atypia grade ≥III (p = 0.0070), and ND1 mutations (p = 0.0006). Multivariate analysis using these factors revealed that mutations in ND1 were significantly associated with the 5-year RFS rate (p = 0.0044). These results suggest a strong correlation between the presence of ND1 mutations in cancer tissue and postoperative recurrence of localized RCC in Japanese patients. PMID:27941608

  2. Effects of local biotic neighbors and habitat heterogeneity on tree and shrub seedling survival in an old-growth temperate forest.

    PubMed

    Bai, Xuejiao; Queenborough, Simon A; Wang, Xugao; Zhang, Jian; Li, Buhang; Yuan, Zuoqiang; Xing, Dingliang; Lin, Fei; Ye, Ji; Hao, Zhanqing

    2012-11-01

    Seedling dynamics play a crucial role in determining species distributions and coexistence. Exploring causes of variation in seedling dynamics can therefore provide key insights into the factors affecting these phenomena. We examined the relative importance of biotic neighborhood processes and habitat heterogeneity using survival data for 5,827 seedlings in 39 tree and shrub species over 2 years from an old-growth temperate forest in northeastern China. We found significant negative density-dependence effects on survival of tree seedlings, and limited effects of habitat heterogeneity (edaphic and topographic variables) on survival of shrub seedlings. The importance of negative density dependence on young tree seedling survival was replaced by habitat in tree seedlings ≥ 4 years old. As expected, negative density dependence was more apparent in gravity-dispersed species compared to wind-dispersed and animal-dispersed species. Moreover, we found that a community compensatory trend existed for trees. Therefore, although negative density dependence was not as pervasive as in other forest communities, it is an important mechanism for the maintenance of community diversity in this temperate forest. We conclude that both negative density dependence and habitat heterogeneity drive seedling survival, but their relative importance varies with seedling age classes and species traits.

  3. Preoperative Magnetic Resonance Imaging and Survival Outcomes in T1–2 Breast Cancer Patients Who Receive Breast-Conserving Therapy

    PubMed Central

    Ryu, Jaegyu; Park, Hyung Seok; Kim, Sanghwa; Kim, Jee Ye; Park, Seho

    2016-01-01

    Purpose The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. Methods A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. Results Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. Conclusion Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS. PMID:28053631

  4. Preoperative Magnetic Resonance Imaging and Survival Outcomes in T1-2 Breast Cancer Patients Who Receive Breast-Conserving Therapy.

    PubMed

    Ryu, Jaegyu; Park, Hyung Seok; Kim, Sanghwa; Kim, Jee Ye; Park, Seho; Kim, Seung Il

    2016-12-01

    The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. A total of 954 patients who had T1-2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. Preoperative MRI did not influence survival outcomes in T1-2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1-2 breast cancer may not translate into longer RFS and OS.

  5. A Prospective Study of Total Glans Resurfacing for Localized Penile Cancer to Maximize Oncologic and Functional Outcomes in a Tertiary Referral Network.

    PubMed

    O'Kelly, Fardod; Lonergan, Peter; Lundon, Dara; Nason, Gregory; Sweeney, Paul; Cullen, Ivor; Hegarty, Paul

    2017-05-01

    Penile cancer is a rare malignancy worldwide, representing only 1% of all cancers affecting men. There are little data outlining the comparative effectiveness of penile preservation techniques and to our knowledge no guidelines regarding their use currently exist. Outcomes data reporting is nonstandardized and followup is not measured consistently. The aim of this study was to analyze the outcomes of total glans resurfacing in terms of oncologic control, form and function in localized penile cancer. From 2013 to 2015, 19 prospectively enrolled patients underwent total glans resurfacing. Demographics, cosmesis, patient satisfaction and disease recurrence were assessed at followup to quantify oncologic and functional outcomes. At 3 months of followup patients completed the IIEF (International Index of Erectile Function) questionnaire detailing erectile and sexual function, and general satisfaction using a visual analog scale. All statistical analysis was performed with Prism® 6. No perioperative complications were experienced. Of the patients 94.7% had complete graft take with a median cosmesis score of 5 of 5 on the visual analog scale. There was 1 local and no regional nodal recurrence at a mean followup of 23 months. One-year progression-free and overall survival rates were 100% and the 1-year recurrence-free survival rate was 95%. Of the patients 81% reported an improved sex life postoperatively. Total glans resurfacing is a viable and acceptable option for glans preservation in patients with localized penile cancer. It demonstrates acceptable functional and oncologic outcomes. We believe that total glans resurfacing should be considered in all cases of localized penile cancer. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Angiosarcoma: A Case Report of Gingival Disease with Both Palatine Tonsils Localization

    PubMed Central

    Chamberland, Frédéric; Maurina, Tristan; Degano-Valmary, Séverine; Spicarolen, Thierry; Chaigneau, Loïc

    2016-01-01

    Angiosarcomas are one of the rarest subtypes of sarcomas; those are malignant vascular tumors arising from vascular endothelial cells. Occurrence of intra-oral angiosarcoma is extremely rare (0.0077% of all cancers in Europe). We present here, to our knowledge, the first case of a 83-year-old man with gingival and both palatine tonsils localization of a grade-two angiosarcoma discovered after a two months history of a painful lesion followed by hematoma and spontaneous bleeding. Chemotherapy with paclitaxel and hemostatic radiotherapy were inefficient and he died seven months after the first symptoms. It is essential to use the vascular markers, such as CD34, CD31, ERG and FLI1, for a correct histological diagnosis, which remains difficult because it displays a wide range of morphological appearances and multiple patterns may be present in the same tumor. The main prognostic factors are chronic pre-existing lymphedema and tumor size greater than five centimeters. Malignancy grade and stage classification should be provided in all cases in which this is feasible because of predictive meaning. When possible, wide surgical resection with negative margins remains the cornerstone for the treatment of localized angiosarcomas, but despite the improvement of surgical techniques the prognosis is poor with more than half of patients died within the first year. Adjuvant radiotherapy is the standard treatment of high–grade (two and three), deep lesions, regardless of size, because it improved the local recurrence-free survival. For advanced disease, if possible, metastasectomy should be considered. The first-line chemotherapy with doxorubicin or paclitaxel should be discussed compared to best supportive care according to patient comorbidities and preference. PMID:27746875

  7. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  8. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  9. Physical examination during chemoradiation predicts outcome of locally advanced head and neck cancer. Secondary results of a randomized phase III trial (SAKK 10/94).

    PubMed

    Ghadjar, Pirus; Sun, Hong; Zimmermann, Frank; Bodis, Stephan; Bernier, Jacques; Studer, Gabriela; Aebersold, Daniel M

    2013-10-01

    To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. The locoregional response at 50.4Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4Gy with or without cisplatin 20mg/m(2) chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. Locoregional response at 50.4Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk, locally advanced/inflammatory, and metastatic breast cancer.

    PubMed

    VanderWalde, A; Ye, W; Frankel, P; Asuncion, D; Leong, L; Luu, T; Morgan, R; Twardowski, P; Koczywas, M; Pezner, R; Paz, I B; Margolin, K; Wong, J; Doroshow, J H; Forman, S; Shibata, S; Somlo, G

    2012-08-01

    Patients with high-risk locally advanced/inflammatory and oligometastatic (≤3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor-positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials.

  11. Hyaluronidase inhibitors (sodium cromoglycate and sodium auro-thiomalate) reduce the local tissue damage and prolong the survival time of mice injected with Naja kaouthia and Calloselasma rhodostoma venoms.

    PubMed

    Yingprasertchai, Senee; Bunyasrisawat, Srisurat; Ratanabanangkoon, Kavi

    2003-11-01

    Experiments have been carried out to find potent inhibitors of hyaluronidases of Naja kaouthia (NK) and Calloselasma rhodostoma (CR) venoms with the aim of reducing local tissue damage and systemic toxicities caused by the venoms. Seven drugs/chemicals known to inhibit hyaluronidases were tested for their activity on venom enzymes. These were: sodium cromoglycate (SC), sodium aurothiomalate (SAT), apigenin, kaemferol, phenylbutazone, oxyphenbutazone and fenoprofen. The results showed that SC or SAT at 10 mM, completely inhibited the enzymes of both venoms. In in vivo experiments, SC or SAT, when incubated with NK venom prior to injection, significantly reduced edema and myonecrosis. In the case of CR venom, hemorrhage, in addition to edema and myonecrosis, was also significantly reduced. In the independent type experiment, SC or SAT were effective if injected within 1 min after the injection of venom. At longer time intervals of 3 and 10 min the inhibitors were effective in reducing some parameters of local tissue necrosis but the extent of inhibition was lower. SC and SAT at 256 and 195 microg/mouse, respectively, significantly prolonged the survival time of mice receiving lethal doses of NK. In the case of CR venoms, the two inhibitors not only prolonged the survival time but also prevented death of mice receiving lethal doses of the venom. The other inhibitors were poorly soluble in water and were studied only on enzyme inhibition and prolongation of survival time; they were mostly ineffective. Thus, SC and SAT when injected immediately at the sites of bites can reduce the systemic and local toxicity of NK and CR venoms. These results suggest that administration of these drugs at the site of venom injection may be useful in reducing venom-induced local tissue damage.

  12. Early initiation of salvage hormone therapy influences survival in patients who failed initial radiation for locally advanced prostate cancer: A secondary analysis of RTOG protocol 86-10

    SciTech Connect

    Shipley, William U. . E-mail: wshipley@partners.org; DeSilvio, Michelle; Pilepich, Michael V.; Roach, Mack; Wolkov, Harvey B.; Sause, William T.; Rubin, Philip; Lawton, Colleen A.

    2006-03-15

    Purpose: We examined overall and disease-specific survival outcomes both from the time of initial treatment and from the start of salvage hormone therapy (HT), by the extent of disease progression at the time salvage HT was started in patients treated on RTOG Protocol 86-10. Methods and Materials: With a median follow-up of 9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall survival (OVS) and disease-specific survival (DSS) were compared by the extent of disease progression at the time salvage HT was started. Results: For those patients with distant metastases (DM) present at the start of salvage HT, the OVS and DSS were significantly reduced when compared with those with DM absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8 years, 38% vs. 65%). A statistically significant increase in DSS was observed among the 143 patients with DM absent when patients with prostate-specific antigen (PSA) less than 20 were compared with those with PSA greater than 20 at the time salvage HT was started. Conclusions: The DSS and the OVS of the relapsed patient are decreased in those with more extensive disease at the time of salvage HT. However, because this protocol could not evaluate the effect of posttreatment PSA velocity on outcomes, which is likely a better predictor of long-term success with salvage HT, these results cannot be taken to demonstrate that early salvage HT in patients with long posttreatment PSA doubling times is necessary for longer survival.

  13. Laparoscopic versus open nephroureterectomy to treat localized and/or locally advanced upper tract urothelial carcinoma: oncological outcomes from a multicenter study.

    PubMed

    Liu, Jian-Ye; Dai, Ying-Bo; Zhou, Fang-Jian; Long, Zhi; Li, Yong-Hong; Xie, Dan; Liu, Bin; Tang, Jin; Tan, Jing; Yao, Kun; He, Le-Ye

    2017-01-17

    Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1-4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1-4/N0-X UTUC. We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1-4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for univariate and multivariate analysis. The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P < 0.05). The predicted 5-year intravesical recurrence- free survival (RFS) (79% vs. 88%, P = 0.204), overall RFS (47% vs. 59%, P = 0.076), cancer-specific survival (CSS) (63% vs. 70%, P = 0.186), and overall survival (OS) (61% vs. 55%, P = 0.908) rates did not differ between the ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46-3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54-1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616-3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81-3.17, P = 0.17). The results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the

  14. The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients - An analysis of NRG Oncology/Gynecologic Oncology Group trials.

    PubMed

    Chan, John K; Java, James J; Fuh, Katherine; Monk, Bradley J; Kapp, Daniel S; Herzog, Thomas; Bell, Jeffrey; Young, Robert

    2016-12-01

    To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients. Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses. Of 497 stage I-II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23days (25th-75th%: 12-33days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: <2weeks, 2-4weeks, and >4weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p=0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p=0.51; p=0.33 - global test). As compared to <2weeks, the hazard ratio for recurrence-free survival was 0.90 (95%CI=0.59-1.37) for 2-4weeks and 0.72 (95%CI=0.46-1.13) for >4weeks. Age, stage, grade, and cytology were important prognostic factors. Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Design and multiseries validation of a web-based gene expression assay for predicting breast cancer recurrence and patient survival.

    PubMed

    Van Laar, Ryan K

    2011-05-01

    Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors. Percentile-ranked expression data were used to train a "metagene" algorithm to stratify patients as having a high or low risk of recurrence. The classifier was applied to 1016 patients from five independent series. The 200-gene algorithm stratifies patients into risk groups with statistically and clinically significant differences in recurrence-free and overall survival. Multivariate analysis revealed the classifier to be the strongest predictor of outcome in each validation series. In untreated node-negative patients, 88% sensitivity and 44% specificity for 10-year recurrence-free survival was observed, with positive and negative predictive values of 32% and 92%, respectively. High-risk patients appear to significantly benefit from systemic adjuvant therapy. A 200-gene prognosis signature has been developed and validated using genomic and clinical data representing a range of breast cancer clinicopathological subtypes. It is a strong independent predictor of patient outcome and is available for research use.

  16. Clinicopathologic and survival analysis of resected ampullary adenocarcinoma.

    PubMed

    Doepker, Matthew P; Thompson, Zachary J; Centeno, Barbara A; Kim, Richard D; Wong, Joyce; Hodul, Pamela J

    2016-08-01

    Ampullary adenocarcinoma (AAC) is a rare neoplasm. We sought to determine the clinicopathologic factors contributing to the overall survival (OS) and recurrence-free (RFS) survival. Patients (pts) with resected AAC were identified from 1996 to 2015 and reviewed for clinicopathologic factors and correlated with outcome. We identified and evaluated 106 pts diagnosed with AAC. The median age was 70.2 years (range 41-86) and 60 (56.6%) were male. Overall, 105 pts (99.1%) had a pancreaticoduodenectomy. An R0 resection was achieved in 101 (95%) pts. Median follow-up was 19 months with a median OS of 49.3 months. Lymph node metastasis and poorly differentiated tumors adversely affected OS on multivariate analysis (MVA). Twenty patients (18.9%) developed recurrence. The median RFS was 27 months. RFS was adversely affected by lymph node count and metastasis, tumor differentiation, and histological subtype on MVA. Survival was not affected by the addition of adjuvant therapy. Retrieval of ≤12 lymph nodes and lymph node ratio ≥0.10 resulted in worse OS on Kaplan-Meier analysis. Our data show retrieval of ≤12 nodes, involvement of nodes with AAC, moderately or poorly differentiated tumors, and pancreaticobiliary subtype adversely affected survival, while the use of adjuvant therapy demonstrated no significant benefit. J. Surg. Oncol. 2016;114:170-175. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

    SciTech Connect

    Kageyama, Ken Yamamoto, Akira Okuma, Tomohisa Hamamoto, Shinichi Takeshita, Toru Sakai, Yukimasa Nishida, Norifumi Matsuoka, Toshiyuki Miki, Yukio

    2013-10-15

    Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

  18. Dose-Escalation Study of Thoracic Radiotherapy in Combination With Pemetrexed Plus Cisplatin in Japanese Patients With Locally Advanced Nonsquamous Non-Small Cell Lung Cancer: A Post Hoc Analysis of Survival and Recurrent Sites.

    PubMed

    Niho, Seiji; Nokihara, Hiroshi; Nihei, Keiji; Akimoto, Tetsuo; Sumi, Minako; Ito, Yoshinori; Yoh, Kiyotaka; Goto, Koichi; Ohmatsu, Hironobu; Horinouchi, Hidehito; Yamamoto, Noboru; Sekine, Ikuo; Kubota, Kaoru; Ohe, Yuichiro; Tamura, Tomohide

    2016-04-01

    We performed a post hoc analysis of progression-free survival (PFS), overall survival (OS), and recurrent sites in patients with locally advanced nonsquamous non-small cell lung cancer who were enrolled in a phase I trial of combination chemotherapy consisting of pemetrexed plus cisplatin with concurrent thoracic radiotherapy. Patients received pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) on day 1 every 3 weeks for 3 cycles plus concurrent thoracic radiotherapy consisting of 60 Gy (n=6) or 66 Gy (n=12); 4 to 6 weeks thereafter, patients received consolidation treatment with pemetrexed (500 mg/m) every 3 weeks for up to 3 cycles. We reviewed the medial records to collect data on progression, recurrent sites, late toxicity, and survival. No late radiation morbidity was observed. Thirteen patients (72%) exhibited disease progression: 8 patients had distant metastases, 8 patients had local recurrence (within the radiation field [n=6], outside the radiation field [n=2], and both [n=1]), and 3 patients had local recurrence plus distant metastases. The median PFS was 10.5 months (95% confidence interval [CI], 8.8-12.3), and the 3-year PFS rate was 28% (95% CI, 7.0-48.6). Ten of the 18 patients died of lung cancer. The median follow-up time for the censored cases was 42.8 months (range, 38.1 to 52.9 mo). The median OS was 27.3 months (95% CI, 13.1-41.6), and the 3-year OS rate was 50% (95% CI, 26.9-73.1). The median PFS and OS in our study were comparable to those of historical chemoradiotherapy controls.

  19. The impact of age on local control in women with pT1 breast cancer treated with conservative surgery and radiation therapy.

    PubMed

    Jobsen, J J; van der Palen, J; Meerwaldt, J H

    2001-10-01

    The aim of the study was to evaluate the importance of young age with regard to local control in a prospective cohort of 1085 women with pathological T1 tumours treated with breast conservative treatment (BCT). Patients were divided into two age groups: 40 years or younger, 7.8%, and older than 40 years, 92.2%. With a median follow-up of 71 months, the local recurrence rate was 10.6% in women < or =40 years, and 3.7% in older women. The local recurrence-free survival (LRFS) was significantly different for the two age groups, respectively 89%, < or =40 years, and 97.6%, >40 years (P=0.0046). A separate analysis showed a significantly decreased LRFS for young women with a positive family history, 75.4% versus 98.4% 5-year LRFS for older women. A worse LRFS for young women with a negative lymph node status was also observed, respectively 84% versus 98% 5-year LRFS (both P<0.001). In a multivariate analysis, taking into account the pre-treatment and treatment factors, age < or =40 years, was the only significant predictor of a decreased LRFS. Thus, young age is an important factor in relation to local control. In a subset analysis, this significant adverse effect of young age on outcome appears to be limited to the node-negative patients and those with a positive family history. To date, there is no evidence that young women with pT1 breast cancer, treated by mastectomy have an improved outcome when compared with those treated with conservative surgery and radiotherapy. Taking into account results from a subset analysis suggests that giving systemic therapy to a subgroup of women who are < or =40 years, node-negative and/or have a positive family history might give a better local control.

  20. Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

    SciTech Connect

    Kinsella, T.J.; Loeffler, J.S.; Fraass, B.A.; Tepper, J.

    1983-08-01

    A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. Local control was achieved in nine patients (90%) with a follow-up of 30 to 119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.

  1. Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base.

    PubMed

    Amini, Arya; Jones, Bernard L; McDermott, Jessica D; Serracino, Hilary S; Jimeno, Antonio; Raben, David; Ghosh, Debashis; Bowles, Daniel W; Karam, Sana D

    2016-05-15

    The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone. The National Cancer Data Base was queried for patients older than 70 years with nonmetastatic oropharyngeal, laryngeal, or hypopharyngeal cancer (T3-4 or N(+)). CRT was defined as chemotherapy started within 14 days of the initiation of RT. Univariate analysis, multivariate analysis (MVA), propensity score matching (PSM), and recursive partitioning analysis (RPA) were performed. The study included 4042 patients: 2538 (63%) received CRT. The median follow-up was 19 months. The unadjusted median OS was longer with the addition of CRT (P < .001). OS was superior with CRT in the MVA (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.58-0.68; P < .001) and PSM analyses (HR, 0.73; 95% CI, 0.66-0.80; P < .001) in comparison with RT alone. According to RPA, CRT was associated with longer OS for patients 81 years or younger with low comorbidity scores and either T1-2/N2-3 disease or T3-4/N0-3 disease. The survival benefit with CRT disappeared for 2 subgroups in the 71- to 81-year age range: those with T1-2, N1, and Charlson-Deyo 0-1 (CD0-1) disease and those with T3-4, N1+, and CD1+ disease. Patients who were older than 81 years did not have increased survival with CRT. The receipt of CRT was associated with a longer duration of RT (odds ratio, 1.74; 95% CI, 1.50-2.01; P < .001). Patients older than 70 years should not be denied concurrent chemotherapy solely on the basis of age; additional factors, including the performance status and the tumor stage, should be taken into account. Cancer 2016;122:1533-43. © 2016 American Cancer Society. © 2016 American Cancer Society.

  2. Pretreatment serum xanthophyll concentrations as predictors of head and neck cancer recurrence and survival

    PubMed Central

    Arthur, Anna E.; Bellile, Emily L.; Rozek, Laura S.; Peterson, Karen E.; Ren, Jianwei; Harris, Ethan; Mueller, Christie; Jolly, Shruti; Peterson, Lisa A.; Wolf, Gregory T.; Djuric, Zora

    2015-01-01

    Background The purpose of this study was to examine associations of pretreatment serum carotenoids, tocopherols, and quercetin with prognosis in 154 newly diagnosed head and neck cancer (HNC) patients. Methods Pretreatment blood and health surveys were collected. Serum micronutrients were measured by HPLC. Data on recurrence and death were collected annually. Cox proportional hazards models measured associations of serum nutrient concentrations with recurrence and overall survival. Results During a median follow-up time of 37 months, there were 32 recurrences and 27 deaths. After controlling for covariates, subjects with high versus low serum xanthophyll and total carotenoid concentrations had significantly longer recurrence-free time (P = 0.002 and P = 0.02, respectively). Overall survival time was significantly longer in subjects with high versus low serum xanthophyll concentrations (P = 0.02). Conclusions Future research should evaluate the possible benefits of interventions to increase intakes of rich food sources of xanthophylls in this patient population. PMID:26614223

  3. Impact of obesity on the survival of patients with early-stage squamous cell carcinoma of the oral tongue.

    PubMed

    Iyengar, Neil M; Kochhar, Amit; Morris, Patrick G; Morris, Luc G; Zhou, Xi K; Ghossein, Ronald A; Pino, Alejandro; Fury, Matthew G; Pfister, David G; Patel, Snehal G; Boyle, Jay O; Hudis, Clifford A; Dannenberg, Andrew J

    2014-04-01

    Although obesity increases risk and negatively affects survival for many malignancies, the prognostic implications in squamous cell carcinoma (SCC) of the oral tongue, a disease often associated with prediagnosis weight loss, are unknown. Patients with T1-T2 oral tongue SCC underwent curative-intent resection in this single-institution study. All patients underwent nutritional assessment prior to surgery. Body mass index (BMI) was calculated from measured height and weight and categorized as obese (≥ 30 kg/m(2) ), overweight (25-29.9 kg/m(2) ), or normal (18.5-24.9 kg/m(2) ). Clinical outcomes, including disease-specific survival, recurrence-free survival, and overall survival, were compared by BMI group using Cox regression. From 2000 to 2009, 155 patients (90 men, 65 women) of median age 57 years (range, 18-86 years) were included. Baseline characteristics were similar by BMI group. Obesity was significantly associated with adverse disease-specific survival compared with normal weight in univariable (hazard ratio [HR] = 2.65, 95% confidence interval [CI] = 1.07-6.59; P = .04) and multivariable analyses (HR = 5.01; 95% CI = 1.69-14.81; P = .004). A consistent association was seen between obesity and worse recurrence-free survival (HR = 1.87; 95% CI = 0.90-3.88) and between obesity and worse overall survival (HR = 2.03; 95% CI = 0.88-4.65) though without reaching statistical significance (P = .09 and P = .10, respectively) in multivariable analyses. In this retrospective study, obesity was an adverse independent prognostic variable. This association may not have been previously appreciated due to confounding by multiple factors including prediagnosis weight loss. © 2013 American Cancer Society.

  4. Growth, survival, longevity, and population size of the Big Mouth Cave salamander (Gyrinophilus palleucus necturoides) from the type locality in Grundy County, Tennessee, USA

    USGS Publications Warehouse

    Niemiller, Matthew L.; Glorioso, Brad M.; Fenolio, Dante B.; Reynolds, R. Graham; Taylor, Steven J.; Miller, Brian T.

    2016-01-01

    Salamander species that live entirely in subterranean habitats have evolved adaptations that allow them to cope with perpetual darkness and limited energy resources. We conducted a 26-month mark–recapture study to better understand the individual growth and demography of a population of the Big Mouth Cave Salamander (Gyrinophilus palleucus necturoides). We employed a growth model to estimate growth rates, age at sexual maturity, and longevity, and an open population model to estimate population size, density, detectability, and survival rates. Furthermore, we examined cover use and evidence of potential predation. Individuals probably reach sexual maturity in 3–5 years and live at least nine years. Survival rates were generally high (>75%) but declined during the study. More than 30% of captured salamanders had regenerating tails or tail damage, which presumably represent predation attempts by conspecifics or crayfishes. Most salamanders (>90%) were found under cover (e.g., rocks, trash, decaying plant material). Based on 11 surveys during the study, population size estimates ranged from 21 to 104 individuals in the ca. 710 m2 study area. Previous surveys indicated that this population experienced a significant decline from the early 1970s through the 1990s, perhaps related to silvicultural and agricultural practices. However, our data suggest that this population has either recovered or stabilized during the past 20 years. Differences in relative abundance between early surveys and our survey could be associated with differences in survey methods or sampling conditions rather than an increase in population size. Regardless, our study demonstrates that this population is larger than previously thought and is in no immediate risk of extirpation, though it does appear to exhibit higher rates of predation than expected for a species believed to be an apex predator of subterranean food webs.

  5. Racial disparity in survival from early breast cancer in the department of defense healthcare system.

    PubMed

    Rizzo, Julie A; Sherman, William E; Arciero, Cletus A

    2015-06-01

    Racial disparity is often identified as a factor in survival from breast cancer in the United States. Current data regarding survival in patients treated in the Department of Defense Military Healthcare System is lacking. The Department of Defense Automated Central Tumor Registry (ACTUR) was queried for all women diagnosed with Stage I or II breast cancer from January 1, 1996 through December 31, 2008. Statistical analyses evaluated demographics, surgical treatment, tumor stage, and survival rates. There were 8,890 patients meeting inclusion criteria. Patients who were younger, Asian American (versus white or black), lower T and/or N stage had significantly improved survival rates. Interestingly, white and black patients demonstrated similar survival in this study. Patients with a longer period of time between diagnosis and treatment had no decrement in survival. As would be expected, patients with a longer recurrence free period enjoyed longer survival. Survival from early stage breast cancer is equivalent between white and black patients in the Department of Defense Healthcare System. This finding is contrary to reports from our civilian counterparts and may be indicative of improved access to care and overall improved cancer surveillance. © 2015 Wiley Periodicals, Inc.

  6. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma

    PubMed Central

    Huang, Yun-Ching; Chang, Ying-Hsu; Chiu, Kuo-Hsiung; Shindel, Alan W.; Lai, Chia-Hsuan

    2016-01-01

    There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients. PMID:27910890

  7. Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer

    PubMed Central

    Tahara, Tomomitsu; Shibata, Tomoyuki; Okamoto, Yasuyuki; Yamazaki, Jumpei; Kawamura, Tomohiko; Horiguchi, Noriyuki; Okubo, Masaaki; Nakano, Naoko; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Ohmiya, Naoki

    2016-01-01

    Background and aim TP53 gene is frequently mutated in gastric cancer (GC), but the relationship with clinicopathological features and prognosis is conflicting. Here, we screened TP53 mutation spectrum of 214 GC patients in relation to their clinicopathological features and prognosis. Results TP53 nonsilent mutations were detected in 80 cases (37.4%), being frequently occurred as C:G to T:A single nucleotide transitions at 5′-CpG-3′ sites. TP53 mutations occurred more frequently in differentiated histologic type than in undifferentiated type in the early stage (48.6% vs. 7%, P=0.0006), while the mutations correlated with venous invasion among advanced stage (47.7% vs. 20.7%, P=0.04). Subset of GC with TP53 hot spot mutations (R175, G245, R248, R273, R282) presented significantly worse overall survival and recurrence free survival compared to others (both P=0.001). Methods Matched biopsies from GC and adjacent tissues from 214 patients were used for the experiment. All coding regions of TP53 gene (exon2 to exon11) were examined using Sanger sequencing. Conclusion Our data suggest that GC with TP53 mutations seems to develop as differentiated histologic type and show aggressive biological behavior such as venous invasion. Moreover, our data emphasizes the importance of discriminating TP53 hot spot mutations (R175, G245, R248, R273, R282) to predict worse overall survival and recurrence free survival of GC patients. PMID:27323394

  8. Quality of life, morbidity, and mortality results of a prospective phase II study of intermittent androgen suppression for men with evidence of prostate-specific antigen relapse after radiation therapy for locally advanced prostate cancer.

    PubMed

    Bruchovsky, Nicholas; Klotz, Laurence; Crook, Juanita; Phillips, Norman; Abersbach, Jonas; Goldenberg, S Larry

    2008-03-01

    Observations of quality of life (QOL), morbidity, and mortality were obtained from the results of a prospective phase II study of intermittent androgen suppression for recurrent prostate cancer after radiation therapy. Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen level after external-beam radiation of the prostate were treated intermittently with a 36-week course of cyproterone and leuprolide. At predetermined intervals, QOL was assessed using the Southwest Oncology Group 9346 QOL and the American Urological Association symptom score questionnaires. Progression-free and overall survival rates were estimated using the Kaplan-Meier method. Parameters related to progression were explored with univariate and multivariate analyses. The incidence of adverse events was higher when patients were on treatment. Fatigue, dyspnea, and hematuria were the most common symptoms and signs recorded (50.5%, 24.8%, and 17.4%, respectively). Less frequent were myocardial infarction (7.3%), cerebrovascular accident (6.4%), and deep vein thrombosis (5.5%). Quality of life improved when off treatment, as indicated by a shift toward baseline levels in the scales depicting physical and work functions, hot flashes, impotence, sexual performance, urgency, and nocturia. Biochemical recurrence-free survival at 5 years was 70%, with a median > 6 years. The overall 5-year survival was 80%, similar to that of an age-matched population of normal men. Intermittent androgen suppression is a potentially useful treatment for locally recurrent prostate cancer after radiation therapy with QOL benefits in the off-treatment interval and no apparent deleterious effects on short- to medium-term survival.

  9. Long-Term Outcome and Morbidity After Treatment With Accelerated Radiotherapy and Weekly Cisplatin for Locally Advanced Head-and-Neck Cancer: Results of a Multidisciplinary Late Morbidity Clinic

    SciTech Connect

    Ruetten, Heidi; Pop, Lucas A.M.; Janssens, Geert O.R.J.; Takes, Robert P.; Knuijt, Simone; Berg, Manon van den; Merkx, Matthias A.; Herpen, Carla M.L. van; Kaanders, Johannes H.A.M.

    2011-11-15

    Purpose: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. Methods and Materials: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. Results: Compliance with the treatment protocol was high, with 87% of the patients receiving at least five cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. Conclusion: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.

  10. An Eight-Year Experience of HDR Brachytherapy Boost for Localized Prostate Cancer: Biopsy and PSA Outcome

    SciTech Connect

    Bachand, Francois; Martin, Andre-Guy; Beaulieu, Luc; Harel, Francois M.Sc.; Vigneault, Eric

    2009-03-01

    Purpose: To evaluate the biochemical recurrence-free survival (bRFS), the 2-year biopsy outcome and the prostate-specific antigen (PSA) bounce in patients with localized prostate cancer treated with an inversely planned high-dose-rate (HDR) brachytherapy boost. Materials and methods: Data were collected from 153 patients treated between 1999 and 2006 with external beam pelvic radiation followed by an HDR Ir-192 prostate boost. These patients were given a boost of 18 to 20 Gy using inverse-planning with simulated annealing (IPSA).We reviewed and analyzed all prostate-specific antigen levels and control biopsies. Results: The median follow-up was 44 months (18-95 months). When categorized by risk of progression, 74.5% of patients presented an intermediate risk and 14.4% a high one. Prostate biopsies at 2 years posttreatment were negative in 86 of 94 patients (91.5%), whereas two biopsies were inconclusive. Biochemical control at 60 months was at 96% according to the American Society for Therapeutic Radiology and Oncology and the Phoenix consensus definitions. A PSA bounce (PSA values of 2 ng/mL or more above nadir) was observed in 15 patients of 123 (9.8%). The median time to bounce was 15.2 months (interquartile range, 11.0-17.7) and the median bounce duration 18.7 months (interquartile range, 12.1-29). The estimate of overall survival at 60 months was 97.1% (95% CI, 91.6-103%). Conclusions: Considering that inverse planned HDR brachytherapy prostate boosts led to an excellent biochemical response, with a 2-year negative biopsy rate, we recommend a conservative approach in face of a PSA bounce even though it was observed in 10% of patients.

  11. Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

    PubMed

    Bazan, Jose G; Duan, Fenghai; Snyder, Bradley S; Horng, Dunstan; Graves, Edward E; Siegel, Barry A; Machtay, Mitchell; Loo, Billy W

    2017-01-01

    To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT). This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS. Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS (p = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered (p = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61-69 Gy or ≥70 Gy (p = 0.001). Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.

  12. Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer.

    PubMed

    Khwaja, Shariq S; Ivanovich, Jennifer; DeWees, Todd A; Ochoa, Laura; Mullen, Daniel F; Thomas, Maria; Margenthaler, Julie A; Cyr, Amy; Naughton, Michael; Sanati, Souzan; Eberlein, Timothy J; Gillanders, William E; Aft, Rebecca L; Zoberi, Jacqueline E; Zoberi, Imran

    2016-02-01

    Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient-, tumor-, and treatment-related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence-free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23-39 years) with a median follow-up of 47 months (8-138 months). Breast-conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty-two percent of patients had triple negative tumors (TN, ER-/PR-/HER2 nonamplified). Four-year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  13. Second hand smoke exposure and survival in early-stage non-small-cell lung cancer patients.

    PubMed

    Zhou, Wei; Heist, Rebecca S; Liu, Geoffrey; Asomaning, Kofi; Miller, David P; Neuberg, Donna S; Wain, John C; Lynch, Thomas J; Christiani, David C

    2006-12-01

    Second hand smoke (SHS) exposure is associated with higher risk of lung cancer. However, the role of SHS in lung cancer survival is not clear. We examined the association between self-reported SHS exposure before diagnosis and overall survival and recurrence-free survival in 393 early-stage non-small-cell lung cancer patients. SHS exposure was analyzed by both duration and location of exposure using log-rank test and Cox proportional hazard models, adjusting for covariates including pack-years of smoking. The median follow-up time was 66 months (range, 0.2-140 months). There were 135 recurrences and 213 deaths. The 5-year overall survival rates were 71% [95% confidence interval (95% CI), 62-81%], 61% (51-72%), 49% (38-60%), and 47% (37-58%), respectively, for patients with the lowest to highest quartile of SHS exposure durations (P < 0.001, log-rank test), with the adjusted hazard ratio (AHR) of 1.57 (95% CI, 1.02-2.41) for the highest versus lowest quartile of SHS exposure durations (P(trend) = 0.04). For different SHS exposure locations, a stronger association was found for SHS exposure at work (AHR of the highest versus lowest quartile, 1.71; 95% CI, 1.12-2.61; P(trend) = 0.03) than for exposure at home (AHR, 1.26; 95% CI, 0.86-1.86; P(trend) = 0.20) or leisure places (AHR, 1.28; 95% CI, 0.83-1.95; P(trend) = 0.16). Similar associations were observed when SHS exposure durations were dichotomized into two or three groups and between SHS exposure and recurrence-free survival. SHS exposure is associated with worse survival in early-stage non-small-cell lung cancer patients, especially for SHS exposure at the work.

  14. Expression of human poly (ADP-ribose) polymerase 1 in Saccharomyces cerevisiae: Effect on survival, homologous recombination and identification of genes involved in intracellular localization.

    PubMed

    La Ferla, Marco; Mercatanti, Alberto; Rocchi, Giulia; Lodovichi, Samuele; Cervelli, Tiziana; Pignata, Luca; Caligo, Maria Adelaide; Galli, Alvaro

    2015-04-01

    The poly (ADP-ribose) polymerase 1 (PARP-1) actively participates in a series of functions within the cell that include: mitosis, intracellular signaling, cell cycle regulation, transcription and DNA damage repair. Therefore, inhibition of PARP1 has a great potential for use in cancer therapy. As resistance to PARP inhibitors is starting to be observed in patients, thus the function of PARP-1 needs to be studied in depth in order to find new therapeutic targets. To gain more information on the PARP-1 activity, we expressed PARP-1 in yeast and investigated its effect on cell growth and UV induced homologous recombination. To identify candidate genes affecting PARP-1 activity and cellular localization, we also developed a yeast genome wide genetic screen. We found that PARP-1 strongly inhibited yeast growth, but when yeast was exposed to the PARP-1 inhibitor 6(5-H) phenantridinone (PHE), it recovered from the growth suppression. Moreover, we showed that PARP-1 produced PAR products in yeast and we demonstrated that PARP-1 reduced UV-induced homologous recombination. By genome wide screening, we identified 99 mutants that suppressed PARP-1 growth inhibition. Orthologues of human genes were found for 41 of these yeast genes. We determined whether the PARP-1 protein level was altered in strains which are deleted for the transcription regulator GAL3, the histone H1 gene HHO1, the HUL4 gene, the deubiquitination enzyme gene OTU1, the nuclear pore protein POM152 and the SNT1 that encodes for the Set3C subunit of the histone deacetylase complex. In these strains the PARP-1 level was roughly the same as in the wild type. PARP-1 localized in the nucleus more in the snt1Δ than in the wild type strain; after UV radiation, PARP-1 localized in the nucleus more in hho1 and pom152 deletion strains than in the wild type indicating that these functions may have a role on regulating PARP-1 level and activity in the nucleus. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Alternative Lengthening of Telomeres in Primary Pancreatic Neuroendocrine Tumors Is Associated with Aggressive Clinical Behavior and Poor Survival.

    PubMed

    Kim, Joo Young; Brosnan-Cashman, Jacqueline A; An, Soyeon; Kim, Sung Joo; Song, Ki-Byung; Kim, Min-Sun; Kim, Mi-Ju; Hwang, Dae Wook; Meeker, Alan K; Yu, Eunsil; Kim, Song Cheol; Hruban, Ralph H; Heaphy, Christopher M; Hong, Seung-Mo

    2017-03-15

    Purpose: Alternative lengthening of telomeres (ALT), a telomerase-independent telomere maintenance mechanism, is strongly associated with ATRX and DAXX alterations and occurs frequently in pancreatic neuroendocrine tumors (PanNET).Experimental Design: In a Korean cohort of 269 surgically resected primary PanNETs and 19 sporadic microadenomas, ALT status and nuclear ATRX and DAXX protein expression were assessed and compared with clinicopathologic factors.Results: In PanNETs, ALT or loss of ATRX/DAXX nuclear expression was observed in 20.8% and 19.3%, respectively, whereas microadenomas were not altered. ALT-positive PanNETs displayed a significantly higher grade, size, and pT classification (all, P < 0.001). ALT also strongly correlated with lymphovascular (P < 0.001) and perineural invasion (P = 0.001) and the presence of lymph node (P < 0.001) and distant metastases (P = 0.002). Furthermore, patients with ALT-positive primary PanNETs had a shorter recurrence-free survival [HR = 3.38; 95% confidence interval (CI), 1.83-6.27; P < 0.001]. Interestingly, when limiting to patients with distant metastases, those with ALT-positive primary tumors had significantly better overall survival (HR = 0.23; 95% CI, 0.08-0.68; P = 0.008). Similarly, tumors with loss of ATRX/DAXX expression were significantly associated with ALT (P < 0.001), aggressive clinical behavior, and reduced recurrence-free survival (P < 0.001). However, similar to ALT, when limiting to patients with distant metastases, loss of ATRX/DAXX expression was associated with better overall survival (P = 0.003).Conclusions: Both primary ALT-positive and ATRX/DAXX-negative PanNETs are independently associated with aggressive clinicopathologic behavior and displayed reduced recurrence-free survival. In contrast, ALT activation and loss of ATRX/DAXX are both associated with better overall survival in patients with metastases. Therefore, these biomarkers may be used as prognostic markers depending on the context of

  16. Improving Survival after Cardiac Arrest.

    PubMed

    Bjørshol, Conrad Arnfinn; Søreide, Eldar

    2017-02-01

    Each year, approximately half a million people suffer out-of-hospital cardiac arrest (CA) in Europe: The majority die. Survival after CA varies greatly between regions and countries. The authors give an overview of the important elements necessary to promote improved survival after CA as a function of the chain of survival and formula for survival concepts. The chain of survival incorporates bystanders (who identify warning symptoms, call the emergency dispatch center, initiate cardiopulmonary resuscitation [CPR]), dispatchers (who identify CA, and instruct and reassure the caller), first responders (who provide high-quality CPR, early defibrillation), paramedics and other prehospital care providers (who continue high-quality CPR, and provide timely defibrillation and advanced life support, transport to CA center), and hospitals (targeted temperature management, percutaneous coronary intervention, delayed prognostication). The formula for survival concept consists of (1) medical science (international guidelines), (2) educational efficiency (e.g., low-dose, high-frequency training for lay people, first responders, and professionals; and (3) local implementation of all factors in the chain of survival and formula for survival. Survival rates after CA can be advanced through the improvement of the different factors in both the chain of survival and the formula for survival. Importantly, the neurologic outcome in the majority of CA survivors has continued to improve.

  17. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.

    PubMed

    Beuschlein, Felix; Weigel, Jens; Saeger, Wolfgang; Kroiss, Matthias; Wild, Vanessa; Daffara, Fulvia; Libé, Rosella; Ardito, Arianna; Al Ghuzlan, Abir; Quinkler, Marcus; Oßwald, Andrea; Ronchi, Cristina L; de Krijger, Ronald; Feelders, Richard A; Waldmann, Jens; Willenberg, Holger S; Deutschbein, Timo; Stell, Anthony; Reincke, Martin; Papotti, Mauro; Baudin, Eric; Tissier, Frédérique; Haak, Harm R; Loli, Paola; Terzolo, Massimo; Allolio, Bruno; Müller, Hans-Helge; Fassnacht, Martin

    2015-03-01

    Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. The aim of this study was to identify markers with prognostic value for patients in this clinical setting. From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

  18. Long Term Progression-Free Survival in a Patient with Locally Advanced Prostate Cancer under Low Dose Intermittent Androgen Deprivation Therapy with Bicalutamide Only.

    PubMed

    Latz, Stefan; Fisang, Christian; Ebert, Wolfram; Orth, Stefan; Engehausen, Dirk G; Müller, Stefan C; Anding, Ralf

    2015-01-01

    Androgen deprivation is a common treatment option in patients with locally advanced or metastatic prostate cancer. No case of long term treatment with an intermittent approach with only low dose bicalutamide (50 mg daily) has been described yet. We report a 60-year-old patient, initially presenting with a PSA elevation of 19.2 ng/mL in 1996. After diagnosis of well to moderately differentiated prostate cancer by transrectal biopsy, the patient underwent an open radical prostatectomy. Final diagnosis was adenocarcinoma of the prostate, classified as pT3a, pR1, pV0, and pL1. Adjuvant intermittent androgen deprivation therapy with flutamide 250 mg was applied, which was changed to bicalutamide 50 mg once daily when it became available in 2001. Six on-phases were performed and PSA values never exceeded 20 ng/mL. The patient did not experience any serious side effects. To date, there are no clinical or radiological signs of progression. Current PSA value is 3.5 ng/mL.

  19. Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast.

    PubMed

    Yonemori, Kan; Hasegawa, Tadashi; Shimizu, Chikako; Shibata, Taro; Matsumoto, Koji; Kouno, Tsutomu; Ando, Masashi; Katsumata, Noriyuki; Fujiwara, Yasuhiro

    2006-01-01

    Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

  20. Unresectable localized neuroblastoma: improved survival after primary chemotherapy including carboplatin-etoposide. Neuroblastoma Study Group of the Société Française d'Oncologie Pédiatrique (SFOP).

    PubMed Central

    Rubie, H.; Michon, J.; Plantaz, D.; Peyroulet, M. C.; Coze, C.; Frappaz, D.; Chastagner, P.; Baranzelli, M. C.; Méchinaud, F.; Boutard, P.; Lutz, P.; Perel, Y.; Leverger, G.; de Lumley, L.; Millot, F.; Stéphan, J. L.; Margueritte, G.; Hartmann, O.

    1998-01-01

    Neuroblastomas (NBs) were assessed according to INSS recommendations including MIBG scan and extensive bone marrow staging to eliminate metastatic spread. Patients with unresectable tumour received primary chemotherapy including two courses of carboplatin-etoposide (CE) and two of vincristine-cyclophosphamide-doxorubicin (CAdO). Post-operative treatment was to be given only in children over 1 year of age at diagnosis who had residual disease or lymph node (LN) involvement. Between 1990 and 1994, 130 consecutive children were registered. In comparison with resectable primaries, these tumours were more commonly abdominal, larger and associated with N-myc amplification (NMA). Complete, very good and partial response (CR, VGPR, PR) to CE were, respectively, 1%, 7% and 44%, overall response rate (RR) to two courses of CE and two courses of CAdO was 71%, and the tumour could be removed in all but four of the children. The toxicity was manageable. The 5-year overall survival (OS) and event-free survival (EFS) were, respectively, 88% and 78% with a median follow-up of 38 months. In multivariate analysis, only NMA and LN involvement adversely influenced the outcome, particularly NMA. Children with unresectable NBs and no NMA fared as well as children with resectable ones as OS were, respectively, 95% and 99% and EFS 89% and 91%. Our data show encouraging results in localized but unresectable NBs as 90% of children may be considered as definitely cured, especially those without NMA. PMID:9649151

  1. Polo-like kinase 3 and phosphoT273 caspase-8 are associated with improved local tumor control and survival in patients with anal carcinoma treated with concomitant chemoradiotherapy

    PubMed Central

    Helmke, Christina; Balermpas, Panagiotis; Fokas, Emmanouil; Wieland, Ulrike; Rave-Fränk, Margret; Kitz, Julia; Matthess, Yves; Raab, Monika; Strebhardt, Klaus; Rödel, Claus

    2016-01-01

    We have recently shown that caspase-8 is a new substrate of Polo-like kinase 3 (Plk3) that phosphorylates the protein on residue T273 thereby promoting its pro-apoptotic function. In the present study we aimed to investigate the clinical relevance of Plk3 expression and phosphorylation of caspase-8 at T273 in patients with anal squamous cell carcinoma (SSC) treated with 5-fluorouracil and mitomycin C-based chemoradiotherapy (CRT). Immunohistochemical detection of the markers was performed in pretreatment biopsy specimens of 95 patients and was correlated with clinical/histopathologic characteristics including HPV-16 virus load/p16INK4a expression and cumulative incidence of local and distant failure, cancer specific survival (CSS), and overall survival (OS). We observed significant positive correlations between Plk3 expression, pT273 caspase-8 signal, and levels of HPV-16 virus DNA load/p16INK4a detection. Patients with high scores of Plk3 and pT273 caspase-8 showed increased local control (p = 0.011; p = 0.001), increased CSS (p = 0.011; p = 0.013) and OS (p = 0.024; p = 0.001), while the levels of pT273 caspase-8 were significantly associated (p = 0.033) with distant metastases. In multivariate analyses Plk3 expression remained significant for local failure (p = 0.018), CSS (p = 0.016) and OS (p = 0.023). Moreover, a combined HPV16 DNA load and Plk3 or pT273 caspase-8 variable revealed a significant correlation to decreased local failure (p = 0.001; p = 0.009), increased CSS (p = 0.016; p = 0.023) and OS (p = 0.003; p = 0.003). In conclusion these data indicate that elevated levels of Plk3 and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal SCC treated with concomitant CRT. PMID:27462786

  2. Impact of Time from Completion of Neoadjuvant Chemotherapy to Surgery on Survival Outcomes in Breast Cancer Patients.

    PubMed

    Sanford, Rachel A; Lei, Xiudong; Barcenas, Carlos H; Mittendorf, Elizabeth A; Caudle, Abigail S; Valero, Vicente; Tripathy, Debu; Giordano, Sharon H; Chavez-MacGregor, Mariana

    2016-05-01

    No studies have examined the impact of the interval from conclusion of neoadjuvant chemotherapy to surgery in breast cancer patients. This study was undertaken to investigate the relationship between time interval from neoadjuvant chemotherapy to surgery and survival outcomes. Breast cancer patients diagnosed with stage I-III disease who received neoadjuvant chemotherapy June 1995 to April 2007 were identified. The effect of neoadjuvant chemotherapy to surgery interval, defined as ≤4, 4-6, or >6 weeks, on survival outcomes was examined. Descriptive statistics and Cox proportional hazards models were used. A total of 1101 patients were identified. Median time to surgery was 33 (range 8-159) days; 335 patients (30.4 %) had surgery within 4 weeks of their last dose of neoadjuvant chemotherapy, 524 (47.6 %) within 4-6 weeks, and 242 (22.0 %) after more than 6 weeks. Median follow-up was 94 (range 3-178) months. The 5-year overall survival (OS) estimates were 79, 87, and 81 % in patients who underwent surgery ≤4, 4-6, and >6 weeks after neoadjuvant chemotherapy, respectively (p = 0.03). The three groups did not differ in 5-year recurrence-free survival (RFS) or locoregional recurrence-free survival (LRFS). In multivariable analysis, compared with an interval of ≤4 weeks, patients who underwent surgery at 4-6 or >6 weeks had equivalent OS, LRFS, and RFS; a sensitivity analysis suggested worse OS in patients who underwent surgery at >8 weeks. Patients with neoadjuvant chemotherapy to surgery intervals of up to 8 weeks had equivalent OS, RFS, and LRFS.

  3. The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation.

    PubMed

    Charalampakis, Nikolaos; Nogueras González, Graciela M; Elimova, Elena; Wadhwa, Roopma; Shiozaki, Hironori; Shimodaira, Yusuke; Blum, Mariela A; Rogers, Jane E; Harada, Kazuto; Matamoros, Aurelio; Sagebiel, Tara; Das, Prajnan; Minsky, Bruce D; Lee, Jeffrey H; Weston, Brian; Bhutani, Manoop S; Estrella, Jeannelyn S; Badgwell, Brian D; Ajani, Jaffer A

    2016-01-01

    Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or survival (OS) (p = 0.046 and p = 0.038, respectively). yp stage independently prognosticated OS and recurrence-free survival (p < 0.001). Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted. © 2016 S. Karger AG, Basel.

  4. NR1H3 Expression is a Prognostic Factor of Overall Survival for Patients with Muscle-Invasive Bladder Cancer

    PubMed Central

    Wu, Junlong; Wan, Fangning; Sheng, Haoyue; Shi, Guohai; Shen, Yijun; Lin, Guowen; Dai, Bo; Zhu, Yiping; Ye, Dingwei

    2017-01-01

    Background: Nuclear receptors (NRs) are a class of transcription factors that regulate many cellular functions through manipulation of gene expression and also play important roles in tumorigenesis, proliferation, progression and prognosis in various kinds of cancers according to recent studies. This work aimed to determine the predictive ability of NRs in muscle-invasive bladder cancer (MIBC). Patients and methods: A total of 308 MIBC patients with complete clinicopathological and RNASeq data from The Cancer Genome Atlas (TCGA) cohort were collected for filtration. Genes showed clear correlations with overall survival (OS) and recurrence free survival (RFS) were further validated in 123 MIBC patients recruited consecutively from 2008 to 2012 in Fudan University Shanghai Cancer Center (FUSCC) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. Results: In TCGA cohort, we found that high NR1H3 (HR=0.779, 95% CI: 0.634 - 0.957), NR2C1 (HR=0.673, 95% CI: 0.458 - 0.989) and NR2F6 (HR=0.750, 95% CI: 0.574 - 0.980) expressions were independent factors of favorable OS, while only low NR1H3 (log-rank test, P=0.0076) and NR2F6 (log-rank test, P=0.0395) expressions had the ability to predict poor prognosis for RFS. Further, in FUSCC validating cohort, we confirmed that low NR1H3 expression level was independent factor of poor OS (HR=1.295, 95% CI: 1.064 - 1.576) and it had the ability to predict poor RFS (log-rank test, P=0.0059). Conclusions: Low NR1H3 expression level is an independent prognostic factor of poor OS, and can also predict worse RFS in MIBC patients. Our “TCGA filtrating and local database validating” model can help reveal more prognostic biomarkers and cast a new light in understanding certain gene function in MIBC. PMID:28382148

  5. Prognostic significance of body mass index in Asian patients with localized renal cell carcinoma.

    PubMed

    Komura, Kazumasa; Inamoto, Teruo; Black, Peter C; Koyama, Kohei; Katsuoka, Yoji; Watsuji, Toshikazu; Azuma, Haruhito

    2011-01-01

    We investigated the prognostic value of BMI (body mass index) in Asian patients with RCC (renal cell carcinoma). We evaluated 170 Asian patients who underwent surgery for localized RCC (pathologic T1-4 tumors in the absence of nodal or distant metastases) between 1996 and 2004 at our institution. Patients were stratified by BMI: 22 or less vs. greater than 22. Overall, CSS (cancer-specific survival) and RFS (recurrence-free survival) was estimated using the Kaplan-Meier method. Multivariate analysis was performed with the Cox regression model. The mean age and BMI of all patients was 62.4 ± 11.4 yr and 23.1 ± 3.2 kg/m(2), respectively. Patients' population consisted of 114 (67.1%) men and 56 (32.9%) women. The median follow-up was 50 mo. The BMI was less than 22 in 83 (49%) patients and greater than 22 in 87 (51%). There was a trend toward worse Eastern Cooperative Oncology Group (ECOG) performance status, less likely to have an incidentaloma, higher pathological stage, and more frequent microvascular invasion with lower BMI. Only the correlations between BMI and ECOG performance status (P = 0.003) and pathological stage (P = 0.015) were statistically significant. Of other relevant factors including gender, mode of presentation, ECOG performance status, C-reactive protein, histological type, Fuhrman nuclear grade, microvascular invasion, pathological stage, and adjuvant cytokine therapy, smaller BMI remained an independent predictor for worse CSS (44.5 mo vs. 56.0 mo, P = 0.041, HR = 10.99) and RFS (43.0 mo vs. 55.0 mo, P = 0.03, HR = 2.653), but not for OS (overall survival) (46.0 mo vs. 55.5 mo, P = 0.13, HR = 2.217) on multivariate analysis. Our findings identify increasing BMI in the Asian population as an independent predictor for favorable CSS and RFS in patients with RCC treated by surgery. Further studies, including a multiinstitutional, prospective Asian cohort, are required to confirm these findings.

  6. Impact of body mass index on perioperative outcomes and survival after resection for gastric cancer.

    PubMed

    Ejaz, Aslam; Spolverato, Gaya; Kim, Yuhree; Poultsides, George A; Fields, Ryan C; Bloomston, Mark; Cho, Clifford S; Votanopoulos, Konstantinos; Maithel, Shishir K; Pawlik, Timothy M

    2015-05-01

    Among patients undergoing resection for gastric cancer, the impact of body mass index (BMI) on outcomes is not well understood. We sought to define the impact of non-normal BMI on short- and long-term outcomes after gastric cancer resection. We identified 775 patients who underwent gastrectomy for adenocarcinoma between 2000 and 2012 from the multi-institutional US Gastric Cancer Collaborative. Clinicopathologic characteristics, operative details, and oncologic outcomes were collected, and patients were stratified according to BMI. Most patients in the cohort were classified as having normal BMI (n = 338, 43.6%), followed by overweight (n = 229, 29.6%), obese (n = 153, 19.7%), and underweight (n = 55, 7.1%). After stratifying by BMI, there were no significant differences in the incidence of postoperative blood transfusions, perioperative morbidity, postoperative infectious complications, length of stay, perioperative 30-d in-hospital death, or readmission across groups (all P > 0.05). BMI did not impact overall or recurrence-free survival after stratifying by stage (all P > 0.05). However, underweight patients with low preoperative albumin levels had worse overall survival (OS) compared with that of patients of normal BMI. BMI did not impact perioperative morbidity, recurrence-free, or OS in patients undergoing gastric resection for adenocarcinoma. Underweight patients with BMI <18.5 kg/m(2) and low preoperative albumin levels, however, had a significantly decreased OS after gastrectomy for cancer. These high-risk patients should have their nutritional status optimized both before and after gastrectomy in an attempt to modify this risk factor and, in turn, achieve better outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02).

    PubMed

    Jost, Christian; Binek, Janek; Schuller, Jan C; Bauerfeind, Peter; Metzger, Urs; Werth, Baseli; Knuchel, Juerg; Frossard, Jean-Louis; Bertschinger, Philipp; Brauchli, Peter; Meyenberger, Christa; Ruhstaller, Thomas

    2010-06-01

    EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures. Predictive and prognostic values of a prospectively defined maximum tumor thickness (MTT). Prospective open-label phase ll study (SAKK 75/02). Multicenter, nationwide. Of 66 patients with primary CRT, 56 underwent en bloc esophagectomy. EUS-measured MTT before and 2-5 weeks after CRT (yMTT). Cutoffs: (1) absolute thickness (yMTT) after CRT < or = 6 mm; (2) relative reduction compared with baseline (ratio yMTT/MTT) < or = 50%. Correlation between EUS measurements and histopathologic tumor regression grade (TRG) and overall survival (OS). Sixteen of 56 patients were not included for EUS evaluation (10 severe stenosis, 5 MTT not measured, 1 intolerance to second EUS). Characteristics (n = 40) were as follow: median age, 60 years; squamous cell carcinoma, 42%; and adenocarcinoma (AC), 58%. Initial stage was: 10 T2N1, 3 T3N0, 26 T3N1, 1 T3Nx; 14 of 23 AC Siewert type 1. Wilcoxon rank sum test showed significant correlation of TRG1 with yMTT < or = 6 mm (P = .008) and yMTT/MTT < or = 50% (P = .003). The effect of yMTT on TRG1 was significant (P = .0193; odds ratio, 0.687 [95% CI, 0.502-0.941]). The predefined cutoff of < or = 6 mm for yMTT was predictive for TRG1 (P = .0037; Fisher exact test). After a median follow-up of 28.6 months, there was a clear trend for benefit in OS with yMTT < or = 6 mm and yMTT/MTT < or = 50%. Small sample size. In a multicenter setting, MTT measured by EUS after CRT was highly predictive for response and showed a clear trend for predicting survival. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  8. Alcohol consumption and survival of colorectal cancer patients: a population-based study from Germany.

    PubMed

    Walter, Viola; Jansen, Lina; Ulrich, Alexis; Roth, Wilfried; Bläker, Hendrik; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann

    2016-06-01

    Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: >0-12 g/d; men: >0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence

  9. Predictors of survival and recurrence after temporal bone resection for cancer

    PubMed Central

    Morris, Luc G. T.; Mehra, Saral; Shah, Jatin P.; Bilsky, Mark H.; Selesnick, Samuel H.; Kraus, Dennis H.

    2014-01-01

    Background The purpose of this study was to identify factors predictive of outcome in patients undergoing temporal bone resection (TBR) for head and neck cancer. Methods This was a retrospective study of 72 patients undergoing TBR. Factors associated with survival and recurrence were identified on multivariable regression. Results Most tumors were epithelial (81%), commonly (69%) involving critical structures. Cervical metastases were uncommon (6%). Squamous cell carcinoma (SCC) of the external auditory canal carried a high rate of parotid invasion (25%) and parotid nodal metastases (43%). The 5-year rate of overall survival (OS) was 62%; disease-specific survival (DSS), 70%; recurrence-free survival (RFS), 46%. Factors independently associated with outcome on multivariable analysis were margin status and extratemporal spread of disease to the parotid, mandible, or regional nodes. Recurrence was common (72%) in cT3–4 tumors. Conclusions Margin status and extratemporal disease spread are the strongest independent predictors of survival and recurrence. In SCC of the external auditory canal, high rates of parotid involvement support adjunctive parotidectomy. Risk of recurrence in T3–T4 tumors may support a role for adjuvant therapy. PMID:21953902

  10. Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients.

    PubMed

    Binder, Pratibha S; Peipert, Jeffrey F; Kallogjeri, D; Brooks, Rebecca A; Massad, L Stewart; Mutch, David G; Powell, Matthew A; Thaker, Premal H; McCourt, Carolyn K

    2016-12-01

    The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. Although a few cohort studies of <500 patients showed an association between comorbidity and survival in patients with endometrial cancer, the degree of association must be better described. The Adult Comorbidity Evaluation 27 is a validated comorbidity instrument that provides a score of 0-3 based on the number of and severity of medical comorbidities. This study was performed to explore the association between medical comorbidities and survival of patients with endometrial cancer. Patients who were diagnosed with endometrial cancer from 2000-2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients who underwent primary surgical treatment for endometrioid, serous, and clear cell endometrial carcinoma were included. Patients who primarily were treated with radiation, chemotherapy, or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing Adult Comorbidity Evaluation 27 scores were also excluded from analysis. Information that included patient demographics, Adult Comorbidity Evaluation 27 score, tumor characteristics, adjuvant treatment, and survival data were extracted from the database. The association of Adult Comorbidity Evaluation 27 and overall and recurrence-free survival was explored in a multivariable Cox regression analysis after being controlled for variables that have been found to be associated significantly with survival in univariable analysis. A total of 2073 patients with a median age of 61 years (range, 20-94 years) at diagnosis were identified. The Adult Comorbidity Evaluation 27 score was 0, 1, 2, and 3 in 22%, 38%, 28%, and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%), and IV (7%), and grade distribution was 1 (52%), 2 (23%), and 3 (25%). Most patients had endometrioid

  11. Accelerated Partial Breast Irradiation With Interstitial Implants: Risk Factors Associated With Increased Local Recurrence

    SciTech Connect

    Ott, Oliver J.; Hildebrandt, Guido; Poetter, Richard; Hammer, Josef; Hindemith, Marion; Resch, Alexandra; Spiegl, Kurt; Lotter, Michael; Uter, Wolfgang; Kortmann, Rolf-Dieter; Schrauder, Michael; Beckmann, Matthias W.; Fietkau, Rainer; Strnad, Vratislav

    2011-08-01

    Purpose: To analyze patient, disease, and treatment-related factors regarding their impact on local control after interstitial multicatheter accelerated partial breast irradiation (APBI). Methods and Materials: Between November 2000 and April 2005, 274 patients with early breast cancer were recruited for the German-Austrian APBI Phase II trial ( (ClinicalTrials.gov) identifier: NCT00392184). In all, 64% (175/274) of the patients received pulsed-dose-rate (PDR) brachytherapy and 36% (99/274) received high-dose-rate (HDR) brachytherapy. Prescribed reference dose for HDR brachytherapy was 32 Gy in eight fractions of 4 Gy, twice daily. Prescribed reference dose in PDR brachytherapy was 49.8 Gy in 83 consecutive fractions of 0.6 Gy each hour. Total treatment time was 3 to 4 days. Results: The median follow-up time was 64 months (range, 9-110). The actuarial 5-year local recurrence free survival rate (5-year LRFS) was 97.7%. Comparing patients with an age <50 years (49/274) vs. {>=}50 years (225/274), the 5-year LRFS resulted in 92.5% and 98.9% (exact p = 0.030; 99% confidence interval, 0.029-0.032), respectively. Antihormonal treatment (AHT) was not applied in 9% (24/274) of the study population. The 5-year LRFS was 99% and 84.9% (exact p = 0.0087; 99% confidence interval, 0.0079-0.0094) in favor of the patients who received AHT. Lobular histology (45/274) was not associated with worse local control compared with all other histologies (229/274). The 5-year LRFS rates were 97.6% and 97.8%, respectively. Conclusions: Local control at 5 years is excellent and comparable to therapeutic successes reported from corresponding whole-breast irradiation trials. Our data indicate that patients <50 years of age ought to be excluded from APBI protocols, and that patients with hormone-sensitive breast cancer should definitely receive adjuvant AHT when interstitial multicatheter APBI is performed. Lobular histology need not be an exclusion criterion for future APBI trials.

  12. Allogeneic versus autologous blood transfusion and survival after radical prostatectomy

    PubMed Central

    Chalfin, Heather J.; Frank, Steven M.; Feng, Zhaoyong; Trock, Bruce J.; Drake, Charles G.; Partin, Alan W.; Humphreys, Elizabeth; Ness, Paul M.; Jeong, Byong C.; Lee, Seung B.; Han, Misop

    2016-01-01

    BACKGROUND Potential adverse effects of blood transfusion (BT) remain controversial, especially for clinical outcomes after curative cancer surgery. Some postulate that immune modulation after allogeneic BT predisposes to recurrence and death, but autologous superiority is not established. This study assessed whether BT is associated with long-term prostate cancer recurrence and survival a large single-institutional radical prostatectomy (RP) database. STUDY DESIGN AND METHODS Between 1994 and 2012, a total of 11,680 patients had RP with available outcome and transfusion data. A total of 7443 (64%) had complete covariate data. Clinical variables associated with biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) were identified with Cox proportional hazards models for three groups: no BT (reference, 27.7%, n = 2061), autologous BT only (68.8%, n = 5124), and any allogeneic BT (with or without autologous, 3.5%, n = 258). RESULTS Median (range) follow-up was 6 (1–18) years. Kaplan-Meier analysis showed significantly decreased OS (but not BRFS or PCSS) in the allogeneic group versus autologous and no BT groups (p = 0.006). With univariate analysis, any allogeneic BT had a hazard ratio (HR) of 2.29 (range, 1.52–3.46; p < 0.0001) for OS, whereas autologous BT was not significant (HR, 1.04 [range, 0.82–1.32], p = 0.752). In multivariable models, neither autologous nor allogeneic BT was independently associated with BRFS, CSS, or OS, and a dose response was not observed for allogeneic units and BRFS. CONCLUSION Although allogeneic but not autologous BT was associated with decreased long-term OS, after adjustment for confounding clinical variables, BT was not independently associated with OS, BRFS, or CSS regardless of transfusion type. Notably, no association was observed between allogeneic BT and cancer recurrence. Observed differences in OS may reflect confounding. PMID:24601996

  13. Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

    PubMed

    Bozec, Alexandre; Benezery, Karen; Chamorey, Emmanuel; Ettaiche, Marc; Vandersteen, Clair; Dassonville, Olivier; Poissonnet, Gilles; Riss, Jean-Christophe; Hannoun-Lévi, Jean-Michel; Chand, Marie-Eve; Leysalle, Axel; Saada, Esma; Sudaka, Anne; Haudebourg, Juliette; Hebert, Christophe; Falewee, Marie-Noelle; Demard, François; Santini, José; Peyrade, Frédéric

    2016-09-01

    The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

  14. Recurrence and Survival After Segmentectomy in Patients With Prior Lung Resection for Early-Stage Non-Small Cell Lung Cancer.

    PubMed

    Brown, Lisa M; Louie, Brian E; Jackson, Nicole; Farivar, Alexander S; Aye, Ralph W; Vallières, Eric

    2016-10-01

    Lobectomy is the standard of care for patients with early-stage non-small cell lung cancer (NSCLC). However, the treatment of choice for patients with prior lung resection and a second primary NSCLC has not been established. We compared rates and patterns of recurrence and survival in patients with and without prior lung resection treated by segmentectomy and determined predictors of recurrence. This was a retrospective cohort study of 90 patients who underwent 91 consecutive segmentectomies for early-stage NSCLC between April 2004 and December 2014. Logistic regression was used to determine predictors of recurrence, and Kaplan-Meier curves were used to determine survival. Of the 91 segmentectomies, 21 (23%) had a prior lung cancer resection and 70 (77%) were primary resections. There were 18 recurrences (20%): 9 of 21 (43%) in those with prior lung resection and 9 of 70 (13%) in those without. The 90-day mortality was 0%. The recurrence-free survival and 5-year survival were 61% and 55% in those with prior lung resection (p = 0.09) and 84% and 65% in those without (p = 0.4). Close parenchymal margin and number of lymph nodes examined were significant modifiable predictors of recurrence. Segmentectomy is a reasonable option for patients with early-stage NSCLC who have had a prior lung resection. It results in similar survival but trends toward lower recurrence-free survival compared with patients undergoing primary resection. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Expression and localization of fibroblast growth factor (FGF) family in buffalo ovarian follicle during different stages of development and modulatory role of FGF2 on steroidogenesis and survival of cultured buffalo granulosa cells.

    PubMed

    Mishra, S R; Thakur, N; Somal, A; Parmar, M S; Reshma, R; Rajesh, G; Yadav, V P; Bharti, M K; Bharati, Jaya; Paul, A; Chouhan, V S; Sharma, G T; Singh, G; Sarkar, M

    2016-10-01

    The present study investigated the expression and localization of FGF and its functional receptors in the follicle of buffalo and the treatment of FGF2 on mRNA expression of CYP19A1 (aromatase), PCNA, and BAX (BCL-2 associated X protein) in cultured buffalo granulosa cells (GCs). Follicles were classified into four groups based on size and E2 level in follicular fluid (FF): F1, 4-6mm diameter, E2<0.5ng/ml of FF; F2, 7-9mm, E2=0.5-5ng/ml; F3, 10-13mm, E2=5-40ng/ml; F4, >14mm, E2>180ng/ml. The qPCR studies revealed that the mRNA expression of FGF1, FGF2 and FGF7 were maximum (P<0.05) in theca interna (TI) whereas the transcripts of FGFR1, FGFR2, FGFR2IIIB and FGFR2IIIC were up-regulated (P<0.05) in GCs of F4 follicles. Protein expression of most members were maximum (P<0.05) in F4 follicles except FGFR3 and FGFR4. All members were localized in GC and TI with a stage specific immunoreactivity. Primary culture of GCs with treatment of FGF2 at different dose-time combinations revealed that the mRNA expression and immunoreactivity of CYP19A1 and PCNA were maximum (P<0.05) whereas BAX was minimum (P<0.05) with 200ng/ml at 72h of incubation. The findings indicate that FGF family members are expressed in a regulated manner in buffalo ovarian follicles during different stages of development where FGF2 may promote steroidogenesis and GC survival through autocrine and paracrine manner.

  16. Accelerated Partial Breast Irradiation With Low-Dose-Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial

    SciTech Connect

    Hattangadi, Jona A.; Powell, Simon N.; MacDonald, Shannon M.; Mauceri, Thomas; Ancukiewicz, Marek; Freer, Phoebe; Lawenda, Brian; Alm El-Din, Mohamed A.; Gadd, Michele A.; Smith, Barbara L.; Taghian, Alphonse G.

    2012-07-01

    Purpose: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). Materials and Methods: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau ({tau}{sub {beta}}) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. Results: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome ({tau}{sub {beta}} 0.6, p < .0001), lower patient satisfaction ({tau}{sub {beta}} 0.5, p < .001), and worse fibrosis ({tau}{sub {beta}} 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias {>=}1 cm{sup 2}. Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose ({tau}{sub {beta}} 0.3-0.5, p {<=} .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival

  17. Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy

    PubMed Central

    Na, Feifei; Wang, Jingwen; Li, Cong; Deng, Lei; Xue, Jianxin

    2014-01-01

    Introduction: The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non–small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUVmax remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect. Methods: We performed a meta-analysis of published literature for primary tumor SUVmax-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUVmax were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy. Results: Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUVmax and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02–1.08) and 1.32 (95% CI, 1.15–1.51) for pre-RT SUVmax and post-RT SUVmax, respectively; 1.26 (95% CI, 1.05–1.52) and 2.01 (95% CI, 1.16–3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06–1.18) and 2.19 (95% CI, 1.34–3.60) for pre-SBRT SUVmax and post-SBRT SUVmax, respectively. Conclusion: Both pre-RT and post-RT primary tumor SUVmax can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUVmax seemed to have poorer overall survival and LC. PMID:24787963

  18. Results of brachytherapy for cancer of the tongue with special emphasis on local prognosis

    SciTech Connect

    Horiuchi, J.; Okuyama, T.; Shibuya, H.; Takeda, M.

    1982-05-01

    One hundred and sixty-six patients with squamous cell carcinoma of the tongue were treated with radiation. Treatment modalities were mainly interstitial implant with or without external beam irradiation, except for early lesions, which were treated with intraoral electron beam therapy. Analysis was made on the local prognosis of the lesion to clarify the indications for interstitial therapy, especially the combined program with external beam therapy, and the time-dose relationship of the brachytherapy. Local recurrence-free rates (two years) were 94% in T1, 77% in T2 and 32% in T3 lesions, respectively. For T1 and surperficial or exophytic T2 lesions, the local recurrence-free rate was excellent with the interstitial therapy alone using either permanent implants of gold grain or radium implants. Therefore, prior external beam therapy seemed to be unnecessary for these lesions. When the treated area was less than 10 cm/sup 2/, subsequent complications were not likely even if the TDF (time-dose factor) value was high. Most of the patients who received combined external beam and interstitial therapy showed infiltrative T2 and a majority of the T3 lesions. In these patients, it was apparent that most of the total dose should be given from the interstitial implant after a small prior dose with external irradiation, because these lesions could not be cured even if the external dose was increased.

  19. Survival Outcomes and Predictive Factors for Female Urethral Cancer: Long-term Experience with Korean Patients.

    PubMed

    Kang, Minyong; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

    2015-08-01

    The aim of this study was to evaluate female urethral cancer (UCa) patients treated and followed-up during a time period spanning more than 20 yr at single institution in Korea. We reviewed medical records of 21 consecutive patients diagnosed with female UCa at our institution between 1991 and 2012. After exclusion of two patients due to undefined histology, we examined clinicopathological variables, as well as survival outcomes of 19 patients with female UCa. A Cox proportional hazards ratio model was used to identify significant predictors of prognosis according to variables. The median age at diagnosis was 59 yr, and the median follow-up duration was 87.0 months. The most common initial symptoms were voiding symptoms and blood spotting. The median tumor size was 3.4 cm, and 55% of patients had lesions involving the entire urethra. The most common histologic type was adenocarcinoma, and the second most common type was urothelial carcinoma. Fourteen patients underwent surgery, and 7 of these patients received adjuvant radiation or systemic chemotherapy. Eleven patients experienced tumor recurrence after primary therapy. Patients with high stage disease, advanced T stage (≥T3), and positive lymph nodes had worse survival outcomes compared to their counterparts. Particularly, lymph node positivity and advanced T stage were significant predictive factors for all survival outcomes. Tumor location was the only significant predictor for recurrence-free survival. Although our study included a small number of patients, it conveys valuable information about this rare female urologic malignancy in a Korean population.

  20. CD4+ Th1 cells promote CD8+ Tc1 cell survival, memory response, tumor localization and therapy by targeted delivery of interleukin 2 via acquired pMHC I complexes.

    PubMed

    Huang, Hui; Hao, Siguo; Li, Fang; Ye, Zhenmin; Yang, Junbao; Xiang, Jim

    2007-02-01

    The cooperative role of CD4+ helper T (Th) cells has been reported for CD8+ cytotoxic T (Tc) cells in tumor eradication. However, its molecular mechanisms have not been well elucidated. We have recently demonstrated that CD4+ Th cells can acquire major histocompatibility complex/peptide I (pMHC I) complexes and costimulatory molecules by dendritic cell (DC) activation, and further stimulate naïve CD8+ T cell proliferation and activation. In this study, we used CD4+ Th1 and CD8+ Tc1 cells derived from ovalbumin (OVA)-specific T cell receptor (TCR) transgenic OT II and OT I mice to study CD4+ Th1 cell's help effects on active CD8+ Tc1 cells and the molecular mechanisms involved in CD8+ Tc1-cell immunotherapy of OVA-expressing EG7 tumors. Our data showed that CD4+ Th1 cells with acquired pMHC I by OVA-pulsed DC (DCOVA) stimulation are capable of prolonging survival and reducing apoptosis formation of active CD8+ Tc1 cells in vitro, and promoting CD8+ Tc1 cell tumor localization and memory responses in vivo by 3-folds. A combined adoptive T-cell therapy of CD8+ Tc1 with CD4+ Th1 cells resulted in regression of well-established EG7 tumors (5 mm in diameter) in all 10/10 mice. The CD4+ Th1's help effect is mediated via the helper cytokine IL-2 specifically targeted to CD8+ Tc1 cells in vivo by acquired pMHC I complexes. Taken together, these results will have important implications for designing adoptive T-cell immunotherapy protocols in treatment of solid tumors.

  1. Expression and localization of angiopoietin family in buffalo ovarian follicles during different stages of development and modulatory role of angiopoietins on steroidogenesis and survival of cultured buffalo granulosa cells.

    PubMed

    Mishra, S R; Thakur, N; Somal, A; Parmar, M S; Yadav, V P; Bharati, Jaya; Bharti, M K; Paul, A; Verma, M R; Chouhan, V S; Sharma, G Taru; Singh, G; González, L A; D'Occhio, M J; Sarkar, M

    2016-10-15

    The present study investigated the expression and localization of angiopoietin (ANPT) family members in buffalo ovarian follicles of different size. It also looked at the role of ANPTs in estradiol secretion and mRNA expression of phosphoinositide-3-kinase-protein kinase B signaling pathway cellular proliferation (phosphoinositide-dependant kinase and protein kinase B [AKT]) and proapoptotic (BAD) factors with caspase 3 in cultured buffalo granulosa cells (GCs). The mRNA and protein expression of ANPT-1 was greatest (P < 0.05), whereas ANPT-2 was reduced (P < 0.05) in preovulatory follicles as compared to F1 follicle. Tyrosine kinase with immunoglobulin-like and EGF-like domains 1 transcripts and protein expression did not change in all follicular groups, whereas tyrosine kinase with immunoglobulin-like and EGF-like domains 2 mRNA was highest (P < 0.05) in theca interna but not GC layer of preovulatory follicle. All members of ANPT family were localized in GC and theca interna showing a stage specific immunoreactivity. Cultured GCs were treated with ANPT-1 and ANPT-2 separately at doses of 1, 10, and 100 ng/mL and in combination at 100 ng/mL for three incubation periods (24, 48, and 72 hours). Estradiol secretion was highest (P < 0.05) at 100 ng/mL at 72 hours of incubation when GCs were treated with either protein alone. The mRNA expression of phosphoinositide-dependant kinase and AKT was highest (P < 0.05), and BAD with caspase 3 was lowest (P < 0.05) at 100 ng/mL at 72 hours of incubation, when cultured GCs were treated separately with each protein or in combination. The immuoreactivity of AKT, pAKT, and pBAD were maximal, whereas BAD was minimal with 100 ng/mL at 72 hours when cultured GCs treated with either protein alone. The findings indicate that ANPTs are expressed in a regulated manner in buffalo ovarian follicle during different stages of development where they may promote steroidogenesis and GC survival through autocrine and paracrine

  2. Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy

    SciTech Connect

    Jeremic, Branislav . E-mail: b.jeremic@iaea.org; Milicic, Biljana

    2007-06-01

    Purpose: To investigate the influence of interfraction interval (IFI) on local recurrence-free survival (LRFS) in patients with limited-disease small-cell lung cancer (LD SCLC) treated with accelerated hyperfractionated radiotherapy (Acc Hfx RT) and concurrent cisplatin and etoposide (PE). Methods and Materials: A total of 103 patients were treated with either 'early' (Cycle 1) or 'late' (Cycle 4) concurrent Acc Hfx RT/PE. Two daily fractions were nonrandomly given using an IFI of either 4.5-5.0 h ('shorter') (n = 52) or 5.5-6.0 h ('longer') (n = 51). Results: The median LRFS and 5-year LRFS rate for all 103 patients were 52 months and 48%, respectively. Besides gender, Karnofsky performance status, and treatment group, IFI also influenced LRFS, whereas age and weight loss did not. When a multivariate model was used, IFI was marginally insignificant (p = 0.0770) as a predictor of LRFS. In terms of individual treatment groups, IFI was not significant in 'early' Acc Hfx RT/PE but showed a strong trend in a 'late' Acc Hfx RT/PE regimen. Although a shorter IFI led to a higher incidence of high-grade ({>=}3) esophagitis, leukopenia, and infection, a correlation analysis of toxicities with all potential prognostic factors showed that a shorter IFI was not an independent predictor of any acute high-grade toxicity. Conclusion: 'Shorter' IFI had a marginally insignificant influence on LRFS. A strong trend favoring it was observed in patients treated with 'late' concurrent Acc Hfx RT/PE. This may be of interest because it could contribute to further understanding of potential biologic parameters influencing treatment outcome.

  3. Adenovirus vector carrying REIC/DKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy

    PubMed Central

    Kumon, H; Ariyoshi, Y; Sasaki, K; Sadahira, T; Araki, M; Ebara, S; Yanai, H; Watanabe, M; Nasu, Y

    2016-01-01

    As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kattan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 × 1010, 1.0 × 1011 and 1.0 × 1012 viral particles (vp) in 1.0–1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 × 1012 vp in 3.6 ml (n=6) was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration with cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+3. PMID:27767086

  4. Association of Body Mass Index Changes during Neoadjuvant Chemotherapy with Pathologic Complete Response and Clinical Outcomes in Patients with Locally Advanced Breast Cancer.

    PubMed

    Kogawa, Takahiro; Fouad, Tamer M; Wei, Caimiao; Masuda, Hiroko; Kai, Kazuharu; Fujii, Takeo; El-Zein, Randa; Chavez-MacGregor, Mariana; Litton, Jennifer K; Brewster, Abenaa; Alvarez, Ricardo H; Hortobagyi, Gabriel N; Valero, Vicente; Theriault, Richard; Ueno, Naoto T

    2015-01-01

    The purpose of this study was to determine the association between body mass index (BMI) measurements (baseline BMI and changes in BMI during neoadjuvant systemic treatment [NST]) and clinical efficacy (pathologic complete response [pCR] rate and survival outcomes) in locally advanced breast cancer (LABC). We hypothesized that high baseline BMI and increases in BMI during NST are associated with lower pCR rates and poorer clinical outcomes in LABC. We retrospectively reviewed the medical records of 1002 patients, 204 with primary inflammatory breast cancer (IBC) and 798 with stage III non-IBC, who underwent standard NST and definitive surgery between November 1, 2006, and December 31, 2012. The median follow-up time for the survivors was 19.6 months (0.4 - 67.8 months). The pCR rates of patients whose BMI increased or decreased were 23.2% and 18.1%, respectively, (p=0.048). The unadjusted overall survival (OS) was significantly better in the group with increased BMI (p=0.006). However, increased BMI was not an independent predictor of pCR and clinical outcomes (recurrence-free survival and OS) after adjusting for other clinical variables. In subset analyses, increased BMI as a continuous variable was an independent predictor of higher pCR rates in the normal BMI/underweight group (odds ratio [OR]=1.35, 95% confidence interval [CI]: 1.06-0.71, p=0.015). Increased BMI (BMI change ≥0 vs. <0) was also an independent predictor of pCR (OR=1.65, 95% CI: 1.00-2.72, p=0.049) in the postmenopausal group. Our results show that increasing BMI shows improved clinical outcome in terms of better pCR rates in normal BMI/underweight group and in the postmenopausal group. These results contradict previously reported findings on the association between high BMI and poor clinical efficacy regarding pCR rate and survival outcomes in early-stage breast cancer. Thus, the role of BMI in breast cancer may depend on patients' clinical characteristics such as advanced stage.

  5. More Lake States Tree Survival Predictions

    Treesearch

    Roland G. Buchman; Ellen L. Lentz

    1984-01-01

    Species coefficients are reported for predicting individual tree survival for nine Lake States species, supplementing a previous report for 10 species. Tree attributes are diameter growth rate and diameter at breast height. Regional and local performances are summarized.

  6. The clinical implication of the number of lymph nodes harvested during sentinel lymph node biopsy and its effects on survival outcome in patients with node-negative breast cancer.

    PubMed

    Kim, Mi Kyoung; Park, Hyung Seok; Kim, Jee Ye; Kim, Sanghwa; Nam, Sanggeun; Park, Seho; Kim, Seung Il

    2017-10-01

    The optimal number of sentinel lymph nodes (SLN) that need to be harvested to achieve favorable survival outcome during a SLN biopsy (SLNB) has not yet been established. Six hundred and thirteen patients with clinically node-negative breast cancer who underwent SLNB were reviewed. Survival outcomes according to the number of total harvested lymph nodes (THLNs), defined as the sum of enumerated SLNs and non-SLNs were analyzed. Patients with only 1 THLN showed lower recurrence-free survival (RFS) as compared to those with ≥2 THLNs (p = 0.049). In multivariate analysis, only 1 THLN was associated with poor RFS (HR = 2.711; p = 0.029). Removing at least 2 lymph nodes during SLNB may be acceptable. Harvesting only 1 lymph node should be undertaken cautiously because of false negative results and increasing the subsequent recurrence rate. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Preoperative lymphocyte-to-monocyte ratio predicts survival in primary hepatitis B virus-positive hepatocellular carcinoma after curative resection

    PubMed Central

    Li, Guang-Jun; Ji, Juan-Juan; Yang, Fang; Xu, Hong-Wei; Bai, Yu

    2017-01-01

    Background Both inflammation and immunity are associated with the development of malignancy. The lymphocyte-to-monocyte ratio (LMR) has been confirmed as a prognostic factor for several malignant diseases. The purpose of our study was to analyze prognostic significance of preoperative LMR in hepatitis B virus (HBV)-related hepatocellular carcinoma after curative resection. Patients and methods A total of 253 patients with primary HBV-positive hepatocellular carcinoma who underwent a curative operation were enrolled in this retrospective study. The relationship between preoperative LMR and survival outcomes was analyzed through Kaplan–Meier curves and multivariate Cox regression analyses. Results Patients with a high LMR had a significantly higher mean overall survival than those with a low LMR (67 months vs 55 months, P=0.023), and high LMR remained significant for longer survival in the multivariate analysis (hazard ratio, 0.147; 95% confidence interval [CI]: 0.085–0.253; P=0.021). Furthermore, patients with a high LMR also had a higher median recurrence-free survival than those with a low LMR in univariate analyses (60 months vs 48 months, P=0.026) and multivariate analyses (hazard ratio, 0.317; 95% CI: 0.042–1.023; P=0.032). However, the survival benefit was limited to patients with advanced cancer. Conclusion LMR was confirmed as an independent prognostic biomarker for primary HBV-positive hepatocellular carcinoma after curative resection. PMID:28260933

  8. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer

    PubMed Central

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A.; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J. H.; Kuppen, Peter J. K.

    2016-01-01

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated. PMID:28035987

  9. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer.

    PubMed

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J H; Kuppen, Peter J K

    2016-12-27

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03-2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13-3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.

  10. High level of viral microRNA-BART20-5p expression is associated with worse survival of patients with Epstein-Barr virus-associated gastric cancer

    PubMed Central

    Kwon, Oh Kyoung; Lee, Seung Soo; Chung, Ho Young; Yu, Wansik; Bae, Han Ik; Seo, An Na; Kang, Hyojeung; Lee, Suk Kyeong; Jeon, Seong Woo; Hur, Keun; Kim, Jong Gwang

    2017-01-01

    This study analyzed the relationship between several Epstein-Barr virus (EBV) microRNA (miRNA) expression profiles and the clinicopathologic features of patients with EBV-associated gastric cancer. The miRNA expression was examined in 59 tumor and 39 paired normal mucosal tissues from available formalin-fixed paraffin embedded tissue samples. The expression levels of miR-BamHI fragment A rightward transcript (BART)1-5p, miR-BART4-5p, and miR-BART20-5p were determined using a quantitative real-time polymerase chain reaction. The expression of all three analyzed EBV microRNAs was significantly higher in the tumor tissue than in the paired normal tissue (P < 0.001 for each). When the median value of the EBV microRNA expression levels was used as the cutoff point, a high BART20-5p expression was associated with worse recurrence-free survival (P = 0.034) in a multivariate analysis including age and pathologic stage. In conclusion, the expression level of BART20-5p may predict recurrence-free survival for patients with EBV-associated gastric cancer. Further studies are warranted to clarify the roles of EBV BART microRNAs in the carcinogenesis, and their potential as a biomarker and therapeutic target for EBV-associated gastric cancer. PMID:28122341

  11. [Long-term oncologic outcomes of localized high-risk prostate cancer undergoing brachytherapy combined with external-beam radiation therapy and maximal androgen blockade].

    PubMed

    Luo, Y; Li, M C; Qi, H Z; Zhao, J H; Han, Y L; Lin, Y H; Hou, Z; Jiang, Y G

    2017-07-11

    Objective: To investigate the oncologic outcome and PSA kinetics of localized high-risk prostate cancer (PCa) patients treated with combination strategy of radiation therapy (RT) and maximal androgen blockade (MAB). Methods: We retrospectively reviewed the clinical data of 320 localized PCa patients undergoing RT+ MAB from 2001 to 2015. And radiation treatment protocol consisted of permanent prostate brachytherapy (PPB) at 110 Gy and EBRT at 45 Gy/23 fractions. Results: The median follow-up time was 90 (range: 12-186) months. And 117 (36.6%) cases underwent MAB + external-beam radiotherapy (EBRT), and other 203 (63.4%) cases received MAB+ EBRT+ PPB. Multivariate Cox regression analyses showed that PSA kinetics were positive indicators of oncologic outcomes. Furthermore, PSA kinetics were aberrantly improved by supplemental PPB to MAB+ EBRT as following, PSA nadir (1.3±0.7)μg/L vs(0.11±0.06)μg/L, time of PSA decrease to nadir (7.5±1.8)months vs (3.2±2.1)months, PSA doubling time (15.6±4.2)months vs (22.6±6.1)months, PSA decreasing amplitude (84.6±6.2)%vs(95.8±3.4)%. Additionally, the median time of several important oncologic events in MAB+ EBRT+ PPB group were also prolonged than that in MAB+ EBRT group as following, overall survival (12.3 years vs 9.1 years, P<0.001), biochemical recurrence-free survival (9.8 years vs 6.5 years, P<0.001), skeletal-related event (10.4years vs 8.2 years, P<0.001), and cytotoxic chemotherapy (11.6 years vs 8.8 years, P=0.007). Conclusion: MAB+ EBRT+ PPB is extremely effective combination strategy for localized high-risk PCa patients, and PPB plays the important synergistic role in improving PSA kinetics, which are independent predictor for oncologic outcomes.

  12. Long-term results of a phase II study with neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high-risk prostate cancer.

    PubMed

    Thalgott, Mark; Horn, Thomas; Heck, Matthias M; Maurer, Tobias; Eiber, Matthias; Retz, Margitta; Autenrieth, Michael; Herkommer, Kathleen; Krause, Bernd J; Gschwend, Jürgen E; Treiber, Uwe; Kübler, Hubert R

    2014-03-05

    Patients with locally advanced and high-risk prostate cancer (LAPC) are prone to experience biochemical recurrence despite radical prostatectomy (RP). We evaluated feasibility, safety and activity of a neoadjuvant chemohormonal therapy (NCHT) with 3-weekly full dose docetaxel and complete androgen blockade (CAB) in locally advanced and high-risk prostate cancer patients (LAPC) undergoing RP. Patients (n = 30) were selected by Kattans' preoperative score and received trimestral buserelin 9,45 mg, bicalutamide 50 mg/day and 3 cycles docetaxel (75 mg/m²) followed by RP. Primary endpoints were biochemical (PSA) and local downstaging. Secondary endpoints included toxicity and operability assessments, pathological complete response (pCR), time to PSA progression, 5-year biochemical recurrence free survival (bRFS) and overall survival (OS). Median baseline PSA was 25.8 ng/ml (2.1-293), and the predicted probability of 5-year bRFS was 10% (0-55). NCHT induced PSA-reduction was 97.3% (81.3-99.9%; p < 0.001) and post-RP 96.7% of patients were therapy responders, with undetectable PSA-values. Post- vs. pretreatment MRI indicated a median tumor volume reduction of 46.4% (-31.3-82.8; p < 0.001). A pathological downstaging was observed in 48.3%. Severe hematologic toxicities (≥CTC3) were frequent with 53.8% leucopenia, 90% neutropenia and 13.3% febrile neutropenia. RP was performed in all patients. While resectability was hindered in 26.7%, continence was achieved in 96.7%. Pathologic analyses revealed no pCR. Lymph node- and extracapsular involvement was observed in 36.7% and 56.7% with 33.3% positive surgical margins. After a median of 48.6 (19.9-87.8) months, 55.2% of therapy responders experienced PSA-recurrence. The estimated median time to PSA-progression was 38.6 months (95%CI 30.9-46.4) and 85.3 months (95%CI 39.3-131.3) for OS. The 5-year bRFS was improved to 40%, but limiting for interpretation adjuvant treatment was individualized. NCHT is feasible

  13. Local Foods, Local Places

    EPA Pesticide Factsheets

    The Local Foods, Local Places technical assistance program protects human health and the environment, spurs revitalization, increases access to healthy foods, and creates economic opportunities by promoting local foods.

  14. Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial

    PubMed Central

    Machtay, Mitchell; Duan, Fenghai; Siegel, Barry A.; Snyder, Bradley S.; Gorelick, Jeremy J.; Reddin, Janet S.; Munden, Reginald; Johnson, Douglas W.; Wilf, Larry H.; DeNittis, Albert; Sherwin, Nancy; Cho, Kwan Ho; Kim, Seok-ki; Videtic, Gregory; Neumann, Donald R.; Komaki, Ritsuko; Macapinlac, Homer; Bradley, Jeffrey D.; Alavi, Abass

    2013-01-01

    Purpose In this prospective National Cancer Institute–funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non–small-cell lung cancer (NSCLC). Patients and Methods Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. Results Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. Conclusion Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic

  15. Melanoma risk loci as determinants of melanoma recurrence and survival

    PubMed Central

    2013-01-01

    Background Steadily high melanoma mortality rates urge for the availability of novel biomarkers with a more personalized ability to predict melanoma clinical outcomes. Germline risk variants are promising candidates for this purpose; however, their prognostic potential in melanoma has never been systematically tested. Methods We examined the effect of 108 melanoma susceptibility single nucleotide polymorphisms (SNPs), associated in recent GWAS with melanoma and melanoma-related phenotypes, on recurrence-free survival (RFS) and overall survival (OS), in 891 prospectively accrued melanoma patients. Cox proportional hazards models (Cox PH) were used to test the associations between 108 melanoma risk SNPs and RFS and OS adjusted by age at diagnosis, gender, tumor stage, histological subtype and other primary tumor characteristics. Results We identified significant associations for rs7538876 (RCC2) with RFS (HR = 1.48, 95% CI = 1.20-1.83, p = 0.0005) and rs9960018 (DLGAP1) with both RFS and OS (HR = 1.43, 95% CI = 1.07-1.91, p = 0.01, HR = 1.52, 95% CI = 1.09-2.12, p = 0.01, respectively) using multivariable Cox PH models. In addition, we developed a logistic regression model that incorporates rs7538876, rs9960018, primary tumor histological type and stage at diagnosis that has an improved discriminatory ability to classify 3-year recurrence (AUC = 82%) compared to histological type and stage alone (AUC = 78%). Conclusions We identified associations between melanoma risk variants and melanoma outcomes. The significant associations observed for rs7538876 and rs9960018 suggest a biological implication of these loci in melanoma progression. The observed predictive patterns of associated variants with clinical end-points suggest for the first time the potential for utilization of genetic risk markers in melanoma prognostication. PMID:24188633

  16. Induction chemotherapy-based larynx preservation program for locally advanced hypopharyngeal cancer: oncologic and functional outcomes and prognostic factors.

    PubMed

    Bozec, Alexandre; Benezery, Karen; Ettaiche, Marc; Chamorey, Emmanuel; Vandersteen, Clair; Dassonville, Olivier; Poissonnet, Gilles; Riss, Jean-Christophe; Hannoun-Lévi, Jean-Michel; Chand, Marie-Eve; Leysalle, Axel; Saada, Esma; Guigay, Joël; Sudaka, Anne; Demard, François; Santini, José; Peyrade, Frédéric

    2016-10-01

    To evaluate oncologic and functional outcomes and prognostic factors in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program in daily clinical practice. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngo-laryngectomy, treated by docetaxel (75 mg/m(2), day 1), cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (750 mg/m(2)/day, day 1-5) (TPF)-ICT (2-3 cycles) for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Prognostic factors of oncologic (overall, cause-specific and recurrence-free survival: OS, SS and RFS) and functional (dysphagia outcome and severity scale, permanent enteral nutrition, larynx preservation) outcomes were assessed in univariate and multivariate analyses. A total of 53 patients (42 men and 11 women, mean age 58.6 ± 8.2 years) were included in this study. Grade 3-4 toxicities were experienced by 17 (32 %) patients during ICT. The rate of poor response (response <50 % without larynx remobilization) to ICT was 10 %. At 5 years, OS, SS and RFS rates were 56, 60 and 54 %, respectively. Four patients required definitive enteral nutrition (permanent enteral tube feeding). The rate of patients alive, disease-free and with a functional larynx at 2 years was 58 %. T4 tumor stage (p = 0.005) and response to ICT <50 % (p = 0.02) were independent prognostic factors of OS. Response to ICT was significantly associated with the risk of permanent enteral nutrition (p = 0.04) and larynx preservation (p = 0.01). In daily clinical practice, a TPF-ICT-based larynx preservation protocol can be used in patients with locally advanced hypopharyngeal cancer with satisfactory results in terms of tolerance, efficacy and oncologic and functional outcomes.

  17. Influence of positive surgical margin status after radical nephroureterectomy on upper urinary tract urothelial carcinoma survival.

    PubMed

    Colin, Pierre; Ouzzane, Adil; Yates, David R; Audenet, François; François, Audenet; Pignot, Géraldine; Arvin-Berod, Alexis; Merigot de Treigny, Olivier; Laurent, Guy; Valeri, Antoine; Irani, Jacques; Jacques, Irani; Saint, Fabien; Gardic, Solène; Gres, Pascal; Rozet, François; Neuzillet, Yann; Ruffion, Alain; Rouprêt, Morgan

    2012-10-01

    The influence of a positive surgical margin (PSM) on survival outcome of post radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UUT-UC) is unclear. The objectives of this study were to determine the significance of PSM on cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) post RNU. From a multicenter collaborative database, data on SM status, stage, grade, lymph node status, lymphovascular invasion (LVI), tumor location, follow-up, and survival was retrieved for 472 patients. Patients underwent open RNU with bladder cuff excision. Clinicopathological features were compared using χ(2) or Fisher exact test and unpaired t test for categorical and continuous variables, respectively. Survival was estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards regression models were calculated. Median follow-up was 27.5 months (12.1-49.3 months). PSM was identified in 44 patients (9.3%) and correlated with pT stage (p = 0.002), grade (p < 0.001), LVI (p < 0.001), and location (p < 0.001). Univariate analyses revealed that PSM was a poor prognostic factor for CSS, RFS, and MFS (p = 0.003, 0.04, and <0.001, respectively). The 5-yr CSS and MFS for PSM was 59.1 and 51.6%, respectively, compared with 83.3 and 79.3% for patients with negative SM. Multivariate analyses revealed that SM status was an independent predictor of MFS [hazard ratio 2.7; p = 0.001). PSM after RNU is an important prognostic factor for developing UUT-UC metastases. The status of the surgical margin should be systematically reported on the pathological report and may be a useful variable to include in nomogram risk prediction tools.

  18. Extremes in body mass index affect overall survival in women with cervical cancer.

    PubMed

    Clark, Leslie H; Jackson, Amanda L; Soo, Adrianne E; Orrey, Danielle C; Gehrig, Paola A; Kim, Kenneth H

    2016-06-01

    To examine the effect of BMI on pathologic findings, cancer recurrence and survival in cervical cancer patients. A retrospective cohort study of cervical cancer patients treated from July 2000 to March 2013 was performed. BMI was calculated, and patients were classified by BMI. The primary outcome was overall survival (OS). Secondary outcomes included stage, histopathology, disease-specific survival (DSS) and recurrence free survival (RFS). Kaplan-Meier survival curves were generated and compared using Cox proportional hazard ratios. Of 632 eligible patients, 24 (4%) were underweight, 191 (30%) were normal weight, 417 (66%) were overweight/obese. There was no difference in age (p=0.91), stage at presentation (p=0.91), grade (p=0.46), or histology (p=0.76) between weight categories. There were fewer White patients in the underweight (54%) and overweight/obese (58%) groups compared to the normal weight (71%) group (p=0.04). After controlling for prognostic factors, underweight and overweight/obese patients had worse median RFS than normal weight patients (7.6 v 25.0months, p=0.01 and 20.3 v 25.0months, p=0.03). Underweight patients also had worse OS (10.4 v 28.4months, p=0.031) and DSS (13.8 v 28.4months, p=0.04) compared to normal weight patients. Overweight/obese patients had worse OS than normal weight patients (22.2 v 28.4months, p=0.03) and a trend toward worse DSS (21.9 v 28.4months, p=0.09). Both extremes of weight (underweight and overweight/obesity) were associated with worse survival in patients with cervical cancer. Optimizing weight in cervical cancer patients may improve outcomes in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Survival improvement in hormone-responsive young breast cancer patients with endocrine therapy.

    PubMed

    Yoon, Tae In; Hwang, Ui-Kang; Kim, Eui Tae; Lee, SaeByul; Sohn, Guiyun; Ko, Beom Seok; Lee, Jong Won; Son, Byung Ho; Kim, Seonok; Ahn, Sei Hyun; Kim, Hee Jeong

    2017-09-01

    We investigated the oncologic outcomes by intrinsic subtype and age in young breast cancer patients and whether survival differences were related to treatment changes over time. A retrospective analysis was performed on 9633 invasive breast cancer patients treated at Asan Medical Center from January 1989 to December 2008. We also enrolled a matched cohort adjusting for tumor size, lymph node metastasis, subtypes, and tumor grade. Patients aged <35 years were included in the younger group (n = 602) and those aged ≥35 years were included in the older group (n = 3009). The younger patients showed a significantly higher T stage, a more frequent axillary node presentation, higher histologic grade, and higher incidence of triple-negative subtype tumors than older patients and also received more chemotherapy and were less likely to undergo hormone therapy. The younger patients with hormone receptor (HR)-positive tumors showed significantly poorer disease-free survival (DFS), loco-regional recurrence-free survival, distant metastasis-free survival, and breast cancer-specific survival outcomes than older patients. Younger patients with HR-positive and human epidermal growth factor receptor 2 (HER2)-negative tumor subtypes had a significantly improved DFS over time (p = 0.032). Within the HR-positive/Her2-negative subtype, more women received gonadotropin-releasing hormone agonist and tamoxifen treatment from 2003 to 2008 compared with 1989 to 2002 (p = 0.001 and p = 0.075, respectively). HR-positive young breast cancer patients have a poorer survival compared with older patients, even with more frequent chemotherapy, but more recent use of tamoxifen and ovarian suppression might improve this outcome in these patients.

  20. Are Biopsy Tracts a Concern for Seeding and Local Recurrence in Sarcomas?

    PubMed

    Barrientos-Ruiz, Irene; Ortiz-Cruz, Eduardo José; Serrano-Montilla, José; Bernabeu-Taboada, Daniel; Pozo-Kreilinger, Jose Juan

    2017-02-01

    the biopsy tract specimen; during the period in question, our routine practice was to excise the biopsy tract whenever possible at the time of the definitive resection. Using the logistic regression test and Mantel-Haenszel test, we compared open with percutaneous biopsies in terms of the proportion of those that were contaminated at our site and for outside referral biopsies separately, because we do not assume the level of expertise was the same (our site is a referral tumor center). We compared the local recurrence-free survival between patients with and without contamination and between open and percutaneous biopsies using the Kaplan Meier test, again separating those performed at our site from those referred for purposes of this analysis. Twenty-one of 180 biopsy tracts were contaminated (12%). Twenty of 62 (32%) of the open biopsies and one of 118 (0.8%) of the percutaneous core needle biopsies had cell seeding (odds ratio [OR], 56; 95% CI, 7-428; p < 0.001. One of 97 (1%) percutaneous biopsies performed in our center, and none of the 21 (0%) percutaneous biopsies performed in other centers had contaminated biopsy tracts (p = 0.047). Two of 15 (13%) open biopsies performed at our center and 18 of 41(38%) open biopsies performed at other centers had contaminated biopsy tracts (OR, 4; 95% CI, 1-7; p = 0.001). Four of 74 (5%) bone sarcomas and 18 of 106 (17%) soft tissue sarcomas had biopsy tract contamination (OR, 3; 95% CI, 1-10; p = 0.023). The local recurrence-free survival was longer for patients without contaminated tracts (mean, 107 months; 95% CI, 74-141 months) than for those with biopsy tract seeding (mean, 11 months; 95% CI, 1-20 months; p < 0.001). Open biopsies were associated with an increased risk of tumoral seeding of the biopsy site, and tumoral seeding was associated with an increased risk of local recurrence. However, it is possible that other factors, such as increased complexity of the tumor or a difficult location, influenced the decision to

  1. Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients.

    PubMed

    Coscio, Angela; Chang, David W; Roth, Jack A; Ye, Yuanqing; Gu, Jian; Yang, Ping; Wu, Xifeng

    2014-06-01

    Early-stage non-small cell lung cancer (NSCLC) is potentially curative. Nevertheless, many patients will show disease recurrence after curative treatment. The Wnt signaling pathway is a developmental and stem cell pathway that plays an important role in tumorigenesis and may affect cancer progression. We hypothesize that genetic variants of the Wnt pathway may influence clinical outcome in early-stage NSCLC patients. We genotyped 441 functional and tagging single nucleotide polymorphisms (SNPs) from 54 genes of the Wnt pathway in 535 early-stage NSCLC patients treated with curative intent therapy including surgery and chemotherapy. For validation, 4 top SNPs were genotyped in 301 early-stage NSCLC patients from the Mayo Clinic. Cox proportional hazard model and combined SNP analyses were performed to identify significant SNPs correlated with recurrence-free and overall survival. Results from discovery group showed a total of 40 SNPs in 20 genes correlated with disease recurrence (P < 0.05). After correction for multiple comparisons, rs2536182 near Wnt16 remained significant (q < 0.1), which was validated in the replication population. Thirty-nine SNPs in 16 genes correlated with overall survival (P < 0.05) in the discovery group, and seven remained significant after multiple comparisons were considered (q < 0.1). In patients receiving surgery-only treatment, rs10898563 of FZD4 gene was associated with both recurrence-free and overall survival. Joint SNP analyses identified predictive markers for recurrence stratified by treatment. Our findings suggest inherited genetic variation in the Wnt signaling pathway may contribute to variable clinical outcomes for patients with early-stage NSCLC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. In Papillary Thyroid Cancer, Preoperative Central Neck Ultrasound Detects Only Macroscopic Surgical Disease, But Negative Findings Predict Excellent Long-Term Regional Control and Survival

    PubMed Central

    Moreno, Mauricio A.; Edeiken-Monroe, Beth S.; Siegel, Eric R.; Sherman, Steven I.

    2012-01-01

    Background Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC. Methods A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival. Results There were 112 males and 219 females with a median age of 44 years (range 11–87). The median follow-up time for the series was 71.5 months (range 12.7–148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease

  3. A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection

    PubMed Central

    Fu, Yi-Peng; Ni, Xiao-Chun; Yi, Yong; Cai, Xiao-Yan; He, Hong-Wei; Wang, Jia-Xing; Lu, Zhu-Feng; Han, Xu; Cao, Ya; Zhou, Jian; Fan, Jia; Qiu, Shuang-Jian

    2016-01-01

    Abstract As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy. Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature. In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone. IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy. PMID:26886627

  4. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  5. Recurrence and survival following resection of bronchioloalveolar carcinoma of the lung--The Lung Cancer Study Group experience.

    PubMed Central

    Grover, F L; Piantadosi, S

    1989-01-01

    Bronchioloalveolar carcinoma (BAC) of the lung is a controversial form of adenocarcinoma with varying presentations. The 1977 to 1988 Lung Study Group experience with this tumor was reviewed to more precisely define the incidence of recurrence and survival of surgically resected and staged patients, to determine the incidence of BAC in the adenocarcinoma population, and to evaluate the impact of age, sex, smoking, and chronic lung-disease history on the incidence of BAC. Of 1635 patients reviewed, 235 patients had pure BAC. It was found that resectable BAC presents at an earlier disease stage than does adenocarcinoma; BAC occurs more frequently in older patients and in those without smoking history or chronic lung disease than adenocarcinoma; BAC patients have less weight loss, brain recurrences, and recurrences without second primaries than adenocarcinoma; survival and recurrence-free survival are better for BAC than for non-BAC adenocarcinoma and large-cell carcinoma; early BAC survival is better than squamous-cell survival but after 2 years is equivalent; T1-N0 BAC patients have recurrence and survival rates similar to squamous-cell survival rates and better than non-BAC adeno survival rates; T1-N1/T2-N0 and Stage 2 and 3 BAC recurs more frequently than either squamous-cell or non-BAC adenocarcinoma; stage 2 and 3 BAC has a higher mortality rate than does squamous-cell carcinoma or non-BAC adenocarcinoma; BAC is a favorable prognostic factor when adjusted for extent of disease and age; and BAC's better prognosis is a result of presenting at an earlier stage of disease and because it appears to be less aggressive than other adenocarcinomas even after adjustment for extent of disease and other known prognostic factors. It is concluded that early diagnosis and resection are particularly important for patients with BAC. Images Fig. 5. Fig. 6. Figs. 7A and B. Fig. 8. PMID:2543339

  6. Treatment patterns and survival outcomes in patients with cervical cancer complicated by complete uterine prolapse: a systematic review of literature.

    PubMed

    Matsuo, Koji; Fullerton, Morgan E; Moeini, Aida

    2016-01-01

    Cervical cancer complicated by complete uterine prolapse is a rare clinical entity and uniform management recommendations have yet to be determined. The aim of the current review was to examine the effects of management patterns on survival outcomes in cervical cancer patients with complete uterine prolapse. A systematic review of the literature was conducted using three public search engines. This included case reports with detailed descriptions of tumor characteristics, cancer management, and survival outcomes. Treatment patterns and tumor characteristics were correlated to survival outcomes. There were 78 patients with cervical cancer with complete uterine prolapse. Their mean age was 63.7 years. The median duration of prolapse was 147.9 months and 22.2% of the patients experienced persistent/recurrent prolapse after cancer treatment. The mean tumor size was 8.9 cm and squamous cell carcinoma (83.9%) was the most common histologic type. The majority of patients (56.2%) had stage I cancer. Tumor characteristics were similar across the treatment patterns. Survival outcomes were more favorable with surgery-based treatment (48 patients) than with radiation-based treatment (30 patients): 5-year recurrence-free survival rate 72.0% vs. 62.9% (p = 0.057), and 5-year disease-specific overall survival rate 77.0% vs. 68.2% (p = 0.017). After controlling for age and stage, surgery-based therapy remained an independent prognostic factor for better disease-specific overall survival outcome (hazard ratio 0.32, 95% confidence interval 0.11 - 0.94, adjusted p =