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

PubMed

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

2016-11-22

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

Prognostic significance of perioperative nutritional parameters in patients with gastric cancer.

PubMed

Oh, Sung Eun; Choi, Min-Gew; Seo, Jeong-Meen; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung

2018-02-20

It has been suggested that nutritional status is related to the survival outcomes of cancer patients. The purpose of the current research is to evaluate the importance of the prognosis of various nutritional parameters during the perioperative period in patients with gastric cancer. This study enrolled patients with gastric cancer who underwent D2 gastrectomy at the Department of Surgery, Samsung Medical Center, in 2008. The prognostic significance of nutritional parameters was analyzed, along with other clinical and pathological variables, preoperatively and postoperatively at 3, 6, and 12 months. The total number of patients was 1415. The mean values of nutritional parameters, weight, body mass index (BMI), hemoglobin, total cholesterol, and total lymphocyte count (TLC) decreased significantly over time after surgery. On the contrary, albumin and prognostic nutritional index (PNI) score increased significantly during the postoperative follow-up period. Preoperatively, low BMI (<18.5 kg/m 2 ) and low TLC level (<1000 per mm 3 ) were revealed as independent prognostic factors in multivariate analysis. Low preoperative TLC level and decline in PNI (ΔPNI < -2.2) at postoperative 3 months; low preoperative TLC level and decline in TLC (ΔTLC < -279.9 per mm 3 ) at postoperative 6 months; and low preoperative BMI, albumin, and TLC levels at postoperative 12 months were independent nutritional prognostic indicators. Various perioperative nutritional parameters were confirmed as independent prognostic factors in patients with gastric cancer. Our results imply prognostic benefit from careful nutritional support for patients with poor nutritional parameters. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

PubMed Central

Ajani, Jaffer A.; Winter, Kathryn A.; Gunderson, Leonard L.; Pedersen, John; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2009-01-01

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. PMID:19139424

Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection.

PubMed

Higashikawa, Toshihiro; Okuro, Masashi; Ishigami, Keiichirou; Mae, Kunihiro; Sangen, Ryusho; Mizuno, Takurou; Usuda, Daisuke; Saito, Atushi; Kasamaki, Yuji; Fukuda, Akihiro; Saito, Hitoshi; Morimoto, Shigeto; Kanda, Tsugiyasu

2018-01-01

Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and PCT-positive (≥0.5 ng/mL) groups comprised 155 and 115 patients, respectively. Logistic regression analysis was performed with various clinical laboratory test values as independent variables and PCT positivity/negativity as the dependent variable. Results C-reactive protein (CRP) was the only independent variable significantly associated with PCT positivity/negativity. In the survival analysis, the 30-day in-hospital death rate was significantly higher in the PCT-positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

Practical prognostic index for patients with metastatic recurrent breast cancer: retrospective analysis of 2,322 patients from the GEICAM Spanish El Alamo Register.

PubMed

Puente, Javier; López-Tarruella, Sara; Ruiz, Amparo; Lluch, Ana; Pastor, Miguel; Alba, Emilio; de la Haba, Juan; Ramos, Manuel; Cirera, Luis; Antón, Antonio; Llombart, Antoni; Plazaola, Arrate; Fernández-Aramburo, Antonio; Sastre, Javier; Díaz-Rubio, Eduardo; Martin, Miguel

2010-07-01

Women with recurrent metastatic breast cancer from a Spanish hospital registry (El Alamo, GEICAM) were analyzed in order to identify the most helpful prognostic factors to predict survival and to ultimately construct a practical prognostic index. The inclusion criteria covered women patients diagnosed with operable invasive breast cancer who had metastatic recurrence between 1990 and 1997 in GEICAM hospitals. Patients with stage IV breast cancer at initial diagnosis or with isolated loco-regional recurrence were excluded from this analysis. Data from 2,322 patients with recurrent breast cancer after primary treatment (surgery, radiation and systemic adjuvant treatment) were used to construct the prognostic index. The prognostic index score for each individual patient was calculated by totalling up the scores of each independent variable. The maximum score obtainable was 26.1. Nine-hundred and sixty-two patients who had complete data for all the variables were used in the computation of the prognostic index score. We were able to stratify them into three prognostic groups based on the prognostic index score: 322 patients in the good risk group (score < or =13.5), 308 patients in the intermediate risk group (score 13.51-15.60) and 332 patients in the poor risk group (score > or =15.61). The median survivals for these groups were 3.69, 2.27 and 1.02 years, respectively (P < 0.0001). In conclusion, risk scores are extraordinarily valuable tools, highly recommendable in the clinical practice.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

PubMed

Candido Dos Reis, Francisco J; Wishart, Gordon C; Dicks, Ed M; Greenberg, David; Rashbass, Jem; Schmidt, Marjanka K; van den Broek, Alexandra J; Ellis, Ian O; Green, Andrew; Rakha, Emad; Maishman, Tom; Eccles, Diana M; Pharoah, Paul D P

2017-05-22

PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer.

Development and Validation of a Novel Platform-Independent Metastasis Signature in Human Breast Cancer

PubMed Central

Speers, Corey; Liu, Meilan; Wilder-Romans, Kari; Lawrence, Theodore S.; Pierce, Lori J.; Feng, Felix Y.

2015-01-01

Purpose The molecular drivers of metastasis in breast cancer are not well understood. Therefore, we sought to identify the biological processes underlying distant progression and define a prognostic signature for metastatic potential in breast cancer. Experimental design In vivo screening for metastases was performed using Chick Chorioallantoic Membrane assays in 21 preclinical breast cancer models. Expressed genes associated with metastatic potential were identified using high-throughput analysis. Correlations with biological function were determined using the Database for Annotation, Visualization and Integrated Discovery. Results We identified a broad range of metastatic potential that was independent of intrinsic breast cancer subtypes. 146 genes were significantly associated with metastasis progression and were linked to cancer-related biological functions, including cell migration/adhesion, Jak-STAT, TGF-beta, and Wnt signaling. These genes were used to develop a platform-independent gene expression signature (M-Sig), which was trained and subsequently validated on 5 independent cohorts totaling nearly 1800 breast cancer patients with all p-values < 0.005 and hazard ratios ranging from approximately 2.5 to 3. On multivariate analysis accounting for standard clinicopathologic prognostic variables, M-Sig remained the strongest prognostic factor for metastatic progression, with p-values < 0.001 and hazard ratios > 2 in three different cohorts. Conclusion M-Sig is strongly prognostic for metastatic progression, and may provide clinical utility in combination with treatment prediction tools to better guide patient care. In addition, the platform-independent nature of the signature makes it an excellent research tool as it can be directly applied onto existing, and future, datasets. PMID:25974184

CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease.

PubMed

Hamblin, Terry J; Orchard, Jenny A; Ibbotson, Rachel E; Davis, Zadie; Thomas, Peter W; Stevenson, Freda K; Oscier, David G

2002-02-01

Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgV(H)) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgV(H) mutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3%). Multivariate analysis demonstrated that Binet stage, IgV(H) mutations and CD38 were independent prognostic indicators. Median survival time in patients whose cells had unmutated IgV(H) genes and expressed CD38 was 8 years; in those with mutated IgV(H) genes not expressing CD38, it was 26 years. For those with discordant results, median survival time was 15 years. Thus, although CD38 expression does not identify the same 2 subsets as IgV(H) mutations in CLL, it is an independent risk factor that can be used with IgV(H) mutations and clinical stage to select patients with B-CLL with the worst prognoses. Using cryopreserved cells taken at intervals during the course of the disease, however, changes of CD38 expression over time were demonstrated in 10 of 41 patients. Causes of the variation of CD38 expression require further study. Additional prospective studies are required for comparing CD38 expression with other prognostic factors and for taking sequential measurements during the course of the disease.

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

PubMed

Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

2016-04-01

Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity.

Current state of prognostication and risk stratification in myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Gore, Steven D; Padron, Eric; Komrokji, Rami S

2015-03-01

Myelodysplastic syndromes (MDS) are characterized by significant biologic and clinical heterogeneity. Because of the wide outcome variability, accurate prognostication is vital to high-quality risk-adaptive care of MDS patients. In this review, we discuss the current state of prognostic schemes for MDS and overview efforts aimed at utilizing molecular aberrations for prognostication in clinical practice. Several prognostic instruments have been developed and validated with increasing accuracy and complexity. Oncologists should be aware of the inherent limitations of these prognostic tools as they counsel patients and make clinical decisions. As more therapies are becoming available for MDS, the focus of model development is shifting from prognostic to treatment-specific predictive instruments. In addition to providing additional prognostic data beyond traditional clinical and pathologic parameters, the improved understanding of the genetic landscape and pathophysiologic consequences in MDS may allow the construction of treatment-specific predictive instruments. How to best use the results of molecular mutation testing to inform clinical decision making in MDS is still a work in progress. Important steps in this direction include standardization in performance and interpretation of assays and better understanding of the independent prognostic importance of the recurrent mutations, especially the less frequent ones.

Very high levels of soluble CD30 recognize the patients with classical Hodgkin's lymphoma retaining a very poor prognosis.

PubMed

Visco, Carlo; Nadali, Gianpaolo; Vassilakopoulos, Theodoros P; Bonfante, Valeria; Viviani, Simonetta; Gianni, Alessandro M; Federico, Massimo; Luminari, Stefano; Peethambaram, Prema; Witzig, Thomas E; Pangalis, Gerassimos; Cabanillas, Fernando; Medeiros, L Jeffrey; Sarris, Andreas H; Pizzolo, Giovanni

2006-11-01

To evaluate the prognostic role of pretreatment serum levels of soluble CD30 (sCD30) in patients with advanced stage classical Hodgkin's lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine or equivalent regimens. We identified 321 previously untreated patients with cHL who presented to the participating centers between 1985 and 2002, and had serum samples available for the determination of sCD30 levels. With a median follow-up of 72 months, the actuarial 5-year overall survival was 82%, and failure-free survival (FFS) was 71%. The median serum level of sCD30 was 65 U/mL (range: 1-2230), and was significantly higher (P < 0.0001) when compared with a group of 113 healthy controls (4 U/mL, range: 0-20). Increasing level of sCD30 was associated with a continuous worsening of FFS and OS, and patients with sCD30 >or=200 U/mL had a 5-year FFS of 39%. With multivariate analysis, sCD30, Ann Arbor stage, and lactic acid dehydrogenase were significant independent factors in terms of FFS. The association of the above-mentioned three independent prognostic variables could discriminate 22% of patients with 5-year FFS of 40%. Our data confirm the independent prognostic role of sCD30 in identifying the patients with high risk of treatment failure, and show that its association with other variables can recognize patients with FFS considerably lower than 50%.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer.

PubMed

Nobashi, Tomomi; Koyasu, Sho; Nakamoto, Yuji; Kubo, Takeshi; Ishimori, Takayoshi; Kim, Young H; Yoshizawa, Akihiko; Togashi, Kaori

2016-01-01

To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

Independent Prognostic Value of Stroke Volume Index in Patients With Immunoglobulin Light Chain Amyloidosis.

PubMed

2018-05-01

Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37-3.66), 2.36 (1.96-2.85), and 2.32 (1.91-2.80). For the subset that had left ventricular strain performed, the prognostic cut point was -14% (hazard ratios, 2.70; 95% confidence intervals, 1.84-3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients. © 2018 American Heart Association, Inc.

Edmondson-Steiner grade: A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasio.

PubMed

Zhou, Li; Rui, Jing-An; Zhou, Wei-Xun; Wang, Shao-Bin; Chen, Shu-Guang; Qu, Qiang

2017-07-01

Microvascular invasion (MVI), an important pathologic parameter, has been proven to be a powerful predictor of long-term prognosis in hepatocellular carcinoma (HCC). However, prognostic factors in HCC without MVI remain unknown. The present study aimed to identify the risk factors of recurrence and poor post-resectional survival in this type of HCC. A total of 109 patients with MVI-absent HCC underwent radical hepatectomy were enrolled. The influence of clinicopathologic variables on recurrence and patient survival was assessed using univariate and multivariate analyses. Chi-square test found that Edmondson-Steiner grade and satellite nodule were significantly associated with recurrence, while the former was the single marker for early recurrence. Stepwise logistic regression analysis demonstrated the independent predictive role of Edmondson-Steiner grade for recurrence. On the other hand, Edmondson-Steiner grade, serum AFP level and satellite nodule were significant for overall and disease-free survival in univariate analysis, whereas tumor size was linked to disease-free survival. Of the variables, Edmondson-Steiner grade, serum AFP level and satellite nodule were independent indicators. Edmondson-Steiner grade, a histological classification, carries robust prognostic implications for all the endpoints for prognosis, thus being potential to be a crucial prognosticator in HCC without MVI. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

PubMed

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

2014-01-01

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

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

PubMed

Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia.

PubMed

Such, Esperanza; Germing, Ulrich; Malcovati, Luca; Cervera, José; Kuendgen, Andrea; Della Porta, Matteo G; Nomdedeu, Benet; Arenillas, Leonor; Luño, Elisa; Xicoy, Blanca; Amigo, Mari L; Valcarcel, David; Nachtkamp, Kathrin; Ambaglio, Ilaria; Hildebrandt, Barbara; Lorenzo, Ignacio; Cazzola, Mario; Sanz, Guillermo

2013-04-11

The natural course of chronic myelomonocytic leukemia (CMML) is highly variable but a widely accepted prognostic scoring system for patients with CMML is not available. The main aim of this study was to develop a new CMML-specific prognostic scoring system (CPSS) in a large series of 558 patients with CMML (training cohort, Spanish Group of Myelodysplastic Syndromes) and to validate it in an independent series of 274 patients (validation cohort, Heinrich Heine University Hospital, Düsseldorf, Germany, and San Matteo Hospital, Pavia, Italy). The most relevant variables for overall survival (OS) and evolution to acute myeloblastic leukemia (AML) were FAB and WHO CMML subtypes, CMML-specific cytogenetic risk classification, and red blood cell (RBC) transfusion dependency. CPSS was able to segregate patients into 4 clearly different risk groups for OS (P < .001) and risk of AML evolution (P < .001) and its predictive capability was confirmed in the validation cohort. An alternative CPSS with hemoglobin instead of RBC transfusion dependency offered almost identical prognostic capability. This study confirms the prognostic impact of FAB and WHO subtypes, recognizes the importance of RBC transfusion dependency and cytogenetics, and offers a simple and powerful CPSS for accurately assessing prognosis and planning therapy in patients with CMML.

Prognostic implications of adhesion molecule expression in colorectal cancer.

PubMed

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

2015-01-01

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

Prognostic implications of adhesion molecule expression in colorectal cancer

PubMed Central

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

2015-01-01

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

Development and validation of a prognostic index for 4-year mortality in older adults.

PubMed

Lee, Sei J; Lindquist, Karla; Segal, Mark R; Covinsky, Kenneth E

2006-02-15

Both comorbid conditions and functional measures predict mortality in older adults, but few prognostic indexes combine both classes of predictors. Combining easily obtained measures into an accurate predictive model could be useful to clinicians advising patients, as well as policy makers and epidemiologists interested in risk adjustment. To develop and validate a prognostic index for 4-year mortality using information that can be obtained from patient report. Using the 1998 wave of the Health and Retirement Study (HRS), a population-based study of community-dwelling US adults older than 50 years, we developed the prognostic index from 11,701 individuals and validated the index with 8009. Individuals were asked about their demographic characteristics, whether they had specific diseases, and whether they had difficulty with a series of functional measures. We identified variables independently associated with mortality and weighted the variables to create a risk index. Death by December 31, 2002. The overall response rate was 81%. During the 4-year follow-up, there were 1361 deaths (12%) in the development cohort and 1072 deaths (13%) in the validation cohort. Twelve independent predictors of mortality were identified: 2 demographic variables (age: 60-64 years, 1 point; 65-69 years, 2 points; 70-74 years, 3 points; 75-79 years, 4 points; 80-84 years, 5 points, >85 years, 7 points and male sex, 2 points), 6 comorbid conditions (diabetes, 1 point; cancer, 2 points; lung disease, 2 points; heart failure, 2 points; current tobacco use, 2 points; and body mass index <25, 1 point), and difficulty with 4 functional variables (bathing, 2 points; walking several blocks, 2 points; managing money, 2 points, and pushing large objects, 1 point. Scores on the risk index were strongly associated with 4-year mortality in the validation cohort, with 0 to 5 points predicting a less than 4% risk, 6 to 9 points predicting a 15% risk, 10 to 13 points predicting a 42% risk, and 14 or more points predicting a 64% risk. The risk index showed excellent discrimination with a cstatistic of 0.84 in the development cohort and 0.82 in the validation cohort. This prognostic index, incorporating age, sex, self-reported comorbid conditions, and functional measures, accurately stratifies community-dwelling older adults into groups at varying risk of mortality.

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PubMed Central

Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

2015-01-01

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients. PMID:26438120

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.

PubMed

Scarisbrick, Julia J; Prince, H Miles; Vermeer, Maarten H; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L; Rodríguez-Peralto, Jose L; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T; Duvic, Madeleine; Whittaker, Sean J; Kim, Youn H

2015-11-10

Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients. © 2015 by American Society of Clinical Oncology.

Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.

PubMed

Andreiuolo, Felipe; Le Teuff, Gwénaël; Bayar, Mohamed Amine; Kilday, John-Paul; Pietsch, Torsten; von Bueren, André O; Witt, Hendrik; Korshunov, Andrey; Modena, Piergiorgio; Pfister, Stefan M; Pagès, Mélanie; Castel, David; Giangaspero, Felice; Chimelli, Leila; Varlet, Pascale; Rutkowski, Stefan; Frappaz, Didier; Massimino, Maura; Grundy, Richard; Grill, Jacques

2017-01-01

Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.

The degree of circumferential tumour involvement as a prognostic factor in oesophageal cancer.

PubMed

Sillah, Karim; Pritchard, Susan A; Watkins, Gillian R; McShane, James; West, Catharine M; Page, Richard; Welch, Ian M

2009-08-01

Tumour length is an adverse prognostic factor in oesophageal cancer. However, the prognostic role of the degree of oesophageal circumference (DOC) involved by tumour with or without resection margin invasion is not clear. This work assessed the relationship between DOC involved by tumour, clinico-pathological variables and prognosis. The clinico-pathological details of 320 patients who underwent potentially curative oesophagogastrectomy for cancer between 1994 and 2007 were analysed. The DOC involved with tumour measured macroscopically on the resected specimen was classified as small (<2.5 cm, n = 115), large (> or = 2.5 cm, n = 144) or circumferential (i.e. involving the whole circumference, n = 61). Univariate and multivariate survival analyses were carried out. The DOC with tumour was higher in ulcerating tumours than stenosing or polypoidal types (p = 0.017). Tumour length, T-stage, neoadjuvant chemotherapy and vascular invasion were independently associated with DOC with tumour on multivariate analysis (p < 0.05 for all). DOC > or = 2.5 cm was an adverse prognostic factor in univariate analysis (p = 0.002) with a hazard ratio of 1.52 [95% CI 1.13-2.04] compared with those <2.5 cm. Circumferential tumours had a similar prognosis to tumours > or = 2.5 cm (p = 0.60). The prognostic significance of DOC with tumour was lost in multivariate analysis where the factors retaining independence were patient age, T-stage, lymph node metastasis, vascular invasion and positive resection margins. However, when patients were stratified by use of neoadjuvant chemotherapy (n = 121), the DOC with tumour retained prognostic significance on multivariate analysis in the 199 patients who did not undergo neoadjuvant chemotherapy (p = 0.04). The DOC with tumour appears to provide prognostic information in oesophageal cancer surgery, especially in patients who do not undergo preoperative chemotherapy.

A four-gene signature predicts survival in clear-cell renal-cell carcinoma.

PubMed

Dai, Jun; Lu, Yuchao; Wang, Jinyu; Yang, Lili; Han, Yingyan; Wang, Ying; Yan, Dan; Ruan, Qiurong; Wang, Shaogang

2016-12-13

Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.

Novel immunological and nutritional-based prognostic index for gastric cancer.

PubMed

Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long

2015-05-21

To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.

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

PubMed Central

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

2017-01-01

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

Sex and SUVmax: sex-dependent prognostication in early non-small cell lung cancer.

PubMed

Wainer, Zoe; Daniels, Marissa G; Callahan, Jason; Binns, David; Hicks, Rodney J; Antippa, Phillip; Russell, Prudence A; Alam, Naveed Z; Conron, Matthew; Solomon, Benjamin; Wright, Gavin M

2012-11-01

The identification of robust prognostic factors for patients with early-stage non-small cell lung cancer (NSCLC) is clinically important. The International Association for the Study of Lung Cancer has identified both sex and the maximum standardized uptake value (SUVmax) of (18)F-FDG in the primary tumor as measured by PET as potential prognostic variables. We examined the prognostic value of SUVmax in a surgical cohort of patients with NSCLC and disaggregated the findings by sex. Patients who had undergone a preoperative PET/CT scan and surgical resection with curative intent from 2001 to 2009 were identified from a prospective database. An SUVmax cutoff was calculated using receiver-operating-characteristic curves. Overall survival was correlated with SUVmax for the whole cohort and disaggregated by sex. Inclusion criteria were met by 189 patients: 127 (67%) men and 62 (33%) women. Five-year survival was 54.6% for the whole cohort, 47.7% for men, and 68.2% for women. SUVmax correlated negatively with survival in a univariate analysis for the whole cohort (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.54-4.09; P < 0.001) and men (HR, 3.42; 95% CI, 1.94-6.05; P < 0.001) but not for women (HR, 1.61; 95% CI, 0.43-3.12; P = 0.77), using 8 as a cutoff. In multivariate analysis, SUVmax correlated with overall survival for the whole cohort (HR, 1.70; 95% CI, 1.05-2.99; P = 0.05) and men (HR, 2.40; 95% CI, 1.32-4.37; P = 0.004) but not for women (HR, 0.80; 95% CI, 0.15-4.47; P = 0.80). SUVmax independently predicted overall survival for men but not for women in this surgical cohort. Our results suggest that SUVmax is an independent prognostic variable in men with surgically treated early NSCLC.

An integrated mRNA and microRNA expression signature for glioblastoma multiforme prognosis.

PubMed

Xiong, Jie; Bing, Zhitong; Su, Yanlin; Deng, Defeng; Peng, Xiaoning

2014-01-01

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures.

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue.

PubMed

Nielsen, H J; Hansen, U; Christensen, I J; Reimert, C M; Brünner, N; Moesgaard, F

1999-12-01

Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p< 0.0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth. Copyright 1999 John Wiley & Sons, Ltd.

An Integrated mRNA and microRNA Expression Signature for Glioblastoma Multiforme Prognosis

PubMed Central

Xiong, Jie; Bing, Zhitong; Su, Yanlin; Deng, Defeng; Peng, Xiaoning

2014-01-01

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures. PMID:24871302

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study

PubMed Central

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment. PMID:28458303

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

PubMed

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Risk factors for adverse outcomes in older adults with blunt chest trauma: A systematic review.

PubMed

Sawa, Jake; Green, Robert S; Thoma, Brent; Erdogan, Mete; Davis, Philip J

2017-08-11

The objective of this study was to systematically review the published literature for risk factors associated with adverse outcomes in older adults sustaining blunt chest trauma. EMBASE and MEDLINE were searched from inception until March 2017 for prognostic factors associated with adverse outcomes in older adults sustaining blunt chest trauma using a pre-specified search strategy. References were independently screened for inclusion by two reviewers. Study quality was assessed using the Quality in Prognostic Studies tool. Where appropriate, descriptive statistics were used to evaluate study characteristics and predictors of adverse outcomes. Thirteen cohort studies representing 79,313 patients satisfied our selection criteria. Overall, 26 prognostic factors were examined across studies and were reported for morbidity (8 studies), length of stay (7 studies), mortality (6 studies), and loss of independence (1 study). No studies examined patient quality of life or emergency department recidivism. Prognostic factors associated with morbidity and mortality included age, number of rib fractures, and injury severity score. Although age and rib fractures were found to be associated with adverse outcomes in more than 3 studies, meta-analysis was not performed due to heterogeneity amongst included studies in how these variables were measured. While blunt chest wall trauma in older adults is relatively common, the literature on prognostic factors for adverse outcomes in this patient population remains inadequate due to a paucity of high quality studies and lack of consistent reporting standards.

Telomere length is an independent prognostic marker in MDS but not in de novo AML.

PubMed

Williams, Jenna; Heppel, Nicole H; Britt-Compton, Bethan; Grimstead, Julia W; Jones, Rhiannon E; Tauro, Sudhir; Bowen, David T; Knapper, Steven; Groves, Michael; Hills, Robert K; Pepper, Chris; Baird, Duncan M; Fegan, Chris

2017-07-01

Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P < 0·0001) where telomere length was also significantly shorter in younger AML patients (age <60 years) (P = 0·02) and in FLT3 internal tandem duplication-mutated AML patients (P = 0·03). Using a previously determined telomere length threshold for telomere dysfunction (3·81 kb) did not provide prognostic resolution in AML [Hazard ratio (HR) = 0·68, P = 0·2]. In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5·0, P < 0·0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and International Prognostic Scoring System (IPSS) score (HR = 2·27, P < 0·0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS. © 2017 John Wiley & Sons Ltd.

Heart rate variability enhances the prognostic value of established parameters in patients with congestive heart failure.

PubMed

Krüger, C; Lahm, T; Zugck, C; Kell, R; Schellberg, D; Schweizer, M W F; Kübler, W; Haass, M

2002-12-01

This prospective study evaluated whether heart rate variability (HRV) assessed from Holter ECG has prognostic value in addition to established parameters in patients with congestive heart failure (CHF). The study included 222 patients with CHF due to dilated or ischemic cardiomyopathy (left ventricular ejection fraction LVEF 21+/-1%; mean+/-SEM). During a mean follow-up of 15+/-1 months, 38 (17%) patients died and 45 (20%) were hospitalized due to worsening of CHF. The HRV parameter SDNN (standard deviation of all intervals between normal beats) was significantly lower in non-surviving or hospitalized than in event-free patients (118+/-6 vs 142+/-5 ms), as were LVEF (18+/-1 vs 23+/-1%), and peak oxygen uptake during exercise (peak VO(2)) (12.8+/-0.5 vs 15.6+/-0.5 ml/min/kg). While each of these parameters was a risk predictor in univariate analysis, multivariate analysis revealed that HRV provides both independent and additional prognostic information with respect to the risk 'cardiac mortality or deterioration of CHF'. It is concluded that the determination of HRV enhances the prognostic power given by the most widely used parameters LVEF and peak VO(2) in the prediction of mortality or deterioration of CHF and thus enables to improve risk stratification.

Type 2 diabetes is an independent negative prognostic factor in patients undergoing surgical resection of a WHO grade I meningioma.

PubMed

Nayeri, Arash; Chotai, Silky; Prablek, Marc A; Brinson, Philip R; Douleh, Diana G; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola

2016-10-01

In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma. We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P<0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. 33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p<0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045). A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma. Copyright © 2016 Elsevier B.V. All rights reserved.

A New Prognostic Staging System for Rectal Cancer

PubMed Central

Ueno, Hideki; Price, Ashley B.; Wilkinson, Kay H.; Jass, Jeremy R.; Mochizuki, Hidetaka; Talbot, Ian C.

2004-01-01

Objective: To clarify the appropriateness of tumor “budding,” a quantifiable histologic variable, as 1 parameter in the construction of a new prognostic grading system for rectal cancer. Summary Background Data: Patient division according to an accurate prognostic prediction could enhance the effectiveness of postoperative adjuvant therapy and follow-up. Patients and Methods: Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than 5 cells in the invasive frontal region, and was divided into 2 grades based on its number within a microscopic field of ×250. We analyzed 2 discrete cohorts comprising 638 and 476 patients undergoing potentially curative surgery. Results: In the first cohort, high-grade budding (10 or more foci in a field) was observed in 30% of patients and was significantly associated with a lower 5-year survival rate (41%) than low-grade budding (84%). Similarly, in the second cohort, the 5-year survival rate was 43% in high-grade budding patients and 83% in low-grade budding patients. In both cohorts, multivariate analyses verified budding to be an independent prognosticator, together with nodal involvement and extramural spread. These 3 variables were given weighted scores, and the score range was divided to provide 5 prognostic groups (97%; 86%; 61%; 39%; 17% 5-year survival). The model was tested on the second cohort, and similar prognostic results were obtained. Conclusions: We propose that because of its relevance to prognosis and its reproducibility, budding is an excellent parameter for use in a grading system to provide a confident prediction of clinical outcome. PMID:15492565

Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

PubMed Central

Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella

2014-01-01

Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk. PMID:25373410

Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

PubMed

Abidov, Aiden; Hachamovitch, Rory; Rozanski, Alan; Hayes, Sean W; Santos, Marcia M; Sciammarella, Maria G; Cohen, Ishac; Gerlach, James; Friedman, John D; Germano, Guido; Berman, Daniel S

2004-09-01

The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). The prognostic significance of AF in patients undergoing MPS is not known. A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

PubMed

Cheng, Nai-Ming; Fang, Yu-Hua Dean; Lee, Li-yu; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Liao, Chun-Ta; Yang, Lan-Yan; Hsu, Ching-Han; Yen, Tzu-Chen

2015-03-01

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

PubMed

Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie

2017-10-01

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

A Prognostic Gene Expression Profile That Predicts Circulating Tumor Cell Presence in Breast Cancer Patients

PubMed Central

Molloy, Timothy J.; Roepman, Paul; Naume, Bjørn; van't Veer, Laura J.

2012-01-01

The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into “good prognosis” or “poor prognosis” are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the “CTC profile” also provided prognostic information independent of the well-established and powerful ‘70-gene’ prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays. PMID:22384245

Using Cox's proportional hazards model for prognostication in carcinoma of the upper aero-digestive tract.

PubMed

Wolfensberger, M

1992-01-01

One of the major short comings of the traditional TNM system is its limited potential for prognostication. With the development of multifactorial analysis techniques, such as Cox's proportional hazards model, it has become possible to simultaneously evaluate a large number of prognostic variables. Cox's model allows both the identification of prognostically relevant variables and the quantification of their prognostic influence. These characteristics make it a helpful tool for analysis as well as for prognostication. The goal of the present study was to develop a prognostic index for patients with carcinoma of the upper aero-digestive tract which makes use of all prognostically relevant variables. To accomplish this, the survival data of 800 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were analyzed. Sixty-one variables were screened for prognostic significance; of these only 19 variables (including age, tumor location, T, N and M stages, resection margins, capsular invasion of nodal metastases, and treatment modality) were found to significantly correlate with prognosis. With the help of Cox's equation, a prognostic index (PI) was computed for every combination of prognostic factors. To test the proposed model, the prognostic index was applied to 120 patients with carcinoma of the oral cavity or oropharynx. A comparison of predicted and observed survival showed good overall correlation, although actual survival tended to be better than predicted.

Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

PubMed

Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

2014-07-04

Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

Clinical relevance of sentinel lymph node status examined with conventional histology and molecular biology.

PubMed

Micciolo, Rocco; Boi, Sebastiana; Paoli, Loredana; Cristofolini, Paolo; Girlando, Salvatore; Dalla Palma, Paolo; Cristofolini, Mario

2009-01-01

The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.

Superior Prognostic Value of Cumulative Intracranial Tumor Volume Relative to Largest Intracranial Tumor Volume for Stereotactic Radiosurgery-Treated Brain Metastasis Patients.

PubMed

Hirshman, Brian R; Wilson, Bayard; Ali, Mir Amaan; Proudfoot, James A; Koiso, Takao; Nagano, Osamu; Carter, Bob S; Serizawa, Toru; Yamamoto, Masaaki; Chen, Clark C

2018-04-01

Two intracranial tumor volume variables have been shown to prognosticate survival of stereotactic-radiosurgery-treated brain metastasis patients: the largest intracranial tumor volume (LITV) and the cumulative intracranial tumor volume (CITV). To determine whether the prognostic value of the Scored Index for Radiosurgery (SIR) model can be improved by replacing one of its components-LITV-with CITV. We compared LITV and CITV in terms of their survival prognostication using a series of multivariable models that included known components of the SIR: age, Karnofsky Performance Score, status of extracranial disease, and the number of brain metastases. Models were compared using established statistical measures, including the net reclassification improvement (NRI > 0) and integrated discrimination improvement (IDI). The analysis was performed in 2 independent cohorts, each consisting of ∼3000 patients. In both cohorts, CITV was shown to be independently predictive of patient survival. Replacement of LITV with CITV in the SIR model improved the model's ability to predict 1-yr survival. In the first cohort, the CITV model showed an NRI > 0 improvement of 0.2574 (95% confidence interval [CI] 0.1890-0.3257) and IDI of 0.0088 (95% CI 0.0057-0.0119) relative to the LITV model. In the second cohort, the CITV model showed a NRI > 0 of 0.2604 (95% CI 0.1796-0.3411) and IDI of 0.0051 (95% CI 0.0029-0.0073) relative to the LITV model. After accounting for covariates within the SIR model, CITV offers superior prognostic value relative to LITV for stereotactic radiosurgery-treated brain metastasis patients.

Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.

PubMed

Tang, Weidong; Ruan, Feng; Chen, Qi; Chen, Suping; Shao, Xuebo; Gao, Jianbo; Zhang, Mao

2016-07-01

Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis. The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors. Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value. High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis. Copyright © 2016 by Daedalus Enterprises.

The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

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

Rutkowski, Tomasz; Suwinski, Rafal; Idasiak, Adam

2007-11-15

Purpose: To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials: The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3-T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (-8.8; 5.0 g/dl).more » Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results: Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion: Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients.« less

Big data and computational biology strategy for personalized prognosis.

PubMed

Ow, Ghim Siong; Tang, Zhiqun; Kuznetsov, Vladimir A

2016-06-28

The era of big data and precision medicine has led to accumulation of massive datasets of gene expression data and clinical information of patients. For a new patient, we propose that identification of a highly similar reference patient from an existing patient database via similarity matching of both clinical and expression data could be useful for predicting the prognostic risk or therapeutic efficacy.Here, we propose a novel methodology to predict disease/treatment outcome via analysis of the similarity between any pair of patients who are each characterized by a certain set of pre-defined biological variables (biomarkers or clinical features) represented initially as a prognostic binary variable vector (PBVV) and subsequently transformed to a prognostic signature vector (PSV). Our analyses revealed that Euclidean distance rather correlation distance measure was effective in defining an unbiased similarity measure calculated between two PSVs.We implemented our methods to high-grade serous ovarian cancer (HGSC) based on a 36-mRNA predictor that was previously shown to stratify patients into 3 distinct prognostic subgroups. We studied and revealed that patient's age, when converted into binary variable, was positively correlated with the overall risk of succumbing to the disease. When applied to an independent testing dataset, the inclusion of age into the molecular predictor provided more robust personalized prognosis of overall survival correlated with the therapeutic response of HGSC and provided benefit for treatment targeting of the tumors in HGSC patients.Finally, our method can be generalized and implemented in many other diseases to accurately predict personalized patients' outcomes.

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

PubMed

Augustin, Jérémy; Mandavit, Marion; Outh-Gauer, Sophie; Grard, Ophélie; Gasne, Cassandre; Lépine, Charles; Mirghani, Haïtham; Hans, Stéphane; Bonfils, Pierre; Denize, Thomas; Bruneval, Patrick; Bishop, Justin A; Fontugne, Jacqueline; Péré, Hélène; Tartour, Eric; Badoual, Cécile

2018-06-20

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

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

PubMed

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

2018-04-01

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

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data

PubMed Central

Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C

2016-01-01

Summary Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest—namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial—ENTHUSE M1—in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39–4·62, p<0·0001; reference model: 2·56, 1·85–3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. Funding Sanofi US Services, Project Data Sphere. PMID:27864015

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data.

PubMed

Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C

2017-01-01

Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39-4·62, p<0·0001; reference model: 2·56, 1·85-3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. Sanofi US Services, Project Data Sphere. Copyright © 2017 Elsevier Ltd. All rights reserved.

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

Intraepithelial Attack Rather than Intratumorally Infiltration of CD8+T Lymphocytes is a Favorable Prognostic Indicator in Pancreatic Ductal Adenocarcinoma.

PubMed

Zhang, J; Wang, Y F; Wu, B; Zhong, Z X; Wang, K X; Yang, L Q; Wang, Y Q; Li, Y Q; Gao, J; Li, Z S

2017-01-01

Tumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear. To evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy. Immunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC. Two major variables for the spatial distributions of CD4+T and CD8+T cells in PDAC tissues, intraepithelial attack and intratumoral infiltration, were used to evaluate the state of immunoreactions, and the interrelationships with the clinicopathological variables were analyzed. Our data showed that both the intraepithelial CD4+T and CD8+T attack were less frequent than the intratumoral infiltration. CD8+T intraepithelial attack and intratumoral infiltration were more intense than CD4+T. CD8+T intraepithelial attack was an independent favorable prognostic factor for overall survival, correlating negatively with vascular invasion and positively with CD4+T and CD8+T high intratumoral infiltration. CD8+T high intratumoral infiltration without CD8+T intraepithelial attack was a poor prognostic factor. CD8+T high intratumoral infiltration was accompanied by T stage progression. Conclusively, in PDAC progression, imbalances of T cells occurred in CD4+ and CD8+ immunoreactions. The CD8+T intraepithelial attack was an independent favorable prognostic indicator, however the intraepithelial attack of CD4+T and the both intratumoral infiltration of CD8+T and CD4+T played an ambiguous role. Our data suggested that it is a potential approach to increasing the number of intraepithelial attacking CD8+T cells for tumor immunotherapy, and exploring a new mechanism for immunosuppression in a tumor microenvironment with high T cell infiltration without attack. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Variable selection under multiple imputation using the bootstrap in a prognostic study

PubMed Central

Heymans, Martijn W; van Buuren, Stef; Knol, Dirk L; van Mechelen, Willem; de Vet, Henrica CW

2007-01-01

Background Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values. PMID:17629912

Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations

PubMed Central

2014-01-01

Introduction Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. Methods An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). Results The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Conclusions Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments. PMID:24996446

Prognostic value of myocardial perfusion SPECT versus exercise electrocardiography in patients with ST-segment depression on resting electrocardiography.

PubMed

De Lorenzo, Andrea; Hachamovitch, Rory; Kang, Xingping; Gransar, Heidi; Sciammarella, Maria G; Hayes, Sean W; Friedman, John D; Cohen, Ishac; Germano, Guido; Berman, Daniel S

2005-01-01

The value of exercise-induced ST-segment depression for the prognostic evaluation of patients with 1 mm of ST depression or greater on the resting electrocardiogram is controversial. Patients who underwent exercise myocardial perfusion single photon emission computed tomography (MPS) and had resting ST depression of 1 mm or greater with a nondiagnostic exercise electrocardiographic response (n = 1122) were followed up for 3.4 +/- 2.3 years. Those with paced rhythm, pre-excitation, left bundle branch block, or myocardial revascularization within the first 60 days after MPS were excluded. Additional exercise-induced ST-segment depression was considered significant if > or = 2 mm MPS was scored semiquantitatively by use of a 20-segment model of the left ventricle; the percentage of myocardium involved with stress defects (% myo) was derived by normalizing to the maximal possible score of 80. Hard events were defined as nonfatal myocardial infarction or cardiac death. A Cox analysis was used to determine independent predictors of hard events among clinical, exercise, and nuclear variables. Hard event rates increased as a function of % myo for either patients with exercise-induced ST depression (1.4%/y for normal MPS vs 4.1%/y for % myo >10%, P < .03) or those without it (0.7%/y for normal MPS vs 3.0%/y for % myo >10%, P = .0001). Age, diabetes mellitus, shortness of breath as the presenting symptom, and % myo were independent predictors of hard events. Exercise-induced ST depression was predictive of hard events only when it was 3 mm or greater. The presence and extent of perfusion defects, reflected in the % myo, had incremental prognostic value over clinical variables and also over all degrees of exercise-induced ST depression. Although MPS effectively risk-stratifies patients with resting ST depression of 1 mm or greater, the prognostic value of exercise-induced ST depression is limited in these patients, with a small added risk when severe (> or = 3 mm).

Prognostic Value of the Amount of Bleeding After Aneurysmal Subarachnoid Hemorrhage: A Quantitative Volumetric Study.

PubMed

Lagares, Alfonso; Jiménez-Roldán, Luis; Gomez, Pedro A; Munarriz, Pablo M; Castaño-León, Ana M; Cepeda, Santiago; Alén, José F

2015-12-01

Quantitative estimation of the hemorrhage volume associated with aneurysm rupture is a new tool of assessing prognosis. To determine the prognostic value of the quantitative estimation of the amount of bleeding after aneurysmal subarachnoid hemorrhage, as well the relative importance of this factor related to other prognostic indicators, and to establish a possible cut-off value of volume of bleeding related to poor outcome. A prospective cohort of 206 patients consecutively admitted with the diagnosis of aneurysmal subarachnoid hemorrhage to Hospital 12 de Octubre were included in the study. Subarachnoid, intraventricular, intracerebral, and total bleeding volumes were calculated using analytic software. For assessing factors related to prognosis, univariate and multivariate analysis (logistic regression) were performed. The relative importance of factors in determining prognosis was established by calculating their proportion of explained variation. Maximum Youden index was calculated to determine the optimal cut point for subarachnoid and total bleeding volume. Variables independently related to prognosis were clinical grade at admission, age, and the different bleeding volumes. The proportion of variance explained is higher for subarachnoid bleeding. The optimal cut point related to poor prognosis is a volume of 20 mL both for subarachnoid and total bleeding. Volumetric measurement of subarachnoid or total bleeding volume are both independent prognostic factors in patients with aneurysmal subarachnoid hemorrhage. A volume of more than 20 mL of blood in the initial noncontrast computed tomography is related to a clear increase in poor outcome risk. : aSAH, aneurysmal subarachnoid hemorrhage.

Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

PubMed Central

Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI. PMID:23724031

Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients.

PubMed

Kim, Yun Hak; Jeong, Dae Cheon; Pak, Kyoungjune; Goh, Tae Sik; Lee, Chi-Seung; Han, Myoung-Eun; Kim, Ji-Young; Liangwen, Liu; Kim, Chi Dae; Jang, Jeon Yeob; Cha, Wonjae; Oh, Sae-Ock

2017-09-29

Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients.

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

PubMed

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

2015-07-10

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

Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system.

PubMed

Boxberg, Melanie; Jesinghaus, Moritz; Dorfner, Christiane; Mogler, Carolin; Drecoll, Enken; Warth, Arne; Steiger, Katja; Bollwein, Christine; Meyer, Petra; Wolff, Klaus D; Kolk, Andreas; Weichert, Wilko

2017-06-01

Oral squamous cell carcinoma (OSCC) is a common malignancy with a variable clinical course. One of the established survival predictors in carcinomas in general is tumour grade; in OSCC, however, grading according to the World Health Organization (WHO) has no independent prognostic impact. Recently, a novel grading scheme associated with high impact on patient outcome has been proposed for squamous cell carcinoma of the lung. To probe whether this scheme could be applied to the upper aerodigestive tract, we retrospectively evaluated 157 chemo- and radiotherapy-naive OSCCs with complete clinical follow-up data and standardized treatment for tumour budding activity (BA), cell nest size (CNS), extent of keratinization, stromal content, nuclear size and mitotic count. Histomorphological characteristics were correlated with clinicopathological data and patient outcome. As in squamous cell carcinoma of the lung, high BA and small CNS were correlated significantly with shortened overall, disease-specific and disease-free survival. A three-tiered grading system based on a sum score of these two prognostic markers proved to be a strong age-, stage- and sex-independent prognosticator for survival with a hazard ratio for overall survival of 2.1 for intermediately differentiated (G2) tumours and 3.4 for poorly differentiated (G3) tumours compared to well-differentiated (G1) tumours (P < 0.001). We recapitulated and validated almost exactly the strong prognostic impact of a grading algorithm proposed recently for squamous cell carcinoma of the lung in OSCC. Our data may pave the way for a prognostically highly relevant future squamous cell carcinoma grading system broadly applicable in the aerodigestive tract. © 2017 John Wiley & Sons Ltd.

Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients

PubMed Central

Kim, Yun Hak; Jeong, Dae Cheon; Pak, Kyoungjune; Goh, Tae Sik; Lee, Chi-Seung; Han, Myoung-Eun; Kim, Ji-Young; Liangwen, Liu; Kim, Chi Dae; Jang, Jeon Yeob; Cha, Wonjae; Oh, Sae-Ock

2017-01-01

Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients. PMID:29100405

Clinical performance validation of PITX2 DNA methylation as prognostic biomarker in patients with head and neck squamous cell carcinoma.

PubMed

Sailer, Verena; Gevensleben, Heidrun; Dietrich, Joern; Goltz, Diane; Kristiansen, Glen; Bootz, Friedrich; Dietrich, Dimo

2017-01-01

Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc.). A total of 528 HNSCC patients from The Cancer Genome Atlas (TCGA) were included in the study. Death was defined as primary endpoint. PITX2 methylation was correlated with overall survival and clinicopathological parameters. PITX2 methylation was significantly associated with sex, tumor site, p16 status, and grade. In univariate Cox proportional hazards analysis, PITX2 hypermethylation analyzed as continuous and dichotomized variable was significantly associated with prolonged overall survival of HNSCC patients (continuous: hazard ratio (HR) = 0.19 [95%CI: 0.04-0.88], p = 0.034; dichotomized: HR = 0.52 [95%CI: 0.33-0.84], p = 0.007). In multivariate Cox analysis including established clinicopathological parameters, PITX2 promoter methylation was confirmed as prognostic factor (HR = 0.28 [95%CI: 0.09-0.84], p = 0.023). Using an independent analytical platform, PITX2 methylation was validated as a prognostic biomarker in HNSCC patients, identifying patients that potentially benefit from intensified surveillance and/or administration of adjuvant/neodjuvant treatment, i.e. immunotherapy.

High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor Extension.

PubMed

Sakurai, Manabu; Satoh, Toyomi; Matsumoto, Koji; Michikami, Hiroo; Nakamura, Yuko; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki

2015-05-01

Elevated plasma D-dimer (DD) is associated with decreased survival among patients with breast, lung, and colon cancers. The present study clarifies the prognostic significance of pretreatment plasma DD levels in patients with epithelial ovarian cancer (EOC). We investigated pretreatment DD levels and other variables for overall survival using univariate and multivariate analyses in 134 consecutive patients with EOC stages II to IV who were initially treated between November 2004 and December 2010. The median follow-up period was 53 (7-106) months. Univariate analysis significantly associated elevated pretreatment DD (≥2.0 μg/mL) levels to poor 5-year overall survival rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%, P = 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P = 0.011), distant metastases (P = 0.0004), residual tumors (P < 0.0001), and International Federation of Gynecology and Obstetrics stage III/IV (P = 0.0033) were also poor prognostic factors. Multivariate analysis independently associated DD levels of 2.0 μg/mL or higher (P = 0.041), distant metastases (P = 0.013), and residual tumors (P < 0.0001) with poor overall survival. High pretreatment DD levels are associated with poor overall survival in patients with EOC independently of venous thromboembolism and tumor extension and might comprise a promising prognostic biomarker for patients with EOC.

Risk and prognostic factors of ventilator-associated pneumonia in trauma patients.

PubMed

Cavalcanti, Manuela; Ferrer, Miquel; Ferrer, Ricard; Morforte, Ramon; Garnacho, Angel; Torres, Antoni

2006-04-01

To assess the risk and prognostic factors of ventilator-associated pneumonia in trauma patients, with an emphasis on the inflammatory response. Case-control study. Trauma intensive care unit. Of 190 consecutive mechanically ventilated patients, those with microbiologically confirmed pneumonia (n = 62) were matched with 62 controls without pneumonia. None. Clinical, microbiological, and outcome variables were recorded. Cytokines were measured in serum and blind bronchoalveolar lavage specimens at onset of pneumonia. Multivariate analyses of risk and prognostic factors for ventilator-associated pneumonia were done. Increased severity of head and neck injury (odds ratio, 11.9; p < .001) was the only independent predictor of pneumonia. Among patients with pneumonia, serum levels of interleukin-6 (p = .019) and interleukin-8 (p = .036) at onset of pneumonia were higher in nonresponders to treatment. Moreover, serum levels of tumor necrosis factor-alpha (p = .028) and interleukin-6 (p = .007) at onset of pneumonia were higher in nonsurvivors. Mortality in the intensive care unit was 23% in cases and controls. Nonresponse to antimicrobial treatment (odds ratio, 22.2; p = .001) and the use of hyperventilation (p = .021) were independent predictors of mortality in the intensive care unit for patients with pneumonia. Severe head and neck trauma is strongly associated with ventilator-associated pneumonia. A higher inflammatory response is associated with nonresponse to treatment and mortality among patients with pneumonia. Although pneumonia did not influence mortality, nonresponse to treatment independently predicted mortality among these patients.

Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure.

PubMed

Bajraktari, Gani; Dini, Frank Lloyd; Fontanive, Paolo; Elezi, Shpend; Berisha, Venera; Napoli, Anna Maria; Ciuti, Manrico; Henein, Michael

2011-05-05

A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF). To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF. Patients (n=107; age 68±12 years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF)<45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model. Follow-up period was 37±18 months. Multivariate predictors of events were T-IVT≥12.3% s/min, mean E/Em ratio≥10, log NT-pro-BNP levels≥2.47 pg/ml and LV EF≤32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/Em ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001). Prolonged T-IVT added to the prognostic stratification of patients with systolic HF. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Marine Aerosol Precursor Emissions for Earth System Models

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

Maltrud, Mathew Einar

2016-07-25

Dimethyl sulfide (DMS) is generated by marine ecosystems and plays a major role in cloud formation over the ocean. Currently, Earth System Models use imposed flux of DMS from the ocean to the atmosphere that is independent of the climate state. We have added DMS as a prognostic variable to the Community Earth System Model (CESM) that depends on the distribution of phytoplankton species, and thus changes with climate.

Prognostic Factors in Severe Chagasic Heart Failure

PubMed Central

Costa, Sandra de Araújo; Rassi, Salvador; Freitas, Elis Marra da Madeira; Gutierrez, Natália da Silva; Boaventura, Fabiana Miranda; Sampaio, Larissa Pereira da Costa; Silva, João Bastista Masson

2017-01-01

Background Prognostic factors are extensively studied in heart failure; however, their role in severe Chagasic heart failure have not been established. Objectives To identify the association of clinical and laboratory factors with the prognosis of severe Chagasic heart failure, as well as the association of these factors with mortality and survival in a 7.5-year follow-up. Methods 60 patients with severe Chagasic heart failure were evaluated regarding the following variables: age, blood pressure, ejection fraction, serum sodium, creatinine, 6-minute walk test, non-sustained ventricular tachycardia, QRS width, indexed left atrial volume, and functional class. Results 53 (88.3%) patients died during follow-up, and 7 (11.7%) remained alive. Cumulative overall survival probability was approximately 11%. Non-sustained ventricular tachycardia (HR = 2.11; 95% CI: 1.04 - 4.31; p<0.05) and indexed left atrial volume ≥ 72 mL/m2 (HR = 3.51; 95% CI: 1.63 - 7.52; p<0.05) were the only variables that remained as independent predictors of mortality. Conclusions The presence of non-sustained ventricular tachycardia on Holter and indexed left atrial volume > 72 mL/m2 are independent predictors of mortality in severe Chagasic heart failure, with cumulative survival probability of only 11% in 7.5 years. PMID:28443956

Prognostic factors and scoring system for survival in colonic perforation.

PubMed

Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

2005-01-01

No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing.

PubMed

Khatri, Vinod; Neal, Jennifer E; Burger, Charles D; Lee, Augustine S

2015-02-06

The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Although multiple SET variables correlated with the RRRS on univariate analyses, only V E /V CO2 (r = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the V E /V CO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). SETs, particularly the V E /V CO2 , appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Prognostic significance of DNA ploidy in adenocarcinoma of the pancreas. A flow cytometric study of paraffin-embedded specimens.

PubMed

Porschen, R; Remy, U; Bevers, G; Schauseil, S; Hengels, K J; Borchard, F

1993-06-15

The prognostic significance of tumor DNA ploidy in patients with cancer of the pancreas has not been defined because conflicting results have been reported. DNA content was measured in 56 ductal adenocarcinomas of the pancreas. DNA ploidy status was evaluated by flow cytometry in nuclei isolated from paraffin-embedded tumor tissues. An abnormal DNA stemline was observed in 27 (48%) patients. The percentage of aneuploid tumors was significantly increased in tumors classified as Stage III/IV (53%) compared with those classified as Stage I (22%). A borderline significant association existed between DNA ploidy and radicality of surgery (P = 0.08). The median survival of patients with diploid carcinomas was 6.9 months (standard error, +/- 0.9) in comparison to 4.5 +/- 1.2 months for patients with aneuploid tumors (P = 0.013 by generalized Wilcoxon test; P = 0.023 by generalized Savage test). Although a selection bias cannot be excluded, survival of patients with a radical resection was longer than that of patients with a nonradical resection (P = 0.0008 and P = 0.0085, respectively). In addition, presence of distant metastasis (P = 0.0006 [Wilcoxon test] and P = 0.033 [Savage test]) could be identified as a prognostic factor. In a Cox regression model, results of surgery and DNA ploidy were independent prognostic variables. Because DNA ploidy has a significant impact on prognosis in pancreatic cancer, it should be used as a variable for stratified randomization of patients in therapeutic trials.

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

PubMed

Mikkola, Arto; Aro, Jussi; Rannikko, Sakari; Ruutu, Mirja

2009-01-01

To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

PubMed Central

Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

2015-01-01

Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white blood cell count were independent prognostic factors. PMID:26190424

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Preferences for Life-Sustaining Treatments and Associations With Accurate Prognostic Awareness and Depressive Symptoms in Terminally Ill Cancer Patients' Last Year of Life.

PubMed

Tang, Siew Tzuh; Wen, Fur-Hsing; Hsieh, Chia-Hsun; Chou, Wen-Chi; Chang, Wen-Cheng; Chen, Jen-Shi; Chiang, Ming-Chu

2016-01-01

The stability of life-sustaining treatment (LST) preferences at end of life (EOL) has been established. However, few studies have assessed preferences more than two times. Furthermore, associations of LST preferences with modifiable variables of accurate prognostic awareness, physician-patient EOL care discussions, and depressive symptoms have been investigated in cross-sectional studies only. To explore longitudinal changes in LST preferences and their associations with accurate prognostic awareness, physician-patient EOL care discussions, and depressive symptoms in terminally ill cancer patients' last year. LST preferences (cardiopulmonary resuscitation, intensive care unit [ICU] care, intubation, and mechanical ventilation) were measured approximately every two weeks. Changes in LST preferences and their associations with independent variables were examined by hierarchical generalized linear modeling with logistic regression. Participants (n = 249) predominantly rejected cardiopulmonary resuscitation, ICU care, intubation, and mechanical ventilation at EOL without significant changes as death approached. Patients with inaccurate prognostic awareness were significantly more likely than those with accurate understanding to prefer ICU care, intubation, and mechanical ventilation than to reject these LSTs. Patients with more severe depressive symptoms were less likely to prefer ICU care and to be undecided about wanting ICU care and mechanical ventilation than to reject such LSTs. LST preferences were not associated with physician-patient EOL care discussions, which were rare in our sample. LST preferences are stable in cancer patients' last year. Facilitating accurate prognostic awareness and providing adequate psychological support may counteract the increasing trend for aggressive EOL care and minimize emotional distress during EOL care decisions. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Differing prognostic value of pulse pressure in patients with heart failure with reduced or preserved ejection fraction: results from the MAGGIC individual patient meta-analysis.

PubMed

Jackson, Colette E; Castagno, Davide; Maggioni, Aldo P; Køber, Lars; Squire, Iain B; Swedberg, Karl; Andersson, Bert; Richards, A Mark; Bayes-Genis, Antoni; Tribouilloy, Christophe; Dobson, Joanna; Ariti, Cono A; Poppe, Katrina K; Earle, Nikki; Whalley, Gillian; Pocock, Stuart J; Doughty, Robert N; McMurray, John J V

2015-05-07

Low pulse pressure is a marker of adverse outcome in patients with heart failure (HF) and reduced ejection fraction (HF-REF) but the prognostic value of pulse pressure in patients with HF and preserved ejection fraction (HF-PEF) is unknown. We examined the prognostic value of pulse pressure in patients with HF-PEF [ejection fraction (EF) ≥ 50%] and HF-REF. Data from 22 HF studies were examined. Preserved left ventricular ejection fraction (LVEF) was defined as LVEF ≥ 50%. All-cause mortality at 3 years was evaluated in 27 046 patients: 22 038 with HF-REF (4980 deaths) and 5008 with HF-PEF (828 deaths). Pulse pressure was analysed in quintiles in a multivariable model adjusted for the previously reported Meta-Analysis Global Group in Chronic Heart Failure prognostic variables. Heart failure and reduced ejection fraction patients in the lowest pulse pressure quintile had the highest crude and adjusted mortality risk (adjusted hazard ratio 1.68, 95% confidence interval 1.53-1.84) compared with all other pulse pressure groups. For patients with HF-PEF, higher pulse pressure was associated with the highest crude mortality, a gradient that was eliminated after adjustment for other prognostic variables. Lower pulse pressure (especially <53 mmHg) was an independent predictor of mortality in patients with HF-REF, particularly in those with an LVEF < 30% and systolic blood pressure <140 mmHg. Overall, this relationship between pulse pressure and outcome was not consistently observed among patients with HF-PEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

PubMed

Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

2018-02-01

Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (p<0.001). Necrosis and invasive front inflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients With Melanoma Treated With Pembrolizumab.

PubMed

Joseph, Richard W; Elassaiss-Schaap, Jeroen; Kefford, Richard F; Hwu, Wen-Jen; Wolchok, Jedd D; Joshua, Anthony Michael; Ribas, Antoni; Hodi, F Stephen; Hamid, Omid; Robert, Caroline; Daud, Adil I; Dronca, Roxana S; Hersey, Peter; Weber, Jeffrey S; Patnaik, Amita; de Alwis, Dinesh P; Perrone, Andrea M; Zhang, Jin; Kang, Soonmo Peter; Ebbinghaus, Scot W; Anderson, Keaven M; Gangadhar, Tara

2018-04-23

To assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites) (all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs 23%; P < 0.001) and improved OS (hazard ratio, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma. Copyright ©2018, American Association for Cancer Research.

Combined evaluation of the Glasgow prognostic score and carcinoembryonic antigen concentration prior to hepatectomy predicts postoperative outcomes in patients with liver metastasis from colorectal cancer.

PubMed

Kobayashi, Takashi; Kawakamil, Masayo; Hara, Yoshiaki; Shioiri, Sadaaki; Yasuno, Masamichi; Teruya, Masanori; Kaminishi, Michio

2014-01-01

Little is known about the ability of the inflammation-based Glasgow prognostic score (GPS). 106 patients who underwent curative resection for colorectal liver metastasis (CRLM) were analyzed. Patients with an elevated Creactive protein concentration (>10 mg/L) and hypoalbuminemia (<35 g/L) at admission were assigned a GPS 2, those with only 1 of these biochemical abnormalities were assigned a GPS 1, and those without either abnormality were assigned a GPS 0. Multivariate analysis showed that 2 variables, carcinoembryonic antigen (CEA) concentration > 30 ng/mL and a GPS 1 or 2, were independently prognostic of survival. Patients were classified into 3 groups on the basis of these 2 variables. Patients with GPS 1 or 2 and CEA concentration > 30 ng/mL were assigned a new score of 2, those with either 1 factor were assigned a new score of 1, and those with neither factors were assigned a new score of 0. The 5-year overall survival rates of new scores of 0, 1, 2 were 71.5%, 31.6%, and 0%, respectively (P < 0.0001). This simple staging system may be able to identify a subgroup of patients who are eligible for curative resection but show poor prognosis.

Development and validation of a prognostic nomogram for terminally ill cancer patients.

PubMed

Feliu, Jaime; Jiménez-Gordo, Ana María; Madero, Rosario; Rodríguez-Aizcorbe, José Ramón; Espinosa, Enrique; Castro, Javier; Acedo, Jesús Domingo; Martínez, Beatriz; Alonso-Babarro, Alberto; Molina, Raquel; Cámara, Juan Carlos; García-Paredes, María Luisa; González-Barón, Manuel

2011-11-02

Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease. From February 1, 2003, to December 31, 2005, 406 consecutive terminally ill patients were entered into the study. We analyzed 38 features prognostic of life expectancy among terminally ill patients by multivariable Cox regression and identified the most accurate and parsimonious model by backward variable elimination according to the Akaike information criterion. Five clinical and laboratory variables were built into a nomogram to estimate the probability of patient survival at 15, 30, and 60 days. We validated and calibrated the nomogram with an external validation cohort of 474 patients who were treated from June 1, 2006, through December 31, 2007. The median overall survival was 29.1 days for the training set and 18.3 days for the validation set. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, lymphocyte levels, albumin levels, and time from initial diagnosis to diagnosis of terminal disease were retained in the multivariable Cox proportional hazards model as independent prognostic factors of survival and formed the basis of the nomogram. The nomogram had high predictive performance, with a bootstrapped corrected concordance index of 0.70, and it showed good calibration. External independent validation revealed 68% predictive accuracy. We developed a highly accurate tool that uses basic clinical and analytical information to predict the probability of survival at 15, 30, and 60 days in terminally ill cancer patients. This tool can help physicians making decisions on clinical care at the end of life.

Marital status is a prognostic factor in amyotrophic lateral sclerosis.

PubMed

Spataro, R; Volanti, P; Lo Coco, D; La Bella, V

2017-12-01

Several variables have been linked to a shorter survival in patients with amyotrophic lateral sclerosis (ALS), for example, female sex, older age, site of disease onset, rapid disease progression, and a relatively short diagnostic delay. With regard to marital status, previous studies suggested that living with a partner might be associated to a longer survival and a higher likelihood to proceed to tracheostomy. Therefore, to further strengthen this hypothesis, we investigated the role of marital status as a prognostic variable in a cohort of ALS patients. We performed a retrospective analysis on 501 consecutive ALS patients for which a complete disease's natural history and clinical/demographic data were available. At diagnosis, 409 patients (81.6%) were married or lived with a stable partner, whereas 92 patients (18.4%) were single/widowed/divorced. In our ALS cohort, being married was associated with a median longer survival (married, 35 months [24-50] vs unmarried, 27 months [18-42]; P<.004). Moreover, married and unmarried patients were significantly different in many clinical and demographic variables, including age at disease onset, gender, body mass index, and number of children. Cox regression analysis showed that age at onset, diagnostic delay, and marital status were independent predictors of survival. In unmarried patients, female sex was also significantly associated with shorter survival. Marital status is a prognostic factor in ALS, and it significantly affects survival. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interpretative variability and its impact on the prognostic value of myocardial fatty acid imaging in asymptomatic hemodialysis patients in a multicenter trial in Japan.

PubMed

Kiriyama, Tomonari; Kumita, Shin-Ichiro; Moroi, Masao; Nishimura, Tsunehiko; Tamaki, Nagara; Hasebe, Naoyuki; Kikuchi, Kenjiro

2015-01-01

The severity of impaired fatty acid utilization in the myocardium can predict cardiac death in asymptomatic patients on hemodialysis. However, interpretive variability and its impact on the prognostic value of myocardial fatty acid imaging are unknown. A total of 677 patients who received hemodialysis for ≥ 20 years and had one or more cardiovascular risk factors underwent (123)I-labeled β-methyl iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) at 48 hospitals across Japan. SPECT images were interpreted by experts at the nuclear core laboratory and by readers with varying skill levels at clinical centers, based on the standard 17-segment model and 5-point scoring systems, independently. The κ values only reached fair agreement both for overall impression (κ=0.298, normal vs. abnormal) and for categorical impression (κ=0.244, normal vs. mildly abnormal vs. severely abnormal). The normalcy rate was lower in readers at the clinical centers (60.9%) than in experts (69.9%). In contrast to the results assessed by experts, a Kaplan-Meier analysis based on the interpretation by readers at the clinical centers failed to distinguish the risk of events in patients with normal scans from that of patients with mildly abnormal scans. Considerable variability and its impact on prognostic value were observed in the visual interpretation of BMIPP SPECT images between experts and readers at the clinical centers.

The biological and prognostic significance of angiotropism in uveal melanoma.

PubMed

Barnhill, Raymond L; Ye, Mengliang; Batistella, Aude; Stern, Marc-Henri; Roman-Roman, Sergio; Dendale, Rémi; Lantz, Olivier; Piperno-Neumann, Sophie; Desjardins, Laurence; Cassoux, Nathalie; Lugassy, Claire

2017-02-27

Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of an alternative metastatic pathway.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.16.

Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction: results of the biomarker substudy of the Surgical Treatment for Ischemic Heart Failure trials.

PubMed

Feldman, Arthur M; Mann, Douglas L; She, Lilin; Bristow, Michael R; Maisel, Alan S; McNamara, Dennis M; Walsh, Ryan; Lee, Dorellyn L; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H; Schmedtje, John F; Pauly, Daniel F; Sueta, Carla A; Di Maio, Michael; Kron, Irving L; Velazquez, Eric J; Lee, Kerry L

2013-05-01

Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ(2)=40.6; P<0.0001 and sTNFR-1: χ(2)=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; P=0.049) and sTNFR-1 (χ(2)=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

The Prognostic Significance of Biomarkers in Predicting Outcome in Patients With Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Biomarker Sub-Study of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

PubMed Central

Feldman, Arthur M.; Mann, Douglas L.; She, Lilin; Bristow, Michael R.; Maisel, Alan S.; McNamara, Dennis M.; Walsh, Ryan; Lee, Dorellyn L.; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H.; Schmedtje, John F.; Pauly, Daniel F.; Sueta, Carla A.; Di Maio, Michael; Kron, Irving L.; Velazquez, Eric J.; Lee, Kerry L.

2013-01-01

Background Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting (CABG) but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the Biomarker Sub-studies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or CABG whereas those in STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Methods and Results In sub-study patients assigned to STICH Hypothesis 1 (n=606), plasma levels of sTNFR-1 and BNP were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP χ2=40.6; p<0.0001: sTNFR-1 χ2=38,9; p<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ2=30.3) and sTNFR-1 (χ2=45.5) were highly predictive in univariate analysis (p<0.0001) as well as in multivariable analysis for the primary endpoint of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ2=6.0; p=0.049) and sTNFR-1 (χ2=8.8; p=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤ 0.1), Net Reclassification Improvement (NRI) for the primary endpoints was 0.29 for BNP and 0.21 for sTNFR-1in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in two large and independent studies, thus providing important cross-validation for the prognostic importance of these two biomarkers. PMID:23584092

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

PubMed

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

2016-01-01

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

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

PubMed

Xu, C-h; Wang, W; Wei, Y; Hu, H-d; Zou, J; Yan, J; Yu, L-k; Yang, R-s; Wang, Y

2015-10-01

Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy. Copyright © 2015. Published by Elsevier Ltd.

EphA4 is a prognostic factor in gastric cancer

PubMed Central

2013-01-01

Background Erythropoietin-producing hepatocellular (Eph) receptor, consisting of a family of receptor tyrosine kinases, plays critical roles in tumour development and is considered an attractive target for cancer therapy. Methods Tumour samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy. The expressions of EphA2, EphA4, and ephrinA1 were evaluated immunohistochemically. Results High expressions of EphA2, EphA4, and ephrinA1 significantly correlated with variables related to tumour progression, including the depth of invasion, metastatic lymph nodes, pathological stage, and distant metastasis or recurrent disease. High expressions of EphA2, EphA4, and ephrinA1 were significantly associated with poorer disease-specific survival (DSS; p < 0.001, p < 0.001, p = 0.026). On multivariate analysis, EphA4 was an independent prognostic factor of DSS (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.1-4.8; p = 0.028), and EphA2 tended to be a prognostic factor (HR, 2.4; 95% CI, 1.0-5.8; p = 0.050). In stage II and III cancer, EphA4 and EphA2 were both significantly associated with shorter survival (p = 0.007 and 0.019), but only EphA2 was an independent prognostic factor (HR, 2.6; 95% CI, 1.1-6.3; p = 0.039). Conclusion EphA4 may play important roles in tumor progression and outcomes in patients with gastric cancer. PMID:23738943

Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study.

PubMed

Melcarne, Luigi; Sopeña, Julia; Martínez-Cerezo, Francisco José; Vergara, Mercedes; Miquel, Mireia; Sánchez-Delgado, Jordi; Dalmau, Blai; Machlab, Salvador; Portilla, Dustin; González-Padrón, Yonaisy; Real Álvarez, Mónica; Carpintero, Chantal; Casas, Meritxell

2018-02-01

Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival.

Prognostic factors and recurrence of hepatitis B-related hepatocellular carcinoma after argon-helium cryoablation: a prospective study.

PubMed

Wang, Chunping; Lu, Yinying; Chen, Yan; Feng, Yongyi; An, Linjing; Wang, Xinzhen; Su, Shuhui; Bai, Wenlin; Zhou, Lin; Yang, Yongping; Xu, Dongping

2009-01-01

To determine the long-term prognosis of hepatocellular carcinoma (HCC) after argon-helium cryoablation and identify the risk factors that predict metastasis and recurrence. A total of 156 patients with hepatitis B-related HCC less than 5 cm in diameter who underwent curative cryoablation were followed up prospectively for tumor metastasis and recurrence. Immunohistochemistry was used to analyze the expression of vascular endothelial growth factor (VEGF). HBV basal core promoter (BCP) and precore mutations were detected by DNA sequence analysis. Post-treatment prognostic factors influencing survival, tumor metastasis and recurrence were assessed by univariate and multivariate analyses. The variables included the expression of VEGF in HCC tissues, clinical and pathologic characteristics of patients, and HBV features (HBV DNA level, HBV genotype, BCP mutation). The median follow-up period of the 156 patients was 37 months (range 8-48 months). The 1-, 2-, and 3-year overall survival rates were 92, 82 and 64%, respectively. The 1-, 2-, and 3-year recurrence-free survival rates were 72, 56 and 43%, respectively. Eighty-five patients (54.5%) had tumor recurrence or metastasis. The multivariate analysis showed that Child-Pugh class and the expression of VEGF in HCC tissues could be used as independent prognostic factors for overall survival. Meanwhile, the expression of VEGF in HCC tissues and HBV BCP mutations were found to be independent prognostic factors for recurrence-free survival. Strong expression of VEGF in HCC tissues and HBV BCP mutations are important risk predictors for recurrence or metastasis of HCC smaller than 5 cm in diameter.

Statistical considerations on prognostic models for glioma

PubMed Central

Molinaro, Annette M.; Wrensch, Margaret R.; Jenkins, Robert B.; Eckel-Passow, Jeanette E.

2016-01-01

Given the lack of beneficial treatments in glioma, there is a need for prognostic models for therapeutic decision making and life planning. Recently several studies defining subtypes of glioma have been published. Here, we review the statistical considerations of how to build and validate prognostic models, explain the models presented in the current glioma literature, and discuss advantages and disadvantages of each model. The 3 statistical considerations to establishing clinically useful prognostic models are: study design, model building, and validation. Careful study design helps to ensure that the model is unbiased and generalizable to the population of interest. During model building, a discovery cohort of patients can be used to choose variables, construct models, and estimate prediction performance via internal validation. Via external validation, an independent dataset can assess how well the model performs. It is imperative that published models properly detail the study design and methods for both model building and validation. This provides readers the information necessary to assess the bias in a study, compare other published models, and determine the model's clinical usefulness. As editors, reviewers, and readers of the relevant literature, we should be cognizant of the needed statistical considerations and insist on their use. PMID:26657835

The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions.

PubMed

Lee, Eun-Ju; Podoltsev, Nikolai; Gore, Steven D; Zeidan, Amer M

2016-01-01

The clinical course of patients with myelodysplastic syndromes (MDS) is characterized by wide variability reflecting the underlying genetic and biological heterogeneity of the disease. Accurate prediction of outcomes for individual patients is an integral part of the evidence-based risk/benefit calculations that are necessary for tailoring the aggressiveness of therapeutic interventions. While several prognostication tools have been developed and validated for risk stratification, each of these systems has limitations. The recent progress in genomic sequencing techniques has led to discoveries of recurrent molecular mutations in MDS patients with independent impact on relevant clinical outcomes. Reliable assays of these mutations have already entered the clinic and efforts are currently ongoing to formally incorporate mutational analysis into the existing clinicopathologic risk stratification tools. Additionally, mutational analysis holds promise for going beyond prognostication to therapeutic selection and individualized treatment-specific prediction of outcomes; abilities that would revolutionize MDS patient care. Despite these exciting developments, the best way of incorporating molecular testing for use in prognostication and prediction of outcomes in clinical practice remains undefined and further research is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Distributed Approach to System-Level Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

2012-01-01

Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

Prognostication in Philadelphia Chromosome Negative Myeloproliferative Neoplasms: a Review of the Recent Literature.

PubMed

Zhou, Amy; Afzal, Amber; Oh, Stephen T

2017-10-01

The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have identified several clinical factors and non-driver mutations to have prognostic impact on Ph-negative MPNs independent of conventional risk stratification and prognostic models. In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors. In essential thrombocythemia (ET), JAK2 V617F mutation, splenomegaly, and mutations in SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2 were found to be additional negative prognostic factors. Bone marrow fibrosis and mutations in ASXL1, SRSF2, EZH2, and IDH1/2 have been found to be additional prognostic factors in primary myelofibrosis (PMF). CALR mutations appear to be a favorable prognostic factor in PMF, which has not been clearly demonstrated in ET. The prognosis for patients with PV, ET, and PMF is dependent upon the presence or absence of several clinical, biological, and molecular risk factors. The significance of additional risk factors identified in these recent studies will need further validation in prospective studies to determine how they may be best utilized in the management of these disorders.

Soluble ST2 protein in the short-term prognosis after hospitalisation in chronic systolic heart failure.

PubMed

Wojtczak-Soska, Karolina; Sakowicz, Agata; Pietrucha, Tadeusz; Lelonek, Małgorzata

2014-01-01

The prognosis in patients with chronic heart failure (CHF) is poor. ST2 protein is a promising prognostic biomarker for CHF. ST2 belongs to the cardioprotective signalling pathway involving interleukin-33 and its concentration in the serum depends on the biomechanical stress of cardiomyocytes (biomechanical strain). To determine the prognostic value of ST2 in short term follow-up after hospitalisation among patients with CHF. The study included 167 patients (mean age 62 years, 83% men) in stable NYHA class I-III with left ventricular ejection fraction (LVEF) of ≤ 45% (average 29.65%, ranges 13-45%). We analysed 58 variables including: demographics, co-morbidities, resting ECG, echocardiographic and coronary arteriography data, basic laboratory tests including N-terminal prohormone B-type natriuretic peptide (NT-proBNP), serum concentration of soluble form of ST2 (sST2) using quantitative ELISA test ST2 Kit (Medical and Biological Laboratories; Japan) and adverse cardiovascular events during a one year observation. In the study, the primary endpoint (death) and the composite endpoint (hospitalisation for HF worsening, worsening in NYHA functional class, the need to increase the dose of diuretics, and/or death in a one year observation) were determined. Patients who died (n = 24; 14.55%) were in more advanced NYHA class, had prolonged QRS duration, higher levels of sST2, NT-proBNP, and lower estimated glomerular filtration rate. From multivariate analysis, the independent variable for the primary endpoint was NT-proBNP (OR = 1.00012; 95% CI 1.00002-1.00022; p = 0.018). 93 (56%) patients reached the composite endpoint. Multivariate analysis revealed that fasting glucose (OR = 1.343; 95% CI 1.041-1.732; p = 0.023) and sST2 (OR = 3.593; 95% CI 1.427-9.05; p = 0.007) independently enhanced the risk of composite endpoint occurrence in a one year observation. In patients with CHF with LVEF ≤ 45%, the prognostic value of sST2 protein in a short-term observation of one year was confirmed. sST2 protein was an independent variable for the composite endpoint, which consisted of worsening NYHA functional class, hospitalisation for worsening of HF, the need to increase the dose of diuretics, and/or death.

Development of Predictive Algorithms for Pre-Treatment Motor Deficit and 90-Day Mortality in Spinal Epidural Abscess.

PubMed

Shah, Akash A; Ogink, Paul T; Harris, Mitchel B; Schwab, Joseph H

2018-06-20

Spinal epidural abscess is a high-risk condition that can lead to paralysis or death. It would be of clinical and prognostic utility to identify which subset of patients with spinal epidural abscess is likely to develop a motor deficit or die within 90 days of discharge. We identified all patients ≥18 years of age who were admitted to our hospital system with a diagnosis of spinal epidural abscess during the period of 1993 to 2016. Explanatory variables were collected retrospectively. Bivariate and multivariable logistic regression was performed using these variables to identify independent predictors of motor deficit and 90-day mortality. Nomograms were then constructed to quantify the risk of these outcomes. Of the 1,053 patients we identified with spinal epidural abscess, 362 presented with motor weakness. One hundred and thirty-four patients died within 90 days of discharge, inclusive of those who died during hospitalization. Multivariable logistic regression yielded 8 independent predictors of pre-treatment motor deficit and 8 independent predictors of 90-day mortality. We constructed nomograms that generated a probability of pre-treatment motor deficit or 90-day mortality on the basis of the presence of these factors. By quantifying the risk of pre-treatment motor deficit and 90-day mortality, our nomograms may provide useful prognostic information for the treatment team. Timely treatment of neurologically intact patients with a high risk of developing a motor deficit is necessary to avoid residual motor weakness and improve survival. Therapeutic Level IV. See Instructions for Authors for a complete description of Levels of Evidence.

Survival and prognostic factors for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience.

PubMed

Abdelaziz, Ashraf Omar; Elbaz, Tamer Mahmoud; Shousha, Hend Ibrahim; Ibrahim, Mostafa Mohamed; Rahman El-Shazli, Mostafa Abdel; Abdelmaksoud, Ahmed Hosni; Aziz, Omar Abdel; Zaki, Hisham Atef; Elattar, Inas Anwar; Nabeel, Mohamed Mahmoud

2014-01-01

Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was 56.5 ± 7.7 years. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

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

PubMed

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

2018-03-01

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

FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

PubMed

Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-22

Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure.

PubMed

Tsutamoto, Takayoshi; Nishiyama, Keizo; Sakai, Hiroshi; Tanaka, Toshinari; Fujii, Masanori; Yamamoto, Takashi; Yamaji, Masayuki; Horie, Minoru

2008-12-01

No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF). To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF. We measured haemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF. During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273+/-276 vs. 472+/-433 pg/mL, p<0.0001), NT-proBNP (417+/-700 vs. 928+/-1093 pg/mL, p<0.0001) and NE (114+/-160 vs. 473+/-992 pg/mL, p<0.0001) were significantly higher in non-survivors than survivors. After adjustment for clinical variables associated with CHF including haemodynamics and neurohumoral factors, the transcardiac gradient of NE (p<0.0001) and plasma log NT-proBNP (p<0.0001) were independent prognostic predictors. Among 67 patients in whom 123I-metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE was correlated with the washout rate (r=0.398, p=0.0009) and was a superior predictor of mortality than MIBG parameters on stepwise multivariable Cox proportional hazards regression analyses. The transcardiac increase in NE is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients.

Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients

PubMed Central

Hohl, Alexandre; Zanela, Fernando Areas; Ghisi, Gabriela; Ronsoni, Marcelo Fernando; Diaz, Alexandre Paim; Schwarzbold, Marcelo Liborio; Dafre, Alcir Luiz; Reddi, Benjamin; Lin, Kátia; Pizzol, Felipe Dal; Walz, Roger

2018-01-01

Traumatic brain injury (TBI) is a worldwide core public health problem affecting mostly young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults as well as a tremendous resource burden on the health and welfare sector. Hormone dysfunction is highly prevalent during the acute phase of severe TBI. In particular, investigation of the luteinizing hormone (LH) and testosterone levels during the acute phase of severe TBI in male has identified a high incidence of low testosterone levels in male patients (36.5–100%) but the prognostic significance of which remains controversial. Two independent studies showed that normal or elevated levels of LH levels earlier during hospitalization are significantly associated with higher mortality/morbidity. The association between LH levels and prognosis was independent of other predictive variables such as neuroimaging, admission Glasgow coma scale, and pupillary reaction. The possible mechanisms underlying this association and further research directions in this field are discussed. Overall, current data suggest that LH levels during the acute phase of TBI might contribute to accurate prognostication and further prospective multicentric studies are required to develop more sophisticated predictive models incorporating biomarkers such as LH in the quest for accurate outcome prediction following TBI. Moreover, the potential therapeutic benefits of modulating LH during the acute phase of TBI warrant investigation. PMID:29487565

A potential prognostic long non-coding RNA signature to predict metastasis-free survival of breast cancer patients.

PubMed

Sun, Jie; Chen, Xihai; Wang, Zhenzhen; Guo, Maoni; Shi, Hongbo; Wang, Xiaojun; Cheng, Liang; Zhou, Meng

2015-11-09

Long non-coding RNAs (lncRNAs) have been implicated in a variety of biological processes, and dysregulated lncRNAs have demonstrated potential roles as biomarkers and therapeutic targets for cancer prognosis and treatment. In this study, by repurposing microarray probes, we analyzed lncRNA expression profiles of 916 breast cancer patients from the Gene Expression Omnibus (GEO). Nine lncRNAs were identified to be significantly associated with metastasis-free survival (MFS) in the training dataset of 254 patients using the Cox proportional hazards regression model. These nine lncRNAs were then combined to form a single prognostic signature for predicting metastatic risk in breast cancer patients that was able to classify patients in the training dataset into high- and low-risk subgroups with significantly different MFSs (median 2.4 years versus 3.0 years, log-rank test p < 0.001). This nine-lncRNA signature was similarly effective for prognosis in a testing dataset and two independent datasets. Further analysis showed that the predictive ability of the signature was independent of clinical variables, including age, ER status, ESR1 status and ERBB2 status. Our results indicated that lncRNA signature could be a useful prognostic marker to predict metastatic risk in breast cancer patients and may improve upon our understanding of the molecular mechanisms underlying breast cancer metastasis.

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

PubMed

Atanasov, Georgi; Schierle, Katrin; Hau, Hans-Michael; Dietel, Corinna; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Englisch, Julianna Paulina; Robson, Simon C; Reutzel-Selke, Anja; Pascher, Andreas; Jonas, Sven; Pratschke, Johann; Benzing, Christian; Schmelzle, Moritz

2017-02-01

Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

PubMed Central

2010-01-01

Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID:20584321

Construction of a new, objective prognostic score for terminally ill cancer patients: a multicenter study.

PubMed

Suh, Sang-Yeon; Choi, Youn Seon; Shim, Jae Yong; Kim, Young Sung; Yeom, Chang Hwan; Kim, Daeyoung; Park, Shin Ae; Kim, Sooa; Seo, Ji Yeon; Kim, Su Hyun; Kim, Daegyeun; Choi, Sung-Eun; Ahn, Hong-Yup

2010-02-01

The goal of this study was to develop a new, objective prognostic score (OPS) for terminally ill cancer patients based on an integrated model that includes novel objective prognostic factors. A multicenter study of 209 terminally ill cancer patients from six training hospitals in Korea were prospectively followed until death. The Cox proportional hazard model was used to adjust for the influence of clinical and laboratory variables on survival time. The OPS was calculated from the sum of partial scores obtained from seven significant predictors determined by the final model. The partial score was based on the hazard ratio of each predictor. The accuracy of the OPS was evaluated. The overall median survival was 26 days. On the multivariate analysis, reduced oral intake, resting dyspnea, low performance status, leukocytosis, elevated bilirubin, elevated creatinine, and elevated lactate dehydrogenase (LDH) were identified as poor prognostic factors. The range of OPS was from 0.0 to 7.0. For the above cutoff point of 3.0, the 3-week prediction sensitivity was 74.7%, the specificity was 76.5%, and the overall accuracy was 75.5%. We developed the new OPS, without clinician's survival estimates but including a new prognostic factor (LDH). This new instrument demonstrated accurate prediction of the 3-week survival. The OPS had acceptable accuracy in this study population (training set). Further validation is required on an independent population (testing set).

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

PubMed

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

2018-03-26

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

The appropriate number of ELNs for lymph node negative breast cancer patients underwent MRM: a population-based study.

PubMed

Chi, Huiying; Zhang, Chenyue; Wang, Haiyong; Wang, Zhehai

2017-09-12

Whether number of examed lymph nodes (ELNs) would bring survival benefit for patients with negative lymph nodes after modified radical mastectomy (MRM) is uncertain. In our study, using the Surveillance Epidemiology and End Results (SEER) database between 2004 and 2009, we screened the appropriate patients with negative lymph nodes underwent MRM. The Cox proportional hazard analysis was used to determine the effect of number of ELNs on cancer specific survival (CSS). The results showed that the number of ELNs was not an independent prognostic factor on CSS ( P = 0.940). Then the X-tile mode was used to determine the appropriate threshold for ELNs count. The results showed that 9 was the appropriate cut-off point. Next, the log-rank χ 2 test was used to analyze the CSS based on different subgroup variables. The results showed that some subgroup variables including age < 50/ ≥ 50, grade I/III, AJCC T1/T2, ER positive/negative and PR positive/negative ,demonstrated significant CSS benefits among the patients with the number of ELNs ≤ 9 (all, P < 0.05). However, three subgroup variables including grade II, AJCC T3 and AJCC T4, the patients with the number of ELNs ≤ 9 did not bring significant CSS benefits (all, P > 0.1). In conclusion, our study demonstrated that the number of ELNs was not an independent prognostic factor on CSS, and 9 can be selected as the appropriate cut-off point of ELNs for patients with negative lymph nodes who underwent MRM.

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

PubMed Central

Fu, Hangcheng; Liu, Yidong; Xu, Le; Chang, Yuan; Zhou, Lin; Zhang, Weijuan; Yang, Yuanfeng; Xu, Jiejie

2016-01-01

Abstract Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC. The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram. In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy. MUC4 expression is an independent prognostic factor for OS in patients with ccRCC. PMID:27124015

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

PubMed

Kim, Eun Young; Kim, Nambeom; Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

2016-01-01

Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136). The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI is a simple and useful prognostic indicator in SCLC.

Platelet-lymphocyte ratio is an independent prognostic factor in patients with ALK-positive non-small-cell lung cancer.

PubMed

Han, Ying; Wang, Jing; Hong, Liping; Sun, Leina; Zhuang, Hongqing; Sun, Bingsheng; Wang, Hua; Zhang, Xinwei; Ren, Xiubao

2017-01-01

As the prognostic value of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear in patients with ALK-positive non-small-cell lung cancer (NSCLC), this study assessed the importance of these factors was in this patient subset. In 173 patients with primary ALK-positive NSCLC at pathological stages I-IV, neutrophil, platelet, lymphocyte, D-dimer and eosinophil levels were recorded before starting treatment. The patients' median NLR and PLR values were 2.10 and 127.69, respectively. Univariate analyses showed that NLR and PLR values, the D-dimer level and the eosinophil count were all associated with survival. Although multivariate analysis showed PLR to be an independent prognostic factor for overall survival (p = 0.018), NLR was not. PLR is an independent prognostic factor in ALK-positive NSCLC.

Prognostic significance of day-by-day variability of home blood pressure on progression to macroalbuminuria in patients with diabetes.

PubMed

Ushigome, Emi; Matsumoto, Shinobu; Oyabu, Chikako; Kitagawa, Noriyuki; Tanaka, Toru; Hasegawa, Goji; Ohnishi, Masayoshi; Tsunoda, Sei; Ushigome, Hidetaka; Yokota, Isao; Nakamura, Naoto; Oda, Yohei; Asano, Mai; Tanaka, Muhei; Yamazaki, Masahiro; Fukui, Michiaki

2018-05-01

Previously, we have shown in cross-sectional analysis of patients with type 2 diabetes mellitus that the presence of diabetic nephropathy is associated with increased home blood pressure (HBP) variability. We now examine the prognostic significance of HBP variability in substantially the same cohort. We performed a prospective cohort study of type 2 diabetes patients. We analyzed 714 patients. Major exclusion criteria are missing data of urinary albumin excretion and newly prescribed or stopped renin-angiotensin system inhibitors during 2-year follow-up. Patients were instructed to perform triplicate morning and evening HBP measurements for 14 consecutive days. We computed day-by-day HBP variability as within-patient standard deviation (SD) and coefficient of variation (CV) of measurements. During the follow-up period of 2 years, 23 patients progressed to macroalbuminuria. The changing risk of progression to macroalbuminuria with increasing day-by-day variability of morning SBP was better depicted using smoothing spline analyses. Patients with greater SD of morning SBP tended to significantly progress to macroalbuminuria [odds ratio: 5.24 (95% confidence interval: 2.10-13.03; P > 0.001)]. Patients with greater CV of morning SBP also tended to significantly progress to macroalbuminuria [odds ratio: 3.36 (95% confidence interval: 1.39-8.12; P = 0.007)]. Day-by-day variability of morning SBP was proven as an independent predictor for progression to macroalbuminuria in patients with type 2 diabetes.

Prognostic value of tumor size in gastric cancer: an analysis of 2,379 patients.

PubMed

Guo, Pengtao; Li, Yangming; Zhu, Zhi; Sun, Zhe; Lu, Chong; Wang, Zhenning; Xu, Huimian

2013-04-01

Tumor size has been included into the staging systems of many solid tumors, such as lung and breast. However, tumor size is not integrated in the staging of gastric cancer, and its prognostic value for gastric cancer needs to be reappraised. A total of 2,379 patients who received radical resection for histopathologically confirmed gastric adenocarcinoma were enrolled in the present study. Tumor size, originally presented as continuous variable, was categorized into small gastric cancer (SGC) group and large gastric cancer (LGC) group using an optimal cutoff point determined by Cox proportional hazards model. The associations between tumor size and other clinicopathological factors were checked using Chi-square test. Survival of gastric cancer patients was estimated by using univariate Kaplan-Meier method, and the survival difference was checked by using the log-rank test. The significant clinicopathological factors were included into the Cox proportional hazards model to determine the independent prognostic factors, and their hazard ratios were calculated. With the optimal cutoff point of 4 cm, tumor size was categorized into SGC group (≤ 4 cm) and LGC group (>4 cm). Tumor size closely correlated with age, tumor location, macroscopic type, Lauren classification, and lymphatic vessel invasion. Moreover, tumor size was also significantly associated with depth of tumor invasion and status of regional lymph nodes. The 5-year survival rate was 68.7 % for SGC group which was much higher than 40.2 % for LGC group. Univariate analysis showed that SGC had a better survival than LGC, mainly for patients with IIA, IIB, and IIIA stage. Multivariate analysis revealed that tumor size as well as age, tumor location, macroscopic type, Lauren classification, lymphatic vessel invasion, depth of tumor invasion, and status of regional lymph nodes were independent prognostic factors for gastric cancer. Tumor size is a reliable prognostic factor for patients with gastric cancer, and the measurement of tumor size would be helpful to the staging and management of gastric cancer.

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

PubMed Central

Gönen, Mithat; Sun, Zhuoxin; Figueroa, Maria E.; Patel, Jay P.; Abdel-Wahab, Omar; Racevskis, Janis; Ketterling, Rhett P.; Fernandez, Hugo; Rowe, Jacob M.; Tallman, Martin S.; Melnick, Ari; Levine, Ross L.

2012-01-01

We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML. PMID:22855599

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

PubMed

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

2016-03-22

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

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

PubMed

Baquero, Maria T; Lostritto, Karen; Gustavson, Mark D; Bassi, Kimberly A; Appia, Franck; Camp, Robert L; Molinaro, Annette M; Harris, Lyndsay N; Rimm, David L

2011-11-02

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

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

Mestre, Francisco; Gutiérrez, Antonio, E-mail: antoniom.gutierrez@ssib.es; Rodriguez, Jose

Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2more » defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.« less

Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

PubMed

Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

2015-08-15

Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

Inflammation scores predict survival for hepatitis B virus-related hepatocellular carcinoma patients after transarterial chemoembolization

PubMed Central

Zhou, Dong-Sheng; Xu, Li; Luo, Yao-Ling; He, Feng-Ying; Huang, Jun-Ting; Zhang, Yao-Jun; Chen, Min-Shan

2015-01-01

AIM: To compare the prognostic ability of inflammation scores for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: Data of 224 consecutive patients who underwent TACE for unresectable HBV-related HCC from September 2009 to November 2011 were retrieved from a prospective database. The association of inflammation scores with clinicopathologic variables and overall survival (OS) were analyzed, and receiver operating characteristic curves were generated, and the area under the curve (AUC) was calculated to evaluate the discriminatory ability of each inflammation score and staging system, including tumor-node-metastasis, Barcelona Clinic Liver Cancer, and Cancer of the Liver Italian Program (CLIP) scores. RESULTS: The median follow-up period was 390 d, the one-, two-, and three-year OS were 38.4%, 18.3%, and 11.1%, respectively, and the median OS was 390 d. The Glasgow Prognostic Score (GPS), modifed GPS, neutrophil-lymphocyte ratio, and Prognostic Index were associated with OS. The GPS consistently had a higher AUC value at 6 mo (0.702), 12 mo (0.676), and 24 mo (0.687) in comparison with other inflammation scores. CLIP consistently had a higher AUC value at 6 mo (0.656), 12 mo (0.711), and 24 mo (0.721) in comparison with tumor-node-metastasis and Barcelona Clinic Liver Cancer staging systems. Multivariate analysis revealed that alanine aminotransferase, GPS, and CLIP were independent prognostic factors for OS. The combination of GPS and CLIP (AUC = 0.777) was superior to CLIP or GPS alone in prognostic ability for OS. CONCLUSION: The prognostic ability of GPS is superior to other inflammation scores for HCC patients undergoing TACE. Combining GPS and CLIP improved the prognostic power for OS. PMID:25987783

A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors.

PubMed

Andersen, N S; Jensen, M K; de Nully Brown, P; Geisler, C H

2002-02-01

This study presents the first large clinical analysis of 105 unselected mantle cell lymphoma (MCL) patients diagnosed from 1992 to 2000 in a well-defined Danish population. The annual incidences were 0.7/100000 for men and 0.2/100000 for women, with no significant change during the study period. Of 97 evaluable cases, 43% achieved a complete response (CR) after initial therapy. The median disease-free (DFS) and overall survival (OS) rates were 15 and 30 months, respectively. In multivariate analysis, splenomegaly (P=0.002), anaemia (P=0.0001) and age (P=0.002), but not the international prognostic index (IPI) and the Ann Arbor staging system, had an independent impact on survival. Moreover, in a sub-analysis of 45 younger MCL patients (<65 years), a trend towards an OS plateau of 58% was observed in cases without splenomegaly and anaemia (n=29). Thus, in contrast to previously suggested prognostic factors, these variables may prove useful for clinical decisions in a significant subset of MCL patients.

Lack of independent significance of a close (<1 mm) circumferential resection margin involvement in esophageal and junctional cancer.

PubMed

O'Farrell, N J; Donohoe, C L; Muldoon, C; Costelloe, J M; King, S; Ravi, N; Reynolds, J V

2013-08-01

For rectal cancer, an involved circumferential resection margin (CRM), defined as tumor cells within 1 mm of the CRM, is of established prognostic significance. This definition for the esophagus, however, is controversial, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advises that only tumor cells at the cut margin (0 mm) define an incomplete (R1) resection. The aim of this study was to compare the clinical significance of both definitions in patients with pT3 tumors. CAP- and RCP-defined CRM status in patients treated by surgery only or by multimodal therapy was recorded prospectively in a comprehensive database from May 2003 to May 2011. Kaplan-Meier survival curves were generated, and factors affecting survival were assessed by univariate and multivariate analysis. A total of 157 of 340 patients had pT3 esophageal tumors, with RCP-positive CRM in 60 %, and 18 % by CAP. There were no significant differences between RCP-positive CRM and negative margins for node-positive disease, local recurrence, and survival. CAP-positive CRM was associated with positive nodes (P = 0.036) and poorer survival (P = 0.023). Multivariate analysis revealed nodal invasion to be the only independent prognostic variable (P = 0.004). A CRM margin of <1 mm is common in pT3 esophageal tumors, a finding consistent with other reports. The <1 mm definition was not associated with node positivity, local recurrence, or survival, in contrast to actual involvement at the margin, suggesting lack of independent prognostic significance of the RCP definition and possible superiority of the CAP criteria for prospective registration of CRM.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

PubMed

Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

2016-11-01

Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

Prognostic factors in patients with spinal metastasis: a systematic review and meta-analysis.

PubMed

Luksanapruksa, Panya; Buchowski, Jacob M; Hotchkiss, William; Tongsai, Sasima; Wilartratsami, Sirichai; Chotivichit, Areesak

2017-05-01

Incidence of symptomatic spinal metastasis has increased owing to improvement in treatment of the disease. One of the key factors that influences decision-making is expected patient survival. To our knowledge, no systematic reviews or meta-analysis have been conducted that review independent prognostic factors in spinal metastases. This study aimed to determine independent prognostic factors that affect outcome in patients with metastatic spine disease. This is a systematic literature review and meta-analysis of publications for prognostic factors in spinal metastatic disease. Pooled patient results from cohort and observational studies. Meta-analysis for poor prognostic factors as determined by hazard ratio (HR) and 95% confidential interval (95% CI). We systematically searched relevant publications in PubMed and Embase. The following search terms were used: ("'spinal metastases'" OR "'vertebral metastases'" OR "spinal metastasis" OR 'vertebral metastases') AND ('"prognostic factors"' OR "'survival'"). Inclusion criteria were prospective and retrospective cohort series that report HR and 95% CI of independent prognostic factors from multivariate analysis. Two reviewers independently assessed all papers. The quality of included papers was assessed by using Newcastle-Ottawa Scale for cohort studies and publication bias was assessed by using funnel plot, Begg test, and Egger test. The prognostic factors that were mentioned in at least three publications were pooled. Meta-analysis was performed using HR and 95% CI as the primary outcomes of interest. Heterogeneity was assessed using the I 2 method. A total of 3,959 abstracts (1,382 from PubMed and 2,577 from Embase) were identified through database search and 40 publications were identified through review of cited publications. The reviewers selected a total of 51 studies for qualitative synthesis and 43 studies for meta-analysis. Seventeen poor prognostic factors were identified. These included presence of a neurologic deficit before surgery, non-ambulatory status before radiotherapy (RT), non-ambulatory status before surgery, presence of bone metastases, presence of multiple bone metastases (>2 sites), presence of multiple spinal metastases (>3 sites), development of motor deficit in <7 days before initiating RT, development of motor deficit in <14 days before initiating RT, time interval from cancer diagnosis to RT <15 months, Karnofsky Performance Score (KPS) 10-40, KPS 50-70, KPS<70, Eastern Cooperative Oncology Group (ECOG) grade 3-4, male gender, presence of visceral metastases, moderate growth tumor on Tomita score (TS) classification, and rapid growth tumor on TS classification. Seventeen independent poor prognostic factors were identified in this study. These can be categorized into cancer-specific and nonspecific prognostic factors. A tumor-based prognostic scoring system that combines all specific and general factors may enhance the accuracy of survival prediction in patients with metastatic spine disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined prognostic value of pretreatment anemia and cervical node necrosis in patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: A large-scale retrospective study.

PubMed

Zhang, Lu-Lu; Zhou, Guan-Qun; Li, Yi-Yang; Tang, Ling-Long; Mao, Yan-Ping; Lin, Ai-Hua; Ma, Jun; Qi, Zhen-Yu; Sun, Ying

2017-12-01

This study investigated the combined prognostic value of pretreatment anemia and cervical node necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC). Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy. Patients were classified into four groups according to anemia and CNN status. Survival was compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. The primary end-point was overall survival (OS); secondary end-points were disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS). Pretreatment anemia was an independent, adverse prognostic factor for DMFS; pretreatment CNN was an independent adverse prognostic factor for all end-points. Five-year survival for non-anemia and non-CNN, anemia, CNN, and anemia and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P < 0.001), DFS (87.0%, 84.0%, 73.9%, 64.6%, P < 0.001), DMFS (94.1%, 92.1%, 82.4%, 72.5%, P < 0.001), and LRRFS (92.8%, 92.4%, 88.7%, 84.0%, P = 0.012). The non-anemia and non-CNN group had best survival outcomes; anemia and CNN group, the poorest. Multivariate analysis demonstrated combined anemia and CNN was an independent prognostic factor for OS, DFS, DMFS, and LRRFS (P < 0.05). The combination of anemia and CNN is an independent adverse prognostic factor in patients with NPC treated using IMRT ± chemotherapy. Assessment of pretreatment anemia and CNN improved risk stratification, especially for patients with anemia and CNN who have poorest prognosis. This study may aid the design of individualized treatment plans to improve treatment outcomes. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Comparison of the Prognostic Utility of the Diverse Molecular Data among lncRNA, DNA Methylation, microRNA, and mRNA across Five Human Cancers

PubMed Central

Xu, Li; Fengji, Liang; Changning, Liu; Liangcai, Zhang; Yinghui, Li; Yu, Li; Shanguang, Chen; Jianghui, Xiong

2015-01-01

Introduction Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored. Materials and Methods We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types. We assessed the predictive performance of both single molecular data and integrated multi-type molecular data in patient survival stratification, and compared their relative importance in each type of cancer, respectively. Survival analysis using multivariate Cox regression was performed to investigate the impact of the IDFO-identified markers and traditional variables on clinical outcome. Results Using the IDFO approach, we obtained good predictive performance of the molecular datasets (bootstrap accuracy: 0.71–0.97) in five cancer types. Impressively, lncRNA was identified as the best prognostic predictor in the validated cohorts of four cancer types, followed by DNA methylation, mRNA, and then microRNA. We found the incorporating of multi-type molecular data showed similar predictive power to single-type molecular data, but with the exception of the lncRNA + DNA methylation combinations in two cancers. Survival analysis of proportional hazard models confirmed a high robustness for lncRNA and DNA methylation as prognosis factors independent of traditional clinical variables. Conclusion Our study provides insight into systematically understanding the prognostic performance of diverse molecular data in both single and aggregate patterns, which may have specific reference to subsequent related studies. PMID:26606135

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Duarte, Kevin; Coiro, Stefano; McMurray, John J V; Dargie, Henry J; Pitt, Bertram; Dickstein, Kenneth; Testani, Jeffrey M; Zannad, Faiez; Rossignol, Patrick

2017-02-01

Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay. © 2017 American Heart Association, Inc.

A Nomogram to Predict Anastomotic Leakage in Open Rectal Surgery-Hope or Hype?

PubMed

Klose, Johannes; Tarantino, Ignazio; von Fournier, Armin; Stowitzki, Moritz J; Kulu, Yakup; Bruckner, Thomas; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Büchler, Markus W; Ulrich, Alexis

2018-05-18

Anastomotic leakage is the most dreaded complication after rectal resection and total mesorectal excision, leading to increased morbidity and mortality. Formation of a diverting ileostomy is generally performed to protect anastomotic healing. Identification of variables predicting anastomotic leakage might help to select patients who are under increased risk for the development of anastomotic leakage prior to surgery. The objective of this study was to assess the applicability of a nomogram as prognostic model for the occurrence of anastomotic leakage after rectal resection in a cohort of rectal cancer patients. Nine hundred seventy-two consecutive patients who underwent surgery for rectal cancer were retrospectively analyzed. Univariate and multivariable Cox regression analyses were used to determine independent risk factors associated with anastomotic leakage. Receiver operating characteristics (ROC) curve analysis was performed to calculate the sensitivity, specificity, and overall model correctness of a recently published nomogram and an adopted risk score based on the variables identified in this study as a predictive model. Male sex (p = 0.042), obesity (p = 0.017), smoking (p = 0.012), postoperative bleeding (p = 0.024), and total protein level ≤ 5.6 g/dl (p = 0.007) were identified as independent risk factors for anastomotic leakage. The investigated nomogram and the adopted risk score failed to reach relevant areas under the ROC curve greater than 0.700 for the prediction of anastomotic leakage. The proposed nomogram and the adopted risk score failed to reliably predict the occurrence of anastomotic leakage after rectal resection. Risk scores as prognostic models for the prediction of anastomotic leakage, independently of the study population, still need to be identified.

Prognostic value of plasma neutrophil gelatinase-associated lipocalin in patients with heart failure.

PubMed

Villacorta, Humberto; Santos, Rochele Alberto Martins; Marroig, Marcelle Alves Baco; Pereira, Guilherme Pinella Guedes; Xavier, Analucia Rampazzo; Kanaan, Salim

2015-01-01

Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We sought to assess the prognostic value of this biomarker in patients with stable chronic heart failure (HF). We studied 61 patients with chronic systolic HF who had been receiving optimal medical treatment for at least six months. Biomarkers were measured at baseline and included plasma NGAL, microalbuminuria, serum creatinine, and B-type natriuretic peptide (BNP). Estimated glomerular filtration rate (eGFR) was also calculated. Mean follow-up was 10.6±6.6 months. The primary endpoint was time to first cardiovascular event, defined as a combination of cardiovascular death, HF hospitalization or emergency department visit due to HF. Variables independently related to events were determined using a Cox proportional hazards model. Fifteen (24.6%) patients reached the primary endpoint. Patients with events were more likely to have worse renal function at baseline and also higher NGAL levels (median 316 [interquartile range 122-705] vs. 107 [78-170]; p=0.006). NGAL correlated significantly with creatinine (r=0.50; p<0.0001), albuminuria (r=0.33; p=0.008), and eGFR (r=-0.47; p=0.0001) but not with BNP (r=0.003; p=0.97). The best NGAL cutoff as determined by ROC curve analysis was 179 ng/ml. Event-free survival was lower in patients with NGAL above this cutoff. Variables independently related to events were NGAL (HR 1.0035, 95% CI 1.0019-1.0052; p<0.0001) and male gender (HR 5.9, 95% CI 1.22-28.6; p=0.028). NGAL correlated with other biomarkers of renal function but not with BNP and was independently associated with outcomes. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Validation of the prognostic value of lymph node ratio in patients with cutaneous melanoma: a population-based study of 8,177 cases.

PubMed

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo Riccardo; Nitti, Donato

2011-07-01

The proportion of positive among examined lymph nodes (lymph node ratio [LNR]) has been recently proposed as an useful and easy-to-calculate prognostic factor for patients with cutaneous melanoma. However, its independence from the standard prognostic system TNM has not been formally proven in a large series of patients. Patients with histologically proven cutaneous melanoma were identified from the Surveillance Epidemiology End Results database. Disease-specific survival was the clinical outcome of interest. The prognostic ability of conventional factors and LNR was assessed by multivariable survival analysis using the Cox regression model. Eligible patients (n = 8,177) were diagnosed with melanoma between 1998 and 2006. Among lymph node-positive cases (n = 3,872), most LNR values ranged from 1% to 10% (n = 2,187). In the whole series (≥5 lymph nodes examined) LNR significantly contributed to the Cox model independently of the TNM effect on survival (hazard ratio, 1.28; 95% confidence interval, 1.23-1.32; P < .0001). On subgroup analysis, the significant and independent prognostic value of LNR was confirmed both in patients with ≥10 lymph nodes examined (n = 4,381) and in those with TNM stage III disease (n = 3,658). In all cases, LNR increased the prognostic accuracy of the survival model. In this large series of patients, the LNR independently predicted disease-specific survival, improving the prognostic accuracy of the TNM system. Accordingly, the LNR should be taken into account for the stratification of patients' risk, both in clinical and research settings. Copyright © 2011 Mosby, Inc. All rights reserved.

Nonsentinel lymph node status in patients with cutaneous melanoma: results from a multi-institution prognostic study.

PubMed

Pasquali, Sandro; Mocellin, Simone; Mozzillo, Nicola; Maurichi, Andrea; Quaglino, Pietro; Borgognoni, Lorenzo; Solari, Nicola; Piazzalunga, Dario; Mascheroni, Luigi; Giudice, Giuseppe; Patuzzo, Roberto; Caracò, Corrado; Ribero, Simone; Marone, Ugo; Santinami, Mario; Rossi, Carlo Riccardo

2014-03-20

We investigated whether the nonsentinel lymph node (NSLN) status in patients with melanoma improves the prognostic accuracy of common staging features; then we formulated a proposal for including the NSLN status in the current melanoma staging system. We retrospectively collected the clinicopathologic data of 1,538 patients with positive SLN status who underwent completion lymph node dissection (CLND) at nine Italian centers. Multivariable Cox regression survival analysis was used to identify independent prognostic factors. Literature meta-analysis was used to summarize the available evidence on the prognostic value of the NSLN status in patients with positive SLN. NSLN metastasis was observed in 353 patients (23%). After a median follow-up of 45 months, NSLN status was an independent prognostic factor for melanoma-specific survival (hazard ratio [HR] = 1.34; 95% CI, 1.18 to 1.52; P < .001). NSLN status efficiently stratified the prognosis of patients with two to three positive lymph nodes (n = 387; HR = 1.39; 95% CI, 1.07 to 1.81; P = .013), independently of other staging features. Searching the literature, this patient subgroup was investigated in other two studies. Pooling the results (n = 620 patients; 284 NSLN negative and 336 NSLN positive), we found that NSLN status is a highly significant prognostic factor (summary HR = 1.59; 95% CI, 1.27 to 1.98; P < .001) in patients with two to three positive lymph nodes. These findings support the independent prognostic value of the NSLN status in patients with two to three positive lymph nodes, suggesting that this information should be considered for the routine staging in patients with melanoma.

Comprehensive analysis and validation of contemporary survival prognosticators in Korean patients with metastatic renal cell carcinoma treated with targeted therapy: prognostic impact of pretreatment neutrophil-to-lymphocyte ratio.

PubMed

Koo, Kyo Chul; Lee, Kwang Suk; Cho, Kang Su; Rha, Koon Ho; Hong, Sung Joon; Chung, Byung Ha

2016-06-01

In line with the era of targeted therapy (TT), an increasing number of prognosticators are becoming available for patients with metastatic renal cell carcinoma (mRCC). Here, potential prognosticators of cancer-specific survival (CSS) were identified based on the contemporary literature and were comprehensively validated in an independent cohort of patients treated for mRCC. Data were collected from 478 patients treated with TT for mRCC between January 1999 and July 2013 at a single institution. The analysis included 25 clinicopathological covariates that included both traditional and contemporary prognosticators. Multivariate Cox regression models were used to quantify the effect of covariates on CSS. Median survival from the initial diagnosis of metastasis was 24.5 (IQR, 11.5-55.7) months. There were 303 (63.4 %) cancer-specific deaths, yielding a 2-year CSS rate of 62.5 %. Low Karnofsky performance status (KPS), hypercalcemia, neutrophil-to-lymphocyte ratio (NLR), the number of metastatic sites (≥2), and the presence of brain metastases were independent adverse prognosticators of CSS. The C-index of the model was 0.78. Patients with at least one adverse prognosticator demonstrated lower 2-year CSS rates compared to those with no prognosticators (53.9 vs. 70.6 %; log rank p < 0.001). Together with traditional prognosticators such as KPS, hypercalcemia, and the number and location of metastases, the NLR was an independent predictor of CSS in patients with mRCC treated with TT. Our findings could be useful for guiding clinical decision making including stratification of patients for TT and inclusion in clinical trials.

Characteristics predicting outcomes of allogeneic stem-cell transplantation in relapsed acute myelogenous leukemia.

PubMed

Frazer, J; Couban, S; Doucette, S; Shivakumar, S

2017-04-01

Allogeneic hematopoietic stem-cell transplantation (ahsct) is associated with significant morbidity and mortality, but it can cure carefully selected patients with acute myeloid leukemia (aml) in second remission (cr2). In a cohort of patients with aml who underwent ahsct in cr2, we determined the pre-transplant factors that predicted for overall survival (os), relapse, and non-relapse mortality. We also sought to validate the prognostic risk groups derived by Michelis and colleagues in this independent population. In a retrospective chart review, we obtained data for 55 consecutive patients who underwent ahsct for aml in cr2. Hazard ratios were used to describe the independent effects of pre-transplant variables on outcome, and Kaplan-Meier curves were used to assess outcomes in the three prognostic groups identified by Michelis and colleagues. At 1, 3, and 5 years post-transplant, os was 60%, 45.5%, and 37.5% respectively. Statistically significant differences in os, relapse mortality, and non-relapse mortality were not identified between the prognostic risk groups identified by Michelis and colleagues. Women were less likely than men to relapse, and a modified European Society for Blood and Marrow Transplantation (mebmt) score of 3 or less was associated with a lower non-relapse mortality. The 37.5% 5-year os in this cohort suggests that, compared with other options, ahsct offers patients with aml in cr2 a better chance of cure. Our study supports the use of the mebmt score to predict non-relapse mortality in this population.

A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery.

PubMed

Mao, Qixing; Xia, Wenjie; Dong, Gaochao; Chen, Shuqi; Wang, Anpeng; Jin, Guangfu; Jiang, Feng; Xu, Lin

2018-04-01

Postoperative survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is highly heterogeneous. Here, we aimed to identify variables associated with postoperative survival and develop a tool for survival prediction. A retrospective review was performed in the Surveillance, Epidemiology, and End Results database from January 2004 to December 2009. Significant variables were selected by use of the backward stepwise method. The nomogram was constructed with multivariable Cox regression. The model's performance was evaluated by concordance index and calibration curve. The model was validated via an independent cohort from the Jiangsu Cancer Hospital Lung Cancer Center. A total of 1809 patients with stage IIIA-N2 NSCLC who underwent surgery were included in the training cohort. Age, sex, grade, histology, tumor size, visceral pleural invasion, positive lymph nodes, lymph nodes examined, and surgery type (lobectomy vs pneumonectomy) were identified as significant prognostic variables using backward stepwise method. A nomogram was developed from the training cohort and validated using an independent Chinese cohort. The concordance index of the model was 0.673 (95% confidence interval, 0.654-0.692) in training cohort and 0.664 in validation cohort (95% confidence interval, 0.614-0.714). The calibration plot showed optimal consistency between nomogram predicted survival and observed survival. Survival analyses demonstrated significant differences between different subgroups stratified by prognostic scores. This nomogram provided the individual survival prediction for patients with stage IIIA-N2 NSCLC after surgery, which might benefit survival counseling for patients and clinicians, clinical trial design and follow-up, as well as postoperative strategy-making. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Prognostic value of the oxygen uptake efficiency slope and other exercise variables in patients with coronary artery disease.

PubMed

Coeckelberghs, Ellen; Buys, Roselien; Goetschalckx, Kaatje; Cornelissen, Véronique A; Vanhees, Luc

2016-02-01

Peak exercise capacity is an independent predictor for mortality in patients with coronary artery disease. However, sometimes cardiopulmonary exercise tests are stopped prematurely. Therefore, submaximal exercise measures such as the oxygen uptake efficiency slope have been introduced. The aim of this study was to assess the prognostic value of the oxygen uptake efficiency slope and other exercise parameters, in patients with coronary artery disease. Between 2000 and 2011, 1409 patients with coronary artery disease (age 60.7 ± 9.9 years; 1205 males) underwent cardiopulmonary exercise tests. A maximal effort was not reached in 161 (11.5%) patients. The oxygen uptake efficiency slope was calculated and information on mortality was obtained. Cox proportional hazards regression analyses were used to assess the relation of oxygen uptake efficiency slope and other gas exchange variables with all-cause and cardiovascular mortality. Receiver operating characteristic curve analyses was performed to define optimal cut-off values. During an average follow-up of 7.45 ± 3.20 years (range 0.16-13.95 years), 158 patients died, among which 68 patients for cardiovascular reasons. The oxygen uptake efficiency slope was related to all-cause (hazard ratio: 0.568, p < 0.001) and cardiovascular (hazard ratio: 0.461, p < 0.001) mortality. When significant covariates were entered in the analysis, oxygen uptake efficiency slope remained related to mortality (p < 0.05). When other submaximal exercise parameters were added to the model, oxygen uptake efficiency slope and minute ventilation/carbon dioxide production slope also remained significantly related to mortality. The oxygen uptake efficiency slope is an independent predictor for all-cause and cardiovascular mortality in patients with coronary artery disease, irrespective of a truly maximal effort during cardiopulmonary exercise tests. Furthermore, the oxygen uptake efficiency slope provides prognostic information, complementary to the minute ventilation/carbon dioxide production slope and peak exercise capacity. © The European Society of Cardiology 2015.

Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients.

PubMed

Liu, Wen-Yue; Lin, Shi-Gang; Zhu, Gui-Qi; Poucke, Sven Van; Braddock, Martin; Zhang, Zhongheng; Mao, Zhi; Shen, Fei-Xia; Zheng, Ming-Hua

2016-01-01

Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813-0.834, P< 0.001) and 0.738 (95% CI: 0.725-0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group.

Bicarbonate can improve the prognostic value of the MELD score for critically ill patients with cirrhosis.

PubMed

Chen, Cheng-Yi; Pan, Chi-Feng; Wu, Chih-Jen; Chen, Han-Hsiang; Chen, Yu-Wei

2014-07-01

The prognosis of critically ill patients with cirrhosis is poor. Our aim was to identify an objective variable that can improve the prognostic value of the Model of End-Stage Liver Disease (MELD) score in patients who have cirrhosis and are admitted to the intensive care unit (ICU). This retrospective cohort study included 177 patients who had liver cirrhosis and were admitted to the ICU. Data pertaining to arterial blood gas-related parameters and other variables were obtained on the day of ICU admission. The overall ICU mortality rate was 36.2%. The bicarbonate (HCO3) level was found to be an independent predictor of ICU mortality (odds ratio, 2.3; 95% confidence interval [CI], 1.0-4.8; p = 0.038). A new equation was constructed (MELD-Bicarbonate) by replacing total bilirubin by HCO3 in the original MELD score. The area under the receiver operating characteristic curve for predicting ICU mortality was 0.76 (95% CI, 0.69-0.84) for the MELD-Bicarbonate equation, 0.73 (95% CI, 0.65-0.81) for the MELD score, and 0.71 (95% CI, 0.63-0.80) for the Acute Physiology and Chronic Health Evaluation II score. Bicarbonate level assessment, as an objective and reproducible laboratory test, has significant predictive value in critically ill patients with cirrhosis. In contrast, the predictive value of total bilirubin is not as prominent in this setting. The MELD-Bicarbonate equation, which included three variables (international normalized ratio, creatinine level, and HCO3 level), showed better prognostic value than the original MELD score in critically ill patients with cirrhosis.

A Prognostic Model for One-year Mortality in Patients Requiring Prolonged Mechanical Ventilation

PubMed Central

Carson, Shannon S.; Garrett, Joanne; Hanson, Laura C.; Lanier, Joyce; Govert, Joe; Brake, Mary C.; Landucci, Dante L.; Cox, Christopher E.; Carey, Timothy S.

2009-01-01

Objective A measure that identifies patients who are at high risk of mortality after prolonged ventilation will help physicians communicate prognosis to patients or surrogate decision-makers. Our objective was to develop and validate a prognostic model for 1-year mortality in patients ventilated for 21 days or more. Design Prospective cohort study. Setting University-based tertiary care hospital Patients 300 consecutive medical, surgical, and trauma patients requiring mechanical ventilation for at least 21 days were prospectively enrolled. Measurements and Main Results Predictive variables were measured on day 21 of ventilation for the first 200 patients and entered into logistic regression models with 1-year and 3-month mortality as outcomes. Final models were validated using data from 100 subsequent patients. One-year mortality was 51% in the development set and 58% in the validation set. Independent predictors of mortality included requirement for vasopressors, hemodialysis, platelet count ≤150 ×109/L, and age ≥50. Areas under the ROC curve for the development model and validation model were 0.82 (se 0.03) and 0.82 (se 0.05) respectively. The model had sensitivity of 0.42 (se 0.12) and specificity of 0.99 (se 0.01) for identifying patients who had ≥90% risk of death at 1 year. Observed mortality was highly consistent with both 3- and 12-month predicted mortality. These four predictive variables can be used in a simple prognostic score that clearly identifies low risk patients (no risk factors, 15% mortality) and high risk patients (3 or 4 risk factors, 97% mortality). Conclusions Simple clinical variables measured on day 21 of mechanical ventilation can identify patients at highest and lowest risk of death from prolonged ventilation. PMID:18552692

Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by (18)F-FDG PET/CT in squamous cell carcinoma of the oral cavity.

PubMed

Ryu, In Sun; Kim, Jae Seung; Roh, Jong-Lyel; Cho, Kyung-Ja; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2014-03-01

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by (18)F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Of 162 patients with OSCC evaluated preoperatively by (18)F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUVmax), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). The median (range) SUVmax, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36%). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0% and 62.0%, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS. Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.

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

PubMed

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

2015-01-01

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

A systematic review of prognostic factors for return to work following work-related traumatic hand injury.

PubMed

Shi, Qiyun; Sinden, Kathryn; MacDermid, Joy C; Walton, David; Grewal, Ruby

2014-01-01

Systematic review. Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. 2a. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction.

PubMed

Gavara, Jose; Rodriguez-Palomares, Jose F; Valente, Filipa; Monmeneu, Jose V; Lopez-Lereu, Maria P; Bonanad, Clara; Ferreira-Gonzalez, Ignacio; Garcia Del Blanco, Bruno; Rodriguez-Garcia, Julian; Mutuberria, Maria; de Dios, Elena; Rios-Navarro, Cesar; Perez-Sole, Nerea; Racugno, Paolo; Paya, Ana; Minana, Gema; Canoves, Joaquim; Pellicer, Mauricio; Lopez-Fornas, Francisco J; Barrabes, Jose; Evangelista, Arturo; Nunez, Julio; Chorro, Francisco J; Garcia-Dorado, David; Bodi, Vicente

2017-12-08

The aim of this study was to evaluate the prognostic value of strain as assessed by tissue tracking (TT) cardiac magnetic resonance (CMR) soon after ST-segment elevation myocardial infarction (STEMI). The prognostic value of myocardial strain as assessed post-STEMI by TT-CMR is unknown. The authors studied the prognostic value of TT-CMR in 323 patients who underwent CMR 1 week post-STEMI. Global (average of peak segmental values [%]) and segmental (number of altered segments) longitudinal (LS), circumferential, and radial strain were assessed using TT-CMR. Global and segmental strain cutoff values were derived from 32 control patients. CMR-derived left ventricular ejection fraction, microvascular obstruction, and infarct size were determined. Results were validated in an external cohort of 190 STEMI patients. During a median follow-up of 1,085 days, 54 first major adverse cardiac events (MACE), which included 10 cardiac deaths, 25 readmissions for heart failure, and 19 readmissions for reinfarction were documented. MACE was associated with more severe abnormalities in all strain indexes (p < 0.001), although only global LS was an independent predictor (p < 0.001). The MACE rate was higher in patients with a global LS of ≥-11% (22% vs. 9%; p = 0.001). After adjustment for baseline and CMR variables, global LS (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.11 to 1.32; p < 0.001) was associated with MACE. In the external validation cohort, a global LS ≥-11% was seen in a higher proportion of patients with MACE (34% vs. 9%; p < 0.001). Global LS predicted MACE after adjustment for baseline and CMR variables (HR: 1.18; 95% CI: 1.04 to 1.33; p = 0.008). The addition of global LS to the multivariate models, including baseline and CMR variables, did not significantly improve the categorical net reclassification improvement index in either the study group (-0.015; p = 0.7) or in the external validation cohort (-0.019; p = 0.9). TT-CMR provided prognostic information soon after STEMI. However, it did not substantially improve risk reclassification beyond traditional CMR indexes. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Variability in Predictions from Online Tools: A Demonstration Using Internet-Based Melanoma Predictors.

PubMed

Zabor, Emily C; Coit, Daniel; Gershenwald, Jeffrey E; McMasters, Kelly M; Michaelson, James S; Stromberg, Arnold J; Panageas, Katherine S

2018-02-22

Prognostic models are increasingly being made available online, where they can be publicly accessed by both patients and clinicians. These online tools are an important resource for patients to better understand their prognosis and for clinicians to make informed decisions about treatment and follow-up. The goal of this analysis was to highlight the possible variability in multiple online prognostic tools in a single disease. To demonstrate the variability in survival predictions across online prognostic tools, we applied a single validation dataset to three online melanoma prognostic tools. Data on melanoma patients treated at Memorial Sloan Kettering Cancer Center between 2000 and 2014 were retrospectively collected. Calibration was assessed using calibration plots and discrimination was assessed using the C-index. In this demonstration project, we found important differences across the three models that led to variability in individual patients' predicted survival across the tools, especially in the lower range of predictions. In a validation test using a single-institution data set, calibration and discrimination varied across the three models. This study underscores the potential variability both within and across online tools, and highlights the importance of using methodological rigor when developing a prognostic model that will be made publicly available online. The results also reinforce that careful development and thoughtful interpretation, including understanding a given tool's limitations, are required in order for online prognostic tools that provide survival predictions to be a useful resource for both patients and clinicians.

Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

PubMed

Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

2015-12-01

Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

Importance of Metastatic Lymph Node Ratio in Non-Metastatic, Lymph Node-Invaded Colon Cancer: A Clinical Trial

PubMed Central

Isik, Arda; Peker, Kemal; Firat, Deniz; Yilmaz, Bahri; Sayar, Ilyas; Idiz, Oguz; Cakir, Coskun; Demiryilmaz, Ismail; Yilmaz, Ismayil

2014-01-01

Background The aim of this study was to evaluate the prognostic importance of the metastatic lymph node ratio for stage III colon cancer patients and to find a cut-off value at which the overall survival and disease-free survival change. Material/Methods Patients with pathological stage III colon cancer were retrospectively evaluated for: age; preoperative values of Crp, Cea, Ca 19-9, and Afp; pathologic situation of vascular, perineural, lymphatic, and serosal involvement; and metastatic lymph node ratio values were calculated. Results The study included 58 stage III colon cancer patients: 20 (34.5%) females and 38 (65.5%) males were involved in the study. Multivariate analysis was applied to the following variables to evaluate significance for overall survival and disease-free survival: age, Crp, Cea, perineural invasion, and metastatic lymph node ratio. The metastatic lymph node ratio (<0.25 or ≥0.25) is the only independent variable significant for overall and disease-free survival. Conclusions Metastatic lymph node ratio is an ideal prognostic marker for stage III colon cancer patients, and 0.25 is the cut-off value for prognosis. PMID:25087904

Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.

PubMed

Lee, Seung Jun; Kim, Hyo-Jung; Kim, Ju-Young; Ju, Sunmi; Lim, Sujin; Yoo, Jung Wan; Nam, Sung-Jin; Lee, Gi Dong; Cho, Hyun Seop; Kim, Rock Bum; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog

2017-08-01

A clinical classification system has been developed to define the severity and predict the prognosis of subjects with non-cystic fibrosis (CF) bronchiectasis. We aimed to identify laboratory parameters that are correlated with the bronchiectasis severity index (BSI) and FACED score. The medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED scores could be calculated were retrospectively reviewed. The correlations between the laboratory parameters and BSI or FACED score were assessed, and multiple-linear regression analysis was performed to identify variables independently associated with BSI and FACED score. An additional subgroup analysis was performed according to sex. Among all of the enrolled subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED scores were 9.43 ± 3.81 and 1.92 ± 1.59, respectively. The serum albumin level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r = 0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and bilirubin level (r = -0.25) showed a significant correlation with the FACED score. Multiple-linear regression analysis showed that the serum bilirubin level was independently associated with BSI, and the serum albumin level was independently associated with both scoring systems. Subgroup analysis revealed that the level of uric acid was also a significant variable independently associated with the BSI in male bronchiectasis subjects. Several laboratory variables were identified as possible prognostic factors for non-CF bronchiectasis. Among them, the serum albumin level exhibited the strongest correlation and was identified as an independent variable associated with the BSI and FACED scores. Copyright © 2017 by Daedalus Enterprises.

[The prognostic value of variables from the quality assurance program and of the rehabilitation-discharge report of the LVA Baden-Württemberg for early retirement: results of a retrospective cohort-study].

PubMed

Küpper-Nybelen, J; Rothenbacher, D; Jacobi, E; Brenner, H

2003-12-01

Since 1997 the LVA Baden-Württemberg pension insurance agency has implemented an instrument to measure the outcome quality of in-patient rehabilitation. The objective of this study was to evaluate the prognostic value of various short-term rehabilitation success markers and of variables of the quality assurance program and the rehab-discharge report of the LVA Baden-Württemberg on early retirement by means of a retrospective cohort study. The analysis was based on routinely registered data of patients who underwent in-hospital rehabilitation in a hospital accredited by the LVA Baden-Württemberg between June 1997 and June 1999. Baseline data included information from medical discharge reports and from the quality assurance programme. Follow-up information with regard to disability was collected until July 2000. The prognostic value of the quality assurance programme and of 4 standardized documented items from the medical discharge report was estimated by proportional hazards regression. In this analysis 6,823 patients aged 30-59 years who underwent an in-patient rehab programme between June 1997 and July 1999 in 5 of 6 LVA rehab clinics were included. During follow-up (mean duration: 1.8 years) 908 (13.3%) patients retired because of health-related disability. The variables with the strongest prognostic values were the evaluation of the patient health status by the physician and the patients themselves and the capacity to work. The variables with the highest prognostic value were the evaluation on a 1-6 visual analogue scale; a better assessment by one mark of the health status by physician and patient himself, respectively, was associated with a 53% and 40% reduced risk of disability. Fitness for work at discharge was the most prognostic variable from the discharge report. Patients who were able to work had a 78% reduced risk of disability compared to patients unable to work. Also of prognostic relevance were a positive performance and the duration of the inability to work the year before rehabilitation. The variables of the newly developed quality assurance programme of the LVA clearly demonstrated a prognostic value in terms of risk for subsequent early retirement. It should be considered to include the ability to work at discharge in the programme to further improve its prognostic value.

Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors: a study from the Japanese Breast Cancer Registry.

PubMed

Kataoka, Akemi; Iwamoto, Takayuki; Tokunaga, Eriko; Tomotaki, Ai; Kumamaru, Hiraku; Miyata, Hiroaki; Niikura, Naoki; Kawai, Masaaki; Anan, Keisei; Hayashi, Naoki; Masuda, Shinobu; Tsugawa, Koichiro; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

2016-11-01

The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. Of the 53,670 patients registered between 2004 and 2006 and surveyed after a 5-year follow-up prognosis, 25,898 breast cancer patients (48.3 %), who were obtained prognostic data, were examined. Clinicopathological factors were compared between young adult (YA; <35 years), middle-aged adult (MA; 35-50 years), and older adult (OA; >50 years) patients. Five-year disease-free survival (DFS) and overall survival (OS) rates were studied. YA patients were associated with an advanced TNM stage and aggressive characteristics (e.g. human epidermal growth factor receptor 2 (HER2)-positive or oestrogen receptor (ER)-negative breast cancers) compared to MA and OA patients (P < 0.001). The 5-year DFS and OS rates were 79.4 % and 90.8, 88.5 and 95.0 %, and 87.8 % and 91.6 % for YA, MA, and OA patients, respectively. From the multivariable regression analysis, young age at onset was confirmed as an independent prognostic factor for both DFS (hazard ratio 1.73, 95 % confidence interval 1.42-2.10; P < 0.001) and OS (hazard ratio 1.58, 95 % confidence interval 1.16-2.15; P = 0.004). Young age at onset is an independent negative prognostic factor in breast cancer. Further studies are required to develop new therapeutic strategies for YA breast cancer patients.

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer.

PubMed

Kimbung, Siker; Johansson, Ida; Danielsson, Anna; Veerla, Srinivas; Egyhazi Brage, Suzanne; Frostvik Stolt, Marianne; Skoog, Lambert; Carlsson, Lena; Einbeigi, Zakaria; Lidbrink, Elisabet; Linderholm, Barbro; Loman, Niklas; Malmström, Per-Olof; Söderberg, Martin; Walz, Thomas M; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2016-01-01

The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. ©2015 American Association for Cancer Research.

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

PubMed

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

2014-01-01

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

Clinicopathological categorization of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease: an analysis of 42 cases with an emphasis on prognostic implications.

PubMed

Paik, Jin Ho; Choe, Ji-Young; Kim, Hyojin; Lee, Jeong-Ok; Kang, Hyoung Jin; Shin, Hee Young; Lee, Dong Soon; Heo, Dae Seog; Kim, Chul-Woo; Cho, Kwang-Hyun; Kim, Tae Min; Jeon, Yoon Kyung

2017-01-01

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) include several overlapping EBV-related conditions with variably aggressive courses. For prognostic categorization, we retrospectively analyzed 42 EBV-T/NK-LPD cases. Male (79% [33/42]), young (≤40 years; 83% [35/42]) patients and T-cell lineage (81% [34/42]; CD8/CD4 = 1.8) were predominant. Clinicopathologically, three systemic and one cutaneous category were developed: hemophagocytic lymphohistiocytosis (HLH; 26% [11/42]), chronic active EBV infection (CAEBV; 31% [13/42]), systemic unclassifiable disease (24% [10/42]), and hydroa vacciniforme/hydroa vacciniforme-like lymphoma (HV/HVL; 19% [8/42]). Prognostically, cutaneous disease (HV/HVL) was better than systemic disease (p = 0.014; median, 285 vs. 10 months). In systemic diseases, HLH was worst (p = 0.002; 3[HLH] vs. 4[unclassifiable] vs. not reached [CAEBV]). Univariate survival analysis (n = 42) revealed cytopenia (≥one lineage; p < 0.001), onset age (>40 years; p = 0.001), T-cell lineage (p = 0.041), hemophagocytic histiocytes (p = 0.031), elevated lactate dehydrogenase (p = 0.020), and liver dysfunction (p = 0.023) predicted shorter survival. In multivariate analysis, T-cell lineage (p = 0.025 [HR =11.3]) and cytopenia (p = 0.028 [HR =5.4]) were independent prognostic factors. Therefore, EBV-T/NK-LPD could be classified into four prognostic categories.

Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

PubMed

Guadagno, Elia; Del Basso De Caro, Marialaura; Pignatiello, Sara; Sciammarella, Concetta; Solari, Domenico; Cappabianca, Paolo; Maiuri, Francesco; Dones, Flavia

2016-09-01

According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

PubMed

Fonseca, E; Cruz, J J; Dueñas, A; Gómez, A; Sánchez, P; Martín, G; Nieto, A; Soria, P; Muñoz, A; Gómez, J L; Pardal, J L

1996-01-01

Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study.

PubMed

Giussani, G; Canelli, V; Bianchi, E; Erba, G; Franchi, C; Nobili, A; Sander, J W; Beghi, E

2016-07-01

Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs. © 2016 EAN.

Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis.

PubMed

Psallidas, Ioannis; Kanellakis, Nikolaos I; Gerry, Stephen; Thézénas, Marie Laëtitia; Charles, Philip D; Samsonova, Anastasia; Schiller, Herbert B; Fischer, Roman; Asciak, Rachelle; Hallifax, Robert J; Mercer, Rachel; Dobson, Melissa; Dong, Tao; Pavord, Ian D; Collins, Gary S; Kessler, Benedikt M; Pass, Harvey I; Maskell, Nick; Stathopoulos, Georgios T; Rahman, Najib M

2018-06-13

The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival. In this multicohort study, we used five separate and independent datasets from randomised controlled trials to investigate potential biomarkers of survival and pleurodesis. Mass spectrometry-based discovery was used to investigate pleural fluid samples for differential protein expression in patients from the discovery group with different survival and pleurodesis outcomes. Clinical, radiological, and biological variables were entered into least absolute shrinkage and selection operator regression to build a model that predicts 3-month mortality. We evaluated the model using internal and external validation. 17 biomarker candidates of survival and seven of pleurodesis were identified in the discovery dataset. Three independent datasets (n=502) were used for biomarker validation. All pleurodesis biomarkers failed, and gelsolin, macrophage migration inhibitory factor, versican, and tissue inhibitor of metalloproteinases 1 (TIMP1) emerged as accurate predictors of survival. Eight variables (haemoglobin, C-reactive protein, white blood cell count, Eastern Cooperative Oncology Group performance status, cancer type, pleural fluid TIMP1 concentrations, and previous chemotherapy or radiotherapy) were validated and used to develop a survival score. Internal validation with bootstrap resampling and external validation with 162 patients from two independent datasets showed good discrimination (C statistic values of 0·78 [95% CI 0·72-0·83] for internal validation and 0·89 [0·84-0·93] for external validation of the clinical PROMISE score). To our knowledge, the PROMISE score is the first prospectively validated prognostic model for malignant pleural effusion that combines biological and clinical parameters to accurately estimate 3-month mortality. It is a robust, clinically relevant prognostic score that can be applied immediately, provide important information on patient prognosis, and guide the selection of appropriate management strategies. European Respiratory Society, Medical Research Funding-University of Oxford, Slater & Gordon Research Fund, and Oxfordshire Health Services Research Committee Research Grants. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prognostic, predictive and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer.

PubMed

Bruun, Jarle; Sveen, Anita; Barros, Rita; Eide, Peter W; Eilertsen, Ina; Kolberg, Matthias; Pellinen, Teijo; David, Leonor; Svindland, Aud; Kallioniemi, Olli; Guren, Marianne G; Nesbakken, Arild; Almeida, Raquel; Lothe, Ragnhild A

2018-06-14

We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I-IV primary CRCs by gene expression (n=403) or immunohistochemistry (n=642) and in relation to 5-year relapse-free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines. CDX2 expression was lost in 11.6% of cases and showed independent poor prognostic value in multivariable models. For individual stages, CDX2 was prognostic only in stage IV, independent of chemotherapy. Among stage I-III patients not treated in an adjuvant setting, CDX2 loss was associated with a particularly poor survival in the BRAF-mutated subgroup, but prognostic value was independent of microsatellite instability status and the consensus molecular subtypes In stage III, the 5-year RFS rate was higher among patients with loss of CDX2 who received adjuvant chemotherapy than among patients who did not. The CDX2-negative cell lines were significantly more sensitive to chemotherapeutics than CDX2-positive cells, and the multidrug resistance genes MDR1 and CFTR were significantly downregulated both in CDX2-negative cells and patient tumors. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP.

PubMed

Green, Tina M; Jensen, Andreas K; Holst, René; Falgreen, Steffen; Bøgsted, Martin; de Stricker, Karin; Plesner, Torben; Mourits-Andersen, Torben; Frederiksen, Mikael; Johnsen, Hans E; Pedersen, Lars M; Møller, Michael B

2016-09-01

We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Including International Prognostic Index (IPI) as a variable in a penalized Cox regression, we investigated the association with disease progression for single genes or gene combinations in four models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B. This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P < 0·001). However, a simpler, IPI independent model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs. 82% for low risk group (P < 0·001). We have documented the impact of a few single genes added to IPI for assignment in new drug trials. © 2016 John Wiley & Sons Ltd.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

PubMed

Jin, Zhaohui; Hartgers, Mindy L; Sanhueza, Cristobal T; Shubert, Christopher R; Alberts, Steven R; Truty, Mark J; Muppa, Prasuna; Nagorney, David M; Smyrk, Thomas C; Hassan, Mohamed; Mahipal, Amit

2018-05-01

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Evaluating a 4-marker signature of aggressive prostate cancer using time-dependent AUC.

PubMed

Gerke, Travis A; Martin, Neil E; Ding, Zhihu; Nuttall, Elizabeth J; Stack, Edward C; Giovannucci, Edward; Lis, Rosina T; Stampfer, Meir J; Kantoff, Phillip W; Parmigiani, Giovanni; Loda, Massimo; Mucci, Lorelei A

2015-12-01

We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer. Using data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n = 276). Based on these models, we generated prognostic risk scores in an independent population, the Health Professionals Follow-up Study (HPFS; n = 347) to evaluate external validity. In each cohort, men were followed prospectively from cancer diagnosis through 2011 for development of distant metastasis or cancer mortality. We measured protein tumor expression of PTEN, SMAD4, SPP1, and CCND1 on tissue microarrays. During a median of 11.9 and 14.3 years follow-up in the PHS and HPFS cohorts, 24 and 32 men (9%) developed lethal disease. When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. Although the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in aggressive prostate tumors and highlight the challenges that may result from overfitting in discovery-based research. © 2015 Wiley Periodicals, Inc.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more appropriate patient follow up according to risk stratification. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Epithelial–mesenchymal transition-associated secretory phenotype predicts survival in lung cancer patients

PubMed Central

Reka, Ajaya Kumar; Chen, Guoan; Keshamouni, Venkateshwar G.

2014-01-01

In cancer cells, the process of epithelial–mesenchymal transition (EMT) confers migratory and invasive capacity, resistance to apoptosis, drug resistance, evasion of host immune surveillance and tumor stem cell traits. Cells undergoing EMT may represent tumor cells with metastatic potential. Characterizing the EMT secretome may identify biomarkers to monitor EMT in tumor progression and provide a prognostic signature to predict patient survival. Utilizing a transforming growth factor-β-induced cell culture model of EMT, we quantitatively profiled differentially secreted proteins, by GeLC-tandem mass spectrometry. Integrating with the corresponding transcriptome, we derived an EMT-associated secretory phenotype (EASP) comprising of proteins that were differentially upregulated both at protein and mRNA levels. Four independent primary tumor-derived gene expression data sets of lung cancers were used for survival analysis by the random survival forests (RSF) method. Analysis of 97-gene EASP expression in human lung adenocarcinoma tumors revealed strong positive correlations with lymph node metastasis, advanced tumor stage and histological grade. RSF analysis built on a training set (n = 442), including age, sex and stage as variables, stratified three independent lung cancer data sets into low-, medium- and high-risk groups with significant differences in overall survival. We further refined EASP to a 20 gene signature (rEASP) based on variable importance scores from RSF analysis. Similar to EASP, rEASP predicted survival of both adenocarcinoma and squamous carcinoma patients. More importantly, it predicted survival in the early-stage cancers. These results demonstrate that integrative analysis of the critical biological process of EMT provides mechanism-based and clinically relevant biomarkers with significant prognostic value. PMID:24510113

Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non-Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center.

PubMed

Dinglin, Xiao-Xiao; Ma, Shu-Xiang; Wang, Fang; Li, De-Lan; Liang, Jian-Zhong; Chen, Xin-Ru; Liu, Qing; Zeng, Yin-Duo; Chen, Li-Kun

2017-05-01

The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non-small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

PubMed Central

2011-01-01

Introduction Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. Methods MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Results Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Conclusions Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy. PMID:21888627

Comorbidity and prognosis in advanced hypopharyngeal-laryngeal cancer under combined therapy.

PubMed

Montero, Elena Hernández; Trufero, Javier Martínez; Romeo, Javier Azúa; Terré, Fernando Clau

2008-01-01

The success of combined treatment in head and neck cancer resides largely in its completion, which can be compromised when the patient's general health status is precarious. The objective of this investigation was to study the role of comorbidity as a prognostic factor in a large, homogeneous population affected by locally advanced pharyngeal-laryngeal cancer, under a combined protocol treatment. The a priori hypothesis is that comorbidity strongly conditions overall survival and specific overall survival in these patients and can aid in the selection and individualization of treatments. After a 24-month follow-up, a univariate and multivariate retrospective analysis of survival and prognostic factors was performed using 14 clinical, pathological and molecular variables including the comorbidity index calculated following the Picarillo method. The settings were the Otolaryngology, Oncology and Pathology Departments of the Miguel Servet University Hospital, Zaragoza, Spain, a referral center of the National Health System. Of the original 114 patients selected, 15 were withdrawn because the tumor spread to maxillofacial areas, or due to the lack of attendance at the clinic, incomplete clinical data or coexistent primary tumors. The group under analysis consisted of the 99 remaining patients affected by stage III and IV laryngeal and/or hypopharyngeal cancers that had not received previous treatments. The main outcomes to analyze were overall survival, specific overall survival and relative risk. Overall survival at 2.5 years was 68.1% (95% CI, 57.7-78.5). Specific overall survival at 2.5 years was 74.8% (95% CI, 64.9-84.6). In the multivariate analysis, tumor staging, neoadjuvant chemotherapy response and comorbidity (RR = 1.55 and 1.44 for overall and specific overall survival, respectively) present themselves as three prognostic factors independent of overall and specific overall survival. The role of comorbidity as an independent prognostic factor in patients affected by laryngeal and/or hypopharyngeal cancer treated with chemo-radiotherapy should be taken into account in the tailoring of treatments and the improvement of therapeutic results.

Prognostic Factors in Patients With Stemi Undergoing Primary PCI in the Clopidogrel Era: Role of Dual Antiplatelet Therapy at Admission and the Smoking Paradox on Long-Term Outcome.

PubMed

Ciccarelli, Giovanni; Barbato, Emanuele; Golino, Marco; Cimmino, Giovanni; Bartunek, Jozef; Di Serafino, Luigi; Di Girolamo, Domenico; De Bruyne, Bernard; Wijns, William; Golino, Paolo

2017-02-01

Several clinical and laboratory variables have an impact on the prognosis of STEMI patients undergoing PPCI; however, little is known about the role of ongoing DAPT at the time of the event and the smoking status as prognostic factors affecting the outcome of these patients. Seven-hundred and thirteen consecutive STEMI patients undergoing PPCI, admitted to the S. Anna and S. Sebastiano Hospital (Caserta, Italy) and to the OLV Clinic (Aalst, Belgium), between March 2009 and December 2011, were retrospectively enrolled. Rescue PCI was the only exclusion criterion. Primary end-point was the combination of death for all causes, re-infarction, stroke, and target lesion revascularization (TLR). Patients already on DAPT at admission (26.4%) showed a significant increase in the event rate at univariate analysis (HR 2.34, CI 1.62-3.75, P < 0.05), while current smokers (56.5%) had a lower event rate, as compared to non-smokers (HR 0.67, CI 0.46-0.96, P < 0.05). In smoking patients already on DAPT at admission, a lower event rate was observed than in non-smoking patients on DAPT. Although, patients already on DAPT had a higher-risk profile (renal impairment, ongoing statin treatment, ST resolution <50%, and Killip class >1 were more frequently present than in patients not on DAPT), Cox regression analysis confirmed that both DAPT (HR 1.74, 95%CI 1.20-2.53, P < 0.01) and smoking status (HR 0.69, 95%CI 0.48-1.00, P < 0.05) retained their statistical significance, as they and were significantly associated with a worse and a better outcome, respectively, underlying their role as independent prognostic factors. Not being a current smoker and ongoing DAPT at admission, in patients with STEMI undergoing PPCI, represent independent negative prognostic value. © 2016, Wiley Periodicals, Inc.

Distributed Prognostics based on Structural Model Decomposition

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

2014-01-01

Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

PubMed

Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

2018-05-29

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

Systematic Review of Bilateral Independent Periodic Discharges Written for Topical Journal Subject on Periodic Discharges.

PubMed

Freund, Brin; Kaplan, Peter W

2018-05-01

Periodic discharges (PDs) are EEG patterns that may have important clinical and prognostic implications. There are different subtypes of PDs that are delineated by their location, and each type may have different meaning regarding prognosis and clinical associations. Bilateral independent PDs are a subtype that have not been analyzed recently and remain poorly understood. In this article, we systematically review the literature to better describe bilateral independent PDs regarding underlying neuropathology, neuroimaging, and neuroexamination correlates, seizure incidence, EEG characteristics, their comparison with other PD subtypes, and prognostic meaning.

Traumatic axonal injury: the prognostic value of lesion load in corpus callosum, brain stem, and thalamus in different magnetic resonance imaging sequences.

PubMed

Moen, Kent G; Brezova, Veronika; Skandsen, Toril; Håberg, Asta K; Folvik, Mari; Vik, Anne

2014-09-01

The aim of this study was to explore the prognostic value of visible traumatic axonal injury (TAI) loads in different MRI sequences from the early phase after adjusting for established prognostic factors. Likewise, we sought to explore the prognostic role of early apparent diffusion coefficient (ADC) values in normal-appearing corpus callosum. In this prospective study, 128 patients (mean age, 33.9 years; range, 11-69) with moderate (n = 64) and severe traumatic brain injury (TBI) were examined with MRI at a median of 8 days (range, 0-28) postinjury. TAI lesions in fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2*-weighted gradient echo (T2*GRE) sequences were counted and FLAIR lesion volumes estimated. In patients and 47 healthy controls, mean ADC values were computed in 10 regions of interests in the normal-appearing corpus callosum. Outcome measure was the Glasgow Outcome Scale-Extended (GOS-E) at 12 months. In patients with severe TBI, number of DWI lesions and volume of FLAIR lesions in the corpus callosum, brain stem, and thalamus predicted outcome in analyses with adjustment for age, Glasgow Coma Scale score, and pupillary dilation (odds ratio, 1.3-6.9; p = <0.001-0.017). The addition of Rotterdam CT score and DWI lesions in the corpus callosum yielded the highest R2 (0.24), compared to all other MRI variables, including brain stem lesions. For patients with moderate TBI only the number of cortical contusions (p = 0.089) and Rotterdam CT score (p = 0.065) tended to predict outcome. Numbers of T2*GRE lesions did not affect outcome. Mean ADC values in the normal-appearing corpus callosum did not differ from controls. In conclusion, the loads of visible TAI lesions in the corpus callosum, brain stem, and thalamus in DWI and FLAIR were independent prognostic factors in patients with severe TBI. DWI lesions in the corpus callosum were the most important predictive MRI variable. Interestingly, number of cortical contusions in MRI and CT findings seemed more important for patients with moderate TBI.

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

PubMed

Dakwar, Elias; Nunes, Edward V; Bisaga, Adam; Carpenter, Kenneth C; Mariani, John P; Sullivan, Maria A; Raby, Wilfrid N; Levin, Frances R

2011-01-01

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001), while cocaine dependence was highly associated with substance-induced depression (p< .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p< .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p< .05). Cannabis dependence (p< .001) and female gender (p< .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process. © American Academy of Addiction Psychiatry.

Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

PubMed

Cates, Justin Mm; Dupont, William D

2017-01-01

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis.

PubMed

Choi, Ivy Y; Karpus, Olga N; Turner, Jason D; Hardie, Debbie; Marshall, Jennifer L; de Hair, Maria J H; Maijer, Karen I; Tak, Paul P; Raza, Karim; Hamann, Jörg; Buckley, Christopher D; Gerlag, Danielle M; Filer, Andrew

2017-01-01

Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers. We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables. Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.

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

PubMed Central

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

2013-01-01

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

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

PubMed Central

Pang, Qing; Zhang, Ling-Qiang; Wang, Rui-Tao; Bi, Jian-Bin; Zhang, Jing-Yao; Qu, Kai; Liu, Su-Shun; Song, Si-Dong; Xu, Xin-Sen; Wang, Zhi-Xin; Liu, Chang

2015-01-01

AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients. PMID:26074706

Independent surgical validation of the new prostate cancer grade-grouping system.

PubMed

Spratt, Daniel E; Cole, Adam I; Palapattu, Ganesh S; Weizer, Alon Z; Jackson, William C; Montgomery, Jeffrey S; Dess, Robert T; Zhao, Shuang G; Lee, Jae Y; Wu, Angela; Kunju, Lakshmi P; Talmich, Emily; Miller, David C; Hollenbeck, Brent K; Tomlins, Scott A; Feng, Felix Y; Mehra, Rohit; Morgan, Todd M

2016-11-01

To report the independent prognostic impact of the new prostate cancer grade-grouping system in a large external validation cohort of patients treated with radical prostatectomy (RP). Between 1994 and 2013, 3 694 consecutive men were treated with RP at a single institution. To investigate the performance of and validate the grade-grouping system, biochemical recurrence-free survival (bRFS) rates were assessed using Kaplan-Meier tests, Cox-regression modelling, and discriminatory comparison analyses. Separate analyses were performed based on biopsy and RP grade. The median follow-up was 52.7 months. The 5-year actuarial bRFS for biopsy grade groups 1-5 were 94.2%, 89.2%, 73.1%, 63.1%, and 54.7%, respectively (P < 0.001). Similarly, the 5-year actuarial bRFS based on RP grade groups was 96.1%, 93.0%, 74.0%, 64.4%, and 49.9% for grade groups 1-5, respectively (P < 0.001). The adjusted hazard ratios for bRFS relative to biopsy grade group 1 were 1.98, 4.20, 5.57, and 9.32 for groups 2, 3, 4, and 5, respectively (P < 0.001), and for RP grade groups were 2.09, 5.27, 5.86, and 10.42 (P < 0.001). The five-grade-group system had a higher prognostic discrimination compared with the commonly used three-tier system (Gleason score 6 vs 7 vs 8-10). In an independent surgical cohort, we have validated the prognostic benefit of the new prostate cancer grade-grouping system for bRFS, and shown that the benefit is maintained after adjusting for important clinicopathological variables. The greater predictive accuracy of the new system will improve risk stratification in the clinical setting and aid in patient counselling. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Does self-regulation and autonomic regulation have an influence on survival in breast and colon carcinoma patients? results of a prospective outcome study

PubMed Central

2011-01-01

Background Cancer Related Fatigue (CRF) and circadian rhythm have a great impact on the quality of life (HRQL) of patients with breast (BC) and colon cancer (CRC). Other patient related outcomes in oncology are measured by new instruments focusing on adaptive characteristics such as sense of coherence or self-regulation, which could be more appropriate as a prognostic tool than classical HRQL. The aim of this study was to assess the association of autonomic regulation (aR) and self-regulation (SR) with survival. Methods 146 cancer patients and 120 healthy controls took part in an initial evaluation in 2000/2001. At a median follow up of 5.9 years later, 62 of 95 BC, 17 of 51 CRC patients, and 85 of 117 healthy controls took part in the follow-up study. 41 participants had died. For the follow-up evaluation, participants were requested to complete the standardized aR and SR questionnaires. Results On average, cancer patients had survived for 10.1 years with the disease. Using a Cox proportional hazard regression with stepwise variables such as age, diagnosis group, Charlson co-morbidity index, body mass index (BMI)) aR and SR. SR were identified as independent parameters with potential prognostic relevance on survival While aR did not significantly influence survival, SR showed a positive and independent impact on survival (OR = 0.589; 95%-CI: 0.354 - 0.979). This positive effect persisted significantly in the sensitivity analysis of the subgroup of tumour patients and in the subscale 'Achieve satisfaction and well-being' and by tendency in the UICC stages nested for the different diagnoses groups. Conclusions Self-regulation might be an independent prognostic factor for the survival of breast and colon carcinoma patients and merits further prospective studies. PMID:21961625

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.

PubMed

Yoshimoto, Toshiaki; Morine, Yuji; Imura, Satoru; Ikemoto, Tetsuya; Iwahashi, Syuichi; Saito, Y U; Yamada, Sinichiro; Ishikawa, Daichi; Teraoku, Hiroki; Yoshikawa, Masato; Higashijima, Jun; Takasu, Chie; Shimada, Mitsuo

2017-01-01

Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ≥30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ≥30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

PubMed

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

2017-09-01

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

Clinical Prediction Models for Patients With Nontraumatic Knee Pain in Primary Care: A Systematic Review and Internal Validation Study.

PubMed

Panken, Guus; Verhagen, Arianne P; Terwee, Caroline B; Heymans, Martijn W

2017-08-01

Study Design Systematic review and validation study. Background Many prognostic models of knee pain outcomes have been developed for use in primary care. Variability among published studies with regard to patient population, outcome measures, and relevant prognostic factors hampers the generalizability and implementation of these models. Objectives To summarize existing prognostic models in patients with knee pain in a primary care setting and to develop and internally validate new summary prognostic models. Methods After a sensitive search strategy, 2 reviewers independently selected prognostic models for patients with nontraumatic knee pain and assessed the methodological quality of the included studies. All predictors of the included studies were evaluated, summarized, and classified. The predictors assessed in multiple studies of sufficient quality are presented in this review. Using data from the Musculoskeletal System Study (BAS) cohort of patients with a new episode of knee pain, recruited consecutively by Dutch general medical practitioners (n = 372), we used predictors with a strong level of evidence to develop new prognostic models for each outcome measure and internally validated these models. Results Sixteen studies were eligible for inclusion. We considered 11 studies to be of sufficient quality. None of these studies validated their models. Five predictors with strong evidence were related to function and 6 to recovery, and were used to compose 2 prognostic models for patients with knee pain at 1 year. Running these new models in another data set showed explained variances (R 2 ) of 0.36 (function) and 0.33 (recovery). The area under the curve of the recovery model was 0.79. After internal validation, the adjusted R 2 values of the models were 0.30 (function) and 0.20 (recovery), and the area under the curve was 0.73. Conclusion We developed 2 valid prognostic models for function and recovery for patients with nontraumatic knee pain, based on predictors with strong evidence. A longer duration of complaints predicted poorer function but did not adequately predict chance of recovery. Level of Evidence Prognosis, levels 1a and 1b. J Orthop Sports Phys Ther 2017;47(8):518-529. Epub 16 Jun 2017. doi:10.2519/jospt.2017.7142.

A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

PubMed Central

2018-01-01

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients' survival independent of clinicopathological variables. Five networks were significantly associated with patients' survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients' survival in two test sets and training set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients' prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction. PMID:29581968

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

PubMed

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

2015-12-01

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

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

PubMed Central

Garg, Abhishek D.; De Ruysscher, Dirk; Agostinis, Patrizia

2016-01-01

ABSTRACT The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale meta-analysis involving 3,983 patients (‘discovery’ dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in ‘validation’ datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICD-derived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) ‘attracted’ highly co-expressing sets of genes or convergent-metagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an ‘attractor’ for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a platform for discovery of novel prognostic metagenes. PMID:27057433

Heterogeneity of Prognostic Studies of 24-Hour Blood Pressure Variability: Systematic Review and Meta-Analysis

PubMed Central

Taylor, Kathryn S.; Heneghan, Carl J.; Stevens, Richard J.; Adams, Emily C.; Nunan, David; Ward, Alison

2015-01-01

In addition to mean blood pressure, blood pressure variability is hypothesized to have important prognostic value in evaluating cardiovascular risk. We aimed to assess the prognostic value of blood pressure variability within 24 hours. Using MEDLINE, EMBASE and Cochrane Library to April 2013, we conducted a systematic review of prospective studies of adults, with at least one year follow-up and any day, night or 24-hour blood pressure variability measure as a predictor of one or more of the following outcomes: all-cause mortality, cardiovascular mortality, all cardiovascular events, stroke and coronary heart disease. We examined how blood pressure variability is defined and how its prognostic use is reported. We analysed relative risks adjusted for covariates including the appropriate mean blood pressure and considered the potential for meta-analysis. Our analysis of methods included 24 studies and analysis of predictions included 16 studies. There were 36 different measures of blood pressure variability and 13 definitions of night- and day-time periods. Median follow-up was 5.5 years (interquartile range 4.2–7.0). Comparing measures of dispersion, coefficient of variation was less well researched than standard deviation. Night dipping based on percentage change was the most researched measure and the only measure for which data could be meaningfully pooled. Night dipping or lower night-time blood pressure was associated with lower risk of cardiovascular events. The interpretation and use in clinical practice of 24-hour blood pressure variability, as an important prognostic indicator of cardiovascular events, is hampered by insufficient evidence and divergent methodologies. We recommend greater standardisation of methods. PMID:25984791

Influence of marital status on the survival of adults with extrahepatic/intrahepatic cholangiocarcinoma.

PubMed

Chen, Zhiqiang; Pu, Liyong; Gao, Wen; Zhang, Long; Han, Guoyong; Zhu, Qin; Li, Xiangcheng; Wu, Jindao; Wang, Xuehao

2017-04-25

Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others.

Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.

PubMed

Sáez, Carmen; Martínez-Brocca, M Asunción; Castilla, Carolina; Soto, Alfonso; Navarro, Elena; Tortolero, María; Pintor-Toro, José A; Japón, Miguel A

2006-04-01

Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. The study was conducted at a tertiary university hospital. Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied. The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05). Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.

Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer.

PubMed

de Oca, Javier; Azuara, Daniel; Sanchez-Santos, Raquel; Navarro, Matilde; Capella, Gabriel; Moreno, Victor; Sola, Anna; Hotter, Georgina; Biondo, Sebastiano; Osorio, Alfonso; Martí-Ragué, Joan; Rafecas, Antoni

2008-01-01

The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy. We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] >5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed. Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p=0.001), showing a statistically significant correlation (r=0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR=3.53 [1.13-10.90], p=0.02), age (OR=1.09 [1.01-1.18], p=0.03), Dukes stage (OR=1.93 [1.01-3.70]), caspase-3 activity in normal mucosa (OR=1.02 [1.01-1.04], p=0.017) and caspase-3 activity in tumour (OR=1.02 [1.01-1.03], p=0.013). Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.

Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

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

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Kim, Dae Yong, E-mail: radiopiakim@hanmail.net

2012-02-01

Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints weremore » disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.« less

[Prognostic value of three different staging schemes based on pN, MLR and LODDS in patients with T3 esophageal cancer].

PubMed

Wang, L; Cai, L; Chen, Q; Jiang, Y H

2017-10-23

Objective: To evaluate the prognostic value of three different staging schemes based on positive lymph nodes (pN), metastatic lymph nodes ratio (MLR) and log odds of positive lymph nodes (LODDS) in patients with T3 esophageal cancer. Methods: From 2007 to 2014, clinicopathological characteristics of 905 patients who were pathologically diagnosed as T3 esophageal cancer and underwent radical esophagectomy in Zhejiang Cancer Hospital were retrospectively analyzed. Kaplan-Meier curves and Multivariate Cox proportional hazards models were used to evaluate the independent prognostic factors. The values of three lymph node staging schemes for predicting 5-year survival were analyzed by using receiver operating characteristic (ROC) curves. Results: The 1-, 3- and 5-year overall survival rates of patients with T3 esophageal cancer were 80.9%, 50.0% and 38.4%, respectively. Multivariate analysis showed that MLR stage, LODDS stage and differentiation were independent prognostic survival factors ( P <0.05 for all). ROC curves showed that the area under the curve of pN stage, MLR stage, LODDS stage was 0.607, 0.613 and 0.618, respectively. However, the differences were not statistically significant ( P >0.05). Conclusions: LODDS is an independent prognostic factor for patients with T3 esophageal cancer. The value of LODDS staging system may be superior to pN staging system for evaluating the prognosis of these patients.

Adjusted Analyses in Studies Addressing Therapy and Harm: Users' Guides to the Medical Literature.

PubMed

Agoritsas, Thomas; Merglen, Arnaud; Shah, Nilay D; O'Donnell, Martin; Guyatt, Gordon H

2017-02-21

Observational studies almost always have bias because prognostic factors are unequally distributed between patients exposed or not exposed to an intervention. The standard approach to dealing with this problem is adjusted or stratified analysis. Its principle is to use measurement of risk factors to create prognostically homogeneous groups and to combine effect estimates across groups.The purpose of this Users' Guide is to introduce readers to fundamental concepts underlying adjustment as a way of dealing with prognostic imbalance and to the basic principles and relative trustworthiness of various adjustment strategies.One alternative to the standard approach is propensity analysis, in which groups are matched according to the likelihood of membership in exposed or unexposed groups. Propensity methods can deal with multiple prognostic factors, even if there are relatively few patients having outcome events. However, propensity methods do not address other limitations of traditional adjustment: investigators may not have measured all relevant prognostic factors (or not accurately), and unknown factors may bias the results.A second approach, instrumental variable analysis, relies on identifying a variable associated with the likelihood of receiving the intervention but not associated with any prognostic factor or with the outcome (other than through the intervention); this could mimic randomization. However, as with assumptions of other adjustment approaches, it is never certain if an instrumental variable analysis eliminates bias.Although all these approaches can reduce the risk of bias in observational studies, none replace the balance of both known and unknown prognostic factors offered by randomization.

Profiles of neurological outcome prediction among intensivists.

PubMed

Racine, Eric; Dion, Marie-Josée; Wijman, Christine A C; Illes, Judy; Lansberg, Maarten G

2009-12-01

Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability. Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient's specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians' demographic and practice characteristics. Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good-poor) and a confidence dimension (certain-uncertain). More experienced physicians tended to be more pessimistic about the patient's functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good-poor) and a "style" dimension (objective-subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts. Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians' age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.

Gastric cancer, nutritional status, and outcome.

PubMed

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

2017-01-01

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

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

Hu, Zhi; Huang, Ge; Sadanandam, Anguraj

Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growthmore » and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of HJURP in human breast cancer cells using shRNA reduced the sensitivity to radiation treatment. HJURP mRNA levels were significantly correlated with CENPA mRNA levels. Conclusions: HJURP mRNA level is a prognostic factor for disease-free and overall survival in patients with breast cancer and is a predictive biomarker for sensitivity to radiotherapy.« less

Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients

PubMed Central

Liu, Wen-Yue; Lin, Shi-Gang; Zhu, Gui-Qi; Poucke, Sven Van; Braddock, Martin; Zhang, Zhongheng; Mao, Zhi; Shen, Fei-Xia

2016-01-01

Background and Aims Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Methods Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. Results 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813–0.834, P< 0.001) and 0.738 (95% CI: 0.725–0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). Conclusions We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group. PMID:27824941

[PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].

PubMed

Tsvetkov, Ch; Gorchev, G; Tomov, S; Nikolova, M; Genchev, G

2016-01-01

The aim of the research was to evaluate and analyse prognosis and prognostic factors in patients with squamous cell vulvar carcinoma after primary surgery with individual approach applied during the course of treatment. In the period between January 2000 and July 2010, 113 patients with squamous cell carcinoma of the vulva were diagnosed and operated on at Gynecologic Oncology Clinic of Medical University, Pleven. All the patients were monitored at the same clinic. Individual approach was applied to each patient and whenever it was possible, more conservative operative techniques were applied. The probable clinicopathological characteristics influencing the overall survival and recurrence free survival were analyzed. Univariate statistical analysis and Cox regression analysis were made in order to evaluate the characteristics, which were statistically significant for overall survival and survival without recurrence. A multivariate logistic regression analysis (Forward Wald procedure) was applied to evaluate the combined influence of the significant factors. While performing the multivariate analysis, the synergic effect of the independent prognostic factors of both kinds of survivals was also evaluated. Approaching individually each patient, we applied the following operative techniques: 1. Deep total radical vulvectomy with separate incisions for lymph dissection (LD) or without dissection--68 (60.18 %) patients. 2. En-bloc vulvectomy with bilateral LD without vulva reconstruction--10 (8.85%) 3. Modified radical vulvactomy (hemivulvectomy, patial vulvactomy)--25 (22.02%). 4. wide-local excision--3 (2.65%). 5. Simple (total /partial) vulvectomy--5 (4.43%) patients. 6. En-bloc resection with reconstruction--2 (1.77%) After a thorough analysis of the overall survival and recurrence free survival, we made the conclusion that the relapse occurrence and clinical stage of FIGO were independent prognostic factors for overall survival and the independent prognostic factors for recurrence free survival were: metastatic inguinal nodes (unilateral or bilateral), tumor size (above or below 3 cm) and lymphovascular space invasion. On the basis of these results we created two prognostic models: 1. A prognostic model of overall survival 2. A prognostic model for survival without recurrence. Following the surgical staging of the disease, were able to gather and analyse important clinicopathological indexes, which gave us the opportunity to form prognostic groups for overall survival and recurrence-free survival.

Preoperative tumor size at MRI predicts deep myometrial invasion, lymph node metastases, and patient outcome in endometrial carcinomas.

PubMed

Ytre-Hauge, Sigmund; Husby, Jenny A; Magnussen, Inger J; Werner, Henrica M J; Salvesen, Øyvind O; Bjørge, Line; Trovik, Jone; Stefansson, Ingunn M; Salvesen, Helga B; Haldorsen, Ingfrid S

2015-03-01

The aim of this study was to explore the relation between preoperative tumor size based on magnetic resonance imaging (MRI) and the surgical pathologic staging parameters (deep myometrial invasion, cervical stroma invasion, and metastatic lymph nodes) and to assess the prognostic impact of tumor size in endometrial carcinomas. Interobserver variability for the different tumor size measurements was also assessed. Preoperative pelvic MRI of 212 patients with histologically confirmed endometrial carcinomas was read independently by 3 radiologists. Maximum tumor diameters were measured in 3 orthogonal planes (anteroposterior, transverse, and craniocaudal planes [CC]), and tumor volumes were estimated. Tumor size was analyzed in relation to surgical staging results and patient survival. The multivariate analyses were adjusted for preoperative risk status based on endometrial biopsy. Intraclass correlation coefficients and receiver operating characteristics curves for the different tumor measurements were also calculated. Anteroposterior tumor diameter independently predicted deep myometrial invasion (P < 0.001), whereas CC tumor diameter tended to independently predict lymph node metastases (P = 0.06). Based on receiver operating characteristic curves, the following tumor size cutoff values were identified: anteroposterior diameter greater than 2 cm predicted deep myometrial invasion (unadjusted odds ratio [OR], 12.4; P < 0.001; adjusted OR, 6.7; P < 0.001) and CC diameter greater than 4 cm predicted lymph node metastases (unadjusted OR, 6.2; P < 0.001; adjusted OR, 4.9; P = 0.009). Large tumor size was associated with reduced progression/recurrence-free survival (P ≤ 0.005 for all size parameters), and CC diameter had an independent impact on survival (adjusted hazards ratio, 1.04; P = 0.009). The interobserver variability for the different size measurements was very low (intraclass correlation coefficient, 0.78-0.85). Anteroposterior tumor diameter greater than 2 cm predicts deep myometrial invasion, and CC tumor diameter greater than 4 cm predicts lymph node metastases. Tumor size is a strong prognostic factor in endometrial carcinomas. Preoperative tumor measurements based on MRI may potentially improve preoperative risk stratification models and thus enable better tailored surgical treatment in endometrial cancer.

Heart rate variability measured early in patients with evolving acute coronary syndrome and 1-year outcomes of rehospitalization and mortality.

PubMed

Harris, Patricia R E; Stein, Phyllis K; Fung, Gordon L; Drew, Barbara J

2014-01-01

This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS). Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established. Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with ≥18 hours of sinus rhythm were selected for HRV analysis (number [N] =193). Time domain, frequency domain, and nonlinear HRV were examined. Survival analysis was performed. During the 1-year follow-up, 94 patients were event-free, 82 were readmitted, and 17 died. HRV was altered in relation to outcomes. Predictors of rehospitalization included increased normalized high frequency power, decreased normalized low frequency power, and decreased low/high frequency ratio. Normalized high frequency >42 ms(2) predicted rehospitalization while controlling for clinical variables (hazard ratio [HR] =2.3; 95% confidence interval [CI] =1.4-3.8, P=0.001). Variables significantly associated with death included natural logs of total power and ultra low frequency power. A model with ultra low frequency power <8 ms(2) (HR =3.8; 95% CI =1.5-10.1; P=0.007) and troponin >0.3 ng/mL (HR =4.0; 95% CI =1.3-12.1; P=0.016) revealed that each contributed independently in predicting mortality. Nonlinear HRV variables were significant predictors of both outcomes. HRV measured close to the ACS onset may assist in risk stratification. HRV cut-points may provide additional, incremental prognostic information to established assessment guidelines, and may be worthy of additional study.

A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic Nutritional Index.

PubMed

Hayıroğlu, Mert İlker; Keskin, Muhammed; Keskin, Taha; Uzun, Ahmet Okan; Altay, Servet; Kaya, Adnan; Öz, Ahmet; Çinier, Göksel; Güvenç, Tolga Sinan; Kozan, Ömer

2018-05-01

The prognostic impact of nutritional status in patients with pulmonary embolism (PE) is poorly understood. A well-accepted nutritional status parameter, prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and gastrointestinal surgery, was introduced to patients with PE. Our aim was to evaluate the predictive value of PNI in outcomes of patients with PE. We evaluated the in-hospital and long-term (53.8 ± 5.4 months) prognostic impact of PNI on 251 patients with PE. During a median follow-up of 53.8 ± 5.4 months, 27 (11.6%) patients died in hospital course and 31 (13.4%) died in out-of-hospital course. The patients with lower PNI had significantly higher in-hospital and long-term mortality. The Cox proportional hazard analyses showed that PNI was associated with an increased risk of all-cause death for both unadjusted model and adjusted for all covariates. Our study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients with PE.

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

Koh, Kyoung Hwan; Cho, Eun Yoon; Kim, Dong Wook; Seo, Sung Wook

2009-11-01

Many studies have described the diversity of synovial sarcoma in terms of its biological characteristics and clinical features. Moreover, much effort has been expended on the identification of prognostic factors because of unpredictable behaviors of synovial sarcomas. However, with the exception of tumor size, published results have been inconsistent. We attempted to identify independent risk factors using survival analysis. Forty-one consecutive patients with synovial sarcoma were prospectively followed from January 1997 to March 2008. Overall and progression-free survival for age, sex, tumor size, tumor location, metastasis at presentation, histologic subtype, chemotherapy, radiation therapy, and resection margin were analyzed, and standard multivariate Cox proportional hazard regression analysis was used to evaluate potential prognostic factors. Tumor size (>5 cm), nonlimb-based tumors, metastasis at presentation, and a monophasic subtype were associated with poorer overall survival. Multivariate analysis showed metastasis at presentation and monophasic tumor subtype affected overall survival. For the progression-free survival, monophasic subtype was found to be only 1 prognostic factor. The study confirmed that histologic subtype is the single most important independent prognostic factors of synovial sarcoma regardless of tumor stage.

A consensus prognostic gene expression classifier for ER positive breast cancer

PubMed Central

Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

2006-01-01

Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH analysis.

PubMed

Aust, D E; Muders, M; Köhler, A; Schmidt, M; Diebold, J; Müller, C; Löhrs, U; Waldman, F M; Baretton, G B

2004-08-01

Amplification of 20q13 is a frequent chromosomal alteration in solid tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or Aurora2). Amplifications on 20q13 have been identified as an independent prognostic marker indicating worse survival in breast and ovarian cancer. However, little is known about the prognostic significance of 20q13 gains in sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains in sporadic colorectal cancers with other known prognostic factors, tumor progression, and overall survival. Nuclei were extracted from 146 paraffin-embedded colorectal cancers of different UICC stages and used for fluorescence in situ hybridization (FISH) with a directly labeled probe for 20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was considered gained when > or =40% of the nuclei showed 3 or more FISH signals. Statistical correlations were tested with log-rank tests and Kaplan-Meier survival curves. Signal numbers for 20q13.2 were gained in 78 cases (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the gain of 20q13.2 was an independent prognostic marker for overall survival (P=0.006) as well as tumor progression (P=0.012) in univariate and multivariate analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was a significant association between 20q13.2 gains and tumor location in the left-sided colon and an inverse correlation between histologic grade and 20q13.2 gains. These data indicate that gains on 20q13.2 correlate with faster tumor progression and worse patient survival independent from tumor size and lymph node involvement. Therefore, alterations on 20q13 are an important biological event in colorectal tumor progression with independent prognostic relevance.

Elevated C-reactive protein and hypoalbuminemia measured before resection of colorectal liver metastases predict postoperative survival.

PubMed

Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

2010-01-01

Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score measured before resection of colorectal liver metastasis (CRLM), can predict postoperative survival. Sixty-three consecutive patients who underwent curative resection for CRLM were investigated. GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminemia (<35 g/l) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. Significant factors concerning survival were the number of liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph node metastases around the primary cancer (p = 0.0087). Multivariate analysis showed the two independent prognostic variables: liver metastases > or =3 (relative risk 2.83) and GPS1/2 (relative risk 3.07). GPS measured before operation and the number of liver metastases may be used as novel predictors of postoperative outcomes in patients who underwent curative resection for CRLM. Copyright 2010 S. Karger AG, Basel.

Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype

PubMed Central

Domingues, Patrícia Henriques; Sousa, Pablo; Otero, Álvaro; Gonçalves, Jesus Maria; Ruiz, Laura; de Oliveira, Catarina; Lopes, Maria Celeste; Orfao, Alberto; Tabernero, Maria Dolores

2014-01-01

Background Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. Methods Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. Results Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). Conclusions Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse. PMID:24536048

Prognostic Role of Multiple Lymphatic Basin Drainage in Sentinel Lymph Node-Negative Trunk Melanoma Patients: A Multicenter Study from the Italian Melanoma Intergroup.

PubMed

Ribero, Simone; Osella-Abate, Simona; Pasquali, Sandro; Rossi, Carlo Riccardo; Borgognoni, Lorenzo; Piazzalunga, Dario; Solari, Nicola; Schiavon, Mauro; Brandani, Paola; Ansaloni, Luca; Ponte, Erica; Silan, Francesco; Sommariva, Antonio; Bellucci, Francesco; Macripò, Giuseppe; Quaglino, Pietro

2016-05-01

Multiple lymphatic basin drainage (MLBD) is frequently observed in patients with trunk melanoma undergoing sentinel lymph node (SLN) biopsy. Conflicting data regarding the prognostic association of MLBD in SLN-negative patients have been reported. This study aimed to investigate the prognostic role of MLBD in patients with negative SLN biopsy. Retrospective data from 656 melanoma patients who underwent a SLN biopsy (1991-2012) at six Italian centers were gathered in a multicenter database. MLBD was defined as lymphoscintigraphic and intraoperative identification of an SLN in more than one nodal basin. Clinical and pathologic variables were recorded and analyzed for their impact on survival. SLN-negative patients with MLBD were at lower risk of melanoma recurrence [hazard ratio (HR) 0.73, P = 0.05) and melanoma-related death (HR 0.68, P = 0.001) independent of common staging features. Multivariable Cox analyses of disease-free interval (DFI) and disease-specific survival (DSS) showed that MLBD maintained a favorable role and ulceration an unfavorable role. Histologic regression was independently associated only with DFI. When survival was stratified according to presence of MLBD, histologic regression and Breslow thickness <2 mm were associated with improved DFI (5-year DFI: 96.9 vs. 66,1 %, respectively; HR 0.48, P < 0.001) and DSS (5-year DSS: 96.7 vs. 71.8 %, respectively; HR 0.52, P = 0.005) compared to patients without these three favorable parameters. Patients with negative SLN biopsy results have better prognosis when two or more lymphatic basins are identified and analyzed. Further research is required to investigate the mechanisms behind this evidence.

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

PubMed

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

2018-06-01

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

Prognostic capacity of a clinically indicated exercise test for cardiovascular mortality is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

PubMed

Minkkinen, Mikko; Nieminen, Tuomo; Verrier, Richard L; Leino, Johanna; Lehtimäki, Terho; Viik, Jari; Lehtinen, Rami; Nikus, Kjell; Kööbi, Tiit; Turjanmaa, Väinö; Kähönen, Mika

2015-09-01

Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information. A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method. During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 μV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 μV for T-wave alternans). The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans. © The European Society of Cardiology 2014.

Clinical Manifestations and Prognostic Factors of Pneumocystis jirovecii Pneumonia without HIV.

PubMed

Asai, Nobuhiro; Motojima, Shinji; Ohkuni, Yoshihiro; Matsunuma, Ryo; Iwasaki, Takuya; Nakashima, Kei; Sogawa, Keiji; Nakashita, Tamao; Kaneko, Norihiro

2017-01-01

Pneumocystis jirovecii pneumonia (PCP) can occur in HIV patients but also in those without HIV (non-HIV PCP) but with other causes of immunodeficiency including malignancy or rheumatic diseases. To evaluate the clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all patients diagnosed as having PCP without HIV at Kameda Medical Center, Chiba, Japan, from January 2005 until June 2012. For the purpose of examining a prognostic factor for non-HIV PCP with 30-day mortality, we compared the characteristics of patients, clinical symptoms, radiological images, Eastern Cooperative Oncology Group performance status (PS), and the time from the onset of respiratory symptoms to the start of therapy, in both survival and fatality groups. A total of 38 patients were eligible in this study. Twenty-five survived and 13 had died. The non-HIV PCP patients in the survivor group had a better PS and received anti-PCP therapy earlier than those in the nonsurvivor group. Rales upon auscultation and respiratory failure at initial visits were seen more frequently in the nonsurvivor group than in the survivor group. Lactate dehydrogenase and C-reactive protein values tended to be higher in the nonsurvivor group, but this was not statistically significant. Multivariate analyses using 5 variables showed that a poor PS of 2-4 was an independent risk factor for non-HIV PCP patients and resulted in death (odds ratio 15.24; 95% confidence interval 1.72-135.21). We suggest that poor PS is an independent risk factor in non-HIV PCP, and a patient's PS and disease activity may correlate with outcome. © 2017 S. Karger AG, Basel.

CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis.

PubMed

Rossi, Daniela; Volanti, Paolo; Brambilla, Liliana; Colletti, Tiziana; Spataro, Rossella; La Bella, Vincenzo

2018-03-01

Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF of ALS patients from a single tertiary Center and investigated their relationship with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%; Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were recruited. Demographic and clinical variables were recorded, and ΔFS was used to rate the disease progression. Controls were divided into two cohorts: (1) patients with non-inflammatory neurological diseases (CTL-1); (2) patients with acute/subacute inflammatory diseases and tumors, expected to lead to significant axonal and tissue damage (CTL-2). For each patient and control, CSF was taken at the time of the diagnostic work-up and stored following the published guidelines. CSF NF-L and pNF-H were assayed with commercially available ELISA-based methods. Standard curves (from independent ELISA kits) were highly reproducible for both NFs, with a coefficient of variation < 20%. We found that CSF NF-L and pNF-H levels in ALS were significantly increased when compared to CTL-1 (NF-L: ALS, 4.7 ng/ml vs CTL-1, 0.61 ng/ml, p < 0.001; pNF-H: ALS, 1.7 ng/ml vs CTL-1, 0.03 ng/ml, p < 0.0001), but not to CTL-2. Analysis of different clinical and prognostic variables disclosed meaningful correlations with both NF-L and pNF-H levels. Our results, from a relatively large ALS cohort, confirm that CSF NF-L and pNF-H represent valuable diagnostic and prognostic biomarkers in ALS.

Heart failure and anemia: Effects on prognostic variables.

PubMed

Cattadori, Gaia; Agostoni, Piergiuseppe; Corrà, Ugo; Sinagra, Gianfranco; Veglia, Fabrizio; Salvioni, Elisabetta; Bonomi, Alice; La Gioia, Rocco; Scardovi, Angela B; Ferraironi, Alessandro; Emdin, Michele; Metra, Marco; Di Lenarda, Andrea; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Caravita, Sergio; Magrì, Damiano; Lombardi, Carlo; Frigerio, Maria; Oliva, Fabrizio; Girola, Davide; Mezzani, Alessandro; Farina, Stefania; Mapelli, Massimo; Scrutinio, Domenico; Pacileo, Giuseppe; Apostolo, Anna; Iorio, AnnaMaria; Paolillo, Stefania; Filardi, Pasquale Perrone; Gargiulo, Paola; Bussotti, Maurizio; Marchese, Giovanni; Correale, Michele; Badagliacca, Roberto; Sciomer, Susanna; Palermo, Pietro; Contini, Mauro; Giannuzzi, Pantaleo; Battaia, Elisa; Cicoira, Mariantonietta; Clemenza, Francesco; Minà, Chiara; Binno, Simone; Passino, Claudio; Piepoli, Massimo F

2017-01-01

Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO 2 ), ventilatory efficiency (VE/VCO 2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO 2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO 2 slope was associated with poor prognosis only in patients with low and normal Hb. Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO 2 and LVEF, but not VE/VCO 2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

PubMed

Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Lee, Hyang Rae; Kim, Yire; Kim, Rock Bum; Lee, Soon Il; Lee, Gyeong-Won

2016-12-01

Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). Treatment-related mortality (21.7 vs. 5.0%, P  = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P  = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group ( P  < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non-sarcopenic group ( P  < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P  = 0.009; revised-IPI, 0.74, P  < 0.001; National Comprehensive Cancer Network-IPI, 0.77, P  = 0.062). Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

Comparison of prognostic and diagnostic approached to modeling evapotranspiration in the Nile river basin

USDA-ARS?s Scientific Manuscript database

Actual evapotranspiration (ET) can be estimated using both prognostic and diagnostic modeling approaches, providing independent yet complementary information for hydrologic applications. Both approaches have advantages and disadvantages. When provided with temporally continuous atmospheric forcing d...

Clinical Efficacy and Its Prognostic Factor of Percutaneous Endoscopic Lumbar Annuloplasty and Nucleoplasty for the Treatment of Patients with Discogenic Low Back Pain.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2017-09-01

The choice of appropriate treatment of discogenic low back pain (DLBP) frequently is difficult. This study sought to identify the clinical efficacy of percutaneous endoscopic lumbar annuloplasty and nucleoplasty (PELAN) to treat patients with DLBP and to investigate prognostic clinical or radiologic variables. Eighty-nine patients with a diagnosis of DLBP who underwent PELAN were included. Numeric Rating Scale (NRS) for back pain, Oswestry Disability Index % (ODI%), and modified Macnab criteria were measured at short-term (3-4 weeks) and long-term follow-up period (at least 12 months) to investigate clinical efficacy of PELAN. The subjects were defined as successful group in case of 50% or more reduction of NRS, 40% or more reduction of ODI%, and good or excellent response of Macnab criteria. Clinical and radiologic variables were compared between successful and unsuccessful outcomes group to determine prognostic variables. NRS and ODI% were significantly reduced at short- and long-term follow-up after PELAN. Sixty-two (69.7%) and 68 (76.4%) obtained successful NRS reduction and 59 (66.3%) and 68 (76.4%) accomplished successful ODI% reduction at short-term and long-term follow-up, respectively. Successful Mcnab response was found in 61% at short term and 65.2% at long term. Pain during waist flexion among clinical variables was significantly related to good clinical outcomes and Modic change among radiologic variables was significantly related to poor clinical outcomes. PELAN provided favorable outcomes in patients with DLBP who were refractory to conservative treatments. Flexion pain was good prognostic, and Modic change was a poor prognostic variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcranial Duplex Sonography Predicts Outcome following an Intracerebral Hemorrhage.

PubMed

Camps-Renom, P; Méndez, J; Granell, E; Casoni, F; Prats-Sánchez, L; Martínez-Domeño, A; Guisado-Alonso, D; Martí-Fàbregas, J; Delgado-Mederos, R

2017-08-01

Several radiologic features such as hematoma volume are related to poor outcome following an intracerebral hemorrhage and can be measured with transcranial duplex sonography. We sought to determine the prognostic value of transcranial duplex sonography in patients with intracerebral hemorrhage. We conducted a prospective study of patients diagnosed with spontaneous intracerebral hemorrhage. Transcranial duplex sonography examinations were performed within 2 hours of baseline CT, and we recorded the following variables: hematoma volume, midline shift, third ventricle and lateral ventricle diameters, and the pulsatility index in both MCAs. We correlated these data with the CT scans and assessed the prognostic value of the transcranial duplex sonography measurements. We assessed early neurologic deterioration during hospitalization and mortality at 1-month follow-up. We included 35 patients with a mean age of 72.2 ± 12.8 years. Median baseline hematoma volume was 9.85 mL (interquartile range, 2.74-68.29 mL). We found good agreement and excellent correlation between transcranial duplex sonography and CT when measuring hematoma volume ( r = 0.791; P < .001) and midline shift ( r = 0.827; P < .001). The logistic regression analysis with transcranial duplex sonography measurements showed that hematoma volume was an independent predictor of early neurologic deterioration (OR, 1.078; 95% CI, 1.023-1.135) and mortality (OR, 1.089; 95% CI, 1.020-1.160). A second regression analysis with CT variables also demonstrated that hematoma volume was associated with early neurologic deterioration and mortality. When we compared the rating operation curves of both models, their predictive power was similar. Transcranial duplex sonography showed an excellent correlation with CT in assessing hematoma volume and midline shift in patients with intracerebral hemorrhage. Hematoma volume measured with transcranial duplex sonography was an independent predictor of poor outcome. © 2017 by American Journal of Neuroradiology.

Anthropometric parameters of nutritional assessment as predictive factors of arteriovenous fistula malfunction in patients undergoing hemodialysis.

PubMed

Gagliardi, Gian Manlio; Mancuso, Domenico; Falbo, Enrica; Mollica, Francesco; Mollica, Agata; Barcellona, Elisabetta; Senatore, Massimo; Bonofiglio, Renzo

2012-01-01

To evaluate the role of body mass index (BMI), waist circumference (W-C) and waist/hip ratio (WHR) on arteriovenous fistula (AVF) dysfunction. We evaluated 84 HD patients with an average follow-up period of 31.3 ± 8.1 months, identifying 8 stenosis (STN) and 17 thrombosis (THR) cases. The association between paired variables was tested with Pearson's coefficient (r) and p-value, whereas the prognostic value on STN and THR was analysed using Cox's regression. The significant independent variables were indentified with an inverse step-wise approach defining the data as hazard ratio (HR). A double-event (Stenosis/Thrombosis) model, function of Body mass index and Waist/hip ratio was used. Arteriovenous fistula survival was assessed with the Kaplan-Meyer curve and the calculations were carried out with Graph-Pad. On univariate analysis, THR showed direct correlation with BMI (r=0.44, p<0.01), W-C (r=0.39, p<0.05) WHR (r=0.37, p<0.01), Hemoglobin (p<0.001), C-Reactive protein (p=0.01), Calcium/Phosforus product (p=0.03), Parathyroid hormone (p=0.03) and inverse with albumin (p<0.001) and systolic blood pressure (p=0.003). On multivariate analysis, BMI variations were not predictive of STN and THR, whereas each unitary WHR and W-C increase was predictive of an increase of risk of events (3.8% and 2.1% respectively). The prognostic power of W-C per STN (HR 1: 1.19; p<0.05) and THR (HR: 1.28; p<0.01) remained significant even after being adjusted to account for traditional risk factors. Abdominal obesity increases the risk of AVF dysfunction. The W-C and WHR parameters, not BMI, emerge as independent STN and THR predictors.

[Neutrophil to lymphocyte ratio in peripheral blood: a novel independent prognostic factor in patients with head and neck squamous cell carcinoma].

PubMed

Wu, F; Wu, L L; Zhu, L X

2017-01-23

Objective: To investigate whether neutrophil to lymphocyte ratio (NLR) in peripheral blood can be an independent prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Clinical data of 97 HNSCC patients who received surgical treatment in our department between January 2008 and January 2012 were analyzed retrospectively. The 97 patients were divided into low NLR group (NLR≤5, n =69) and high NLR group (NLR>5, n =28) according to the NLR in preoperative peripheral blood. The relationships of NLR and clinicopathological features were analyzed. Kaplan-Meier method was used for univariate survival analysis and Cox proportional hazard model for multivariate survival analysis. Results: The clinical stages were significantly different between high NLR group and low NLR group ( P <0.05), however, the age, gender, location, lymph node metastasis, smoking and alcohol of the two groups showed no significant differences ( P > 0.05 of all). Univariate survival analysis showed that smoking, lymph node metastasis, clinical stage and NLR value were risk factors for 3-year overall survival (OS) rate and relapse-free survival (RFS) rate of HNSCC patients ( P <0.05). The OS rate of high NLR and low NLR groups was 42.9% and 91.3%, and the RFS rate was 44.2% and 80.1%, respectively, with a statistically significant difference ( P <0.05 for both). Cox multivariate survival analysis showed that clinical stage and NLR were independent factors for prognostic evaluation of HNSCC patients ( P <0.05 for both). Conclusions: NLR level is significantly associated with clinical stage of HNSCC. High NLR is an independent prognostic rick factor and plays an important role in prognostic evaluation of HNSCC patients.

Tumor-infiltrating Neutrophils is Prognostic and Predictive for Postoperative Adjuvant Chemotherapy Benefit in Patients With Gastric Cancer.

PubMed

Zhang, Heng; Liu, Hao; Shen, Zhenbin; Lin, Chao; Wang, Xuefei; Qin, Jing; Qin, Xinyu; Xu, Jiejie; Sun, Yihong

2018-02-01

This study was aimed to investigate the prognostic value of tumor-infiltrating neutrophils (TINs) and to generate a predictive model to refine postoperative risk stratification system for patients with gastric cancer. TIN presents in various malignant tumors, but its clinical significance in gastric cancer remains obscure. The study enrolled 3 independent sets of patients with gastric cancer from 2 institutional medical centers of China. TIN was estimated by immunohistochemical staining of CD66b, and its relationship with clinicopathological features and clinical outcomes were evaluated. Prognostic accuracies were evaluated by C-index and Akaike information criterion. TINs in gastric cancer tissues ranged from 0 to 192 cells/high magnification filed (HPF), 0 to 117 cells/HPF, and 0 to 142 cells/HPF in the training, testing, and validation sets, respectively. TINs were negatively correlated with lymph node classification (P = 0.007, P = 0.041, and P = 0.032, respectively) and tumor stage (P = 0.019, P = 0.013, and P = 0.025, respectively) in the 3 sets. Moreover, multivariate analysis identified TINs and tumor node metastasis (TNM) stage as 2 independent prognostic factors for overall survival. Incorporation of TINs into well-established TNM system generated a predictive model that shows better predictive accuracy for overall survival. More importantly, patients with higher TINs were prone to overall survival benefit from postoperative adjuvant chemotherapy. These results were validated in the independent testing and validation sets. TIN in gastric cancer was identified as an independent prognostic factor, which could be incorporated into standard TNM staging system to refine risk stratification and predict for overall survival benefit from postoperative chemotherapy in patients with gastric cancer.

Prognostic Factors of Uterine Serous Carcinoma-A Multicenter Study.

PubMed

Zhong, Xiaozhu; Wang, Jianliu; Kaku, Tengen; Wang, Zhiqi; Li, Xiaoping; Wei, Lihui

2018-04-04

The prognostic factors of uterine serous carcinoma (USC) vary among studies, and there is no report of Chinese USC patients. The aim of this study was to investigate the clinicopathological characteristics and prognostic factors in Chinese patients with USC. Patients with USC from 13 authoritative university hospitals in China and treated between 2004 and 2014 were retrospectively reviewed. Three-year disease-free survival rate (DFSR), cumulative recurrence, and cumulative mortality were estimated by Kaplan-Meier analyses and log-rank tests. Multivariate Cox regression analysis was used to model the association of potential prognostic factors with clinical outcomes. Data of a total of 241 patients were reviewed. The median follow-up was 26 months (range, 1-128 months). Median age was 60 years (range, 39-84 years), and 58.0% had stages I-II disease. The 3-year DFSR and cumulative recurrence were 46.8% and 27.7%. Advanced stage (III and IV) (P = 0.004), myometrial invasion (P = 0.001), adnexal involvement (P < 0.001), lymph node metastasis (P = 0.025), and positive peritoneal cytology (P = 0.007) were independently associated with 3-year DFSR. Advanced stage (P = 0.017), myometrial invasion (P = 0.008), adnexal involvement (odds ratio, 2.987; P = 0.001), lymph node metastasis (P = 0.031), and positive peritoneal cytology (P = 0.001) were independently associated with the cumulative recurrence. Myometrial invasion (P = 0.004) and positive peritoneal cytology (P = 0.025) were independently associated with 3-year cumulative mortality. Peritoneal cytology and myometrial invasion could be independent prognostic factors for 3-year DFSR, cumulative recurrence, and cumulative mortality of patients with USC. Prospective studies are needed to confirm these results.

Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

PubMed

Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

2013-07-09

The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

The generic MESSy submodel TENDENCY (v1.0) for process-based analyses in Earth system models

NASA Astrophysics Data System (ADS)

Eichinger, R.; Jöckel, P.

2014-07-01

The tendencies of prognostic variables in Earth system models are usually only accessible, e.g. for output, as a sum over all physical, dynamical and chemical processes at the end of one time integration step. Information about the contribution of individual processes to the total tendency is lost, if no special precautions are implemented. The knowledge on individual contributions, however, can be of importance to track down specific mechanisms in the model system. We present the new MESSy (Modular Earth Submodel System) infrastructure submodel TENDENCY and use it exemplarily within the EMAC (ECHAM/MESSy Atmospheric Chemistry) model to trace process-based tendencies of prognostic variables. The main idea is the outsourcing of the tendency accounting for the state variables from the process operators (submodels) to the TENDENCY submodel itself. In this way, a record of the tendencies of all process-prognostic variable pairs can be stored. The selection of these pairs can be specified by the user, tailor-made for the desired application, in order to minimise memory requirements. Moreover, a standard interface allows the access to the individual process tendencies by other submodels, e.g. for on-line diagnostics or for additional parameterisations, which depend on individual process tendencies. An optional closure test assures the correct treatment of tendency accounting in all submodels and thus serves to reduce the model's susceptibility. TENDENCY is independent of the time integration scheme and therefore the concept is applicable to other model systems as well. Test simulations with TENDENCY show an increase of computing time for the EMAC model (in a setup without atmospheric chemistry) of 1.8 ± 1% due to the additional subroutine calls when using TENDENCY. Exemplary results reveal the dissolving mechanisms of the stratospheric tape recorder signal in height over time. The separation of the tendency of the specific humidity into the respective processes (large-scale clouds, convective clouds, large-scale advection, vertical diffusion and methane oxidation) show that the upward propagating water vapour signal dissolves mainly because of the chemical and the advective contribution. The TENDENCY submodel is part of version 2.42 or later of MESSy.

The generic MESSy submodel TENDENCY (v1.0) for process-based analyses in Earth System Models

NASA Astrophysics Data System (ADS)

Eichinger, R.; Jöckel, P.

2014-04-01

The tendencies of prognostic variables in Earth System Models are usually only accessible, e.g., for output, as sum over all physical, dynamical and chemical processes at the end of one time integration step. Information about the contribution of individual processes to the total tendency is lost, if no special precautions are implemented. The knowledge on individual contributions, however, can be of importance to track down specific mechanisms in the model system. We present the new MESSy (Modular Earth Submodel System) infrastructure submodel TENDENCY and use it exemplarily within the EMAC (ECHAM/MESSy Atmospheric Chemistry) model to trace process-based tendencies of prognostic variables. The main idea is the outsourcing of the tendency accounting for the state variables from the process operators (submodels) to the TENDENCY submodel itself. In this way, a record of the tendencies of all process-prognostic variable pairs can be stored. The selection of these pairs can be specified by the user, tailor-made for the desired application, in order to minimise memory requirements. Moreover a standard interface allows the access to the individual process tendencies by other submodels, e.g., for on-line diagnostics or for additional parameterisations, which depend on individual process tendencies. An optional closure test assures the correct treatment of tendency accounting in all submodels and thus serves to reduce the models susceptibility. TENDENCY is independent of the time integration scheme and therefore applicable to other model systems as well. Test simulations with TENDENCY show an increase of computing time for the EMAC model (in a setup without atmospheric chemistry) of 1.8 ± 1% due to the additional subroutine calls when using TENDENCY. Exemplary results reveal the dissolving mechanisms of the stratospheric tape recorder signal in height over time. The separation of the tendency of the specific humidity into the respective processes (large-scale clouds, convective clouds, large-scale advection, vertical diffusion and methane-oxidation) show that the upward propagating water vapour signal dissolves mainly because of the chemical and the advective contribution. The TENDENCY submodel is part of version 2.42 or later of MESSy.

Osmotic indices and kidney concentrating activity: population-based data on correlates and prognostic power.

PubMed

Cirillo, Massimo; Bilancio, Giancarlo; Lombardi, Cinzia; Cavallo, Pierpaolo; Terradura Vagnarelli, Oscar; Zanchetti, Alberto; Laurenzi, Martino

2018-02-01

Research data are limited on indices of osmotic equilibrium and of kidney concentrating activity (KCA). This study investigated correlates and prognostic power of these indices in a sample of the general population. Urine osmolality (U-osm), plasma osmolality (P-osm), plasma creatinine and other variables were measured by the Gubbio Study for the 1988-92 exam (baseline). Plasma creatinine and other variables were re-measured in the 2001-07 exam (follow-up). KCA was assessed as the U-osm/P-osm ratio and kidney function as estimated glomerular filtration rate (eGFR). Baseline data were complete in 4220 adults, of whom 852 died before follow-up and 2795 participated in the follow-up. At baseline, the following independent cross-sectional associations were identified: female sex and higher urine flow with lower values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); obesity with higher values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); older age and lower eGFR with lower U-osm, lower U-osm/P-osm ratio and higher P-osm (P < 0.05); hypertension and smoking with lower U-osm and lower U-osm/P-osm ratio (P < 0.05) but not with P-osm. From baseline to follow-up, the annualized rate was 1.26% for mortality and -0.74 ± 0.76 mL/min × 1.73 m2 for eGFR change. Mortality was independently predicted by baseline U-osm and baseline U-osm/P-osm ratio (hazard ratio for one higher standard deviation was ≤0.91, 95% confidence interval was ≤0.97, P < 0.01), but not by baseline P-osm. The eGFR change was not independently predicted by baseline values of U-osm, P-osm and U-osm/P-osm ratio (P ≥ 0.4). Sex, age, obesity, eGFR, urine flow, hypertension and smoking independently associated with U-osm and KCA. U-osm and KCA independently predicted mortality, but not kidney function change over time. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer

PubMed Central

Blok, Erik J.; van den Bulk, Jitske; Dekker-Ensink, N. Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.

2017-01-01

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression. PMID:28121628

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer.

PubMed

Blok, Erik J; van den Bulk, Jitske; Dekker-Ensink, N Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R; van de Velde, Cornelis J H; Kuppen, Peter J K

2017-02-28

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression.

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

PubMed Central

Li, Yong-Jiang; Yang, Xi; Zhang, Wen-Biao; Yi, Cheng; Wang, Feng; Li, Ping

2017-01-01

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. PMID:29033609

Cross-national validation of prognostic models predicting sickness absence and the added value of work environment variables.

PubMed

Roelen, Corné A M; Stapelfeldt, Christina M; Heymans, Martijn W; van Rhenen, Willem; Labriola, Merete; Nielsen, Claus V; Bültmann, Ute; Jensen, Chris

2015-06-01

To validate Dutch prognostic models including age, self-rated health and prior sickness absence (SA) for ability to predict high SA in Danish eldercare. The added value of work environment variables to the models' risk discrimination was also investigated. 2,562 municipal eldercare workers (95% women) participated in the Working in Eldercare Survey. Predictor variables were measured by questionnaire at baseline in 2005. Prognostic models were validated for predictions of high (≥30) SA days and high (≥3) SA episodes retrieved from employer records during 1-year follow-up. The accuracy of predictions was assessed by calibration graphs and the ability of the models to discriminate between high- and low-risk workers was investigated by ROC-analysis. The added value of work environment variables was measured with Integrated Discrimination Improvement (IDI). 1,930 workers had complete data for analysis. The models underestimated the risk of high SA in eldercare workers and the SA episodes model had to be re-calibrated to the Danish data. Discrimination was practically useful for the re-calibrated SA episodes model, but not the SA days model. Physical workload improved the SA days model (IDI = 0.40; 95% CI 0.19-0.60) and psychosocial work factors, particularly the quality of leadership (IDI = 0.70; 95% CI 053-0.86) improved the SA episodes model. The prognostic model predicting high SA days showed poor performance even after physical workload was added. The prognostic model predicting high SA episodes could be used to identify high-risk workers, especially when psychosocial work factors are added as predictor variables.

Investigating the relationship between predictability and imbalance in minimisation: a simulation study

PubMed Central

2013-01-01

Background The use of restricted randomisation methods such as minimisation is increasing. This paper investigates under what conditions it is preferable to use restricted randomisation in order to achieve balance between treatment groups at baseline with regard to important prognostic factors and whether trialists should be concerned that minimisation may be considered deterministic. Methods Using minimisation as the randomisation algorithm, treatment allocation was simulated for hypothetical patients entering a theoretical study having values for prognostic factors randomly assigned with a stipulated probability. The number of times the allocation could have been determined with certainty and the imbalances which might occur following randomisation using minimisation were examined. Results Overall treatment balance is relatively unaffected by reducing the probability of allocation to optimal treatment group (P) but within-variable balance can be affected by any P <1. This effect is magnified by increased numbers of prognostic variables, the number of categories within them and the prevalence of these categories within the study population. Conclusions In general, for smaller trials, probability of treatment allocation to the treatment group with fewer numbers requires a larger value P to keep treatment and variable groups balanced. For larger trials probability of allocation values from P = 0.5 to P = 0.8 can be used while still maintaining balance. For one prognostic variable there is no significant benefit in terms of predictability in reducing the value of P. However, for more than one prognostic variable, significant reduction in levels of predictability can be achieved with the appropriate choice of P for the given trial design. PMID:23537389

Investigating the relationship between predictability and imbalance in minimisation: a simulation study.

PubMed

McPherson, Gladys C; Campbell, Marion K; Elbourne, Diana R

2013-03-27

The use of restricted randomisation methods such as minimisation is increasing. This paper investigates under what conditions it is preferable to use restricted randomisation in order to achieve balance between treatment groups at baseline with regard to important prognostic factors and whether trialists should be concerned that minimisation may be considered deterministic. Using minimisation as the randomisation algorithm, treatment allocation was simulated for hypothetical patients entering a theoretical study having values for prognostic factors randomly assigned with a stipulated probability. The number of times the allocation could have been determined with certainty and the imbalances which might occur following randomisation using minimisation were examined. Overall treatment balance is relatively unaffected by reducing the probability of allocation to optimal treatment group (P) but within-variable balance can be affected by any P <1. This effect is magnified by increased numbers of prognostic variables, the number of categories within them and the prevalence of these categories within the study population. In general, for smaller trials, probability of treatment allocation to the treatment group with fewer numbers requires a larger value P to keep treatment and variable groups balanced. For larger trials probability of allocation values from P = 0.5 to P = 0.8 can be used while still maintaining balance. For one prognostic variable there is no significant benefit in terms of predictability in reducing the value of P. However, for more than one prognostic variable, significant reduction in levels of predictability can be achieved with the appropriate choice of P for the given trial design.

Impact of tumor grade on prognosis in pancreatic cancer: should we include grade in AJCC staging?

PubMed

Wasif, Nabil; Ko, Clifford Y; Farrell, James; Wainberg, Zev; Hines, Oscar J; Reber, Howard; Tomlinson, James S

2010-09-01

AJCC staging of pancreatic cancer (PAC) is used to determine prognosis, yet survival within each stage shows wide variation and remains unpredictable. We hypothesized that tumor grade might be responsible for some of this variation and that the addition of grade to current AJCC staging would provide improved prognostication. The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was used to identify 8082 patients with resected PAC. The impact of grade on overall and stage-specific survival was assessed using Cox regression analysis. Variables in the model were age, sex, tumor size, lymph node status, and tumor grade. For each AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. On multivariate analysis, high tumor grade was an independent predictor of survival for the entire cohort (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.31-1.48) as well as for stage I (HR 1.28, 95% CI 1.07-1.54), stage IIA (HR 1.43, 95% CI 1.26-1.61), stage IIB (HR 1.38, 95% CI 1.27-1.50), stage III (HR 1.28, 95% CI 1.02-1.59), and stage IV (HR 1.58, 95% CI 1.21-2.05) patients. The addition of grade to staging results in a statistically significant survival discrimination between all stages. Tumor grade is an important prognostic variable of survival in PAC. We propose a novel staging system incorporating grade into current AJCC staging for pancreas cancer. The improved prognostication is more reflective of tumor biology and may impact therapy decisions and stratification of future clinical trials.

The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis.

PubMed

Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H; Taveira-DaSilva, Angelo M; Beck, Gerald J; Lee, Jar-Chi; McCarthy, Kevin; Finlay, Geraldine A; Brown, Kevin K; Ruoss, Stephen J; Avila, Nilo A; Moss, Joel; McCormack, Francis X

2018-06-22

The natural history of lymphangioleiomyomatosis is mainly derived from retrospective cohort analyses and remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. A linear mixed effects model was employed to compute the rate of decline of FEV1, and identify variables impacting FEV1 decline among 217 registry patients who enrolled from 1998-2001. Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Mean annual decline of FEV1 was 89±53 ml/year, and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scan (p=0.02), and in premenopausal subjects (118ml/year) compared to postmenopausal subjects (74ml/year), (p=0.003). There were 26 deaths and 43 lung transplants during the evaluation period. Estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 95%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio 0.30, p=0.0002) and higher baseline FEV1 (hazard ratio 0.97, p=0.008) or DLCO (hazard ratio 0.97, p=0.001) were independently associated with a lower risk of progression to death or lung transplantation. The median transplant-free survival in patients with LAM is greater than 20 years. Menopausal status as well as structural and physiological markers of disease severity significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM. Copyright © 2018. Published by Elsevier Inc.

The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis.

PubMed

Carbone, Marco; Sharp, Stephen J; Flack, Steve; Paximadas, Dimitrios; Spiess, Kelly; Adgey, Carolyn; Griffiths, Laura; Lim, Reyna; Trembling, Paul; Williamson, Kate; Wareham, Nick J; Aldersley, Mark; Bathgate, Andrew; Burroughs, Andrew K; Heneghan, Michael A; Neuberger, James M; Thorburn, Douglas; Hirschfield, Gideon M; Cordell, Heather J; Alexander, Graeme J; Jones, David E J; Sandford, Richard N; Mells, George F

2016-03-01

The biochemical response to ursodeoxycholic acid (UDCA)--so-called "treatment response"--strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90). The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care. © 2015 by the American Association for the Study of Liver Diseases.

Serial changes and prognostic implications of CT findings in combined pulmonary fibrosis and emphysema: comparison with fibrotic idiopathic interstitial pneumonias alone.

PubMed

Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo

2017-05-01

Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.

Health assessment questionnaire score is the best predictor of 5-year quality of life in early rheumatoid arthritis.

PubMed

Cohen, Jean-David; Dougados, Maxime; Goupille, Philippe; Cantagrel, Alain; Meyer, Olivier; Sibilia, Jean; Daurès, Jean-Pierre; Combe, Bernard

2006-10-01

To evaluate and determine prognostic factors of 5-year quality of life in patients with early rheumatoid arthritis (RA). A cohort of 191 patients with RA and disease duration < 1 year was prospectively followed over 5 years. The outcome measure was quality of life as assessed by the Arthritis Impact Measurement Scales 2 (AIMS2). Univariate analysis, then stepwise multiple logistic regression, was used to find independent baseline prognostic variables. After accounting for death, loss of followup, and missing data, 158 patients (82.72%) were included in the analysis. The mean AIMS2 physical, symptom, psychological, social interaction, and work scores after 5 years were 1.6 (range 0-6.88), 4.0 (0-10), 3.48 (0-9.22), 4.06 (0-8.69), and 1.87 (0-8.13), respectively. The AIMS2 physical component was significantly correlated with Health Assessment Questionnaire (HAQ) score at 5 years. Logistic regression analysis revealed that the baseline values able to predict the 5-year physical, psychological, symptom, social interaction, and work status were, respectively: HAQ score and erythrocyte sedimentation rate (ESR), body mass index (BMI), HAQ; erosion score and sex, HAQ; ESR and anti-perinuclear antibody; matrix metalloproteinase-3 (MMP3) level, joint space narrowing, and tender joint scores; HAQ score and age. The multidimensional structure of the AIMS2 allowed us to assess the 5-year health-related quality of life in early RA. Using this instrument as an outcome variable, prognostic factors were selected and varied widely depending on the evaluated domain. The baseline HAQ score was the best predictive factor of 4 of the 5 domains of the AIMS2.

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

2016-11-15

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

Phosphohistone-H3 (PHH3) is prognostic relevant in Merkel cell carcinomas but Merkel cell polyomavirus is a more powerful prognostic factor than AJCC clinical stage, PHH3, Ki-67 or mitotic indices.

PubMed

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kato, Masako; Nagata, Keiko; Murakami, Ichiro; Hayashi, Kazuhiko

2015-08-01

Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV) have better prognosis than those without MCPyV. The relationship between mitotic index (MI) and MCC outcome has remained elusive because of the difficulty in differentiating mitotic cells from apoptotic ones. We evaluated the role of phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV-positive or -negative MCC patients, and assessed its prognostic value in comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE) staining. We compared the prognostic value of PHH3 mitotic index with that of MI by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive immunoreactivity was mostly observed in mitotic figures. Multivariate analysis significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51) were observed as significantly independent prognostic factors for OS. PHH3-positive cell counts/10 HPF was a slightly significant independent prognostic factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in MCC patients are useful in prognostication, although MCPyV-infection is a more powerful prognostic factor in MCCs than the AJCC scheme on proliferation or mitotic indices. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

PubMed

Ramsey, Sara; Lamb, Gavin W A; Aitchison, Michael; Graham, John; McMillan, Donald C

2007-01-15

Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma

PubMed Central

Ong, Chin-Ann J.; Shapiro, Joel; Nason, Katie S.; Davison, Jon M.; Liu, Xinxue; Ross-Innes, Caryn; O'Donovan, Maria; Dinjens, Winand N.M.; Biermann, Katharina; Shannon, Nicholas; Worster, Susannah; Schulz, Laura K.E.; Luketich, James D.; Wijnhoven, Bas P.L.; Hardwick, Richard H.; Fitzgerald, Rebecca C.

2013-01-01

Purpose Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. Patients and Methods We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666). Results Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). Conclusion We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage. PMID:23509313

Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study.

PubMed

Espelund, Ulrick; Renehan, Andrew G; Cold, Søren; Oxvig, Claus; Lancashire, Lee; Su, Zhenqiang; Flyvbjerg, Allan; Frystyk, Jan

2018-05-03

Measurement of circulating insulin-like growth factors (IGFs), in particular IGF-binding protein (IGFBP)-2, at the time of diagnosis, is independently prognostic in many cancers, but its clinical performance against other routinely determined prognosticators has not been examined. We measured IGF-I, IGF-II, pro-IGF-II, IGF bioactivity, IGFBP-2, -3, and pregnancy-associated plasma protein A (PAPP-A), an IGFBP regulator, in baseline samples of 301 women with breast cancer treated on four protocols (Odense, Denmark: 1993-1998). We evaluated performance characteristics (expressed as area under the curve, AUC) using Cox regression models to derive hazard ratios (HR) with 95% confidence intervals (CIs) for 10-year recurrence-free survival (RFS) and overall survival (OS), and compared those against the clinically used Nottingham Prognostic Index (NPI). We measured the same biomarkers in 531 noncancer individuals to assess multidimensional relationships (MDR), and evaluated additional prognostic models using survival artificial neural network (SANN) and survival support vector machines (SSVM), as these enhance capture of MDRs. For RFS, increasing concentrations of circulating IGFBP-2 and PAPP-A were independently prognostic [HR biomarker doubling : 1.474 (95% CIs: 1.160, 1.875, P = 0.002) and 1.952 (95% CIs: 1.364, 2.792, P < 0.001), respectively]. The AUC RFS for NPI was 0.626 (Cox model), improving to 0.694 (P = 0.012) with the addition of IGFBP-2 plus PAPP-A. Derived AUC RFS using SANN and SSVM did not perform superiorly. Similar patterns were observed for OS. These findings illustrate an important principle in biomarker qualification-measured circulating biomarkers may demonstrate independent prognostication, but this does not necessarily translate into substantial improvement in clinical performance. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

PubMed

Eilertsen, Marte; Andersen, Sigve; Al-Saad, Samer; Kiselev, Yury; Donnem, Tom; Stenvold, Helge; Pettersen, Ingvild; Al-Shibli, Khalid; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M

2014-01-01

Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC. Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS. We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Reporting and Methodology of Multivariable Analyses in Prognostic Observational Studies Published in 4 Anesthesiology Journals: A Methodological Descriptive Review.

PubMed

Guglielminotti, Jean; Dechartres, Agnès; Mentré, France; Montravers, Philippe; Longrois, Dan; Laouénan, Cedric

2015-10-01

Prognostic research studies in anesthesiology aim to identify risk factors for an outcome (explanatory studies) or calculate the risk of this outcome on the basis of patients' risk factors (predictive studies). Multivariable models express the relationship between predictors and an outcome and are used in both explanatory and predictive studies. Model development demands a strict methodology and a clear reporting to assess its reliability. In this methodological descriptive review, we critically assessed the reporting and methodology of multivariable analysis used in observational prognostic studies published in anesthesiology journals. A systematic search was conducted on Medline through Web of Knowledge, PubMed, and journal websites to identify observational prognostic studies with multivariable analysis published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, and Anaesthesia in 2010 and 2011. Data were extracted by 2 independent readers. First, studies were analyzed with respect to reporting of outcomes, design, size, methods of analysis, model performance (discrimination and calibration), model validation, clinical usefulness, and STROBE (i.e., Strengthening the Reporting of Observational Studies in Epidemiology) checklist. A reporting rate was calculated on the basis of 21 items of the aforementioned points. Second, they were analyzed with respect to some predefined methodological points. Eighty-six studies were included: 87.2% were explanatory and 80.2% investigated a postoperative event. The reporting was fairly good, with a median reporting rate of 79% (75% in explanatory studies and 100% in predictive studies). Six items had a reporting rate <36% (i.e., the 25th percentile), with some of them not identified in the STROBE checklist: blinded evaluation of the outcome (11.9%), reason for sample size (15.1%), handling of missing data (36.0%), assessment of colinearity (17.4%), assessment of interactions (13.9%), and calibration (34.9%). When reported, a few methodological shortcomings were observed, both in explanatory and predictive studies, such as an insufficient number of events of the outcome (44.6%), exclusion of cases with missing data (93.6%), or categorization of continuous variables (65.1%.). The reporting of multivariable analysis was fairly good and could be further improved by checking reporting guidelines and EQUATOR Network website. Limiting the number of candidate variables, including cases with missing data, and not arbitrarily categorizing continuous variables should be encouraged.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

PubMed Central

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

2015-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis.

PubMed

Gunia, Sven; Kakies, Christoph; Erbersdobler, Andreas; Hakenberg, Oliver W; Koch, Stefan; May, Matthias

2012-03-01

To evaluate the role of p53, p21 and cyclin D1 expression in patients with penile cancer (PC). Paraffin-embedded tissues from PC specimens from six pathology departments were subjected to a central histopathological review performed by one pathologist. The tissue microarray technique was used for immunostaining which was evaluated by two independent pathologists and correlated with cancer-specific survival (CSS). κ-statistics were used to assess interobserver variability. Uni- and multivariable Cox proportional hazards analysis was applied to assess the independent effects of several prognostic factors on CSS over a median of 32 months (IQR 6-66 months). Specimens and clinical data from 110 men treated surgically for primary PC were collected. p53 staining was positive in 30 and negative in 62 specimens. κ-statistics showed substantial interobserver reproducibility of p53 staining evaluation (κ=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%. Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin D1 and p21 expression were not correlated with survival. However, incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting CSS. In patients with PC, the expression of p53 in the primary tumour specimen can be reproducibly assessed and is negatively associated with cancer specific survival.

Risk stratification using stress echocardiography: incremental prognostic value over historic, clinical, and stress electrocardiographic variables across a wide spectrum of bayesian pretest probabilities for coronary artery disease.

PubMed

Bangalore, Sripal; Gopinath, Devi; Yao, Siu-Sun; Chaudhry, Farooq A

2007-03-01

We sought to evaluate the risk stratification ability and incremental prognostic value of stress echocardiography over historic, clinical, and stress electrocardiographic (ECG) variables, over a wide spectrum of bayesian pretest probabilities of coronary artery disease (CAD). Stress echocardiography is an established technique for the diagnosis of CAD. However, data on incremental prognostic value of stress echocardiography over historic, clinical, and stress ECG variables in patients with known or suggested CAD is limited. We evaluated 3259 patients (60 +/- 13 years, 48% men) undergoing stress echocardiography. Patients were grouped into low (<15%), intermediate (15-85%), and high (>85%) pretest CAD likelihood subgroups using standard software. The historical, clinical, stress ECG, and stress echocardiographic variables were recorded for the entire cohort. Follow-up (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 66) and cardiac death (n = 105) was obtained. For the entire cohort, an ischemic stress echocardiography study confers a 5.0 times higher cardiac event rate than the normal stress echocardiography group (4.0% vs 0.8%/y, P < .0001). Furthermore, Cox proportional hazard regression model showed incremental prognostic value of stress echocardiography variables over historic, clinical, and stress ECG variables across all pretest probability subgroups (global chi2 increased from 5.1 to 8.5 to 20.1 in the low pretest group, P = .44 and P = .01; from 20.9 to 28.2 to 116 in the intermediate pretest group, P = .47 and P < .0001; and from 17.5 to 36.6 to 61.4 in the high pretest group, P < .0001 for both groups). A normal stress echocardiography portends a benign prognosis (<1% event rate/y) in all pretest probability subgroups and even in patients with high pretest probability and yields incremental prognostic value over historic, clinical, and stress ECG variables across all pretest probability subgroups. The best incremental value is, however, in the intermediate pretest probability subgroup.

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease

PubMed Central

Romito, Giovanni; Guglielmini, Carlo; Diana, Alessia; Pelle, Nazzareno G.; Contiero, Barbara; Cipone, Mario

2018-01-01

Background The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. Objectives To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). Animals One‐hundred and fifteen dogs of different breeds with MMVD. Methods Prospective cohort study. Conventional morphologic and echo‐Doppler variables, LA areas and volumes, and STE‐based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac‐related death. Results Most of the tested variables, including all LA STE‐derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76‐11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10‐4.89; P = .024) remained statistically significant in the multivariable analysis. Conclusions and Clinical Importance The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE‐derived variables. PMID:29572938

Prognostic significance of pleural lavage cytology after thoracotomy and before closure of the chest in lung cancer.

PubMed

Taniguchi, Yuji; Nakamura, Hiroshige; Miwa, Ken; Adachi, Yoshin; Fujioka, Shinji; Haruki, Tomohiro; Horie, Yasushi

2009-07-01

Some reports have described pleural lavage cytology (PLC) to be a prognostic factor for non-small cell lung cancer (NSCLC) patients. However, there have only been a few reports describing the findings both immediately after thoracotomy (PLC after thoracotomy) and before the closure of the chest (PLC before closure). From April 2002 to April 2008, both PLC after thoracotomy and PLC before closure were performed in 296 consecutive patients who underwent resections for NSCLC. PLC after thoracotomy was positive in 14 patients. The survival rate in the PLC after thoracotomy positive cases was significantly poorer than in PLC after thoracotomy negative cases (P=0.047). In contrast, there were 26 PLC before closure positive cases. The survival rate in the PLC before closure positive cases was significantly poorer than in the PLC before closure negative cases (P<0.0001). Multivariate analyses revealed that PLC after thoracotomy is not an independent prognostic factor in our study. However, PLC before closure was an independent prognostic factor based on multivariate analyses. We conclude that PLC before closure was found to be a better prognostic factor than PLC after thoracotomy for NSCLC patients.

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer

PubMed Central

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-01-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC. PMID:29725416

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer.

PubMed

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-05-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC.

Multivariate outcome prediction in traumatic brain injury with focus on laboratory values.

PubMed

Nelson, David W; Rudehill, Anders; MacCallum, Robert M; Holst, Anders; Wanecek, Michael; Weitzberg, Eddie; Bellander, Bo-Michael

2012-11-20

Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Identifying factors relevant to outcome can provide a better understanding of TBI pathophysiology, in addition to aiding prognostication. Many common laboratory variables have been related to outcome but may not be independent predictors in a multivariate setting. In this study, 757 patients were identified in the Karolinska TBI database who had retrievable early laboratory variables. These were analyzed towards a dichotomized Glasgow Outcome Scale (GOS) with logistic regression and relevance vector machines, a non-linear machine learning method, univariately and controlled for the known important predictors in TBI outcome: age, Glasgow Coma Score (GCS), pupil response, and computed tomography (CT) score. Accuracy was assessed with Nagelkerke's pseudo R². Of the 18 investigated laboratory variables, 15 were found significant (p<0.05) towards outcome in univariate analyses. In contrast, when adjusting for other predictors, few remained significant. Creatinine was found an independent predictor of TBI outcome. Glucose, albumin, and osmolarity levels were also identified as predictors, depending on analysis method. A worse outcome related to increasing osmolarity may warrant further study. Importantly, hemoglobin was not found significant when adjusted for post-resuscitation GCS as opposed to an admission GCS, and timing of GCS can thus have a major impact on conclusions. In total, laboratory variables added an additional 1.3-4.4% to pseudo R².

Differences in Bordetella pertussis DNA load according to clinical and epidemiological characteristics of patients with whooping cough.

PubMed

Brotons, Pedro; de Paz, Hector D; Toledo, Diana; Villanova, Marta; Plans, Pedro; Jordan, Iolanda; Dominguez, Angela; Jane, Mireia; Godoy, Pere; Muñoz-Almagro, Carmen

2016-04-01

To identify associations between nasopharyngeal Bordetella pertussis DNA load and clinical and epidemiological characteristics and evaluate DNA load prognostic value in pertussis severity. Prospective observational multi-centre study including nasopharyngeal samples positive to pertussis DNA by real-time PCR collected from children and adult patients in more than 200 health centres of Catalonia (Spain) during 2012-2013. B. pertussis load was inversely correlated with age (rho = -0.32, p < 0.001), time to diagnosis (rho = -0.33, p < 0.001) and number of symptoms (rho = 0.13, p = 0.002). Median bacterial load was significantly higher in inpatients versus outpatients (4.91 vs. 2.55 log10 CFU/mL, p < 0.001), patients with complications versus those without (6.05 vs. 2.82 log10 CFU/mL, p < 0.001), disease incidence in summer and autumn versus spring and winter (3.50 vs. 2.21 log10 CFU/mL, p = 0.002), and unvaccinated-partially vaccinated patients versus vaccinated (4.20 vs. 2.76 log10 CFU/mL, p = 0.004). A logistic regression model including bacterial load and other candidate prognostic factors showed good prediction for hospital care (AUC = 0.94) although only age and unvaccinated status were found to be prognostic factors. We observed strong positive associations of nasopharyngeal bacterial load with severity outcomes of hospitalisation and occurrence of complications. Bacterial load and other independent variables contributed to an accurate prognostic model for hospitalisation. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Does tumor size have its prognostic role in colorectal cancer? Re-evaluating its value in colorectal adenocarcinoma with different macroscopic growth pattern.

PubMed

Dai, Weixing; Li, Yaqi; Meng, Xianke; Cai, Sanjun; Li, Qingguo; Cai, Guoxiang

2017-09-01

Few previous studies have taken the growth pattern into consideration when analyzing the prognostic value of tumor size in colorectal cancer (CRC). We sought to reveal the prognostic role of tumor size in different macroscopic growth patterns of CRC. Using Cancer Center datasets, we identified 4057 cases with colorectal adenocarcinoma treated with curative resection. Macroscopic growth patterns of tumors were classified into three types: infiltrative, ulcerative and expansive types based on tumor gross appearance. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic factors for overall survival (OS) and disease-free survival (DFS). In whole cohort, tumor size was an independent factor for OS (HR 1.10, 95%CI 1.04-1.16, p < 0.001). Subgroup analysis based on macroscopic growth pattern suggested that tumor size was an independent factor for OS both in the infiltrative (HR 1.37, 95%CI 1.12-1.66, p = 0.002) group and ulcerative group (HR 1.08, 95%CI 1.00-1.16, p = 0.044) and tumor size (HR 1.22, 95%CI 1.06-1.40, p = 0.004) was found as an independent factor for DFS only in infiltrative group. Tumor size is an independent factor for OS and DFS in patients with colorectal adenocarcinoma of infiltrative type, while only for OS in patients of ulcerative type. Copyright © 2017. Published by Elsevier Ltd.

A novel prognostic six-CpG signature in glioblastomas.

PubMed

Yin, An-An; Lu, Nan; Etcheverry, Amandine; Aubry, Marc; Barnholtz-Sloan, Jill; Zhang, Lu-Hua; Mosser, Jean; Zhang, Wei; Zhang, Xiang; Liu, Yu-He; He, Ya-Long

2018-03-01

We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management. © 2018 John Wiley & Sons Ltd.

MicroDAIMON study: Microcirculatory DAIly MONitoring in critically ill patients: a prospective observational study.

PubMed

Scorcella, Claudia; Damiani, Elisa; Domizi, Roberta; Pierantozzi, Silvia; Tondi, Stefania; Carsetti, Andrea; Ciucani, Silvia; Monaldi, Valentina; Rogani, Mara; Marini, Benedetto; Adrario, Erica; Romano, Rocco; Ince, Can; Boerma, E Christiaan; Donati, Abele

2018-05-15

Until now, the prognostic value of microcirculatory alterations in critically ill patients has been mainly evaluated in highly selected subgroups. Aim of this study is to monitor the microcirculation daily in mixed group of Intensive Care Unit (ICU)-patients and to establish the association between (the evolution of) microcirculatory alterations and outcome. This is a prospective longitudinal observational single-centre study in adult patients admitted to a 12-bed ICU in an Italian teaching hospital. Sublingual microcirculation was evaluated daily, from admission to discharge/death, using Sidestream Dark Field imaging. Videos were analysed offline to assess flow and density variables. Laboratory and clinical data were recorded simultaneously. A priori, a Microvascular Flow Index (MFI) < 2.6 was defined as abnormal. A binary logistic regression analysis was performed to evaluate the association between microcirculatory variables and outcomes; a Kaplan-Meier survival curve was built. Outcomes were ICU and 90-day mortality. A total of 97 patients were included. An abnormal MFI was present on day 1 in 20.6%, and in 55.7% of cases during ICU admission. Patients with a baseline MFI < 2.6 had higher ICU, in-hospital and 90-day mortality (45 vs. 15.6%, p = 0.012; 55 vs. 28.6%, p = 0.035; 55 vs. 26%, p = 0.017, respectively). An independent association between baseline MFI < 2.6 and outcome was confirmed in a binary logistic analysis (odds ratio 4.594 [1.340-15.754], p = 0.015). A heart rate (HR) ≥ 90 bpm was an adjunctive predictor of mortality. However, a model with stepwise inclusion of mean arterial pressure < 65 mmHg, HR ≥ 90 bpm, lactate > 2 mmol/L and MFI < 2.6 did not detect significant differences in ICU mortality. In case an abnormal MFI was present on day 1, ICU mortality was significantly higher in comparison with patients with an abnormal MFI after day 1 (38 vs. 6%, p = 0.001), indicating a time-dependent significant difference in prognostic value. In a general ICU population, an abnormal microcirculation at baseline is an independent predictor for mortality. In this setting, additional routine daily microcirculatory monitoring did not reveal extra prognostic information. Further research is needed to integrate microcirculatory monitoring in a set of commonly available hemodynamic variables. Trial registration NCT 02649088, www.clinicaltrials.gov . Date of registration: 23 December 2015, retrospectively registered.

Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score.

PubMed

George, Elizabeth C; Walker, A Sarah; Kiguli, Sarah; Olupot-Olupot, Peter; Opoka, Robert O; Engoru, Charles; Akech, Samuel O; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Berkley, James A; Mpoya, Ayub; Levin, Michael; Crawley, Jane; Gibb, Diana M; Maitland, Kathryn; Babiker, Abdel G

2015-07-31

Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0-10 and had an AUROC of 0.82 (95 % CI, 0.77-0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72-0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82-0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies.

Big genomics and clinical data analytics strategies for precision cancer prognosis.

PubMed

Ow, Ghim Siong; Kuznetsov, Vladimir A

2016-11-07

The field of personalized and precise medicine in the era of big data analytics is growing rapidly. Previously, we proposed our model of patient classification termed Prognostic Signature Vector Matching (PSVM) and identified a 37 variable signature comprising 36 let-7b associated prognostic significant mRNAs and the age risk factor that stratified large high-grade serous ovarian cancer patient cohorts into three survival-significant risk groups. Here, we investigated the predictive performance of PSVM via optimization of the prognostic variable weights, which represent the relative importance of one prognostic variable over the others. In addition, we compared several multivariate prognostic models based on PSVM with classical machine learning techniques such as K-nearest-neighbor, support vector machine, random forest, neural networks and logistic regression. Our results revealed that negative log-rank p-values provides more robust weight values as opposed to the use of other quantities such as hazard ratios, fold change, or a combination of those factors. PSVM, together with the classical machine learning classifiers were combined in an ensemble (multi-test) voting system, which collectively provides a more precise and reproducible patient stratification. The use of the multi-test system approach, rather than the search for the ideal classification/prediction method, might help to address limitations of the individual classification algorithm in specific situation.

Predictors of survival in mucosal melanoma of the head and neck.

PubMed

Jethanamest, Daniel; Vila, Peter M; Sikora, Andrew G; Morris, Luc G T

2011-10-01

The head and neck is the most common site of mucosal melanoma, a cancer with poor prognosis. In contrast to cutaneous melanoma, mucosal melanoma of the head and neck (MMHN) is uncommon, with limited data regarding outcomes and prognostic factors drawn from small, single-institution case series. In order to identify factors predictive of survival, we analyzed MMHN outcomes in a large US cohort. MMHN cases (n = 815) diagnosed in the USA between 1973 and 2007 were analyzed in the Surveillance, Epidemiology, and End Results registry, and cause of death was individually determined in 778 (95.5%) cases. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to analyze prognostic variables. Disease-specific survival status was determined in 778 (95.5%) cases. The 5- and 10-year rates of overall survival (OS) were 25.2 and 12.2%; disease-specific survival (DSS), 32.4 and 19.3%. On multivariable analysis, anatomic primary site was an independent predictor of OS and DSS, with tumors in the nasal cavity and oral cavity associated with survival superior to tumors in the nasopharynx and paranasal sinuses. Age > 70 years, tumor size, nodal status, and distant metastasis status were additional independent predictors of poorer survival. In this large cohort of patients with MMHN, we have identified several novel factors robustly predictive of overall and melanoma-specific survival.

C-reactive protein as an adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): confirmatory results

PubMed Central

Prins, Renee C.; Rademacher, Brooks L.; Mongoue-Tchokote, Solange; Alumkal, Joshi J.; Graff, Julie N.; Eilers, Kristine M.; Beer, Tomasz M.

2010-01-01

We previously reported that higher serum concentrations of C-reactive protein (CRP) are associated with shorter survival in men with castration-resistant prostate cancer (CRPC). To confirm this finding in an independent data set, we used 119 CRPC patients enrolled in 6 phase II clinical trials and examined the relationship of CRP, alkaline phosphatase, hemoglobin, age, ECOG PS, and prostate specific antigen (PSA) with survival. Median follow-up was 19.7 months (0.9–98.5 months) and 89% have died. After analyzing the form of the risk function using the generalized additive model method, univariate and multivariate Cox proportional hazard models were used to assess associations between baseline individual categorical and continuous variables. Quartiles of CRP were: 1: 0–1.0, 1.1–4.9, 5.0–17.0, and 17.1 to 311 mg/L. In a Cox multivariate model, log2(CRP) (HR 1.106 p=0.013) as well as hemoglobin and alkaline phosphatase were independently associated with survival, confirming that higher CRP is associated with shorter survival in CRPC. Since CRP is a marker of inflammation, this finding suggests that inflammation may play an important role in the natural history of advanced prostate cancer. CRP is a readily measurable biomarker that has the potential to improve prognostic models and should be validated in a prospective clinical trial. PMID:20207556

Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia: a Danish population-based study

PubMed Central

Øvlisen, Andreas K.; Oest, Anders; Bendtsen, Mette D.; Bæch, John; Johansen, Preben; Lynggaard, Line S.; Mølle, Ingolf; Mortensen, Thomas B.; Weber, Duruta; Ertner, Gideon; Schöllkopf, Claudia; Thomassen, Jesper Q.; Nielsen, Ove Juul; Østgård, Lene Sofie Granfeldt; Bøgsted, Martin; Dybkær, Karen; Johnsen, Hans E.

2018-01-01

Stringent complete remission (sCR) of acute myeloid leukemia is defined as normal hematopoiesis after therapy. Less sCR, including non-sCR, was introduced as insufficient blood platelet, neutrophil, or erythrocyte recovery. These latter characteristics were defined retrospectively as postremission transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie, <5% blasts in the postinduction bone marrow analysis). Individual patients were classified as having sCR (n = 360; 46.8%) or non-sCR (n = 409; 53.2%) based on data from our national laboratory and transfusion databases. Survival analysis revealed that patients achieving sCR had superior overall survival (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64) as well as relapse-free survival (HR, 1.25; 95% CI, 1.03-1.51) compared with those with non-sCR after adjusting for covariates. Cox regression analysis regarding the impact of the stringent criteria for blood cell recovery identified these as significant and independent variables. In conclusion, this real-life register study supports the international criteria for response evaluation on prognosis and, most importantly, documents each of the 3 lineage recovery criteria as contributing independently. PMID:29523528

Validation of serum amyloid α as an independent biomarker for progression-free and overall survival in metastatic renal cell cancer patients.

PubMed

Vermaat, Joost S; Gerritse, Frank L; van der Veldt, Astrid A; Roessingh, Wijnand M; Niers, Tatjana M; Oosting, Sjoukje F; Sleijfer, Stefan; Roodhart, Jeanine M; Beijnen, Jos H; Schellens, Jan H; Gietema, Jourik A; Boven, Epie; Richel, Dick J; Haanen, John B; Voest, Emile E

2012-10-01

We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model. Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs). For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009). Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect. Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome. SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Mode of detection: an independent prognostic factor for women with breast cancer.

PubMed

Hofvind, Solveig; Holen, Åsne; Román, Marta; Sebuødegård, Sofie; Puig-Vives, Montse; Akslen, Lars

2016-06-01

To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment. © The Author(s) 2015.

[Neuroendocrine neoplasm of digestive system with different grades: a clinicopathologic and prognostic study].

PubMed

Zhang, Ming-hui; Liu, Yan-hui; Luo, Xin-lan; Lin, Xing-tao; Zhuang, Heng-guo

2012-07-01

To study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. The clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model. Amongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05). There is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

Fractal correlation properties of R-R interval dynamics and mortality in patients with depressed left ventricular function after an acute myocardial infarction

NASA Technical Reports Server (NTRS)

Huikuri, H. V.; Makikallio, T. H.; Peng, C. K.; Goldberger, A. L.; Hintze, U.; Moller, M.

2000-01-01

BACKGROUND: Preliminary data suggest that the analysis of R-R interval variability by fractal analysis methods may provide clinically useful information on patients with heart failure. The purpose of this study was to compare the prognostic power of new fractal and traditional measures of R-R interval variability as predictors of death after acute myocardial infarction. METHODS AND RESULTS: Time and frequency domain heart rate (HR) variability measures, along with short- and long-term correlation (fractal) properties of R-R intervals (exponents alpha(1) and alpha(2)) and power-law scaling of the power spectra (exponent beta), were assessed from 24-hour Holter recordings in 446 survivors of acute myocardial infarction with a depressed left ventricular function (ejection fraction

A nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma

PubMed Central

Liu, Jin-Shi; Huang, Ying; Yang, Xun; Feng, Ji-Feng

2015-01-01

Background: Inflammation plays an important role in cancer progression and prognosis. However, the prognostic values of inflammatory biomarkers in esophageal cancer (EC) were not established. In the present study, therefore, we initially used a nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 326 ESCC patients were included in this retrospective study. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) were analyzed in the current study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analysis was also performed to evaluate the prognostic factors. A nomogram was established to predict the prognosis for CSS. Results: Patients were divided into 3 groups according to GPS (GPS 0, 1 and 2) and 2 groups according to NLR (≤3.45 and >3.45), PLR (≤166.5 and >166.5) and LMR (≤2.30 and >2.30). The 5-year CSS in patients with GPS 0, 1 and 2 were 49.2%, 26.8% and 11.9%, respectively (P<0.001). In addition, patients with NLR (>3.45), PLR (>166.5) and LMR (≤2.30) were significantly associated with decreased CSS, respectively (P<0.001). Multivariate analysis revealed that GPS (P<0.001), PLR (P=0.002) and LMR (P=0.002) were independent prognostic factors in patients with ESCC. In addition, a nomogram was established according to all significantly independent factors for CSS. The Harrell’s c-index for CSS prediction was 0.72. Conclusion: GPS, PLR and LMR were potential prognostic biomarkers in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC. PMID:26328248

Prediction of Everolimus Toxicity and Prognostic Value of Skeletal Muscle Index in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Auclin, Edouard; Bourillon, Camille; De Maio, Eleonora; By, Marie Agnes; Seddik, Sofiane; Fournier, Laure; Auvray, Marie; Dautruche, Antoine; Vano, Yann-Alexandre; Thibault, Constance; Joly, Florence; Brunereau, Laurent; Gomez-Roca, Carlos; Chevreau, Christine; Elaidi, Reza; Oudard, Stéphane

2017-06-01

The objective of the study was to assess the prognostic role of skeletal muscle index (SMI) in metastatic renal cell carcinoma (mRCC) patients treated with everolimus, and its effect of on everolimus-induced toxicity. Consecutive mRCC patients treated with everolimus between February 2007 and November 2014 underwent computed tomography scans at a single center performed by the same radiologist. SMI was assessed before everolimus treatment using the L3 cross-sectional area. Overall survival (OS) was analyzed according to SMI value. Results were adjusted using the International Metastatic Database Consortium (IMDC) prognostic group, body mass index (BMI), and/or number of previous tyrosine kinase inhibitor lines (NPL). One hundred twenty-four mRCC patients (mean age, 60.21 years) were treated with everolimus as second- or third-line (82.3%) or > third-line (17.7%) therapy. Most patients (87.9%) had clear cell carcinoma. IMDC prognostic group was "favorable" (32.3%), "intermediate" (50%), or "poor" (17.7%). Median SMI was 40.75. OS was longer in patients from the highest versus lowest SMI tercile: 21.9 versus 10 months (P = .002). Continuous SMI at baseline was not significantly associated with OS after adjustment for IMDC prognostic group, BMI, or NPL but the highest versus lowest SMI tercile was an independent prognostic factor in multivariate analysis (P = .025). There was no difference in everolimus toxicity between SMI tercile groups. SMI was an independent prognostic factor for mRCC patients treated with everolimus. Whether this provides additional prognostic value to IMDC criteria needs to be confirmed in a larger cohort. SMI does not seem to be predictive of everolimus-induced toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Signatures of Mucinous and Poorly Differentiated Subtypes of Colorectal Adenocarcinomas by a Propensity Score Analysis of an Independent Patient Database from Three Phase III Trials.

PubMed

Kanda, Mitsuro; Oba, Koji; Aoyama, Toru; Kashiwabara, Kosuke; Mayanagi, Shuhei; Maeda, Hiromichi; Honda, Michitaka; Hamada, Chikuma; Sadahiro, Sotaro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

2018-04-01

Although colorectal cancer comprises several histological subtypes, the influences of histological subtypes on disease progression and treatment responses remain controversial. We sought to evaluate the prognostic relevance of mucinous and poorly differentiated histological subtypes of colorectal cancer by the propensity score weighting analysis of prospectively collected data from multi-institute phase III trials. Independent patient data analysis of a pooled database from 3 phase III trials was performed. An integrated database of 3 multicenter prospective clinical trials (the Japanese Foundation for Multidisciplinary Treatment of Cancer 7, 15, and 33) was the source of study data. Surgery alone or postoperative adjuvant chemotherapy was offered in patients with resectable colorectal cancer. To balance essential variables more strictly for the comparison analyses, propensity score weighting was conducted with the use of a multinomial logistic regression model. We evaluated the clinical signatures of mucinous and poorly differentiated subtypes with regard to postoperative survival, recurrence, and chemosensitivity. Of 5489 patients, 136 (2.5%) and 155 (2.8%) were pathologically diagnosed with poorly differentiated and mucinous subtypes. The poorly differentiated subtypes were associated with a poorer prognosis than the "others" group (HR, 1.69; 95% CI, 1.00-2.87; p = 0.051), particularly in the patient subgroup of adjuvant chemotherapy (HR, 2.16). Although the mucinous subtype had a marginal prognostic impact among patients with stage I to III colorectal cancer (HR, 1.33; 95% CI, 0.90-1.96), it was found to be an independent prognostic factor in the subpopulation of patients with stage II disease, being associated with a higher prevalence of peritoneal recurrence. The treatment regimens of postoperative chemotherapy are now somewhat outdated. Both mucinous and poorly differentiated subtypes have distinct clinical characteristics. Patients with the mucinous subtype require special attention during follow-up, even for stage II disease, because of the risk of peritoneal or local recurrence. See Video Abstract at http://links.lww.com/DCR/A531.

Variable prognostic value of blood pressure response to exercise.

PubMed

Kato, Yuko; Suzuki, Shinya; Uejima, Tokuhisa; Semba, Hiroaki; Yamashita, Takeshi

2018-01-01

The aim of this study was to evaluate the impact of patient background including exercise capacity on the relationship between the blood pressure (BP) response to exercise and prognosis in patients visiting a cardiovascular hospital. A total of 2134 patients who were referred to our hospital underwent symptom-limited maximal cardiopulmonary exercise testing, and were followed through medical records and mail. The BP response to exercise was defined as the difference between peak and rest systolic BP. The end point was set as cardiovascular events including cardiovascular death, acute coronary syndrome, hospitalization for heart failure, and cerebral infarction. During a median follow-up period of 3 years, 179 (8%) patients reached the end point (2.5%/year). Multivariate analysis showed that BP response was independently and negatively associated with the occurrence of the end point. This prognostic significance of BP response was consistent regardless of left ventricular ejection fraction, renal function, presence of heart failure symptoms, the presence of organic heart disease, and hypertension. However, peak VO 2 showed a significant interaction with the effects of BP response on the end point, suggesting that the prognostic value of BP response was limited in patients with preserved exercise capacity. The role of BP response to exercise as the predictor depends on exercise capacity of each patient. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

PubMed

Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

2016-01-01

The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunological tumor status may predict response to neoadjuvant chemotherapy and outcome after radical cystectomy in bladder cancer.

PubMed

Tervahartiala, Minna; Taimen, Pekka; Mirtti, Tuomas; Koskinen, Ilmari; Ecke, Thorsten; Jalkanen, Sirpa; Boström, Peter J

2017-10-04

Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387 + cells and CLEVER-1 + macrophages associated with poor NAC response, while CLEVER-1 + vessels associated with more favourable response to NAC. Higher counts of CLEVER-1 + macrophages associated with poorer overall survival and CD68 + macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.

Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.

PubMed

Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Di Donato, Violante; Laufer, Joel; Scasso, Santiago; Chiappa, Valentina; Signorelli, Mauro; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2016-07-01

The aim of the study was to evaluate the surgical management and the role of different prognostic factors on survival outcomes of women affected by genital (i.e., vulvar and vaginal) melanoma. Data of patients undergoing primary surgical treatment for genital melanoma were evaluated in this retrospective study. Baseline, pathological, and postoperative variables were tested to identify prognostic factors. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Overall, 98 patients met the inclusion criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors influencing DFS, we observed that at multivariate analysis, only vaginal localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal status was the only independent factor influencing 5-year OS in patients with vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI = 1.08-12.3; p = .03) melanoma. Genital melanomas are characterized by a poor prognosis. Number of mitoses and lymph node status are the main factors influencing survival. Surgery is the mainstay of treatment. A correct and prompt diagnosis is paramount.

Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide).

PubMed

Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R; Sanadhya, Dheera; Shah, Zafar A; Naikoo, Niyaz A

2018-04-30

O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.

Disease-free survival in patients with non-metastatic breast cancer.

PubMed

Diniz, Roberta Wolp; Guerra, Maximiliano Ribeiro; Cintra, Jane Rocha Duarte; Fayer, Vívian Assis; Teixeira, Maria Teresa Bustamante

2016-01-01

Breast cancer is the second most common malignancy in the world and the one with highest incidence in the female population; it is also a major cause of death from cancer among women. To analyze the disease-free survival (DFS) at 5 years and prognostic factors in women with non-metastatic invasive breast cancer treated at a referral center for cancer care located in a medium-sized city in the Southeast of Brazil. Patients diagnosed with the disease between 2003 and 2005 and identified through the institution's cancer hospital records were analyzed. The follow-up of cases was carried out through hospital records, and complemented by search in the database of the Mortality Information System (SIM) as well as telephone contact. The variables analyzed were distributed in the following blocks: socio-demographic data, tumor-related characteristics, and treatment-related characteristics. Survival functions were calculated using the Kaplan-Meier method and the prognostic factors were analyzed based on Cox proportional hazard model. The study showed a DFS at 5 years of 72% (95CI 67.6-75.9). The main variables independently associated with DFS were lymph node involvement, use of hormone therapy, and education level. This study reinforces the importance of early diagnosis for DFS, pointing to the role of social aspects in this regard. The relevance of this research in the country is also highlighted, given the scarcity of studies on DFS in the Brazilian population.

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

Decreased expression of class III β-tubulin is associated with unfavourable prognosis in patients with malignant melanoma.

PubMed

Shimizu, Akira; Kaira, Kyoichi; Yasuda, Masahito; Asao, Takayuki; Ishikawa, Osamu

2016-02-01

Class III β-tubulin (TUBB3) has been recognized as being associated with resistance to taxane-based regimens in several cancers. However, little is known about the clinicopathological significance of TUBB3 expression in patients with cutaneous malignant melanoma. The aim of this study was to examine the prognostic significance of TUBB3 expression in cutaneous malignant melanoma. A total of 106 patients with surgically resected cutaneous malignant melanoma were assessed. Tumour sections were immunohistochemically stained for TUBB3, Ki-67 and microvessel density with CD34. TUBB3 was highly expressed in 80% (85/106) of patients. No statistically significant relationship was observed between the high expression of TUBB3 and any variables. On univariate analysis, ulceration, disease stage, TUBB3 and CD34 revealed a significant relationship with overall survival and progression-free survival. Multivariate analysis confirmed that a low TUBB3 expression was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The decreased expression of TUBB3 could be a significant marker for predicting unfavourable prognosis in patients with cutaneous malignant melanoma.

Long telomere length predicts poor clinical outcome in esophageal cancer patients.

PubMed

Lv, Yanyan; Zhang, Yong; Li, Xinru; Ren, Xiaojuan; Wang, Meichen; Tian, Sijia; Hou, Peng; Shi, Bingyin; Yang, Qi

2017-02-01

Abnormal telomere length is widely reported in various human cancers, and it is considered to be an important hallmark of cancer. However, there is remarkably little consensus on the value of telomere length in the prognostic evaluation of esophageal cancers. Here, we attempted to determine the association of variable telomere length with clinical outcome of esophageal cancer patients. Using real-time quantitative PCR, we examined relative telomere lengths (RTL) in a cohort of esophageal cancer and normal esophageal tissues, and statistically investigated the association between RTL and clinical outcomes of esophageal cancer patients. The majority of esophageal cancers in this study had longer RTLs as compared to adjacent non-tumor tissues. Enhanced tumor RTL was associated with smoking habit, poor differentiation, advanced tumor stage, lymph node metastasis and cancer related death. In particular, a close relationship between longer RTL and poor survival was fully demonstrated by using cox regression and Kaplan-Maier survival curves. We found frequent telomere elongation in esophageal cancer tissues, and demonstrated longer RTL may be an independent poor prognostic factor for esophageal cancer patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

PubMed

Salah, Khibar; Pinto, Yigal M; Eurlings, Luc W; Metra, Marco; Stienen, Susan; Lombardi, Carlo; Tijssen, Jan G; Kok, Wouter E

2015-09-01

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

A Multifactorial Analysis of Melanoma: Prognostic Histopathological Features Comparing Clark's and Breslow's Staging Methods

PubMed Central

Balch, Charles M.; Murad, Tariq M.; Soong, Seng-Jaw; Ingalls, Anna Lee; Halpern, Norman B.; Maddox, William A.

1978-01-01

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (≥4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors. PMID:736651

Early prognostic factors of outcomes in monochorionic twin pregnancy: systematic review and meta-analysis.

PubMed

Mackie, Fiona L; Hall, Matthew J; Morris, R Katie; Kilby, Mark D

2018-05-12

Assess ability of first trimester pregnancy related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies DATA SOURCES: MEDLINE, EMBASE, ISI Web of Science, CINAHL, the Cochrane Central Registration of Controlled Trials and Research Registers, and Google Scholar, from inception to 12 May 2017. Grey literature and bibliographies of articles were checked. Studies that reported ultrasound measurements, maternal characteristics, or potential biomarkers, measured in the first trimester in monochorionic diamniotic twin pregnancies, where the potential prognostic ability between the variable and twin-twin transfusion syndrome, growth restriction, or intrauterine fetal death could be assessed. Quality assessment was evaluated using the STROBE checklist by 2 reviewers independently. For meta-analysis, odds ratios using a random effects model, or standardized mean difference were calculated. If a moderate association was found, the prognostic ability was evaluated by calculating the sensitivity and specificity. Risk of heterogeneity was reported as I 2 and publication bias was visually assessed by funnel plots and quantitatively by Egger's test. Forty-eight studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: NT>95th centile in one/both fetuses and TTTS (OR 2.29 [95%CI 1.05, 4.96] I 2 =6.6%, 4 studies, 615 pregnancies); CRL discordance ≥10% and TTTS (OR 2.43 [95%CI 1.13, 5.21] I 2 =14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and TTTS (OR 2.12 [95%CI 1.17, 3.83] I 2 =0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation. It is not currently possible to predict adverse outcomes in monochorionic twin pregnancies. We have revealed a lack of research investigating first trimester biomarkers in monochorionic twin pregnancies. Different assessment methods and definitions of each variable and outcome were an issue and this highlights the need for a large cohort study to evaluate these factors. Copyright © 2018 Elsevier Inc. All rights reserved.

Does the width of the surgical margin of safety or premalignant dermatoses at the negative surgical margin affect outcome in surgically treated penile cancer?

PubMed

Gunia, Sven; Koch, Stefan; Jain, Anjun; May, Matthias

2014-03-01

To evaluate the prognostic impact of the width of negative surgical margins (NSM) and associated and preinvasive lesions at the NSM in patients with penile squamous cell cancer (PSC). Enrolling 87 patients with NSM who underwent surgery for PSC, the archived margin slides and entirely wax-embedded surgical margins were retrieved from the pathology files. After step sections were cut, margins were stained with antibodies against CK5/6, p16, p53 and Ki-67 and subjected to in situ hybridisation for high-risk human papillomavirus (HPV). All NSM were histologically examined for squamous hyperplasia (SH), lichen sclerosus (LS) and subtypes of penile intraepithelial neoplasia (PeIN). Then, histological findings were correlated with cancer-specific mortality (CSM, median follow-up 34 months; IQR 6-70). All NSM were negative for high-risk HPV and exhibited SH (p16 and p53 negative, Ki-67 variably positive), LS (p16 negative, variable p53 and Ki-67 positivity) and differentiated PeIN (dPeIN; p16 negative, Ki-67 positive, variable p53 positivity) in 28 (32%), 30 (34%) and 22 (25%) cases, respectively, whereas PeIN subtypes other then dPeIN did not occur. Pathological tumour stage was the only independent predictive parameter with respect to CSM in the multivariable analysis (p=0.001). SH, LS and dPeIN are frequent histological findings at the NSM of surgically treated PSC. However, neither the width of the NSM nor dPeIN, LS or SH at the NSM influences prognostic outcome.

[Pulmonary embolism in patients with cancer: foundations of the EPIPHANY study].

PubMed

Font, Carme; Carmona-Bayonas, Alberto; Plasencia, Juana M; Calvo-Temprano, David; Sánchez, Marcelo; Jiménez-Fonseca, Paula; Beato, Carmen; Biosca, Mercè; Vicente, Vicente; Otero, Remedios

2015-01-01

Pulmonary thromboembolism (PE) is a common cause of morbidity and mortality in patients with cancer. Having cancer is an independent risk factor for death in the general series of patients with PE and is included as a variable in the prognostic scales of acute symptomatic PE. This fact limits the discriminatory power of these general scales for patients with cancer and has prompted the development of specific prognostic tools: POMPE-C and a scale derived from the RIETE registry. Whether the increased risk of death by PE in patients with cancer is due to complications related to the neoplasm or to a greater severity of the thromboembolic episode in this population has not been well studied. Moreover, the introduction of computed multidetector tomography in recent years has led to a growing diagnosis of incidental PE, which currently represents up to half of pulmonary embolisms in patients with cancer. The EPIPHANY study attempts to further the understanding of the characteristics of pulmonary embolisms in patients with cancer by including incidental and symptomatic events. Its primary objectives are a) to understand the clinical and epidemiological patterns of pulmonary embolism associated with cancer and b) to develop and validate a specific prognosis model for PE in this population. The registry includes variables of interest to oncology (cancer type and extent, oncospecific treatments, patient's functional condition, cancer progression), radiological variables (thrombotic burden, signs of ventricular overload and other findings), location of treatment (hospital or outpatient), acute complications and causes of death in patients with PE associated with cancer. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Ultrasonographic reproductive tract measures and pelvis measures as predictors of pregnancy failure and anestrus in restricted bred beef heifers.

PubMed

Holm, Dietmar E; Nielen, Mirjam; Jorritsma, Ruurd; Irons, Peter C; Thompson, Peter N

2016-02-01

Previous reports have shown that reproductive tract score (RTS) can predict reproduction outcomes in seasonally bred beef heifers, although the accuracy can vary. Some ultrasonographic measures of the female reproductive tract and pelvis area have also been associated with reproductive outcome in young heifers. The objectives of this study were to determine which transrectal ultrasound or pelvis measures taken at a single examination are independent predictors of reproductive failure and whether the RTS system can be optimized with this information. In this observational study, year-old beef heifers (n = 488) in 2 birth cohorts were followed from just before the first breeding until confirmation of pregnancy. A single pre-breeding examination included body condition score, RTS, ultrasound measures of the reproductive tract (length and diameter of the left and right ovaries, presence and diameter of a CL, largest follicle diameter and left uterus horn diameter) and transverse and vertical diameters of the pelvis. Additional farm records including dam parity, sire, birth weight and birth date, weaning weight, weaning date, prebreeding body weight, AI dates, and semen used were available. Breeding consisted of 50 days of AI, followed 5 to 7 days later by a 42-day bull breeding period. Pregnancy failure was defined as the failure to become pregnant after the AI and bull breeding periods, while anestrus was defined as the failure to be detected in estrus during the 50-day AI period. From the prebreeding data and farm records, independent predictors of pregnancy failure and anestrus were identified using stepwise reduction in multiple logistic regression models. Age at the onset of breeding was the only consistent independent predictor of pregnancy failure and anestrus in both cohorts of this study (P < 0.05). Body condition score, uterus horn diameter, absence of a CL, largest follicle of less than 13 mm, and pelvis area (PA) were the prebreeding examination variables that remained in prognostic models (P < 0.1). Combining either the model based on the 3 remaining ultrasound measures or RTS with PA provided more accurate prognostic models for pregnancy failure and anestrus than using RTS alone (P < 0.05). It is concluded that ultrasound measures have prognostic value for pregnancy failure in restricted bred yearling heifers as a result of their association with anestrus, and that smaller PA has additional prognostic value for poorly performing heifers. Copyright © 2016 Elsevier Inc. All rights reserved.

A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis

PubMed Central

Kato, Akihiko; Tsuji, Takayuki; Sakao, Yukitoshi; Ohashi, Naro; Yasuda, Hideo; Fujimoto, Taiki; Takita, Takako; Furuhashi, Mitsuyoshi; Kumagai, Hiromichi

2013-01-01

Background/Aims Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD) patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes. Methods We calculated the 6 prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI), which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85) and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality. Results Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC) was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p < 0.01) and for a PNI of 0.616 (95% CI: 0.553-0.768; p = 0.01). However, AUC for hypoalbuminemia (<3.5 g/dl) was comparable to that of GPS (0.695, 95% CI: 0.632-0.759; p < 0.01). Conclusion GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients. PMID:24403910

Additional value of anaerobic threshold in a general mortality prediction model in a urban patient cohort with Chagas cardiomyopathy.

PubMed

Silva, Roberto Ribeiro da; Reis, Michel Silva; Pereira, Basílio de Bragança; Nascimento, Emilia Matos do; Pedrosa, Roberto Coury

2017-12-01

Anaerobic threshold (AT) is recognized as objective and direct measurement that reflects variations in metabolism of skeletal muscles during exercise. Its prognostic value in heart diseases of non-chagasic etiology is well established. However, the assessment of risk of death in Chagas heart disease is relatively well established by Rassi score. But, the added value that AT can bring to Rassi score has not been studied yet. To assess whether AT presents additional effect to Rassi score in patients with chronic Chagas' heart disease. Prospective research of dynamic cohort by review of 150 medical records of patients. Were selected for cohort 45 medical records of patients who underwent cardiopulmonary exercise testing between 1996-1997 and followed until September 2015. Data analysis to detect association between studied variables can be seen using a logistic regression model. The suitability of the models was verified using ROC curves and the coefficient of determination R 2 . 8 patients (17.78%) died by September 2015, with 7 of them (87.5%) from cardiovascular causes, of which 4 (57.14%) were considered on high risk by Rassi score. With Rassi score as independent variable, and death being the outcome, we obtained an area under the curve (AUC)=0.711, with R 2 =0.214. Instituting AT as independent variable, we found AUC=0.706, with R 2 =0.078. When we define Rassi score and AT as independent variables, it was obtained AUC=0.800 and R 2 =0.263. when AT is included in logistic regression, it increases by 5% the explanation (R 2 ) to the death estimation. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

High Myeloperoxidase Positive Cell Infiltration in Colorectal Cancer Is an Independent Favorable Prognostic Factor

PubMed Central

Eppenberger-Castori, Serenella; Zlobec, Inti; Viehl, Carsten T.; Frey, Daniel M.; Nebiker, Christian A.; Rosso, Raffaele; Zuber, Markus; Amicarella, Francesca; Iezzi, Giandomenica; Sconocchia, Giuseppe; Heberer, Michael; Lugli, Alessandro; Tornillo, Luigi; Oertli, Daniel

2013-01-01

Background Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). Methods A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. Results MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO−. Conclusions High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC. PMID:23734221

Twenty-four-hour packed red blood cell requirement is the strongest independent prognostic marker of mortality in ED trauma patients.

PubMed

Arslan, Albert; Flax, Lindsey; Fraser, Robert; Kanter, Marc; Simon, Ronald; Caputo, Nicholas D

2016-06-01

Injury severity score, serum lactate, and shock index help the physician determine the severity of injuries present and have been shown to relate to mortality. We sought to determine if an increasing amount of packed red blood cells (PRBCs) given in the first 24hours of admission is an independent predictor of mortality and how it compares to other validated markers. A 6-year retrospective, observational study of adult trauma patients was conducted at a level 1 trauma center. Charts were reviewed for demographic data, amount of PRBC received in the first 24hours, injury severity score, shock index, and lactate levels. Subgroups were used to determine if each variable was an independent predictor of mortality. Correlation coefficients and linear regression were used to determine the strength of correlation between each variable and mortality. One hundred fifty-seven patients met criteria over a 6-year period. The average age was 28years, 93% were male, and 86% had penetrating injuries. The average injury severity score, serum lactate, and shock index were 18, 6.1, and 0.9, respectively. The average amount of blood given was 6.7 U. Twenty-four-hour PRBC requirement is both a novel independent predictor of and has the greatest correlation to mortality in adult trauma patients when compared to injury severity score, shock index, and serum lactate. Copyright © 2016 Elsevier Inc. All rights reserved.

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

PubMed

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Campbell, Michael J; Hurdman, Judith; Thomas, Steve; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2014-01-01

There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.

PubMed

Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H

2014-09-01

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

PubMed

Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2012-03-10

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

[Exercise stress test and dobutamine stress echocardiography for the prognostic stratification after uncomplicated acute myocardial infarction].

PubMed

Vitiello, Nicola; Cirillo, Raffaele; Granato, Luigi; Coppola, Vincenzo; di Palma, Francesco

2007-05-01

Exercise stress test and dobutamine stress echocardiography are usually performed early after an uncomplicated acute myocardial infarction in the prognostic stratification of patients to define the optimal diagnostic and therapeutic procedure. The aim of this study was to evaluate if the association of an imaging test could increase exercise test capability to identify patients with residual ischemia and patients at high risk of events in the follow-up. Four hundred and forty-two consecutive patients underwent exercise stress testing and dobutamine stress echocardiography before discharge and subsequently coronary angiography within 30 days. In case of submaximal negative result at the exercise test, this was repeated 20 days after discharge. The follow-up lasted 26.8 +/- 9 months. The endpoints were death, reinfarction, and unstable angina requiring hospitalization or revascularization intervention. Both tests and their association showed a higher sensitivity in males; in females dobutamine stress echocardiography had a higher specificity. In females, the addition of dobutamine stress echocardiography increased either the negative or the positive prognostic values of exercise stress test by 31% and 5.6%, respectively. In males, the negative prognostic value increased by 15.5%, whereas the positive prognostic value decreased by 12%. A low exercise capability (<6 METs) showed an event predictive value independent of test results and any other variables. The event-free survival curves correlated with exercise capability differed shortly after the first months both in males and females. These results suggest different stratification procedures with regard to gender: in males, the exercise stress test might be sufficient at discharge, to be repeated 20 days later, if submaximal negative. In females, it seems to be useful to associate an imaging test at discharge. In any case, the exercise stress test remains the main step in the stratification procedure also for its capability to identify patients who are at high risk of events in the follow-up.

Prognostic value of the physical examination in patients with heart failure and atrial fibrillation: insights from the AF-CHF trial (atrial fibrillation and chronic heart failure).

PubMed

Caldentey, Guillem; Khairy, Paul; Roy, Denis; Leduc, Hugues; Talajic, Mario; Racine, Normand; White, Michel; O'Meara, Eileen; Guertin, Marie-Claude; Rouleau, Jean L; Ducharme, Anique

2014-02-01

This study sought to assess the prognostic value of physical examination in a modern treated heart failure population. The physical examination is the cornerstone of the evaluation and monitoring of patients with heart failure. Yet, the prognostic value of congestive signs (i.e., peripheral edema, jugular venous distension, a third heart sound, and pulmonary rales) has not been assessed in the current era. A post-hoc analysis was conducted on all 1,376 patients, 81% male, mean age 67 ± 11 years, with symptomatic left ventricular systolic dysfunction enrolled in the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial. The prognostic value of baseline physical examination findings was assessed in univariate and multivariate Cox regression analyses. Peripheral edema was observed in 425 (30.9%), jugular venous distension in 297 (21.6%), a third heart sound in 207 (15.0%), and pulmonary rales in 178 (12.9%) patients. Death from cardiovascular causes occurred in 357 (25.9%) patients over a mean follow-up of 37 ± 19 months. All 4 physical examination findings were associated with cardiovascular mortality in univariate analyses (all p values <0.01). In multivariate analyses, taking all 4 signs as potential covariates, only rales (hazard ratio 1.41; 95% confidence interval: 1.07 to 1.86; p = 0.013) and peripheral edema (hazard ratio: 1.25; 95% confidence interval: 1.00 to 1.57; p = 0.048) were associated with cardiovascular mortality, independent of other variables. In the modern era, congestive signs on the physical examination (i.e., peripheral edema, jugular venous distension, a third heart sound, and pulmonary rales) continue to provide important prognostic information in patients with congestive heart failure. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Ion channel gene expression predicts survival in glioma patients

PubMed Central

Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

2015-01-01

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283

A Finite-Volume "Shaving" Method for Interfacing NASA/DAO''s Physical Space Statistical Analysis System to the Finite-Volume GCM with a Lagrangian Control-Volume Vertical Coordinate

NASA Technical Reports Server (NTRS)

Lin, Shian-Jiann; DaSilva, Arlindo; Atlas, Robert (Technical Monitor)

2001-01-01

Toward the development of a finite-volume Data Assimilation System (fvDAS), a consistent finite-volume methodology is developed for interfacing the NASA/DAO's Physical Space Statistical Analysis System (PSAS) to the joint NASA/NCAR finite volume CCM3 (fvCCM3). To take advantage of the Lagrangian control-volume vertical coordinate of the fvCCM3, a novel "shaving" method is applied to the lowest few model layers to reflect the surface pressure changes as implied by the final analysis. Analysis increments (from PSAS) to the upper air variables are then consistently put onto the Lagrangian layers as adjustments to the volume-mean quantities during the analysis cycle. This approach is demonstrated to be superior to the conventional method of using independently computed "tendency terms" for surface pressure and upper air prognostic variables.

Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations.

PubMed

Miyata, Tatsunori; Yamashita, Yo-Ichi; Yamao, Takanobu; Umezaki, Naoki; Tsukamoto, Masayo; Kitano, Yuki; Yamamura, Kensuke; Arima, Kota; Kaida, Takayoshi; Nakagawa, Shigeki; Imai, Katsunori; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Baba, Hideo

2017-06-01

The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations. We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model. Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications. Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma.

Low Platelet to White Blood Cell Ratio Indicates Poor Prognosis for Acute-On-Chronic Liver Failure.

PubMed

Jie, Yusheng; Gong, Jiao; Xiao, Cuicui; Zhu, Shuguang; Zhou, Wenying; Luo, Juan; Chong, Yutian; Hu, Bo

2018-01-01

Background. Platelet to white blood cell ratio (PWR) was an independent prognostic predictor for outcomes in some diseases. However, the prognostic role of PWR is still unclear in patients with hepatitis B related acute-on-chronic liver failure (ACLF). In this study, we evaluated the clinical performances of PWR in predicting prognosis in HBV-related ACLF. Methods. A total of 530 subjects were recruited, including 97 healthy controls and 433 with HBV-related ACLF. Liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing were performed at admission. Results . At baseline, PWR in patients with HBV-related ACLF (14.03 ± 7.17) was significantly decreased compared to those in healthy controls (39.16 ± 9.80). Reduced PWR values were clinically associated with the severity of liver disease and the increased mortality rate. Furthermore, PWR may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 0.660, 95% CI: 0.438-0.996, p = 0.048) as well as model for end-stage liver disease (MELD) score. Conclusions . The PWR values were markedly decreased in ACLF patients compared with healthy controls and associated with severe liver disease. Moreover, PWR was an independent prognostic indicator for the mortality rate in patients with ACLF. This investigation highlights that PWR comprised a useful biomarker for prediction of liver severity.

Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer.

PubMed

Nakamura, Kenichi; Yoshida, Naoya; Baba, Yoshifumi; Kosumi, Keisuke; Uchihara, Tomoyuki; Kiyozumi, Yuki; Ohuchi, Mayuko; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Sakamoto, Yasuo; Watanabe, Masayuki; Baba, Hideo

2017-06-01

The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.

The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature

PubMed Central

Díaz-Beyá, Marina; Brunet, Salut; Nomdedéu, Josep; Pratcorona, Marta; Cordeiro, Anna; Gallardo, David; Escoda, Lourdes; Tormo, Mar; Heras, Inmaculada; Ribera, Josep Maria; Duarte, Rafael; de Llano, María Paz Queipo; Bargay, Joan; Sampol, Antonia; Nomdedeu, Mertixell; Risueño, Ruth M.; Hoyos, Montserrat; Sierra, Jorge; Monzo, Mariano; Navarro, Alfons; Esteve, Jordi

2015-01-01

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown. We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients. The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33- microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004). Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature. PMID:26436590

Latent class analysis derived subgroups of low back pain patients - do they have prognostic capacity?

PubMed

Molgaard Nielsen, Anne; Hestbaek, Lise; Vach, Werner; Kent, Peter; Kongsted, Alice

2017-08-09

Heterogeneity in patients with low back pain is well recognised and different approaches to subgrouping have been proposed. One statistical technique that is increasingly being used is Latent Class Analysis as it performs subgrouping based on pattern recognition with high accuracy. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two-stage approach. However, their prognostic capacity was unexplored. This study (i) determined whether the subgrouping approaches were associated with the future outcomes of pain intensity, pain frequency and disability, (ii) assessed whether one of these two approaches was more strongly or more consistently associated with these outcomes, and (iii) assessed the performance of the novel subgroupings as compared to the following variables: two existing subgrouping tools (STarT Back Tool and Quebec Task Force classification), four baseline characteristics and a group of previously identified domain-specific patient categorisations (collectively, the 'comparator variables'). This was a longitudinal cohort study of 928 patients consulting for low back pain in primary care. The associations between each subgroup approach and outcomes at 2 weeks, 3 and 12 months, and with weekly SMS responses were tested in linear regression models, and their prognostic capacity (variance explained) was compared to that of the comparator variables listed above. The two previously identified subgroupings were similarly associated with all outcomes. The prognostic capacity of both subgroupings was better than that of the comparator variables, except for participants' recovery beliefs and the domain-specific categorisations, but was still limited. The explained variance ranged from 4.3%-6.9% for pain intensity and from 6.8%-20.3% for disability, and highest at the 2 weeks follow-up. Latent Class-derived subgroups provided additional prognostic information when compared to a range of variables, but the improvements were not substantial enough to warrant further development into a new prognostic tool. Further research could investigate if these novel subgrouping approaches may help to improve existing tools that subgroup low back pain patients.

Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging.

PubMed

Pu, Yonglin; Zhang, James X; Liu, Haiyan; Appelbaum, Daniel; Meng, Jianfeng; Penney, Bill C

2018-06-07

We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging. We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG-avid tumor divided into modeling and validation cohorts based on the type of PET/CT scanner used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system. The cut-off values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both the modeling and validation cohorts to determine each patient's MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p < 0.01), independent of TNM stage together with other clinical prognostic factors, and the discriminatory power of the MTVwb risk stratification system, as measured by Gönen and Heller's concordance index, was not significantly different from that of TNM stage in both cohorts. Also, the prognostic value of the MTVwb risk stratum was robust in the two randomized cohorts. The discordance rate between the MTVwb risk stratum and TNM stage or substage was 45.1% in the modeling cohort and 50.3% in the validation cohort. This study developed and validated a novel MTVwb risk stratification system, which has prognostic value independent of the TNM stage and other clinical prognostic factors in NSCLC, suggesting that it could be used for further NSCLC pretreatment assessment and for refining treatment decisions in individual patients.

Prognostic factors of primary gastrointestinal stromal tumors: a cohort study based on high-volume centers.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2018-02-01

We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Of the included patients, 1,375 (53.5%) were male, and the patient age range was 18 to 95 (median, 58) years. The tumors were mostly found in the stomach (64.5%), small intestine (25.1%) and colorectal region (5.1%). At the time of diagnosis, the median tumor size was 4.0 (range: 0.1-55.0) cm, and the median mitotic index per 50 high power fields (HPFs) was 3 (range: 0-254). Of the 2,168 resected patients, 2,009 (92.7%) received curative resection. According to the modified National Institutes of Health (NIH) classification, 21.9%, 28.9%, 14.1% and 35.1% were very low-, low-, intermediate- and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1 (DOG-1), 8.0% for S-100, 31.0% for smooth muscle actin (SMA) and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib (P<0.001), whereas intermediate-risk patients did not (P=0.954). Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma.

PubMed

Ning, Zhong-Hua; Zhao, Wei; Li, Xiao-Dong; Chen, Lu-Jun; Xu, Bin; Gu, Wen-Dong; Shao, Ying-Jie; Xu, Yun; Huang, Jin; Pei, Hong-Lei; Jiang, Jing-Ting

2015-01-01

Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.

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

PubMed

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

2015-08-01

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

Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

PubMed

Berry, C; Poppe, K K; Gamble, G D; Earle, N J; Ezekowitz, J A; Squire, I B; McMurray, J J V; McAlister, F A; Komajda, M; Swedberg, K; Maggioni, A P; Ahmed, A; Whalley, G A; Doughty, R N; Tarantini, L

2016-06-01

Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). Individual person data meta-analysis. Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Metric substage according to micro and extensive lamina propria invasion improves prognostics in T1 bladder cancer.

PubMed

Fransen van de Putte, Elisabeth E; Otto, Wolfgang; Hartmann, Arndt; Bertz, Simone; Mayr, Roman; Bründl, Johannes; Breyer, Johannes; Manach, Quentin; Compérat, Eva M; Boormans, Joost L; Bosschieter, Judith; Jewett, Michael A S; Stoehr, Robert; van Leenders, Geert J L H; Nieuwenhuijzen, Jakko A; Zlotta, Alexandre R; Hendricksen, Kees; Rouprêt, Morgan; Burger, Maximilian; van der Kwast, Theo H; van Rhijn, Bas W G

2018-06-04

Reliable prognosticators for T1 bladder cancer (T1BC) are urgently needed. To compare the prognostic value of 2 substage systems for T1BC in patients treated by transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin therapy. The slides of 601 primary T1BCs from four institutes were reviewed by 2 uropathologists and substaged according to 2 classifications: metric substage according to T1 microinvasive (T1m-lamina propria invasion <0.5mm) and T1 extensive invasive (pT1e-invasion ≥ 0.5mm), and according to invasion of the muscularis mucosae (MM) (T1a-invasion above or into MM/T1b). Multivariable analyses for progression-free (PFS) and cancer-specific survival (CSS) were performed including substage, size, multiplicity, carcinoma in situ, sex, age, WHO-grade 1973, and WHO-grade 2004 as variables. Median follow-up was 5.9 years (interquartile range: 3.3-9.0). Progression to T2BC was observed in 148 (25%) patients and 94 (16%) died of BC. The MM was not present at the invasion front in 135 (22%) of tumors. Slides were substaged as follows: 213 T1m and 388 T1e and 281 T1a and 320 T1b. On multivariable analysis, T1m/e substage and WHO 1973 grade were the strongest prognosticators for PFS (hazard ratio [HR] = 3.8 and HR = 1.8) and CSS (HR = 2.7 and HR = 2.6), respectively. Other prognostic factors for CSS were age (HR = 1.03), and tumor size (HR = 1.8). Substage according to MM-invasion was not significant. Our study was limited by its retrospective design and that standard re-TUR was not performed if TUR was macroscopically complete and muscularis propria was present in resected specimens. Metric substaging of T1BC was possible in all cases of 601 T1BC patients and it was a strong independent prognosticator of both PFS and CSS. Copyright © 2018 Elsevier Inc. All rights reserved.

Methodological issues and recommendations for systematic reviews of prognostic studies: an example from cardiovascular disease.

PubMed

Dretzke, Janine; Ensor, Joie; Bayliss, Sue; Hodgkinson, James; Lordkipanidzé, Marie; Riley, Richard D; Fitzmaurice, David; Moore, David

2014-12-03

Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be 'good practice' approaches. The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether 'aspirin resistance' (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors. Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results. Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.

Prognostic significance of lactate/proton symporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder.

PubMed

Choi, Jung-Woo; Kim, Younghye; Lee, Ju-Han; Kim, Young-Sik

2014-07-01

To investigate the prognostic significance of lactate/proton monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder (UCB). We examined the expressions of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by immunohistochemistry. The immunohistochemical expressions were quantified using an ImageJ-based analysis program. MCT1, MCT4, and CD147 expressions were increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively. Most tumor cells showed diffuse membranous staining, whereas normal urothelial cells showed negative or weak staining. High levels of MCT1 expression correlated with high World Health Organization grade (P<.001), advanced tumor node metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic tumor invasion (P=.010), whereas high levels of MCT4 expression did not significantly correlate with any of these variables. High CD147 expression was associated with high World Health Organization grade (P<.001), advanced tumor node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were associated with poor overall survival and that high MCT4 expression was correlated with poor recurrence-free survival (P=.036). Multivariate analyses revealed that high MCT1 and MCT4 expressions were independent prognostic factors for poor overall survival and poor recurrence-free survival, respectively, in UCB patients. Our results indicate that increased MCT1, MCT4, and CD147 expressions have prognostic implications in UCB and suggest their roles in urothelial cancer metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Prognostic and diagnostic significance of mid-regional pro-atrial natriuretic peptide in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 Study.

PubMed

Pervez, Mohammad Osman; Winther, Jacob A; Brynildsen, Jon; Strand, Heidi; Christensen, Geir; Høiseth, Arne Didrik; Myhre, Peder L; Røysland, Ragnhild; Lyngbakken, Magnus Nakrem; Omland, Torbjørn; Røsjø, Helge

2018-05-07

To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n = 313), on day 2 (n = 234), and before discharge (n = 91) and compared for diagnosing acute heart failure (HF; n = 143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n = 84) separately. The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p < 0.001) and the receiver-operating area under the curve was 0.85 (95% CI 0.81-0.89) for MR-proANP and 0.86 (0.82-0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816 days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio ( ln MR-proANP) 1.98 (95% CI 1.17-3.34). MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.

mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group

PubMed Central

Rodríguez, Marta; Cantos, Blanca; Sabín, Pilar; Quero, Cristina; García-Arroyo, Francisco R.; Rueda, Antonio; Maximiano, Constanza; Rodríguez-Abreu, Delvys; Sánchez, Antonio; Silva, Javier

2017-01-01

Purpose To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. Patients and Methods Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. Results In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of PTEN and BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate. The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in follicular lymphomas, were associated with short progression-free survival. BCL-6 and C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA may provide prognostic information with respect to overall survival. BCL-XL mRNA and increase of BCL-6 mRNA in post-treatment samples could serve as molecular monitoring markers. Conclusions This is the first large study to evaluate the prognostic and predictive values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA positivity in pretreatment samples were predictors of worse PFS compared to patients with mRNA negativity. C-MYC mRNA positivity was also a statistically significant predictor of inability to obtain complete response with first-line therapy. PMID:28881619

mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group.

PubMed

Provencio, Mariano; Rodríguez, Marta; Cantos, Blanca; Sabín, Pilar; Quero, Cristina; García-Arroyo, Francisco R; Rueda, Antonio; Maximiano, Constanza; Rodríguez-Abreu, Delvys; Sánchez, Antonio; Silva, Javier; García, Vanesa

2017-08-01

To determine the feasibility of mRNAs ( C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT ) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of PTEN and BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate. The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in follicular lymphomas, were associated with short progression-free survival. BCL-6 and C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA may provide prognostic information with respect to overall survival. BCL-XL mRNA and increase of BCL-6 mRNA in post-treatment samples could serve as molecular monitoring markers. This is the first large study to evaluate the prognostic and predictive values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA positivity in pretreatment samples were predictors of worse PFS compared to patients with mRNA negativity. C-MYC mRNA positivity was also a statistically significant predictor of inability to obtain complete response with first-line therapy.

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

PubMed

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

2018-03-01

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

Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation.

PubMed

Magrì, Damiano; Agostoni, Piergiuseppe; Corrà, Ugo; Passino, Claudio; Scrutinio, Domenico; Perrone-Filardi, Pasquale; Correale, Michele; Cattadori, Gaia; Metra, Marco; Girola, Davide; Piepoli, Massimo F; Iorio, AnnaMaria; Emdin, Michele; Raimondo, Rosa; Re, Federica; Cicoira, Mariantonietta; Belardinelli, Romualdo; Guazzi, Marco; Limongelli, Giuseppe; Clemenza, Francesco; Parati, Gianfranco; Frigerio, Maria; Casenghi, Matteo; Scardovi, Angela B; Ferraironi, Alessandro; Di Lenarda, Andrea; Bussotti, Maurizio; Apostolo, Anna; Paolillo, Stefania; La Gioia, Rocco; Gargiulo, Paola; Palermo, Pietro; Minà, Chiara; Farina, Stefania; Battaia, Elisa; Maruotti, Antonello; Pacileo, Giuseppe; Contini, Mauro; Oliva, Fabrizio; Ricci, Roberto; Sinagra, Gianfranco

2015-08-01

Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p = 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted. © The European Society of Cardiology 2014.

Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421.

PubMed

Lara, Primo N; Ely, Benjamin; Quinn, David I; Mack, Philip C; Tangen, Catherine; Gertz, Erik; Twardowski, Przemyslaw W; Goldkorn, Amir; Hussain, Maha; Vogelzang, Nicholas J; Thompson, Ian M; Van Loan, Marta D

2014-04-01

Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration-resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value of bone biomarkers in sera from CRPC patients treated on a placebo-controlled phase III trial of docetaxel with or without the bone targeted endothelin-A receptor antagonist atrasentan (SWOG S0421). Markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) were assayed in pretreatment and serial sera. Cox proportional hazards regression models were fit for overall survival. Models were fit with main effects for marker levels and with/without terms for marker-treatment interaction, adjusted for clinical variables, to assess the prognostic and predictive value of atrasentan. Analysis was adjusted for multiple comparisons. Two-sided P values were calculated using the Wald test. Sera from 778 patients were analyzed. Elevated baseline levels of each of the markers were associated with worse survival (P < .001). Increasing marker levels by week nine of therapy were also associated with subsequent poor survival (P < .001). Patients with the highest marker levels (upper 25th percentile for all markers) not only had a poor prognosis (hazard ratio [HR] = 4.3; 95% confidence interval [CI] = 2.41 to 7.65; P < .001) but also had a survival benefit from atrasentan (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months [placebo]; P interaction = .005). Serum bone metabolism markers have statistically significant independent prognostic value in CRPC. Importantly, a small group of patients (6%) with highly elevated markers of bone turnover appear to preferentially benefit from atrasentan therapy.

Prognostic pathologic factors in radical cystectomy after neoadjuvant chemotherapy.

PubMed

Brimo, Fadi; Downes, Michelle R; Jamaspishvili, Tamara; Berman, David; Barkan, Guliz A; Athanazio, Daniel; Abro, Schuharazad; Visram, Kash; Yilmaz, Asli; Solanki, Shraddha; Hahn, Elan; Siemens, Robert; Kassouf, Wassim; Trpkov, Kiril

2018-05-18

We undertook a systematic evaluation of the prognostic value of numerous histologic factors in 165 radical cystectomies (RC) of patients with invasive urothelial carcinoma who underwent surgery after neoadjuvant chemotherapy (NAC). Tumor regression grade (TRG) and therapy-related stromal and epithelial changes were also recorded. Locally advanced disease (≥pT2 and/or pN+) was present in 64% of patients, 22% had no evidence of residual carcinoma (pT0+pN0) and 28% had no evidence of residual muscle invasive carcinoma (≤pT1+N0). TRG 1, 2, and 3 were found in 32%, 15%, and 50% of patients, respectively. Histologic variants of UC were reported in 25% of cases. The most common therapy-related stromal change was fibroblastic reaction (78%) and the most common epithelial change in residual UC was smudgy and poorly preserved chromatin (28%). Prominent stromal and epithelial changes were noted in 41% and 5% of RC, respectively. Progression was found in 45% of patients and cancer-related deaths occurred in 30%. Multivariate analysis showed that the only independent prognostic parameters for progression were T stage, N stage, lymphovascular invasion, and the margin status. Similarly, only T stage, N stage, and the margin status correlated with cancer-related deaths. Neither TRG, nor any of the stromal or epithelial-related variables correlated with outcome. We confirm that the traditional and routinely-reported histologic parameters in RC post-NAC remain the most powerful prognosticators of disease course. The significance of TRG in the bladder remains unconfirmed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.

PubMed

Reddy, Sreekanth P; Britto, Ramona; Vinnakota, Katyayni; Aparna, Hebbar; Sreepathi, Hari Kishore; Thota, Balaram; Kumari, Arpana; Shilpa, B M; Vrinda, M; Umesh, Srikantha; Samuel, Cini; Shetty, Mitesh; Tandon, Ashwani; Pandey, Paritosh; Hegde, Sridevi; Hegde, A S; Balasubramaniam, Anandh; Chandramouli, B A; Santosh, Vani; Kondaiah, Paturu; Somasundaram, Kumaravel; Rao, M R Satyanarayana

2008-05-15

Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.

Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma.

PubMed

Dimopoulou, Maria; Kirpensteijn, Jolle; Moens, Hester; Kik, Marja

2008-07-01

To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated. Retrospective study. Cats (n=62) and dogs (22). Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis. Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator. Feline and canine skeletal OS have similar histologic but different prognostic characteristics. Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.

Prognostic indicators for dogs with dilated cardiomyopathy.

PubMed

Borgarelli, Michele; Santilli, Roberto A; Chiavegato, David; D'Agnolo, Gino; Zanatta, Renato; Mannelli, Alessandro; Tarducci, Alberto

2006-01-01

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.

The wisdom of the commons: ensemble tree classifiers for prostate cancer prognosis.

PubMed

Koziol, James A; Feng, Anne C; Jia, Zhenyu; Wang, Yipeng; Goodison, Seven; McClelland, Michael; Mercola, Dan

2009-01-01

Classification and regression trees have long been used for cancer diagnosis and prognosis. Nevertheless, instability and variable selection bias, as well as overfitting, are well-known problems of tree-based methods. In this article, we investigate whether ensemble tree classifiers can ameliorate these difficulties, using data from two recent studies of radical prostatectomy in prostate cancer. Using time to progression following prostatectomy as the relevant clinical endpoint, we found that ensemble tree classifiers robustly and reproducibly identified three subgroups of patients in the two clinical datasets: non-progressors, early progressors and late progressors. Moreover, the consensus classifications were independent predictors of time to progression compared to known clinical prognostic factors.

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease.

PubMed

Baron Toaldo, Marco; Romito, Giovanni; Guglielmini, Carlo; Diana, Alessia; Pelle, Nazzareno G; Contiero, Barbara; Cipone, Mario

2018-05-01

The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). One-hundred and fifteen dogs of different breeds with MMVD. Prospective cohort study. Conventional morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac-related death. Most of the tested variables, including all LA STE-derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10-4.89; P = .024) remained statistically significant in the multivariable analysis. The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE-derived variables. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

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

PubMed

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

2018-01-02

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

[Clinical research IV. Relevancy of the statistical test chosen].

PubMed

Talavera, Juan O; Rivas-Ruiz, Rodolfo

2011-01-01

When we look at the difference between two therapies or the association of a risk factor or prognostic indicator with its outcome, we need to evaluate the accuracy of the result. This assessment is based on a judgment that uses information about the study design and statistical management of the information. This paper specifically mentions the relevance of the statistical test selected. Statistical tests are chosen mainly from two characteristics: the objective of the study and type of variables. The objective can be divided into three test groups: a) those in which you want to show differences between groups or inside a group before and after a maneuver, b) those that seek to show the relationship (correlation) between variables, and c) those that aim to predict an outcome. The types of variables are divided in two: quantitative (continuous and discontinuous) and qualitative (ordinal and dichotomous). For example, if we seek to demonstrate differences in age (quantitative variable) among patients with systemic lupus erythematosus (SLE) with and without neurological disease (two groups), the appropriate test is the "Student t test for independent samples." But if the comparison is about the frequency of females (binomial variable), then the appropriate statistical test is the χ(2).

Do the key prognostic factors for non-specific neck pain have moderation effects? - A study protocol.

PubMed

Balasundaram, Arun Prasad; Robinson, Hilde Stendal; Vøllestad, Nina Køpke

2018-05-01

Neck pain is one of the common musculoskeletal conditions prevalent in the general population in Norway. Patients with neck pain, seek treatment from different health professionals such as general practitioners, physiotherapists, chiropractors and alternative medicine practitioners. The interventions for neck pain are typically provided in a primary care or specialised healthcare setting depending on the general practitioners' referral patterns. Clinicians are interested to know the various prognostic factors that can explain the recovery from neck pain. In order to know this, studies have explored and reported on a range of prognostic factors that contribute to the outcomes in patients with neck pain. This information is currently available only for neck pain following whiplash injury that has a traumatic origin. There is limited information on the role of prognostic factors specifically for non-specific neck pain without a traumatic episode. Moreover, there is a lack of data on whether there are interactions (moderation effects) between the prognostic factors. Therefore, we propose a hypothesis to elucidate whether the same set of prognostic factors found in neck pain associated with whiplash injuries are also identified in patients with neck pain without trauma. Additionally, we hypothesize that the association between a prognostic factor and the outcome variable (s) would be dependent on the third variable, thereby confirming the moderation effects. Clinicians could make informed decisions in the clinical management of neck pain with the knowledge of prognostic factors that explain the outcomes. It could also be used for the development of new interventions or for modifying the existing ones. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination).

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Lubatti, Chiara; Meani, Laura; Zahalkova, Lenka; Zeni, Silvana; Fantini, Flavio

2008-07-01

To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5-year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs). The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1-8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries). The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P = 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm-based prognostic index. The model was internally and externally validated. Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.

Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy.

PubMed

Jokeit, H; Ebner, A; Holthausen, H; Markowitsch, H J; Moch, A; Pannek, H; Schulz, R; Tuxhorn, I

1997-08-01

Prognostic variables for individual memory outcome after left anterior temporal lobectomy (ATL) were studied in 27 patients with refractory temporal lobe epilepsy. The difference between pre- and postoperative performance in the delayed recall of two prose passages (Story A and B) from the Wechsler Memory Scale served as measure of postoperative memory change. Fifteen independent clinical, neuropsychological, and electrophysiological variables were submitted to a multiple linear regression analysis. Preoperative immediate and delayed recall of story content and right hemisphere Wada memory performance for pictorial and verbal items explained very well postoperative memory changes in recall of Story B. Delayed recall of Story B, but not of Story A, had high concurrent validity to other measures of memory. Patients who became seizure-free did not differ in memory change from patients who continued to have seizures after ATL. The variables age at epilepsy onset and probable age at temporal lobe damage provided complementary information for individual prediction but with less effectiveness than Wada test data. Our model confirmed that good preoperative memory functioning and impaired right hemispheric Wada memory performance for pictorial items predict a high risk of memory loss after left ATL. The analyses demonstrate that the combination of independent measures delivers more information than Wada test performance or any other variable alone. The suggested function can be used routinely to estimate the individual severity of verbal episodic memory impairment that might occur after left-sided ATL and offers a rational basis for the counseling of patients.

Factors affecting outcome in ocular myasthenia gravis.

PubMed

Mazzoli, Marco; Ariatti, Alessandra; Valzania, Franco; Kaleci, Shaniko; Tondelli, Manuela; Nichelli, Paolo F; Galassi, Giuliana

2018-01-01

50%-60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables. We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients. Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL. Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.

Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

PubMed

Findeisen, Peter; Zapatka, Marc; Peccerella, Teresa; Matzk, Heike; Neumaier, Michael; Schadendorf, Dirk; Ugurel, Selma

2009-05-01

Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma, nasal type: a triple-center study.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Tang, Tian; Zhang, Pei-Ying; Jiang, Wen-Qi

2017-07-31

The prognostic significance of ABO blood type for lymphoma is largely unknown. We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers. The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models. The prognostic values of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were also evaluated. Compared with patients with blood type O, those with blood type non-O tended to display elevated baseline serum C-reactive protein levels (P = 0.038), lower rate of complete remission (P = 0.005), shorter progression-free survival (PFS, P < 0.001), and shorter overall survival (OS, P = 0.001). Patients with blood type O/AB had longer PFS (P < 0.001) and OS (P = 0.001) compared with those with blood type A/B. Multivariate analysis demonstrated that age >60 years (P < 0.001), mass ≥5 cm (P = 0.001), stage III/IV (P < 0.001), elevated serum lactate dehydrogenase (LDH) levels (P = 0.001), and blood type non-O were independent adverse predictors of OS (P = 0.001). ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low- and high-to-intermediate-risk groups. ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer.

PubMed

Wikberg, Maria L; Ling, Agnes; Li, Xingru; Öberg, Åke; Edin, Sofia; Palmqvist, Richard

2017-10-01

The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC. The infiltration of CD66b-positive cells was semi-quantitatively evaluated along the tumor invasive front, in the tumor center, and within the tumor epithelium (intraepithelial expression). We found that poor infiltration of CD66b-positive cells in the tumor front indicated a worse patient prognosis. The prognostic significance of CD66b infiltration was found to be mainly independent of tumor molecular characteristics and maintained significance in multivariable analysis of stage I-II colon cancers. We further analyzed the prognostic impact of CD66b-positive cells in relation to other immune markers (NOS2, CD163, Tbet, FOXP3, and CD8) and found that neutrophil infiltration, even though strongly correlated to infiltration of other immune cell subsets, had additional prognostic value. In conclusion, we find that low infiltration of neutrophils in the tumor front is an independent prognostic factor for a poorer patient prognosis in early stages of colon cancers. Further studies are needed to elucidate the biological role of neutrophils in colorectal carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: Systematic review and meta-analysis.

PubMed

Adams, Hugo J A; Kwee, Thomas C

2016-10-01

This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MEDLINE and EMBASE were systematically searched for suitable studies. Included studies were methodologically appraised, and results were summarized both descriptively and meta-analytically. Nine studies, comprising a total of 996 R-CHOP-treated DLBCL patients, were included. Overall, studies were of moderate methodological quality. The area under the summary receiver operating curve (AUC) of interim FDG-PET in predicting treatment failure and death were 0.651 and 0.817, respectively. There was no heterogeneity in diagnostic odds ratios across available studies (I(2)=0.0%). At multivariable analysis, 2 studies reported interim FDG-PET to have independent prognostic value in addition to the International Prognostic Index (IPI) in predicting treatment failure, whereas 3 studies reported that this was not the case. One study reported interim FDG-PET to have independent prognostic value in addition to the IPI in predicting death, whereas 2 studies reported that this was not the case. In conclusion, interim FDG-PET in R-CHOP-treated DLBCL has some correlation with outcome, but its prognostic value is homogeneously suboptimal across studies and it has not consistently proven to surpass the prognostic potential of the IPI. Moreover, there is a lack of studies that compared interim FDG-PET to the recently developed and superior National Comprehensive Cancer Network-IPI. Therefore, at present there is no scientific base to support the clinical use of interim FDG-PET in R-CHOP-treated DLBCL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study.

PubMed

Cotte, E; Peyrat, P; Piaton, E; Chapuis, F; Rivoire, M; Glehen, O; Arvieux, C; Mabrut, J-Y; Chipponi, J; Gilly, F-N

2013-07-01

In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria.

PubMed

Goh, Brian K P; Chow, Pierce K H; Yap, Wai-Ming; Kesavan, Sittampalam M; Song, In-Chin; Paul, Pradeep G; Ooi, Boon-Swee; Chung, Yaw-Fui A; Wong, Wai-Keong

2008-08-01

This study aims to validate and compare the performance of the National Institute of Health (NIH) criteria, Huang modified NIH criteria, and Armed Forces Institute of Pathology (AFIP) risk criteria for gastrointestinal stromal tumors (GISTs) in a large series of localized primary GISTs surgically treated at a single institution to determine the ideal risk stratification system for GIST. The clinicopathological features of 171 consecutive patients who underwent surgical resection for GISTs were retrospectively reviewed. Statistical analyses were performed to compare the prognostic value of the three risk criteria by analyzing the discriminatory ability linear trend, homogeneity, monotonicity of gradients, and Akaike information criteria. The median actuarial recurrence-free survival (RFS) for all 171 patients was 70%. On multivariate analyses, size >10 cm, mitotic count >5/50 high-power field, tumor necrosis, and serosal involvement were independent prognostic factors of RFS. All three risk criteria demonstrated a statistically significant difference in the recurrence rate, median actuarial RFS, actuarial 5-year RFS, and tumor-specific death across the different stages. Comparison of the various risk-stratification systems demonstrated that our proposed modified AFIP criteria had the best independent predictive value of RFS when compared with the other systems. The NIH, modified NIH, and AFIP criteria are useful in the prognostication of GIST, and the AFIP risk criteria provided the best prognostication among the three systems for primary localized GIST. However, remarkable prognostic heterogeneity exists in the AFIP high-risk category, and with our proposed modification, this system provides the most accurate prognostic information.

Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

PubMed

Roychowdhury, D F; Hayden, A; Liepa, A M

2003-02-15

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

High Neutrophil-to-lymphocyte Ratio as Prognostic Factor in Patients Affected by Upper Tract Urothelial Cancer: A Systematic Review and Meta-analysis.

PubMed

Marchioni, Michele; Cindolo, Luca; Autorino, Riccardo; Primiceri, Giulia; Arcaniolo, Davide; De Sio, Marco; Schips, Luigi

2017-06-01

Given the increasing interest in the possible role of the neutrophil-to-lymphocyte ratio (NLR) as an easily available oncologic marker for upper tract urothelial cancer (UTUC), we sought to quantify the prognostic effect of this biomarker and assess its consistency in UTUC. A systematic review of the published data was performed up to May 2016 using multiple search engines (PubMed, Ovid, and Scopus) to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing patients with a high and those with a low NLR before surgical treatment of UTUC to determine whether the NLR is an independent predictor of survival. Pooled estimates were calculated using a fixed-effects model if no significant heterogeneity was identified. Alternatively, a random-effects model was used when significant heterogeneity was detected. For continuous outcomes, the weighted mean difference was used as a summary measure. For binary variables, the odds ratio or risk ratio was calculated with the 95% confidence intervals (CIs). Statistical analyses were performed using RevMan, version 5. Six studies with 1710 patients were included. A high NLR was associated with poorer oncologic outcomes in patients affected by UTUC, in particular in terms of overall survival (hazard ratio [HR], 1.97; 95% CI, 1.27-3.04; P = .002) and recurrence-free survival (HR, 1.53; 95% CI, 1.19-1.96; P = .0009) but not cancer-specific survival (HR, 1.25; 95% CI, 0.29-5.41; P = .77). Current evidence suggests that the NLR might have an independent role as a prognostic factor in patients affected by UTUC undergoing surgical treatment. The NLR potentially represents an easily available measurement of prognosis; however, it requires validation in larger prospective studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Myeloid Clusters Are Associated with a Pro-Metastatic Environment and Poor Prognosis in Smoking-Related Early Stage Non-Small Cell Lung Cancer

PubMed Central

Zhang, Wang; Pal, Sumanta K.; Liu, Xueli; Yang, Chunmei; Allahabadi, Sachin; Bhanji, Shaira; Figlin, Robert A.; Yu, Hua; Reckamp, Karen L.

2013-01-01

Background This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients. Methods Uninvolved regional lymph node sections from 67 patients with stage I–III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment. Results CD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01). Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049) and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055). The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively). Conclusions Myeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted. PMID:23717691

Impact of systemic inflammation on gastric cancer outcomes.

PubMed

Liu, Xuechao; Chen, Shangxiang; Liu, Jianjun; Xu, Dazhi; Li, Wei; Zhan, Youqing; Li, Yuanfang; Chen, Yingbo; Zhou, Zhiwei; Sun, Xiaowei

2017-01-01

The prognostic value of neutrophil-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) has been extensively validated in various cancers. We aimed to examine the usefulness of a combination of NLR and GPS (named CNG) for predicting survival outcomes in patients after curative resection for gastric cancer (GC). We retrospectively analyzed the records of 1056 patients who underwent curative resection as initial treatment for GC from October 2000 to September 2012. The preoperative CNG was calculated as follows: patients with hypoalbuminemia (< 35 g/L), elevated C-reactive protein (> 10 mg/L), and elevated NLR (≥ 2) were allocated a score of 3; patients with two, one, or no abnormal values were allocated a score of 2, 1, or 0, respectively. The NLR and GPS were the only inflammatory variables independently associated with overall survival (OS) in multivariate analysis. When they were replaced by CNG in multivariate analysis, CNG was independently associated with OS (hazard ratio [HR] for CNG 1 [1.367, 95% CI: 1.065-1.755; P = 0.014], CNG 2 [1.887, 95% CI: 1.182-3.011; P = 0.008], and CNG 3 [2.224, 95% CI: 1.238-3.997; P = 0.008]; P = 0.020). In stage-matched analysis, the prognostic significance was still maintained in stage I-III (P = 0.002, P = 0.042, and P < 0.001, respectively). In addition, 5-year survival rates ranged from 92% (stage I) to 35% (stage III) and from 65%(CNG 0) to 18%(CNG 3) with tumor-nodes-metastasis (TNM) stage or CNG alone. However, the combination of TNM and CNG stratified 5-year survival rates from 98% (TNM I, CNG 0) to 12% (TNM III, CNG 3). The preoperative CNG is a novel predictor of postoperative survival, and the combination of CNG and TNM effectively stratifies outcomes in patients after curative resection for GC.

Impact of systemic inflammation on gastric cancer outcomes

PubMed Central

Xu, Dazhi; Li, Wei; Zhan, Youqing; Li, Yuanfang; Chen, Yingbo; Zhou, Zhiwei; Sun, Xiaowei

2017-01-01

Background The prognostic value of neutrophil-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) has been extensively validated in various cancers. We aimed to examine the usefulness of a combination of NLR and GPS (named CNG) for predicting survival outcomes in patients after curative resection for gastric cancer (GC). Methods We retrospectively analyzed the records of 1056 patients who underwent curative resection as initial treatment for GC from October 2000 to September 2012. The preoperative CNG was calculated as follows: patients with hypoalbuminemia (< 35 g/L), elevated C-reactive protein (> 10 mg/L), and elevated NLR (≥ 2) were allocated a score of 3; patients with two, one, or no abnormal values were allocated a score of 2, 1, or 0, respectively. Results The NLR and GPS were the only inflammatory variables independently associated with overall survival (OS) in multivariate analysis. When they were replaced by CNG in multivariate analysis, CNG was independently associated with OS (hazard ratio [HR] for CNG 1 [1.367, 95% CI: 1.065–1.755; P = 0.014], CNG 2 [1.887, 95% CI: 1.182–3.011; P = 0.008], and CNG 3 [2.224, 95% CI: 1.238–3.997; P = 0.008]; P = 0.020). In stage-matched analysis, the prognostic significance was still maintained in stage I-III (P = 0.002, P = 0.042, and P < 0.001, respectively). In addition, 5-year survival rates ranged from 92% (stage I) to 35% (stage III) and from 65%(CNG 0) to 18%(CNG 3) with tumor-nodes-metastasis (TNM) stage or CNG alone. However, the combination of TNM and CNG stratified 5-year survival rates from 98% (TNM I, CNG 0) to 12% (TNM III, CNG 3). Conclusion The preoperative CNG is a novel predictor of postoperative survival, and the combination of CNG and TNM effectively stratifies outcomes in patients after curative resection for GC. PMID:28358923

Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance.

PubMed

Nooij, Linda S; Ter Haar, Natalja T; Ruano, Dina; Rakislova, Natalia; van Wezel, Tom; Smit, Vincent T H B M; Trimbos, Baptist J B M Z; Ordi, Jaume; van Poelgeest, Mariette I E; Bosse, Tjalling

2017-11-15

Purpose: Vulvar cancer (VC) can be subclassified by human papillomavirus (HPV) status. HPV-negative VCs frequently harbor TP53 mutations; however, in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers. Experimental Design: We performed targeted next-generation sequencing (17 genes), p53 immunohistochemistry and HPV testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC patients (follow-up cohort). Results: Frequent recurrent mutations were identified in HPV-negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%), and HRAS (20% and 31%). Mutation frequency in HPV-positive vulvar (pre)cancers was significantly lower ( P = 0.001). Furthermore, a substantial subset of the HPV-negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild-type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV + , HPV - /p53wt, HPV - /p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV + , 16.3% for HPV - /p53wt and 22.6% for HPV - /p53abn tumors ( P = 0.044). HPV positivity remained an independent prognostic factor for favorable outcome in the multivariable analysis ( P = 0.020). Conclusions: HPV - and HPV + vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV - /p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV + VC have a significantly lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC. Clin Cancer Res; 23(22); 6781-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework.

PubMed

Mijderwijk, Hendrik-Jan; Stolker, Robert Jan; Duivenvoorden, Hugo J; Klimek, Markus; Steyerberg, Ewout W

2018-01-01

Surgical procedures are increasingly carried out in a day-case setting. Along with this increase, psychological outcomes have become prominent. The objective was to evaluate prospectively the prognostic effects of sociodemographic, medical, and psychological variables assessed before day-case surgery on psychological outcomes after surgery. The study was carried out between October 2010 and September 2011. We analyzed 398 mixed patients, from a randomized controlled trial, undergoing day-case surgery at a university medical center. Structural equation modeling was used to jointly study presurgical prognostic variables relating to sociodemographics (age, sex, nationality, marital status, having children, religion, educational level, employment), medical status (BMI, heart rate), and psychological status associated with anxiety (State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS-A)), fatigue (Multidimensional Fatigue Inventory (MFI)), aggression (State-Trait Anger Scale (STAS)), depressive moods (HADS-D), self-esteem, and self-efficacy. We studied psychological outcomes on day 7 after surgery, including anxiety, fatigue, depressive moods, and aggression regulation. The final prognostic model comprised the following variables: anxiety (STAI, HADS-A), fatigue (MFI), depression (HADS-D), aggression (STAS), self-efficacy, sex, and having children. The corresponding psychological variables as assessed at baseline were prominent (i.e. standardized regression coefficients ≥ 0.20), with STAI-Trait score being the strongest predictor overall. STAI-State (adjusted R2 = 0.44), STAI-Trait (0.66), HADS-A (0.45) and STAS-Trait (0.54) were best predicted. We provide a prognostic model that adequately predicts multiple postoperative outcomes in day-case surgery. Consequently, this enables timely identification of vulnerable patients who may require additional medical or psychological preventive treatment or-in a worst-case scenario-could be unselected for day-case surgery.

Model for breast cancer survival: relative prognostic roles of axillary nodal status, TNM stage, estrogen receptor concentration, and tumor necrosis.

PubMed

Shek, L L; Godolphin, W

1988-10-01

The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

PubMed Central

Rampazzo, Enrica; Del Bianco, Paola; Bertorelle, Roberta; Boso, Caterina; Perin, Alessandro; Spiro, Giovanna; Bergamo, Francesca; Belluco, Claudio; Buonadonna, Angela; Palazzari, Elisa; Leonardi, Sara; De Paoli, Antonino; Pucciarelli, Salvatore; De Rossi, Anita

2018-01-01

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4–8 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (P<0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73–0.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10–4.11)-fold and 4.55 (95% CI 1.48–13.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy. PMID:29449673

Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC

PubMed Central

Petersen, Lars F.; Klimowicz, Alexander C.; Otsuka, Shannon; Elegbede, Anifat A.; Petrillo, Stephanie K.; Williamson, Tyler; Williamson, Chris T.; Konno, Mie; Lees-Miller, Susan P.; Hao, Desiree; Morris, Don; Magliocco, Anthony M.; Bebb, D. Gwyn

2017-01-01

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients. PMID:28418844

Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

PubMed

Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

2017-06-13

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies

PubMed Central

Abrisqueta, Pau; Wright, George W.; Slack, Graham W.; Mottok, Anja; Villa, Diego; Jares, Pedro; Rauert-Wunderlich, Hilka; Royo, Cristina; Clot, Guillem; Pinyol, Magda; Boyle, Merrill; Chan, Fong Chun; Braziel, Rita M.; Chan, Wing C.; Weisenburger, Dennis D.; Cook, James R.; Greiner, Timothy C.; Fu, Kai; Ott, German; Delabie, Jan; Smeland, Erlend B.; Holte, Harald; Jaffe, Elaine S.; Steidl, Christian; Connors, Joseph M.; Gascoyne, Randy D.; Rosenwald, Andreas; Staudt, Louis M.; Campo, Elias; Rimsza, Lisa M.

2017-01-01

Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker—the proliferation signature—using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies. Methods Forty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard. The locked assay was applied to pretreatment FFPE lymph node biopsies from an independent cohort of 110 patients uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Seventeen biopsies were tested across three laboratories to assess assay reproducibility. Results The MCL35 assay, which contained a 17-gene proliferation signature, yielded gene expression of sufficient quality to assign an assay score and risk group in 108 (98%) of 110 archival FFPE biopsies. The MCL35 assay assigned patients to high-risk (26%), standard-risk (29%), and low-risk (45%) groups, with different lengths of overall survival (OS): a median of 1.1, 2.6, and 8.6 years, respectively (log-rank for trend, P < .001). In multivariable analysis, these risk groups and the Mantle Cell Lymphoma International Prognostic Index were independently associated with OS (P < .001 for both variables). Concordance of risk assignment across the three independent laboratories was 100%. Conclusion The newly developed and validated MCL35 assay for FFPE biopsies uses the proliferation signature to define groups of patients with significantly different OS independent of the Mantle Cell Lymphoma International Prognostic Index. Importantly, the analytic and clinical validity of this assay defines it as a reliable biomarker to support risk-adapted clinical trials. PMID:28291392

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

PubMed

Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2017-06-01

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

Progranulin Is a Novel Independent Predictor of Disease Progression and Overall Survival in Chronic Lymphocytic Leukemia

PubMed Central

Göbel, Maria; Eisele, Lewin; Möllmann, Michael; Hüttmann, Andreas; Johansson, Patricia; Scholtysik, René; Bergmann, Manuela; Busch, Raymonde; Döhner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; Dührsen, Ulrich; Dürig, Jan

2013-01-01

Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38+ZAP-70+ as compared to indolent CD38−ZAP-70− chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13–3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05–10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09–3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA. PMID:24009671

Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.

PubMed

Göbel, Maria; Eisele, Lewin; Möllmann, Michael; Hüttmann, Andreas; Johansson, Patricia; Scholtysik, René; Bergmann, Manuela; Busch, Raymonde; Döhner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; Dührsen, Ulrich; Dürig, Jan

2013-01-01

Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13-3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05-10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09-3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA.

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?

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

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural datamore » consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the survival of patients with BMs to a more or less satisfactory degree. Among the 5 PIs evaluated in the present study, GPA was the most powerful in predicting survival. Additional studies should include emerging biologic prognostic factors to improve the sensibility of these PIs.« less

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

PubMed

Aki, Hilal; Uzunaslan, Didem; Saygin, Caner; Batur, Sebnem; Tuzuner, Nukhet; Kafadar, Ali; Ongoren, Seniz; Oz, Buge

2013-01-01

Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

Prognostic factors of whiplash-associated disorders: a systematic review of prospective cohort studies.

PubMed

Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M

2003-07-01

We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e.g. restricted range of motion, high number of complaints), psychosocial (previous psychological problems), neuropsychosocial factors (nervousness), crash related (e.g. accident on highway) and treatment related factors (need to resume physiotherapy) showed limited prognostic value for functional recovery. High initial pain intensity is an important predictor for delayed functional recovery for patients with whiplash injury. Often mentioned factors like age, gender and compensation do not seem to be of prognostic value. Scientific information about prognostic factors can guide physicians or other care providers to direct treatment and to probably prevent chronicity.

D-Cycloserine Augmentation of Cognitive Behavioral Group Therapy of Social Anxiety Disorder: Prognostic and Prescriptive Variables

PubMed Central

Smits, Jasper A. J.; Hofmann, Stefan G.; Rosenfield, David; DeBoer, Lindsey B.; Costa, Paul T.; Simon, Naomi M.; O'Cleirigh, Conall; Meuret, Alicia E.; Marques, Luana; Otto, Michael W.; Pollack, Mark H.

2014-01-01

Objective The aim of the current study was to identify individual characteristics that (1) predict symptom improvement with group cognitive behavioral therapy (CBT) for social anxiety disorder (SAD; i.e., prognostic variables) or (2) moderate the effects of d-cycloserine vs. placebo augmentation of CBT for SAD (i.e., prescriptive variables). Method Adults with SAD (N=169) provided Liebowitz Social Anxiety Scale (LSAS) scores in a trial evaluating DCS augmentation of group CBT. Rate of symptom improvement during therapy and posttreatment symptom severity were evaluated using multilevel modeling. As predictors of these two parameters, we selected the range of variables assessed at baseline (demographic characteristics, clinical characteristics, personality traits). Using step-wise analyses, we first identified prognostic and prescriptive variables within each of these domains and then entered these significant predictors simultaneously in one final model. Results African American ethnicity and cohabitation status were associated with greater overall rates of improvement during therapy and lower posttreatment severity. Higher initial severity was associated with a greater improvement during therapy, but also higher posttreatment severity (the greater improvement was not enough to overcome the initial higher severity). D-cycloserine augmentation was evident only among individuals low in conscientiousness and high in agreeableness. Conclusions African American ethnicity, cohabitation status, and initial severity are prognostic of favorable CBT outcomes in SAD. D-cycloserine augmentation appears particularly useful for patients low in conscientiousness and high in agreeableness. These findings can guide clinicians in making decisions about treatment strategies and can help direct research on the mechanisms of these treatments. PMID:23937345

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

PubMed Central

Pascale, Mariarosa; Aversa, Cinzia; Barbazza, Renzo; Marongiu, Barbara; Siracusano, Salvatore; Stoffel, Flavio; Sulfaro, Sando; Roggero, Enrico; Stanta, Giorgio

2016-01-01

Abstract Background Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. Patients and methods NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. Results NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (≤ 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. Conclusions A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients. PMID:27679548

Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor.

PubMed

Yamada, Yuta; Nakagawa, Tohru; Sugihara, Toru; Horiuchi, Takamasa; Yoshizaki, Uran; Fujimura, Tetsuya; Fukuhara, Hiroshi; Urano, Tomohiko; Takayama, Kenichi; Inoue, Satoshi; Kume, Haruki; Homma, Yukio

2016-11-18

Prognostic value of immune cells is not clear in testicular germ cell tumors (TGCTs). We aimed to investigate the prognostic value of tumor-infiltrating neutrophils in TGCTs. A total of 102 patients who underwent orchiectomy for TGCT were investigated for CD66b positive tumor-infiltrating neutrophils (CD66b + TINs). Immmunostaining for CD66b was performed in 102 sections as described. Clinicopathological parameters as well as cancer specific survival and overall survival were assessed for correlation with CD66b + TIN density. High density group was significantly correlated with tumor diameter ≥ 10 cm, presence of nodal/distant metastasis, S stage, diagnosis of nonseminomatous germ cell tumor (NGCT), and presence of venous invasion (p = 0.0198, p < 0.0001, p = 0.0275, p = 0.0004, and p = 0.0287, respectively). It was also significantly associated with cancer-specific and overall survival (logrank p = 0.0036, and p = 0.0002, respectively). Multivariate analysis showed that increased CD66b + TIN was an independent prognostic factor for overall survival (p = 0.0095). Increased CD66b + TIN was significantly associated with presence of metastasis, S stage, and nonseminomatous germ cell tumor diagnosis. It was also an independent prognostic factor of overall survival in patients with TGCT.

Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.

PubMed

Kimura, J; Kunisaki, C; Makino, H; Oshima, T; Ota, M; Oba, M; Takagawa, R; Kosaka, T; Ono, H A; Akiyama, H; Endo, I

2016-11-01

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes. © 2015 International Society for Diseases of the Esophagus.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

PubMed

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Tejero, R; Díaz, T; Pratcorona, M; Tormo, M; Ribera, J M; Escoda, L; Duarte, R; Gallardo, D; Heras, I; Queipo de Llano, M P; Bargay, J; Monzo, M; Sierra, J; Navarro, A; Esteve, J

2014-04-01

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer.

PubMed

Evans, Joseph R; Zhao, Shuang G; Chang, S Laura; Tomlins, Scott A; Erho, Nicholas; Sboner, Andrea; Schiewer, Matthew J; Spratt, Daniel E; Kothari, Vishal; Klein, Eric A; Den, Robert B; Dicker, Adam P; Karnes, R Jeffrey; Yu, Xiaochun; Nguyen, Paul L; Rubin, Mark A; de Bono, Johann; Knudsen, Karen E; Davicioni, Elai; Feng, Felix Y

2016-04-01

A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification. To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer. A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed. Biochemical recurrence-free, metastasis-free, and overall survival. Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman ρ [ρ], range, -0.07 to 0.24), Gleason score (ρ, range, 0.03 to 0.20), prostate-specific antigen level (ρ, range, -0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (ρ, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95% CI, 1.12-2.50) than in the older patients (HR, 0.77; 95% CI, 0.29-2.07) on multivariate Cox analysis. DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients.

Neurological prognostication of outcome in patients in coma after cardiac arrest.

PubMed

Rossetti, Andrea O; Rabinstein, Alejandro A; Oddo, Mauro

2016-05-01

Management of coma after cardiac arrest has improved during the past decade, allowing an increasing proportion of patients to survive, thus prognostication has become an integral part of post-resuscitation care. Neurologists are increasingly confronted with raised expectations of next of kin and the necessity to provide early predictions of long-term prognosis. During the past decade, as technology and clinical evidence have evolved, post-cardiac arrest prognostication has moved towards a multimodal paradigm combining clinical examination with additional methods, consisting of electrophysiology, blood biomarkers, and brain imaging, to optimise prognostic accuracy. Prognostication should never be based on a single indicator; although some variables have very low false positive rates for poor outcome, multimodal assessment provides resassurance about the reliability of a prognostic estimate by offering concordant evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploration of risk factors predicting outcomes for primary T1 high-grade bladder cancer and validation of the Spanish Urological Club for Oncological Treatment scoring model: Long-term follow-up experience at a single institute.

PubMed

Miyake, Makito; Gotoh, Daisuke; Shimada, Keiji; Tatsumi, Yoshihiro; Nakai, Yasushi; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Tanaka, Nobumichi; Konishi, Noboru; Fujimoto, Kiyohide

2015-06-01

To determine the prognostic factors of primary T1 high-grade bladder cancer and to validate the Spanish Urological Club for Oncological Treatment model in Japanese patients with T1 high-grade bladder cancer treated at a single institution. Records of 106 patients with T1 high-grade bladder cancer treated from 1998 to 2013 were retrospectively reviewed. Variables included various clinicopathological parameters, including lymphovascular invasion and tumor growth pattern at the invasion front. Recurrence-free survival and progression-free survival were analyzed. Multivariate Cox proportional regression analysis was used to verify the prognostic significance of the variables. Scores for recurrence and progression were calculated using the Spanish Urological Club for Oncological Treatment model. Of 106 patients, 44 (42%) had recurrence and 16 (15%) developed progression after a median (interquartile range) follow-up period of 54 months (range 32-81 months). Non-papillary shape was the only independent predictor for recurrence, while broad-based tumor stalk and infiltrative tumor growth pattern at the invasion front were determined to be independent predictors for progression. Stratification of patients according to the number of progression risk factors yielded hazard ratios of 10.1 and 13.1 in patients having one and two risks, respectively, compared with those without any risks. The Spanish Urological Club for Oncological Treatment model successfully stratified our patients with a trend toward different probabilities of recurrence and progression. The results of the present study might be helpful for counseling certain patients towards intensive treatment, such as radical cystectomy and/or platinum-based systemic chemotherapy. In addition, the Spanish Urological Club for Oncological Treatment model might be applicable to Japanese patients with T1 high-grade bladder cancer. © 2015 The Japanese Urological Association.

The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: Refinements in diagnostic criteria and impact of multimodal treatments on survival.

PubMed

Turri-Zanoni, Mario; Maragliano, Roberta; Battaglia, Paolo; Giovannardi, Marta; Antognoni, Paolo; Lombardi, Davide; Morassi, Maria Laura; Pasquini, Ernesto; Tarchini, Paolo; Asioli, Sofia; Foschini, Maria Pia; Sessa, Fausto; Nicolai, Piero; Castelnuovo, Paolo; La Rosa, Stefano

2017-11-01

To provide a comprehensive review of the clinical and histopathological features of olfactory neuroblastoma (ONB) and other sinonasal neuroendocrine neoplasms (NENs), in order to refine diagnostic criteria, analyze treatment outcomes, and identify prognostic factors. Data from an Italian multi-institutional database were analyzed. Patients were treated surgically via a minimally-invasive endoscopic approach followed by adjuvant radiotherapy or radiochemotherapy. Neoadjuvant cisplatin/etoposide chemotherapy was administered in cases of poorly-differentiated tumors. A centralized pathology review was performed in all cases. Patients were prospectively observed for survival. Overall (OS) and Disease-free survival (DFS) estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Statistically significant variables were entered in a multivariate Cox regression model. 98 patients with a median follow-up of 53months were included. Morphology review and the incorporation of cytokeratin 8/18 in the immunohistochemical panel modified the final diagnosis in 8/98 (8.2%) cases. The neoplasms were ultimately classified into four groups with different immunohistochemical profiles and clinical behaviors: ONB in 67 cases (5-year-OS, 91.6%); NEC (poorly-differentiated neuroendocrine carcinoma) in 22 cases (5-year-OS, 42.6%); MiNEN (mixed neuroendocrine/non-neuroendocrine neoplasm) in five cases (5-year-OS, 0%,0/5 cases); and NET (well-differentiated neuroendocrine tumor) in four cases (5-year-OS, 50%, 2/4 cases). Hyams grade and Ki67 index were independent prognostic factors for ONB. Neoadjuvant chemotherapy appeared to be associated with improved OS and DFS for NEC, independent of other clinicopathological variables. Induction chemotherapy improves survival outcomes in patients affected by poorly-differentiated tumors. Recent advances in histopathological diagnosis, including CK8/18 staining, allow to plan the most appropriate range of multimodal treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

The measured effect magnitude of co-morbidities on burn injury mortality.

PubMed

Knowlin, Laquanda; Stanford, Lindsay; Moore, Danier; Cairns, Bruce; Charles, Anthony

2016-11-01

The ability to better prognosticate burn injury outcome is challenging and historically, most center use the Baux or revised Baux score to help prognosticate burn outcome, however, the weighted contribution of comorbidity on burn mortality has traditionally not been accounted for nor adequately studied. We therefore sought to determine the effect of comorbidities, using the Charlson comorbidity index (CCI) on burn mortality. The purpose of this study was to determine the effect of comorbidities on burn injury mortality as determined by the LA50 (lethal TBSA burn at which 50% of the cohort will succumb from the burn injury) in a retrospective analysis of patients admitted to a regional burn center from 2002 to 2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA (total body surface area), length of hospital stay, and pre-existing comorbidities. Bivariate analysis was performed and logistic regression modeling using significant variables was utilized to estimate odds of death. 7640 patients were included in this study. Overall survival rate was 96%. 40% of our burn cohort had at least one comorbidity. There was a linear increase in the likelihood of death with an increase in CCI. The logistic regression model for mortality outcomes identified four statistically significant variables: age, TBSA, inhalational injury and the presence of comorbidities (OR=1.59 for each 1 point increase in CCI; 95% CI 1.44-1.77). The unadjusted LA50 was 53% for the entire cohort. Partial adjustment multivariate regression controlling for burn mechanism and inhalation injury only, produced a slight reduction in LA50 for the 0-18 and 19-64 age categories to 76% and 48% TBSA, respectively, but a significant decrease occurred in the ≥65 years age group with a reduced LA50 to 20% TBSA (p<0.001). After full adjustment for all significant covariates, including comorbidities, the independent magnitude of effect of comorbidities on the LA50 was evident in the <65 cohort. The full adjustment showed a LA50 decreased to 61% and 43% TBSA, respectively in the 0-18 and >18-65 age groups respectively (p<0.001), however, in the >65 years age cohort there was no change in the LA50. Preexisting comorbidities have a significant effect on burn injury mortality in all age groups, particularly the younger burn population. The measured effect of comorbidities in the >65 yr age cohort was mitigated by the co-linearity between age and comorbidities. The inclusion of CCI is imperative so as to better prognosticate burn outcome and help guide expectations and resource utilization, particularly in the younger burn cohort. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

The Measured Effect Magnitude of Co-Morbidities on Burn injury Mortality

PubMed Central

Knowlin, Laquanda; Stanford, Lindsay; Moore, Danier; Cairns, Bruce; Charles, Anthony

2016-01-01

Introduction The ability to better prognosticate burn injury outcome is challenging and historically, most center use the Baux or revised Baux score to help prognosticate burn outcome, however, the weighted contribution of comorbidity on burn mortality has traditionally not been accounted for nor adequately studied. We therefore sought to determine the effect of comorbidities, using the Charlson comorbidity index (CCI) on burn mortality. Methods The purpose of this study was to determine the effect of comorbidities on burn injury mortality as determined by the LA50 (lethal TBSA burn at which 50% of the cohort will succumb from the burn injury) in a retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA (total body surface area), length of hospital stay, and pre-existing comorbidities. Bivariate analysis was performed and logistic regression modeling using significant variables was utilized to estimate odds of death. Results 7640 patients were included in this study. Overall survival rate was 96%. 40% of our burn cohort had at least one comorbidity. There was a linear increase in the likelihood of death with an increase in CCI. The logistic regression model for mortality outcomes identified four statistically significant variables: age, TBSA, inhalational injury and the presence of comorbidities (OR = 1.59 for each 1 point increase in CCI; 95% CI 1.44–1.77). The unadjusted LA50 was 53% for the entire cohort. Partial adjustment multivariate regression controlling for burn mechanism and inhalation injury only, produced a slight reduction in LA50 for the 0–18 and 19–64 age categories to 76% and 48%, respectively, but a significant decrease occurred in the ≥ 65 years age group with a reduced LA50 to 20% (p<0.001). After full adjustment for all significant covariates, including comorbidities, the independent magnitude of effect of comorbidities on the LA50 was evident in the <65 cohort. The full adjustment showed a LA50 decreased by 15 and 5%, respectively in the 0–18 and >18–65 age groups respectively (p<0.001), however, in the >65 years age cohort there was no change in the LA50. Conclusion Preexisting comorbidities have a significant effect on burn injury mortality in all age groups, particularly the younger burn population. The measured effect of comorbidities in the >65yr age cohort was mitigated by the co-linearity between age and comorbidities. The inclusion of CCI is imperative so as to better prognosticate burn outcome and help guide expectations and resource utilization, particularly in the younger burn cohort.. PMID:27593340

Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: combined high CXCL16 expression in tumor stroma and cancer cells yields improved survival.

PubMed

Hald, Sigurd M; Kiselev, Yury; Al-Saad, Samer; Richardsen, Elin; Johannessen, Charles; Eilertsen, Marte; Kilvaer, Thomas K; Al-Shibli, Khalid; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M; Donnem, Tom

2015-05-29

The chemokine CXCL16 and its receptor CXCR6 are expressed by a variety of immune cells and have been shown to influence angiogenesis. The expression of CXCR6 and CXCL16 has been examined in numerous human cancers; however no studies have yet investigated their influence on prognosis in non-small cell lung cancer (NSCLC). We aimed to explore their prognostic significance in NSCLC, in addition to examining associations with previously investigated markers. Resected tumor tissue from 335 consecutive unselected stage I-IIIA NSCLC patients (1990-2005) were collected. Immunohistochemistry was used to evaluate the expression of CXCR6 and CXCL16 on tissue microarrays. In vitro, NSCLC cells (NCI-H460, A549 cells) were transfected with CXCL16 siRNA to examine effects on proliferation. In univariate analysis, ↑ stromal cell CXCL16 expression was a significant positive prognostic factor (P = 0.016). CXCR6 was expressed in cancer cells, but did not show any prognostic impact. In the multivariate analysis, combined ↑cancer, and ↑stromal cell CXCL16 expression was an independent positive prognostic factor when compared to ↓stromal and ↓cancer cell expression (HR: 0.42; 95 % CI: 0.20-0.88; P = 0.022). Knockdown of CXCL16 by siRNA resulted in accelerated proliferation of NSCLC cell lines. We have shown that combined ↑cancer and ↑stromal cell CXCL16 expression is an independent positive prognostic factor in NSCLC. Further studies are warranted to elucidate the biological mechanism underlying this finding.

The prognostic value of preoperative inflammation-based prognostic scores and nutritional status for overall survival in resected patients with nonmetastatic Siewert type II/III adenocarcinoma of esophagogastric junction.

PubMed

Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman

2017-07-01

Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.

The modified glasgow prognostic score is an independent prognostic indicator in neoadjuvantly treated adenocarcinoma of the esophagogastric junction

PubMed Central

Jomrich, Gerd; Hollenstein, Marlene; John, Maximilian; Baierl, Andreas; Paireder, Matthias; Kristo, Ivan; Ilhan-Mutlu, Aysegül; Asari, Reza; Preusser, Matthias; Schoppmann, Sebastian F.

2018-01-01

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients’ characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.3–89.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS. PMID:29467943

Classification of microvascular patterns via cluster analysis reveals their prognostic significance in glioblastoma.

PubMed

Chen, Long; Lin, Zhi-Xiong; Lin, Guo-Shi; Zhou, Chang-Fu; Chen, Yu-Peng; Wang, Xing-Fu; Zheng, Zong-Qing

2015-01-01

There are limited researches focusing on microvascular patterns (MVPs) in human glioblastoma and their prognostic impact. We evaluated MVPs of 78 glioblastomas by CD34/periodic acid-Schiff dual staining and by cluster analysis of the percentage of microvascular area for distinct microvascular formations. The distribution of 5 types of basic microvascular formations, that is, microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), glomeruloid vascular proliferation (GVP), and vasculogenic mimicry (VM), was variable. Accordingly, cluster analysis classified MVPs into 2 types: type I MVP displayed prominent MSs and VCs, whereas type II MVP had numerous VGs, GVPs, and VMs. By analyzing the proportion of microvascular area for each type of formation, we determined that glioblastomas with few MSs and VCs had many GVPs and VMs, and vice versa. VG seemed to be a transitional type of formation. In case of type I MVP, expression of Ki-67 and p53 but not MGMT was significantly higher as compared with those of type II MVP (P < .05). Survival analysis showed that the type of MVPs presented as an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) (both P < .001). Type II MVP had a more negative influence on PFS and OS than did type I MVP. We conclude that the heterogeneous MVPs in glioblastoma can be categorized properly by certain histopathologic and statistical analyses and may influence clinical outcome. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Dynamic prognostication using conditional survival analysis for patients with operable lung adenocarcinoma

PubMed Central

Kim, Wooil; Lee, Ho Yun; Jung, Sin-Ho; Woo, Min-Ah; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Zo, Jae Ill; Shim, Young Mog; Han, Joungho; Jeong, Ji Yun; Choi, Joon Young; Lee, Kyung Soo

2017-01-01

Purpose To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time. Patients and Methods We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival. Results Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively. Conclusion Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively. PMID:27793026

High anaplastic lymphoma kinase immunohistochemical staining in neuroblastoma and ganglioneuroblastoma is an independent predictor of poor outcome.

PubMed

Duijkers, Floor A M; Gaal, José; Meijerink, Jules P P; Admiraal, Pieter; Pieters, Rob; de Krijger, Ronald R; van Noesel, Max M

2012-03-01

Anaplastic lymphoma kinase (ALK) mutations occur in 3% to 11% of neuroblastoma (NBL) cases and are associated with high ALK levels. However, high ALK levels appear to be a mutation-independent hallmark of NBL. Evidence about the prognostic relevance of ALK mutations and ALK tumor positivity in patients with NBL has been inconclusive. In this study, we investigated the prognostic relevance of ALK positivity by IHC and ALK mutation status by PCR sequencing in 71 NBL, 12 ganglioneuroblastoma (GNBL), and 20 ganglioneuroma samples in a multivariate model. ALK mutations were present in 2 of 72 NBL and 2 of 12 GNBL samples, which all contained many ALK-positive cells (>50%). In addition, half of all NBL samples showed ALK positivity in most (>50%) of tumor cells, whereas half of the GNBL showed staining in <20% of the tumor cells. In most ganglioneuroma samples, a low percentage of tumor cells stained positive for ALK, which mainly involved ganglion cells. Higher percentages of ALK-positive cells in NBL and GNBL patient samples correlated with inferior survival in univariate and multivariate analyses with established prognostic factors, such as stage, age, and MYCN status. In conclusion, ALK positivity by IHC is an independent, poor prognostic factor in patients with GNBL and NBL. ALK IHC is an easy test suitable for future risk stratification in patients with NBL and GNBL. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Neutrophil-to-lymphocyte ratio is effective prognostic indicator for post-amputation patients with critical limb ischemia

PubMed Central

Wang, Qi; Liu, Han; Sun, Siqiao; Cheng, Zhihua; Zhang, Yang; Sun, Xiwei; Wang, Zhongying; Wang, Shuai

2017-01-01

Objectives: To confirm whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicators for the prognosis of post-amputation patients with critical limb ischemia (CLI). Methods: In this retrospective observational study a total 270 post-amputation patients with CLI were included between January 2010 and December 2014 in the First Hospital of Jilin University, Changchun, China. The neutrophil and lymphocyte counts were recorded before amputations. Neutrophil-to-lymphocyte ratio was calculated and NLR ≥8.08 was defined as elevated. Logistic regression analysis was conducted to test the prognostic value. Results: According to the statistical analysis, it was indicated that NLR ≥8.08 (odds ratio [OR] 26.228, 95% confidence interval [CI]: 5.801-118.583, p<0.001), PLR ≥237.14 (OR: 3.464, 95% CI: 1.289-9.308, p=0.014) and coronary heart disease (OR: 2.739, 95% CI: 1.060-7.082, p=0.038) were the independent prognostic indicators for the patients. Conclusion: Neutrophil-to-lymphocyte ratio, PLR, and coronary heart disease are independent prognostic indicators for post-amputation patients with CLI. PMID:28042626

Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration

PubMed Central

Nosrati, Mehdi; Tong, Schuyler; Wu, Clayton; Thummala, Suresh; Dar, Altaf A.; Leong, Stanley P.L.; Cleaver, James E.; Sagebiel, Richard W.; Miller, James R.; Kashani-Sabet, Mohammed

2013-01-01

Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced DMFS (P = 0.01) and DSS (P = 0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P = 0.03) and DSS (P = 0.03). Increased PHIP copy number was an independent predictor of ulceration status (P = 0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P< 0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of LDH5, HIF1A, and VEGF, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis. PMID:24005052

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma.

PubMed

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-06-27

Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients' overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.

Predicting Long-Term Global Outcome after Traumatic Brain Injury: Development of a Practical Prognostic Tool Using the Traumatic Brain Injury Model Systems National Database.

PubMed

Walker, William C; Stromberg, Katharine A; Marwitz, Jennifer H; Sima, Adam P; Agyemang, Amma A; Graham, Kristin M; Harrison-Felix, Cynthia; Hoffman, Jeanne M; Brown, Allen W; Kreutzer, Jeffrey S; Merchant, Randall

2018-05-16

For patients surviving serious traumatic brain injury (TBI), families and other stakeholders often desire information on long-term functional prognosis, but accurate and easy-to-use clinical tools are lacking. We aimed to build utilitarian decision trees from commonly collected clinical variables to predict Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate-to-severe closed TBI. Flexible classification tree statistical modeling was used on prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study. Enrollments occurred at 17 designated, or previously designated, TBIMS inpatient rehabilitation facilities. Analysis included all participants with nonpenetrating TBI injured between January 1997 and January 2017. Sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration consistently dominated branching hierarchy and was the lone injury characteristic significantly contributing to GOS predictability. Lower-order variables that added predictability were age, pre-morbid education, productivity, and occupational category. Generally, patient outcomes improved with shorter PTA, younger age, greater pre-morbid productivity, and higher pre-morbid vocational or educational achievement. Across all prognostic groups, the best and worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%. Predictability in test data sets ranged from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to 0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful tool to provide prognostic information on long-term functional outcomes for adult survivors of moderate and severe closed TBI. Predictive accuracy for GOS level was demonstrated in an independent test sample. Length of PTA, a clinical marker of injury severity, was by far the most critical outcome determinant.

Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists

PubMed Central

George, S; Primrose, J; Talbot, R; Smith, J; Mullee, M; Bailey, D; du Boulay, C; Jordan, H

2006-01-01

To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5–10 identified, who had in turn a similar advantage over those with 0–4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival. PMID:16969342

Bioelectrical impedance phase angle relates to function, disease severity and prognosis in stable chronic obstructive pulmonary disease.

PubMed

Maddocks, Matthew; Kon, Samantha S C; Jones, Sarah E; Canavan, Jane L; Nolan, Claire M; Higginson, Irene J; Gao, Wei; Polkey, Michael I; Man, William D-C

2015-12-01

Bioelectrical impedance analysis (BIA) provides a simple method to assess changes in body composition. Raw BIA variables such as phase angle provide direct information on cellular mass and integrity, without the assumptions inherent in estimating body compartments, e.g. fat-free mass (FFM). Phase angle is a strong functional and prognostic marker in many disease states, but data in COPD are lacking. Our aims were to describe the measurement of phase angle in patients with stable COPD and determine the construct and discriminate validity of phase angle by assessing its relationship with established markers of function, disease severity and prognosis. 502 outpatients with stable COPD were studied. Phase angle and FFM by BIA, quadriceps strength (QMVC), 4-m gait speed (4MGS), 5 sit-to-stand time (5STS), incremental shuttle walk (ISW), and composite prognostic indices (ADO, iBODE) were measured. Patients were stratified into normal and low phase angle and FFM index. Phase angle correlated positively with FFM and functional outcomes (r = 0.35-0.66, p < 0.001) and negatively with prognostic indices (r = -0.35 to -0.48, p < 0.001). In regression models, phase angle was independently associated with ISW, ADO and iBODE whereas FFM was removed. One hundred and seventy patients (33.9% [95% CI, 29.9-38.1]) had a low phase angle. Phenotypic characteristics included lower QMVC, ISW, and 4MGS, higher 5STS, ADO and iBODE scores, and more exacerbations and hospital days in past year. The proportion of patients to have died was significantly higher in patients with low phase angle compared to those with normal phase angle (8.2% versus 3.6%, p = 0.02). Phase angle relates to markers of function, disease severity and prognosis in patients with COPD. As a directly measured variable, phase angle offers more useful information than fat-free mass indices. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Personalized treatment planning with a model of radiation therapy outcomes for use in multiobjective optimization of IMRT plans for prostate cancer.

PubMed

Smith, Wade P; Kim, Minsun; Holdsworth, Clay; Liao, Jay; Phillips, Mark H

2016-03-11

To build a new treatment planning approach that extends beyond radiation transport and IMRT optimization by modeling the radiation therapy process and prognostic indicators for more outcome-focused decision making. An in-house treatment planning system was modified to include multiobjective inverse planning, a probabilistic outcome model, and a multi-attribute decision aid. A genetic algorithm generated a set of plans embodying trade-offs between the separate objectives. An influence diagram network modeled the radiation therapy process of prostate cancer using expert opinion, results of clinical trials, and published research. A Markov model calculated a quality adjusted life expectancy (QALE), which was the endpoint for ranking plans. The Multiobjective Evolutionary Algorithm (MOEA) was designed to produce an approximation of the Pareto Front representing optimal tradeoffs for IMRT plans. Prognostic information from the dosimetrics of the plans, and from patient-specific clinical variables were combined by the influence diagram. QALEs were calculated for each plan for each set of patient characteristics. Sensitivity analyses were conducted to explore changes in outcomes for variations in patient characteristics and dosimetric variables. The model calculated life expectancies that were in agreement with an independent clinical study. The radiation therapy model proposed has integrated a number of different physical, biological and clinical models into a more comprehensive model. It illustrates a number of the critical aspects of treatment planning that can be improved and represents a more detailed description of the therapy process. A Markov model was implemented to provide a stronger connection between dosimetric variables and clinical outcomes and could provide a practical, quantitative method for making difficult clinical decisions.

PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

PubMed Central

Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

2014-01-01

BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation. SECONDARY CATEGORY: Pediatrics.

Interrelationships in the Variability of Root Canal Anatomy among the Permanent Teeth: A Full-Mouth Approach by Cone-Beam CT

PubMed Central

Peters, Ove A.; Maury, Elisabeth; Telmon, Norbert; Georgelin-Gurgel, Marie; Maret, Delphine

2016-01-01

Objectives In endodontic practice, clinicians should be aware of possible root canal anatomic variations. The aim of this study was to assess using CBCT acquisitions regarding whether one root canal anatomy of a tooth is associated with a specific anatomy of another tooth. Methods A total of 106 CBCT acquisitions were obtained using a CBCT scanner with 200μm voxel size. Numbers of roots and canals of the entire dentition were described. Bivariate analyses and logistic regressions were conducted to explore root canal anatomy on one tooth according to age, gender, jaw, side and the others teeth. Multiple correspondence analysis (MCA) was performed to correlate the different numbers of canals profiles. Results A total of 2424 teeth were analyzed. Independently from the other variables, the presence of an additional root canal on a mandibular incisor increases the risk of having an additional root canal on a mandibular premolar (OR [95%] 3.7 [1.0;13.2]). The mandibular molar variability increases in women compared to men (OR [95%] 0.4 [0.1; 0.9]). MCA showed correspondence between 2-canals maxillary incisor and canines and 5-canals maxillary molars, and some correlation between additional canal on maxillary and mandibular premolars. Conclusions Although CBCT examinations are conducted in the first intention of making a diagnosis or prognostic evaluation, medium FOV acquisitions could be used as an initial database thus furnishing preliminary evaluations and information. In endodontic practice, clinicians should be aware of possible root canal anatomic variations. The visualization of all canals is considered essential in endodontic therapy. The use of multi-correspondence analysis for statistics in endodontic research is a new approach as a prognostic tool. PMID:27764246

The prognostic performance of the complement system in septic patients in emergency department: a cohort study.

PubMed

Zhao, Xin; Chen, Yun-Xia; Li, Chun-Sheng

2015-01-01

To investigate the prognostic performance of complement components in septic patients, complement 3, membrane attack complex (MAC) and mannose-binding lectin were measured and compared among adult patients with sepsis, severe sepsis and septic shock, as well as between in-hospital nonsurvivors and survivors. The prognostic value of complement components was compared with mortality in emergency department sepsis (MEDS) score. Median complement 3, MAC and mannose-binding lectin increased directly with the sepsis, severe sepsis and septic shock groups, and were significantly higher in nonsurvivors than in survivors. MEDS and MAC independently predicted in-hospital mortality. The prognostic performance of MAC was superior to MEDS as analyzed by receiver operating characteristic curve and area under the curve.

The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

PubMed

Painter, Dan; Smith, Alexandra; de Tute, Ruth; Crouch, Simon; Roman, Eve; Jack, Andrew

2015-07-01

This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed. © 2015 John Wiley & Sons Ltd.

Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder cancer.

PubMed

Galmozzi, Fabia; Rubagotti, Alessandra; Romagnoli, Andrea; Carmignani, Giorgio; Perdelli, Luisa; Gatteschi, Beatrice; Boccardo, Francesco

2006-12-01

The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival. Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank test and Cox proportional hazards models. In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient's overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome. Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.

The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review.

PubMed

Schuetz, Philipp; Marlowe, Robert J; Mueller, Beat

2015-03-01

Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for head and neck cancer.

PubMed

Kano, Satoshi; Homma, Akihiro; Hatakeyama, Hiromitsu; Mizumachi, Takatsugu; Sakashita, Tomohiro; Kakizaki, Tomohiko; Fukuda, Satoshi

2017-02-01

The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers. The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor. Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247-253, 2017. © 2016 Wiley Periodicals, Inc.

Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

PubMed Central

Wei, Caimiao; Gould, Rebekah; Yu, Xian; Zhang, Ya; Liu, Mei; Walls, Andrew; Bousamra, Alex; Ramineni, Maheshwari; Sinn, Bruno; Hunt, Kelly; Buchholz, Thomas A.; Valero, Vicente; Buzdar, Aman U.; Yang, Wei; Brewster, Abenaa M.; Moulder, Stacy; Pusztai, Lajos; Hatzis, Christos; Hortobagyi, Gabriel N.

2017-01-01

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated. PMID:28135148

Prevalence and predictors of depressive symptoms and wellbeing during and up to nine years after outpatient cardiac rehabilitation.

PubMed

Koçer, O; Wachter, M; Zellweger, M; Piazzalonga, S; Hoffmann, A

2011-07-30

Depression is an important independent prognostic variable in cardiac patients. The prevalence and predictors of depressive symptoms up to nine years after cardiac rehabilitation were studied. Follow-up questionnaires were sent to 2199 patients who had completed a 12-week exercise-based outpatient cardiac rehabilitation (OCR) programme between June 1999 and March 2006. Medical outcome, general wellbeing, and depressive symptoms were assessed, the latter by using two screening questions according to Arrol. Patients with incomplete data due to language problems, lack of compliance and non-response were excluded. Complete data for analysis was available for 710 patients. The median follow up period was 46 months (Interquartile range (IQR) 22-71, min. 6 months). At follow-up, 132 patients (19%) indicated low wellbeing, whereas 81 (11%) were having depressive symptoms. Multivariate analyses revealed impaired quality of life (p <0.001), diabetes (p = 0.013) and low exercise capacity after OCR (p = 0.003) to be independent predictors of low wellbeing at follow-up. Persistent smoking (p = 0.045) as well as negative mood (p = 0.022) at the end of OCR were independent predictors of depressive symptoms at follow-up. In a selected patient population a mean of four years after OCR, persistent smoking, diabetes, low exercise capacity and impaired quality of life at the end of OCR were independent long term predictors of low wellbeing and depressive symptoms, rather than specific cardiac variables. This highlights the need for close cooperation between cardiovascular and psychological specialists in cardiac rehabilitation.

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

PubMed

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

2017-12-01

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

An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study.

PubMed

Proctor, M J; Morrison, D S; Talwar, D; Balmer, S M; O'Reilly, D S J; Foulis, A K; Horgan, P G; McMillan, D C

2011-02-15

A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and γ-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer. Patients (n=21,669) who had an incidental blood sample taken between 2000 and 2006 for C-reactive protein, albumin and calcium (and liver function tests where available) and a diagnosis of cancer were identified. Of this group 9608 patients who had an ongoing malignant process were studied (sampled within 2 years before diagnosis). Also a subgroup of 5397 sampled at the time of diagnosis (sampled within 2 months prior to diagnosis) were examined. Cancers were grouped by tumour site in accordance with International Classification of Diseases 10 (ICD 10). On follow up, there were 6005 (63%) deaths of which 5122 (53%) were cancer deaths. The median time from blood sampling to diagnosis was 1.4 months. Increasing age, male gender and increasing deprivation was associated with a reduced 5-year overall and cancer-specific survival (all P<0.001). An elevated mGPS, adjusted calcium, bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase and γ-glutamyl transferase were associated with a reduced 5-year overall and cancer-specific survival (independent of age, sex and deprivation in all patients sampled), as well as within the time of diagnosis subgroup (all P<0.001). An increasing mGPS was predictive of a reduced cancer-specific survival in all cancers (all P<0.001). The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer.

Identifying prognostic signature in ovarian cancer using DirGenerank

PubMed Central

Wang, Jian-Yong; Chen, Ling-Ling; Zhou, Xiong-Hui

2017-01-01

Identifying the prognostic genes in cancer is essential not only for the treatment of cancer patients, but also for drug discovery. However, it's still a big challenge to select the prognostic genes that can distinguish the risk of cancer patients across various data sets because of tumor heterogeneity. In this situation, the selected genes whose expression levels are statistically related to prognostic risks may be passengers. In this paper, based on gene expression data and prognostic data of ovarian cancer patients, we used conditional mutual information to construct gene dependency network in which the nodes (genes) with more out-degrees have more chances to be the modulators of cancer prognosis. After that, we proposed DirGenerank (Generank in direct netowrk) algorithm, which concerns both the gene dependency network and genes’ correlations to prognostic risks, to identify the gene signature that can predict the prognostic risks of ovarian cancer patients. Using ovarian cancer data set from TCGA (The Cancer Genome Atlas) as training data set, 40 genes with the highest importance were selected as prognostic signature. Survival analysis of these patients divided by the prognostic signature in testing data set and four independent data sets showed the signature can distinguish the prognostic risks of cancer patients significantly. Enrichment analysis of the signature with curated cancer genes and the drugs selected by CMAP showed the genes in the signature may be drug targets for therapy. In summary, we have proposed a useful pipeline to identify prognostic genes of cancer patients. PMID:28615526

Cyclin D1 expression and facial function outcome after vestibular schwannoma surgery.

PubMed

Lassaletta, Luis; Del Rio, Laura; Torres-Martin, Miguel; Rey, Juan A; Patrón, Mercedes; Madero, Rosario; Roda, Jose Maria; Gavilan, Javier

2011-01-01

The proto-oncogen cyclin D1 has been implicated in the development and behavior of vestibular schwannoma. This study evaluates the association between cyclin D1 expression and other known prognostic factors in facial function outcome 1 year after vestibular schwannoma surgery. Sixty-four patients undergoing surgery for vestibular schwannoma were studied. Immunohistochemistry analysis was performed with anticyclin D1 in all cases. Cyclin D1 expression, as well as other demographic, clinical, radiologic, and intraoperative data, was correlated with 1-year postoperative facial function. Good 1-year facial function (Grades 1-2) was achieved in 73% of cases. Cyclin D1 expression was found in 67% of the tumors. Positive cyclin D1 staining was more frequent in patients with Grades 1 to 2 (75%) than in those with Grades 3 to 6 (25%). Other significant variables were tumor volume and facial nerve stimulation after tumor resection. The area under the receiver operating characteristics curve increased when adding cyclin D1 expression to the multivariate model. Cyclin D1 expression is associated to facial outcome after vestibular schwannoma surgery. The prognostic value of cyclin D1 expression is independent of tumor size and facial nerve stimulation at the end of surgery.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability.

PubMed

Stergiou, George S; Parati, Gianfranco; Vlachopoulos, Charalambos; Achimastos, Apostolos; Andreadis, Emanouel; Asmar, Roland; Avolio, Alberto; Benetos, Athanase; Bilo, Grzegorz; Boubouchairopoulou, Nadia; Boutouyrie, Pierre; Castiglioni, Paolo; de la Sierra, Alejandro; Dolan, Eamon; Head, Geoffrey; Imai, Yutaka; Kario, Kazuomi; Kollias, Anastasios; Kotsis, Vasilis; Manios, Efstathios; McManus, Richard; Mengden, Thomas; Mihailidou, Anastasia; Myers, Martin; Niiranen, Teemu; Ochoa, Juan Eugenio; Ohkubo, Takayoshi; Omboni, Stefano; Padfield, Paul; Palatini, Paolo; Papaioannou, Theodore; Protogerou, Athanasios; Redon, Josep; Verdecchia, Paolo; Wang, Jiguang; Zanchetti, Alberto; Mancia, Giuseppe; O'Brien, Eoin

2016-09-01

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

The wisdom of the commons: ensemble tree classifiers for prostate cancer prognosis

PubMed Central

Koziol, James A.; Feng, Anne C.; Jia, Zhenyu; Wang, Yipeng; Goodison, Seven; McClelland, Michael; Mercola, Dan

2009-01-01

Motivation: Classification and regression trees have long been used for cancer diagnosis and prognosis. Nevertheless, instability and variable selection bias, as well as overfitting, are well-known problems of tree-based methods. In this article, we investigate whether ensemble tree classifiers can ameliorate these difficulties, using data from two recent studies of radical prostatectomy in prostate cancer. Results: Using time to progression following prostatectomy as the relevant clinical endpoint, we found that ensemble tree classifiers robustly and reproducibly identified three subgroups of patients in the two clinical datasets: non-progressors, early progressors and late progressors. Moreover, the consensus classifications were independent predictors of time to progression compared to known clinical prognostic factors. Contact: dmercola@uci.edu PMID:18628288

Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

PubMed

Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

2002-12-30

Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before. Copyright 2002 John Wiley & Sons, Ltd.

The Prognostic Value of 14-3-3 Isoforms in Vulvar Squamous Cell Carcinoma Cases: 14-3-3β and ε Are Independent Prognostic Factors for These Tumors

PubMed Central

Wang, Zhihui; Nesland, Jahn M.; Suo, Zhenhe; Trope, Claes G.; Holm, Ruth

2011-01-01

Background The 14-3-3 family is comprised of highly conserved proteins that are functionally important in the maintenance of homeostasis. Their involvement with the cell cycle, their association with proto-oncogenes and oncogenes, and their abnormal expression in various tumors has linked this family of proteins to the etiology of human cancer. Mounting evidence now indicates that 14-3-3σ is a cancer suppressor gene but the roles of the other 14-3-3 isoforms and their interactions in tumorigenesis have not yet been elucidated. In our current study, we examined the expression of 14-3-3β, γ, ε, ζ, η and τ in a large series of vulvar squamous cell carcinomas to evaluate any clinical significance. Methods Tumor biopsies from 298 vulvar carcinomas were examined by immunohistochemistry for the expression of 14-3-3β, γ, ε, ζ, η and τ. Statistical analyses were employed to validate any associations between the expression of any 14-3-3 isoform and clinicopathologic variables for this disease. Results High cytoplasmic levels of 14-3-3β, γ, ζ, ε and η were observed in 79%, 58%, 50%, 86% and 54% of the vulvar carcinomas analyzed, respectively, whereas a low nuclear expression of 14-3-3τ was present in 80% of these cases. The elevated cytoplasmic expression of 14-3-3β, γ, ε, ζ and η was further found to be associated with advanced disease and aggressive features of these cancers. The overexpression of cytoplasmic 14-3-3β and ε significantly correlated with a poor disease-specific survival by univariate analysis (P = 0.007 and P = 0.04, respectively). The independent prognostic significance of these factors was confirmed by multivariate analysis (P = 0.007 and P = 0.009, respectively). Conclusions We reveal for the first time that the 14-3-3β, γ, ε, ζ, η and τ isoforms may be involved in the progression of vulvar carcinomas. Furthermore, our analyses show that high cytoplasmic levels of 14-3-3β and ε independently correlate with poor disease-specific survival. PMID:21935479

Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

PubMed

Nakagawa, Tateo; Shimada, Mitsuo; Kurita, Nobuhiro; Iwata, Takashi; Nishioka, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Utsunomiya, Tohru

2012-06-01

The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma.

PubMed

Yasutake, Nobuko; Ohishi, Yoshihiro; Taguchi, Kenichi; Hiraki, Yuka; Oya, Masafumi; Oshiro, Yumi; Mine, Mari; Iwasaki, Takeshi; Yamamoto, Hidetaka; Kohashi, Kenichi; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

2018-04-01

The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. IMP3 expression in ULMS could be a marker of a poor prognosis. © 2017 John Wiley & Sons Ltd.

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

PubMed

Botto, Fernando; Alonso-Coello, Pablo; Chan, Matthew T V; Villar, Juan Carlos; Xavier, Denis; Srinathan, Sadeesh; Guyatt, Gordon; Cruz, Patricia; Graham, Michelle; Wang, C Y; Berwanger, Otavio; Pearse, Rupert M; Biccard, Bruce M; Abraham, Valsa; Malaga, German; Hillis, Graham S; Rodseth, Reitze N; Cook, Deborah; Polanczyk, Carisi A; Szczeklik, Wojciech; Sessler, Daniel I; Sheth, Tej; Ackland, Gareth L; Leuwer, Martin; Garg, Amit X; Lemanach, Yannick; Pettit, Shirley; Heels-Ansdell, Diane; Luratibuse, Giovanna; Walsh, Michael; Sapsford, Robert; Schünemann, Holger J; Kurz, Andrea; Thomas, Sabu; Mrkobrada, Marko; Thabane, Lehana; Gerstein, Hertzel; Paniagua, Pilar; Nagele, Peter; Raina, Parminder; Yusuf, Salim; Devereaux, P J; Devereaux, P J; Sessler, Daniel I; Walsh, Michael; Guyatt, Gordon; McQueen, Matthew J; Bhandari, Mohit; Cook, Deborah; Bosch, Jackie; Buckley, Norman; Yusuf, Salim; Chow, Clara K; Hillis, Graham S; Halliwell, Richard; Li, Stephen; Lee, Vincent W; Mooney, John; Polanczyk, Carisi A; Furtado, Mariana V; Berwanger, Otavio; Suzumura, Erica; Santucci, Eliana; Leite, Katia; Santo, Jose Amalth do Espirirto; Jardim, Cesar A P; Cavalcanti, Alexandre Biasi; Guimaraes, Helio Penna; Jacka, Michael J; Graham, Michelle; McAlister, Finlay; McMurtry, Sean; Townsend, Derek; Pannu, Neesh; Bagshaw, Sean; Bessissow, Amal; Bhandari, Mohit; Duceppe, Emmanuelle; Eikelboom, John; Ganame, Javier; Hankinson, James; Hill, Stephen; Jolly, Sanjit; Lamy, Andre; Ling, Elizabeth; Magloire, Patrick; Pare, Guillaume; Reddy, Deven; Szalay, David; Tittley, Jacques; Weitz, Jeff; Whitlock, Richard; Darvish-Kazim, Saeed; Debeer, Justin; Kavsak, Peter; Kearon, Clive; Mizera, Richard; O'Donnell, Martin; McQueen, Matthew; Pinthus, Jehonathan; Ribas, Sebastian; Simunovic, Marko; Tandon, Vikas; Vanhelder, Tomas; Winemaker, Mitchell; Gerstein, Hertzel; McDonald, Sarah; O'Bryne, Paul; Patel, Ameen; Paul, James; Punthakee, Zubin; Raymer, Karen; Salehian, Omid; Spencer, Fred; Walter, Stephen; Worster, Andrew; Adili, Anthony; Clase, Catherine; Cook, Deborah; Crowther, Mark; Douketis, James; Gangji, Azim; Jackson, Paul; Lim, Wendy; Lovrics, Peter; Mazzadi, Sergio; Orovan, William; Rudkowski, Jill; Soth, Mark; Tiboni, Maria; Acedillo, Rey; Garg, Amit; Hildebrand, Ainslie; Lam, Ngan; Macneil, Danielle; Mrkobrada, Marko; Roshanov, Pavel S; Srinathan, Sadeesh K; Ramsey, Clare; John, Philip St; Thorlacius, Laurel; Siddiqui, Faisal S; Grocott, Hilary P; McKay, Andrew; Lee, Trevor W R; Amadeo, Ryan; Funk, Duane; McDonald, Heather; Zacharias, James; Villar, Juan Carlos; Cortés, Olga Lucía; Chaparro, Maria Stella; Vásquez, Skarlett; Castañeda, Alvaro; Ferreira, Silvia; Coriat, Pierre; Monneret, Denis; Goarin, Jean Pierre; Esteve, Cristina Ibanez; Royer, Catherine; Daas, Georges; Chan, Matthew T V; Choi, Gordon Y S; Gin, Tony; Lit, Lydia C W; Xavier, Denis; Sigamani, Alben; Faruqui, Atiya; Dhanpal, Radhika; Almeida, Smitha; Cherian, Joseph; Furruqh, Sultana; Abraham, Valsa; Afzal, Lalita; George, Preetha; Mala, Shaveta; Schünemann, Holger; Muti, Paola; Vizza, Enrico; Wang, C Y; Ong, G S Y; Mansor, Marzida; Tan, Alvin S B; Shariffuddin, Ina I; Vasanthan, V; Hashim, N H M; Undok, A Wahab; Ki, Ushananthini; Lai, Hou Yee; Ahmad, Wan Azman; Razack, Azad H A; Malaga, German; Valderrama-Victoria, Vanessa; Loza-Herrera, Javier D; De Los Angeles Lazo, Maria; Rotta-Rotta, Aida; Szczeklik, Wojciech; Sokolowska, Barbara; Musial, Jacek; Gorka, Jacek; Iwaszczuk, Pawel; Kozka, Mateusz; Chwala, Maciej; Raczek, Marcin; Mrowiecki, Tomasz; Kaczmarek, Bogusz; Biccard, Bruce; Cassimjee, Hussein; Gopalan, Dean; Kisten, Theroshnie; Mugabi, Aine; Naidoo, Prebashini; Naidoo, Rubeshan; Rodseth, Reitze; Skinner, David; Torborg, Alex; Paniagua, Pilar; Urrutia, Gerard; Maestre, Mari Luz; Santaló, Miquel; Gonzalez, Raúl; Font, Adrià; Martínez, Cecilia; Pelaez, Xavier; De Antonio, Marta; Villamor, Jose Marcial; García, Jesús Alvarez; Ferré, Maria José; Popova, Ekaterina; Alonso-Coello, Pablo; Garutti, Ignacio; Cruz, Patricia; Fernández, Carmen; Palencia, Maria; Díaz, Susana; Del Castillo, Teresa; Varela, Alberto; de Miguel, Angeles; Muñoz, Manuel; Piñeiro, Patricia; Cusati, Gabriel; Del Barrio, Maria; Membrillo, Maria José; Orozco, David; Reyes, Fidel; Sapsford, Robert J; Barth, Julian; Scott, Julian; Hall, Alistair; Howell, Simon; Lobley, Michaela; Woods, Janet; Howard, Susannah; Fletcher, Joanne; Dewhirst, Nikki; Williams, C; Rushton, A; Welters, I; Leuwer, M; Pearse, Rupert; Ackland, Gareth; Khan, Ahsun; Niebrzegowska, Edyta; Benton, Sally; Wragg, Andrew; Archbold, Andrew; Smith, Amanda; McAlees, Eleanor; Ramballi, Cheryl; Macdonald, Neil; Januszewska, Marta; Stephens, Robert; Reyes, Anna; Paredes, Laura Gallego; Sultan, Pervez; Cain, David; Whittle, John; Del Arroyo, Ana Gutierrez; Sessler, Daniel I; Kurz, Andrea; Sun, Zhuo; Finnegan, Patrick S; Egan, Cameron; Honar, Hooman; Shahinyan, Aram; Panjasawatwong, Krit; Fu, Alexander Y; Wang, Sihe; Reineks, Edmunds; Nagele, Peter; Blood, Jane; Kalin, Megan; Gibson, David; Wildes, Troy

2014-03-01

Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Functionality predictors in acquired brain damage.

PubMed

Huertas Hoyas, E; Pedrero Pérez, E J; Águila Maturana, A M; García López-Alberca, S; González Alted, C

2015-01-01

Most individuals who have survived an acquired brain injury present consequences affecting the sensorimotor, cognitive, affective or behavioural components. These deficits affect the proper performance of daily living activities. The aim of this study is to identify functional differences between individuals with unilateral acquired brain injury using functional independence, capacity, and performance of daily activities. Descriptive cross-sectional design with a sample of 58 people, with right-sided injury (n=14 TBI; n=15 stroke) or left-sided injury (n = 14 TBI, n = 15 stroke), right handed, and with a mean age of 47 years and time since onset of 4 ± 3.65 years. The functional assessment/functional independence measure (FIM/FAM) and the International Classification of Functioning (ICF) were used for the study. The data showed significant differences (P<.000), and a large size effect (dr=0.78) in the cross-sectional estimates, and point to fewer restrictions for patients with a lesion on their right side. The major differences were in the variables 'speaking' and 'receiving spoken messages' (ICF variables), and 'Expression', 'Writing' and 'intelligible speech' (FIM/FAM variables). In the linear regression analysis, the results showed that only 4 FIM/FAM variables, taken together, predict 44% of the ICF variance, which measures the ability of the individual, and up to 52% of the ICF, which measures the individual's performance. Gait alone predicts a 28% of the variance. It seems that individuals with acquired brain injury in the left hemisphere display important differences regarding functional and communication variables. The motor aspects are an important prognostic factor in functional rehabilitation. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Current status of accurate prognostic awareness in advanced/terminally ill cancer patients: Systematic review and meta-regression analysis.

PubMed

Chen, Chen Hsiu; Kuo, Su Ching; Tang, Siew Tzuh

2017-05-01

No systematic meta-analysis is available on the prevalence of cancer patients' accurate prognostic awareness and differences in accurate prognostic awareness by publication year, region, assessment method, and service received. To examine the prevalence of advanced/terminal cancer patients' accurate prognostic awareness and differences in accurate prognostic awareness by publication year, region, assessment method, and service received. Systematic review and meta-analysis. MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO were systematically searched on accurate prognostic awareness in adult patients with advanced/terminal cancer (1990-2014). Pooled prevalences were calculated for accurate prognostic awareness by a random-effects model. Differences in weighted estimates of accurate prognostic awareness were compared by meta-regression. In total, 34 articles were retrieved for systematic review and meta-analysis. At best, only about half of advanced/terminal cancer patients accurately understood their prognosis (49.1%; 95% confidence interval: 42.7%-55.5%; range: 5.4%-85.7%). Accurate prognostic awareness was independent of service received and publication year, but highest in Australia, followed by East Asia, North America, and southern Europe and the United Kingdom (67.7%, 60.7%, 52.8%, and 36.0%, respectively; p = 0.019). Accurate prognostic awareness was higher by clinician assessment than by patient report (63.2% vs 44.5%, p < 0.001). Less than half of advanced/terminal cancer patients accurately understood their prognosis, with significant variations by region and assessment method. Healthcare professionals should thoroughly assess advanced/terminal cancer patients' preferences for prognostic information and engage them in prognostic discussion early in the cancer trajectory, thus facilitating their accurate prognostic awareness and the quality of end-of-life care decision-making.

Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.

PubMed

Cheng, Mei-Ling; Wang, Chao-Hung; Shiao, Ming-Shi; Liu, Min-Hui; Huang, Yu-Yen; Huang, Cheng-Yu; Mao, Chun-Tai; Lin, Jui-Fen; Ho, Hung-Yao; Yang, Ning-I

2015-04-21

Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF. This study sought to assess the diagnostic and prognostic values of metabolomics in HF. Mass spectrometry-based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the "recovery" group. A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p < 0.0001) independent of BNP and traditional risk factors. The prognostic value of the metabolite panel was better than that of BNP (area under the curve of 0.85 vs. 0.74 for BNP) and Kaplan-Meier curves (log rank: 17.5 vs. 9.95). These findings were corroborated in the validation study. Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection.

PubMed

Zhang, Heng; Wang, Xuefei; Shen, Zhenbin; Xu, Jiejie; Qin, Jing; Sun, Yihong

2015-10-01

Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients. CD68(+) TAMs display polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c(+) TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206(+) TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p < 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p < 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.

Systemic Inflammation-Based Biomarkers and Survival in HIV-Positive Subject With Solid Cancer in an Italian Multicenter Study.

PubMed

Raffetti, Elena; Donato, Francesco; Pezzoli, Chiara; Digiambenedetto, Simona; Bandera, Alessandra; Di Pietro, Massimo; Di Filippo, Elisa; Maggiolo, Franco; Sighinolfi, Laura; Fornabaio, Chiara; Castelnuovo, Filippo; Ladisa, Nicoletta; Castelli, Francesco; Quiros Roldan, Eugenia

2015-08-15

Recently, some systemic inflammation-based biomarkers have been demonstrated useful for predicting risk of death in patients with solid cancer independently of tumor characteristics. This study aimed to investigate the prognostic role of systemic inflammation-based biomarkers in HIV-infected patients with solid tumors and to propose a risk score for mortality in these subjects. Clinical and pathological data on solid AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC), diagnosed between 1998 and 2012 in an Italian cohort, were analyzed. To evaluate the prognostic role of systemic inflammation- and nutrition-based markers, univariate and multivariable Cox regression models were applied. To compute the risk score equation, the patients were randomly assigned to a derivation and a validation sample. A total of 573 patients (76.3% males) with a mean age of 46.2 years (SD = 10.3) were enrolled. 178 patients died during a median of 3.2 years of follow-up. For solid NADCs, elevated Glasgow Prognostic Score, modified Glasgow Prognostic Score, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and Prognostic Nutritional Index were independently associated with risk of death; for solid ADCs, none of these markers was associated with risk of death. For solid NADCs, we computed a mortality risk score on the basis of age at cancer diagnosis, intravenous drug use, and Prognostic Nutritional Index. The areas under the receiver operating characteristic curve were 0.67 (95% confidence interval: 0.58 to 0.75) in the derivation sample and 0.66 (95% confidence interval: 0.54 to 0.79) in the validation sample. Inflammatory biomarkers were associated with risk of death in HIV-infected patients with solid NADCs but not with ADCs.

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy

PubMed Central

Yamashita, Keishi; Ema, Akira; Hosoda, Kei; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Watanabe, Masahiko

2017-01-01

AIM To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer. PMID:28451064

Supraclavicular node disease is not an independent prognostic factor for survival of esophageal cancer patients treated with definitive chemoradiation.

PubMed

Jeene, Paul M; Versteijne, Eva; van Berge Henegouwen, Mark I; Bergmann, Jacques J G H M; Geijsen, Elisabeth D; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M

2017-01-01

The prognostic value of supraclavicular lymph node (SCN) metastases in esophageal cancer is not well established. We analyzed the prognostic value of SCN disease in patients after definitive chemoradiation (dCRT) for esophageal cancer. We retrospectively analyzed 207 patients treated between 2003 and 2013 to identify the prognostic value of metastasis in the SCN on treatment failure and survival. All patients were treated with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel 50 mg/m 2 and carboplatin AUC2. Median follow-up for patients alive was 43.3 months. The median overall survival (OS) for all patients was 17.5 months. OS at one, three and five years was 67%, 36% and 21%, respectively. For patients with metastasis in a SCN, OS was 23.6 months compared to 17.1 months for patients without metastasis in the SCN (p = .51). In multivariate analyses, higher cT status, cN status and adenocarcinoma were found to be prognostically unfavorable, but a positive SCN was not (p = .67). Median OS and median disease-free survival for tumors with SCN involvement and N0/1 disease was 49.0 months and 51.6 months, respectively, compared to 14.2 months and 8.2 months, respectively, in patients with N2/3 disease. In esophageal cancer treated with dCRT, the number of affected lymph nodes is an important independent prognostic factor, whereas involvement of a SCN is not. Supraclavicular lymph nodes should be considered as regional lymph nodes and treated with curative intent if the total number of involved lymph nodes is limited.

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Kofunato, Yasuhide; Okada, Ryo; Ishigame, Teruhide; Kimura, Takashi; Kenjo, Akira; Marubashi, Shigeru; Kono, Koji; Takenoshita, Seiichi

2017-09-19

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.

aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

PubMed

Kato, Shingo; Akimoto, Kazunori; Nagashima, Yoji; Ishiguro, Hitoshi; Kubota, Kensuke; Kobayashi, Noritoshi; Hosono, Kunihiro; Watanabe, Seitaro; Sekino, Yusuke; Sato, Takamitsu; Sasaki, Kazunori; Nakaigawa, Noboru; Kubota, Yoshinobu; Inayama, Yoshiaki; Endo, Itaru; Ohno, Shigeo; Maeda, Shin; Nakajima, Atsushi

2013-01-01

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Serum prognostic biomarkers in head and neck cancer patients.

PubMed

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

2014-08-01

A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Serum Prognostic Biomarkers in Head and Neck Cancer Patients

PubMed Central

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S.; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H.; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J.; Tainsky, Michael A.

2014-01-01

Objectives/Hypothesis A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Study Design Prospective cohort study. Methods A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient’s serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Results Poor overall survival was associated with African Americans (hazard ratio [HR] for death =2.61; 95% confidence interval [CI]: 1.58–4.33; P =.000), advanced stage (HR =2.79; 95% CI: 1.40–5.57; P =.004), and recurrent disease (HR =6.66; 95% CI: 2.54–17.44; P =.000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. Conclusions The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. PMID:24347532

Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

PubMed

Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

2018-05-01

In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Prognostic significance of IDH 1 mutation in patients with glioblastoma multiforme.

PubMed

Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-05-01

Focus of brain tumour research is shifting towards tumour genesis and genetics, and possible development of individualized treatment plans. Genetic analysis shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic significance of IDH 1 mutation on the basis of published evidence. Multiple retrospective clinical analyses correlate the presence of IDH1 mutation in GBM with good prognostic outcomes compared to wild-type IDH1. A systematic review reported similar results. Based on the review of current literature IDH1 mutation is an independent factor for longer overall survival (OS) and progression free survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic significance opens up new avenues for treatment.

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

PubMed Central

Koh, Young W.; Lee, Hyun W.

2017-01-01

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

The prognostic value of histidine-rich glycoprotein RNA in breast tissue using unmodified gold nanoparticles assay.

PubMed

Eissa, Sanaa; Azzazy, Hassan M E; Matboli, Marwa; Shawky, Sherif M; Said, Hebatallah; Anous, Fatin A

2014-09-01

The aim of is this study is to explore the role of tissue histidine-rich glycoprotein (HRG) RNA as a promising clinically useful biomarker for breast cancer patients prognosis using nanogold assay. Expression of the HRG RNA was assessed by gold nanoparticles and conventional RT-PCR after purification by magnetic nanoparticles in breast tissue samples. The study included 120 patients, 60 of which were histologically proven breast carcinoma cases, 30 had benign breast lesions and 30 were healthy individuals who had undergone reductive plastic surgery. ER, PR and HER2 status were also investigated. The prognostic significance of tissue HRG RNA expression in breast cancer was explored. The magnetic nanoparticles coated with specific thiol modified oligonucleotide probe were used successfully in purification of HRG RNA from breast tissue total RNAs with satisfactory yield. The developed HRG AuNPs assay had a sensitivity and a specificity of 90 %, and a detection limit of 1.5 nmol/l. The concordance rate between the HRG AuNPs assay with RT-PCR after RNA purification using magnetic nanoparticles was 93.3 %. The median follow-up period was 60 months. Among traditional prognostic biomarkers, HRG was a significant independent prognostic marker in relapse-free survival (RFS). HRG RNA is an independent prognostic marker for breast cancer and can be detected using gold NPs assay, which is rapid, sensitive, specific, inexpensive to extend the value for breast cancer prognosis.

Prediction of the First Variceal Haemorrhage

PubMed Central

1997-01-01

We followed 87 cirrhotic patients with esophageal varices and without previous hemorrhage for a mean period of 24 mo to prospectively evaluate the occurance of variceal bleeding within (early) or after (late) 6 mo from entry and the contribution of portal Doppler ultrasound parameters to the prediction of early and late hemorrhage. Clinical, biochemical, endoscopic and portal Doppler ultrasound parameters were recorded at entry. Variceal bleeding occurred in 22 patients (25.3%). Nine (40.9%) bled within the first 6 mo. Cox regression analysis identified variceal size, cherry-red spots, serum bilirubin and congestion index of the portal vein (the ratio of portal vein [cross-sectional area] and portal blood flow velocity) as the only independent predictors of first variceal hemorrhage. Discriminant analysis was used to find the prognostic index cut off points to identify patients who bled within 6 mo (prognostic group 1) or after 6 mo (prognostic group 2) or remained free of bleeding (prognostic group 3). The cumulative proportion of patients correctly classified was 73% in prognostic group 1, 47% in prognostic group 2 and more than 80% in prognostic group 3. The addition of Doppler ultrasound flowmetry to clinical, biochemical and endoscopic parameter only improved the classification of patients with early bleeding. PMID:9184882

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PubMed

Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

2017-08-01

The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Prognostic factors in multiple myeloma: selection using Cox's proportional hazard model.

PubMed

Pasqualetti, P; Collacciani, A; Maccarone, C; Casale, R

1996-01-01

The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.

A retrospective study of feline gastric lymphoma in 16 chemotherapy-treated cats.

PubMed

Gustafson, Tanya L; Villamil, Armando; Taylor, Bonnie E; Flory, Andrea

2014-01-01

The purposes of this study were to describe cases of feline gastric lymphoma with regards to signalment, clinical presentation, laboratory and ancillary study findings, response to therapy, and outcomes and to identify prognostic variables. Sixteen cats with stage I and II gastric lymphoma treated with chemotherapy were included in this study. Seventy-five percent of cats experienced remission. Overall, first remission duration was 108 days. Response to treatment was prognostic as in other types of feline lymphoma. Cats with a complete remission (CR) had longer survival times compared with cats with a partial remission (PR). Sex and treatment with a rescue protocol were found to be prognostic with castrated males having longer survivals than spayed females. Cats that received rescue chemotherapy had shorter first remission durations than those that did not. Prior treatment with steroids and stage were not found to be significant prognostic variables. This study characterizes gastric lymphoma treated with chemotherapy in cats. Further studies are needed to determine the comparative efficacy of surgical and chemotherapeutic treatments for feline gastric lymphoma.

Prognostic Factors in Glioblastoma: Is There a Role for Epilepsy?

PubMed Central

DOBRAN, Mauro; NASI, Davide; CHIRIATTI, Stefano; GLADI, Maurizio; di SOMMA, Lucia; IACOANGELI, Maurizio; SCERRATI, Massimo

2018-01-01

The prognostic relevance of epilepsy at glioblastoma (GBMs) onset is still under debate. In this study, we analyzed the value of epilepsy and other prognostic factors on GBMs survival. We retrospectively analyzed the clinical, radiological, surgical and histological data in 139 GBMs. Seizures were the presenting symptoms in 50 patients out of 139 (35.9%). 123 patients (88%) were treated with craniotomy and tumor resection while 16 (12%) with biopsy. The median overall survival was 9.9 months from surgery. At univariable Cox regression, the factors that significantly improved survival were age less than 65 years (P = 0.0015), focal without impairment of consciousness seizures at presentation (P = 0.043), complete surgical resection (P < 0.001), pre-operative Karnofsky performance status (KPS) > 70 (P = 0.015), frontal location (P < 0.001), radiotherapy (XRT) plus concomitant and adjuvant TMZ (P < 0.001). A multivariable Cox regression showed that the complete surgical resection (P < 0.0001), age less than 65 years (P = 0.008), frontal location (P = 0.0001) and XRT adjuvant temozolomide (TMZ) (P < 0.0001) were independent factors on longer survival. In our series epilepsy at presentation is not an independent prognostic factor for longer survival in GBM patients. Only in the subgroup of patients with focal seizures without impairment of consciousness, epilepsy was associated with an increased significant overall survival at univariate analysis (P = 0.043). Main independent factors for relatively favorable GBMs outcome are complete tumor resection plus combined XRT-TMZ, frontal location and patient age below 65 years old. PMID:29343677

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

PubMed

Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

2015-06-03

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

Factors affecting mortality in elderly patients who underwent surgery for gastric cancer.

PubMed

Kayılıoglu, Selami Ilgaz; Göktug, Ufuk Utku; Dinc, Tolga; Sozen, Isa; Yavuz, Zeynep; Coskun, Faruk

2018-03-05

The aim of this study was to determine factors affecting overall mortality in patients over 60 years of age who underwent surgery for gastric cancer in our clinic. Data on histopathological diagnosis (tumor size, lymph node status, and number), pathological stage, serum albumin level, tumor markers, complete blood count, and demographic information of 109 patients over 60 years of age who had surgery for gastric cancer between January 2011 and July 2016 were obtained retrospectively from the patient files. In addition, the survival status of all patients were examined and recorded. Metastatic lymph node ratio (MLR), red cell distribution width platelet ratio (RPR), neutrophil-lymphocyte ratio (NLR), plateletlymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated. On univariate analysis of independent parameters, pathological LN number (p = 0.001), MLR (p <0.001), T3 (p = 0.001) or T4 (p = 0,006) tumor stage according to TNM system, the presence of metastasis (p = 0.063), and male gender (p = 0.066) were found to affect overall mortality (OM). On multivariable Cox regression analysis of these results, MLR (p = 0.005) and T stage (p = 0.006) was determined to be a statistically significant and independent prognostic value. In patients over 60 years of age who underwent surgery for gastric cancer, the factors affecting mortality were determined to be the presence of metastases, number of pathological lymph nodes, and male gender. Metastatic lymph node ratio and T1&T2 stage were determined to be independent prognostic factors. Elderly, Gastric cancer, Mortality, Prognostic factor.

Overexpression of c-kit(CD117), relevant with microvessel density, is an independent survival prognostic factor for patients with HBV-related hepatocellular carcinoma.

PubMed

Yan, Weiwei; Zhu, Zhenyu; Pan, Fei; Huang, Ang; Dai, Guang-Hai

2018-01-01

To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P =0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV ( P <0.001) and TNM stage III ( P <0.001). Moreover, Kaplan-Meier survival analysis showed that c-kit ( P <0.001) expression was correlated with reduced disease-free survival (DFS). Multivariate analysis identified c-kit as an independent poor prognostic factor of DFS in HCC patients ( P <0.001). Increased c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

PubMed Central

Langer, Christian; Radmacher, Michael D.; Ruppert, Amy S.; Whitman, Susan P.; Paschka, Peter; Mrózek, Krzysztof; Baldus, Claudia D.; Vukosavljevic, Tamara; Liu, Chang-Gong; Ross, Mary E.; Powell, Bayard L.; de la Chapelle, Albert; Kolitz, Jonathan E.; Larson, Richard A.; Marcucci, Guido

2008-01-01

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. PMID:18378853

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

PubMed

Mathieu, R; Moschini, M; Beyer, B; Gust, K M; Seisen, T; Briganti, A; Karakiewicz, P; Seitz, C; Salomon, L; de la Taille, A; Rouprêt, M; Graefen, M; Shariat, S F

2017-06-01

We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

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

PubMed

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

2013-04-01

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

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

PubMed Central

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

2014-01-01

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

Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis.

PubMed

Fu, Qiang; Chang, Yuan; An, Huimin; Fu, Hangcheng; Zhu, Yu; Xu, Le; Zhang, Weijuan; Xu, Jiejie

2015-12-01

Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time. We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models. The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years. Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

PubMed Central

Leong, Tora; Rehman, Michaela B.; Pastormerlo, Luigi Emilio; Harrell, Frank E.; Coats, Andrew J. S.; Francis, Darrel P.

2014-01-01

Background Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. Objectives We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). Data Sources and Eligibility Criteria Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. Methods First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. Results 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). Limitations This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. Key Findings First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis. Conclusions Emphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist. PMID:24475020

Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy: A Retrospective Analysis of 7781 Gastric Cancer Patients.

PubMed

Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

2016-05-01

To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760-10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221-1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985-1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence.

DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer

PubMed Central

Cao, Xue-Yuan; Ma, Hong-Xi; Shang, Yan-Hong; Jin, Mei-Shan; Kong, Fei; Jia, Zhi-Fang; Cao, Dong-Hui; Wang, Yin-Ping; Suo, Jian; Jiang, Jing

2014-01-01

AIM: To explore the alteration of DNA methyltransferase expression in gastric cancer and to assess its prognostic value. METHODS: From April 2000 to December 2010, 227 men and 73 women with gastric cancer were enrolled in the study. The expression of DNA methyltransferases (DNMTs), including DNMT1, DNMT3a and DNMT3b, in the 300 cases of gastric carcinoma, of which 85 had paired adjacent normal gastric mucus samples, was evaluated by immunohistochemistry using a tissue microarray. Serum anti-Helicobacter pylori (H. pylori) IgG was detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the above results and the clinicopathological characteristics were analyzed. Their prognostic value was evaluated using the Cox proportional hazards model. RESULTS: In gastric cancer, expression of DNMTs was mainly seen in the nucleus. Weak staining was also observed in the cytoplasm. Expression of DNMT1, DNMT3a and DNMT3b in gastric cancer was significantly higher compared to that in the paired control samples (60.0% vs 37.6%, 61.2% vs 4.7%, and 94.1% vs 71.8%, P < 0.01). The overall survival rate was significantly higher in the DNMT3a negative group than in the DNMT3a positive group in gastric cancer patients (Log-rank test, P = 0.032). No significant correlation was observed between DNMT1 and DNMT3b expression and the overall survival time (Log-rank test, P = 0.289, P = 0.347). Multivariate regression analysis indicated that DNMT3a expression (P = 0.025) and TNM stage (P < 0.001), but not DNMT1 (P = 0.54) or DNMT3b (P = 0.62), were independent prognostic factors in gastric cancer. H. pylori infection did not induce protein expression of DNMTs. CONCLUSION: The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis. PMID:25009393

Clinical and prognostic value of spot urinary creatinine in chronic heart failure-An analysis from GISSI-HF.

PubMed

Ter Maaten, Jozine M; Maggioni, Aldo Pietro; Latini, Roberto; Masson, Serge; Tognoni, Gianni; Tavazzi, Luigi; Signorini, Stefano; Voors, Adriaan A; Damman, Kevin

2017-06-01

This study aimed to identify patient characteristics associated with low urinary creatinine in morning spot urine and investigate its association with clinical outcome. Twenty-four-hour creatinine excretion is an established marker of muscle mass in heart failure and other populations. Spot urine creatinine might be an easy obtainable, cheap marker of muscle wasting and prognosis in heart failure (HF) patients. Spot urine creatinine concentration was measured in 2130 patients included in the GISSI-HF trial. We evaluated the prognostic value of urinary creatinine and its relation with clinical variables. Median spot urinary creatinine was 0.80 (IQR 0.50-1.10) g/L. Lower spot urinary creatinine was associated with older age, smaller height and weight, higher NYHA class, worse renal function and more frequent spironolactone and diuretic use (all P<.02). During a median follow-up of 2.8 years, 655 patients (31%) experienced the combined endpoint of all-cause mortality or HF hospitalization. Lower urinary creatinine was independently associated with an increased risk of all-cause mortality or HF hospitalization (HR, 1.59 [1.21-2.08] per log decrease, P=.001), and all-cause mortality (HR, 1.75 [1.25-2.45] per log decrease, P=.001). Lower urinary creatinine, measured in morning spot urine in patients with chronic HF, is associated with worse renal function, smaller body size, more severe HF and is independently associated with an increased risk of all-cause death and HF hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

Carboxyhemoglobin and methemoglobin levels as prognostic markers in acute pulmonary embolism.

PubMed

Kakavas, Sotirios; Papanikolaou, Aggeliki; Ballis, Evangelos; Tatsis, Nikolaos; Goga, Christina; Tatsis, Georgios

2015-04-01

Carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels have been associated with a poor outcome in patients with various pathological conditions including cardiovascular diseases. Our aim was to retrospectively assess the prognostic value of arterial COHb and MetHb in patients with acute pulmonary embolism (PE). We conducted a retrospective study of 156 patients admitted in a pulmonary clinic due to acute PE. Measured variables during emergency department evaluation that were retrospectively analyzed included the ratio of the partial pressure of oxygen in arterial blood to the fraction of oxygen in inspired gas, Acute Physiology and Chronic Health Evaluation II score, risk stratification indices, and arterial blood gases. The association between arterial COHb and MetHb levels and disease severity or mortality was evaluated using bivariate tests and logistic regression analysis. Arterial COHb and MetHb levels correlated with Acute Physiology and Chronic Health Evaluation II and pulmonary severity index scores. Furthermore, arterial COHb and MetHb levels were associated with troponin T and N-terminal pro-B-type natriuretic peptide levels. In univariate logistic regression analysis, COHb and MetHb levels were both significantly associated with an increased risk of death. However, in multivariate analysis, only COHb remained significant as an independent predictor of in-hospital mortality. Our preliminary data suggest that arterial COHb and MetHb levels reflect the severity of acute PE, whereas COHb levels are independent predictors of in hospital death in patients in this clinical setting. These findings require further prospective validation. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective cohort study of prognostic factors in patients with oral cavity and oropharyngeal squamous cell carcinoma.

PubMed

Carrillo, José F; Carrillo, Liliana C; Cano, Ana; Ramirez-Ortega, Margarita C; Chanona, Jorge G; Avilés, Alejandro; Herrera-Goepfert, Roberto; Corona-Rivera, Jaime; Ochoa-Carrillo, Francisco J; Oñate-Ocaña, Luis F

2016-04-01

Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma (SCC) are debated. The purpose of this study was to investigate the association of prognostic factors with oncologic outcomes. Patients with oral cavity and oropharyngeal SCC treated from 1997 to 2012 were included in this retrospective cohort study. Associations of prognostic factors with locoregional recurrence (LRR) or overall survival (OS) were analyzed using the logistic regression and the Cox models. Six hundred thirty-four patients were included in this study; tumor size, surgical margins, and N classification were associated with LRR (p < .0001); considering histopathology: perineural invasion, lymphocytic infiltration, infiltrative borders, and N classification were significant determinants of LRR. Tumor size, N classification, alcoholism, and surgical margins were associated with OS (p < .0001); considering pathologic prognostic factors, perivascular invasion, islands borders, and surgical margins were independently associated with OS (p < .0001). Surgical margins, perineural and perivascular invasion, lymphocytic infiltration, and infiltrative patterns of tumor invasion are significant prognostic factors in oral cavity and oropharyngeal SCC. © 2015 Wiley Periodicals, Inc.

Prognostic significance of XRCC4 expression in hepatocellular carcinoma

PubMed Central

Huang, Xiao-Ying; Yao, Jin-Guang; Wang, Chao; Wei, Zhong-Hong; Ma, Yun; Wu, Xue-Min; Luo, Chun-Ying; Xia, Qiang; Long, Xi-Dai

2017-01-01

Background Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. Materials and Methods We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50). Results XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin. Conclusions These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma. PMID:29152133

EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival.

PubMed

Monteiro, Luís Silva; Delgado, Maria Leonor; Ricardo, Sara; Garcez, Fernanda; do Amaral, Barbas; Pacheco, José Júlio; Lopes, Carlos; Bousbaa, Hassan

2014-01-01

The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma

PubMed Central

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-01-01

Background Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients’ overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. Results The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Conclusions Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment. PMID:28118615

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A new prognostic score for AIDS-related lymphomas in the rituximab-era

PubMed Central

Barta, Stefan K.; Xue, Xiaonan; Wang, Dan; Lee, Jeannette Y.; Kaplan, Lawrence D.; Ribera, Josep-Maria; Oriol, Albert; Spina, Michele; Tirelli, Umberto; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Dunleavy, Kieron; Noy, Ariela; Sparano, Joseph A.

2014-01-01

While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%). PMID:25150257

Clinical impact and network of determinants of tumour necrosis in colorectal cancer

PubMed Central

Väyrynen, Sara A; Väyrynen, Juha P; Klintrup, Kai; Mäkelä, Jyrki; Karttunen, Tuomo J; Tuomisto, Anne; Mäkinen, Markus J

2016-01-01

Background: The disease outcome in colorectal cancer (CRC) can vary in a wide range within the same tumour stage. The aim of this study was to clarify the prognostic value and the determinants of tumour necrosis in CRC. Methods: The areal proportion (%) of tumour tissue showing coagulative necrosis was evaluated in a cohort of 147 CRC patients and correlated with basic clinicopathological characteristics, microvascular density (MVD), cell proliferation rate, KRAS and BRAF mutations, and survival. To validate the prognostic significance of tumour necrosis, an independent cohort of 418 CRC patients was analysed. Results: Tumour necrosis positively correlated with tumour stage (P=8.5E−4)—especially with T class (4.0E−6)—and inversely correlated with serrated histology (P=0.014), but did not significantly associate with cell proliferation rate, MVD, and KRAS or BRAF mutation. Abundant (10% or more) tumour necrosis associated with worse disease-free survival independent of stage and other biological or clinicopathological characteristics in both cohorts, and the adverse effect was directly related to its extent. High CD105 MVD was also a stage independent marker for worse disease-free survival. Conclusions: Tumour necrosis percentage is a relevant histomorphological prognostic indicator in CRC. More studies are needed to disclose the mechanisms of tumour necrosis. PMID:27195424

Serum level of uric acid, partly secreted from the failing heart, is a prognostic marker in patients with congestive heart failure.

PubMed

Sakai, Hiroshi; Tsutamoto, Takayoshi; Tsutsui, Takashi; Tanaka, Toshinari; Ishikawa, Chitose; Horie, Minoru

2006-08-01

A recent study suggested that xanthine oxidase is activated in congestive heart failure (CHF). However, whether uric acid (UA) is secreted from the failing heart remains unknown, so it is currently unclear whether serum UA can provide prognostic information independent of brain natriuretic peptide (BNP). Serum UA was measured in the aortic root (AO) and the coronary sinus (CS) of 74 patients with CHF. The serum UA level was significantly higher in the CS than in the AO. The transcardiac gradient of UA (CS-AO) increased with the severity of CHF, inversely correlated with left ventricular ejection fraction (LVEF) and positively correlated with left ventricular end-diastolic volume index. The plasma levels of norepinephrine, BNP, UA, and LVEF were monitored prospectively in 150 CHF patients for a mean follow-up of 3 years. High plasma levels of UA (p<0.001) and BNP (p<0.001) were shown by multivariate stepwise analysis to be independent predictors of mortality. High plasma UA level, partly secreted from the failing heart, is a prognostic predictor independent of BNP in patients with CHF. Monitoring a combination of BNP and UA may be useful for the management of patients with CHF.

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

PubMed Central

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

2015-01-01

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

Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor.

PubMed

Haller, Florian; Zhang, Jitao David; Moskalev, Evgeny A; Braun, Alexander; Otto, Claudia; Geddert, Helene; Riazalhosseini, Yasser; Ward, Aoife; Balwierz, Aleksandra; Schaefer, Inga-Marie; Cameron, Silke; Ghadimi, B Michael; Agaimy, Abbas; Fletcher, Jonathan A; Hoheisel, Jörg; Hartmann, Arndt; Werner, Martin; Wiemann, Stefan; Sahin, Ozgür

2015-03-01

Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category. © 2014 UICC.

The metastasis suppressor SOX11 is an independent prognostic factor for improved survival in gastric cancer

PubMed Central

QU, YING; ZHOU, CHENFEI; ZHANG, JIANIAN; CAI, QU; LI, JIANFANG; DU, TAO; ZHU, ZHENGGANG; CUI, XIAOJIANG; LIU, BINGYA

2014-01-01

SOX11 is involved in gastrulation and in malignant diseases. The aim of this study was to investigate the role of SOX11 in gastric cancer and its expression pattern and clinical significance. SOX11 overexpression cell model was used to examine in vitro and in vivo the role of SOX11 in cell growth and metastasis. Cell cycle analysis and Annexin V/PI double staining were used to investigate the effect of SOX11 on cell cycle progression and apoptosis. The expression of SOX11 in human gastric cancer was examined by immunohistochemistry. The correlation of SOX11 expression with clinicopathological characteristics and survival of patients was analyzed by Pearson’s χ2 and Kaplan-Meier analyses, respectively. Cox’s proportional hazard model was employed in multivariate analysis. SOX11 overexpression did not inhibit cell growth but strongly suppressed cell migration/invasion in vitro and in vivo. We found a significant correlation between high SOX11 protein levels and Lauren’s classification (intestinal type), differentiation status (high and medium), and early TNM stage. SOX11 is an independent prognostic factor for improved survival in gastric cancer patients. SOX11 was a potential tumor-suppressor and an independent positive prognostic factor in gastric cancer patients with less advanced clinicopathological features. PMID:24604109

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

PubMed

Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M

1989-12-01

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Neutrophil-lymphocyte ratio predicts survival in patients with advanced cholangiocarcinoma on chemotherapy.

PubMed

Lee, Ban Seok; Lee, Sang Hyub; Son, Jun Hyuk; Jang, Dong Kee; Chung, Kwang Hyun; Lee, Yoon Suk; Paik, Woo Hyun; Ryu, Ji Kon; Kim, Yong-Tae

2016-02-01

The blood neutrophil-to-lymphocyte ratio (NLR) is reported to be a prognostic marker in several cancers. However, the prognostic role of NLR in patients with advanced cholangiocarcinoma on chemotherapy is unknown. A total of 221 patients with pathologically confirmed locally advanced or metastatic cholangiocarcinoma receiving first-line palliative chemotherapy were enrolled. Associations between baseline clinical and laboratory variables including NLR and survival were investigated. Patients were classified into two groups according to the NLR level (≤ 5 vs. >5). Median overall survival (OS) and time to progression (TTP) in patients with NLR ≤ 5 were 10.9 and 6.7 months, respectively, and 6.8 and 4.1 months in patients with NLR > 5 (P < 0.001, P = 0.002, respectively). In multivariate analysis, number of cycles of chemotherapy was a significant predictor of longer OS (HR 0.86, P < 0.001), whereas adverse prognostic factors for OS were CA 19-9 > 300 (HR 1.43, P = 0.025), CEA > 5 (HR 1.44, P = 0.029), higher stage (HR 1.69, P = 0.004), and NLR > 5 (HR 1.87, P < 0.001). NLR > 5 was also associated with reduced TTP (HR 1.66, P = 0.007). Among 50 patients with initial NLR > 5, 33 patients had NLR ≤ 5 after two cycles of chemotherapy and they had significantly better survival than the others (HR 0.48, P = 0.015). NLR independently predicts survival in patients with advanced cholangiocarcinoma undergoing chemotherapy. Considering cost-effectiveness and easy availability, NLR may be a useful biomarker for prognosis prediction.

Prognostic significance of blood lactate and lactate clearance in trauma patients.

PubMed

Régnier, Marie-Alix; Raux, Mathieu; Le Manach, Yannick; Asencio, Yves; Gaillard, Johann; Devilliers, Catherine; Langeron, Olivier; Riou, Bruno

2012-12-01

Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy

PubMed Central

Liu, Lingyun; Wang, Wei; Zhang, Yi; Long, Jianting; Zhang, Zhaohui; Li, Qiao; Chen, Bin; Li, Shaoqiang; Hua, Yunpeng; Shen, Shunli; Peng, Baogang

2018-01-01

Purpose Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. Materials and Methods Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. Results The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. Conclusion Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy. PMID:28602056

High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma.

PubMed

Hu, Baoying; Jiang, Dawei; Chen, Yuyan; Wei, Lixian; Zhang, Shusen; Zhao, Fengbo; Ni, Runzhou; Lu, Cuihua; Wan, Chunhua

2015-04-01

Charged multivesicular body protein 4B (CHMP4B), a subunit of the endosomal sorting complex required for transport (ESCRT)-III complex, plays an important part in cytokinetic membrane abscission and the late stage of mitotic cell division. In this study, we explored the prognostic significance of CHMP4B in human hepatocellular carcinoma (HCC) and its impact on the physiology of HCC cells. Western blot and immunohistochemistrical analyses showed that CHMP4B was significantly upregulated in HCC tissues, compared with adjacent non-tumorous tissues. Meanwhile, clinicopathological analysis revealed that high CHMP4B expression was correlated with multiple clinicopathological variables, including AFP, cirrhosis, AJCC stage, Ki-67 expression, and poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that CHMP4B served as an independent prognostic factor for survival of HCC patients. Using HCC cell cultures, we found that the expression of CHMP4B was progressively upregulated after the release from serum starvation. To verify whether CHMP4B could regulate the proliferation of HCC cells, CHMP4B was knocked down through the transfection of CHMP4B-siRNA oligos. Flow cytometry and CCK-8 assays indicated that interference of CHMP4B led to cell cycle arrest and proliferative impairment of HCC cells. Additionally, depletion of CHMP4B expression could increase the sensitivity to doxorubicin in HepG2 and Huh7 cells. Taken together, our results implied that CHMP4B could be a promising prognostic biomarker as well as a potential therapeutic target of HCC.

Longitudinal follow-up of fibrosing interstitial pneumonia: relationship between physiologic testing, computed tomography changes, and survival rate.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A

2011-08-01

The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.

A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer.

PubMed

Salvucci, Manuela; Würstle, Maximilian L; Morgan, Clare; Curry, Sarah; Cremona, Mattia; Lindner, Andreas U; Bacon, Orna; Resler, Alexa J; Murphy, Áine C; O'Byrne, Robert; Flanagan, Lorna; Dasgupta, Sonali; Rice, Nadege; Pilati, Camilla; Zink, Elisabeth; Schöller, Lisa M; Toomey, Sinead; Lawler, Mark; Johnston, Patrick G; Wilson, Richard; Camilleri-Broët, Sophie; Salto-Tellez, Manuel; McNamara, Deborah A; Kay, Elaine W; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Hennessy, Bryan T; Longley, Daniel B; Rehm, Markus; Prehn, Jochen H M

2017-03-01

Purpose: Apoptosis is essential for chemotherapy responses. In this discovery and validation study, we evaluated the suitability of a mathematical model of apoptosis execution (APOPTO-CELL) as a stand-alone signature and as a constituent of further refined prognostic stratification tools. Experimental Design: Apoptosis competency of primary tumor samples from patients with stage III colorectal cancer ( n = 120) was calculated by APOPTO-CELL from measured protein concentrations of Procaspase-3, Procaspase-9, SMAC, and XIAP. An enriched APOPTO-CELL signature (APOPTO-CELL-PC3) was synthesized to capture apoptosome-independent effects of Caspase-3. Furthermore, a machine learning Random Forest approach was applied to APOPTO-CELL-PC3 and available molecular and clinicopathologic data to identify a further enhanced signature. Association of the signature with prognosis was evaluated in an independent colon adenocarcinoma cohort (TCGA COAD, n = 136). Results: We identified 3 prognostic biomarkers ( P = 0.04, P = 0.006, and P = 0.0004 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively) with increasing stratification accuracy for patients with stage III colorectal cancer.The APOPTO-CELL-PC3 signature ranked highest among all features. The prognostic value of the signatures was independently validated in stage III TCGA COAD patients ( P = 0.01, P = 0.04, and P = 0.02 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively). The signatures provided further stratification for patients with CMS1-3 molecular subtype. Conclusions: The integration of a systems-biology-based biomarker for apoptosis competency with machine learning approaches is an appealing and innovative strategy toward refined patient stratification. The prognostic value of apoptosis competency is independent of other available clinicopathologic and molecular factors, with tangible potential of being introduced in the clinical management of patients with stage III colorectal cancer. Clin Cancer Res; 23(5); 1200-12. ©2016 AACR . ©2016 American Association for Cancer Research.

Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up.

PubMed

Spratt, D E; Jackson, W C; Abugharib, A; Tomlins, S A; Dess, R T; Soni, P D; Lee, J Y; Zhao, S G; Cole, A I; Zumsteg, Z S; Sandler, H; Hamstra, D; Hearn, J W; Palapattu, G; Mehra, R; Morgan, T M; Feng, F Y

2016-09-01

There has been a recent proposal to change the grading system of prostate cancer into a five-tier grade grouping system. The prognostic impact of this has been demonstrated in regards only to biochemical recurrence-free survival (bRFS) with short follow-up (3 years). Between 1990 and 2013, 847 consecutive men were treated with definitive external beam radiation therapy at a single academic center. To validate the new grade grouping system, bRFS, distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS) were calculated. Adjusted Kaplan-Meier and multivariable Cox regression analyses were performed to assess the independent impact of the new grade grouping system. Discriminatory analyses were performed to compare the commonly used three-tier Gleason score system (6, 7 and 8-10) to the new system. The median follow-up of our cohort was 88 months. The 5-grade groups independently validated differing risks of bRFS (group 1 as reference; adjusted hazard ratio (aHR) 1.35, 2.16, 1.79 and 3.84 for groups 2-5, respectively). Furthermore, a clear stratification was demonstrated for DMFS (aHR 2.03, 3.18, 3.62 and 13.77 for groups 2-5, respectively) and PCSS (aHR 3.00, 5.32, 6.02 and 39.02 for groups 2-5, respectively). The 5-grade group system had improved prognostic discrimination for all end points compared with the commonly used three-tiered system (that is, Gleason score 6, 7 and 8-10). In a large independent radiotherapy cohort with long-term follow-up, we have validated the bRFS benefit of the proposed five-tier grade grouping system. Furthermore, we have demonstrated that the system is highly prognostic for DMFS and PCSS. Grade group 5 had markedly worse outcomes for all end points, and future work is necessary to improve outcomes in these patients.

Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

PubMed

Shen, Chaoyong; Yin, Yuan; Chen, Huijiao; Tang, Sumin; Yin, Xiaonan; Zhou, Zongguang; Zhang, Bo; Chen, Zhixin

2017-03-28

This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study.

PubMed

Hebert, Jeffrey J; Koppenhaver, Shane L; Magel, John S; Fritz, Julie M

2010-01-01

Hebert JJ, Koppenhaver SL, Magel JS, Fritz JM. The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study. To examine the relationship between prognostic factors for clinical success with a stabilization exercise program and lumbar multifidus (LM) and transversus abdominis (TrA) muscle activation assessed using rehabilitative ultrasound imaging (RUSI). Cross-sectional study. Outpatient physical therapy clinic. Volunteers with current low back pain (N=40). Not applicable. We examined the relationship between prognostic factors associated with clinical success with a stabilization exercise program (positive prone instability test, age <40y, aberrant movements, straight leg raise >91 degrees , presence of lumbar hypermobility) and degree of TrA and LM muscle activation assessed by RUSI. Significant univariate relationships were identified between LM muscle activation and the number of prognostic factors present (Pearson correlation coefficient [r] =-.558, P=.001), as well as the individual factors of a positive prone instability test (point biserial correlation coefficient [r(pbis)]=.376, P=.018) and segmental hypermobility (r(pbis)=.358, P=.025). The multivariate analyses indicated that after controlling for other variables, the addition of the variable "number of prognostic factors present" resulted in a significant increase in R(2) (P=.006). No significant univariate or multivariate relationships were observed between the prognostic factors and TrA muscle activation. Decreased LM muscle activation, but not TrA muscle activation, is associated with the presence of factors predictive of clinical success with a stabilization exercise program. Our findings provide researchers and clinicians with evidence regarding the construct validity of the prognostic factors examined in this study, as well as the potential clinical importance of the LM muscle as a target for stabilization exercises. Copyright (c) 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis.

PubMed

Kim, Seok Jin; Yoon, Dok Hyun; Jaccard, Arnaud; Chng, Wee Joo; Lim, Soon Thye; Hong, Huangming; Park, Yong; Chang, Kian Meng; Maeda, Yoshinobu; Ishida, Fumihiro; Shin, Dong-Yeop; Kim, Jin Seok; Jeong, Seong Hyun; Yang, Deok-Hwan; Jo, Jae-Cheol; Lee, Gyeong-Won; Choi, Chul Won; Lee, Won-Sik; Chen, Tsai-Yun; Kim, Kiyeun; Jung, Sin-Ho; Murayama, Tohru; Oki, Yasuhiro; Advani, Ranjana; d'Amore, Francesco; Schmitz, Norbert; Suh, Cheolwon; Suzuki, Ritsuro; Kwong, Yok Lam; Lin, Tong-Yu; Kim, Won Seog

2016-03-01

The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted. We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort. We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group. PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy. Samsung Biomedical Research Institute. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic value of magnetic resonance imaging findings in patients with sciatica.

PubMed

El Barzouhi, Abdelilah; Verwoerd, Annemieke J H; Peul, Wilco C; Verhagen, Arianne P; Lycklama À Nijeholt, Geert J; Van der Kallen, Bas F; Koes, Bart W; Vleggeert-Lankamp, Carmen L A M

2016-06-01

OBJECTIVE This study aimed to determine the prognostic value of MRI variables to predict outcome in patients with herniated disc-related sciatica, and whether MRI could facilitate the decision making between early surgery and prolonged conservative care in these patients. METHODS A prospective observational evaluation of patients enrolled in a randomized trial with 1-year follow-up was completed. A total of 283 patients with sciatica who had a radiologically confirmed disc herniation were randomized either to surgery or to prolonged conservative care with surgery if needed. Outcome measures were recovery and leg pain severity. Recovery was registered on a 7-point Likert scale. Complete/near complete recovery was considered a satisfactory outcome. Leg pain severity was measured on a 0- to 100-mm visual analog scale. Multiple MRI characteristics of the degenerated disc herniation were independently scored by 3 spine experts. Cox models were used to study the influence of MRI variables on rate of recovery, and linear mixed models were used to determine the predictive value of MRI variables for leg pain severity during follow-up. The interaction of each MRI predictor with treatment allocation was tested. There were no study-specific conflicts of interest. RESULTS Baseline MRI variables associated with less leg pain severity were the reader's assessment of presence of nerve root compression (p < 0.001), and assessment of extrusion compared with protrusion of the disc herniation (p = 0.006). Both variables tended to be associated, but not significantly, with satisfactory outcome during follow-up (HR 1.45, 95% CI 0.93-2.24, and HR 1.24, 95% CI 0.96-1.61, respectively). The size of disc herniation at baseline was not associated with outcome. There was no significant change in the effects between treatment groups. CONCLUSIONS MRI assessment of the presence of nerve root compression and extrusion of a herniated disc at baseline was associated with less leg pain during 1-year follow-up, irrespective of a surgical or conservative treatment. MRI findings seem not to be helpful in determining which patients might fare better with early surgery compared with a strategy of prolonged conservative care. Clinical trial registration no.: ISRCTN26872154 ( controlled-trials.com ).

Review and Analysis of Algorithmic Approaches Developed for Prognostics on CMAPSS Dataset

NASA Technical Reports Server (NTRS)

Ramasso, Emannuel; Saxena, Abhinav

2014-01-01

Benchmarking of prognostic algorithms has been challenging due to limited availability of common datasets suitable for prognostics. In an attempt to alleviate this problem several benchmarking datasets have been collected by NASA's prognostic center of excellence and made available to the Prognostics and Health Management (PHM) community to allow evaluation and comparison of prognostics algorithms. Among those datasets are five C-MAPSS datasets that have been extremely popular due to their unique characteristics making them suitable for prognostics. The C-MAPSS datasets pose several challenges that have been tackled by different methods in the PHM literature. In particular, management of high variability due to sensor noise, effects of operating conditions, and presence of multiple simultaneous fault modes are some factors that have great impact on the generalization capabilities of prognostics algorithms. More than 70 publications have used the C-MAPSS datasets for developing data-driven prognostic algorithms. The C-MAPSS datasets are also shown to be well-suited for development of new machine learning and pattern recognition tools for several key preprocessing steps such as feature extraction and selection, failure mode assessment, operating conditions assessment, health status estimation, uncertainty management, and prognostics performance evaluation. This paper summarizes a comprehensive literature review of publications using C-MAPSS datasets and provides guidelines and references to further usage of these datasets in a manner that allows clear and consistent comparison between different approaches.

Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

PubMed

Yan, Andrew T; Steg, Philippe Gabriel; Fitzgerald, Gordon; Feldman, Laurent J; Eagle, Kim A; Gore, Joel M; Anderson, Frederick A; López-Sendón, Jose; Gurfinkel, Enrique P; Brieger, David; Goodman, Shaun G

2010-11-05

There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma.

PubMed

Katsuya, Hiroo; Shimokawa, Mototsugu; Ishitsuka, Kenji; Kawai, Kazuhiro; Amano, Masahiro; Utsunomiya, Atae; Hino, Ryosuke; Hanada, Shuichi; Jo, Tatsuro; Tsukasaki, Kunihiro; Moriuchi, Yukiyoshi; Sueoka, Eisaburo; Yoshida, Shinichiro; Suzushima, Hitoshi; Miyahara, Masaharu; Yamashita, Kiyoshi; Eto, Tetsuya; Suzumiya, Junji; Tamura, Kazuo

2017-07-06

Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes: acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a novel prognostic index (PI) for chronic and smoldering ATL. We conducted a nationwide retrospective survey on ATL patients, and 248 fully eligible individuals were used in this analysis. In the univariate analysis, sex, performance status, log 10 (soluble interleukin-2 receptor [sIL-2R]), neutrophils count, and lymphadenopathy showed values of P < .05 in training samples. A multivariate analysis was performed on these factors, and only log 10 (sIL-2R) was identified as an independent prognostic factor in training samples. Using a regression coefficient of this variable, a prognostic model was formulated to identify different levels of risk: indolent ATL-PI (iATL-PI) = 1.51 × log 10 (sIL-2R [U/mL]). The values calculated by iATL-PI were divided into 3 groups using a quartile point. In the validation sample, median survival times (MSTs) were 1.6 years, 5.5 years, and not reached for patients in the high-, intermediate-, and low-risk groups, respectively ( P < .0001). To make the scoring system clinically practicable, we simplified iATL-PI according to trichotomizing sIL-2R at 1000 and 6000 U/mL, using a quartile point. Patients with more than 6000 U/mL sIL-2R were categorized into the high-risk group, less than and equal to 1000 U/mL into the low-risk group, and the others into the intermediate-risk group, and MSTs were 1.6 years, not reached, and 5.5 years, respectively ( P < .0001). iATL-PI has potential as a novel tool for a risk-adapted therapeutic approach. © 2017 by The American Society of Hematology.

Treatment for liver metastases from breast cancer: Results and prognostic factors

PubMed Central

Li, Xiao-Ping; Meng, Zhi-Qiang; Guo, Wei-Jian; Li, Jie

2005-01-01

AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients with metastatic breast cancer. PMID:15968739

Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis

PubMed Central

Lin, Lian-Yu; Chang, Chin-Hao; Chu, Fang-Ying; Lin, Yen-Hung; Wu, Cho-Kai; Lee, Jen-Kuang; Hwang, Juei-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien

2016-01-01

Background and Objectives Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Materials and Methods Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. Results A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617–0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007–0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033–0.362, P = 0.0003). Conclusion Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD. PMID:26828209

Analysis of overall survival in a large multiethnic cohort reveals absolute neutrophil count of 1,100 as a novel prognostic cutoff in African Americans

PubMed Central

Mantzaris, Ioannis; Yu, Yiting; Msaouel, Pavlos; Lam, Anthony P.; Janakiram, Murali; Friedman, Ellen W.; Steidl, Ulrich; Verma, Amit K.

2016-01-01

Although absolute neutrophil counts (ANC) below 1.5x103/uL are used to define neutropenia as a marker of increased susceptibility to infections, their relationship with survival has not been examined. Since low counts trigger extensive investigations, determining prognostic cutoffs especially for different ethnicities and races is critical. A multiethnic cohort of 27,760 subjects, 65 years old and above, was utilized to evaluate the association of neutropenia with overall survival in different ethnicities and races. The mean ANC was 4.6±1.51x103/uL in non-Hispanic whites, 3.6±1.57x103/uL in non-Hispanic blacks and 4.3±1.54x103/uL in Hispanics (p<0.001). An ANC below 1.5x103/uL was associated with significantly shorter overall survival among whites (HR 1.74; 95% CI 1.18 - 2.58; p<0.001), but not in blacks (HR 0.89; 95% CI 0.86 - 1.17; p=0.40) or Hispanics (HR 1.04; 95% CI 0.76 - 1.46; p=0.82), after adjustment for age, sex, comorbidities, anemia and thrombocytopenia. Using Cox regression multivariable models, an ANC below 1.1x103/uL in blacks was found to be associated with increased mortality (HR 1.86; 95%CI 1.21 - 2.87; p<0.01). We found no association between neutropenia and mortality at any ANC cutoff in elderly Hispanics. In conclusion, neutropenia was found to be an independent prognostic variable in the elderly, when determined in race-specific manner. Most importantly, a cutoff of 1.1x103 neutrophils/uL may be a more prognostically relevant marker in elderly blacks and could serve as a novel threshold for further evaluation and intervention in this population. PMID:27144332

Clinical and prognostic utility of cardiovascular magnetic resonance imaging in myeloma patients with suspected cardiac amyloidosis.

PubMed

Bhatti, Sabha; Watts, Evan; Syed, Fahd; Vallurupalli, Srikanth; Pandey, Tarun; Jambekar, Kedar; Mazur, Wojciech; Hakeem, Abdul

2016-09-01

AL amyloidosis affects up to 30% of patients with multiple myeloma (MM), and cardiac involvement is associated with worse outcomes. Traditional screening modalities including EKG, echocardiography and biomarkers have limited value. The aim of this study was to evaluate the clinical and prognostic value of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging in patients with plasma cell dyscrasias and suspected cardiac amyloidosis (CA). A total of 251 consecutive patients with plasma cell dyscrasias who underwent CMR were enrolled in this study. Primary endpoint was all cause mortality. Clinical, ECG, echocardiographic, biomarker and CMR predictors of mortality were analyzed. Mean age of population was 63 ± 10 years, 36% females and 19% African Americans. During a median follow-up duration of 28 months (IQR 5-56), there were 97 deaths (39%). Patients who died were more likely to have diabetes (28% vs. 14%; P = 0.03), CAD (28% vs. 16%; P = 0.04) and CKD (33% vs. 21%; P = 0.04). With endomyocardial biopsy as the gold standard (42 (17%) patients), amyloid pattern on CMR (LGE+) had sensitivity and negative predictive values of 100%; specificity and positive predictive values of 80 and 81% with an AUC 0.9 for CA. History of CAD (HR 1.64, 95% CI 1.01-2.6; P = 0.04), brain natriuretic peptide (HR 1.0003 95% CI 1.0001-1.0006; P = 0.004) and LGE + (HR 1.72, 95% CI 1.05-2.8; P = 0.02) were independent predictors of mortality. LGE+ possessed incremental prognostic value over clinical, laboratory and echocardiographic variables for mortality prediction. CMR is a clinically useful tool for diagnosis and prognostication in myeloma patients with suspected CA. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Intratumoral stromal morphometry predicts disease recurrence but not response to 5-fluorouracil-results from the QUASAR trial of colorectal cancer.

PubMed

Hutchins, Gordon G A; Treanor, Darren; Wright, Alexander; Handley, Kelly; Magill, Laura; Tinkler-Hundal, Emma; Southward, Katie; Seymour, Matthew; Kerr, David; Gray, Richard; Quirke, Philip

2018-02-01

The biological importance of tumour-associated stroma is becoming increasingly apparent, but its clinical utility remains ill-defined. For stage II/Dukes B colorectal cancer (CRC), clinical biomarkers are urgently required to direct therapeutic options. We report here prognostic/predictive analyses, and molecular associations, of stromal morphometric quantification in the Quick and Simple and Reliable (QUASAR) trial of CRC. Relative proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically quantified on digitised haematoxylin and eosin (H&E) sections derived from 1800 patients enrolled in QUASAR, which randomised 3239 (91% stage II) CRC patients between adjuvant fluorouracil/folinic acid (FUFA) chemotherapy and observation. The prognostic and predictive values of PoT/PoS measurements were determined by the use of stratified log-rank analyses. A high proportion of tumour stroma (≥50%) was associated with an increased recurrence risk: 31.3% (143/457) recurrence for ≥50% versus 21.9% (294/1343) for <50% [rate ratio (RR) 1.62; 95% confidence interval (CI) 1.30-2.02; P < 0.0001]. Of patients with stromal proportions of ≥65%, 40% (46/115) had recurrent disease within 10 years. The adverse prognostic effect of a high stromal proportion was independent of established prognostic variables, and was maintained in stage II/Dukes B patients (RR 1.62; 95% CI 1.26-2.08; P = 0.0002). KRAS mutation in the presence of a high stromal proportion augmented recurrence risk (RR 2.93; 95% CI 1.87-4.59; P = 0.0005). Stromal morphometry did not predict response to FUFA chemotherapy. Simple digital morphometry applied to a single representative H&E section identifies CRC patients with a >50% higher risk of disease recurrence. This technique can reliably partition patients into subpopulations with different risks of tumour recurrence in a simple and cost-effective manner. Further prospective validation is warranted. © 2017 John Wiley & Sons Ltd.

Prevalence and prognostic value of exercise-induced ventricular arrhythmias.

PubMed

Partington, Sara; Myers, Jonathan; Cho, Shaun; Froelicher, Victor; Chun, Sung

2003-01-01

The purpose of this study was to determine the prevalence and prognostic significance of exercise-induced ventricular arrhythmias (EIVAs) in patients referred for exercise testing, considering the arrhythmic substrate and exercise-induced ischemia. EIVAs are frequently observed during exercise testing, but their prognostic significance is uncertain. The design of this study was a retrospective analysis of prospectively collected data, and it took place in 2 university-affiliated Veterans Affairs Medical Centers. Patients comprised 6213 consecutive males referred for exercise tests. We measured clinical exercise test responses and all-cause mortality after a mean follow-up of 6 +/- 4 years. EIVAs were defined as frequent premature ventricular contractions (PVCs) constituting >10% of all ventricular depolarizations during any 30 second electrocardiogram recording, or a run of > or =3 consecutive PVCs during exercise or recovery. A total of 1256 patients (20%) died during follow-up. EIVAs occurred in 503 patients (8%); the prevalence of EIVAs increased in older patients and in those with cardiopulmonary disease, resting PVCs, and ischemia during exercise. EIVAs were associated with mortality irrespective of the presence of cardiopulmonary disease or exercise-induced ischemia. In those without cardiopulmonary disease, mortality differed more so later in follow up than earlier. In those without resting PVCs, EIVAs were also predictive of mortality, but in those with resting PVCs, poorer prognosis was not worsened by the presence of EIVAs. Exercise induced ischemia does not affect the prognostic value of EIVAs, whereas the arrhythmic substrate does. EIVAs and resting PVCs are both independent predictors of mortality after consideration of other clinical and exercise-test variables. These findings are of limited clinical significance because of the modest change in risk and the lack of any established intervention. However, they explain some of the previous controversy and highlight the need to consider resting PVCs and follow-up duration in assessing the clinical implications of EIVAs.

Prognostic value of the post-training oxygen uptake efficiency slope in patients with coronary artery disease.

PubMed

Buys, Roselien; Coeckelberghs, Ellen; Cornelissen, Véronique A; Goetschalckx, Kaatje; Vanhees, Luc

2016-09-01

Peak oxygen uptake is an independent predictor of mortality in patients with coronary artery disease (CAD). However, patients with CAD are not always capable of reaching peak effort, and therefore submaximal gas exchange variables such as the oxygen uptake efficiency slope (OUES) have been introduced. Baseline exercise capacity as expressed by OUES provides prognostic information and this parameter responds to training. Therefore, we aimed to assess the prognostic value of post-training OUES in patients with CAD. We included 960 patients with CAD (age 60.6 ± 9.5 years; 853 males) who completed a cardiac rehabilitation program between 2000 and 2011. The OUES was calculated before and after cardiac rehabilitation and information on mortality was obtained. The relationships of post-training OUES with all-cause and cardiovascular (CV) mortality was assessed by Cox proportional hazards regression analyses. Receiver operator characteristic curve analysis was performed in order to obtain the optimal cut-off value. During 7.37 ± 3.20 years of follow-up (range: 0.45-13.75 years), 108 patients died, among whom 47 died due to CV reasons. The post-training OUES was related to all-cause (hazard ratio: 0.50, p < 0.001) and CV (hazard ratio: 0.40, p < 0.001) mortality. When significant covariates, including baseline OUES, were entered into the Cox regression analysis, post-training OUES remained related to all-cause and CV mortality (hazard ratio: 0.40, p < 0.01 and 0.26, p < 0.01, respectively). In addition, the change in OUES due to exercise training was positively related to mortality (hazard ratio: 0.49, p < 0.01). Post-training OUES has stronger prognostic value compared to baseline OUES. The lack of improvement in exercise capacity expressed by OUES after an exercise training program relates to a worse prognosis and can help distinguish patients with favorable and unfavorable prognoses. © The European Society of Cardiology 2016.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy

PubMed Central

Lin, Chen-Sung; Liu, Chao-Yu; Cheng, Chih-Tao; Tsai, Yu-Chen; Chiou, Lun-Wei; Lee, Ming-Yuan

2017-01-01

Background The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. Methods Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3–5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. Results Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3–5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all’s P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3–5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all’s P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. Conclusions Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion. PMID:29221296

Delay discounting rates: a strong prognostic indicator of smoking relapse.

PubMed

Sheffer, Christine E; Christensen, Darren R; Landes, Reid; Carter, Larry P; Jackson, Lisa; Bickel, Warren K

2014-11-01

Recent evidence suggests that several dimensions of impulsivity and locus of control are likely to be significant prognostic indicators of relapse. One-hundred and thirty-one treatment seeking smokers were enrolled in six weeks of multi-component cognitive-behavioral therapy with eight weeks of nicotine replacement therapy. Cox proportional hazard regressions were used to model days to relapse with each of the following: delay discounting of $100, delay discounting of $1000, six subscales of the Barratt Impulsiveness Scale (BIS), Rotter's Locus of Control (RLOC), Fagerstrom's Test for Nicotine Dependence (FTND), and the Perceived Stress Scale (PSS). Hazard ratios for a one standard deviation increase were estimated with 95% confidence intervals for each explanatory variable. Likelihood ratios were used to examine the level of association with days to relapse for different combinations of the explanatory variables while accounting for nicotine dependence and stress level. These analyses found that the $100 delay discounting rate had the strongest association with days to relapse. Further, when discounting rates were combined with the FTND and PSS, the associations remained significant. When the other measures were combined with the FTND and PSS, their associations with relapse non-significant. These findings indicate that delay discounting is independently associated with relapse and adds to what is already accounted for by nicotine dependence and stress level. They also signify that delay discounting is a productive new target for enhancing treatment for tobacco dependence. Consequently, adding an intervention designed to decrease discounting rates to a comprehensive treatment for tobacco dependence has the potential to decrease relapse rates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

PubMed

Hamilton, C A; Miller, A; Casablanca, Y; Horowitz, N S; Rungruang, B; Krivak, T C; Richard, S D; Rodriguez, N; Birrer, M J; Backes, F J; Geller, M A; Quinn, M; Goodheart, M J; Mutch, D G; Kavanagh, J J; Maxwell, G L; Bookman, M A

2018-02-01

To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. Published by Elsevier Inc.

Classification systems for lower extremity amputation prediction in subjects with active diabetic foot ulcer: a systematic review and meta-analysis.

PubMed

Monteiro-Soares, M; Martins-Mendes, D; Vaz-Carneiro, A; Sampaio, S; Dinis-Ribeiro, M

2014-10-01

We systematically review the available systems used to classify diabetic foot ulcers in order to synthesize their methodological qualitative issues and accuracy to predict lower extremity amputation, as this may represent a critical point in these patients' care. Two investigators searched, in EBSCO, ISI, PubMed and SCOPUS databases, and independently selected studies published until May 2013 and reporting prognostic accuracy and/or reliability of specific systems for patients with diabetic foot ulcer in order to predict lower extremity amputation. We included 25 studies reporting a prevalence of lower extremity amputation between 6% and 78%. Eight different diabetic foot ulcer descriptions and seven prognostic stratification classification systems were addressed with a variable (1-9) number of factors included, specially peripheral arterial disease (n = 12) or infection at the ulcer site (n = 10) or ulcer depth (n = 10). The Meggitt-Wagner, S(AD)SAD and Texas University Classification systems were the most extensively validated, whereas ten classifications were derived or validated only once. Reliability was reported in a single study, and accuracy measures were reported in five studies with another eight allowing their calculation. Pooled accuracy ranged from 0.65 (for gangrene) to 0.74 (for infection). There are numerous classification systems for diabetic foot ulcer outcome prediction, but only few studies evaluated their reliability or external validity. Studies rarely validated several systems simultaneously and only a few reported accuracy measures. Further studies assessing reliability and accuracy of the available systems and their composing variables are needed. Copyright © 2014 John Wiley & Sons, Ltd.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study

PubMed Central

Hamilton, C. A.; Miller, A.; Casablanca, Y.; Horowitz, N. S.; Rungruang, B.; Krivak, T. C.; Richard, S. D.; Rodriguez, N.; Birrer, M.J.; Backes, F.J.; Geller, M.A.; Quinn, M.; Goodheart, M.J.; Mutch, D.G.; Kavanagh, J.J.; Maxwell, G. L.; Bookman, M. A.

2018-01-01

Objective To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Methods Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10 years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). Results The analysis dataset included 3,010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. Conclusions The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. PMID:29195926

Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer

PubMed Central

Evans, Joseph R.; Zhao, Shuang G.; Chang, S. Laura; Tomlins, Scott A.; Erho, Nicholas; Sboner, Andrea; Schiewer, Matthew J.; Spratt, Daniel E.; Kothari, Vishal; Klein, Eric A.; Den, Robert B.; Dicker, Adam P.; Karnes, R. Jeffrey; Yu, Xiaochun; Nguyen, Paul L.; Rubin, Mark A.; de Bono, Johann; Knudsen, Karen E.; Davicioni, Elai; Feng, Felix Y.

2017-01-01

IMPORTANCE A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification. OBJECTIVE To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed. MAIN OUTCOMES AND MEASURES Biochemical recurrence-free, metastasis-free, and overall survival. RESULTS Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman ρ [ρ], range, −0.07 to 0.24), Gleason score (ρ, range, 0.03 to 0.20), prostate-specific antigen level (ρ, range, −0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (ρ, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95%CI, 1.12–2.50) than in the older patients (HR, 0.77; 95%CI, 0.29–2.07) on multivariate Cox analysis. CONCLUSIONS AND RELEVANCE DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients. PMID:26746117

Prognostic factors for non-success in patients with sciatica and disc herniation.

PubMed

Haugen, Anne Julsrud; Brox, Jens Ivar; Grøvle, Lars; Keller, Anne; Natvig, Bård; Soldal, Dag; Grotle, Margreth

2012-09-22

Few studies have investigated prognostic factors for patients with sciatica, especially for patients treated without surgery. The aim of this study was to identify factors associated with non-success after 1 and 2 years of follow-up and to test the prognostic value of surgical treatment for sciatica. The study was a prospective multicentre observational study including 466 patients with sciatica and lumbar disc herniation. Potential prognostic factors were sociodemographic characteristics, back pain history, kinesiophobia, emotional distress, pain, comorbidity and clinical examination findings. Study participation did not alter treatment considerations for the patients in the clinics. Patients reported on the questionnaires if surgery of the disc herniation had been performed. Uni- and multivariate logistic regression analyses were used to evaluate factors associated with non-success, defined as Maine-Seattle Back Questionnaire score of ≥5 (0-12) (primary outcome) and Sciatica Bothersomeness Index ≥7 (0-24) (secondary outcome). Rates of non-success were at 1 and 2 years 44% and 39% for the main outcome and 47% and 42% for the secondary outcome. Approximately 1/3 of the patients were treated surgically. For the main outcome variable, in the final multivariate model non-success at 1 year was significantly associated with being male (OR 1.70 [95% CI; 1.06 - 2.73]), smoker (2.06 [1.31 - 3.25]), more back pain (1.0 [1.01 - 1.02]), more comorbid subjective health complaints (1.09 [1.03 - 1.15]), reduced tendon reflex (1.62 [1.03 - 2.56]), and not treated surgically (2.97 [1.75 - 5.04]). Further, factors significantly associated with non-success at 2 years were duration of back problems >; 1 year (1.92 [1.11 - 3.32]), duration of sciatica >; 3 months (2.30 [1.40 - 3.80]), more comorbid subjective health complaints (1.10 [1.03 - 1.17]) and kinesiophobia (1.04 [1.00 - 1.08]). For the secondary outcome variable, in the final multivariate model, more comorbid subjective health complaints, more back pain, muscular weakness at clinical examination, and not treated surgically, were independent prognostic factors for non-success at both 1 and 2 years. The results indicate that the prognosis for sciatica referred to secondary care is not that good and only slightly better after surgery and that comorbidity should be assessed in patients with sciatica. This calls for a broader assessment of patients with sciatica than the traditional clinical assessment in which mainly the physical symptoms and signs are investigated.

Prognostic factors for non-success in patients with sciatica and disc herniation

PubMed Central

2012-01-01

Background Few studies have investigated prognostic factors for patients with sciatica, especially for patients treated without surgery. The aim of this study was to identify factors associated with non-success after 1 and 2 years of follow-up and to test the prognostic value of surgical treatment for sciatica. Methods The study was a prospective multicentre observational study including 466 patients with sciatica and lumbar disc herniation. Potential prognostic factors were sociodemographic characteristics, back pain history, kinesiophobia, emotional distress, pain, comorbidity and clinical examination findings. Study participation did not alter treatment considerations for the patients in the clinics. Patients reported on the questionnaires if surgery of the disc herniation had been performed. Uni- and multivariate logistic regression analyses were used to evaluate factors associated with non-success, defined as Maine–Seattle Back Questionnaire score of ≥5 (0–12) (primary outcome) and Sciatica Bothersomeness Index ≥7 (0–24) (secondary outcome). Results Rates of non-success were at 1 and 2 years 44% and 39% for the main outcome and 47% and 42% for the secondary outcome. Approximately 1/3 of the patients were treated surgically. For the main outcome variable, in the final multivariate model non-success at 1 year was significantly associated with being male (OR 1.70 [95% CI; 1.06 − 2.73]), smoker (2.06 [1.31 − 3.25]), more back pain (1.0 [1.01 − 1.02]), more comorbid subjective health complaints (1.09 [1.03 − 1.15]), reduced tendon reflex (1.62 [1.03 − 2.56]), and not treated surgically (2.97 [1.75 − 5.04]). Further, factors significantly associated with non-success at 2 years were duration of back problems >; 1 year (1.92 [1.11 − 3.32]), duration of sciatica >; 3 months (2.30 [1.40 − 3.80]), more comorbid subjective health complaints (1.10 [1.03 − 1.17]) and kinesiophobia (1.04 [1.00 − 1.08]). For the secondary outcome variable, in the final multivariate model, more comorbid subjective health complaints, more back pain, muscular weakness at clinical examination, and not treated surgically, were independent prognostic factors for non-success at both 1 and 2 years. Conclusions The results indicate that the prognosis for sciatica referred to secondary care is not that good and only slightly better after surgery and that comorbidity should be assessed in patients with sciatica. This calls for a broader assessment of patients with sciatica than the traditional clinical assessment in which mainly the physical symptoms and signs are investigated. PMID:22999108

Prognostic impact of pleural lavage cytology in patients with primary lung cancer.

PubMed

Tomizawa, Kenji; Nishino, Masaya; Sesumi, Yuichi; Kobayashi, Yoshihisa; Sato, Katsuaki; Chiba, Masato; Shimoji, Masaki; Suda, Kenichi; Shimizu, Shigeki; Sato, Takao; Takemoto, Toshiki; Mitsudomi, Tetsuya

2016-12-01

Positive pleural lavage cytology (PLC) has been reported to have a negative prognostic impact in patients with surgically resected non-small cell lung cancer (NSCLC). However, positive PLC does not upgrade the stage according to the 7th edition of TNM classification for lung cancer. The objectives of this study were to evaluate the prognostic impact of positive PLC in patients with NSCLC and to clarify its contribution to TNM classification. Seven hundred fifty-four patients who underwent surgical resection of NSCLC from January 2007 through December 2013 were retrospectively studied. PLC was performed using 50ml of saline immediately after thoracotomy. Thirty-eight of the 754 patients were positive for PLC (5.1%). The overall survival (OS) of patients with positive PLC was significantly shorter than that of those with negative PLC (P=0.007, log-rank test). In multivariate analyses of OS, positive PLC was a significant independent prognostic factor (hazard ratio=2.21, 95% confidence interval: 1.21-4.04, P=0.009). The OS of patients with positive PLC was significantly shorter than that of those with negative PLC and pT1 (P<0.0001) or negative PLC and pT2 (P<0.0001) and almost overlapped with that of those with negative PLC and pT3 disease (P=0.601). Positive PLC is an independent prognostic factor in patients with resected NSCLC. Based on our analyses, we propose that patients with positive PLC be staged as pT3. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma

PubMed Central

He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-01-01

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P=0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P=0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS (P=0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL. PMID:29190934

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma.

PubMed

Luo, Huaichao; Quan, Xiaoying; Song, Xiao-Yu; Zhang, Li; Yin, Yilin; He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-11-03

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P =0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P =0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS ( P =0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL.

New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge

PubMed Central

Schanz, Julie; Tüchler, Heinz; Solé, Francesc; Mallo, Mar; Luño, Elisa; Cervera, José; Granada, Isabel; Hildebrandt, Barbara; Slovak, Marilyn L.; Ohyashiki, Kazuma; Steidl, Christian; Fonatsch, Christa; Pfeilstöcker, Michael; Nösslinger, Thomas; Valent, Peter; Giagounidis, Aristoteles; Aul, Carlo; Lübbert, Michael; Stauder, Reinhard; Krieger, Otto; Garcia-Manero, Guillermo; Faderl, Stefan; Pierce, Sherry; Le Beau, Michelle M.; Bennett, John M.; Greenberg, Peter; Germing, Ulrich; Haase, Detlef

2012-01-01

Purpose The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients. Patients and Methods Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed to confirm the results. Results In total, 19 cytogenetic categories were defined, providing clear prognostic classification in 91% of all patients. The abnormalities were classified into five prognostic subgroups (P < .001): very good (median OS, 61 months; hazard ratio [HR], 0.5; n = 81); good (49 months; HR, 1.0 [reference category]; n = 1,809); intermediate (26 months; HR, 1.6; n = 529); poor (16 months; HR, 2.6; n = 148); and very poor (6 months; HR, 4.2; n = 187). The internal and external validations confirmed the results of the score. Conclusion In conclusion, these data should contribute to the ongoing efforts to update the IPSS by refining the cytogenetic risk categories. PMID:22331955

Low Tumor Infiltrating Mast Cell Density Confers Prognostic Benefit and Reflects Immunoactivation in Colorectal Cancer.

PubMed

Mao, Yihao; Feng, Qingyang; Zheng, Peng; Yang, Liangliang; Zhu, Dexiang; Chang, Wenju; Ji, Meiling; He, Guodong; Xu, Jianmin

2018-06-06

The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, this study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stage I-IV was enrolled in this study. 854 consecutive patients were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stage II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stage II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis. This article is protected by copyright. All rights reserved. © 2018 UICC.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

PubMed

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Hishima, Tsunekazu; Omuro, Yasushi

2018-06-01

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Prognostic value of bone marrow involvement by clonal immunoglobulin gene rearrangements in follicular lymphoma

PubMed Central

Berget, Ellen; Helgeland, Lars; Liseth, Knut; Løkeland, Turid; Molven, Anders; Vintermyr, Olav Karsten

2014-01-01

Aims We aimed to evaluate the prognostic value of routine use of PCR amplification of immunoglobulin gene rearrangements in bone marrow (BM) staging in patients with follicular lymphoma (FL). Methods Clonal rearrangements were assessed by immunoglobulin heavy and light-chain gene rearrangement analysis in BM aspirates from 96 patients diagnosed with FL and related to morphological detection of BM involvement in biopsies. In 71 patients, results were also compared with concurrent flow cytometry analysis. Results BM involvement was detected by PCR in 34.4% (33/96) of patients. The presence of clonal rearrangements by PCR was associated with advanced clinical stage (I–III vs IV; p<0.001), high FL International Prognostic Index (FLIPI) score (0–1, 2 vs ≥3; p=0.003), and detection of BM involvement by morphology and flow cytometry analysis (p<0.001 for both). PCR-positive patients had a significantly poorer survival than PCR-negative patients (p=0.001, log-rank test). Thirteen patients positive by PCR but without morphologically detectable BM involvement, had significantly poorer survival than patients with negative morphology and negative PCR result (p=0.002). The poor survival associated with BM involvement by PCR was independent of the FLIPI score (p=0.007, Cox regression). BM involvement by morphology or flow cytometry did not show a significant impact on survival. Conclusions Our results showed that routine use of PCR-based clonality analysis significantly improved the prognostic impact of BM staging in patients with FL. BM involvement by PCR was also an independent adverse prognostic factor. PMID:25233852

Telomere length variation in tumor cells and cancer‐associated fibroblasts: potential biomarker for hepatocellular carcinoma

PubMed Central

Ma, Li‐Jie; Wang, Xiao‐Ying; Duan, Meng; Liu, Long‐Zi; Shi, Jie‐Yi; Dong, Liang‐Qing; Yang, Liu‐Xiao; Wang, Zhi‐Chao; Ding, Zhen‐Bin; Ke, Ai‐Wu; Cao, Ya; Zhang, Xiao‐Ming; Zhou, Jian; Fan, Jia

2017-01-01

Abstract The role of telomere dysfunction and aberrant telomerase activities in hepatocellular carcinoma (HCC) has been overlooked for many years. This study aimed to delineate the variation and prognostic value of telomere length in HCC. Telomere‐specific fluorescence in situ hybridization (FISH) and qPCR were used to evaluate telomere length in HCC cell lines, tumor tissues, and isolated non‐tumor cells within the tumor. Significant telomere attrition was found in tumor cells and cancer‐associated fibroblasts (CAFs) compared to their normal counterparts, but not in intratumor leukocytes or bile duct epithelial cells. Clinical relevance and prognostic value of telomere length were investigated on tissue microarrays of 257 surgically treated HCC patients. Reduced intensity of telomere signals in tumor cells or CAFs correlated with larger tumor size and the presence of vascular invasion (p < 0.05). Shortened telomeres in tumor cells or CAFs associated with reduced survival and increased recurrence, and were identified as independent prognosticators for HCC patients (p < 0.05). These findings were validated in an independent HCC cohort of 371 HCC patients from The Cancer Genome Atlas (TCGA) database, confirming telomere attrition and its prognostic value in HCC. We also showed that telomerase reverse transcriptase promoter (TERTp) mutation correlated with telomere shortening in HCC. Telomere variation in tumor cells and non‐tumor cells within the tumor microenvironment of HCC was a valuable prognostic biomarker for this fatal malignancy. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:28833123

A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

PubMed

Leow, Jeffrey J; Orsola, Anna; Chang, Steven L; Bellmunt, Joaquim

2015-04-01

Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognostic value of exercise echocardiography: validation of a new risk index combining echocardiographic, treadmill, and exercise electrocardiographic parameters.

PubMed

Mazur, Wojciech; Rivera, Jose M; Khoury, Alexander F; Basu, Abhijeet G; Perez-Verdia, Alejandro; Marks, Gary F; Chang, Su Min; Olmos, Leopoldo; Quiñones, Miguel A; Zoghbi, William A

2003-04-01

Exercise (Ex) echocardiography has been shown to have significant prognostic power, independent of other known predictors of risk from an Ex stress test. The purpose of this study was to evaluate a risk index, incorporating echocardiographic and conventional Ex variables, for a more comprehensive risk stratification and identification of a very low-risk group. Two consecutive, mutually exclusive populations referred for treadmill Ex echocardiography with the Bruce protocol were investigated: hypothesis-generating (388 patients; 268 males; age 55 +/- 13 years) and hypothesis-testing (105 patients; 61 males age: 54 +/- 14 years).Cardiac events included cardiac death, myocardial infarction, late revascularization (>90 days), hospital admission for unstable angina, and admission for heart failure. Mean follow-up in the hypothesis-generating population was 3.1 years. There were 38 cardiac events. Independent predictors of events by multivariate analysis were: Ex wall motion score index (odds ratio [OR] = 2.77/Unit; P <.001); ischemic S-T depression > or = 1 mm (OR = 2.84; P =.002); and treadmill time (OR = 0.87/min; P =.037). A risk index was generated on the basis of the multivariate Cox regression model as: risk index = 1.02 (Ex wall motion score index) + 1.04 (S-T change) - 0.14 (treadmill time). The validity of this index was tested in the hypothesis-testing population. Event rates at 3 years were lowest (0%) in the lower quartile of risk index (-1.22 to -0.47), highest (29.6%) in the upper quartile (+0.66 to +2.02), and intermediate (19.2% to 15.3%) in the intermediate quartiles. The OR of the risk index for predicting cardiac events was 2.94/Unit ([95% confidence interval: 1.4 to 6.2]; P =.0043). Echocardiographic and Ex parameters are independent powerful predictors of cardiac events after treadmill stress testing. A risk index can be derived with these parameters for a more comprehensive risk stratification with Ex echocardiography.

Discovery and Validation of Novel Expression Signature for Postcystectomy Recurrence in High-Risk Bladder Cancer

PubMed Central

Lam, Lucia L.; Ghadessi, Mercedeh; Erho, Nicholas; Vergara, Ismael A.; Alshalalfa, Mohammed; Buerki, Christine; Haddad, Zaid; Sierocinski, Thomas; Triche, Timothy J.; Skinner, Eila C.; Davicioni, Elai; Daneshmand, Siamak; Black, Peter C.

2014-01-01

Background Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone. Methods Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided. Results A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets. Conclusions The validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management. PMID:25344601

Validation and Refinement of Chronic Lung Allograft Dysfunction Phenotypes in Bilateral and Single Lung Recipients

PubMed Central

Todd, Jamie L.; Zhang, Alice; Li, Ning; Mayalall, Aradhna; Finlen Copeland, C. Ashley; Shino, Michael; Pavlisko, Elizabeth N.; Wallace, W. Dean; Gregson, Aric; Ross, David J.; Saggar, Rajan; Lynch, Joseph P.; Belperio, John; Snyder, Laurie D.; Palmer, Scott M.

2016-01-01

Rationale: The clinical course of chronic lung allograft dysfunction (CLAD) is heterogeneous. Forced vital capacity (FVC) loss at onset, which may suggest a restrictive phenotype, was associated with worse survival for bilateral lung transplant recipients in one previously published single-center study. Objectives: We sought to replicate the significance of FVC loss in an independent, retrospectively identified cohort of bilateral lung transplant recipients and to investigate extended application of this approach to single lung recipients. Methods: FVC loss and other potential predictors of survival after the onset of CLAD were assessed using Kaplan-Meier and Cox proportional hazards models. Measurements and Main Results: FVC loss at the onset of CLAD was associated with higher mortality in an independent cohort of bilateral lung transplant recipients (hazard ratio [HR], 2.75; 95% confidence interval [CI], 2.02–3.73; P < 0.0001) and in a multicenter cohort of single lung recipients (HR, 1.80; 95% CI, 1.09–2.98; P = 0.02). Including all subjects, the deleterious impact of FVC loss on survival persisted after adjustment for other relevant clinical variables (HR, 2.36; 95% CI, 1.77–3.15; P < 0.0001). In patients who develop CLAD without FVC loss, chest computed tomography features suggestive of pleural or parenchymal fibrosis also predicted worse survival in both bilateral (HR, 2.01; 95% CI, 1.16–5.20; P = 0.02) and single recipients (HR, 2.47; 95% CI, 1.24–10.57; P = 0.02). Conclusions: We independently validated the prognostic significance of FVC loss for bilateral lung recipients and demonstrated that this approach to CLAD classification also confers prognostic information for single lung transplant recipients. Improved understanding of these discrete phenotypes is critical to the development of effective therapies. PMID:27144793