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Sample records for lymphocytes predicts survival

  1. Infused autograft lymphocyte to monocyte ratio predicts survival in classical Hodgkin lymphoma

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    Porrata LF

    2015-02-01

    Full Text Available Luis F Porrata, David J Inwards, Stephen M Ansell, Ivana N Micallef, Patrick B Johnston, William J Hogan, Svetomir N Markovic Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA Abstract: The infused autograft lymphocyte to monocyte ratio (A-LMR as a surrogate marker of host immunity (ie, absolute lymphocyte count and CD14+ HLA-DRlow/neg immunosuppressive monocytes (ie, absolute monocyte count is a prognostic factor for patients with diffuse large B-cell lymphoma after autologous peripheral hematopoietic stem cell transplantation (APHSCT. Thus, we set out to investigate if A-LMR can also affect survival post-APHSCT in classical Hodgkin lymphoma. From 1994 to 2012, 183 patients with classical Hodgkin lymphoma who underwent APHSCT were studied. The patients were randomly divided into a training set (n=122 and a validation set (n=61. The receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value and validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥1.0 experienced a superior overall survival (OS versus patients with an A-LMR <1.0 (median OS not reached versus 40.4 months, 5-year OS rates of 86% [95% CI 72–93] versus 43% [95% CI 28–58], P<0.0001, respectively in the training set. In the validation set, an A-LMR ≥1 showed a median OS of not reached versus 41.4 months for an A-LMR ,1, 5-year OS rates of 90% (95% CI 73–97 versus 48% (95% CI 28–68; P<0.0001. A-LMR provides a platform to engineer an autograft versus tumor effect to improve clinical outcomes in patients with classical Hodgkin lymphoma undergoing APHSCT. Keywords: autograft absolute lymphocyte to monocyte count ratio, survival, autologous peripheral hematopoietic stem cell transplantation, classical Hodgkin lymphoma

  2. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization.

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    Xue, Tong-Chun; Jia, Qing-An; Ge, Ning-Ling; Zhang, Bo-Heng; Wang, Yan-Hong; Ren, Zheng-Gang; Ye, Sheng-Long

    2015-08-01

    Inflammation is particularly strong in huge hepatocellular carcinoma (HCC). However, it is unclear whether the platelet-to-lymphocyte ratio (PLR), as an inflammatory-related marker, can predict survival of patients with huge HCC. In this study, we enrolled 291 patients with huge HCC (diameter over 10 cm) who were undergoing repeated transarterial chemoembolization (TACE) at our institute. The baseline PLR was calculated from complete serum blood counts before the first chemoembolization. We found that a baseline PLR cutoff value over 150 best predicted huge HCC survival. The 12, 24, and 36 months survival rates in the high PLR group (22.6, 8.1, and 4.1 %, respectively) were significantly lower than in the low PLR group (35.6, 22.4, and 14 %, respectively). Thus, a significant difference was found in overall survival (log-rank test, p huge HCC, a high baseline PLR is a useful predictor of poor survival in patients undergoing chemoembolization. Additional anti-inflammatory or anti-platelet treatments, in combination with TACE, may improve survival in HCC patients with high PLR.

  3. Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization.

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    Yang, Zongguo; Zhang, Jianliang; Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Wang, Qiang; Zhang, Wensi; Chen, Shishi; Lu, Lingqing; Chen, Xiaorong

    2015-12-15

    It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P SII scores (P SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice.

  4. Preoperative red cell distribution width and neutrophil-to-lymphocyte ratio predict survival in patients with epithelial ovarian cancer

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    Li, Zheng; Hong, Na; Robertson, Melissa; Wang, Chen; Jiang, Guoqian

    2017-01-01

    Several parameters of preoperative complete blood count (CBC) and inflammation-associated blood cell markers derived from them have been reported to correlate with prognosis in patients with epithelial ovarian cancer (EOC), but their prognostic importance and optimal cutoffs are still needed be elucidated. Clinic/pathological parameters, 5-year follow-up data and preoperative CBC parameters were obtained retrospectively in 654 EOC patients underwent primary surgery at Mayo Clinic. Cutoffs for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were optimized by receiver operating characteristic (ROC) curve. Prognostic significance for overall survival (OS) and recurrence free survival (RFS) were determined by Cox proportional hazards models and Kaplan-Meier method. Associations of RDW and NLR with clinic/pathological parameters were analyzed using non-parametric tests. RDW with cutoff 14.5 and NLR with cutoff 5.25 had independent prognostic significance for OS, while combined RDW and NLR scores stratified patients into low (RDW-low and NLR-low), intermediate (RDW-high or NLR-high) and high risk (RDW-high and NLR-high) groups, especially in patients with high-grade serous ovarian cancer (HGSOC). Moreover, high NLR was associated with poor RFS as well. Elevated RDW was strongly associated with age, whereas high NLR was strongly associated with stage, preoperative CA125 level and ascites at surgery. PMID:28223716

  5. The Predictive Role of the Neutrophil/Lymphocyte Ratio in Survival with Multiple Myeloma: A Single Center Experience.

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    Onec, Birgul; Okutan, Harika; Albayrak, Murat; Saribacak Can, Esra; Aslan, Vedat; Unver Koluman, Basak; Soyer Kosemehmetoglu, Ozge; Albayrak, Aynur; Kos, Durdu Mehmet

    2017-03-01

    Recent studies have shown a positive correlation between tumor-related immune response markers and the poor outcome in solid tumors. In this study, we aimed to investigate the neutrophil/lymphocyte ratio (NLR) in multiple myeloma. To the best of our knowledge, this would be the second report concerning this topic. We retrospectively reviewed the data for 52 multiple myeloma patients. The patients were grouped using the baseline NLR as NLR ≤ 1.72 and NLR > 1.72 using receiver operating characteristic analysis to determine a cut off. We compared the two groups in terms of both the known prognostic factors of the myeloma and the overall survival (OS). Our study showed that NLR is associated with C-reactive protein and β2 microglobulin (P = 0.02 and P = 0.001, respectively). The patients with NLR > 1.72 had significantly worse stages, performance status, and kidney functions. The whole group's OS was estimated as 35.1 months while the patients with lower NLR had better OS when compared with those with NLR > 1.72 (42.75 and 26.14 months, respectively, P: 0.04). Neutrophil/lymphocyte ratio, which is associated with stage, performance status, and kidney functions, can be used in daily practice as a predictor for survival in multiple myeloma. Simply adding NLR to the routine charts may enrich our data for larger studies. © 2016 Wiley Periodicals, Inc.

  6. Elevated preoperative neutrophil-to-lymphocyte ratio predicts poor disease-free survival in Chinese women with breast cancer.

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    Hong, Jin; Mao, Yan; Chen, Xiaosong; Zhu, Li; He, Jianrong; Chen, Weiguo; Li, Yafen; Lin, Lin; Fei, Xiaochun; Shen, Kunwei

    2016-03-01

    Inflammation and tumor immune microenviroment are critical factors for prognosis in numerous cancers. The aim of this study was to determine the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in breast cancer. We performed a retrospective analysis of 487 patients diagnosed with primary breast cancer at Shanghai Ruijin hospital from January 2009 to December 2010. Hematological parameters before surgery, clinicopathological data, and survival status were obtained. Survival analysis was used to evaluate the prognostic value of NLR. The optimal cutoff value was determined as 1.93 for NLR and the median follow-up time was 55.0 months. On univariate analysis, patients with high NLR (>1.93) had worse 5-year disease-free survival (DFS) compared to those with low NLR (77.9 vs 88.0 %, p = 0.002). Regarding overall survival, there was no significant difference between patients with high NLR and low NLR, with 5-year overall survival of 90.8 and 91.7 % (p = 0.707). In triple-negative breast cancer, patients with high NLR was associated with worse 5-year DFS compared with patients with low NLR (63.4 vs 84.9 %, p = 0.040). Mutivariate analysis revealed that NLR was an independent prognostic factor for DFS in breast cancer (HR = 1.867, 95 % confidence interval; (95%CI) = 1.155-3.017, p = 0.011). Preoperative NLR is an independent predictor of DFS in breast cancer patients, especially in triple-negative subtype. Further studies are required to validate the prognostic value of NLR before clinical application.

  7. Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

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    Chen L

    2017-05-01

    Full Text Available Li Chen,1 Yanjiao Zuo,1 Lihua Zhu,2 Yuxin Zhang,3 Sen Li,1 Fei Ma,4 Yu Han,5 Hongjiang Song,1 Yingwei Xue11Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, 3Department of General Surgery, Mudanjiang First People’s Hospital, Mudanjiang, 4Department of Breast Surgery, 5Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaBackground: Accurate and useful predictors of gastric carcinoma treated with neoadjuvant chemotherapy are lacking at present. We aim to explore the potential prognostic significance of the neutrophil-to-lymphocyte ratio (NLR in advanced gastric cancer receiving S-1 plus oxaliplatin (SOX or oxaliplatin and capecitabine (XELOX regimen.Methods: We enrolled 91 patients with advanced gastric cancer treated with neoadjuvant chemotherapy from August 2008 to September 2015. The peripheral venous blood samples were collected before neoadjuvant chemotherapy. The NLR was divided into two groups: low NLR <2.17 group and high NLR ≥2.17 group. Univariate analysis on disease-free survival (DFS and overall survival (OS were generated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were assessed by univariate analyses, and the independent prognostic factors were evaluated using multivariate analysis (Cox’s proportional-hazards regression model.Results: The univariate analysis showed that median DFS and median OS were worse for high NLR values than low NLR values before neoadjuvant chemotherapy (median DFS: 19.97 and 26.87 months, respectively, P=0.299; median OS: 25.83 and 29.73 months, respectively, P=0.405. Multivariate analysis showed that the NLR before neoadjuvant

  8. Postoperative neutrophil-to-lymphocyte ratio change predicts survival of patients with small hepatocellular carcinoma undergoing radiofrequency ablation.

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    Jiaqiang Dan

    Full Text Available BACKGROUND: An elevated preoperative neutrophil-to-lymphocyte ratio (NLR has been reported to be a prognostic factor for hepatocellular carcinoma (HCC patients after treatment. However, the clinical implication of postoperative NLR change remains unclear. MATERIALS AND METHODS: From May 2005 to Aug 2008, a cohort of consecutive 178 small HCC patients treated with radiofrequency ablation (RFA was retrospectively reviewed. The NLR was recorded within 3 days before and 1 month after RFA. Baseline characteristics, overall survival (OS and recurrence free survival (RFS were compared according to preoperative NLR and/or postoperative NLR change. Prognostic factors were assessed by multivariate analysis. RESULTS: Compared with preoperative NLR level, postoperative NLR decreased in 87 patients and increased in 91 patients after RFA. No significant differences were identified between two groups in commonly used clinic-pathologic features. The 1, 3, 5 years OS was 98.8%, 78.6%, 67.1% for NLR decreased group, and 92.2%, 55.5%, 35.4% for NLR increased group respectively (P<0.001; the corresponding RFS was 94.2%, 65.2%, 33.8% and 81.7%, 46.1%, 12.4% respectively (P<0.001. In subgroup analysis, the survival of patients with lower or higher preoperative NLR can be distinguished more accurate by postoperative NLR change. Multivariate analysis showed that postoperative NLR change, but not preoperative NLR, was an independent prognostic factor for both OS (P<0.001, HR = 2.39, 95%CI 1.53-3.72 and RFS (P = 0.003, HR = 1.69, 95%CI 1.87-8.24. CONCLUSION: The postoperative NLR change was an independent prognostic factor for small HCC patient undergoing RFA, and patients with decreased NLR indicated better survival than those with increased NLR.

  9. LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts overall survival in untreated patients

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    Duzkale, Hatice; Schweighofer, Carmen D.; Coombes, Kevin R.; Barron, Lynn L.; Ferrajoli, Alessandra; O'Brien, Susan; Wierda, William G.; Pfeifer, John; Majewski, Tadeusz; Czerniak, Bogdan A.; Jorgensen, Jeffrey L.; Medeiros, L. Jeffrey; Freireich, Emil J; Keating, Michael J.

    2011-01-01

    We previously identified LDOC1 as one of the most significantly differentially expressed genes in untreated chronic lymphocytic leukemia (CLL) patients with respect to the somatic mutation status of the immunoglobulin heavy-chain variable region genes. However, little is known about the normal function of LDOC1, its contribution to the pathophysiology of CLL, or its prognostic significance. In this study, we have investigated LDOC1 mRNA expression in a large cohort of untreated CLL patients, as well as in normal peripheral blood B-cell (NBC) subsets and primary B-cell lymphoma samples. We have confirmed that LDOC1 is dramatically down-regulated in mutated CLL cases compared with unmutated cases, and have identified a new splice variant, LDOC1S. We show that LDOC1 is expressed in NBC subsets (naive > memory), suggesting that it may play a role in normal B-cell development. It is also expressed in primary B-cell lymphoma samples, in which its expression is associated with somatic mutation status. In CLL, we show that high levels of LDOC1 correlate with biomarkers of poor prognosis, including cytogenetic markers, unmutated somatic mutation status, and ZAP70 expression. Finally, we demonstrate that LDOC1 mRNA expression is an excellent predictor of overall survival in untreated CLL patients. PMID:21310924

  10. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome.

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    Chang, Ying-Jun; Zhao, Xiang-Yu; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Chen, Yu-Hong; Wang, Yu; Zhang, Xiao-Hui; Zhao, Xiao-Su; Han, Wei; Chen, Huan; Wang, Feng-Rong; Lv, Meng; Huang, Xiao-Jun

    2013-12-01

    We investigated whether early lymphocyte recovery, after unmanipulated, haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in 78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC-30). Patients with high ALC-30 (≥ 300 cells/μL) had lower relapse rates (13.8% vs. 35.5%, p = 0.049) and lower incidence of bacterial infections (3.4% vs. 25.8%, p = 0.015) than those with low ALC-30 values. Multivariate analysis showed that a high ALC-30 was associated with improved overall survival (OS, hazard ratio [HR]: 0.099, 95% confidence interval [CI]: 0.029-0.337; p leukemia-free survival (HR: 0.245, 95% CI: 0.112-0.539; p after unmanipulated HBMT.

  11. The postoperative neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after the complete resection of stage I non-small cell lung cancer

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    Jin, Feng; Han, Anqin; Shi, Fang; Kong, Li; Yu, Jinming

    2016-01-01

    Purpose Although numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent complete resection of stage I NSCLC. The aim of this retrospective study was to evaluate the prognostic significance of postoperative NLR and ΔNLR in 123 patients with stage I NSCLC. Patients and methods This retrospective study included preoperative and postoperative data of 123 patients who underwent surgical resection for stage I NSCLC. The relationship between disease-free survival (DFS), overall survival (OS), and clinicopathological factors, including NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and their changes, was analyzed using both univariate Kaplan–Meier and multivariate Cox regression methods. Results The 5-year DFS and OS rates in our cohort were 60.16% and 67.48%, respectively. Univariate analysis revealed that age (P=0.045), smoking status (P=0.033), preoperative NLR (P=0.032), postoperative NLR (P<0.001), ΔNLR (P=0.004), and change in LMR (ΔLMR) (P=0.025) were significant predictors of DFS and that age (P=0.039), smoking status (P=0.042), postoperative NLR (P<0.001), ΔNLR (P=0.004), and ΔLMR (P=0.011) were independent predictors of OS. Multivariate analysis confirmed that postoperative NLR (hazard ratio [HR] =2.435, P=0.001) and ΔNLR (HR =2.103, P=0.012) were independent predictors of DFS and that postoperative NLR (HR =2.747, P=0.001) and ΔNLR (HR =2.052, P=0.018) were significant prognostic factors of OS. Conclusion Our study reported for the first time that postoperative NLR and ΔNLR – but not preoperative NLR – were independent prognostic factors of DFS and OS in patients with stage I NSCLC who underwent complete resection. This easily available biomarker might be helpful in individual risk

  12. IAN family critically regulates survival and development of T lymphocytes.

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    Takeshi Nitta

    2006-04-01

    Full Text Available The IAN (immune-associated nucleotide-binding protein family is a family of functionally uncharacterized GTP-binding proteins expressed in vertebrate immune cells and in plant cells during antibacterial responses. Here we show that all eight IAN family genes encoded in a single cluster of mouse genome are predominantly expressed in lymphocytes, and that the expression of IAN1, IAN4, and IAN5 is significantly elevated upon thymic selection of T lymphocytes. Gain-of-function experiments show that the premature overexpression of IAN1 kills immature thymocytes, whereas short hairpin RNA-mediated loss-of-function studies show that IAN4 supports positive selection. The knockdown of IAN5 perturbs the optimal generation of CD4/CD8 double-positive thymocytes and reduces the survival of mature T lymphocytes. We also show evidence suggesting that IAN4 and IAN5 are associated with anti-apoptotic proteins Bcl-2 and Bcl-xL, whereas IAN1 is associated with pro-apoptotic Bax. Thus, the IAN family is a novel family of T cell-receptor-responsive proteins that critically regulate thymic development and survival of T lymphocytes and that potentially exert regulatory functions through the association with Bcl-2 family proteins.

  13. Elevated preoperative neutrophil-to-lymphocyte ratio can predict poor survival in early stage gastric cancer patients receiving radical gastrectomy: The Fujian prospective investigation of cancer (FIESTA) study.

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    Hu, Dan; Zhang, Hejun; Lin, Xiandong; Chen, Gang; Li, Chao; Liang, Binying; Chen, Yan; Cui, Zhaolei; Peng, Feng; Zheng, Xiongwei; Niu, Wenquan

    2017-01-01

    Aims: This cohort study was conducted to evaluate the prognostic impact of blood-routine parameters before radical gastrectomy on gastric cancer mortality. Methods: Total 3012 patients with gastric cancer were consecutively enrolled from a mono-center between 2000 and 2010, and the latest follow-up was completed in 2015. Results: The median follow-up time was 44.05 months. Finally, 1331 out of 3012 gastric cancer patients died from gastric cancer. Per standard deviation increment in neutrophil (hazard ratio or HR=1.08, P2.61 with ≤2.61 and NLR>1.87 with ≤1.87 were respectively associated with a 5.21-fold (P=0.004) and 2.36-fold (P=0.001) increased risk of gastric cancer mortality. The effect-size magnitude of NLR was further potentiated in patients with invasion depth T1/T2 (HR=1.73, P=0.001), regional lymph node metastasis N0 (HR=1.60, P<0.001), TNM stage I/II (HR=1.36, P=0.009) and tumor size ≤ 4.5 cm (HR=1.17, P<0.001). Conclusions: Our findings consolidated the prognostic impact of preoperative NLR on gastric mortality, and demonstrated that elevated preoperative NLR was a robust indicator of poor survival in patients at early stage.

  14. Preoperative neutrophil-to-lymphocyte ratio plusplatelet-to-lymphocyte ratio inpredicting survival forpatients withstage I-II gastric cancer

    Institute of Scientific and Technical Information of China (English)

    XiaoweiSun; ZhiweiZhou; XuechaoLiu; JianjunLiu; ShangxiangChen; DazhiXu; WeiLi; YouqingZhan; YuanfangLi; YingboChen

    2016-01-01

    Background:The preoperative neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are associated with poor prognosis of gastric cancer. We aimed to determine whether the combination of NLR and PLR (NLR–PLR) could better predict survival of patients after curative resection for stage I–II gastric cancer. Methods:We collected data from the medical records of patients with stage I–II gastric cancer undergoing curative resection between December 2000 and November 2012 at the Sun Yat-sen Cancer Center. The preoperative NLR–PLR was calculated as follows: patients with both elevated NLR (≥2.1) and PLR (≥120) were given a score of 2, and patients with only one or neither were given a score of 1 or 0, respectively. Results:Kaplan–Meier analysis and log-rank tests revealed signiifcant differences in overall survival (OS) among patients with NLR–PLR scores of 0, 1 and 2 (P Conclusion:The preoperative NLR-PLR score is a useful predictor of postoperative survival in the patients with stage I–II gastric cancer and may help identify high-risk patients for rational therapy and timely follow-up.

  15. PREDICT : model for prediction of survival in localized prostate cancer

    NARCIS (Netherlands)

    Kerkmeijer, Linda G W; Monninkhof, Evelyn M.; van Oort, Inge M.; van der Poel, Henk G.; de Meerleer, Gert; van Vulpen, Marco

    2016-01-01

    Purpose: Current models for prediction of prostate cancer-specific survival do not incorporate all present-day interventions. In the present study, a pre-treatment prediction model for patients with localized prostate cancer was developed.Methods: From 1989 to 2008, 3383 patients were treated with I

  16. Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

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    Ordonez, R.; Federico, M. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Valenciano, A. [Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Bordon, E. [Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Rodriguez-Gallego, C. [Hospital Universitario de Gran Canaria Dr. Negrin, Immunology Department, Las Palmas de Gran Canaria (Spain)

    2014-02-15

    A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

  17. Expression of molecules involved in B lymphocyte survival and differentiation by synovial fibroblasts.

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    Edwards, J C; Leigh, R D; Cambridge, G

    1997-06-01

    The synovitis of rheumatoid arthritis (RA) is one of few pathological lesions in which B lymphocyte accumulation progresses to the extent of germinal centre formation. The present study was designed to assess the ability of synovial fibroblasts to express molecules implicated in B lymphocyte survival and differentiation, both in vivo, and in response to cytokines in vitro. Normal and diseased synovia were examined by indirect immunofluorescence. In all tissues synovial intimal fibroblasts showed co-expression of vascular cell adhesion molecule-1 (VCAM-1) and complement decay-accelerating factor (DAF) comparable to that of follicular dendritic cells (FDC), but not complement receptor 2 (CR2). In rheumatoid synovia, subintimal cells showed variable expression of VCAM-1 and DAF, with bright co-expression of VCAM-1, DAF and CR2 in lymphoid follicle centres. B lymphocytes, some of which were proliferating cell nuclear antigen-positive, were present in contact with subintimal cells expressing VCAM-1 with or without DAF or CR2. B lymphocytes were rarely present in the intimal layer, and, where present, showed fragmentation. In vitro, synovial fibroblasts exposed to tumour necrosis factor-alpha (TNF-alpha) in combination with interferon-gamma (IFN-gamma) showed enhanced expression of VCAM-1, in comparison with fibroblasts from skin and lung and, unlike skin and lung fibroblasts, also expressed DAF and CR2. These findings support the hypothesis that synovial targeting in RA involves an enhanced ability of synovial fibroblasts to support B lymphocyte survival. This appears to be dependent, not on the constitutive expression of VCAM-1 and DAF on intimal cells, but on the increased ability of subintimal cells to respond to proinflammatory cytokines, perhaps critically in the expression of VCAM-1.

  18. C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo.

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    Akesson, Ch; Pero, R W; Ivars, F

    2003-01-01

    Water extracts of the bark of Uncaria tomentosa, a vine indigenous to South America, has been used for generations as an "immuno modulator". To understand the basis of this immuno modulatory effect we fed mice in their drinking water with C-Med 100, which is a commercially available water extract from Uncaria tomentosa. We found a dose-dependent increase in spleen cell numbers in the supplemented mice, but the proportions of B cells, T cells, NK cells, granulocytes, and memory lymphocytes were normal. However, there were no detectable changes of the lymphoid architecture of the spleen even after long-term treatment. Further, when C-Med 100 treatment was interrupted the cellularity returned to normal level within four weeks. The increased number of lymphocytes was most likely not due to increased production because C-Med 100 did not have any significant effect on precursor cells nor on the accumulation of recent thymic emigrants in the spleen. We conclude that accumulation is most likely due to prolonged cell survival, because adoptive transfer experiments demonstrated that C-Med 100 treatment significantly prolonged lymphocyte survival in peripheral lymphoid organs, without increasing their proliferation rate. Since the accumulation was reversible and without detectable pathological effects, these results suggest the use of C-Med 100 as a potential agent for clinically accelerating the recovery of patients from leukopenia.

  19. Tumor-infiltrating CD45RO(+) Memory T Lymphocytes Predict Favorable Clinical Outcome in Solid Tumors.

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    Hu, Guoming; Wang, Shimin

    2017-09-04

    The prognostic role of tumor-infiltrating CD45RO(+) memory T lymphocytes (CD45RO(+) T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO(+) T cells in human solid tumors. We found that CD45RO(+) T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, CD45RO(+) T cell infiltration significantly improved 1-year, 3-year and 5-year OS in colorectal, gastric and esophageal cancer, but only 5-year OS in hepatocellular carcinoma. And these cells were positively associated with 1-year, 3-year and 5-year DFS in hepatocellular, colorectal and esophageal cancer. In addition, high density of intratumoral CD45RO(+) T cells inversely correlated with TNM stage of solid tumor. In conclusion, CD45RO(+) memory T lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances.

  20. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictors of survival after heart transplantation.

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    Seropian, Ignacio M; Romeo, Francisco J; Pizarro, Rodolfo; Vulcano, Norberto O; Posatini, Ricardo A; Marenchino, Ricardo G; Berrocal, Daniel H; Belziti, Cesar A

    2017-07-31

    The aim of this study was to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict outcome in heart failure (HF) patients undergoing heart transplantation (HTX). Data from 111 HF patients undergoing HTX 2010-2015 were retrospectively reviewed. NLR and PLR were calculated before HTX, immediately after HTX, and at 6 and 24 hours. Primary endpoint was in-hospital mortality, and secondary endpoints were 1 year mortality and renal replacement therapy (RRT). Prognostic factors were assessed by multivariate analysis, and the predictive values of NLR and PLR for mortality were compared. The discriminatory performance for predicting in-hospital mortality was better for NLR [area under the receiver operating characteristic curve (AUC) = 0.644, 95% confidence interval 0.492-0.797] than for PLR (AUC = 0.599, 95% confidence interval 0.423-0.776). Best cut-off value was 2.41 for NLR (sensitivity 86%, specificity 67%) and 92.5 for PLR (sensitivity 86%, specificity 68%). When divided according to best cut-off value, in-hospital mortality was significantly higher in the high NLR group (17.5% vs. 3.2%, P < 0.05), but not in the high PLR group (16.5% vs. 6.3%, P = ns). One year mortality was not significantly higher for either group (37.5% vs. 6.5% for NLR; 36.7% vs. 9.4% for PLR, P = ns for both), while RRT was significantly higher in both the NLR and PLR high groups (33.8% vs. 0%; 32.9% vs. 3.1%, respectively, P < 0.001). Multivariate analysis indicated that only high NLR (hazard ratio = 3.403, P < 0.05) and pre-transplant diabetes (hazard ratio = 3.364, P < 0.05) were independent prognostic factors for 1 year mortality. High NLR was a predictor for in-hospital mortality, and an independent prognostic factor for 1 year mortality. Both high NLR and high PLR were predictors for RRT. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  1. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy.

    Science.gov (United States)

    Miao, Yi; Yan, Qin; Li, Shuangdi; Li, Bilan; Feng, Youji

    2016-06-07

    The aim of present study was to investigate the role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) used as prognostic markers for predicting chemotherapeutic response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. A total of 344 patients diagnosed with EOC who are receiving platinum-based chemotherapy from 2005 to 2010 in the hospital were enrolled. NLR and PLR were calculated from complete blood cell count taken before operation. The patients were divided into platinum-resistant (P-R) group and platinum-sensitive (P-S) group according to chemotherapeutic response. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. We used receiver operating characteristic (ROC) curves to calculate optimal cut-off values for NLR and PLR to predict chemotherapeutic response and prognosis. The AUC, sensitivity, specificity of NLR > 3.02 to predict platinum resistance were 0.819, 75.0% and 81.45%, respectively. The corresponding values of PLR > 207 were 0.727, 60.42% and 85.48%, respectively. Patients with lower value of NLR (NLR platinum resistance in patients with EOC.

  2. Clinical Characteristics, Response to Therapy, and Survival of African American Patients Diagnosed With Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Falchi, Lorenzo; Keating, Michael J.; Wang, Xuemei; Coombs, Catherine C.; Lanasa, Mark C.; Strom, Sara; Wierda, William G.; Ferrajoli, Alessandra

    2015-01-01

    Background Little is known regarding racial disparities in characteristics and outcomes among patients with chronic lymphocytic leukemia (CLL). Methods The characteristics and outcomes of untreated African American (AA) patients with CLL (n=84) were analyzed and compared with a reference nonblack (NB) patient population (n=1571). Results At the time of presentation, AA patients had lower median hemoglobin levels (12.9 g/dL vs 13.7 g/dL), higher β2 microglobulin levels (2.7 mg/dL vs 2.4 mg/dL), greater frequency of constitutional symptoms (27% vs 10%), unmutated immunoglobulin heavy-chain variable region (IGHV) mutation status (65% vs 47%), ζ-chain-associated protein kinase 70 (ZAP70) expression (58% vs 32%), and deletion of chromosome 17p or chromosome 11q (28% vs 17%; P ≤ 02 for each comparison). Fifty-one percent of AA patients and 39% of NB patients required first-line therapy and 91% and 88%, respectively, received chemoimmunotherapy. Overall response rates to treatment were 85% for AA patients and 94% for NB patients (P=.06); and the complete response rates were 56% and 58%, respectively (P=.87). The median survival of AA patients was shorter compared with that of NB patients (event-free survival: 36 months vs 61 months; P=.007; overall survival: 152 months vs not reached; P=.0001). AA race was an independent predictor of shorter event-free and overall survival in multivariable regression models. Conclusions The current results indicated that AA patients with CLL have more unfavorable prognostic characteristics and shorter survival compared with their NB counterparts. PMID:24022787

  3. Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Dongxian; Liu, Yalan; Wang, Hao; Wang, Haixing; Song, Qi; Sujie, Akesu; Huang, Jie; Xu, Yifan; Zeng, Haiying; Tan, Lijie; Hou, Yingyong; Xu, Chen

    2017-03-21

    We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin-stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43.0%) and 98 (41.7%), respectively. The median follow-up period was 36.0 months (95% CI 29.929-42.071). Univariate analysis revealed that sTIL (>10%), iTIL (>20%), vessels involvement, lymph node metastasis, and clinical stage were significantly associated with postoperative outcome. In multivariate analysis, high sTIL (HR: 0.664, P = 0.019 for Disease free survival; HR: 0.608, P = 0.005 for Overall survival) was identified as independent better prognostic factor. Further analysis, sTIL was identified as independently prognostic factor in Stage III-IVa disease, which was not found in Stage I-II disease. Our study demonstrated that sTIL was associated with better ESCC patients' survival, especially in Stage III-IVa disease. Assessment of sTIL could be useful to discriminate biological behavior for ESCC patients.

  4. Fludarabine nucleoside modulates nuclear "survival and death" proteins in resistant chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Henrich, Silke; Mactier, Swetlana; Best, Giles; Mulligan, Stephen P; Crossett, Ben; Christopherson, Richard Ian

    2011-12-01

    The nuclear mechanisms by which fludarabine nucleoside (F-ara-A) induces apoptosis have been investigated in human MEC1 cells derived from B-cell chronic lymphocytic leukemia. Upon treatment of cells with F-ara-A (100 μM, 72 hours), 15 nuclear proteins changed in abundance by more than 2-fold. Nuclear proteins up-regulated included calmodulin (4.3-fold), prohibitin (3.9-fold), β-actin variant (3.7-fold), and structure-specific recognition protein 1 (3.7-fold); those down-regulated included 60S ribosomal protein P2B (0.12-fold), fumarate hydratase (0.19-fold), splicing factor arginine/serine-rich 3 (0.35-fold), and replication protein A2 (0.42-fold). These changes in the levels of specific proteins promote survival or apoptosis; because the end result is apoptosis of MEC1 cells, apoptotic effects predominate.

  5. Ebola Blood Test May Help Predict Survival Chances

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163165.html Ebola Blood Test May Help Predict Survival Chances Findings ... help determine a person's chance of surviving an Ebola infection, researchers say. "It is not just defining ...

  6. Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells.

    Directory of Open Access Journals (Sweden)

    Mascha Binder

    Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR, we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as "subset 1" recognize antigens highly expressed in stromal cells--vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20-45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease.

  7. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

    Science.gov (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

  8. Predictive Contribution of Neutrophil/Lymphocyte Ratio in Diagnosis of Brucellosis

    OpenAIRE

    Serdar Olt; Hasan Ergenç; Seyyid Bilal Açıkgöz

    2015-01-01

    Here we wanted to investigate predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the diagnosis of brucellosis. Thirty-two brucellosis patients diagnosed with positive serum agglutination test and thirty-two randomized healthy subjects were enrolled in this study retrospectively. Result with ROC analyzes the baseline NLR and hemoglobin values were found to be significantly associated with brucellosis (P=0.01, P=0.01, resp.). Herein we demonstrated for ...

  9. Predictive Contribution of Neutrophil/Lymphocyte Ratio in Diagnosis of Brucellosis

    OpenAIRE

    Olt, Serdar; Ergenç, Hasan; Açıkgöz, Seyyid Bilal

    2015-01-01

    Here we wanted to investigate predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the diagnosis of brucellosis. Thirty-two brucellosis patients diagnosed with positive serum agglutination test and thirty-two randomized healthy subjects were enrolled in this study retrospectively. Result with ROC analyzes the baseline NLR and hemoglobin values were found to be significantly associated with brucellosis (P = 0.01, P = 0.01, resp.). Herein we demonstrated ...

  10. Asbestos Burden Predicts Survival in Pleural Mesothelioma

    OpenAIRE

    Christensen, Brock C; Roelofs, Cora R.; Longacker, Jennifer L.; Marsit, Carmen J; Nelson, Heather H.; Kelsey, Karl T.; Godleski, John Joseph; Bueno, Raphael; Sugarbaker, David John

    2008-01-01

    Background: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of < 1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors. Objective: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis. Methods: We studied incident cases of MPM...

  11. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score.

    Science.gov (United States)

    Clive, Amelia O; Kahan, Brennan C; Hooper, Clare E; Bhatnagar, Rahul; Morley, Anna J; Zahan-Evans, Natalie; Bintcliffe, Oliver J; Boshuizen, Rogier C; Fysh, Edward T H; Tobin, Claire L; Medford, Andrew R L; Harvey, John E; van den Heuvel, Michel M; Lee, Y C Gary; Maskell, Nick A

    2014-12-01

    Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228-549; n=43), 130 days (47-467; n=129) and 44 days (22-77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, pLENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. High pretreatment neutrophil-lymphocyte ratio predicts recurrence and poor prognosis for combined small cell lung cancer.

    Science.gov (United States)

    Shao, N; Cai, Q

    2015-10-01

    Compared to pure small cell lung cancer (SCLC), combined small cell lung cancer (C-SCLC) has its own characteristics. High neutrophil to lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to be related to poor prognosis in several types of tumors. The aim of this study was to explore the prognosis value of NLR and PLR in patients with C-SCLC. A total of 112 patients diagnosed with C-SCLC between January 2000 and March 2009 were enrolled in the study. The clinicopathological parameters, laboratory analyses, and survival time were collected and analyzed. The correlation between NLR, PLR, and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters for C-SCLC. The pretreatment NLR was elevated in 37.5 % patients (NLR ≥ 4.15; n = 42; H-NLR). NLR was significantly related to disease stage (p = 0.033) and tumor recurrence (p = 0.014). The median overall survival (OS) and progression-free survival (PFS) were significantly worse in the H-NLR group (OS: 22.0 months vs 11.7 months, p = 0.001; PFS: 11.1 vs 6.0 months, p recurrence and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients.

  13. Assessment of performance of survival prediction models for cancer prognosis

    Directory of Open Access Journals (Sweden)

    Chen Hung-Chia

    2012-07-01

    Full Text Available Abstract Background Cancer survival studies are commonly analyzed using survival-time prediction models for cancer prognosis. A number of different performance metrics are used to ascertain the concordance between the predicted risk score of each patient and the actual survival time, but these metrics can sometimes conflict. Alternatively, patients are sometimes divided into two classes according to a survival-time threshold, and binary classifiers are applied to predict each patient’s class. Although this approach has several drawbacks, it does provide natural performance metrics such as positive and negative predictive values to enable unambiguous assessments. Methods We compare the survival-time prediction and survival-time threshold approaches to analyzing cancer survival studies. We review and compare common performance metrics for the two approaches. We present new randomization tests and cross-validation methods to enable unambiguous statistical inferences for several performance metrics used with the survival-time prediction approach. We consider five survival prediction models consisting of one clinical model, two gene expression models, and two models from combinations of clinical and gene expression models. Results A public breast cancer dataset was used to compare several performance metrics using five prediction models. 1 For some prediction models, the hazard ratio from fitting a Cox proportional hazards model was significant, but the two-group comparison was insignificant, and vice versa. 2 The randomization test and cross-validation were generally consistent with the p-values obtained from the standard performance metrics. 3 Binary classifiers highly depended on how the risk groups were defined; a slight change of the survival threshold for assignment of classes led to very different prediction results. Conclusions 1 Different performance metrics for evaluation of a survival prediction model may give different conclusions in

  14. Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates

    Directory of Open Access Journals (Sweden)

    Serakides Rogéria

    2010-06-01

    Full Text Available Abstract Background The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas. Methods Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8 were elected to the immunophenotypic study performed by flow cytometry. Results Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense and the proportion of CD4+ (≥ 66.7% or CD8+ T-cells (P = 0.02 remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P + T-cells was significantly greater in metastasized tumors (both MC-BMT and MC, (P + T-cells was higher in MC-BMT without metastasis. Consequently, the CD4+/CD8+ ratio was significantly increased in both groups with metastasis. Regardless of the tumor type, the animals with high proportions of CD4

  15. Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.

    Directory of Open Access Journals (Sweden)

    Maria Göbel

    Full Text Available 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.

  16. Prediction of survival with alternative modeling techniques using pseudo values

    NARCIS (Netherlands)

    T. van der Ploeg (Tjeerd); F.R. Datema (Frank); R.J. Baatenburg de Jong (Robert Jan); E.W. Steyerberg (Ewout)

    2014-01-01

    textabstractBackground: The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo

  17. Prediction of survival with alternative modeling techniques using pseudo values.

    Directory of Open Access Journals (Sweden)

    Tjeerd van der Ploeg

    Full Text Available BACKGROUND: The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques. METHODS: In this case study, we analyzed survival of 1282 Dutch patients with newly diagnosed Head and Neck Squamous Cell Carcinoma (HNSCC with conventional Kaplan-Meier and Cox regression analysis. We subsequently calculated pseudo values to reflect the individual survival patterns. We used these pseudo values to compare recursive partitioning (RPART, neural nets (NNET, logistic regression (LR general linear models (GLM and three variants of support vector machines (SVM with respect to dichotomous 60-month survival, and continuous pseudo values at 60 months or estimated survival time. We used the area under the ROC curve (AUC and the root of the mean squared error (RMSE to compare the performance of these models using bootstrap validation. RESULTS: Of a total of 1282 patients, 986 patients died during a median follow-up of 66 months (60-month survival: 52% [95% CI: 50%-55%]. The LR model had the highest optimism corrected AUC (0.791 to predict 60-month survival, followed by the SVM model with a linear kernel (AUC 0.787. The GLM model had the smallest optimism corrected RMSE when continuous pseudo values were considered for 60-month survival or the estimated survival time followed by SVM models with a linear kernel. The estimated importance of predictors varied substantially by the specific aspect of survival studied and modeling technique used. CONCLUSIONS: The use of pseudo values makes it readily possible to apply alternative modeling techniques to survival problems, to compare their performance and to search further for promising

  18. Prediction of breast cancer survival through knowledge discovery in databases.

    Science.gov (United States)

    Lotfnezhad Afshar, Hadi; Ahmadi, Maryam; Roudbari, Masoud; Sadoughi, Farahnaz

    2015-01-26

    The collection of large volumes of medical data has offered an opportunity to develop prediction models for survival by the medical research community. Medical researchers who seek to discover and extract hidden patterns and relationships among large number of variables use knowledge discovery in databases (KDD) to predict the outcome of a disease. The study was conducted to develop predictive models and discover relationships between certain predictor variables and survival in the context of breast cancer. This study is Cross sectional. After data preparation, data of 22,763 female patients, mean age 59.4 years, stored in the Surveillance Epidemiology and End Results (SEER) breast cancer dataset were analyzed anonymously. IBM SPSS Statistics 16, Access 2003 and Excel 2003 were used in the data preparation and IBM SPSS Modeler 14.2 was used in the model design. Support Vector Machine (SVM) model outperformed other models in the prediction of breast cancer survival. Analysis showed SVM model detected ten important predictor variables contributing mostly to prediction of breast cancer survival. Among important variables, behavior of tumor as the most important variable and stage of malignancy as the least important variable were identified. In current study, applying of the knowledge discovery method in the breast cancer dataset predicted the survival condition of breast cancer patients with high confidence and identified the most important variables participating in breast cancer survival.

  19. Predictive contribution of neutrophil/lymphocyte ratio in diagnosis of brucellosis.

    Science.gov (United States)

    Olt, Serdar; Ergenç, Hasan; Açıkgöz, Seyyid Bilal

    2015-01-01

    Here we wanted to investigate predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the diagnosis of brucellosis. Thirty-two brucellosis patients diagnosed with positive serum agglutination test and thirty-two randomized healthy subjects were enrolled in this study retrospectively. Result with ROC analyzes the baseline NLR and hemoglobin values were found to be significantly associated with brucellosis (P = 0.01, P = 0.01, resp.). Herein we demonstrated for the first time that NLR values were significantly associated with brucellosis. This situation can help clinicians during diagnosis of brucellosis.

  20. Heterogeneous X-ray survival characteristics of lymphocytes in prolymphocytic leukaemia. Mathematical analysis distinguishing delayed cell death and true radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, A.E.R.; O' Connor, T.W.E.; Slater, N.G.P. (Division of Haematology, United Medical and Dental Schools of Guy' s and St. Thomas' Hospitals, London (United Kingdom)); Peel, W.E. (Computing Services, Manchester Metropolitan University, Manchester (United Kingdom))

    1994-10-01

    The survival of non-dividing (G[sub 0]) leukaemic lymphocytes in culture is generally too short for their radiosensitivity to be quantitatively assessed, since lethally X-irradiated cells may show a long delay before manifestations of cell death ('interphase death') are seen. Counts of surviving cells well therefore include both lethally-hit cells (apparent survivors), and real survivors which have not been lethally hit. Death rates of irradiated leukaemic and normal cells show great variation between individuals, so that comparisons of radiosensitivity between different cell populations based on surviving cell counts at a single time-point are invalid. In this study the supposed radioresistance of prolymphocytic leukaemia lymphocytes was examined in 6 patients with B-cell disease. Survival curves were plotted from serial observations made over several days after graded X-irradiation (0-1000 cGy). We attempted to interpret these radiation responses in terms of their dose dependence (intrinsic radiosensitivity) and time dependence (cell death rate) characteristics using the best-fitting of four mathematical models, all based on classical 'single-hit' target theory. The apparent radioresistance shown in 4 cases could be explained by very slow death rates (T[sub 172] values 55-205 h) of cells proving otherwise radiosensitive (D37 values 38-123 cGy). Genuine radioresistance was found in only 1 case (actual D37 value above 2000 cGy). B ignoring delayed cell death in clinical assessments, pathological lymphocytes could be mistakenly categorized as resistant to elimination by radiotherapy. (au) (30 refs.).

  1. Predicting Mean Survival Time from Reported Median Survival Time for Cancer Patients

    DEFF Research Database (Denmark)

    Lousdal, Mette L; Kristiansen, Ivar S; Møller, Bjørn;

    2016-01-01

    BACKGROUND: Mean duration of survival following treatment is a prerequisite for cost-effectiveness analyses used for assessing new and costly life-extending therapies for cancer patients. Mean survival time is rarely reported due to censoring imposed by limited follow-up time, whereas the median...... survival time often is. The empirical relationship between mean and median survival time for cancer patients is not known. AIM: To derive the empirical associations between mean and median survival time across cancer types and to validate this empirical prediction approach and compare it with the standard...... approach of fitting a Weibull distribution. METHODS: We included all patients in Norway diagnosed from 1960 to 1999 with one of the 13 most common solid tumor cancers until emigration, death, or 31 December 2011, whichever came first. Observed median, restricted mean, and mean survival times were obtained...

  2. Clinical prediction of 5-year survival in systemic sclerosis

    DEFF Research Database (Denmark)

    Fransen, Julie Munk; Popa-Diaconu, D; Hesselstrand, R

    2011-01-01

    Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate...

  3. Distinct regulation of cell cycle and survival in lymphocytes from patients with Alzheimer's disease and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bartolomé, Fernando; Muñoz, Ursula; Esteras, Noemí; Esteban, Jesús; Bermejo-Pareja, Félix; Martín-Requero, Angeles

    2009-01-01

    Alterations in cell cycle progression seem to be associated with neuronal death in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). We previously reported disturbances in the control of cell survival/death fate in immortalized lymphocytes from AD patients. These cell cycle dysfunction and impaired apoptosis were considered systemic manifestations of AD disease. The purpose of this study was to evaluate whether these abnormalities are characteristic of AD, or they may be seen in other neurodegenerative disorders such ALS. Our results indicate that alterations in signaling molecules, Akt and ERK1/2, and in the cyclin-dependent kinase complex inhibitors (CDKis) p21(Cip1) and p27(Kip1) are detectable in lymphoblasts from AD patients, but not in ALS patients, suggesting that these variables may be considered for the development of biomarkers of AD. However, lymphocytes from ALS patients do not represent a useful model to study cell cycle-related events associated with neurodegeneration of motoneurons.

  4. Physician predictions of graft survival following liver transplantation

    Science.gov (United States)

    Feurer, Irene D.; Austin, Mary T.; Porayko, Michael K.; Wright, J. Kelly; Lorenzi, Nancy M.; Pinson, C. Wright; Aronsky, Dominik

    2007-01-01

    Introduction. Due to the scarcity of cadaveric livers, clinical judgment must be used to avoid futile transplants. However, the accuracy of human judgment for predicting outcomes following liver transplantation is unknown. The study aim was to assess expert clinicians’ ability to predict graft survival and to compare their performance to published survival models. Materials and methods. Pre-transplant case summaries were prepared based on 16 actual, randomly selected liver transplants. Clinicians specializing in the care of liver transplant patients were invited to assess the likelihood of 90-day graft survival for each case using (1) a 4-point Likert scale ranging from poor to excellent, and (2) a visual analog scale denoting the probability of survival. Four published models were also used to predict survival for the 16 cases. Results. Completed instruments were received from 50 clinicians. Prognostic estimates on the two scales were highly correlated (median r=0.88). Individual clinicians’ predictive ability was 0.61±0.13, by area under the receiver operating characteristic curve. The performance of published models was MELD 0.59, Desai 0.66, Ghobrial 0.61, and Thuluvath 0.45. For three cases, clinicians consistently overestimated the probability of survival (87±10%, 89±9%, 86±9%); these patients had early graft failures caused by postoperative complications. Discussion. Clinicians varied in their ability to predict survival for a set of pre-transplant scenarios, but performed similarly to published models. When clinicians overestimated the chance of transplant success, either sepsis or hepatic artery thrombosis was involved; such events may be hard to predict before surgery. PMID:18345303

  5. Prediction of patient survival in cases of acute paraquat poisoning.

    Science.gov (United States)

    Hong, Sae-Yong; Lee, Ji-Sung; Sun, In O; Lee, Kwang-Young; Gil, Hyo-Wook

    2014-01-01

    Paraquat concentration-time data have been used to predict the clinical outcome following ingestion. However, these studies have included only small populations, although paraquat poisoning has a very high mortality rate. The purpose of this study was to develop a simple and reliable model to predict survival according to the time interval post-ingestion in patients with acute paraquat poisoning. Data were retrospectively collected for patients who were admitted with paraquat poisoning to Soonchunhyang University Choenan Hospital between January 2005 and December 2012. Plasma paraquat levels were measured using high-performance liquid chromatography. To validate the model we developed, we used external data from 788 subjects admitted to the Presbyterian Medical Center, Jeonju, Korea, between January 2007 and December 2012. Two thousand one hundred thirty six patients were included in this study. The overall survival rate was 44% (939/2136). The probability of survival for any specified time and concentration could be predicted as (exp(logit))/(1+exp(logit)), where logit = 1.3544+[-3.4688 × log10(plasma paraquat μg/M[Formula: see text])]+[-2.3169 × log10(hours since ingestion)]. The external validation study showed that our model was highly accurate for the prediction of survival (C statics 0.964; 95% CI [0.952-0.975]). We have developed a model that is effective for predicting survival after paraquat intoxication.

  6. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis

    Science.gov (United States)

    Nishida, Yu; Yamagami, Hirokazu; Yukawa, Tomomi; Otani, Koji; Nagami, Yasuaki; Tanaka, Fumio; Taira, Koichi; Kamata, Noriko; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro

    2017-01-01

    Objectives Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn’s disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. Materials and Methods Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. Results Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20–12.4, P = 0.023). Conclusions Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab. PMID:28076386

  7. A novel role for IL-27 in mediating the survival of activated mouse CD4 T lymphocytes.

    Science.gov (United States)

    Kim, Gisen; Shinnakasu, Ryo; Saris, Christiaan J M; Cheroutre, Hilde; Kronenberg, Mitchell

    2013-02-15

    IL-27, an IL-12 family cytokine, has pleiotropic functions in the differentiation and expansion of CD4(+) T cell subsets. In this study, we discovered a novel function of IL-27. CD4(+)CD45RB(high) T cells from mice deficient for the α-chain of IL-27 receptor failed to induce colitis in Rag(-/-) recipients, because of an inability of activated donor cells to survive. Interestingly, IL-27 was indispensable for the prevention of colitis by regulatory T cells, also because of a defect in long-term cell survival. IL-27 affected the survival of activated T lymphocytes, rather than promoting cell proliferation, by inhibiting Fas-mediated activation-induced T cell death, acting through the STAT3 signaling pathway. The addition of IL-27 during activation resulted in an increased cell number, which was correlated with decreased activation of both caspases 3 and 8. This prosurvival effect was attributed to downregulation of FasL and to the induction of the antiapoptotic protein cFLIP. Although activation induced cell death is an important mechanism for the maintenance of immunological homeostasis, protection of lymphocytes from excessive cell death is essential for effective immunity. Our data indicate that IL-27 has a crucial role in the inhibition of activation-induced cell death, thereby permitting Ag-driven T cell expansion.

  8. UV-induced chromosome aberrations, sister-chromatid exchanges and cell survival in cultured lymphocytes from malnourished children

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, P.B.; Rahiman, M.A.; Tulpule, P.G.

    1982-08-01

    Cultured lymphocytes from children with kwashiorkor and from normal children were examined for their susceptibility to ultraviolet (UV)-induced chromosome aberrations, sister-chromatid exchanges and cell survival. Cells from kwashiorkor exhibited increased chromosome aberrations, but not sister-chromatid exchanges, when exposed to higher doses of UV. Furthermore, when cells from these patients were exposed to higher doses of UV, there was a significant reduction in viability. These results indicate that, as compared to normals, cells from kwashiorkor were more sensitive to the lethal effects of UV.

  9. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy

    DEFF Research Database (Denmark)

    da Cunha-Bang, C; Simonsen, J; Rostgaard, K

    2016-01-01

    The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer...... for patients treated with chemo-immunotherapy demonstrated in clinical studies....

  10. Comparing Three Data Mining Methods to Predict Kidney Transplant Survival

    Science.gov (United States)

    Shahmoradi, Leila; Langarizadeh, Mostafa; Pourmand, Gholamreza; fard, Ziba Aghsaei; Borhani, Alireza

    2016-01-01

    Introduction: One of the most important complications of post-transplant is rejection. Analyzing survival is one of the areas of medical prognosis and data mining, as an effective approach, has the capacity of analyzing and estimating outcomes in advance through discovering appropriate models among data. The present study aims at comparing the effectiveness of C5.0 algorithms, neural network and C&RTree to predict kidney transplant survival before transplant. Method: To detect factors effective in predicting transplant survival, information needs analysis was performed via a researcher-made questionnaire. A checklist was prepared and data of 513 kidney disease patient files were extracted from Sina Urology Research Center. Following CRISP methodology for data mining, IBM SPSS Modeler 14.2, C5.0, C&RTree algorithms and neural network were used. Results: Body Mass Index (BMI), cause of renal dysfunction and duration of dialysis were evaluated in all three models as the most effective factors in transplant survival. C5.0 algorithm with the highest validity (96.77%) was the first in estimating kidney transplant survival in patients followed by C&RTree (83.7%) and neural network (79.5%) models. Conclusion: Among the three models, C5.0 algorithm was the top model with high validity that confirms its strength in predicting survival. The most effective kidney transplant survival factors were detected in this study; therefore, duration of transplant survival (year) can be determined considering the regulations set for a new sample with specific characteristics. PMID:28163356

  11. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lundegaard, Claus; Lamberth, K.

    2007-01-01

    BACKGROUND: Reliable predictions of Cytotoxic T lymphocyte (CTL) epitopes are essential for rational vaccine design. Most importantly, they can minimize the experimental effort needed to identify epitopes. NetCTL is a web-based tool designed for predicting human CTL epitopes in any given protein....... of the other methods achieved a sensitivity of 0.64. The NetCTL-1.2 method is available at http://www.cbs.dtu.dk/services/NetCTL.All used datasets are available at http://www.cbs.dtu.dk/suppl/immunology/CTL-1.2.php....

  12. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lundegaard, Claus; Lamberth, K.;

    2007-01-01

    BACKGROUND: Reliable predictions of Cytotoxic T lymphocyte (CTL) epitopes are essential for rational vaccine design. Most importantly, they can minimize the experimental effort needed to identify epitopes. NetCTL is a web-based tool designed for predicting human CTL epitopes in any given protein....... of the other methods achieved a sensitivity of 0.64. The NetCTL-1.2 method is available at http://www.cbs.dtu.dk/services/NetCTL.All used datasets are available at http://www.cbs.dtu.dk/suppl/immunology/CTL-1.2.php....

  13. Improved renal allograft survival using the mixed lymphocyte culture for selection of nonidentical living related donors.

    Science.gov (United States)

    Riggio, R R; Saal, S D; Katz, E B; Tapia, L; White, R; Chami, J; Sheigh, J S; Sullivan, J F; Stenzel, K H; Stubenbord, W T; Whitsell, J C; Rubin, A L

    1975-01-01

    Our results concur with earlier published work, by other groups, showing that LRD-recipient pairs with low MLC stimulation usually have better and more prolonged graft success than do those with higher stimulation. Specific HL-A compatibilities or incompatibilities did not seem to affect these results, nor did the presence of an increased number of common loci, short of increasing the apparent chromosome compatibility. The presence of pre-transplant cytotoxic antibodies, in patients with a high MI, however, may unfavorably affect the LRD transplant. The overall results of our LRD transplant experience is shown in Figure 1, and superimposed upon Figure 2, is the current extrapolation of data showing MLC stimulation and haplotype success. Thus, it appears that graft survival may be improved and more closely approach the levels seen in a full-house, diplotype match, by using the MLC results in considering patients for transplantation. Not all patients with a high MLC, however, (see table) reject their grafts and it is impossible to predict pre-transplant who will develop specific allograft enhancement. Before the MI becomes a specific criteria for transplant selection, additional studies of patient stimulation in MLC should be done. Suppression of stimulation by donor cells in autologous serum, as compared to the response to unrelated controls, might provide pre-transplant clues to the presence of enhancing factors. Such studies could provide an index that would be more meaningful than the MI in AB sera alone. Since overall results from both our series and from the Transplant Registry continue to indicate better long term graft survival for LRD than for cadaver transplants, and since the evidence suggests that a successful transplant offers a patient a better quality of life, as well as decreased morbidity and mortality compared to concomitant time spent on hemodialysis, continued LRD transplants with high MI is warranted in some circumstances with the patient

  14. Predicting ICU survival: A meta-level approach

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    Stamoulis Konstantinos

    2008-07-01

    Full Text Available Abstract Background The performance of separate Intensive Care Unit (ICU status scoring systems vis-à-vis prediction of outcome is not satisfactory. Computer-based predictive modeling techniques may yield good results but their performance has seldom been extensively compared to that of other mature or emerging predictive models. The objective of the present study was twofold: to propose a prototype meta-level predicting approach concerning Intensive Care Unit (ICU survival and to evaluate the effectiveness of typical mining models in this context. Methods Data on 158 men and 46 women, were used retrospectively (75% of the patients survived. We used Glasgow Coma Scale (GCS, Acute Physiology And Chronic Health Evaluation II (APACHE II, Sequential Organ Failure Assessment (SOFA and Injury Severity Score (ISS values to structure a decision tree (DTM, a neural network (NNM and a logistic regression (LRM model and we evaluated the assessment indicators implementing Receiver Operating Characteristics (ROC plot analysis. Results Our findings indicate that regarding the assessment of indicators' capacity there are specific discrete limits that should be taken into account. The Az score ± SE was 0.8773± 0.0376 for the DTM, 0.8061± 0.0427 for the NNM and 0.8204± 0.0376 for the LRM, suggesting that the proposed DTM achieved a near optimal Az score. Conclusion The predicting processes of ICU survival may go "one step forward", by using classic composite assessment indicators as variables.

  15. Combining gene signatures improves prediction of breast cancer survival.

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    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  16. Labour-efficient in vitro lymphocyte population tracking and fate prediction using automation and manual review.

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    Rajib Chakravorty

    Full Text Available Interest in cell heterogeneity and differentiation has recently led to increased use of time-lapse microscopy. Previous studies have shown that cell fate may be determined well in advance of the event. We used a mixture of automation and manual review of time-lapse live cell imaging to track the positions, contours, divisions, deaths and lineage of 44 B-lymphocyte founders and their 631 progeny in vitro over a period of 108 hours. Using this data to train a Support Vector Machine classifier, we were retrospectively able to predict the fates of individual lymphocytes with more than 90% accuracy, using only time-lapse imaging captured prior to mitosis or death of 90% of all cells. The motivation for this paper is to explore the impact of labour-efficient assistive software tools that allow larger and more ambitious live-cell time-lapse microscopy studies. After training on this data, we show that machine learning methods can be used for realtime prediction of individual cell fates. These techniques could lead to realtime cell culture segregation for purposes such as phenotype screening. We were able to produce a large volume of data with less effort than previously reported, due to the image processing, computer vision, tracking and human-computer interaction tools used. We describe the workflow of the software-assisted experiments and the graphical interfaces that were needed. To validate our results we used our methods to reproduce a variety of published data about lymphocyte populations and behaviour. We also make all our data publicly available, including a large quantity of lymphocyte spatio-temporal dynamics and related lineage information.

  17. Predicting the survival of diabetes using neural network

    Science.gov (United States)

    Mamuda, Mamman; Sathasivam, Saratha

    2017-08-01

    Data mining techniques at the present time are used in predicting diseases of health care industries. Neural Network is one among the prevailing method in data mining techniques of an intelligent field for predicting diseases in health care industries. This paper presents a study on the prediction of the survival of diabetes diseases using different learning algorithms from the supervised learning algorithms of neural network. Three learning algorithms are considered in this study: (i) The levenberg-marquardt learning algorithm (ii) The Bayesian regulation learning algorithm and (iii) The scaled conjugate gradient learning algorithm. The network is trained using the Pima Indian Diabetes Dataset with the help of MATLAB R2014(a) software. The performance of each algorithm is further discussed through regression analysis. The prediction accuracy of the best algorithm is further computed to validate the accurate prediction

  18. Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

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    Jiangdong Xiang

    2017-02-01

    Full Text Available PURPOSE: The monocyte-to-lymphocyte ratio (MLR has been shown to be associated with the prognosis of various solid tumors. This study sought to evaluate the important value of the MLR in ovarian cancer patients. METHODS: A total of 133 ovarian cancer patients and 43 normal controls were retrospectively reviewed. The patients' demographics were analyzed along with clinical and pathologic data. The counts of peripheral neutrophils, lymphocytes, monocytes, and platelets were collected and used to calculate the MLR, neutrophil-to-lymphocyte ratio (NLR. and platelet-to-lymphocyte ratio (PLR. The optimal cutoff value of the MLR was determined by using receiver operating characteristic curve analysis. We compared the MLR, NLR, and PLR between ovarian cancer and normal control patients and among patients with different stages and different grades, as well as between patients with lymph node metastasis and non–lymph node metastasis. We then investigated the value of the MLR in predicting the stage, grade, and lymph node positivity by using logistic regression. The impact of the MLR on overall survival (OS was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Statistically significant differences in the MLR were observed between ovarian cancer patients and normal controls. However, no difference was found for the NLR and PLR. Highly significant differences in the MLR were found among patients with different stages (stage I-II and stage III-IV, grades (G1 and >G1, and lymph node metastasis status. The MLR was a significant and independent risk factor for lymph node metastasis, as determined by logistic regression. The optimal cutoff value of the MLR was 0.23. We also classified the data according to tumor markers (CA125, CA199, HE4, AFP, and CEA and conventional coagulation parameters (International Normalized Ratio [INR] and fibrinogen. Highly significant differences in CA125, CA199, HE4, INR, fibrinogen levels, and lactate

  19. Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.

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    Jiali Zhu

    Full Text Available BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF-alpha, interleukin (IL-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3(+ T cell was inhibited in the thymus. The numbers of CD4(+, CD8(+ T lymphocytes and dendritic cells (DCs were higher, while the number of CD4(+CD25(+ regulatory T cells was lower in the baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin improves survival of mice

  20. Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Li, Heng; Yi, Shu-Hua; Xiong, Wen-Jie; Liu, Hui-Min; Lyu, Rui; Wang, Ting-Yu; Liu, Wei; Zhong, Shi-Zhen; Yu, Zhen; Zou, De-Hui; Xu, Yan; An, Gang; Li, Zeng-Jun; Qiu, Lu-Gui

    2017-01-01

    Background: The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI). Methods: Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT. Results: The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3–6]) with significantly different TTFT

  1. Significance of bioindicators to predict survival in irradiated minipigs.

    Science.gov (United States)

    Moroni, Maria; Port, Matthias; Koch, Amory; Gulani, Jatinder; Meineke, Viktor; Abend, Michael

    2014-06-01

    The minipig is emerging as a potential alternative non-rodent animal model. Several biological markers (e.g., blood counts, laboratory parameters, and clinical signs) have been proposed for rapid triage of radiation victims. Here, the authors focus on the significance of bio-indicators for prediction of survivors after irradiation and compare it with human data; the relationship between these biomarkers and radiation dose is not part of this study. Male Göttingen minipigs (age 4-5 mo, weight 9-10 kg) were irradiated (or sham-irradiated) bilaterally with gamma-photons (⁶⁰Co, 0.5-0.6 Gy min⁻¹) in the dose range of 1.6-12 Gy. Peripheral blood cell counts, laboratory parameters, and clinical symptoms were collected up to 10 d after irradiation and analyzed using logistic regression analysis and calculating ROC curves. In moribund pigs, parameters such as decreased lymphocyte/granulocyte counts, increased C-reactive protein, alkaline phosphatase values, as well as increased citrulline values and body temperature, significantly (p 0.8). However, most predictive within the first 3 d after exposure was a combination of decreased lymphocyte counts and increased body temperature observed as early as 3 h after radiation exposure (ROC: 0.93-0.96, p < 0.0001). Sham-irradiated animals (corresponding to "worried wells") could be easily discriminated from dying pigs, thus pointing to the diagnostic significance of this analysis. These data corroborate with earlier findings performed on human radiation victims suffering from severe hematological syndrome and provide further evidence for the suitability of the minipig model as a potential alternative non-rodent animal model.

  2. Evaluating Random Forests for Survival Analysis Using Prediction Error Curves

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    Ulla B. Mogensen

    2012-09-01

    Full Text Available Prediction error curves are increasingly used to assess and compare predictions in survival analysis. This article surveys the R package pec which provides a set of functions for efficient computation of prediction error curves. The software implements inverse probability of censoring weights to deal with right censored data and several variants of cross-validation to deal with the apparent error problem. In principle, all kinds of prediction models can be assessed, and the package readily supports most traditional regression modeling strategies, like Cox regression or additive hazard regression, as well as state of the art machine learning methods such as random forests, a nonparametric method which provides promising alternatives to traditional strategies in low and high-dimensional settings. We show how the functionality of pec can be extended to yet unsupported prediction models. As an example, we implement support for random forest prediction models based on the R packages randomSurvivalForest and party. Using data of the Copenhagen Stroke Study we use pec to compare random forests to a Cox regression model derived from stepwise variable selection.

  3. Predicting functional decline and survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ong, Mei-Lyn; Tan, Pei Fang; Holbrook, Joanna D

    2017-01-01

    Better predictors of amyotrophic lateral sclerosis disease course could enable smaller and more targeted clinical trials. Partially to address this aim, the Prize for Life foundation collected de-identified records from amyotrophic lateral sclerosis sufferers who participated in clinical trials of investigational drugs and made them available to researchers in the PRO-ACT database. In this study, time series data from PRO-ACT subjects were fitted to exponential models. Binary classes for decline in the total score of amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) (fast/slow progression) and survival (high/low death risk) were derived. Data was segregated into training and test sets via cross validation. Learning algorithms were applied to the demographic, clinical and laboratory parameters in the training set to predict ALSFRS-R decline and the derived fast/slow progression and high/low death risk categories. The performance of predictive models was assessed by cross-validation in the test set using Receiver Operator Curves and root mean squared errors. A model created using a boosting algorithm containing the decline in four parameters (weight, alkaline phosphatase, albumin and creatine kinase) post baseline, was able to predict functional decline class (fast or slow) with fair accuracy (AUC = 0.82). However similar approaches to build a predictive model for decline class by baseline subject characteristics were not successful. In contrast, baseline values of total bilirubin, gamma glutamyltransferase, urine specific gravity and ALSFRS-R item score-climbing stairs were sufficient to predict survival class. Using combinations of small numbers of variables it was possible to predict classes of functional decline and survival across the 1-2 year timeframe available in PRO-ACT. These findings may have utility for design of future ALS clinical trials.

  4. Prediction of patient survival in cases of acute paraquat poisoning.

    Directory of Open Access Journals (Sweden)

    Sae-Yong Hong

    Full Text Available Paraquat concentration-time data have been used to predict the clinical outcome following ingestion. However, these studies have included only small populations, although paraquat poisoning has a very high mortality rate. The purpose of this study was to develop a simple and reliable model to predict survival according to the time interval post-ingestion in patients with acute paraquat poisoning. Data were retrospectively collected for patients who were admitted with paraquat poisoning to Soonchunhyang University Choenan Hospital between January 2005 and December 2012. Plasma paraquat levels were measured using high-performance liquid chromatography. To validate the model we developed, we used external data from 788 subjects admitted to the Presbyterian Medical Center, Jeonju, Korea, between January 2007 and December 2012. Two thousand one hundred thirty six patients were included in this study. The overall survival rate was 44% (939/2136. The probability of survival for any specified time and concentration could be predicted as (exp(logit/(1+exp(logit, where logit = 1.3544+[-3.4688 × log10(plasma paraquat μg/M[Formula: see text

  5. Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

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    Farina M. Hanif

    2014-10-01

    Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

  6. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: are they useful for predicting gestational diabetes mellitus during pregnancy?

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    Sargın MA

    2016-04-01

    Full Text Available Mehmet Akif Sargın, Murat Yassa, Bilge Dogan Taymur, Ayhan Celik, Emrah Ergun, Niyazi Tug Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Research and Training Hospital, Istanbul, Turkey Objective: We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR could be utilized to screen for gestational diabetes mellitus (GDM.Subjects and methods: NLR and PLR were assessed by retrospective analysis of 762 healthy and pregnant women with GDM. The patients were stratified into four groups, as follows: GDM (n=144, impaired glucose tolerance (n=76, only screen positive (n=238, and control (n=304.Results: The leukocyte, neutrophil, and lymphocyte counts were significantly higher in the study groups compared with the control group (P=0.001; P<0.01. There were no statistically significant differences between the groups with respect to the NLR and PLR (P>0.05.Conclusion: We do not recommend that blood NLR and PLR can be used to screen for GDM. However, increase in the leukocyte count is an important marker for GDM as it provides evidence of subclinical inflammation. Keywords: inflammation, lymphocytes, neutrophils, platelets, pregnancy

  7. Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy

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    Fatih Mehmet Yazar

    2015-11-01

    Full Text Available Acute appendicitis (AA is not uncommon during pregnancy but can be difficult to diagnose. This study evaluated the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR in addition to conventional diagnostic indicators of the disease to diagnose AA during pregnancy. Age, gestational age, white blood cell (WBC count, Alvarado scores, C-reactive protein (CRP, lymphocyte count, NLR and PLR were compared among 28 pregnant women who underwent surgery for AA, 35 pregnant women wrongly suspected as having AA, 29 healthy pregnant women, and 30 nonpregnant healthy women. Mean WBC counts and CRP levels were higher in women with proven AA than in those of control groups (all p < 0.05. Among all the groups, the median NLR and PLR were significantly different in women with proven AA (all p < 0.05. Receiver operating characteristic analysis was used to determine cut-off values for WBC count, CRP, lymphocyte count, NLR and PLR, and multiple logistic regression analysis showed that NLR and PLR used with routine methods could diagnose AA with 90.5% accuracy. Used in addition to routine diagnostic methods, NLR and PLR increased the accuracy of the diagnosis of AA in pregnant women.

  8. A two-gene signature, SKI and SLAMF1, predicts time-to-treatment in previously untreated patients with chronic lymphocytic leukemia.

    Directory of Open Access Journals (Sweden)

    Carmen D Schweighofer

    Full Text Available We developed and validated a two-gene signature that predicts prognosis in previously-untreated chronic lymphocytic leukemia (CLL patients. Using a 65 sample training set, from a cohort of 131 patients, we identified the best clinical models to predict time-to-treatment (TTT and overall survival (OS. To identify individual genes or combinations in the training set with expression related to prognosis, we cross-validated univariate and multivariate models to predict TTT. We identified four gene sets (5, 6, 12, or 13 genes to construct multivariate prognostic models. By optimizing each gene set on the training set, we constructed 11 models to predict the time from diagnosis to treatment. Each model also predicted OS and added value to the best clinical models. To determine which contributed the most value when added to clinical variables, we applied the Akaike Information Criterion. Two genes were consistently retained in the models with clinical variables: SKI (v-SKI avian sarcoma viral oncogene homolog and SLAMF1 (signaling lymphocytic activation molecule family member 1; CD150. We optimized a two-gene model and validated it on an independent test set of 66 samples. This two-gene model predicted prognosis better on the test set than any of the known predictors, including ZAP70 and serum β2-microglobulin.

  9. A Two-Gene Signature, SKI and SLAMF1, Predicts Time-to-Treatment in Previously Untreated Patients with Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Schweighofer, Carmen D.; Coombes, Kevin R.; Barron, Lynn L.; Diao, Lixia; Newman, Rachel J.; Ferrajoli, Alessandra; O'Brien, Susan; Wierda, William G.; Luthra, Rajyalakshmi; Medeiros, L. Jeffrey; Keating, Michael J.; Abruzzo, Lynne V.

    2011-01-01

    We developed and validated a two-gene signature that predicts prognosis in previously-untreated chronic lymphocytic leukemia (CLL) patients. Using a 65 sample training set, from a cohort of 131 patients, we identified the best clinical models to predict time-to-treatment (TTT) and overall survival (OS). To identify individual genes or combinations in the training set with expression related to prognosis, we cross-validated univariate and multivariate models to predict TTT. We identified four gene sets (5, 6, 12, or 13 genes) to construct multivariate prognostic models. By optimizing each gene set on the training set, we constructed 11 models to predict the time from diagnosis to treatment. Each model also predicted OS and added value to the best clinical models. To determine which contributed the most value when added to clinical variables, we applied the Akaike Information Criterion. Two genes were consistently retained in the models with clinical variables: SKI (v-SKI avian sarcoma viral oncogene homolog) and SLAMF1 (signaling lymphocytic activation molecule family member 1; CD150). We optimized a two-gene model and validated it on an independent test set of 66 samples. This two-gene model predicted prognosis better on the test set than any of the known predictors, including ZAP70 and serum β2-microglobulin. PMID:22194822

  10. Survival Predictions of Ceramic Crowns Using Statistical Fracture Mechanics.

    Science.gov (United States)

    Nasrin, S; Katsube, N; Seghi, R R; Rokhlin, S I

    2017-01-01

    This work establishes a survival probability methodology for interface-initiated fatigue failures of monolithic ceramic crowns under simulated masticatory loading. A complete 3-dimensional (3D) finite element analysis model of a minimally reduced molar crown was developed using commercially available hardware and software. Estimates of material surface flaw distributions and fatigue parameters for 3 reinforced glass-ceramics (fluormica [FM], leucite [LR], and lithium disilicate [LD]) and a dense sintered yttrium-stabilized zirconia (YZ) were obtained from the literature and incorporated into the model. Utilizing the proposed fracture mechanics-based model, crown survival probability as a function of loading cycles was obtained from simulations performed on the 4 ceramic materials utilizing identical crown geometries and loading conditions. The weaker ceramic materials (FM and LR) resulted in lower survival rates than the more recently developed higher-strength ceramic materials (LD and YZ). The simulated 10-y survival rate of crowns fabricated from YZ was only slightly better than those fabricated from LD. In addition, 2 of the model crown systems (FM and LD) were expanded to determine regional-dependent failure probabilities. This analysis predicted that the LD-based crowns were more likely to fail from fractures initiating from margin areas, whereas the FM-based crowns showed a slightly higher probability of failure from fractures initiating from the occlusal table below the contact areas. These 2 predicted fracture initiation locations have some agreement with reported fractographic analyses of failed crowns. In this model, we considered the maximum tensile stress tangential to the interfacial surface, as opposed to the more universally reported maximum principal stress, because it more directly impacts crack propagation. While the accuracy of these predictions needs to be experimentally verified, the model can provide a fundamental understanding of the

  11. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection.

    Science.gov (United States)

    Yamada, Noriyuki; Oizumi, Satoshi; Kikuchi, Eiki; Shinagawa, Naofumi; Konishi-Sakakibara, Jun; Ishimine, Atsushi; Aoe, Keisuke; Gemba, Kenichi; Kishimoto, Takumi; Torigoe, Toshihiko; Nishimura, Masaharu

    2010-10-01

    Defects in human leukocyte antigen (HLA) class I expression may allow tumor cells to escape immune recognition. T cell infiltration is associated with a good prognosis in many cancers. However, the role of HLA class I expression and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM) has not been fully analyzed. In the present study, we investigated the immune profiles and conducted outcome analyses of MPM patients. HLA class I expression and TILs (CD4(+), CD8(+), and NK cells) were detected by immunohistochemistry in a series of 44 MPM cases. To detect HLA class I expression, specimens were stained with the anti-pan HLA class I monoclonal antibody EMR8-5. The expression of HLA class I was positive in all patients. There was no case that showed negative HLA class I expression. The density of CD4(+) and CD8(+) TILs were strongly correlated (R = 0.76, p < 0.001). A high density of CD8(+) TILs was a significantly better prognostic factor for the survival of patients with extrapleural pneumonectomy (p < 0.05). Multivariate analysis revealed that a high density of CD8(+) TILs is an independent prognostic factor for patients who underwent extrapleural pneumonectomy. The presence of intratumoral CD8(+) T cells was correlated with an improved clinical outcome, raising the possibility that CD8(+) T cells might play a pivotal role in the antitumor immune response against MPMs. Thus, the stimulation of CD8(+) lymphocytes might be an efficacious immunotherapy for MPM patients.

  12. National trends in incidence and survival of chronic lymphocytic leukemia in Norway for 1953-2012: a systematic analysis of population-based data.

    Science.gov (United States)

    Lenartova, Andrea; Johannesen, Tom Børge; Tjønnfjord, Geir Erland

    2016-12-01

    Chronic lymphocytic leukemia is a disease of the elderly, and despite major advances in treatment, remains incurable. The Cancer Registry of Norway has registered data on patients with chronic lymphocytic leukemia since 1953. We aimed to analyze trends in incidence and survival of chronic lymphocytic leukemia in Norway. We identified 7664 patients reported with chronic lymphocytic leukemia to the registry between 1953 and 2012. We gathered information on sex, age at diagnosis, date of death and basis for diagnosis. The age-standardized incidence increased from 0.6/100.000 person-years in 1953 to 3.1/100,000 person-years in 2012. We found a significant decrease in median age between 1993-2002 and 2003-2012 (75 vs. 72 years, 95%CI: 2.52-3.98, P survival increased from 3 years in 1952-1963 to 8.5 years in 2003-2012. Five- and 10-year age-standardized net survival increased throughout the whole period across age groups and reached 79% and 57%, respectively. Median observed survival was significantly shorter in men than in women in 1993-2002 (4.9 vs. 6.1 years, P survival rates for men and women was diminishing in 2003-2012 in patients younger than 60 years while it remained considerable in older patients. Despite an aging Norwegian population, chronic lymphocytic leukemia (CLL) patients become younger at diagnosis. A fourfold increase in incidence, a prolonged survival, and major changes in diagnostic methods in Norway were observed.

  13. Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rawstron, Andy C; Kennedy, Ben; Moreton, Paul; Dickinson, Anita J; Cullen, Matthew J; Richards, Stephen J; Jack, Andrew S; Hillmen, Peter

    2004-03-15

    Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 x 10(9)/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 x 10(9)/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.

  14. Early social networks predict survival in wild bottlenose dolphins.

    Directory of Open Access Journals (Sweden)

    Margaret A Stanton

    Full Text Available A fundamental question concerning group-living species is what factors influence the evolution of sociality. Although several studies link adult social bonds to fitness, social patterns and relationships are often formed early in life and are also likely to have fitness consequences, particularly in species with lengthy developmental periods, extensive social learning, and early social bond-formation. In a longitudinal study of bottlenose dolphins (Tursiops sp., calf social network structure, specifically the metric eigenvector centrality, predicted juvenile survival in males. Additionally, male calves that died post-weaning had stronger ties to juvenile males than surviving male calves, suggesting that juvenile males impose fitness costs on their younger counterparts. Our study indicates that selection is acting on social traits early in life and highlights the need to examine the costs and benefits of social bonds during formative life history stages.

  15. A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation.

    Directory of Open Access Journals (Sweden)

    Guo-Ying Wang

    Full Text Available BACKGROUND: Neutrophil to lymphocyte ratio (NLR has been proposed to predict prognosis of hepatocellular carcinoma (HCC. However, the cut-off values are empirical. We determined the optimal cut-off value to predict HCC recurrence after liver transplantation (LT and further established a scoring model based on NLR. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the outcome of 101 HBV-associated HCC patients undergoing LT. Preoperative risk factors for tumor recurrence were evaluated by univariate analysis. By using ROC analysis, NLR≥3 was considered elevated. The disease-free survival (DFS and overall survival (OS for patients with high NLR was significantly worse than that for patients with normal NLR (the 5-year DFS and OS of 28.5% and 19.5% vs. 64.9% and 61.8%, respectively; P5 cm, tumor number >3, macrovascular invasion, AFP≥400 µg/L, NLR≥3, and HBV-DNA level >5 log10 copies/mL were preoperative predictors of DFS. Cox regression analysis showed macrovascular invasion, tumor number, and high NLR were independent prognostic factors. We then established a preoperative prognostic score based on multivariate analysis. Each factor was given a score of 1. Area under the ROC curve of the score was 0.781. All nine patients with score 3 developed recurrence within 6 months after LT. Of 71 patients without vascular invasion, three patients with both tumor number >3 and NLR≥3 developed recurrence within 14 months after LT while the 5-year DFS and OS for patients with a score of 0 or 1 were 68.1% and 62.8%, respectively. CONCLUSIONS/SIGNIFICANCE: Preoperative elevated NLR significantly increases the risk of recurrence in patients underwent LT for HCC. Patients with both NLR≥3 and tumor number >3 are not a good indication for LT. Our score model may aid in the selection of patients that would most benefit from transplantation for HCC.

  16. Machine learning models in breast cancer survival prediction.

    Science.gov (United States)

    Montazeri, Mitra; Montazeri, Mohadeseh; Montazeri, Mahdieh; Beigzadeh, Amin

    2016-01-01

    Breast cancer is one of the most common cancers with a high mortality rate among women. With the early diagnosis of breast cancer survival will increase from 56% to more than 86%. Therefore, an accurate and reliable system is necessary for the early diagnosis of this cancer. The proposed model is the combination of rules and different machine learning techniques. Machine learning models can help physicians to reduce the number of false decisions. They try to exploit patterns and relationships among a large number of cases and predict the outcome of a disease using historical cases stored in datasets. The objective of this study is to propose a rule-based classification method with machine learning techniques for the prediction of different types of Breast cancer survival. We use a dataset with eight attributes that include the records of 900 patients in which 876 patients (97.3%) and 24 (2.7%) patients were females and males respectively. Naive Bayes (NB), Trees Random Forest (TRF), 1-Nearest Neighbor (1NN), AdaBoost (AD), Support Vector Machine (SVM), RBF Network (RBFN), and Multilayer Perceptron (MLP) machine learning techniques with 10-cross fold technique were used with the proposed model for the prediction of breast cancer survival. The performance of machine learning techniques were evaluated with accuracy, precision, sensitivity, specificity, and area under ROC curve. Out of 900 patients, 803 patients and 97 patients were alive and dead, respectively. In this study, Trees Random Forest (TRF) technique showed better results in comparison to other techniques (NB, 1NN, AD, SVM and RBFN, MLP). The accuracy, sensitivity and the area under ROC curve of TRF are 96%, 96%, 93%, respectively. However, 1NN machine learning technique provided poor performance (accuracy 91%, sensitivity 91% and area under ROC curve 78%). This study demonstrates that Trees Random Forest model (TRF) which is a rule-based classification model was the best model with the highest level of

  17. Predicting and Modelling of Survival Data when Cox's Regression Model does not hold

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects...

  18. High Neutrophil-to-Lymphocyte Ratio Predicts Cardiovascular Mortality in Chronic Hemodialysis Patients

    Science.gov (United States)

    Xiong, Ruifang

    2017-01-01

    The neutrophil-to-lymphocyte ratio (NLR) is a novel simple biomarker of inflammation. It has emerged as a predictor of poor prognosis in cancer and cardiovascular disease in general population. But little was known of its prognostic value in chronic hemodialysis (HD) patients. Here we investigated the association between NLR and cardiovascular risk markers, including increased pulse pressure (PP), left ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in HD patients. Two hundred and sixty-eight HD patients were enrolled in this study and were followed for 36 months. The primary end point was all-cause mortality and cardiovascular mortality. Multivariable Cox regression was used to calculate the adjusted hazard ratios for NLR on all-cause and cardiovascular survival. We pinpointed that higher NLR in HD patients was a predictor of increased PP, LVMI, and IMT; HD patients with higher NLR had a lower survival at the end of the study; furthermore, high NLR was an independent predictor of all-cause and cardiovascular mortality when adjusted for other risk factors. In conclusion, higher NLR in HD patients was associated with cardiovascular risk factors and mortality.

  19. The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

    Science.gov (United States)

    Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

    2015-01-01

    Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

  20. Survival model construction guided by fit and predictive strength.

    Science.gov (United States)

    Chauvel, Cécile; O'Quigley, John

    2016-10-05

    Survival model construction can be guided by goodness-of-fit techniques as well as measures of predictive strength. Here, we aim to bring together these distinct techniques within the context of a single framework. The goal is how to best characterize and code the effects of the variables, in particular time dependencies, when taken either singly or in combination with other related covariates. Simple graphical techniques can provide an immediate visual indication as to the goodness-of-fit but, in cases of departure from model assumptions, will point in the direction of a more involved and richer alternative model. These techniques appear to be intuitive. This intuition is backed up by formal theorems that underlie the process of building richer models from simpler ones. Measures of predictive strength are used in conjunction with these goodness-of-fit techniques and, again, formal theorems show that these measures can be used to help identify models closest to the unknown non-proportional hazards mechanism that we can suppose generates the observations. Illustrations from studies in breast cancer show how these tools can be of help in guiding the practical problem of efficient model construction for survival data.

  1. Usefulness of Neutrophil to Lymphocyte Ratio in Prediction of Coronary Artery Lesions in Patients with Kawasaki Disease.

    Science.gov (United States)

    Demir, Fikri; Karadeniz, Cem; Özdemir, Rahmi; Yozgat, Yılmaz; Çelegen, Kübra; Karaaslan, Utku; Demirol, Mustafa; Meşe, Timur; Ünal, Nurettin

    2015-10-01

    Kawasaki disease is an inflammatory condition. Neutrophil to lymphocyte ratio is a marker reflecting inflammation. The aim of the study is to evaluate usefulness of neutrophil to lymphocyte ratio in diagnosis of Kawasaki disease and in prediction of coronary artery lesions. Retrospective cross-sectional study. Seventy-five children with Kawasaki disease and 66 controls were retrospectively enrolled. Their leukocyte, neutrophil, and lymphocyte counts were recorded. Abnormally distributed data were shown as median (interquartile range). Cases having coronary artery diameter two standard deviation above mean were diagnosed to have coronary artery lesions. Median age of Kawasaki disease patients was 34 months. Twentyfive of those (33.33%) had incomplete Kawasaki disease and twenty-six (34.66%) had coronary artery lesions. Leukocyte [12.61 (6.09)×10(3)/µL vs. 8.48 (5.58)×10(3)/µL], neutrophil [6.73 (4.10) ×10(3)/µL vs. 4.62 (5.47)×10(3)/µL], and lymphocyte [4.04 (2.91)×10(3)/µL vs. 3.02 (2.57) ×10(3)/µL] counts were significantly higher in Kawasaki disease patients compared to controls (all p values Kawasaki disease and incomplete Kawasaki disease cases did not differ, while comparison of patients with and without coronary artery lesions revealed significantly higher neutrophil to lymphocyte ratio values in former group [2.02 (1.63) vs. 1.50 (1.28), p=0.01]. The cut-off neutrophil to lymphocyte ratio value for prediction of coronary artery lesions was determined as 1.32. Neutrophil to lymphocyte ratio values in Kawasaki patients with coronary lesions were significantly higher than the ones without and values greater than 1.32 were useful in prediction of coronary lesions.

  2. Increase of bone marrow macrophages and CD8(+) T lymphocytes predict graft failure after allogeneic bone marrow or cord blood transplantation.

    Science.gov (United States)

    Kawashima, N; Terakura, S; Nishiwaki, S; Koyama, D; Ozawa, Y; Ito, M; Miyamura, K

    2017-08-01

    Graft failure (GF) remains an obstacle to survival after allogeneic hematopoietic stem cell transplantation. However, differentiating GF from delayed engraftment (DE) can be difficult. Host CD8(+) lymphocytes have been reported to mediate graft rejection, but the impact of macrophages on DE or GF is yet to be clarified. Peri-engraftment bone marrow (BM) specimens of 32 adult patients with normal engraftment, DE or GF were retrospectively evaluated to identify the potential associations of CD163(+) macrophage and CD8(+) lymphocyte infiltration into BM. The macrophage or CD8(+) lymphocyte number/total nucleated cell number was defined as the Mac ratio and CD8 ratio, respectively. Both DE and GF groups had significantly higher Mac ratios at day 14 than the normal group (PGF groups (P=1.000). The CD8 ratio at day 14 was significantly higher in the GF than in the normal group (P=0.005), whereas the CD8 ratios of the DE and normal groups were similar (P=0.07). A high Mac ratio at day 14 was associated with a risk of DE or subsequent GF. Patients with increased CD8 ratio at day 14 had a further risk of GF. The Mac ratio and the CD8 ratio appear to be well suited for predicting engraftment status.

  3. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival.

    Science.gov (United States)

    Visco, Carlo; Falisi, Erika; Young, Ken H; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca; Pizzolo, Giovanni; Ambrosetti, Achille; Rodeghiero, Francesco

    2015-07-30

    The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL.

  4. Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Luis F. Porrata

    2013-01-01

    Full Text Available Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT to predict clinical outcome in classical Hodgkin lymphoma (cHL patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years. Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS and progression-free survival (PFS compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97% versus 35% (95% CI, 19%–51%, resp., P<0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86% versus 27% (95% CI, 14%–45%, resp., P<0.0001. Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

  5. Business Bankruptcy Prediction Based on Survival Analysis Approach

    Directory of Open Access Journals (Sweden)

    Ming - Chang Lee

    2014-04-01

    Full Text Available This study sampled companies listed on Taiwan Stock Exchange that examined financial distress between 200 3 and 20 09 . It uses the survival analysis to find the main indicators which can explain the business bankruptcy in Taiwan. This paper use s the Cox P roportional H azard M odel to assess the usefulness of traditional financial ratios and market variables as predictors of the probability of business failure to a given time. This paper presents empirical results of a study regarding 12 financial ratios as predictors of business failure in Taiwan. It showed that it does not need many ratios to be able to anticipate potential business bankruptcy. T he financial distress probability model is constructed using Profitability, Leverage, Efficiency and Valuation ratio variables. In the proposed steps of business failure prediction model , it used detail SAS procedure. The study proves that t he accuracies of classification of the mode in o verall accuracy of classification are 87.93%

  6. Interoceptive Ability Predicts Survival on a London Trading Floor.

    Science.gov (United States)

    Kandasamy, Narayanan; Garfinkel, Sarah N; Page, Lionel; Hardy, Ben; Critchley, Hugo D; Gurnell, Mark; Coates, John M

    2016-09-19

    Interoception is the sensing of physiological signals originating inside the body, such as hunger, pain and heart rate. People with greater sensitivity to interoceptive signals, as measured by, for example, tests of heart beat detection, perform better in laboratory studies of risky decision-making. However, there has been little field work to determine if interoceptive sensitivity contributes to success in real-world, high-stakes risk taking. Here, we report on a study in which we quantified heartbeat detection skills in a group of financial traders working on a London trading floor. We found that traders are better able to perceive their own heartbeats than matched controls from the non-trading population. Moreover, the interoceptive ability of traders predicted their relative profitability, and strikingly, how long they survived in the financial markets. Our results suggest that signals from the body - the gut feelings of financial lore - contribute to success in the markets.

  7. Neutrophil-to-Lymphocyte Ratio in the Prediction of Microscopic Colitis

    Directory of Open Access Journals (Sweden)

    Feyzullah Ucmak

    2016-01-01

    Full Text Available Aim: The aim of this study was to investigate the importance of the neutrophil-to-lymphocyte ratio (NLR in predicting microscopic colitis (MC in patients with diarrhea-dominant type irritable bowel syndrome (IBS-D. Material and Method: Between January 1, 2010 and December 31, 2012, 49 patients who fulfilled the Roma III criteria for IBS-D were included in the study. All patients had underwent colonoscopy and colonoscopic biopsy (cecum, ascending, transverse, descending and rectosigmoid sections to diagnose MC (25 patients with MC. Complete blood count parameters were evaluated in the two groups (IBS-D and MC using standard methodology. Results: The patients were evaluated in two groups: MC and IBS-D. The groups were similar with respect to age, gender and presence of hypertension. The NLO was significantly higher in the MC group compared to the IBS-D group (2.48±0.99, 1.92±0.84; p=0.041, respectively. A cut-off value of 1.86 had a sensitivity of 76% and spesificity of 55% in predicting MC in patients with symptoms of IBS-D. Discussion: A significant association was found between the presence of MC in patients with IBS-D and increased NLR. The NLR may be a useful marker in predicting MC in patients with symptoms of IBS-D.

  8. Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

    DEFF Research Database (Denmark)

    Donskov, F; Bennedsgaard, K M; Von Der Maase, H

    2002-01-01

    The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty...... response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0...... of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients....

  9. Epstein–Barr Virus MicroRNAs are Expressed in Patients with Chronic Lymphocytic Leukemia and Correlate with Overall Survival

    Directory of Open Access Journals (Sweden)

    Alessandra Ferrajoli

    2015-06-01

    Full Text Available Although numerous studies highlighted the role of Epstein–Barr Virus (EBV in B-cell transformation, the involvement of EBV proteins or genome in the development of the most frequent adult leukemia, chronic lymphocytic leukemia (CLL, has not yet been defined. We hypothesized that EBV microRNAs contribute to progression of CLL and demonstrated the presence of EBV miRNAs in B-cells, in paraffin-embedded bone marrow biopsies and in the plasma of patients with CLL by using three different methods (small RNA-sequencing, quantitative reverse transcription PCR [q-RT-PCR] and miRNAs in situ hybridization [miRNA-ISH]. We found that EBV miRNA BHRF1-1 expression levels were significantly higher in the plasma of patients with CLL compared with healthy individuals (p < 0 · 0001. Notably, BHRF1-1 as well as BART4 expression were detected in the plasma of either seronegative or seropositive (anti-EBNA-1 IgG and EBV DNA tested patients; similarly, miRNA-ISH stained positive in bone marrow specimens while LMP1 and EBER immunohistochemistry failed to detect viral proteins and RNA. We also found that BHRF1-1 plasma expression levels were positively associated with elevated beta-2-microglobulin levels and advanced Rai stages and observed a correlation between higher BHRF1-1 expression levels and shorter survival in two independent patients' cohorts. Furthermore, in the majority of CLL cases where BHRF1-1 was exogenously induced in primary malignant B cells the levels of TP53 were reduced. Our findings suggest that EBV may have a role in the process of disease progression in CLL and that miRNA RT-PCR and miRNAs ISH could represent additional methods to detect EBV miRNAs in patients with CLL.

  10. Epstein-Barr Virus MicroRNAs are Expressed in Patients with Chronic Lymphocytic Leukemia and Correlate with Overall Survival.

    Science.gov (United States)

    Ferrajoli, Alessandra; Ivan, Cristina; Ciccone, Maria; Shimizu, Masayoshi; Kita, Yoshiaki; Ohtsuka, Masahisha; D'Abundo, Lucilla; Qiang, Jun; Lerner, Susan; Nouraee, Nazila; Rabe, Kari G; Rassenti, Laura Z; Van Roosbroeck, Katrien; Manning, John T; Yuan, Yuan; Zhang, Xinna; Shanafelt, Tait D; Wierda, William G; Sabbioni, Silvia; Tarrand, Jeffrey J; Estrov, Zeev; Radovich, Milan; Liang, Han; Negrini, Massimo; Kipps, Thomas J; Kay, Neil E; Keating, Michael; Calin, George A

    2015-06-01

    Although numerous studies highlighted the role of Epstein-Barr Virus (EBV) in B-cell transformation, the involvement of EBV proteins or genome in the development of the most frequent adult leukemia, chronic lymphocytic leukemia (CLL), has not yet been defined. We hypothesized that EBV microRNAs contribute to progression of CLL and demonstrated the presence of EBV miRNAs in B-cells, in paraffin-embedded bone marrow biopsies and in the plasma of patients with CLL by using three different methods (small RNA-sequencing, quantitative reverse transcription PCR [q-RT-PCR] and miRNAs in situ hybridization [miRNA-ISH]). We found that EBV miRNA BHRF1-1 expression levels were significantly higher in the plasma of patients with CLL compared with healthy individuals (p < 0 · 0001). Notably, BHRF1-1 as well as BART4 expression were detected in the plasma of either seronegative or seropositive (anti-EBNA-1 IgG and EBV DNA tested) patients; similarly, miRNA-ISH stained positive in bone marrow specimens while LMP1 and EBER immunohistochemistry failed to detect viral proteins and RNA. We also found that BHRF1-1 plasma expression levels were positively associated with elevated beta-2-microglobulin levels and advanced Rai stages and observed a correlation between higher BHRF1-1 expression levels and shorter survival in two independent patients' cohorts. Furthermore, in the majority of CLL cases where BHRF1-1 was exogenously induced in primary malignant B cells the levels of TP53 were reduced. Our findings suggest that EBV may have a role in the process of disease progression in CLL and that miRNA RT-PCR and miRNAs ISH could represent additional methods to detect EBV miRNAs in patients with CLL.

  11. CD49d Is the Strongest Flow Cytometry–Based Predictor of Overall Survival in Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Bulian, Pietro; Shanafelt, Tait D.; Fegan, Chris; Zucchetto, Antonella; Cro, Lilla; Nückel, Holger; Baldini, Luca; Kurtova, Antonina V.; Ferrajoli, Alessandra; Burger, Jan A.; Gaidano, Gianluca; Del Poeta, Giovanni; Pepper, Chris; Rossi, Davide; Gattei, Valter

    2014-01-01

    Purpose Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. Patients and Methods A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry–based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. Results Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry–based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. Conclusion In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry–based predictor of OS and TFS in CLL. PMID:24516016

  12. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....

  13. Significance of preoperative neutrophil–lymphocyte count ratio on predicting postoperative sepsis after percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Volkan Sen

    2016-10-01

    Full Text Available We evaluated the usefulness of preoperative neutrophil–lymphocyte count ratio (NLCR in predicting postoperative sepsis after percutaneous nephrolithotomy (PCNL. In total, 487 patients who underwent PCNL for renal stones were included in the present retrospective study. The stone burden, number of tracts and location, operation time, fluoroscopy time, presence of residual stones, and blood transfusion rates were postoperatively recorded in all patients. All patients were followed up for signs of systemic inflammatory response syndrome (SIRS and sepsis. The association of sepsis/SIRS with the risk factors of infectious complications, including NLCR, was evaluated. SIRS was detected in 91 (18.7% patients, 25 (5.1% of whom were diagnosed with sepsis. Stone burden, operation time, irrigation rate, previous surgery, nephrostomy time, access number, blood transfusion, residual stone, postoperative urinary culture, renal pelvis urinary culture, and stone culture were found to be predictive factors for SIRS and sepsis development. Receiver operating characteristic curve analysis revealed an NLCR cutoff of 2.50 for predicting the occurrence of SIRS/sepsis. We found that the incidence of sepsis was significantly higher in patients with NLCR ≥ 2.50 than in patients with NLCR < 2.50 (p = 0.006. Preoperative and postoperative urine culture positivity were associated with high NLCR (p = 0.039 and p = 0.003, respectively. We believe that preoperative NLCR may be a promising additive predictor of bacteremia and postoperative sepsis in patients who undergo PCNL for renal stones. This marker is simple, easily measured, and easy to use in daily practice without extra costs.

  14. Trends in survival of chronic lymphocytic leukemia patients in Germany and the USA in the first decade of the twenty-first century

    Directory of Open Access Journals (Sweden)

    Dianne Pulte

    2016-03-01

    Full Text Available Abstract Background Recent population-based studies in the United States of America (USA and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997–2011. Methods Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS. Results Five- and 10-year RS estimates in 2009–2011 of 80.2 and 59.5 %, respectively, in Germany and 82.4 and 64.7 %, respectively, in the USA were observed. Overall, 5-year RS increased significantly in Germany and the difference compared to the survival in the USA which slightly decreased between 2003–2005 and 2009–2011. However, age-specific analyses showed persistently higher survival for all ages except for 15–44 in the USA. In general, survival decreased with age, but the age-related disparity was small for patients younger than 75. In both countries, 5-year RS was >80 % for patients less than 75 years of age but <70 % for those age 75+. Conclusions Overall, 5-year survival for patients with CLL is good, but 10-year survival is significantly lower, and survival was much lower for those age 75+. Major differences in survival between countries were not observed. Further research into ways to increase survival for older CLL patients are needed to reduce the persistent large age-related survival disparity.

  15. Use of Tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer.

    Science.gov (United States)

    Kashiwagi, Shinichiro; Asano, Yuka; Goto, Wataru; Takada, Koji; Takahashi, Katsuyuki; Noda, Satoru; Takashima, Tsutomu; Onoda, Naoyoshi; Tomita, Shuhei; Ohsawa, Masahiko; Hirakawa, Kosei; Ohira, Masaichi

    2017-01-01

    Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker. TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively. Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063). The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

  16. Postoperative Elevation of the Neutrophil: Lymphocyte Ratio Predicts Complications Following Esophageal Resection.

    Science.gov (United States)

    Vulliamy, Paul; McCluney, Simon; Mukherjee, Samrat; Ashby, Luke; Amalesh, Thangadorai

    2016-06-01

    Complications following esophagectomy are a significant source of morbidity. The aim of this study was to investigate the utility of the neutrophil:lymphocyte ratio (NLR) in the early identification of complications following esophagectomy, as compared to other routinely available parameters. We performed a retrospective cohort study of patients undergoing Ivor-Lewis esophagectomy at a single centre. Baseline characteristics and complications occurring within the first 30 days of surgery were recorded. White blood cell counts and C-reactive protein (CRP) levels immediately following surgery (day 0) and over the subsequent three postoperative days were analysed. Sixty-five patients were included, of whom 29 (45 %) developed complications. The median NLR was similar among patients with and without a complicated recovery on day 0 (12.7 vs 13.6, p = 0.70) and day 1 (10.0 vs 9.3, p = 0.29). Patients who subsequently developed complications had a higher NLR on day 2 (11.8 vs 7.5, p 8.3 on day 2 had a sensitivity of 93 % and a specificity of 72 % for predicting complications. The NLR is a simple and routinely available parameter which has a high sensitivity in the early detection of complications following esophagectomy.

  17. Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

    2017-07-01

    This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

  18. Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.

    Science.gov (United States)

    Lutzny, Gloria; Kocher, Thomas; Schmidt-Supprian, Marc; Rudelius, Martina; Klein-Hitpass, Ludger; Finch, Andrew J; Dürig, Jan; Wagner, Michaela; Haferlach, Claudia; Kohlmann, Alexander; Schnittger, Susanne; Seifert, Marc; Wanninger, Stefan; Zaborsky, Nadja; Oostendorp, Robert; Ruland, Jürgen; Leitges, Michael; Kuhnt, Toni; Schäfer, Yvonne; Lampl, Benedikt; Peschel, Christian; Egle, Alexander; Ringshausen, Ingo

    2013-01-14

    Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-βII and the subsequent activation of NF-κB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-β knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-βII-NF-κB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-βII in biopsies from patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies.

  19. Conditional survival predictions after nephrectomy for renal cell carcinoma.

    NARCIS (Netherlands)

    Karakiewicz, P.I.; Suardi, N.; Capitanio, U.; Isbarn, H.; Jeldres, C.; Perrotte, P.; Sun, M.; Ficarra, V.; Zigeuner, R.; Tostain, J.; Mejean, A.; Cindolo, L.; Pantuck, A.J.; Belldegrun, A.S.; Zini, L.; Taille, A. De La; Chautard, D.; Descotes, J.L.; Shariat, S.F.; Valeri, A.; Mulders, P.F.A.; Lang, H.; Lechevallier, E.; Patard, J.J.

    2009-01-01

    PURPOSE: Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS: We studied 3,560 patients with renal cell carcinoma of all stag

  20. Elevated Neutrophil-to-Lymphocyte Ratio Predicts Intermediate-Term Outcomes in Patients Who Have Advanced Chronic Kidney Disease with Peripheral Artery Disease Receiving Percutaneous Transluminal Angioplasty

    Science.gov (United States)

    Chen, I-Chih; Yu, Chao-Chin; Wu, Yi-Hsuan; Chao, Ting-Hsing

    2016-01-01

    Background Inflammation plays an important role in the pathogenesis of cardiovascular disease in patients with advanced chronic kidney disease (CKD). Neutrophil-to-lymphocyte ratio (NLR), an inflammatory biomarker, has not been evaluated in patients who have advanced CKD with peripheral artery disease (PAD) undergoing percutaneous transluminal angioplasty (PTA), especially in Taiwan. Methods We retrospectively evaluated 148 advanced CKD (creatinine clearance rate ≤ 30 mL/min/1.73 m2) identified from a prospective registry in our hospital (303 PTA cases in total). Kaplan-Meier analysis with log-rank test was used to study event-free survival, and all univariables (p value Rutherford grade 6, either NLR or NLR ≥ 3.76, and a history of hypertension had a positively prognostic impact on the occurrence of primary composite endpoint, whereas higher albumin level (≥ 3.0 mg/dL) and technical success had a significantly protective effect. History of hypertension, either NLR or NLR ≥ 3.76, and age were associated with all-cause mortality. In addition, Rutherford 6, higher albumin level (≥ 3.0 mg/dL), technical success, NLR, and age could predict the occurrence of major amputation. Conclusions NLR, but not C-reactive protein or platelet-lymphocyte ratio, is an important prognostic predictor of all major clinical outcomes in patients with advanced CKD and PAD receiving PTA. Further studies are warranted to establish a better strategy and healthcare program in this clinical setting. PMID:27713601

  1. Predicting survival and morbidity-free survival to very old age

    NARCIS (Netherlands)

    R.S. Newson (Rachel); J.C.M. Witteman (Jacqueline); O.H. Franco (Oscar); B.H.Ch. Stricker (Bruno); M.M.B. Breteler (Monique); A. Hofman (Albert); H.W. Tiemeier (Henning)

    2010-01-01

    textabstractAs life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify factors that increase the chance of survival free of major morbidities. As such, the current study assessed 45 common diseas

  2. Preoperative thrombocytosis predicts poor survival in patients with glioblastoma

    Science.gov (United States)

    Brockmann, Marc A.; Giese, Alf; Mueller, Kathrin; Kaba, Finjap Janvier; Lohr, Frank; Weiss, Christel; Gottschalk, Stefan; Nolte, Ingo; Leppert, Jan; Tuettenberg, Jochen; Groden, Christoph

    2007-01-01

    Thrombocytosis, which is defined as a platelet count greater than 400 platelets/nl, has been found to be an independent predictor of shorter survival in various tumors. Release of growth factors from tumors has been proposed to increase platelet counts. Preoperative platelet counts and other clinical and hematological parameters were reviewed from the records of 153 patients diagnosed between 1999 and 2004 with histologically confirmed glioblastoma in order to evaluate the prognostic significance of preoperative thrombocytosis in these patients. The relationship between thrombocytosis and survival was initially analyzed in all patients regardless of further therapy. Univariate log-rank tests showed that the median survival time of 29 patients with preoperative thrombocytosis (19%) was significantly shorter (4 months; 95% confidence interval [95% CI], 3–6 months) compared to 124 patients with normal platelet counts (11 months; 95% CI, 8–13 months; p = 0.0006). Multivariate analysis (Cox proportional hazards model) confirmed preoperative platelet count, age, prothrombin time, and activated partial thromboplastin time to be prognostic factors of survival (all p thrombocytosis was diagnosed (6 months; 95% CI, 4–12 months) compared to patients with normal platelet count (13 months; 95% CI, 11–15 months; p = 0.0359). In multivariate analysis, age, platelet count, preoperative prothrombin time, and degree of tumor resection retained significance as prognostic factors of survival (all p thrombocytosis to be a prognostic factor associated with shorter survival time in patients with glioblastoma. PMID:17504931

  3. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    OpenAIRE

    Hannelore K. van der Burgh; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A.; van den Berg, Leonard H; Van Den Heuvel, Martijn P.

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high...

  4. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH)

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U

    1998-01-01

    Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased...... similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility........ No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were...

  5. Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia.

    Science.gov (United States)

    Mulligan, Stephen P; Karlsson, Karin; Strömberg, Mats; Jønsson, Viggo; Gill, Devinder; Hammerström, Jens; Hertzberg, Mark; McLennan, Roger; Uggla, Bertil; Norman, John; Wallvik, Jonas; Sundström, Gunnel; Johansson, Hemming; Brandberg, Yvonne; Liliemark, Jan; Juliusson, Gunnar

    2014-12-01

    We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

  6. Immune phenotypes predict survival in patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Haouraa Mostafa

    2016-09-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM, a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.

  7. Predicted Water Immersion Survival Times for Anti-Exposure Ensembles

    Science.gov (United States)

    2005-10-01

    which to determine what garments need to be worn and when. Therefore, the goal of this study was to develop a family of risk curves based on the...females who are known to lose more body heat than men3, and also does not account for wave effects, fatigue, last mealtime , injuries, attitude, etc...garments. These heat stress data combined with the immersion survivability estimates can be used to generate a family of curves to provide comprehensive

  8. The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone.

    Science.gov (United States)

    Boegemann, Martin; Schlack, Katrin; Thomes, Stefan; Steinestel, Julie; Rahbar, Kambiz; Semjonow, Axel; Schrader, Andres Jan; Aringer, Martin; Krabbe, Laura-Maria

    2017-02-11

    The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR 5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9-2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0-1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3-4.0); p 0-1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to change to change to 5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully.

  9. The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

    Science.gov (United States)

    Boegemann, Martin; Schlack, Katrin; Thomes, Stefan; Steinestel, Julie; Rahbar, Kambiz; Semjonow, Axel; Schrader, Andres Jan; Aringer, Martin; Krabbe, Laura-Maria

    2017-01-01

    The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR 5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9–2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0–1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3–4.0); p 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to 5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully. PMID:28208664

  10. Survival of the fittest clone: Pro-apoptotic protein Noxa controls selection of lymphocytes under competitive conditions

    NARCIS (Netherlands)

    Wensveen, F.M.

    2010-01-01

    Darwinistic selection, or ‘survival of the fittest’, is based on intrinsic capacity, relative to that of its competitors in a given niche. This process drives the generation of species by allowing survival of organisms in with favorable, specialized characteristics for a certain niche. However, mere

  11. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy.

    Science.gov (United States)

    Rawstron, A C; Kennedy, B; Evans, P A; Davies, F E; Richards, S J; Haynes, A P; Russell, N H; Hale, G; Morgan, G J; Jack, A S; Hillmen, P

    2001-07-01

    Previous studies have suggested that the level of residual disease at the end of therapy predicts outcome in chronic lymphocytic leukemia (CLL). However, available methods for detecting CLL cells are either insensitive or not routinely applicable. A flow cytometric assay was developed that can differentiate CLL cells from normal B cells on the basis of their CD19/CD5/CD20/CD79b expression. The assay is rapid and can detect one CLL cell in 10(4) to 10(5) leukocytes in all patients. We have compared this assay to conventional assessment in 104 patients treated with CAMPATH-1H and/or autologous transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly depleted in responding patients, but remained detectable in nonresponders. Patients with more than 0.01 x 10(9)/L circulating CLL cells always had significant (> 5%) marrow disease, and blood monitoring could be used to time marrow assessments. In 25 out of 104 patients achieving complete remission by National Cancer Institute (NCI) criteria, the detection of residual bone marrow disease at more than 0.05% of leukocytes in 6 out of 25 patients predicted significantly poorer event-free (P =.0001) and overall survival (P =.007). CLL cells are detectable at a median of 15.8 months (range, 5.5-41.8) posttreatment in 9 out of 18 evaluable patients with less than 0.05% CLL cells at end of treatment. All patients with detectable disease have progressively increasing disease levels on follow-up. The use of sensitive techniques, such as the flow assay described here, allow accurate quantitation of disease levels and provide an accurate method for guiding therapy and predicting outcome. These results suggest that the eradication of detectable disease may lead to improved survival and should be tested in future studies.

  12. Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy.

    Science.gov (United States)

    Chua, Terence C; Chong, Chanel H; Liauw, Winston; Zhao, Jing; Morris, David L

    2012-08-01

    The study examines the role inflammatory and tumor markers as biomarkers to preoperatively predict outcome in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy. Associations between baseline variables, tumor markers [CEA (carcinoembyronic antigen], CA125, CA199), inflammatory markers including neutrophils-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP) with progression-free survival (PFS) and overall survival (OS) were examined in patients undergoing surgical cytoreduction and intraperitoneal chemotherapy for epithelial appendiceal neoplasm. A total of 174 patients with epithelial appendiceal neoplasm (low-grade pseudomyxoma, n = 117; appendiceal cancer, n = 57) underwent cytoreduction. On univariate analysis, all 3 inflammatory and tumor markers predicted for both PFS and OS, respectively; NLR ≤ 2.6 (P = 0.01, P = 0.002), PLR ≤ 166 (P = 0.006, P = 0.016), CRP ≤ 12.5 (P = 0.001, P = 0.008), CEA (P 37 (P = 0.003), and a CRP > 12.5 (P = 0.013). A higher peritoneal cancer index (PCI > 24) was associated with elevation in CEA > 12, CA125 > 39, CA199 > 37, PLR > 166 and CRP > 12. The tumor histologic subtype was associated with CA 199 levels. The results from this investigation suggest that preoperative inflammatory markers in blood and serologic tumor markers may predict outcomes and are associated with tumor biology in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy treatment.

  13. Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biological therapy in psoriasis.

    Science.gov (United States)

    Jókai, Hajnalka; Szakonyi, József; Kontár, Orsolya; Barna, Gábor; Inotai, Dóra; Kárpáti, Sarolta; Holló, Péter

    2013-03-01

    A considerable number of patients with psoriasis show secondary resistance during long-term TNF-alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte-associated antigen (CLA) was investigated. Thirty-eight severe patients with psoriasis were treated for a 24-week-long study period. Clinical responsiveness (PASI) and changes in flow cytometry-measured peripheral lymphocyte CLA expression (week 0-2-6) were statistically analysed. Regarding 24-week-long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF-alpha inhibitor therapy in psoriasis.

  14. Pre-transplant quality of life does not predict survival after lung transplantation

    NARCIS (Netherlands)

    Vermeulen, Karin M.; TenVergert, Elisabeth M.; Verschuuren, Erik A. M.; Erasmus, Michiel E.; van der Bij, Wim

    2008-01-01

    Background: Currently, the goal of lung transplantation is not only to improve survival but also includes' improvement of health-related quality of life (HRQL). Limited knowledge is available about the value of HRQL before lung transplantation with regard to predicting survival after lung transplant

  15. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data

  16. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data

  17. Predicting survival of Salmonella in low-water activity foods: an analysis of literature data.

    Science.gov (United States)

    Santillana Farakos, Sofia M; Schaffner, Donald W; Frank, Joseph F

    2014-09-01

    Factors such as temperature, water activity (aw), substrate, culture media, serotype, and strain influence the survival of Salmonella in low-aw foods. Predictive models for Salmonella survival in low-aw foods at temperatures ranging from 21 to 80(u) C and water activities below 0.6 were previously developed. Literature data on survival of Salmonella in low-aw foods were analyzed in the present study to validate these predictive models and to determine global influencing factors. The results showed the Weibull model provided suitable fits to the data in 75% of the curves as compared with the log-linear model. The secondary models predicting the time required for log-decimal reduction (log δ) and shape factor (log β) values were useful in predicting the survival of Salmonella in low-aw foods. Statistical analysis indicated overall fail-safe secondary models, with 88% of the residuals in the acceptable and safe zones (foods and its influencing factors.

  18. Prediction of survival in patients with Stage IV kidney cancer

    Directory of Open Access Journals (Sweden)

    L. V. Mirilenko

    2015-01-01

    Full Text Available The efficiency of treatment was evaluated and the predictors of adjusted survival (AS were identified in patients with disseminated kidney cancer treated at the Republican Research and Practical Center for Oncology and Medical Radiology in 1999 to 2011 (A.E. Okeanov, P.I. Moiseev, L.F. Levin. Malignant tumors in Belarus, 2001–2012. Edited by O.G. Sukonko. Seven factors (regional lymph node metastases; distant bone metastases; a high-grade tumor; sarcomatous tumor differentiation; hemoglobin levels of < 125 g/l in women and < 150 g/l in men; an erythrocyte sedimentation rate of 40 mm/h; palliative surgery were found to have an independent, unfavorable impact on AS. A multidimensional model was built to define what risk group low (no more than 2 poor factors, moderate (3–4 poor factors, and high (more than 4 poor factors the patients with Stage IV kidney cancer belonged to. In these groups, the median survival was 34.7, 17.2, and 4.0 months and 3-year AS rates were 48.6, 24.6, and 3.2 %, respectively. 

  19. Predicting survival of pancreatic cancer patients treated with gemcitabine using longitudinal tumour size data.

    Science.gov (United States)

    Wendling, Thierry; Mistry, Hitesh; Ogungbenro, Kayode; Aarons, Leon

    2016-05-01

    Measures derived from longitudinal tumour size data have been increasingly utilised to predict survival of patients with solid tumours. The aim of this study was to examine the prognostic value of such measures for patients with metastatic pancreatic cancer undergoing gemcitabine therapy. The control data from two Phase III studies were retrospectively used to develop (271 patients) and validate (398 patients) survival models. Firstly, 31 baseline variables were screened from the training set using penalised Cox regression. Secondly, tumour shrinkage metrics were interpolated for each patient by hierarchical modelling of the tumour size time-series. Subsequently, survival models were built by applying two approaches: the first aimed at incorporating model-derived tumour size metrics in a parametric model, and the second simply aimed at identifying empirical factors using Cox regression. Finally, the performance of the models in predicting patient survival was evaluated on the validation set. Depending on the modelling approach applied, albumin, body surface area, neutrophil, baseline tumour size and tumour shrinkage measures were identified as potential prognostic factors. The distributional assumption on survival times appeared to affect the identification of risk factors but not the ability to describe the training data. The two survival modelling approaches performed similarly in predicting the validation data. A parametric model that incorporates model-derived tumour shrinkage metrics in addition to other baseline variables could predict reasonably well survival of patients with metastatic pancreatic cancer. However, the predictive performance was not significantly better than a simple Cox model that incorporates only baseline characteristics.

  20. Pretreatment Lymphocyte Monocyte Ratio Predicts Long-Term Outcomes in Patients with Digestive System Tumor: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jingwen Zhang

    2016-01-01

    Full Text Available Purpose. The prognostic value of pretreatment lymphocyte monocyte ratio (LMR in digestive system cancer patients remains controversial. The aim of this study was to quantify the prognostic impact of this biomarker and assess its consistency in digestive system tumors. Methods. We searched “PubMed,” “Embase,” and “CBM” for published eligible studies before June 2016 and conducted a meta-analysis to estimate the pooled hazard ratios (HRs for disease recurrence and mortality focusing on LMR. Subgroup analyses, meta-regression, and sensitivity analyses were also performed. Results. A total of 22 cohort studies enrolling 12829 patients with digestive system cancer were included. The summary results showed that lower LMR was significantly associated with worse overall survival (OS, cancer-specific survival (CSS, and tumor disease or recurrence-free survival (DFS/RFS in analyses using the studies reporting HRs either by the univariate analyses (HR = 1.32, HR = 1.35, and HR = 1.26 for OS, CSS, and DFS/RFS, resp. or by multivariate analyses (HR = 1.21, HR = 1.18, and HR = 1.26 for OS, CSS, and DFS/RFS, resp.. Conclusion. Our results support the fact that decreased LMR indicates worse prognosis in multiple digestive system tumors.

  1. Application of Artificial Neural Network in Predicting the Survival Rate of Gastric Cancer Patients

    OpenAIRE

    Biglarian, A; E. Hajizadeh; Kazemnejad, A; Zali, MR

    2011-01-01

    "nBackground: The aim of this study was to predict the survival rate of Iranian gastric cancer patients using the Cox proportional hazard and artificial neural network models as well as comparing the ability of these approaches in predicting the survival of these patients."nMethods: In this historical cohort study, the data gathered from 436 registered gastric cancer patients who have had surgery between 2002 and 2007 at the Taleghani Hospital (a referral center for gastrointestinal...

  2. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    OBJECTIVE: To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis. DESIGN: A prospective study of mortality in patients with sepsis whose serum levels of sL-selectin were measured on admission to an intensive care unit (ICU) and 4 days later. Follow-up data...... organs, and 14 control subjects. MEASUREMENTS AND RESULTS: On admission to the ICU the Simplified Acute Physiology Score (SAPS) II was calculated, and relevant microbial cultures were performed. Mortality was registered at various follow-up points: 7 days after admission, at discharge from hospital......, and 3 and 12 months after admission. Serum sL-selectin levels were significantly lower in the patients than in the controls. Sepsis nonsurvivors had significantly lower levels than survivors. Efficiency analysis and receiver operation characteristics showed that the ideal cutoff point for s...

  3. The oncogene DEK promotes leukemic cell survival and is downregulated by both Nutlin-3 and chlorambucil in B-chronic lymphocytic leukemic cells.

    Science.gov (United States)

    Secchiero, Paola; Voltan, Rebecca; di Iasio, Maria Grazia; Melloni, Elisabetta; Tiribelli, Mario; Zauli, Giorgio

    2010-03-15

    To characterize the role of the oncogene DEK in modulating the response to either Nutlin-3, a small-molecule inhibitor of the MDM2/p53 interaction, or chlorambucil in primary B-chronic lymphocytic leukemia (B-CLL) cells. DEK mRNA and protein levels were evaluated in primary B-CLL samples (n = 21), p53(wild-type) SKW6.4, p53(mutated) BJAB lymphoblastoid cell lines, and normal CD19(+) B lymphocytes-treated Nutlin-3 or chlorambucil (10 micromol/L, each). Knocking down experiments with either p53 or DEK small interfering RNA (siRNA) were done to investigate the potential role of p53 in controlling the expression of DEK and the role of DEK in leukemic cell survival/apoptosis. Both Nutlin-3 and chlorambucil downregulated DEK in primary B-CLL samples (n = 21) and SKW6.4 but not in BJAB cells. Knocking down p53 attenuated the effect of Nutlin-3 on DEK expression, whereas knocking down DEK significantly increased both spontaneous and Nutlin-3-induced apoptosis. Conversely, counteracting DEK downmodulation by using p53 small interfering RNA reduced Nutlin-3-mediated apoptosis. On the other hand, Nutlin-3 potently induced p53 accumulation, but it did not affect DEK levels in normal CD19(+) B lymphocytes. These data show that the downregulation of DEK in response to either Nutlin-3 or chlorambucil represents an important molecular determinant in the cytotoxic response of leukemic cells, and suggest that strategies aimed to downregulate DEK might improve the therapeutic potential of these drugs.

  4. CD137 is induced by the CD40 signal on chronic lymphocytic leukemia B cells and transduces the survival signal via NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Yukana Nakaima

    Full Text Available CD137 is a member of the tumor necrosis factor receptor family that is expressed on activated T cells. This molecule provides a co-stimulatory signal that enhances the survival, and differentiation of cells, and has a crucial role in the development of CD8 cytotoxic T cells and anti-tumor immunity. Here we report that CD137 expression is also induced on normal or malignant human B cells by CD40 ligation by its ligand CD154. This CD137 induction was more prominent in chronic lymphocytic leukemia (CLL cells than in other types of B cells. CD137 stimulation on B cells by its ligand induced the nuclear translocation of p52 (a non-canonical NF-κB factor. In agreement with this finding, expression of the survival factor BCL-XL was upregulated. Consequently, the CD137 signal augmented the survival of CD154-stimulated CLL B cells in vitro. This unexpected induction of CD137 on B cells by CD40 signal may influence the clinical course of CLL.

  5. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science.

    Science.gov (United States)

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

    2016-01-01

    One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets.

  6. Respiratory Muscle Strength as a Predictive Biomarker for Survival in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Polkey, Michael I; Lyall, Rebecca A; Yang, Ke; Johnson, Erin; Leigh, P Nigel; Moxham, John

    2017-01-01

    Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would facilitate the development of novel drugs. Although respiratory muscle weakness is a known predictor of poor prognosis, a comprehensive comparison of different tests is lacking. To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years. From a previously published report respiratory muscle strength measurements were available for 78 patients with ALS. Time to death and/or ventilation were ascertained. Receiver operating characteristic analysis was used to determine the cutoff point of each parameter. Each respiratory muscle strength assessment individually achieved statistical significance for prediction of survival or ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and maximal static expiratory mouth pressure were significant predictors of ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure for absolute survival. Although all measures had good specificity, there were differing sensitivities. All cutoff points for the VC were greater than 80% of normal, except for prediction of 3-month outcomes. Sequential data showed a linear decline for direct measures of respiratory muscle strength, whereas VC showed little to no decline until 12 months before death/ventilation. The most powerful biomarker for mortality stratification was Tw Pdi, but the predictive power of sniff nasal inspiratory pressure was also excellent. A VC within normal range suggested a good prognosis at 3 months but was of little other value.

  7. A simple protein-energy wasting score predicts survival in maintenance hemodialysis patients.

    Science.gov (United States)

    Moreau-Gaudry, Xavier; Jean, Guillaume; Genet, Leslie; Lataillade, Dominique; Legrand, Eric; Kuentz, François; Fouque, Denis

    2014-11-01

    Nutritional status is a powerful predictor of survival in maintenance hemodialysis patients but remains challenging to assess. We defined a new Protein Energy Wasting (PEW) score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008. This score, graded from 0 (worse) to 4 (best) was derived from 4 body nutrition compartments: serum albumin, body mass index, a normalized serum creatinine value, and protein intake as assessed by nPNA. We applied this score to 1443 patients from the ARNOS prospective dialysis cohort and provide survival data from 2005 until 2008. Patients survival at 3.5 year. Survival ranged from 84%-69% according to the protein-energy wasting score. There was a clear-cut reduction in survival (5%-7%; P < 0.01) for each unit decrement in the score grade. There was a 99% survival at 1 year for patients with the score of 4. In addition, the 6-month variation of this PEW score also strongly predicted patients' survival (P < 0.01). A new simple and easy-to-get PEW score predicts survival in maintenance hemodialysis patients. Furthermore, increase of this nutritional score over time also indicates survival improvement, and may help to better identify subgroups of patients with a high mortality rate, in which nutrition support should be enforced. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. Does Metastatic Lymph Node SUVmax Predict Survival in Patients with Esophageal Cancer?

    Directory of Open Access Journals (Sweden)

    Betül Vatankulu

    2015-10-01

    Full Text Available Objective: We aimed to investigate the SUVmax of primary tumor and metastatic lymph node in predicting survival in patients with esophageal cancer. Methods: We retrospectively analyzed patients with esophageal cancer between 2009 and 2011 who had FDG positronemission tomography (PET/computed tomography (CT. All patients were followed-up to 2013. Clinical staging, SUVmax of primary tumor and metastatic lymph node were evaluated. Results: One hundred seven patients were included in the study. All patients were followed-up between 2 and 49 months. The mean SUVmax of primary tumor and metastatic lymph node were 19.3±8.8 and 10.4±9.1, respectively. Metastatic lymph node SUVmax had an effect in predicting survival whereas primary tumor SUVmax did not have an effect (p=0.014 and p=0.262, respectively. Multivariate Cox regression analysis showed that clinical stage of the disease was the only independent factor predicting survival (p=0.001. Conclusion: Among patients with esophageal cancer, the value of primary tumor SUVmax did not have an effect on survival. Clinical stage assessed with FDG PET/CT imaging was found to predict survival in esophageal carcinoma. Additionally, lymph node SUVmax was identified as a new parameter in predicting survival in the present study

  9. Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs

    Directory of Open Access Journals (Sweden)

    Lara Pedro C

    2009-11-01

    Full Text Available Abstract Background Cervical cancer is treated mainly by surgery and radiotherapy. Toxicity due to radiation is a limiting factor for treatment success. Determination of lymphocyte radiosensitivity by radio-induced apoptosis arises as a possible method for predictive test development. The aim of this study was to analyze radio-induced apoptosis of peripheral blood lymphocytes. Methods Ninety four consecutive patients suffering from cervical carcinoma, diagnosed and treated in our institution, and four healthy controls were included in the study. Toxicity was evaluated using the Lent-Soma scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24, 48 and 72 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide to determine early and late apoptosis. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Results Radiation-induced apoptosis (RIA increased with radiation dose and time of incubation. Data strongly fitted to a semi logarithmic model as follows: RIA = βln(Gy + α. This mathematical model was defined by two constants: α, is the origin of the curve in the Y axis and determines the percentage of spontaneous cell death and β, is the slope of the curve and determines the percentage of cell death induced at a determined radiation dose (β = ΔRIA/Δln(Gy. Higher β values (increased rate of RIA at given radiation doses were observed in patients with low sexual toxicity (Exp(B = 0.83, C.I. 95% (0.73-0.95, p = 0.007; Exp(B = 0.88, C.I. 95% (0.82-0.94, p = 0.001; Exp(B = 0.93, C.I. 95% (0.88-0.99, p = 0.026 for 24, 48 and 72 hours respectively. This relation was also found with rectal (Exp(B = 0.89, C.I. 95% (0.81-0.98, p = 0.026; Exp(B = 0.95, C.I. 95% (0.91-0.98, p = 0.013 for 48 and 72 hours respectively and urinary (Exp(B = 0.83, C.I. 95% (0.71-0.97, p = 0.021 for 24 hours toxicity. Conclusion Radiation induced apoptosis at different time points and radiation

  10. Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival

    Directory of Open Access Journals (Sweden)

    Silverman Lee

    2007-07-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 causes adult T-cell leukemia/lymphoma and is linked to a number of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13 and p30, whose roles are still being defined in the virus life cycle and in HTLV-1 virus-host cell interactions. Proviral clones of HTLV-1 with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. p30 expressed exogenously differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and while acting as a repressor of many genes including Tax, in part by blocking tax/rex RNA nuclear export, selectively enhances key gene pathways involved in T-cell signaling/activation. Results Herein, we analyzed the role of p30 in cell cycle regulation. Jurkat T-cells transduced with a p30 expressing lentivirus vector accumulated in the G2-M phase of cell cycle. We then analyzed key proteins involved in G2-M checkpoint activation. p30 expression in Jurkat T-cells resulted in an increase in phosphorylation at serine 216 of nuclear cell division cycle 25C (Cdc25C, had enhanced checkpoint kinase 1 (Chk1 serine 345 phosphorylation, reduced expression of polo-like kinase 1 (PLK1, diminished phosphorylation of PLK1 at tyrosine 210 and reduced phosphorylation of Cdc25C at serine 198. Finally, primary human lymphocyte derived cell lines immortalized by a HTLV-1 proviral clone defective in p30 expression were more susceptible to camptothecin induced apoptosis. Collectively these data are consistent with a cell survival role of p30 against genotoxic insults to HTLV-1 infected lymphocytes. Conclusion Collectively, our data are the first to indicate that HTLV-1 p30 expression results in activation of the G2-M cell cycle checkpoint, events that would promote early viral spread and T

  11. Unbiased Prediction and Feature Selection in High-Dimensional Survival Regression

    Science.gov (United States)

    Laimighofer, Michael; Krumsiek, Jan; Theis, Fabian J.

    2016-01-01

    Abstract With widespread availability of omics profiling techniques, the analysis and interpretation of high-dimensional omics data, for example, for biomarkers, is becoming an increasingly important part of clinical medicine because such datasets constitute a promising resource for predicting survival outcomes. However, early experience has shown that biomarkers often generalize poorly. Thus, it is crucial that models are not overfitted and give accurate results with new data. In addition, reliable detection of multivariate biomarkers with high predictive power (feature selection) is of particular interest in clinical settings. We present an approach that addresses both aspects in high-dimensional survival models. Within a nested cross-validation (CV), we fit a survival model, evaluate a dataset in an unbiased fashion, and select features with the best predictive power by applying a weighted combination of CV runs. We evaluate our approach using simulated toy data, as well as three breast cancer datasets, to predict the survival of breast cancer patients after treatment. In all datasets, we achieve more reliable estimation of predictive power for unseen cases and better predictive performance compared to the standard CoxLasso model. Taken together, we present a comprehensive and flexible framework for survival models, including performance estimation, final feature selection, and final model construction. The proposed algorithm is implemented in an open source R package (SurvRank) available on CRAN. PMID:26894327

  12. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  13. [Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer].

    Science.gov (United States)

    Xu, W J; Kang, Y M; Zhou, L; Chen, F F; Song, Y H; Zhang, C Q

    2017-02-23

    Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

  14. Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients.

    Science.gov (United States)

    Nicolasjilwan, Manal; Hu, Ying; Yan, Chunhua; Meerzaman, Daoud; Holder, Chad A; Gutman, David; Jain, Rajan; Colen, Rivka; Rubin, Daniel L; Zinn, Pascal O; Hwang, Scott N; Raghavan, Prashant; Hammoud, Dima A; Scarpace, Lisa M; Mikkelsen, Tom; Chen, James; Gevaert, Olivier; Buetow, Kenneth; Freymann, John; Kirby, Justin; Flanders, Adam E; Wintermark, Max

    2015-07-01

    The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type. The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients' clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis. The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679±0.068, Akaike's information criterion 566.7, P<0.001). A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Addition of MR Imaging Features and Genetic Biomarkers Strengthen Glioblastoma Survival Prediction in TCGA Patients

    Science.gov (United States)

    Nicolasjilwan, Manal; Hu, Ying; Yan, Chunhua; Meerzaman, Daoud; Holder, Chad A.; Gutman, David; Jain, Rajan; Colen, Rivka; Rubin, Daniel L.; Zinn, Pascal O.; Hwang, Scott N.; Raghavan, Prashant; Hammoud, Dima A; Scarpace, Lisa M; Mikkelsen, Tom; Chen, James; Gevaert, Olivier; Buetow, Kenneth; Freymann, John; Kirby, Justin; Flanders, Adam E.; Wintermark, Max

    2017-01-01

    PURPOSE The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type. METHODS The study was conducted leveraging the Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients’ clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis. RESULTS The features that were significantly associated with survival were: 1) clinical factors: chemotherapy; 2) imaging: proportion of tumor contrast enhancement on MRI, and 3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679 ± 0.068, Akaike’s information criterion 566.7, p < 0.001). CONCLUSION A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM. PMID:24997477

  16. Ion channel gene expression predicts survival in glioma patients.

    Science.gov (United States)

    Wang, Rong; Gurguis, Christopher I; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

    2015-08-03

    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.

  17. Predictive value of platelet-to-lymphocyte ratio in exacerbation of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Karadeniz, Gülistan; Aktoğu, Serir; Erer, Onur Fevzi; Kır, Serpil Bulaç; Doruk, Sibel; Demir, Melike; Sonat, Kübra

    2016-07-01

    We aimed to assess the platelet-to-lymphocyte ratio (PLR) and platelet parameters in patients with chronic obstructive pulmonary disease (COPD). A total of 60 stable COPD patients, 50 acute exacerbation COPD patients and 50 healthy controls were enrolled in this study. The platelet distribution width and PLR were higher and the mean platelet volume was lower in the COPD patients during acute exacerbation compared with the stable patients and controls. The PLR was negatively correlated with the forced expiratory volume in 1 s. The PLR may be used as a useful and easily accessible tool for evaluating the ongoing inflammation during stable period and the disease severity during acute exacerbations in COPD patients.

  18. For prediction of elder survival by a Gompertz model, number dead is preferable to number alive.

    Science.gov (United States)

    Easton, Dexter M; Hirsch, Henry R

    2008-12-01

    The standard Gompertz equation for human survival fits very poorly the survival data of the very old (age 85 and above), who appear to survive better than predicted. An alternative Gompertz model based on the number of individuals who have died, rather than the number that are alive, at each age, tracks the data more accurately. The alternative model is based on the same differential equation as in the usual Gompertz model. The standard model describes the accelerated exponential decay of the number alive, whereas the alternative, heretofore unutilized model describes the decelerated exponential growth of the number dead. The alternative model is complementary to the standard and, together, the two Gompertz formulations allow accurate prediction of survival of the older as well as the younger mature members of the population.

  19. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma.

    Science.gov (United States)

    Keizman, Daniel; Ish-Shalom, Maya; Huang, Peng; Eisenberger, Mario A; Pili, Roberto; Hammers, Hans; Carducci, Michael A

    2012-01-01

    Sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). The neutrophil to lymphocyte ratio (NLR), an index of systemic inflammation, is associated with outcome in several cancer types. To study the association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival (PFS) and overall survival (OS) of patients treated with sunitinib for mRCC. We retrospectively studied an unselected cohort of patients with mRCC, who were treated with sunitinib. Logistic regression model was used to analyse response rate. Cox regression models were fitted to identify risk factors associated with PFS and OS. We investigated how pre-treatment NLR is associated with these clinical outcomes after adjusting for confounding covariates. Regression tree for censored data method was used to find the best NLR cut-off value. Between 2004 and 2011, 133 patients with mRCC were treated with sunitinib. One hundred and nine were included in the NLR analysis, from which were excluded patients without available data on pre-treatment NLR or with comorbidities/recent treatments known to be associated with a change of blood counts. Factors associated with PFS were low NLR ≤ 3 (HR = 0.285, p HR = 0.38, p = 0.035), sunitinib dose reduction/treatment interruption (HR = 0.6, p = 0.014) and the use of antiotensin system inhibitors (HR = 0.537, p = 0.008). Low NLR ≤ 3 was associated with OS (HR = 0.3, p = 0.043). In patients with mRCC treated with sunitinib, pre-treatment NLR may be associated with PFS and OS. This should be investigated prospectively, and if validated applied in clinical practice and clinical trials. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Genomic Variation by Whole-Genome SNP Mapping Arrays Predicts Time-to-Event Outcome in Patients with Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Schweighofer, Carmen D.; Coombes, Kevin R.; Majewski, Tadeusz; Barron, Lynn L.; Lerner, Susan; Sargent, Rachel L.; O'Brien, Susan; Ferrajoli, Alessandra; Wierda, William G.; Czerniak, Bogdan A.; Medeiros, L. Jeffrey; Keating, Michael J.; Abruzzo, Lynne V.

    2013-01-01

    Genomic abnormalities, such as deletions in 11q22 or 17p13, are associated with poorer prognosis in patients with chronic lymphocytic leukemia (CLL). We hypothesized that unknown regions of copy number variation (CNV) affect clinical outcome and can be detected by array-based single-nucleotide polymorphism (SNP) genotyping. We compared SNP genotypes from 168 untreated patients with CLL with genotypes from 73 white HapMap controls. We identified 322 regions of recurrent CNV, 82 of which occurred significantly more often in CLL than in HapMap (CLL-specific CNV), including regions typically aberrant in CLL: deletions in 6q21, 11q22, 13q14, and 17p13 and trisomy 12. In univariate analyses, 35 of total and 11 of CLL-specific CNVs were associated with unfavorable time-to-event outcomes, including gains or losses in chromosomes 2p, 4p, 4q, 6p, 6q, 7q, 11p, 11q, and 17p. In multivariate analyses, six CNVs (ie, CLL-specific variations in 11p15.1-15.4 or 6q27) predicted time-to-treatment or overall survival independently of established markers of prognosis. Moreover, genotypic complexity (ie, the number of independent CNVs per patient) significantly predicted prognosis, with a median time-to-treatment of 64 months versus 23 months in patients with zero to one versus two or more CNVs, respectively (P = 3.3 × 10−8). In summary, a comparison of SNP genotypes from patients with CLL with HapMap controls allowed us to identify known and unknown recurrent CNVs and to determine regions and rates of CNV that predict poorer prognosis in patients with CLL. PMID:23273604

  1. Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Christensen, Karina; Offenberg, Hanne Kjær

    2009-01-01

    In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas...... with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival...

  2. Introduction of a prediction model to assigning periodontal prognosis based on survival rates.

    Science.gov (United States)

    Martinez-Canut, Pedro; Alcaraz, Jaime; Alcaraz, Jaime; Alvarez-Novoa, Pablo; Alvarez-Novoa, Carmen; Marcos, Ana; Noguerol, Blas; Noguerol, Fernando; Zabalegui, Ion

    2017-09-04

    To develop a prediction model for tooth loss due to periodontal disease (TLPD) in patients following periodontal maintenance (PM), and assess its performance using a multicentre approach. A multilevel analysis of eleven predictors of TLPD in 500 patients following PM was carried out to calculate the probability of TLPD. This algorithm was applied to three different TLPD samples (369 teeth) gathered retrospectively by nine periodontist, associating several intervals of probability with the corresponding survival rates, based on significant differences in the mean survival rates. The reproducibility of these associations was assessed in each sample (One-way ANOVA and pair-wise comparison with Bonferroni corrections). The model presented high specificity and moderate sensitivity, with optimal calibration and discrimination measurements. Seven intervals of probability were associated with seven survival rates and these associations contained close to 80% of the cases: the probability predicted the survival rate at this percentage. The model performed well in the three samples, since the mean survival rates of each association were significantly different within each sample, while no significant differences between the samples were found in pair-wise comparisons of means. This model might be useful for predicting survival rates in different TLPD samples This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    Science.gov (United States)

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

    2017-04-01

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

  4. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  5. Impact of MELD score in predicting short-term survival after primary liver transplantation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the efficacy of model for end-stage liver disease (MEL D) in predicting short-term outcomes in patients undergoing liver transplantation (LT). Methods: The consecutive 62 patients who had received primary LT in our hospital from November 2000 to January 2005 were retrospectively analyzed. The pretransplantation MELD and Child-Turcotte-Pugh (CTP) scores of these patients were calculated. Concordance c-statistic was used to assess the efficacies of MELD and CTP scores in predicting the first posttransplantation 3-month survival rate. Results: Among the 62 patients receiving primary LT, 12 died during the first 3-month period and the posttransplantation 3-month survival rate was 80.65%. The 3-month survival rate predicted by using CTP score and MELD score was0.685 and 0.873, respectively. Unlike CTP calssification, MELD score indentified two subgroups of patients with CTP C with different overall survival (0.8824 vs 0.4545, χ2 = 7.00, P = 0.0081). Conclusion: Our present study shows that MELD score could offer more accurate prediction for short-term survival in patients who undergo primary LT than CTP score.

  6. Body Composition Predicts Survival in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

    Science.gov (United States)

    Parikh, Neehar D; Zhang, Peng; Singal, Amit G; Derstine, Brian A; Krishnamurthy, Venkat; Barman, Pranab; Waljee, Akbar K; Su, Grace L

    2017-06-01

    The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize analytic morphomics, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival. We included patients from a single center (Ann Arbor VA) who had TACE as the primary treatment for HCC and had a pre-treatment CT scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of one-year survival. were validated in an external cohort (University of Michigan Health System) of HCC patients who underwent TACE as their primary treatment. In the 75 patients in the derivation cohort, median survival was 439 (IQR: 377-685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (phepatic decompensation after TACE (phepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.

  7. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Ankita Singh Rathore

    2014-01-01

    Full Text Available Background & objectives: Tumour infiltrating lymphocytes (TILs represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome. Methods: Immunohistochemistry (IHC was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively. Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++ CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001 showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001 and CD8+ (OR=2.58, 95% CI=1.55-5.86, p0 =0.001 the least when compared to respective low (+ counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, p0 <0.001 showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, p0 <0.001 and CD3+ (OR=2.45, 95% CI=1.53-6.73, p0 =0.002 the least. Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer.

  8. Non-Hodgkin's lymphoma, poorly differentiated lymphocytic and mixed cell types. Results of sequential staging procedures, response to therapy, and survival of 100 patients

    Energy Technology Data Exchange (ETDEWEB)

    Bitran, J.D.; Golomb, H.M.; Ultmann, J.E.

    1978-07-01

    The results of sequential staging procedures including laparotomy, radiotherapy, and combination chemotherapy are reported for 100 patients with poorly differentiated lymphocytic (PDL) and mixed cell (MC) non-Hodgkin's lymphoma (NHL). Twelve patients were found to have localized disease, pathologic stage (PS) I or II; 88 patients had PS III or IV disease. Bone marrow biopsy showed a high incidence of involvement and advanced 34% of the patients from PS I, II, and III to PS IV. Staging laparotomy has a very limited role in the evaluation of these patients. All of 12 patients with PS I and II NHL were treated with radiotherapy; at 5 years, they had 100% survival, 80% being disease-free. Fifteen patients with PS III disease were treated with total nodal radiotherapy (TNRT) alone and had a median disease-free survival of 41 months. The remaining patients with PS III and IV disease were treated with chemotherapy consisting of vincristine and prednisone (V and P); cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (COPP); cyclophosphamide, vincristine (Oncovin), adriamycin, and prednisone (COPA); or palliative therapy consisting of chlorambucil and prednisone. Two-year and 4-year survivals for patients with diffuse lymphoma were 93% and 60%, respectively; for patients with +2 nodular lymphoma, 80% and 30%; and for patients with nodular lymphomas, 76 to 93% and 50%, respectively. Treatment with COPP showed no advantage over V and P, palliative therapy, or TNRT for patients with +2 nodular and nodular disease. The likelihood of cure appears most promising for patients in complete remission (CR) with diffuse lymphoma; patients in CR with nodular lymphoma show a high rate of relapse over 5 years of observation. We conclude that staging laparotomy in PDL and MC NHL is of limited value, and that the role of aggressive chemotherapy for patients with +2 nodular and nodular lymphoma needs to be redefined.

  9. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis.

    Science.gov (United States)

    van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high-resolution diffusion-weighted and T1-weighted images were acquired at the first visit to the outpatient clinic. Next, each of the patients was monitored carefully and survival time to death was recorded. Patients were labeled as short, medium or long survivors, based on their recorded time to death as measured from the time of disease onset. In the deep learning procedure, the total group of 135 patients was split into a training set for deep learning (n = 83 patients), a validation set (n = 20) and an independent evaluation set (n = 32) to evaluate the performance of the obtained deep learning networks. Deep learning based on clinical characteristics predicted survival category correctly in 68.8% of the cases. Deep learning based on MRI predicted 62.5% correctly using structural connectivity and 62.5% using brain morphology data. Notably, when we combined the three sources of information, deep learning prediction accuracy increased to 84.4%. Taken together, our findings show the added value of MRI with respect to predicting survival in ALS, demonstrating the advantage of deep learning in disease prognostication.

  10. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Hannelore K. van der Burgh

    2017-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high-resolution diffusion-weighted and T1-weighted images were acquired at the first visit to the outpatient clinic. Next, each of the patients was monitored carefully and survival time to death was recorded. Patients were labeled as short, medium or long survivors, based on their recorded time to death as measured from the time of disease onset. In the deep learning procedure, the total group of 135 patients was split into a training set for deep learning (n = 83 patients, a validation set (n = 20 and an independent evaluation set (n = 32 to evaluate the performance of the obtained deep learning networks. Deep learning based on clinical characteristics predicted survival category correctly in 68.8% of the cases. Deep learning based on MRI predicted 62.5% correctly using structural connectivity and 62.5% using brain morphology data. Notably, when we combined the three sources of information, deep learning prediction accuracy increased to 84.4%. Taken together, our findings show the added value of MRI with respect to predicting survival in ALS, demonstrating the advantage of deep learning in disease prognostication.

  11. Cardiopulmonary exercise factors predict survival in patients with advanced interstitial lung disease referred for lung transplantation.

    Science.gov (United States)

    Layton, Aimee M; Armstrong, Hilary F; Kim, Hanyoung P; Meza, Kimbery S; D'Ovidio, Frank; Arcasoy, Selim M

    2017-05-01

    The purpose of this work was to determine if parameters assessed during Cardiopulmonary Exercise Testing (CPET) while using supplemental oxygen can independently predict one-year transplant-free survival in patients with Interstitial Lung Disease (ILD) referred for lung transplant evaluation. We performed a chart review of patients with ILD who completed CPET with 30% FiO2 and gathered spirometry, pulmonary hemodynamic, six-minute walk, and CPET data. The primary end-point was death or lung transplantation within one-year of CPET. The final data set included 192 patients. 79 patients died/underwent transplant, 113 survived transplant-free. Multivariable Cox regression revealed peak workload % predicted, nadir CPET SpO2, and FVC% predicted as independent predictors of one-year transplant-free survival. Of the independent predictors of survival, receiver operating characteristics analysis revealed peak workload %predicted cutoff of 35% to be highly discriminatory, more so than nadir CPET SpO2 or FVC % predicted in identifying patients at risk for one-year mortality or transplant (peak workload % predicted < 35% HR = 4.71, 95% CI = 2.64-8.38 and area under the curve (AUC) = 0.740, nadir CPET SpO2 < 86% HR = 2.27, 95%CI = 1.41-3.68, AUC = 0.645, FVC %predicted <45% HR = 1.82, 95% CI = 1.15-2.87, AUC = 0.624). Peak workload % predicted, nadir CPET SpO2, and FVC% predicted in ILD patients referred for lung transplant evaluation are independently predictive of one-year mortality or need for transplant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Improved survival prediction from lung function data in a large population sample

    DEFF Research Database (Denmark)

    Miller, M.R.; Pedersen, O.F.; Lange, P.

    2008-01-01

    mortality in the Copenhagen City Heart Study data. Cox regression models were derived for survival over 25 years in 13,900 subjects. Age on entry, sex, smoking status, body mass index, previous myocardial infarction and diabetes were putative predictors together with FEV1 either as raw data, standardised....... In univariate predictions of all cause mortality the HR for FEV1/ht(2) categories was 2-4 times higher than those for FEV1PP and 3-10 times higher for airway related tung disease mortality. We conclude that FEV1/ht(2) is superior to FEV1PP for predicting survival. in a general population and this method...

  13. How well does pathologic stage predict survival for esophageal adenocarcinoma after neoadjuvant therapy?

    Science.gov (United States)

    Nelson, Rebecca A.; Kim, Joseph; Raz, Dan

    2015-01-01

    Background Cancer staging systems are designed to predict survival and stratify patients. The 7th edition of the American Joint Commission on Cancer (AJCC7) staging system for esophageal cancer was modeled using survival data on patients who underwent esophagectomy without induction or adjuvant therapy. In the United States, the standard of care for patients with locally advanced tumors often includes neoadjuvant therapy. The prognostic value of the pathologic stage for these patients is unknown. Methods Data from the Surveillance Epidemiology and End Results (SEER) were used to identify 1,243 patients with adenocarcinoma of the esophagus who underwent surgery after neoadjuvant therapy from 1988-2009. Included in the analysis were pathologically-staged, non-metastatic patients who had radiation as part of their neoadjuvant therapy. The AJCC7 staging system and an alternate system were modeled using Kaplan-Meier survival methods. The two systems were compared using log-rank chi-squared statistics, with large chi-squared values indicating accuracy in survival prediction. Results The AJCC staging system was able to predict survival for patients who had neoadjuvant therapy (P<0.001, chi-squared =81.8); however, there was little distinction between stage subgroups. Patients with neoadjuvant radiotherapy had improved survival for pathologic stage II and III disease. An alternative, simpler staging system was better able to stratify patients with neoadjuvant therapy (P<0.001, chi-squared =100.5). Conclusions The current AJCC staging system is able to predict survival in esophageal adenocarcinoma patients undergoing neoadjuvant therapy, however, there is less distinction among stage subgroups. An alternative, simpler stage grouping may better stratify patients receiving neoadjuvant therapy. PMID:25973240

  14. Predicting the survival rate of mouse embryonic stem cells cryopreserved in alginate beads.

    Science.gov (United States)

    Sambu, S; Xu, X; Ye, H; Cui, Z F

    2011-11-01

    Stem cell cryopreservation in three-dimensional (3D) scaffolds may offer better protection to cells leading to higher survival rates. However, it introduces heterogeneity in cryoprotective agent (CPA) concentrations, durations of exposure to CPA, and freezing and thawing rate within constructs. This paper applies a mathematical model which couples the mass transport of dimethyl sulphoxide (DMSO) in a cell-seeded spherical construct and cell membrane transport into mouse embryonic stem cells (mESCs) to predict overall cell survival rate (CSR) based on CPA equilibrium exposure times (t(E)) and concentrations. The effect of freeze-concentration is also considered. To enable such a prediction, a contour plot was constructed using experimental data obtained in cryopreservation of cell suspensions with DMSO at a cooling rate of 1 degrees C/min. Thereafter, the diffusion in the alginate bead and the membrane transport of CPA was numerically simulated. Results were mapped onto the survival rate contours yielding 'predicted' CSR. The effects of loading time, hindrance, construct radius, and CPA concentration on predicted CSR were examined. From these results, an operation window with upper and lower t(E) of 12-19 min (for 0.6 mm radius beads and 1.4 M DMSO) yielded an overall viability of 60 per cent. The model predictions and the best experimental cryopreservation results with encapsulated mESCs were in agreement. Hence, optimization based on post-thaw CSR can accelerate the identification of cryopreservation protocols and parameters for maximizing cell survival.

  15. Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fendler, Wolfgang Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Paprottka, Philipp M. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Jakobs, Tobias F. [Hospital Barmherzige Brueder, Department of Diagnostic and Interventional Radiology, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter; Haug, Alexander R. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Khalaf, Feras [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Ezziddin, Samer [Saarland University Medical Center, Department of Nuclear Medicine, Homburg (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)

    2015-09-15

    Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5 x upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. (orig.)

  16. Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2017-01-01

    Full Text Available We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA and platelet to lymphocyte ratio (PLR in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%. On univariate analysis, N2 stage (P = 0.013, stage III (P = 0.016, increased CEA level (P = 0.006, and higher PLR value (P = 0.020 before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014 and PLR ≥ 120 (P = 0.036 remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704. Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

  17. Imaging descriptors improve the predictive power of survival models for glioblastoma patients.

    Science.gov (United States)

    Mazurowski, Maciej Andrzej; Desjardins, Annick; Malof, Jordan Milton

    2013-10-01

    Because effective prediction of survival time can be highly beneficial for the treatment of glioblastoma patients, the relationship between survival time and multiple patient characteristics has been investigated. In this paper, we investigate whether the predictive power of a survival model based on clinical patient features improves when MRI features are also included in the model. The subjects in this study were 82 glioblastoma patients for whom clinical features as well as MR imaging exams were made available by The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). Twenty-six imaging features in the available MR scans were assessed by radiologists from the TCGA Glioma Phenotype Research Group. We used multivariate Cox proportional hazards regression to construct 2 survival models: one that used 3 clinical features (age, gender, and KPS) as the covariates and 1 that used both the imaging features and the clinical features as the covariates. Then, we used 2 measures to compare the predictive performance of these 2 models: area under the receiver operating characteristic curve for the 1-year survival threshold and overall concordance index. To eliminate any positive performance estimation bias, we used leave-one-out cross-validation. The performance of the model based on both clinical and imaging features was higher than the performance of the model based on only the clinical features, in terms of both area under the receiver operating characteristic curve (P < .01) and the overall concordance index (P < .01). Imaging features assessed using a controlled lexicon have additional predictive value compared with clinical features when predicting survival time in glioblastoma patients.

  18. Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

    Science.gov (United States)

    Rubio-Tapia, A; Malamut, G; Verbeek, W H M; van Wanrooij, R L J; Leffler, D A; Niveloni, S I; Arguelles-Grande, C; Lahr, B D; Zinsmeister, A R; Murray, J A; Kelly, C P; Bai, J C; Green, P H; Daum, S; Mulder, C J J; Cellier, C

    2016-10-01

    Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. To create a prognostic model to estimate survival of patients with refractory coeliac disease. We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. © 2016 John Wiley & Sons Ltd.

  19. DWCox: A density-weighted Cox model for outlier-robust prediction of prostate cancer survival

    OpenAIRE

    Jinfeng Xiao; Sheng Wang; Jingbo Shang; Henry Lin; Doris Xin; Xiang Ren; Jiawei Han; Jian Peng

    2016-01-01

    Reliable predictions on the risk and survival time of prostate cancer patients based on their clinical records can help guide their treatment and provide hints about the disease mechanism. The Cox regression is currently a commonly accepted approach for such tasks in clinical applications. More complex methods, like ensemble approaches, have the potential of reaching better prediction accuracy at the cost of increased training difficulty and worse result interpretability. Better performance o...

  20. Predicting survival of endoscopic gastrostomy candidates using the underlying disease, serum cholesterol, albumin and transferrin levels

    Directory of Open Access Journals (Sweden)

    Jorge Fonseca

    2013-08-01

    Full Text Available Background: Endoscopic gastrostomy (PEG is the gold standard for long-term enteral feeding. An adequate PEG candidate must have life expectancy longer than a few weeks. Patients surviving less than three weeks should have a nasogastric tube, and gastrostomy should be avoid. There are few studies looking to prognostic factors and fewer attempts of creating a predictor model for PEG patient's survival. Aim: The aim of this study was creating a predictive survival model for PEG candidates, using underlying disease, cholesterol, albumin and transferrin. Methods: Data was obtained from records of adult patients that underwent PEG between 1999 and 2011. Patients surviving 3 weeks were considered adequate survivors. A full logistic regression model was used to classify future cases into one of the two groups of survival. Results: An equation for the probability of future cases was generated, in order to obtain a P value. In the future, patients with a P > 0,88 will have a 64,7% probability of adequate surviving; patients with a P < 0,88 will have a 70.3% probability of short surviving. Conclusions: When clinical evaluation alone does not display a clear prognosis, this equation should be included in the evaluation of gastrostomy candidates, avoiding useless gastrostomy.

  1. Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment.

    Science.gov (United States)

    Morabito, Fortunato; Cutrona, Giovanna; Mosca, Laura; D'Anca, Marianna; Matis, Serena; Gentile, Massimo; Vigna, Ernesto; Colombo, Monica; Recchia, Anna Grazia; Bossio, Sabrina; De Stefano, Laura; Maura, Francesco; Manzoni, Martina; Ilariucci, Fiorella; Consoli, Ugo; Vincelli, Iolanda; Musolino, Caterina; Cortelezzi, Agostino; Molica, Stefano; Ferrarini, Manlio; Neri, Antonino

    2015-08-01

    ZAP-70 is a marker of clinical outcome in chronic lymphocytic leukemia (CLL), however its assessment suffers from a lack of standardization consensus. To identify novel markers able to surrogate IGHV mutational status, CD19(+)CD5(+)-B-lymphocytes from 216 patients enrolled in a prospective study (ClinicalTrial.gov Identifier:NCT00917540), underwent gene expression profiling. Samples were split into CLL-Training (n=102) and CLL-Validation (n=114) sets, and an independent supervised analysis for IGHV mutational status was performed considering all genes with gene expression equal or above that of ZAP-70. Thirty-one genes (23 up- and 8 down-regulated) and 23 genes (18 up- and 5 down-regulated) satisfied these criteria in the CLL-Training and CLL-Validation sets, respectively, and 20 common genes (15 up and 5 down) were found to be differentially regulated in both sets. Two (SNORA70F, NRIP1) of the down-regulated and 6 (SEPT10, ZNF667, TGFBR3, MBOAT1, LPL, CRY1) of the up-regulated genes were significantly associated with a reduced risk of disease progression in both sets. Forcing the afore-mentioned genes in a Cox multivariate model together with IGHV mutational status, only CRY1 (HR=2.3, 95% CI: 1.1-4.9, P=.027) and MBOAT1 (HR=2.1, 95% CI: 1.1-3.7, P=.018) retained their independent prognostic impact, supporting the hypothesis that these genes may potentially act as surrogates for predicting IGHV mutational status.

  2. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  3. Comparison of Elixhauser and Charlson Methods for Predicting Oral Cancer Survival.

    Science.gov (United States)

    Chang, Heng-Jui; Chen, Po-Chun; Yang, Ching-Chieh; Su, Yu-Chieh; Lee, Ching-Chih

    2016-02-01

    Cancer survival correlates not only with the features of primary malignancy but also with the degree of underlying comorbidities. Of the multiple methods used for evaluating the impact of comorbidities on survival, the Charlson and Elixhauser methods are most common. This study compared these 2 comorbidity measures for predicting survival in oral cancer patients. Using the Taiwan National Health Insurance claims data (2008-2011), we acquired data regarding patients' characteristics, comorbidities, and survival from 3583 oral cancer patients. Comorbidity was classified according to both the Charlson comorbidity and Elixhauser comorbidity based on the International Classification of Diseases, 9th Revision. The Elixhauser comorbidity score and Charlson comorbidity score were also calculated. The prediction of survival was determined using measures of discrimination, including the Akaike information criterion and Harrell C (C-statistic). The mean age of the study cohort was 52 ± 10 years, and 94.9% of the patients were male. The median follow-up time was 30.1 months, and the 3-year overall survival was 61.6%. Elixhauser comorbidity method added higher discrimination, compared with the Charlson comorbidity method (Harrell C, 0.677 vs 0.651). Furthermore, the Elixhauser comorbidity score outperformed the Charlson comorbidity score in continuous variable (Harrell C, 0.654 vs 0.646) and category (Harrell C, 0.658 vs 0.645). The Elixhauser method is a superior comorbidity risk-adjustment model for oral cancer survival prediction. Utilization of the Elixhauser comorbidity method may be encouraged for risk adjustment in oral cancer study.

  4. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    NARCIS (Netherlands)

    M. Loeve (Martine); W.C.J. Hop (Wim); M. de Bruijne (Marleen); P.Th.W. van Hal (Peter); P. Robinson; A. Aitken; J.D. Dodd (Jonathan); H.A.W.M. Tiddens (Harm)

    2012-01-01

    textabstractRationale: Up to one-third of patients with cystic fibrosis (CF) awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS). Objectives: This study investigated the

  5. Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest.

    Science.gov (United States)

    Miao, Fen; Cai, Yun-Peng; Zhang, Yu-Xiao; Li, Ye; Zhang, Yuan-Ting

    2015-01-01

    Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis.

  6. Amyloid Load in Fat Tissue Reflects Disease Severity and Predicts Survival in Amyloidosis

    NARCIS (Netherlands)

    Van Gameren, Ingrid I.; Hazenberg, Bouke P. C.; Bijzet, Johan; Haagsma, Elizabeth B.; Vellenga, Edo; Posthumus, Marcel D.; Jager, Pieter L.; Van Rijswijk, Martin H.

    2010-01-01

    Objective. The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival. Methods. We studied all consecutive patients with systemic amyloidosis seen between January 199

  7. Procalcitonin Clearance for Early Prediction of Survival in Critically Ill Patients with Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Mohd Basri Mat Nor

    2014-01-01

    Full Text Available Introduction. Serum procalcitonin (PCT diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48 was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS. 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76 but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84. Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90. Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.

  8. Native cardiac reserve predicts survival in acute post infarction heart failure in mice

    Science.gov (United States)

    Täng, Margareta Scharin; Råmunddal, Truls; Lindbom, Malin; Omerovic, Elmir

    2007-01-01

    Cardiac reserve can be used to predict survival and outcome in patients with heart failure. The aim of this study was to investigate if native cardiac reserve could predict survival after myocardial infarction (MI) in mice. Method We investigated 27 healthy C57Bl6 mice (♂10–12 weeks old) with echocardiography using a high-frequency 15-MHz linear transducer. Investigations were performed both at rest and after pharmacological stress induced by dobutamine (1 μg/g body weight i.p.). The day after the echocardiography examination, a large MI was induced by ligation of the left anterior descending (LAD) coronary artery for evaluation of mortality rate. Results Two weeks after induction of MI, 7 mice were alive (26%). Evaluation of the difference between the surviving and deceased animals showed that the survivors had a better native ability to increase systolic performance (ΔLVESd -1.86 vs -1.28mm p = 0.02) upon dobutamine challenge, resulting in a better cardiac reserve (ΔFS 37 vs 25% p = 0.02 and ΔCO 0.27 vs -0.10 ml/min p = 0.02) and a better chronotropic reserve (ΔR-R interval -68 vs -19 ms p < 0.01). A positive relationship was found between ability to survive and both cardiac (p < 0.05) and chronotropic reserve (p < 0.05) when the mice were divided into three groups: survivors, surviving < 7 days, and surviving < 1 day. Conclusion We conclude that before MI induction the surviving animals had a better cardiac function compared with the deceased. This indicates that native cardiac and chronotropic reserve may be an important determinant and predictor of survival in the setting of large MI and post-infarction heart failure. PMID:18053159

  9. Dynamic model for predicting survival of mature larvae of Tribolium confusum during facility heat treatments.

    Science.gov (United States)

    Boina, Dhana Raj; Subramanyam, Bhadriraju; Alavi, Sajid

    2008-06-01

    Structural heat treatment, a viable alternative to methyl bromide fumigation, involves raising the ambient temperature of food-processing facilities between 50 and 60 degrees C by using gas, electric, or steam heaters, and holding these elevated temperatures for 24 h or longer to kill stored-product insects. A dynamic model was developed to predict survival of mature larvae, which is the most heat-tolerant stage of the confused flour beetle, Tribolium confusum (Jacquelin du Val), at elevated temperatures between 46 and 60 degrees C. The model is based on two nonlinear relationships: 1) logarithmic survival of T. confusum mature larvae as a function of time, and 2) logarithmic reduction in larval survival as a function of temperature. The dynamic model was validated with nine independent data sets collected during actual facility heat treatments conducted on two separate occasions at the Kansas State University pilot flour and feed mills. The rate of increase of temperature over time varied among the nine locations where mature larvae of T. confusum were exposed, and the approximate heating rates during the entire heat treatment ranged from 1.1 to 13.2 degrees C/h. The absolute deviation in the predicted number of larvae surviving the heat treatment was within 3-7% of the actual observed data. Comparison of the absolute deviation in the time taken for equivalent larval survival showed that the model predictions were within 2-6% of the observed data. The dynamic model can be used to predict survival of mature larvae of T. confusum during heat treatments of food-processing facilities based on time-dependent temperature profiles obtained at any given location.

  10. Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    IL-4 is an important B cell survival and growth factor.IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts.Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3' kinase in both resting and activated cells.By contrast,association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed.However,IL-4 induced association of IRS2 with GRB2 in B cell blasts.The pattern of IL-4-induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice.While IL-4 alone does not induce activation of MEK,a MEK1 inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts.These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation.Furthermore,proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

  11. Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Cicognani, A.; Cacciari, E.; Vecchi, V.; Cau, M.; Balsamo, A.; Pirazzoli, P.; Tosi, M.T.; Rosito, P.; Paolucci, G.

    1988-11-01

    To evaluate the effects of two different doses of cranial irradiation on growth and growth hormone (GH) release, we studied 61 children with acute lymphocytic leukemia who had survived at least five years in continuous complete remission. Forty-three children received 24 Gy (group 1) and 18 children received 18 Gy (group 2). Height was evaluated at diagnosis, at the end of treatment, and 6, 12, and 24 months later. Growth hormone release was evaluated by arginine and levodopa tests after the end of treatment. After diagnosis, the height SD score decreased significantly in both groups; two years after the end of treatment, only group 1 showed an SD score for height that was still significantly lower than at diagnosis. Group 1 showed impaired GH responses to the tests and, compared with controls, group 1 in fact included a percentage of subjects with a normal response to levodopa (ie, greater than 8 micrograms/L) that was significantly lower (56.4% vs 83.3%) and a percentage of nonresponders to both tests that was significantly higher (21.6% vs 0%). These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests.

  12. Addressing issues associated with evaluating prediction models for survival endpoints based on the concordance statistic.

    Science.gov (United States)

    Wang, Ming; Long, Qi

    2016-09-01

    Prediction models for disease risk and prognosis play an important role in biomedical research, and evaluating their predictive accuracy in the presence of censored data is of substantial interest. The standard concordance (c) statistic has been extended to provide a summary measure of predictive accuracy for survival models. Motivated by a prostate cancer study, we address several issues associated with evaluating survival prediction models based on c-statistic with a focus on estimators using the technique of inverse probability of censoring weighting (IPCW). Compared to the existing work, we provide complete results on the asymptotic properties of the IPCW estimators under the assumption of coarsening at random (CAR), and propose a sensitivity analysis under the mechanism of noncoarsening at random (NCAR). In addition, we extend the IPCW approach as well as the sensitivity analysis to high-dimensional settings. The predictive accuracy of prediction models for cancer recurrence after prostatectomy is assessed by applying the proposed approaches. We find that the estimated predictive accuracy for the models in consideration is sensitive to NCAR assumption, and thus identify the best predictive model. Finally, we further evaluate the performance of the proposed methods in both settings of low-dimensional and high-dimensional data under CAR and NCAR through simulations.

  13. Immune infiltrates as predictive markers of survival in pancreatic cancer patients

    Directory of Open Access Journals (Sweden)

    Maria Pia eProtti

    2013-08-01

    Full Text Available Pancreatic cancer is a devastating disease with dismal prognosis. The tumor microenvironment is composed by multiple cell types, molecular factors and extracellular matrix forming a strong desmoplastic reaction, which is a hallmark of the disease. A complex cross-talk between tumor cells and the stroma exists with reciprocal influence that dictates tumor progression and ultimately the clinical outcome. In this context, tumor infiltrating immune cells through secretion of chemokine and cytokines exert an important regulatory role. Here we review the correlation between the immune infiltrates, evaluated on tumor samples of pancreatic cancer patients underwent surgical resection, and disease free and/or overall survival after surgery. Specifically, we focus on tumor infiltrating lymphocytes, mast cells and macrophages that all contribute to a Th2-type inflammatory and immunosuppressive microenvironment. In these patients tumor immune infiltrates not only do not contribute to disease eradication but rather the features of Th2-type inflammation and immunosuppression is significantly associated with more rapid disease progression and reduced survival.

  14. Predicting survival outcomes using subsets of significant genes in prognostic marker studies with microarrays

    Directory of Open Access Journals (Sweden)

    Matsui Shigeyuki

    2006-03-01

    Full Text Available Abstract Background Genetic markers hold great promise for refining our ability to establish precise prognostic prediction for diseases. The development of comprehensive gene expression microarray technology has allowed the selection of relevant marker genes from a large pool of candidate genes in early-phased, developmental prognostic marker studies. The primary analytical task in such studies is to select a small fraction of relevant genes, typically from a list of significant genes, for further investigation in subsequent studies. Results We develop a methodology for predicting survival outcomes using subsets of significant genes in prognostic marker studies with microarrays. Key components in this methodology include building prediction models, assessing predictive performance of prediction models, and assessing significance of prediction results. As particular specifications, we assume Cox proportional hazard models with a compound covariate. For assessing predictive accuracy, we propose to use the cross-validated log partial likelihood. To assess significance of prediction results, we apply permutation procedures in cross-validated prediction. As an additional key component peculiar to prognostic prediction, we also consider incorporation of standard prognostic factors. The methodology is evaluated using both simulated and real data. Conclusion The developed methodology for prognostic prediction using a subset of significant genes can provide new insights based on predictive capability, possibly incorporating standard prognostic factors, in selecting a fraction of relevant genes for subsequent studies.

  15. Baseline Quality of Life Factors Predict Long Term Survival after Elective Resection for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Abhiram Sharma

    2013-01-01

    Full Text Available Background. Studies have shown an association between baseline quality of life (Qol and survival in advanced cancers. The aim of this study was to investigate their predictive value in long term survival after elective colorectal cancer resection. Methods. A consecutive series of patients undergoing elective colorectal cancer surgery for nonmetastatic disease were recruited in 2003/04. Patients completed standardized quality of life questionnaires (HADS, FACTC, MRS, and PANAS prior to and 6 weeks after surgery. Univariate (log-rank test and multivariate analyses (Cox proportional hazards were performed to predict long term survival. Results. Ninety-seven patients met the inclusion criteria. Sixty-five (67% were male and the median age of the group was 70 years. Forty-six (47.5% patients had died and the mean survival was 1,741 days (median 2159, range 9–2923 days. Preoperative mood rating scale and functional assessment of cancer therapy-colorectal FACT C emotional well-being and postoperative FACT C additional concerns were independent predictors of long term survival. Conclusion. Incorporating psychosocial measures in preoperative assessment of cancer patients could help to identify patients who require assessment with a view to implementing psychosocial interventions. These active interventions to maximize mood and well-being should form an integral part of multidisciplinary treatment in these patients.

  16. Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.

    Directory of Open Access Journals (Sweden)

    Po-sung Chu

    Full Text Available Hepatitis C virus (HCV genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3- NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.

  17. Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.

    Directory of Open Access Journals (Sweden)

    Junjie Peng

    Full Text Available To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.A total of 883 patients with stage II-III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS, local recurrence (LR and distant metastases (DM. Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients.The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73] and 0.68 (95% CI = [0.64, 0.72] on the original dataset, and 0.76 (95% CI = [0.67, 0.86] and 0.73 (95% CI = [0.63, 0.83] on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category.The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.

  18. High serum uric acid concentration predicts poor survival in patients with breast cancer.

    Science.gov (United States)

    Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

    2017-08-26

    Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017. Published by Elsevier B.V.

  19. A simple model for predicting survival of angler-caught and released largemouth bass

    Science.gov (United States)

    Wilde, G.R.; Pope, K.L.

    2008-01-01

    We conducted a controlled experiment in the laboratory to assess the influence of anatomical hooking location and water temperature on survival of angler-caught and released largemouth bass Micropterus salmoides. Survival was 98% (58 of 59 fish) among fish that were hand-hooked within the oral cavity (including the gills), whereas survival was 66% (33 of 50 fish) among fish that were hand-hooked in the esophagus. Survival of hooked fish was not significantly influenced by water temperature (7-27??C) or the hooking location X water temperature interaction. We combined our results with prior research to develop a predictive model of largemouth bass survival, which was 98.3% (SD = 1.87%) for fish hooked in the oral cavity and 55.0% (SD = 9.70%) for fish hooked in the esophagus. The model is valid for water temperatures ranging from 7??C to 27??C and allows one to estimate, with known precision, the survival of angler-caught and released largemouth bass without the need for controlled studies or for holding fish in pens or cages to assess delayed mortality. ?? Copyright by the American Fisheries Society 2008.

  20. Development of a Summarized Health Index (SHI for use in predicting survival in sea turtles.

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Li

    Full Text Available Veterinary care plays an influential role in sea turtle rehabilitation, especially in endangered species. Physiological characteristics, hematological and plasma biochemistry profiles, are useful references for clinical management in animals, especially when animals are during the convalescence period. In this study, these factors associated with sea turtle surviving were analyzed. The blood samples were collected when sea turtles remained alive, and then animals were followed up for surviving status. The results indicated that significantly negative correlation was found between buoyancy disorders (BD and sea turtle surviving (p < 0.05. Furthermore, non-surviving sea turtles had significantly higher levels of aspartate aminotranspherase (AST, creatinine kinase (CK, creatinine and uric acid (UA than surviving sea turtles (all p < 0.05. After further analysis by multiple logistic regression model, only factors of BD, creatinine and UA were included in the equation for calculating summarized health index (SHI for each individual. Through evaluation by receiver operating characteristic (ROC curve, the result indicated that the area under curve was 0.920 ± 0.037, and a cut-off SHI value of 2.5244 showed 80.0% sensitivity and 86.7% specificity in predicting survival. Therefore, the developed SHI could be a useful index to evaluate health status of sea turtles and to improve veterinary care at rehabilitation facilities.

  1. Can neutrophil to lymphocyte ratio predict lamina propria invasion in patients with non muscle invasive bladder cancer?

    Science.gov (United States)

    Cimen, Haci Ibrahim; Halis, Fikret; Saglam, Hasan Salih; Gokce, Ahmet

    2017-01-01

    ABSTRACT Objective Recent studies have demonstrated the role of systemic inflammation in the development and progression of cancer. In this study, we evaluated whether preoperatively measured neutrophil-to-lymphocyte ratio (NLR) can predict lamina propria invasion in patients with non-muscle-invasive bladder cancer (NMIBC). Material and Methods We reviewed the medical records of 304 consecutive and newly diagnosed patients with bladder cancer who had been treated with transurethral resection between January 2008 and June 2014. In total, 271 patients were included in the study and the patients were divided into two groups according to the pathological stage (Group 1: Ta, Group 2: T1). NLR was calculated by dividing the absolute neutrophil count (N) by the absolute lymphocyte count (L). Results In total, 271 patients (27 women and 244 men) were enrolled. Mean age was higher in Group 2 than in Group 1 (67.3±10.8 vs. 62.9±10.8, pblood cell (WBC) and N counts were statistically insignificant (7.63±1.87 vs. 7.69±1.93, p=0.780; 4.72±1.54 vs. 4.46±1.38, p=0.140; respectively), L was significantly lower and NLR was significantly higher in Group 2 than in Group 1 (2.07±0.75 vs. 2.4±0.87, p=0.001; 2.62±1.5 vs. 2.19±1.62, p=0.029; respectively). Conclusion Our data indicate that high NLR and low L are statistically associated with T1 stage, whereas low L are able to predict lamina propria invasion in patients with NMIBC. These findings suggest that pretreatment measurement of NLR may provide valuable information for the clinical management of patients with NMIBC. Prospective studies are now required to further validate the role of NLR as a risk factor in NMIBC. PMID:28124528

  2. Genomic prediction of survival time in a population of brown laying hens showing cannibalistic behavior.

    Science.gov (United States)

    Alemu, Setegn W; Calus, Mario P L; Muir, William M; Peeters, Katrijn; Vereijken, Addie; Bijma, Piter

    2016-09-13

    Mortality due to cannibalism causes both economic and welfare problems in laying hens. To limit mortality due to cannibalism, laying hens are often beak-trimmed, which is undesirable for animal welfare reasons. Genetic selection is an alternative strategy to increase survival and is more efficient by taking heritable variation that originates from social interactions into account, which are modelled as the so-called indirect genetic effects (IGE). Despite the considerable heritable variation in survival time due to IGE, genetic improvement of survival time in laying hens is still challenging because the detected heritable variation of the trait with IGE is still limited, ranging from 0.06 to 0.26, and individuals that are still alive at the end of the recording period are censored. Furthermore, survival time records are available late in life and only on females. To cope with these challenges, we tested the hypothesis that genomic prediction increases the accuracy of estimated breeding values (EBV) compared to parental average EBV, and increases response to selection for survival time compared to a traditional breeding scheme. We tested this hypothesis in two lines of brown layers with intact beaks, which show cannibalism, and also the hypothesis that the rate of inbreeding per year is lower for genomic selection than for the traditional breeding scheme. The standard deviation of genomic prediction EBV for survival time was around 22 days for both lines, indicating good prospects for selection against mortality in laying hens with intact beaks. Genomic prediction increased the accuracy of the EBV by 35 and 32 % compared to the parent average EBV for the two lines. At the current reference population size, predicted response to selection was 91 % higher when using genomic selection than with the traditional breeding scheme, as a result of a shorter generation interval in males and greater accuracy of selection in females. The predicted rate of inbreeding per

  3. HSP70 mediates survival in apoptotic cells-Boolean network prediction and experimental validation.

    Science.gov (United States)

    Vasaikar, Suhas V; Ghosh, Sourish; Narain, Priyam; Basu, Anirban; Gomes, James

    2015-01-01

    Neuronal stress or injury results in the activation of proteins, which regulate the balance between survival and apoptosis. However, the complex mechanism of cell signaling involving cell death and survival, activated in response to cellular stress is not yet completely understood. To bring more clarity about these mechanisms, a Boolean network was constructed that represented the apoptotic pathway in neuronal cells. FasL and neurotrophic growth factor (NGF) were considered as inputs in the absence and presence of heat shock proteins known to shift the balance toward survival by rescuing pro-apoptotic cells. The probabilities of survival, DNA repair and apoptosis as cellular fates, in the presence of either the growth factor or FasL, revealed a survival bias encoded in the network. Boolean predictions tested by measuring the mRNA level of caspase-3, caspase-8, and BAX in neuronal Neuro2a (N2a) cell line with NGF and FasL as external input, showed positive correlation with the observed experimental results for survival and apoptotic states. It was observed that HSP70 contributed more toward rescuing cells from apoptosis in comparison to HSP27, HSP40, and HSP90. Overexpression of HSP70 in N2a transfected cells showed reversal of cellular fate from FasL-induced apoptosis to survival. Further, the pro-survival role of the proteins BCL2, IAP, cFLIP, and NFκB determined by vertex perturbation analysis was experimentally validated through protein inhibition experiments using EM20-25, Embelin and Wedelolactone, which resulted in 1.27-, 1.26-, and 1.46-fold increase in apoptosis of N2a cells. The existence of a one-to-one correspondence between cellular fates and attractor states shows that Boolean networks may be employed with confidence in qualitative analytical studies of biological networks.

  4. Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Frédéric Di Fiore; Stéphane Lecleire; Olivier Rigal; Marie-Pierre Galais; Emmanuel Ben Soussan; Isabelle David; Bernard Paillot; Jacques-Henri Jacob; Pierre Michel

    2006-01-01

    AIM: The aim of the study was to evaluate the predictive factors of survival in patients with locally advanced squamous cell esophageal carcinoma (LASCOC) treated with definitive chemoradiotherapy (CRT)regimen based on the 5FU/CDDP combination.METHODS: All patients with LASCOC treated with a definitive CRT using the 5FU/CDDP combination between 1994 and 2000 were retrospectively included.Clinical complete response (CCR) to CRT was assessed by esophageal endoscopy and CT-scan 2 mo after CRT completion. Prognostic factors of survival were assessed using univariate and multivariate analysis by the Cox regression model.RESULTS: A total of 116 patients were included in the study. A CCR to CRT was observed in 86/116 (74.1%).The median survival was 20 mo (range 2-114) and the 5-year survival was 9.4%. Median survival of responder patients to CRT was 25 mo (range 3-114) as compared to 9 mo (range 2-81) in non-responder patients (P <0.001). In univariate analysis, survival was associated with CCR (P < 0.001), WHO performance status < 2 (P= 0.01), tumour length < 6 cm (P = 0.045) and weight loss < 10% was in limit of significance (P = 0.053). In multivariate analysis, survival was dependant to CCR (P< 0.0001), weight loss < 10% (P = 0.034) and WHO performance < 2 (P = 0.046).CONCLUSION: Our results suggest that survival in patients with LASCOC treated with definitive CRT was correlated to CCR, weight loss and WHO performance status.

  5. Prediction and identification of mouse cytotoxic T lymphocyte epitopes in Ebola virus glycoproteins

    Directory of Open Access Journals (Sweden)

    Wu Shipo

    2012-06-01

    Full Text Available Abstract Background Ebola viruses (EBOVs cause severe hemorrhagic fever with a high mortality rate. At present, there are no licensed vaccines or efficient therapies to combat EBOV infection. Previous studies have shown that both humoral and cellular immune responses are crucial for controlling Ebola infection. CD8+ T cells play an important role in mediating vaccine-induced protective immunity. The objective of this study was to identify H-2d-specific T cell epitopes in EBOV glycoproteins (GPs. Results Computer-assisted algorithms were used to predict H-2d-specific T cell epitopes in two species of EBOV (Sudan and Zaire GP. The predicted peptides were synthesized and identified in BALB/c mice immunized with replication-deficient adenovirus vectors expressing the EBOV GP. Enzyme-linked immunospot assays and intracellular cytokine staining showed that the peptides RPHTPQFLF (Sudan EBOV, GPCAGDFAF and LYDRLASTV (Zaire EBOV could stimulate splenoctyes in immunized mice to produce large amounts of interferon-gamma. Conclusion Three peptides within the GPs of two EBOV strains were identified as T cell epitopes. The identification of these epitopes should facilitate the evaluation of vaccines based on the Ebola virus glycoprotein in a BALB/c mouse model.

  6. Platelet to lymphocyte ratio in the prediction of adverse outcomes after acute coronary syndrome: a meta-analysis

    Science.gov (United States)

    Li, Wenzhang; Liu, Qianqian; Tang, Yin

    2017-01-01

    Recent studies have shown platelet to lymphocyte ratio (PLR) to be a potential inflammatory marker in cardiovascular diseases. We performed a meta-analysis to systematically evaluate the prognostic role of PLR in acute coronary syndrome (ACS). A comprehensive literature search up to May 18, 2016 was conducted from PUBMED, EMBASE and Web of science to identify related studies. The risk ratio (RR) with 95% confidence interval (CI) was extracted or calculated for effect estimates. Totally ten studies involving 8932 patients diagnosed with ACS were included in our research. We demonstrated that patients with higher PLR level had significantly higher risk of in-hospital adverse outcomes (RR = 2.24, 95%CI = 1.81–2.77) and long-term adverse outcomes (RR = 2.32, 95%CI = 1.64–3.28). Sensitivity analyses confirmed the stability of our results. We didn’t detect significant publication bias by Begg’s and Egger’s test (p > 0.05). In conclusion, our meta-analysis revealed that PLR is promising biomarker in predicting worse prognosis in ACS patients. The results should be validated by future large-scale, standard investigations. PMID:28071752

  7. Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy

    Directory of Open Access Journals (Sweden)

    Brian W. Cross

    2012-01-01

    Full Text Available Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR and overall survival in localized renal cell carcinoma (RCC following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr, intermediate (20.1–50.0 mm/hr, and high risk (>50.0 mm/hr groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI survival was 44.1 (42.6–45.5 months, 35.5 (32.3–38.8 months, and 32.1 (25.5–38.6 months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649 and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228 increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC.

  8. Factors predicting survival in patients with proximal gastric carcinoma involving the esophagus

    Institute of Scientific and Technical Information of China (English)

    Yi-Fen Zhang; Jiong Shi; Hui-Ping Yu; An-Ning Feng; Xiang-Shan Fan; Gregory Y Lauwers; Hiroshi Mashimo

    2012-01-01

    AIM:To investigate the clinicopathologic features which predict surgical overall survival in patients with proximal gastric carcinoma involving the esophagus (PGCE).METHODS:Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009.Each retrieved pathology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were selected as PGCE.Each tumor was re-staged,following the guidelines on esophageal adenocarcinoma,according to the 7th edition of the American Joint Commission on Cancer Staging Manual.All histology slides were studied along with the pathology report for a retrospective analysis of 13 clinicopathologic features,i.e.,age,gender,Helicobacter pylori (H.pylori) infection,surgical modality,Siewert type,tumor Bormann's type,size,differentiation,histology type,surgical margin,lymphovascular and perineural invasion,and pathologic stage in relation to survival after surgical resection.Prognostic factors for overall survival were assessed with uniand multi-variate analyses.RESULTS:Patients' mean age was 65 years (range:47-90 years).The male:female ratio was 3.3.The 1-,3-and 5-year overall survival rates were 87%,61% and 32%,respectively.By univariate analysis,age,male gender,H,pylori,tumor Bormann's type,size,histology type,surgical modality,positive surgical margin,lymphovascular invasion,and pT stage were not predictivefor overall survival; in contrast,perineural invasion (P =0.003),poor differentiation (P =0.0003),> 15 total lymph nodes retrieved (P =0.008),positive lymphnodes (P =0.001),and distant metastasis (P =0.005)predicted poor post-operative overall survival.Celiac axis nodal metastasis was associated with significantly worse overall survival (P =0.007).By multivariate analysis,≥ 16 positive nodes (P =0.018),lymph node ratio > 0.2 (P =0

  9. Antioxidant defenses predict long-term survival in a passerine bird.

    Directory of Open Access Journals (Sweden)

    Nicola Saino

    Full Text Available BACKGROUND: Normal and pathological processes entail the production of oxidative substances that can damage biological molecules and harm physiological functions. Organisms have evolved complex mechanisms of antioxidant defense, and any imbalance between oxidative challenge and antioxidant protection can depress fitness components and accelerate senescence. While the role of oxidative stress in pathogenesis and aging has been studied intensively in humans and model animal species under laboratory conditions, there is a dearth of knowledge on its role in shaping life-histories of animals under natural selection regimes. Yet, given the pervasive nature and likely fitness consequences of oxidative damage, it can be expected that the need to secure efficient antioxidant protection is powerful in molding the evolutionary ecology of animals. Here, we test whether overall antioxidant defense varies with age and predicts long-term survival, using a wild population of a migratory passerine bird, the barn swallow (Hirundo rustica, as a model. METHODOLOGY/PRINCIPAL FINDINGS: Plasma antioxidant capacity (AOC of breeding individuals was measured using standard protocols and annual survival was monitored over five years (2006-2010 on a large sample of selection episodes. AOC did not covary with age in longitudinal analyses after discounting the effect of selection. AOC positively predicted annual survival independently of sex. Individuals were highly consistent in their relative levels of AOC, implying the existence of additive genetic variance and/or environmental (including early maternal components consistently acting through their lives. CONCLUSIONS: Using longitudinal data we showed that high levels of antioxidant protection positively predict long-term survival in a wild animal population. Present results are therefore novel in disclosing a role for antioxidant protection in determining survival under natural conditions, strongly demanding for more

  10. Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101

    Science.gov (United States)

    He, Chao-Bin

    2017-01-01

    Background The systemic inflammatory response plays an important role in cancer development and progression. An original inflammation-based staging system for predicting survival in patients undergoing transarterial chemoembolization (TACE) combined with recombinant human type-5 adenovirus H101 is not available. This study aimed to validate the prognostic value of inflammation scores for patients with hepatocellular carcinoma (HCC) who were treated with TACE combined with H101. Methods The data from 216 patients with HCC who underwent TACE combined with H101 from January 2007 to July 2015 were retrospectively collected, and the association of the inflammation scores with overall survival (OS) was analyzed. Univariate and multivariate analyses were performed to identify variables associated with OS. The prognostic value of the inflammation scores, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil/ platelet-to-lymphocyte ratio (NLR-PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), prognostic index (PI), tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems were analyzed and compared using the areas under the receiver operating characteristic curves (AUROCs). Results The estimated 1-, 2-, and 3-year OS rates were 61.3%, 44.2%, and 40.5% for the entire study cohort, respectively; the median OS was 17 months. According to the multivariate Cox proportional hazards model, the pretreatment NLR, tumor diameter and pretreatment alpha-fetoprotein (AFP) levels were independent predictors of OS. The CLIP score had superior discriminative abilities compared with other staging systems, and the NLR-PLR score consistently displayed a higher AUROC value than the other inflammation-based prognostic scores. The combination of the NLR-PLR and CLIP scores exhibited a superior prognostic ability for OS compared to the NLR-PLR or

  11. Cell survival in carbon beams - comparison of amorphous track model predictions

    DEFF Research Database (Denmark)

    Grzanka, L.; Greilich, S.; Korcyl, M.

    distribution models, and gamma response models was developed. This software can be used for direct numerical comparison between the models, submodels and their parameters and experimental data. In the present paper, we look at 10%-survival data from cell lines irradiated in vitro with carbon and proton beams......Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under ion...... by Tsuruoka et al. [4] . Results and conclusion: Preliminary results show a good agreement of models predictions and the experimental data for clinical doses. When investigating the influence of radial dose distributions on inactivation cross section in the Katz model, we found that one of the most important...

  12. A hemocyte gene expression signature correlated with predictive capacity of oysters to survive Vibrio infections

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    Rosa Rafael

    2012-06-01

    Full Text Available Abstract Background The complex balance between environmental and host factors is an important determinant of susceptibility to infection. Disturbances of this equilibrium may result in multifactorial diseases as illustrated by the summer mortality syndrome, a worldwide and complex phenomenon that affects the oysters, Crassostrea gigas. The summer mortality syndrome reveals a physiological intolerance making this oyster species susceptible to diseases. Exploration of genetic basis governing the oyster resistance or susceptibility to infections is thus a major goal for understanding field mortality events. In this context, we used high-throughput genomic approaches to identify genetic traits that may characterize inherent survival capacities in C. gigas. Results Using digital gene expression (DGE, we analyzed the transcriptomes of hemocytes (immunocompetent cells of oysters able or not able to survive infections by Vibrio species shown to be involved in summer mortalities. Hemocytes were nonlethally collected from oysters before Vibrio experimental infection, and two DGE libraries were generated from individuals that survived or did not survive. Exploration of DGE data and microfluidic qPCR analyses at individual level showed an extraordinary polymorphism in gene expressions, but also a set of hemocyte-expressed genes whose basal mRNA levels discriminate oyster capacity to survive infections by the pathogenic V. splendidus LGP32. Finally, we identified a signature of 14 genes that predicted oyster survival capacity. Their expressions are likely driven by distinct transcriptional regulation processes associated or not associated to gene copy number variation (CNV. Conclusions We provide here for the first time in oyster a gene expression survival signature that represents a useful tool for understanding mortality events and for assessing genetic traits of interest for disease resistance selection programs.

  13. MRI and thallium-201 SPECT in the prediction of survival in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Vos, Maaike J. [VU University Medical Center, Department of Neurology, Amsterdam (Netherlands); Medical Center Haaglanden, Department of Neurology, PO Box 432, The Hague (Netherlands); Berkhof, Johannes [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Hoekstra, Otto S. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Bosma, Ingeborg; Sizoo, Eefje M.; Heimans, Jan J.; Reijneveld, Jaap C.; Postma, Tjeerd J. [VU University Medical Center, Department of Neurology, Amsterdam (Netherlands); Sanchez, Esther [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Lagerwaard, Frank J. [VU University Medical Center, Department of Radiation Oncology, Amsterdam (Netherlands); Buter, Jan [VU University Medical Center, Department of Medical Oncology, Amsterdam (Netherlands); Noske, David P. [VU University Medical Center, Department of Neurosurgery and Neuro-Oncology Research Group, Amsterdam (Netherlands)

    2012-06-15

    This paper aims to study the value of MRI and Thallium 201 ({sup 201}Tl) single-photon emission computed tomography (SPECT) in the prediction of overall survival (OS) in glioma patients treated with temozolomide (TMZ) and to evaluate timing of radiological follow-up. We included patients treated with TMZ chemoradiotherapy for newly diagnosed glioblastoma multiforme (GBM) and with TMZ for recurrent glioma. MRIs and {sup 201}Tl SPECTs were obtained at regular intervals. The value of both imaging modalities in predicting OS was examined using Cox regression analyses. Altogether, 138 MRIs and 113 {sup 201}Tl SPECTs in 46 patients were performed. Both imaging modalities were strongly related to OS (P {<=} 0.02). In newly diagnosed GBM patients, the last follow-up MRI (i.e., after six adjuvant TMZ courses) and SPECT (i.e., after three adjuvant TMZ courses) were the strongest predictors of OS (P = 0.01). In recurrent glioma patients, baseline measurements appeared to be the most predictive of OS (P < 0.01). The addition of one imaging modality to the other did not contribute to the prediction of OS. Both MRI and {sup 201}Tl SPECT are valuable in the prediction of OS. It is adequate to restrict to one of both modalities in the radiological follow-up during treatment. In the primary GBM setting, MRI after six adjuvant TMZ courses contributes significantly to the prediction of survival. In the recurrent glioma setting, baseline MRI appears to be a powerful predictor of survival, whereas follow-up MRIs during TMZ seem to be of little additional value. (orig.)

  14. Staging systems for predicting survival of patients with hepatocellular carcinoma after surgery

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To compare the staging systems for stratifying and predicting the prognosis of patients with hepatocel-lular carcinoma (HCC) after partial hepatectomy (PH). METHODS: Clinical data about 438 HCC patients who underwent PH from January 1991 to December 2004 at our hospital were retrospectively analyzed. Tumor stage was evaluated following the Chinese tumor node me-tastasis (TNM) and barcelona clinic liver cancer (BCLC) staging systems, respectively. Survival curves for the HCC patients were plotted using ...

  15. Enhancing the Lasso Approach for Developing a Survival Prediction Model Based on Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Shuhei Kaneko

    2015-01-01

    Full Text Available In the past decade, researchers in oncology have sought to develop survival prediction models using gene expression data. The least absolute shrinkage and selection operator (lasso has been widely used to select genes that truly correlated with a patient’s survival. The lasso selects genes for prediction by shrinking a large number of coefficients of the candidate genes towards zero based on a tuning parameter that is often determined by a cross-validation (CV. However, this method can pass over (or fail to identify true positive genes (i.e., it identifies false negatives in certain instances, because the lasso tends to favor the development of a simple prediction model. Here, we attempt to monitor the identification of false negatives by developing a method for estimating the number of true positive (TP genes for a series of values of a tuning parameter that assumes a mixture distribution for the lasso estimates. Using our developed method, we performed a simulation study to examine its precision in estimating the number of TP genes. Additionally, we applied our method to a real gene expression dataset and found that it was able to identify genes correlated with survival that a CV method was unable to detect.

  16. Six-Minute-Walk Distance Predicts Waiting List Survival in Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Lederer, David J.; Arcasoy, Selim M.; Wilt, Jessie S.; D'Ovidio, Frank; Sonett, Joshua R.; Kawut, Steven M.

    2006-01-01

    Rationale: Functional studies may be useful to predict survival in idiopathic pulmonary fibrosis (IPF). Various cutoffs of 6-min-walk distance (6MWD) have been suggested to identify patients at a high risk of death. Objectives: To examine the association between 6MWD and survival in patients with IPF listed for lung transplantation, and to identify sensitive and specific cutoffs for predicting death at 6 mo. Methods: We performed a retrospective cohort study of 454 patients classified as having IPF listed for lung transplantation with the United Network for Organ Sharing between June 30, 2004 and July 22, 2005. Measurements and Main Results: Lower 6MWD was associated with an increased mortality rate (p value for linear trend < 0.0001). Patients with a walk distance less than 207 m had a more than fourfold greater mortality rate than those with a walk distance of 207 m or more, despite adjustment for demographics, anthropomorphics, FVC % predicted, pulmonary hypertension, and medical comorbidities (adjusted rate ratio, 4.7; 95% confidence interval, 2.5–8.9; p < 0.0001). 6MWD was a significantly better predictor of 6-mo mortality than was FVC % predicted (c-statistic = 0.73 vs. 0.59, respectively; p = 0.02). Conclusions: Lower 6MWD was strongly and independently associated with an increased mortality rate for wait-listed patients classified as having IPF. 6MWD was a better predictor of death at 6 mo than was FVC % predicted. PMID:16778159

  17. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

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    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Bollen, Laurens; Dijkstra, Sander P. [Department of Orthopedic Surgery, Leiden University Medical Center (Netherlands); Steen-Banasik, Elzbieta M. van der [ARTI Institute for Radiation Oncology Arnhem, Arnhem (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is

  18. MRI features predict survival and molecular markers in diffuse lower-grade gliomas.

    Science.gov (United States)

    Zhou, Hao; Vallières, Martin; Bai, Harrison X; Su, Chang; Tang, Haiyun; Oldridge, Derek; Zhang, Zishu; Xiao, Bo; Liao, Weihua; Tao, Yongguang; Zhou, Jianhua; Zhang, Paul; Yang, Li

    2017-06-01

    Previous studies have shown that MR imaging features can be used to predict survival and molecular profile of glioblastoma. However, no study of a similar type has been performed on lower-grade gliomas (LGGs). Presurgical MRIs of 165 patients with diffuse low- and intermediate-grade gliomas (histological grades II and III) were scored according to the Visually Accessible Rembrandt Images (VASARI) annotations. Radiomic models using automated texture analysis and VASARI features were built to predict isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion status, histological grade, and tumor progression. Interrater analysis showed significant agreement in all imaging features scored (k = 0.703-1.000). On multivariate Cox regression analysis, no enhancement and a smooth non-enhancing margin were associated with longer progression-free survival (PFS), while a smooth non-enhancing margin was associated with longer overall survival (OS) after taking into account age, grade, tumor location, histology, extent of resection, and IDH1 1p/19q subtype. Using logistic regression and bootstrap testing evaluations, texture models were found to possess higher prediction potential for IDH1 mutation, 1p/19q codeletion status, histological grade, and progression of LGGs than VASARI features, with areas under the receiver-operating characteristic curves of 0.86 ± 0.01, 0.96 ± 0.01, 0.86 ± 0.01, and 0.80 ± 0.01, respectively. No enhancement and a smooth non-enhancing margin on MRI were predictive of longer PFS, while a smooth non-enhancing margin was a significant predictor of longer OS in LGGs. Textural analyses of MR imaging data predicted IDH1 mutation, 1p/19q codeletion, histological grade, and tumor progression with high accuracy.

  19. Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

    Science.gov (United States)

    Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

    2017-04-01

    Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

  20. Prediction of survival in patients with cardiogenic shock and multiorgan failure treated with biventricular assist device.

    Science.gov (United States)

    Potapov, Evgenij V; Stepanenko, Alexander; Kukucka, Marian; Ba Fadhl, Faiz H; Qedra, Naser; Weng, Yuguo; Pasic, Miralem; Lehmkuhl, Hans B; Krabatsch, Thomas; Hetzer, Roland

    2010-01-01

    Mechanical circulatory support (MCS) is valuable in saving the lives of patients with severe cardiogenic shock. However, their survival is limited if multiorgan failure (MOF) proves to be irreversible. Although ventricular assist devices (VADs) have been shown to reverse end-organ failure in some patients, the pathophysiological mechanisms of end-organ failure and its regression are not fully understood, and clinical markers and thresholds for the "point of no return" are lacking. We investigated predictors of 30-day survival in patients supported with a biventricular assist device (BVAD). We studied 157 patients implanted with a Berlin Heart EXCOR BVAD between 1987 and 2006. Children younger than 10 years and cases with postcardiotomy syndrome and transplant failure were excluded from the analysis as well as patients with technical or bleeding problems requiring rethoracotomy. In total, 69 clinical, hemodynamic, echocardiographic, and laboratory parameters were evaluated. Most of the patients suffered from ischemic cardiomyopathy or acute myocardial infarction. In addition, the preoperative multiple organ dysfunction syndrome (MODS) and the sequential organ failure assessment (SOFA) scores were calculated. The patients were divided into two groups regarding procedural success: group I-survival >30 days or heart transplantation or weaning from device (n = 105) and group II-death on system shock and MOF do not predict survival on BVAD. As expected, older patients are at higher risk for death on BVAD. Acidosis and high MODS score predict unfavorable outcome. However, the prediction of clinical outcome in patients in severe cardiogenic shock supported by BVAD is possible in extreme situations only.

  1. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

    2016-06-15

    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  2. A signature inferred from Drosophila mitotic genes predicts survival of breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Christian Damasco

    Full Text Available INTRODUCTION: The classification of breast cancer patients into risk groups provides a powerful tool for the identification of patients who will benefit from aggressive systemic therapy. The analysis of microarray data has generated several gene expression signatures that improve diagnosis and allow risk assessment. There is also evidence that cell proliferation-related genes have a high predictive power within these signatures. METHODS: We thus constructed a gene expression signature (the DM signature using the human orthologues of 108 Drosophila melanogaster genes required for either the maintenance of chromosome integrity (36 genes or mitotic division (72 genes. RESULTS: The DM signature has minimal overlap with the extant signatures and is highly predictive of survival in 5 large breast cancer datasets. In addition, we show that the DM signature outperforms many widely used breast cancer signatures in predictive power, and performs comparably to other proliferation-based signatures. For most genes of the DM signature, an increased expression is negatively correlated with patient survival. The genes that provide the highest contribution to the predictive power of the DM signature are those involved in cytokinesis. CONCLUSION: This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible target for antimitotic therapies.

  3. Modelling circulating tumour cells for personalised survival prediction in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Gianluca Ascolani

    2015-05-01

    Full Text Available Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET. In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.

  4. Predictive parameters of survival in hemodialysis patients with restless leg syndrome

    Directory of Open Access Journals (Sweden)

    Radojica V Stolic

    2014-01-01

    Full Text Available Restless leg syndrome (RLS affects the quality of life and survival in patients on hemodialysis (HD. The aim of this study was to determine the characteristics and survival parameters in patients on HD with RLS. This study was a non-randomized clinical study involving 204 patients on HD, of whom 71 were female and 133 were male. Symptoms of RLS were defined as positive responses to four questions comprising the criteria of RLS. We recorded the outcome of treatment, biochemical analyses, demographic, sexual, anthropometric and clinical characteristics in all study patients. Patients with RLS who completed the study had a significantly higher body mass index and lower intima-media thickness and flow through the arteriovenous fistula. Among patients with RLS who died, there were more smokers as well as higher incidences of cardiovascular disease and diabetes mellitus. Among patients with RLS who survived, there were a greater number of patients with preserved diuresis and receiving erythropoietin therapy. Patients who completed the study had significantly higher levels of hemoglobin, creatinine, serum iron and transferrin satura-tion. Diabetes mellitus (B = 1.802; P = 0.002 and low Kt/V (B = -5.218; P = 0.001 were major predictive parameters for survival.

  5. ROCK I Has More Accurate Prognostic Value than MET in Predicting Patient Survival in Colorectal Cancer.

    Science.gov (United States)

    Li, Jian; Bharadwaj, Shruthi S; Guzman, Grace; Vishnubhotla, Ramana; Glover, Sarah C

    2015-06-01

    Colorectal cancer remains the second leading cause of death in the United States despite improvements in incidence rates and advancements in screening. The present study evaluated the prognostic value of two tumor markers, MET and ROCK I, which have been noted in other cancers to provide more accurate prognoses of patient outcomes than tumor staging alone. We constructed a tissue microarray from surgical specimens of adenocarcinomas from 108 colorectal cancer patients. Using immunohistochemistry, we examined the expression levels of tumor markers MET and ROCK I, with a pathologist blinded to patient identities and clinical outcomes providing the scoring of MET and ROCK I expression. We then used retrospective analysis of patients' survival data to provide correlations with expression levels of MET and ROCK I. Both MET and ROCK I were significantly over-expressed in colorectal cancer tissues, relative to the unaffected adjacent mucosa. Kaplan-Meier survival analysis revealed that patients' 5-year survival was inversely correlated with levels of expression of ROCK I. In contrast, MET was less strongly correlated with five-year survival. ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression. As a result, ROCK I may provide a less invasive method of assessing patient prognoses and directing therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer.

    Science.gov (United States)

    Hong, Kwang Dae; Lee, Dooseok; Lee, Youngseok; Lee, Sun Il; Moon, Hong Young

    2013-04-01

    The homeodomain transcription factor CDX2 directs development and maintenance of normal intestinal epithelium. However, the role of CDX2 in colorectal carcinogenesis is poorly understood. Hence, we investigated the CDX2 expression in patients with colorectal cancer and its relationship to tumor cell proliferation and differentiation and evaluated the role of this molecule as a biologic marker for the prediction of poor patient survival. We retrospectively reviewed 207 patients with colorectal cancer, with an available paraffin block, who underwent surgical resection between January 2002 and December 2004 at Korea University Guro Hospital. CDX2 expression was compared between tumor tissue and the adjacent normal mucosa using immunohistochemistry and Western blot analysis. Immunohistochemical staining for CDX2, Ki-67, and CK20 was performed in each tumor tissue. Immunohistochemistry revealed that CDX2 protein is overexpressed by colorectal cancer compared with adjacent normal mucosa (P < 0.001). In the Western blot analysis, tumor tissue showed a trend toward overexpression of CDX2 protein compared with normal mucosa (P = 0.09). CDX2 expression showed a significant direct correlation with the expression of Ki-67 and CK20 in tumor tissue (P = 0.028 and P = 0.042, respectively). Survival analysis showed that reduced CDX2 expression was statistically and significantly related to poor overall survival. Reduced CDX2 expression is associated with poor overall survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.

  7. Probability Prediction in Multistate Survival Models for Patients with Chronic Myeloid Leukaemia

    Institute of Scientific and Technical Information of China (English)

    FANG Ya; Hein Putter

    2005-01-01

    In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis.After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse,especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or afterrelapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.

  8. Survival Prediction and Feature Selection in Patients with Breast Cancer Using Support Vector Regression

    Directory of Open Access Journals (Sweden)

    Shahrbanoo Goli

    2016-01-01

    Full Text Available The Support Vector Regression (SVR model has been broadly used for response prediction. However, few researchers have used SVR for survival analysis. In this study, a new SVR model is proposed and SVR with different kernels and the traditional Cox model are trained. The models are compared based on different performance measures. We also select the best subset of features using three feature selection methods: combination of SVR and statistical tests, univariate feature selection based on concordance index, and recursive feature elimination. The evaluations are performed using available medical datasets and also a Breast Cancer (BC dataset consisting of 573 patients who visited the Oncology Clinic of Hamadan province in Iran. Results show that, for the BC dataset, survival time can be predicted more accurately by linear SVR than nonlinear SVR. Based on the three feature selection methods, metastasis status, progesterone receptor status, and human epidermal growth factor receptor 2 status are the best features associated to survival. Also, according to the obtained results, performance of linear and nonlinear kernels is comparable. The proposed SVR model performs similar to or slightly better than other models. Also, SVR performs similar to or better than Cox when all features are included in model.

  9. An Integrative Pathway-based Clinical-genomic Model for Cancer Survival Prediction.

    Science.gov (United States)

    Chen, Xi; Wang, Lily; Ishwaran, Hemant

    2010-09-01

    Prediction models that use gene expression levels are now being proposed for personalized treatment of cancer, but building accurate models that are easy to interpret remains a challenge. In this paper, we describe an integrative clinical-genomic approach that combines both genomic pathway and clinical information. First, we summarize information from genes in each pathway using Supervised Principal Components (SPCA) to obtain pathway-based genomic predictors. Next, we build a prediction model based on clinical variables and pathway-based genomic predictors using Random Survival Forests (RSF). Our rationale for this two-stage procedure is that the underlying disease process may be influenced by environmental exposure (measured by clinical variables) and perturbations in different pathways (measured by pathway-based genomic variables), as well as their interactions. Using two cancer microarray datasets, we show that the pathway-based clinical-genomic model outperforms gene-based clinical-genomic models, with improved prediction accuracy and interpretability.

  10. The Predictive Value of Total Neutrophil Count and Neutrophil/ Lymphocyte Ratio in Predicting In-hospital Mortality and Complications after STEMI

    Directory of Open Access Journals (Sweden)

    Samad Ghaffari

    2014-03-01

    Full Text Available Introduction: Leukocytosis, predominantly neutrophilia, has previously been described following ST elevation myocardial infarction (STEMI. The exact contribution of this phenomenon to the clinical outcome of STEMI is yet to be shown. We examined cellular inflammatory response to STEMI in the blood and its association with in-hospital mortality and/or adverse clinical events.Methods: In this cross-sectional study, 404 patients who were admitted with the diagnosis of acute STEMI at Madani Heart Hospital from March 2010 to March 2012 were studied. The complete blood cell count (CBC was obtained from all patientswithin12-24 hours of the onset of symptoms. Total leukocytes were counted and differential count was obtained for neutrophils, lymphocytes and neutrophil/lymphocyte ratio (NLR were evaluated. Association of cellular response with the incidence of post-MI mortality/complications was assessed by multiple logistic regression analyses.Results: In-hospital mortality and post-STEMI complication rate were 3.7% and 43.6%, respectively. Higher age (P=0.04, female gender (0.002, lower ejection fraction (P<0.001 and absolute neutrophil count (P=0.04 were predictors of mortality. Pump failure in the form of acute pulmonary edema or cardiogenic shock occurred in 35 (8.9% of patients. Higher leukocyte (P<0.03 and neutrophil counts (P<0.03 and higher NLR (P=0.01 were predictors of failure. The frequency of ventricular tachyarrhythmias (VT/VF at the first day was associated with higher neutrophil count (P<0.001 and higher NLR level (P<0.001. In multivariate analysis neutrophil count was an independent predictor of mortality (OR=2.94; 1.1-8.4, P=0.04, and neutrophil count [OR=1.1, CI (1.01-1.20, P=0.02], female gender [OR=2.34, CI (1.02-4.88, P=0.04] and diabetes [OR=2.52, CI (1.21-5.2, P=0.003] were independent predictors of heart failure.Conclusion: A single CBC analysis may help to identify STEMI patients at risk for mortality and heart failure, and total

  11. Cervical cancer survival prediction using hybrid of SMOTE, CART and smooth support vector machine

    Science.gov (United States)

    Purnami, S. W.; Khasanah, P. M.; Sumartini, S. H.; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    According to the WHO, every two minutes there is one patient who died from cervical cancer. The high mortality rate is due to the lack of awareness of women for early detection. There are several factors that supposedly influence the survival of cervical cancer patients, including age, anemia status, stage, type of treatment, complications and secondary disease. This study wants to classify/predict cervical cancer survival based on those factors. Various classifications methods: classification and regression tree (CART), smooth support vector machine (SSVM), three order spline SSVM (TSSVM) were used. Since the data of cervical cancer are imbalanced, synthetic minority oversampling technique (SMOTE) is used for handling imbalanced dataset. Performances of these methods are evaluated using accuracy, sensitivity and specificity. Results of this study show that balancing data using SMOTE as preprocessing can improve performance of classification. The SMOTE-SSVM method provided better result than SMOTE-TSSVM and SMOTE-CART.

  12. Prediction of survival after surgery due to skeletal metastases in the extremities

    DEFF Research Database (Denmark)

    Sørensen, M S; Gerds, T A; Hindsø, K

    2016-01-01

    AIMS: The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. METHODS: We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females....../54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony...... metastases and American Society of Anaesthesiologist's score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under...

  13. Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: A Multi-Site, Blinded Validation Study

    Science.gov (United States)

    Shedden, Kerby; Taylor, Jeremy M.G.; Enkemann, Steve A.; Tsao, Ming S.; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steve; Jurisica, Igor; Venkatraman, Seshan E.; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang Qi; Strumpf, Dan; Hanash, Samir; Shepherd, Francis A.; Ding, Kuyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan; Weir, Barbara; Verhaak, Roel; Ladd-Acosta, Christine; Golub, Todd; Gruidl, Mike; Szoke, Janos; Zakowski, Maureen; Rusch, Valerie; Kris, Mark; Viale, Agnes; Motoi, Noriko; Travis, William; Sharma, Anupama

    2009-01-01

    Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. PMID:18641660

  14. Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Tiantian Li; Xuezhen Ma; Yuan Yao

    2014-01-01

    Objective:The purpose of the study was to assess prognostic factors to predict overal survival (OS) and progres-sion-free survival (PFS) in non-smal-celllung cancer (NSCLC) with brain metastasis (BM). Methods:From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy (WBRT) combined with tyrosine kinase inhibitor (TKIs). The ef icacy and adverse reaction were evaluated after treatment. Results:In terms of intracranial lesions, the objective response rate (ORR) and the disease control rate (DCR) were 22.6%and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3%and 93.5%, respectively. The median time to progression-free survival (PFS) was 298 days (95%CI:258.624-337.376 days), whereas in the epidermal growth factor receptor (EGFR) mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate (RR) than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxici-ties were rash and diarrhea, but al were wel-tolerated. Conclusion:EGFR-mutations is the independent prognostic factors af ecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be ef ective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.

  15. Polymorphism at 19q13.41 predicts breast cancer survival specifically after endocrine therapy

    Science.gov (United States)

    Khan, Sofia; Fagerholm, Rainer; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Liu, Jianjun

    2015-01-01

    Purpose Although most estrogen receptor (ER)-positive breast cancer patients benefit from endocrine therapies, a significant proportion do not. Our aim was to identify inherited genetic variations that might predict survival among patients receiving adjuvant endocrine therapies. Experimental Design We performed a meta-analysis of two genome-wide studies; Helsinki Breast Cancer Study, 805 patients, with 240 receiving endocrine therapy and Prospective study of Outcomes in Sporadic versus Hereditary breast cancer, 536 patients, with 155 endocrine therapy-patients, evaluating 486,478 single nucleotide polymorphisms (SNPs). The top four associations from the endocrine treatment subgroup were further investigated in two independent datasets totalling 5011 patients, with 3485 receiving endocrine therapy. Results A meta-analysis identified a common SNP rs8113308, mapped to 19q13.41, associating with reduced survival among endocrine treated patients (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.37-2.07, P = 6.34 ×10−7) and improved survival among ER-negative patients, with a similar trend in ER-positive cases not receiving endocrine therapy. In a multivariate analysis adjusted for conventional prognostic factors, we found a significant interaction between the rs8113308 and endocrine treatment indicating a predictive, treatment-specific effect of the SNP rs8113308 on breast cancer survival, with the per-allele HR for interaction 2.16 (95% CI 1.30 – 3.60, Pinteraction = 0.003) and HR=7.77 (95% CI 0.93 – 64.71) for the homozygous genotype carriers. A biological rationale is suggested by in silico functional analyses. Conclusions Our findings suggest carrying the rs8113308 rare allele may identify patients who will not benefit from adjuvant endocrine treatment. PMID:25964295

  16. EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

    Science.gov (United States)

    Husa, Anna-Maria; Magić, Željana; Larsson, Malin; Fornander, Tommy; Pérez-Tenorio, Gizeh

    2016-01-01

    The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan® Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization. PMID:26870995

  17. A new 500 kb haplotype associated with high CD8+ T-lymphocyte numbers predicts a less severe expression of hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Mascarenhas Cláudia

    2008-11-01

    patients were also observed in the geographically different population of Canadian patients, also predicting CD8+ T-lymphocyte numbers and the severity of disease. Conclusion These results may have important implications not only for approaching the question of the penetrance of the hemochromatosis gene in different world populations but also to further narrow the region of interest to find a candidate gene involved in the setting of CD8+ T-lymphocyte numbers in humans.

  18. Radiation therapy for nasopharyngeal carcinoma: the predictive value of interim survival assessment.

    Science.gov (United States)

    Toya, Ryo; Murakami, Ryuji; Saito, Tetsuo; Murakami, Daizo; Matsuyama, Tomohiko; Baba, Yuji; Nishimura, Ryuichi; Hirai, Toshinori; Semba, Akiko; Yumoto, Eiji; Yamashita, Yasuyuki; Oya, Natsuo

    2016-09-01

    Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (interim assessment could predict survival in NPC patients.

  19. Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity

    Science.gov (United States)

    Ilhan, Harun; Higuchi, Takahiro; Buck, Andreas K.; Lehner, Sebastian; Bartenstein, Peter; Bengel, Frank; Schatka, Imke; Muegge, Dirk O.; Papp, László; Zsótér, Norbert; Große-Ophoff, Tobias; Essler, Markus; Bundschuh, Ralph A.

    2017-01-01

    The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management. PMID:27705948

  20. Survival prediction based on compound covariate under Cox proportional hazard models.

    Directory of Open Access Journals (Sweden)

    Takeshi Emura

    Full Text Available Survival prediction from a large number of covariates is a current focus of statistical and medical research. In this paper, we study a methodology known as the compound covariate prediction performed under univariate Cox proportional hazard models. We demonstrate via simulations and real data analysis that the compound covariate method generally competes well with ridge regression and Lasso methods, both already well-studied methods for predicting survival outcomes with a large number of covariates. Furthermore, we develop a refinement of the compound covariate method by incorporating likelihood information from multivariate Cox models. The new proposal is an adaptive method that borrows information contained in both the univariate and multivariate Cox regression estimators. We show that the new proposal has a theoretical justification from a statistical large sample theory and is naturally interpreted as a shrinkage-type estimator, a popular class of estimators in statistical literature. Two datasets, the primary biliary cirrhosis of the liver data and the non-small-cell lung cancer data, are used for illustration. The proposed method is implemented in R package "compound.Cox" available in CRAN at http://cran.r-project.org/.

  1. SHOX2 is a Potent Independent Biomarker to Predict Survival of WHO Grade II–III Diffuse Gliomas

    Directory of Open Access Journals (Sweden)

    Yu-An Zhang

    2016-11-01

    Interpretation: We have identified that SHOX2 expression or methylation are potent independent prognostic indicators for predicting LGG patient survival, and have potential to identify an important subset of LGG patients with IDHwt status with significantly better overall survival. The combination of IDH or other relevant markers with SHOX2 identified LGG subsets with significantly different survival outcomes, and further understanding of these subsets may benefit therapeutic target identification and therapy selections for glioma patients.

  2. The MITOS system predicts long-term survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tramacere, Irene; Dalla Bella, Eleonora; Chiò, Adriano; Mora, Gabriele; Filippini, Graziella; Lauria, Giuseppe

    2015-11-01

    The choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months. Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. The ALS-MITOS system is composed of four key domains included in the ALSFRS-R scale (walking/self-care, swallowing, communicating and breathing), each with a threshold reflecting the loss of function in the specific ALSFRS-R subscores. Sensitivity, specificity and the area under the curve of the receiver operating characteristic curves of the ALS-MITOS system stages and ALSFRS-R decline at 6 months were calculated and compared with the primary outcome (survival, tracheotomy or >23-hour non-invasive ventilation) at 12 and 18 months Predicted probabilities of the ALS-MITO system at 6 months for any event at 12 and 18 months were computed through logistic regression models. Disease progression from baseline to 6 months as defined by the ALS-MITOS system predicted death, tracheotomy or >23-hour non-invasive ventilation at 12 months with 82% sensitivity (95% CI 71% to 93%, n=37/45) and 63% specificity (95% CI 55% to 71%, n=92/146), and at 18 months with 71% sensitivity (95% CI 61% to 82%, n=50/70) and 68% specificity (95% CI 60% to 77%, n=76/111). The analysis of ALS-MITOS and ALSFRS-R progression at 6-month follow-up showed that the best cut-off to

  3. Management of hepatocellular carcinoma: Predictive valueof immunohistochemical markers for postoperative survival

    Institute of Scientific and Technical Information of China (English)

    Zhao-Shan Niu; Xiao-Jun Niu; Mei Wang

    2015-01-01

    Hepatocellular carcinoma (HCC) accounts for over 90%of all primary liver cancers. With an ever increasingincidence trend year by year, it has become the thirdmost common cause of death from cancer worldwide.Hepatic resection is generally considered to be one ofthe most effective therapies for HCC patients, however,there is a high risk of recurrence in postoperativeHCC. In clinical practice, there exists an urgent needfor valid prognostic markers to identify patientswith prognosis, hence the importance of studies onprognostic markers in improving the prediction of HCCprognosis. This review focuses on the most promisingimmunohistochemical prognostic markers in predictingthe postoperative survival of HCC patients.

  4. Developing and Validating a Survival Prediction Model for NSCLC Patients Through Distributed Learning Across 3 Countries.

    Science.gov (United States)

    Jochems, Arthur; Deist, Timo M; El Naqa, Issam; Kessler, Marc; Mayo, Chuck; Reeves, Jackson; Jolly, Shruti; Matuszak, Martha; Ten Haken, Randall; van Soest, Johan; Oberije, Cary; Faivre-Finn, Corinne; Price, Gareth; de Ruysscher, Dirk; Lambin, Philippe; Dekker, Andre

    2017-10-01

    Tools for survival prediction for non-small cell lung cancer (NSCLC) patients treated with chemoradiation or radiation therapy are of limited quality. In this work, we developed a predictive model of survival at 2 years. The model is based on a large volume of historical patient data and serves as a proof of concept to demonstrate the distributed learning approach. Clinical data from 698 lung cancer patients, treated with curative intent with chemoradiation or radiation therapy alone, were collected and stored at 2 different cancer institutes (559 patients at Maastro clinic (Netherlands) and 139 at Michigan university [United States]). The model was further validated on 196 patients originating from The Christie (United Kingdon). A Bayesian network model was adapted for distributed learning (the animation can be viewed at https://www.youtube.com/watch?v=ZDJFOxpwqEA). Two-year posttreatment survival was chosen as the endpoint. The Maastro clinic cohort data are publicly available at https://www.cancerdata.org/publication/developing-and-validating-survival-prediction-model-nsclc-patients-through-distributed, and the developed models can be found at www.predictcancer.org. Variables included in the final model were T and N category, age, performance status, and total tumor dose. The model has an area under the curve (AUC) of 0.66 on the external validation set and an AUC of 0.62 on a 5-fold cross validation. A model based on the T and N category performed with an AUC of 0.47 on the validation set, significantly worse than our model (P<.001). Learning the model in a centralized or distributed fashion yields a minor difference on the probabilities of the conditional probability tables (0.6%); the discriminative performance of the models on the validation set is similar (P=.26). Distributed learning from federated databases allows learning of predictive models on data originating from multiple institutions while avoiding many of the data-sharing barriers. We believe

  5. Cell survival in carbon beams - comparison of amorphous track model predictions

    DEFF Research Database (Denmark)

    Grzanka, L.; Greilich, S.; Korcyl, M.

    . [2] . In addition, a new approach based on microdosimetric distributions is presented and investigated [3] . Material and methods: A suitable software library embrasing the mentioned amorphous track models including numerous submodels with respect to delta-electron range models, radial dose......Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under ion...... irradiation. The aim of this paper is to compare the predictions from different amorphous approaches found in the literature - more specifically the phenomenological, analytical model by Katz and co-workers [1] and a Monte-Carlo based full as implemented for example in the local effect model by Scholz et al...

  6. Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Bertini, Ivano; Cacciatore, Stefano; Jensen, Benny V;

    2012-01-01

    survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of m......Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist...... that is strong enough to predict overall survival (OS). In 153 patients with mCRC and 139 healthy subjects from three Danish hospitals, we profiled two independent sets of serum samples in a prospective phase II study. In the training set, (1)H-NMR metabolomic profiling could discriminate patients with mCRC from...

  7. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Lee SH

    2015-04-01

    Full Text Available Sangheun Lee,1,* Beom Kyung Kim,2–5,* Seung Up Kim,2–5 Jun Yong Park,2–5 Do Young Kim,2–5 Sang Hoon Ahn,2–6 Kwang-Hyub Han2–6 1Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea; 2Department of Internal Medicine, 3Institute of Gastroenterology, 4Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 6Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.   *These authors contributed equally to this work Background: It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC. We investigated whether the α-fetoprotein (AFP response is associated with survival in patients with advanced HCC treated with sorafenib. Methods: We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6–8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival (OS and progression-free survival (PFS were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR was identified in 5 patients (4.0%, stable disease (SD in 65 patients (51.6%, and progressive disease (PD in 57 patients (44.4%, respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response, together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05, and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response, together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05. SD or PR was more frequently found

  8. The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    Cornec-Le Gall, Emilie; Audrézet, Marie-Pierre; Rousseau, Annick; Hourmant, Maryvonne; Renaudineau, Eric; Charasse, Christophe; Morin, Marie-Pascale; Moal, Marie-Christine; Dantal, Jacques; Wehbe, Bassem; Perrichot, Régine; Frouget, Thierry; Vigneau, Cécile; Potier, Jérôme; Jousset, Philippe; Guillodo, Marie-Paule; Siohan, Pascale; Terki, Nazim; Sawadogo, Théophile; Legrand, Didier; Menoyo-Calonge, Victorio; Benarbia, Seddik; Besnier, Dominique; Longuet, Hélène; Férec, Claude

    2016-01-01

    The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD. PMID:26150605

  9. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Bonassi, S; Hagmar, L; Strömberg, U

    2000-01-01

    An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role p...

  10. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit

    NARCIS (Netherlands)

    de Jager, C.P.C.; van Wijk, P.T.I.; Mathoera, R.B.; de Jongh-Leuvenink, J.; van der Poll, T.; Wever, P.C.

    2010-01-01

    Introduction: Absolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients. Methods: We retrospectively eval

  11. Molecular classification and survival prediction in human gliomas based on proteome analysis.

    Science.gov (United States)

    Iwadate, Yasuo; Sakaida, Tsukasa; Hiwasa, Takaki; Nagai, Yuichiro; Ishikura, Hiroshi; Takiguchi, Masaki; Yamaura, Akira

    2004-04-01

    The biological features of gliomas, which are characterized by highly heterogeneous biological aggressiveness even in the same histological category, would be precisely described by global gene expression data at the protein level. We investigated whether proteome analysis based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can identify differences in protein expression between high- and low-grade glioma tissues. Proteome profiling patterns were compared in 85 tissue samples: 52 glioblastoma multiforme, 13 anaplastic astrocytomas, 10 atrocytomas, and 10 normal brain tissues. We could completely distinguish the normal brain tissues from glioma tissues by cluster analysis based on the proteome profiling patterns. Proteome-based clustering significantly correlated with the patient survival, and we could identify a biologically distinct subset of astrocytomas with aggressive nature. Discriminant analysis extracted a set of 37 proteins differentially expressed based on histological grading. Among them, many of the proteins that were increased in high-grade gliomas were categorized as signal transduction proteins, including small G-proteins. Immunohistochemical analysis confirmed the expression of identified proteins in glioma tissues. The present study shows that proteome analysis is useful to develop a novel system for the prediction of biological aggressiveness of gliomas. The proteins identified here could be novel biomarkers for survival prediction and rational targets for antiglioma therapy.

  12. EGFR expression level predicts response and overall survival in gastric cancer PDTX model treated with cetuximab

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:hTe aim of this study was to determine whether the EGFR statuscould significantly predict some benefit in overall survival and response to cetuximab in advanced GC xenografts.Methods: Two hundred xenografts derived from 20 GC patients were established. Then they were divided into cetuximab treated group and control group randomly.Results:Among the cetuximab treated group, 4 GC cases were identified responded to cetuximab.hTose cetuximab treated PDX models had longer OS than non-treated. High EGFR mRNA expression and immunohistochemistry score are more prone to response to cetuximab. EGFR amplification, mRNA and protein overexpression were associated with the OS in cetuximab treated PDX models. Moreover, in the PDX models derived from EGFR ampliifcation, mRNA or protein overexpression cases, the OS is signiifcantly different between the cetuximab treated and control group, while the OS in not statistically different in other cases.Conclusion:EGFR status predicts sensitivity to therapy and survival in GC treated with cetuximab, especially the mRNA and protein expression level.

  13. A survival prediction model of rats in hemorrhagic shock using the random forest classifier.

    Science.gov (United States)

    Choi, Joon Yul; Kim, Sung Kean; Lee, Wan Hyung; Yoo, Tae Keun; Kim, Deok Won

    2012-01-01

    Hemorrhagic shock is the cause of one third of deaths resulting from injury in the world. Although many studies have tried to diagnose hemorrhagic shock early and accurately, such attempts were inconclusive due to compensatory mechanisms of humans. The objective of this study was to construct a survival prediction model of rats in hemorrhagic shock using a random forest (RF) model, which is a newly emerged classifier acknowledged for its performance. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), lactate concentration (LC), and perfusion (PF) measured in rats were used as input variables for the RF model and its performance was compared with that of a logistic regression (LR) model. Before constructing the models, we performed a 5-fold cross validation for RF variable selection and forward stepwise variable selection for the LR model to see which variables are important for the models. For the LR model, sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (ROC-AUC) were 1, 0.89, 0.94, and 0.98, respectively. For the RF models, sensitivity, specificity, accuracy, and AUC were 0.96, 1, 0.98, and 0.99, respectively. In conclusion, the RF model was superior to the LR model for survival prediction in the rat model.

  14. Do conflict resolution and recovery predict the survival of adolescents' romantic relationships?

    Directory of Open Access Journals (Sweden)

    Thao Ha

    Full Text Available Numerous studies have shown that being able to resolve and recover from conflicts is of key importance for relationship satisfaction and stability in adults. Less is known about the importance of these relationship dynamics in adolescent romantic relationships. Therefore, this study investigated whether conflict resolution and recovery predict breakups in middle adolescent couples. Couples who are able to resolve and recover from conflict were expected to demonstrate a lower probability of breaking up. In total, 80 adolescent couples (M age = 15.48, SD = 1.16 participated in a 4-wave prospective questionnaire and observational study, with one year between measurements. In addition to self-report measures, adolescents were observed in real-time during conflicts with their partners. Multilevel Proportional Hazard analyses revealed that, contrary to the hypothesis, conflict resolution and conflict recovery did not predict the likelihood of breakup. Survival differences were not attributable to conflict resolution or conflict recovery. More research is needed to consider the unique relationship factors of adolescent romantic relationships to determine why some relationships survive while others do not.

  15. Utilization of Data Mining Techniques for Prediction and Diagnosis of Tuberculosis Disease Survivability

    Directory of Open Access Journals (Sweden)

    K.R.Lakshmi

    2013-10-01

    Full Text Available The prediction and diagnosis of Tuberculosis survivability has been a challenging research problem for many researchers. Since the early dates of the related research, much advancement has been recorded in several related fields. For instance, thanks to innovative biomedical technologies, better explanatory prognostic factors are being measured and recorded; thanks to low cost computer hardware and software technologies, high volume better quality data is being collected and stored automatically; and finally thanks to better analytical methods, those voluminous data is being processed effectively and efficiently. Tuberculosis is one of the leading diseases for all people in developed countries including India. It is the most common cause of death in human being. The high incidence of Tuberculosis in all people has increased significantly in the last years. In this paper we have discussed various data mining approaches that have been utilized for Tuberculosis diagnosis and prognosis. This study paper summarizes various review and technical articles on Tuberculosis diagnosis and prognosis also we focus on current research being carried out using the data mining techniques to enhance the Tuberculosis diagnosis and prognosis. Here, we took advantage of those available technological advancements to develop the best prediction model for Tuberculosis survivability.

  16. Organism activity levels predict marine invertebrate survival during ancient global change extinctions.

    Science.gov (United States)

    Clapham, Matthew E

    2017-04-01

    Multistressor global change, the combined influence of ocean warming, acidification, and deoxygenation, poses a serious threat to marine organisms. Experimental studies imply that organisms with higher levels of activity should be more resilient, but testing this prediction and understanding organism vulnerability at a global scale, over evolutionary timescales, and in natural ecosystems remain challenging. The fossil record, which contains multiple extinctions triggered by multistressor global change, is ideally suited for testing hypotheses at broad geographic, taxonomic, and temporal scales. Here, I assess the importance of activity level for survival of well-skeletonized benthic marine invertebrates over a 100-million-year-long interval (Permian to Jurassic periods) containing four global change extinctions, including the end-Permian and end-Triassic mass extinctions. More active organisms, based on a semiquantitative score incorporating feeding and motility, were significantly more likely to survive during three of the four extinction events (Guadalupian, end-Permian, and end-Triassic). In contrast, activity was not an important control on survival during nonextinction intervals. Both the end-Permian and end-Triassic mass extinctions also triggered abrupt shifts to increased dominance by more active organisms. Although mean activity gradually returned toward pre-extinction values, the net result was a permanent ratcheting of ecosystem-wide activity to higher levels. Selectivity patterns during ancient global change extinctions confirm the hypothesis that higher activity, a proxy for respiratory physiology, is a fundamental control on survival, although the roles of specific physiological traits (such as extracellular pCO2 or aerobic scope) cannot be distinguished. Modern marine ecosystems are dominated by more active organisms, in part because of selectivity ratcheting during these ancient extinctions, so on average may be less vulnerable to global change

  17. Prediction of the survival and functional ability of severe stroke patients after ICU therapeutic intervention

    Directory of Open Access Journals (Sweden)

    Aoun-Bacha Zeina

    2008-06-01

    Full Text Available Abstract Background This study evaluated the benefits and impact of ICU therapeutic interventions on the survival and functional ability of severe cerebrovascular accident (CVA patients. Methods Sixty-two ICU patients suffering from severe ischemic/haemorrhagic stroke were evaluated for CVA severity using APACHE II and the Glasgow coma scale (GCS. Survival was determined using Kaplan-Meier survival tables and survival prediction factors were determined by Cox multivariate analysis. Functional ability was assessed using the stroke impact scale (SIS-16 and Karnofsky score. Risk factors, life support techniques and neurosurgical interventions were recorded. One year post-CVA dependency was investigated using multivariate analysis based on linear regression. Results The study cohort constituted 6% of all CVA (37.8% haemorrhagic/62.2% ischemic admissions. Patient mean(SD age was 65.8(12.3 years with a 1:1 male: female ratio. During the study period 16 patients had died within the ICU and seven in the year following hospital release. The mean(SD APACHE II score at hospital admission was 14.9(6.0 and ICU mean duration of stay was 11.2(15.4 days. Mechanical ventilation was required in 37.1% of cases. Risk ratios were; GCS at admission 0.8(0.14, (p = 0.024, APACHE II 1.11(0.11, (p = 0.05 and duration of mechanical ventilation 1.07(0.07, (p = 0.046. Linear coefficients were: type of CVA – haemorrhagic versus ischemic: -18.95(4.58 (p = 0.007, GCS at hospital admission: -6.83(1.08, (p = 0.001, and duration of hospital stay -0.38(0.14, (p = 0.40. Conclusion To ensure a better prognosis CVA patients require ICU therapeutic interventions. However, as we have shown, where tests can determine the worst affected patients with a poor vital and functional outcome should treatment be withheld?

  18. Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival.

    Science.gov (United States)

    Koreth, John; Kim, Haesook T; Nikiforow, Sarah; Milford, Edgar L; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Ho, Vincent T; Antin, Joseph H; Soiffer, Robert J; Ritz, Jerome; Alyea, Edwin P

    2014-10-01

    The impact of early donor cell chimerism on outcomes of T cell-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse, and nonrelapse mortality (NRM). We evaluated 688 patients with hematologic malignancies (48% myeloid and 52% lymphoid) and a median age of 57 years (range, 18 to 74) undergoing RIC HSCT with T cell-replete donor grafts (97% peripheral blood; 92% HLA-matched), with a median follow-up of 58.2 months (range, 12.6 to 120.7). In multivariable analysis, total donor cell and T cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism D100 total donor cell chimerism or T cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts who may benefit from additional therapeutic interventions. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Gene expression-based classification of non-small cell lung carcinomas and survival prediction.

    Directory of Open Access Journals (Sweden)

    Jun Hou

    Full Text Available BACKGROUND: Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Gene expression profiling holds promise to improve clinical stratification, thus paving the way for individualized therapy. METHODOLOGY AND PRINCIPAL FINDINGS: A genome-wide gene expression analysis was performed on a cohort of 91 patients. We used 91 tumor- and 65 adjacent normal lung tissue samples. We defined sets of predictor genes (probe sets with the expression profiles. The power of predictor genes was evaluated using an independent cohort of 96 non-small cell lung cancer- and 6 normal lung samples. We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of non-small cell lung cancer. Correlation analysis identified 17 genes which showed the best association with post-surgery survival time. This signature was used for stratification of all patients in two risk groups. Kaplan-Meier survival curves show that the two groups display a significant difference in post-surgery survival time (p = 5.6E-6. The performance of the signatures was validated using a patient cohort of similar size (Duke University, n = 96. Compared to previously published prognostic signatures for NSCLC, the 17 gene signature performed well on these two cohorts. CONCLUSIONS: The gene signatures identified are promising tools for histo-pathological classification of non-small cell lung cancer, and may improve the prediction of clinical outcome.

  20. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Robak, Tadeusz; Dmoszynska, Anna; Solal-Céligny, Philippe

    2010-01-01

    Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized...

  1. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Robak, Tadeusz; Dmoszynska, Anna; Solal-Céligny, Philippe;

    2010-01-01

    Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized...

  2. Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

    Science.gov (United States)

    Glei, Dana A; Goldman, Noreen; Risques, Rosa Ana; Rehkopf, David H; Dow, William H; Rosero-Bixby, Luis; Weinstein, Maxine

    2016-01-01

    Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally representative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mortality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reported variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists

  3. Distance in cancer gene expression from stem cells predicts patient survival.

    Science.gov (United States)

    Riester, Markus; Wu, Hua-Jun; Zehir, Ahmet; Gönen, Mithat; Moreira, Andre L; Downey, Robert J; Michor, Franziska

    2017-01-01

    The degree of histologic cellular differentiation of a cancer has been associated with prognosis but is subjectively assessed. We hypothesized that information about tumor differentiation of individual cancers could be derived objectively from cancer gene expression data, and would allow creation of a cancer phylogenetic framework that would correlate with clinical, histologic and molecular characteristics of the cancers, as well as predict prognosis. Here we utilized mRNA expression data from 4,413 patient samples with 7 diverse cancer histologies to explore the utility of ordering samples by their distance in gene expression from that of stem cells. A differentiation baseline was obtained by including expression data of human embryonic stem cells (hESC) and human mesenchymal stem cells (hMSC) for solid tumors, and of hESC and CD34+ cells for liquid tumors. We found that the correlation distance (the degree of similarity) between the gene expression profile of a tumor sample and that of stem cells orients cancers in a clinically coherent fashion. For all histologies analyzed (including carcinomas, sarcomas, and hematologic malignancies), patients with cancers with gene expression patterns most similar to that of stem cells had poorer overall survival. We also found that the genes in all undifferentiated cancers of diverse histologies that were most differentially expressed were associated with up-regulation of specific oncogenes and down-regulation of specific tumor suppressor genes. Thus, a stem cell-oriented phylogeny of cancers allows for the derivation of a novel cancer gene expression signature found in all undifferentiated forms of diverse cancer histologies, that is competitive in predicting overall survival in cancer patients compared to previously published prediction models, and is coherent in that gene expression was associated with up-regulation of specific oncogenes and down-regulation of specific tumor suppressor genes associated with regulation of

  4. Pretreatment T lymphocyte numbers are contributing to the prognostic significance of absolute lymphocyte numbers in B-cell non-Hodgkins lymphomas.

    Science.gov (United States)

    Gergely, Lajos; Váncsa, Andrea; Miltényi, Zsófia; Simon, Zsófia; Baráth, Sándor; Illés, Árpád

    2011-06-01

    Targeted immuno-chemotherapy resulted in greatly improved survival of B cell lymphoma patients. Several prognostic markers are investigated, amongst them the pretreatment absolute lymphocyte numbers. We investigated lymphocyte subpopulations and correlated this data with prognosis of patients. 88 patients (mean age: 56 years, 18-88, median follow up 32 months) with B cell lymphomas were investigated. There were 51 DLBCL, 16 Follicular NHL, 4 MALT, 7 Marginal Zone NHL, 10 Small lymphocytic cases were investigated. Our data showed that overall survival was statistically significant up to the 0.9 G/l absolute lymphocyte numbers as dividers between the subgroups. The CD19+ B cell numbers, or the CD56+/CD3- NK cell numbers did not represent any significant differences between subgroups. However CD3+, CD4+ and CD8+ T cells were differentiating statistically significant subgroups. Pretreatment CD3+ cell number less than 700/ul and CD8+ cell number less than 200/ul were corresponding with significantly inferior overall survival. These could be verified in the bad prognostic IPI group as well. Our data further support the importance of pretreatment lymphocyte numbers and highlight CD3+ and CD8+ lymphocytes to be the key factors in predicting outcome.

  5. Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Cox regression is commonly used to predict the outcome by the time to an event of interest and in addition, identify relevant features for survival analysis in cancer genomics. Due to the high-dimensionality of high-throughput genomic data, existing Cox models trained on any particular dataset usually generalize poorly to other independent datasets. In this paper, we propose a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network information into the Cox's proportional hazard model to explore the co-expression or functional relation among high-dimensional gene expression features in the gene network. Net-Cox was applied to analyze three independent gene expression datasets including the TCGA ovarian cancer dataset and two other public ovarian cancer datasets. Net-Cox with the network information from gene co-expression or functional relations identified highly consistent signature genes across the three datasets, and because of the better generalization across the datasets, Net-Cox also consistently improved the accuracy of survival prediction over the Cox models regularized by L(2 or L(1. This study focused on analyzing the death and recurrence outcomes in the treatment of ovarian carcinoma to identify signature genes that can more reliably predict the events. The signature genes comprise dense protein-protein interaction subnetworks, enriched by extracellular matrix receptors and modulators or by nuclear signaling components downstream of extracellular signal-regulated kinases. In the laboratory validation of the signature genes, a tumor array experiment by protein staining on an independent patient cohort from Mayo Clinic showed that the protein expression of the signature gene FBN1 is a biomarker significantly associated with the early recurrence after 12 months of the treatment in the ovarian cancer patients who are

  6. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

    Directory of Open Access Journals (Sweden)

    Elena Pereira

    Full Text Available High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools.Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival.Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential

  7. Can survival prediction be improved by merging gene expression data sets?

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    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  8. Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Cox regression is commonly used to predict the outcome by the time to an event of interest and in addition, identify relevant features for survival analysis in cancer genomics. Due to the high-dimensionality of high-throughput genomic data, existing Cox models trained on any particular dataset usually generalize poorly to other independent datasets. In this paper, we propose a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network information into the Cox's proportional hazard model to explore the co-expression or functional relation among high-dimensional gene expression features in the gene network. Net-Cox was applied to analyze three independent gene expression datasets including the TCGA ovarian cancer dataset and two other public ovarian cancer datasets. Net-Cox with the network information from gene co-expression or functional relations identified highly consistent signature genes across the three datasets, and because of the better generalization across the datasets, Net-Cox also consistently improved the accuracy of survival prediction over the Cox models regularized by L(2 or L(1. This study focused on analyzing the death and recurrence outcomes in the treatment of ovarian carcinoma to identify signature genes that can more reliably predict the events. The signature genes comprise dense protein-protein interaction subnetworks, enriched by extracellular matrix receptors and modulators or by nuclear signaling components downstream of extracellular signal-regulated kinases. In the laboratory validation of the signature genes, a tumor array experiment by protein staining on an independent patient cohort from Mayo Clinic showed that the protein expression of the signature gene FBN1 is a biomarker significantly associated with the early recurrence after 12 months of the treatment in the ovarian cancer patients who are

  9. PREDICTIVE MODEL FOR SURVIVAL AND GROWTH OF SALMONELLA TYPHIMURIUM DT104 ON CHICKEN SKIN DURING TEMPERATURE ABUSE

    Science.gov (United States)

    To better predict risk of Salmonella infection from chicken subjected to temperature abuse, a study was undertaken to develop a predictive model for survival and growth of Salmonella Typhimurium DT104 on chicken skin with native micro flora. For model development, chicken skin portions were inocula...

  10. LncRNA Expression Discriminates Karyotype and Predicts Survival in B-lymphoblastic Leukemia

    Science.gov (United States)

    Fernando, Thilini R.; Rodriguez-Malave, Norma I.; Waters, Ella V.; Yan, Weihong; Casero, David; Basso, Giuseppe; Pigazzi, Martina; Rao, Dinesh S.

    2015-01-01

    Long non-coding RNAs (lncRNAs) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by RT-qPCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. Implications lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis. PMID:25681502

  11. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma

    DEFF Research Database (Denmark)

    Porter, Sarah; Span, Paul N; Sweep, Fred C G J;

    2006-01-01

    We recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non-neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup......% C.I. = 2.16-13.5, p prediction of poor prognosis by ADAMTS8 and ADAMTS15 expression was found to be independent of other classical clinicopathological factors. Results observed in FVB-PyMT mice, a robust transgenic model of highly metastatic...... breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients...

  12. Consciousness levels one week after admission to a palliative care unit improve survival prediction in advanced cancer patients.

    Science.gov (United States)

    Tsai, Jaw-Shiun; Chen, Chao-Hsien; Wu, Chih-Hsun; Chiu, Tai-Yuan; Morita, Tatsuya; Chang, Chin-Hao; Hung, Shou-Hung; Lee, Ya-Ping; Chen, Ching-Yu

    2015-02-01

    Consciousness is an important factor of survival prediction in advanced cancer patients. However, effects on survival of changes over time in consciousness in advanced cancer patients have not been fully explored. This study evaluated changes in consciousness after admission to a palliative care unit and their correlation with prognosis in terminal cancer patients. This is a prospective observational study. From a palliative care unit in Taiwan, 531 cancer patients (51.8% male) were recruited. Consciousness status was assessed at admission and one week afterwards and recorded as normal or impaired. The mean age was 65.28±13.59 years, and the average survival time was 23.41±37.69 days. Patients with normal consciousness at admission (n=317) had better survival than those with impaired consciousness at admission (n=214): (17.0 days versus 6.0 days, pconsciousness at admission had a higher percentage of survival than the impaired (78.9% versus 44.3%, pconsciousness levels: (1) normal at admission and one week afterwards, (2) impaired at admission but normal one week afterwards, (3) normal at admission but impaired one week afterwards, and (4) impaired both at admission and one week afterwards. The former two groups had significantly better survival than the latter two groups: (median survival counted from day 7 after admission), 25.5, 27.0, 7.0, and 7.0 days, respectively. Consciousness levels one week after admission should be integrated into survival prediction in advanced cancer patients.

  13. Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation.

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    Deng-Mei Tian

    Full Text Available Rapid immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT is significantly associated with lower infection, relapse and possibly secondary malignancy rates. The aim of this study was to investigate the role of peripheral lymphocyte subsets, especially CD3+CD8+ cytotoxic T cell recovery, in predicting transplant outcomes, including the overall survival (OS and non-relapse mortality (NRM rates after unmanipulated haploidentical blood and marrow transplantation (HBMT.Peripheral blood samples were obtained from 214 HBMT recipients with hematological malignancies. The peripheral lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, and CD19+ B cells were analyzed by flow cytometry at days 30, 60, 90, 180, 270 and 360 after HBMT.The CD3+CD8+ cytotoxic T cell recovery at day 90 (CD3+CD8+-90 was correlated with bacterial infection (P = 0.001, NRM (P = 0.001, leukemia-free survival (LFS, P = 0.005, and OS (P = 0.001 at a cutoff value of 375 cells/μL CD3+CD8+ T cells. The incidence of bacterial infection in patients with the CD3+CD8+-90 at ≥375 cells/μL was significantly lower than that of cases with the CD3+CD8+-90 at <375 cells/μL after HBMT (14.6% versus 41.6%, P<0.001. Multivariate analysis showed the rapid recovery of CD3+CD8+ T cells at day 90 after HBMT was strongly associated with a lower incidence of NRM (HR = 0.30; 95% CI: 0.15-0.60; P = 0.000 and superior LFS (HR = 0.51; 95% CI: 0.32-0.82; P = 0.005 and OS (HR = 0.38; 95% CI: 0.23-0.63; P = 0.000.The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes.

  14. The value of tumor infiltrating lymphocytes (TILs for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

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    Yan Mao

    Full Text Available We carried out a systematic review and meta-analysis to evaluate the predictive roles of tumor infiltrating lymphocytes (TILs in response to neoadjuvant chemotherapy (NAC in breast cancer.A PubMed and Web of Science literature search was designed. Random or fixed effect models were adopted to estimate the summary odds ratio (OR. Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. Publication bias was evaluated using a funnel plot, Egger's test and Begg's test. We included studies where the predictive significance of TILs, and/or TILs subset on the pathologic complete response (pCR were determined in NAC of breast cancer.A total of 13 published studies (including 3251 patients were eligible. In pooled analysis, the detection of higher TILs numbers in pre-treatment biopsy was correlated with better pCR to NAC (OR = 3.93, 95% CI, 3.26-4.73. Moreover, TILs predicted higher pCR rates in triple negative (OR = 2.49, 95% CI: 1.61-3.83, HER2 positive (OR = 5.05, 95% CI: 2.86-8.92 breast cancer, but not in estrogen receptor (ER positive (OR = 6.21, 95%CI: 0.86-45.15 patients. In multivariate analysis, TILs were still an independent marker for high pCR rate (OR = 1.41, 95% CI: 1.19-1.66. For TILs subset, higher levels of CD8+ and FOXP3+ T-lymphocytes in pre-treatment biopsy respectively predicted better pathological response to NAC (OR = 6.44, 95% CI: 2.52-16.46; OR = 2.94, 95% CI: 1.05-8.26. Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80 and multivariate (OR = 0.36, 95% CI: 0.13-0.95 analysis.Higher TILs levels in pre-treatment biopsy indicated higher pCR rates for NAC. TILs subset played different roles in predicting response to NAC.

  15. Single sample expression-anchored mechanisms predict survival in head and neck cancer.

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    Xinan Yang

    2012-01-01

    Full Text Available Gene expression signatures that are predictive of therapeutic response or prognosis are increasingly useful in clinical care; however, mechanistic (and intuitive interpretation of expression arrays remains an unmet challenge. Additionally, there is surprisingly little gene overlap among distinct clinically validated expression signatures. These "causality challenges" hinder the adoption of signatures as compared to functionally well-characterized single gene biomarkers. To increase the utility of multi-gene signatures in survival studies, we developed a novel approach to generate "personal mechanism signatures" of molecular pathways and functions from gene expression arrays. FAIME, the Functional Analysis of Individual Microarray Expression, computes mechanism scores using rank-weighted gene expression of an individual sample. By comparing head and neck squamous cell carcinoma (HNSCC samples with non-tumor control tissues, the precision and recall of deregulated FAIME-derived mechanisms of pathways and molecular functions are comparable to those produced by conventional cohort-wide methods (e.g. GSEA. The overlap of "Oncogenic FAIME Features of HNSCC" (statistically significant and differentially regulated FAIME-derived genesets representing GO functions or KEGG pathways derived from HNSCC tissue among three distinct HNSCC datasets (pathways:46%, p<0.001 is more significant than the gene overlap (genes:4%. These Oncogenic FAIME Features of HNSCC can accurately discriminate tumors from control tissues in two additional HNSCC datasets (n = 35 and 91, F-accuracy = 100% and 97%, empirical p<0.001, area under the receiver operating characteristic curves = 99% and 92%, and stratify recurrence-free survival in patients from two independent studies (p = 0.0018 and p = 0.032, log-rank. Previous approaches depending on group assignment of individual samples before selecting features or learning a classifier are limited by design to

  16. Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    DeVries, Alexander Friedrich [Department of Radio-Oncology, Academic Teaching Hospital Feldkirch, Feldkirch (Austria); Piringer, Gudrun, E-mail: gudrun.piringer@hotmail.com [Department of Oncology, Wels-Grieskirchen Medical Hospital, Wels (Austria); Kremser, Christian; Judmaier, Werner [Department of Radiology, Innsbruck Medical University, Innsbruck (Austria); Saely, Christoph Hubert [Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch (Austria); Lukas, Peter [Department of Radio-Oncology, Innsbruck Medical University, Innsbruck (Austria); Öfner, Dietmar [Department of Surgery, Paracelsus Medical University, Salzburg (Austria)

    2014-12-01

    Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

  17. Developing and comparing two different prognostic indexes for predicting disease-free survival of nonmetastatic breast cancer patients

    OpenAIRE

    TOKATLI, Zehra Füsun; Türe, Mevlüt; Ömürlü, İmran Kurt; ALAS, Ruşen Çoşar; Uzal, Mustafa Cem

    2011-01-01

    To determine 2 different prognostic indexes (PI) for the differentiation of subgroups of nonmetastatic breast cancer patients with the Cox regression analysis and survival tree (ST) methods and the additional usage of the Kaplan-Meier estimates to investigate the predictive power of these methods. Materials and methods: Prognostic factors data were collected for 410 patients. The Cox regression analysis examines the relationship of the survival distribution and covariates. The ST method is ...

  18. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    Science.gov (United States)

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  19. A Transcriptional Fingerprint of Estrogen in Human Breast Cancer Predicts Patient Survival

    Directory of Open Access Journals (Sweden)

    Jianjun Yu

    2008-01-01

    Full Text Available Estrogen signaling plays an essential role in breast cancer progression, and estrogen receptor (ER status has long been a marker of hormone responsiveness. However, ER status alone has been an incomplete predictor of endocrine therapy, as some ER+ tumors, nevertheless, have poor prognosis. Here we sought to use expression profiling of ER+ breast cancer cells to screen for a robust estrogen-regulated gene signature that may serve as a better indicator of cancer outcome. We identified 532 estrogen-induced genes and further developed a 73-gene signature that best separated a training set of 286 primary breast carcinomas into prognostic subtypes by stepwise cross-validation. Notably, this signature predicts clinical outcome in over 10 patient cohorts as well as their respective ER+ subcohorts. Further, this signature separates patients who have received endocrine therapy into two prognostic subgroups, suggesting its specificity as a measure of estrogen signaling, and thus hormone sensitivity. The 73-gene signature also provides additional predictive value for patient survival, independent of other clinical parameters, and outperforms other previously reported molecular outcome signatures. Taken together, these data demonstrate the power of using cell culture systems to screen for robust gene signatures of clinical relevance.

  20. Comparison of the RTS and ISS scores on prediction of survival chances in multiple trauma patients.

    Science.gov (United States)

    Akhavan Akbari, G; Mohammadian, A

    2012-01-01

    Trauma represents the third cause of death after cardio vascular disease and tumors. Also in Iran, road accidents are one of the leading causes of death. Rapid evaluation of trauma severity and prediction of prognosis and mortality rate and probability of survival and rapid treatment of patients is necessary. One of the useful instruments for this is ISS and RTS scoring systems. This study evaluated 70 multi trauma patients in Fatemi trauma center affiliated to Ardabil University of medical science. This study was prospective study populations were 70 trauma patients admitted in Fatemi trauma center. During the II month, and patients data was collected by clinical evaluating of patients and follow up them and arranged as a questionnaire then related findings were evaluated by SPSS software. The average age of patients was 37.6±23.5 years and minimum and maximum age was 1 and 85 years. The most common involved group was 10-19 years (13 men and 1 woman). 81.4% of patients (57 cases were male) and 18.6% were female (13 cases). The most common causes of trauma was car accident with 64.2% frequency (43 cases) and then motorcycle accident with 16.4% frequency (11 cases) and all injured patient due to motorcycle accident compose the age group less than 40 years old. Also car accident had the highest frequency in both gender. Other causes of trauma were fall down with 13.5% frequency (9 cases) and under debris 5.9% (4 cases). Also from 70 studied patients, 67 cases (95.7%) had blunt trauma and 3 cases (4.3%) had penetrating trauma. The most penetrating trauma occurs in ages less than 50 years and was in the range of 30-50 years. The average RTS and ISS was 10.67±1.45 and 18.11±8.64, high and low scores of ISS existed in all age groups but a low score of RTS was highest in the children age group. The average length of ICU stay was 12.14±11.11 days. Overall mortality was 15.7 (11 cases). In this study, by the ISS increasing, the mortality rate also increased. But there

  1. Target inhibition networks: predicting selective combinations of druggable targets to block cancer survival pathways.

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    Jing Tang

    Full Text Available A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of non-additive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced

  2. The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas.

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    Lee A D Cooper

    Full Text Available The Cancer Genome Atlas Project (TCGA has produced an extensive collection of '-omic' data on glioblastoma (GBM, resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt, which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium's expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6, but also among 75 grade II and grade III samples (p  =  2.65e-4. This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n =  43, p  =  1.25e-4. Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor

  3. A Mycobacterium avium subsp. paratuberculosis predicted serine protease is associated with acid stress and intraphagosomal survival

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    Abirami Kugadas

    2016-08-01

    Full Text Available AbstractThe ability to maintain intra-cellular pH is crucial for bacteria and other microbes to survive in diverse environments, particularly those that undergo fluctuations in pH. Mechanisms of acid resistance remain poorly understood in mycobacteria. Although studies investigating acid stress in M. tuberculosis are gaining traction, few center on Mycobacterium avium subsp. paratuberculosis (MAP, the etiological agent of chronic enteritis in ruminants. We identified a MAP acid stress response network involved in macrophage infection. The central node of this network was MAP0403, a predicted serine protease that shared an 86% amino acid identity with MarP in M. tuberculosis. Previous studies confirmed MarP as a serine protease integral to maintaining intra-bacterial pH and survival in acid in vitro and in vivo. We show that MAP0403 is upregulated in infected macrophage and MAC-T cells and coincided with phagosome acidification. Treatment of mammalian cells with bafilomcyin A1, a potent inhibitor of phagosomal vATPases, diminished MAP0403 transcription. MAP0403 expression was also noted in acidic medium. A surrogate host, M. smegmatis mc2 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increase bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5 conditions. These data suggest that MAP0403 may be the equivalent of MarP in MAP. Future studies confirming MAP0403 as a serine protease and exploring its structure and possible substrates are warranted.

  4. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  5. NanOx, a new model to predict cell survival in the context of particle therapy

    Science.gov (United States)

    Cunha, M.; Monini, C.; Testa, E.; Beuve, M.

    2017-02-01

    Particle therapy is increasingly attractive for the treatment of tumors and the number of facilities offering it is rising worldwide. Due to the well-known enhanced effectiveness of ions, it is of utmost importance to plan treatments with great care to ensure tumor killing and healthy tissues sparing. Hence, the accurate quantification of the relative biological effectiveness (RBE) of ions, used in the calculation of the biological dose, is critical. Nevertheless, the RBE is a complex function of many parameters and its determination requires modeling. The approaches currently used have allowed particle therapy to thrive, but still show some shortcomings. We present herein a short description of a new theoretical framework, NanOx, to calculate cell survival in the context of particle therapy. It gathers principles from existing approaches, while addressing some of their weaknesses. NanOx is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, integrating also the chemical aspects of radiation-matter interaction. The latter are included in the model by means of a chemical specific energy, determined from the production of reactive chemical species induced by irradiation. Such a production represents the accumulation of oxidative stress and sublethal damage in the cell, potentially generating non-local lethal events in NanOx. The complementary local lethal events occur in a very localized region and can, alone, lead to cell death. Both these classes of events contribute to cell death. The comparison between experimental data and model predictions for the V79 cell line show a good agreement. In particular, the dependence of the typical shoulders of cell survival curves on linear energy transfer are well described, but also the effectiveness of different ions, including the overkill effect. These results required the adjustment of a number of parameters compatible with the application of the model in

  6. Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Marquart, Hanne Vibeke; Friis, Lone Smidstrup

    2016-01-01

    Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate...... the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013. In multivariate analysis NK cell numbers...... on day 30 (NK30) > 150 cells/µL were independently associated with superior overall survival (hazard ratio, .79; 95% confidence interval, .66 to .95; P = .01). Cumulative incidence analyses showed that patients with NK30 > 150 cells/µL had significantly less transplant-related mortality (TRM), P = .01...

  7. Preimplantation biopsy predicts delayed graft function, glomerular filtration rate and long-term graft survival of transplanted kidneys

    Directory of Open Access Journals (Sweden)

    José A. Pedroso

    2016-01-01

    Full Text Available The predictive value of preimplantation biopsies for long-term graft function is often limited by conflicting results. The aim of this study was to evaluate the influence of time-zero graft biopsy histological scores on early and late graft function, graft survival and patient survival, at different time points. We retrospectively analyzed 284 preimplantation biopsies at a single center, in a cohort of recipients with grafts from live and deceased donors (standard and nonstandard, and their impact in posttransplant renal function after a mean follow-up of 7 years (range 1-16. Implantation biopsy score (IBS, a combination score derived from 4 histopathological aspects, was determined from each sample. The correlation with incidence of delayed graft function (DGF, creatinine clearance (1st, 3rd and 5th posttransplant year and graft and patient survival at 1 and 5 years were evaluated. Preimplantation biopsies provided somewhat of a prognostic index of early function and outcome of the transplanted kidney in the short and long term. In the immediate posttransplantation period, the degree of arteriolosclerosis and interstitial fibrosis correlated better with the presence of DGF. IBS values between 4 and 6 were predictive of worst renal function at 1st and 3rd years posttransplant and 5-year graft survival. The most important histological finding, in effectively transplanted grafts, was the grade of interstitial fibrosis. Patient survival was not influenced by IBS. Higher preimplantation biopsy scores predicted an increased risk of early graft losses, especially primary nonfunction. Graft survival (at 1st and 5th years after transplant but not patient survival was predicted by IBS.

  8. Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients

    Energy Technology Data Exchange (ETDEWEB)

    Paprottka, K.J.; Schoeppe, F.; Ingrisch, M.; Ruebenthaler, J.; Sommer, N.N.; Paprottka, P.M. [LMU - University of Munich, Department of Clinical Radiology, Munich (Germany); Toni, E. de [LMU - University of Munich, Department of Hepatology, Munich (Germany); Ilhan, H.; Zacherl, M.; Todica, A. [LMU - University of Munich, Department of Nuclear Medicine, Munich (Germany)

    2017-07-15

    To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. (orig.)

  9. Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study

    Science.gov (United States)

    Ganly, Ian; Amit, Moran; Kou, Lei; Palmer, Frank L.; Migliacci, Jocelyn; Katabi, Nora; Yu, Changhong; Kattan, Michael W.; Binenbaum, Yoav; Sharma, Kanika; Naomi, Ramer; Abib, Agbetoba; Miles, Brett; Yang, Xinjie; Lei, Delin; Bjoerndal, Kristine; Godballe, Christian; Mücke, Thomas; Wolff, Klaus-Dietrich; Fliss, Dan; Eckardt, André M.; Chiara, Copelli; Sesenna, Enrico; Ali, Safina; Czerwonka, Lukas; Goldstein, David P.; Gil, Ziv; Patel, Snehal G.

    2016-01-01

    Background Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. Methods ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. Findings Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1–306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. Interpretation Using an international collaborative database we have created the first nomograms which

  10. Predicting censored survival data based on the interactions between meta-dimensional omics data in breast cancer.

    Science.gov (United States)

    Kim, Dokyoon; Li, Ruowang; Dudek, Scott M; Ritchie, Marylyn D

    2015-08-01

    Evaluation of survival models to predict cancer patient prognosis is one of the most important areas of emphasis in cancer research. A binary classification approach has difficulty directly predicting survival due to the characteristics of censored observations and the fact that the predictive power depends on the threshold used to set two classes. In contrast, the traditional Cox regression approach has some drawbacks in the sense that it does not allow for the identification of interactions between genomic features, which could have key roles associated with cancer prognosis. In addition, data integration is regarded as one of the important issues in improving the predictive power of survival models since cancer could be caused by multiple alterations through meta-dimensional genomic data including genome, epigenome, transcriptome, and proteome. Here we have proposed a new integrative framework designed to perform these three functions simultaneously: (1) predicting censored survival data; (2) integrating meta-dimensional omics data; (3) identifying interactions within/between meta-dimensional genomic features associated with survival. In order to predict censored survival time, martingale residuals were calculated as a new continuous outcome and a new fitness function used by the grammatical evolution neural network (GENN) based on mean absolute difference of martingale residuals was implemented. To test the utility of the proposed framework, a simulation study was conducted, followed by an analysis of meta-dimensional omics data including copy number, gene expression, DNA methylation, and protein expression data in breast cancer retrieved from The Cancer Genome Atlas (TCGA). On the basis of the results from breast cancer dataset, we were able to identify interactions not only within a single dimension of genomic data but also between meta-dimensional omics data that are associated with survival. Notably, the predictive power of our best meta-dimensional model

  11. SIRT1 and c-Myc Promote Liver Tumor Cell Survival and Predict Poor Survival of Human Hepatocellular Carcinomas

    Science.gov (United States)

    Jang, Kyu Yun; Noh, Sang Jae; Lehwald, Nadja; Tao, Guo-Zhong; Bellovin, David I.; Park, Ho Sung; Moon, Woo Sung; Felsher, Dean W.; Sylvester, Karl G.

    2012-01-01

    The increased expression of SIRT1 has recently been identified in numerous human tumors and a possible correlation with c-Myc oncogene has been proposed. However, it remains unclear whether SIRT1 functions as an oncogene or tumor suppressor. We sought to elucidate the role of SIRT1 in liver cancer under the influence of c-Myc and to determine the prognostic significance of SIRT1 and c-Myc expression in human hepatocellular carcinoma. The effect of either over-expression or knock down of SIRT1 on cell proliferation and survival was evaluated in both mouse and human liver cancer cells. Nicotinamide, an inhibitor of SIRT1, was also evaluated for its effects on liver tumorigenesis. The prognostic significance of the immunohistochemical detection of SIRT1 and c-Myc was evaluated in 154 hepatocellular carcinoma patients. SIRT1 and c-Myc regulate each other via a positive feedback loop and act synergistically to promote hepatocellular proliferation in both mice and human liver tumor cells. Tumor growth was significantly inhibited by nicotinamide in vivo and in vitro. In human hepatocellular carcinoma, SIRT1 expression positively correlated with c-Myc, Ki67 and p53 expression, as well as high á-fetoprotein level. Moreover, the expression of SIRT1, c-Myc and p53 were independent prognostic indicators of hepatocellular carcinoma. In conclusion, this study demonstrates that SIRT1 expression supports liver tumorigenesis and is closely correlated with oncogenic c-MYC expression. In addition, both SIRT1 and c-Myc may be useful prognostic indicators of hepatocellular carcinoma and SIRT1 targeted therapy may be beneficial in the treatment of hepatocellular carcinoma. PMID:23024800

  12. Higher Levels of GATA3 Predict Better Survival in Women with Breast Cancer

    Science.gov (United States)

    Yoon, Nam K.; Maresh, Erin L.; Shen, Dejun; Elshimali, Yahya; Apple, Sophia; Horvath, Steve; Mah, Vei; Bose, Shikha; Chia, David; Chang, Helena R.; Goodglick, Lee

    2010-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. GATA3 in particular is necessary for mammary gland maturation, and its loss has been implicated in breast cancer development. Our goal was to validate the ability of GATA3 expression to predict survival in breast cancer patients. Protein expression of GATA3 was analyzed on a high density tissue microarray consisting of 242 cases of breast cancer. We associated GATA3 expression with patient outcomes and clinicopathological variables. Expression of GATA3 was significantly increased in breast cancer, in situ lesions, and hyperplastic tissue compared to normal breast tissue. GATA3 expression decreased with increasing tumor grade. Low GATA3 expression was a significant predictor of disease-related death in all patients, as well as in subgroups of estrogen receptor positive or low grade patients. Additionally, low GATA3 expression correlated with increased tumor size and estrogen and progesterone receptor negativity. GATA3 is an important predictor of disease outcome in breast cancer patients. This finding has been validated in a diverse set of populations. Thus, GATA3 expression has utility as a prognostic indicator in breast cancer. PMID:21078439

  13. Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Steedman Tracey

    2008-08-01

    Full Text Available Abstract Background Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR permits assessment of the central arteries to measure aortic function. Methods We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate Results Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events. Conclusion Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.

  14. Genomic variation by whole-genome SNP mapping arrays predicts time-to-event outcome in patients with chronic lymphocytic leukemia: a comparison of CLL and HapMap genotypes.

    Science.gov (United States)

    Schweighofer, Carmen D; Coombes, Kevin R; Majewski, Tadeusz; Barron, Lynn L; Lerner, Susan; Sargent, Rachel L; O'Brien, Susan; Ferrajoli, Alessandra; Wierda, William G; Czerniak, Bogdan A; Medeiros, L Jeffrey; Keating, Michael J; Abruzzo, Lynne V

    2013-03-01

    Genomic abnormalities, such as deletions in 11q22 or 17p13, are associated with poorer prognosis in patients with chronic lymphocytic leukemia (CLL). We hypothesized that unknown regions of copy number variation (CNV) affect clinical outcome and can be detected by array-based single-nucleotide polymorphism (SNP) genotyping. We compared SNP genotypes from 168 untreated patients with CLL with genotypes from 73 white HapMap controls. We identified 322 regions of recurrent CNV, 82 of which occurred significantly more often in CLL than in HapMap (CLL-specific CNV), including regions typically aberrant in CLL: deletions in 6q21, 11q22, 13q14, and 17p13 and trisomy 12. In univariate analyses, 35 of total and 11 of CLL-specific CNVs were associated with unfavorable time-to-event outcomes, including gains or losses in chromosomes 2p, 4p, 4q, 6p, 6q, 7q, 11p, 11q, and 17p. In multivariate analyses, six CNVs (ie, CLL-specific variations in 11p15.1-15.4 or 6q27) predicted time-to-treatment or overall survival independently of established markers of prognosis. Moreover, genotypic complexity (ie, the number of independent CNVs per patient) significantly predicted prognosis, with a median time-to-treatment of 64 months versus 23 months in patients with zero to one versus two or more CNVs, respectively (P = 3.3 × 10(-8)). In summary, a comparison of SNP genotypes from patients with CLL with HapMap controls allowed us to identify known and unknown recurrent CNVs and to determine regions and rates of CNV that predict poorer prognosis in patients with CLL.

  15. Combined heavy smoking and drinking predicts overall but not disease-free survival after curative resection of locoregional esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sun P

    2016-07-01

    Full Text Available Peng Sun,1,2,* Cui Chen,3,* Fei Zhang,1,2,* Hang Yang,1,2 Xi-Wen Bi,1,2 Xin An,1,2 Feng-Hua Wang,1,2 Wen-Qi Jiang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 3Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The prognostic impact of smoking and drinking on esophageal squamous cell carcinoma (ESCC was scarcely discussed. We investigated the prognostic value of smoking and drinking and their relationships with clinicopathological characteristics in a large cohort of patients with locoregional ESCC.Patients and methods: We retrospectively analyzed 488 patients who underwent curative treatment at a single institution between January 2007 and December 2008. A chi-square test was used to evaluate the relationships between smoking and drinking and clinicopathological variables, the Kaplan–Meier method was used for 5-year overall survival (OS and disease-free survival, and Cox proportional hazards models were applied for univariate and multivariate analyses of variables with respect to OS and disease-free survival.Results: Heavy smokers were more likely to have advanced Tumor-Node-Metastases (TNM stage and higher neutrophil/lymphocyte ratio at diagnosis (P<0.05. Drinkers were more likely to have advanced TNM stage, to present with a larger tumor, and to undergo multidisciplinary treatment (P<0.05. For patients who used neither heavy tobacco nor alcohol, used either tobacco or alcohol, and used both, the 5-year OS rates and OS times were 57.4%, 46.4%, and 39.1% (P<0.05 and not reached, 55.2 months, and 41.2 months (P<0.05, respectively. On multivariate analysis, patients who both heavily smoked and drank had 1.392 times the risk of dying during follow-up compared with

  16. Higher percentage of CD3⁺CD154⁺ T lymphocytes predicts efficacy of TNF-α inhibitors in active axial SpA patients.

    Science.gov (United States)

    Lin, Zhiming; Lin, Qu; Liao, Zetao; Li, Qiuxia; Zhang, Fucheng; Wei, Qiujing; Cao, Shuangyan; Gu, Jieruo

    2014-12-01

    The objective of this study was to evaluate which subtypes of T lymphocytes (CD3(+)CD28(+) and CD3(+)CD154(+)) could predict clinical efficacy after TNF-α inhibitor treatment in active axial SpA patients. Patients who fulfilled Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA had a BASDAI of ≥40 mm. All patients received TNF-α inhibitor treatment for 12 weeks. ASAS20 was used to evaluate the effect of the treatment at week 12. We detected the percentage of CD3(+)CD28(+) and CD3(+)CD154(+) T lymphocytes on lymphocyte cells in the peripheral blood in patients and healthy controls. We evaluated whether the percentage of the above subtypes of T lymphocytes could predict clinical efficacy by ROC curve analysis. Fifty-eight healthy controls and 74 active axial SpA patients were included. Mean age was 26.28 ± 9.08 and 26.95 ± 8.13 years for healthy controls and patients, respectively (p = 0.767). The percentage of CD3(+)CD154(+) T lymphocytes was significantly higher in axial SpA patients than in healthy controls (1.62 ± 1.89 % vs 0.79 ± 0.52 %, p SpA patients with TNF-α inhibitor treatment (AUC = 0.733, p = 0.014). High percentage of CD3(+)CD154(+) is over-expressed on lymphocytes in peripheral blood of active SpA patients and can be down-regulated by TNF-α inhibitor therapy. High-percentage of CD3(+)CD154(+) T lymphocytes may predict clinical efficacy of TNF-α inhibitor treatment in active axial SpA patients.

  17. Stomach position in prediction of survival in left-sided congenital diaphragmatic hernia with or without fetoscopic endoluminal tracheal occlusion.

    Science.gov (United States)

    Cordier, A-G; Jani, J C; Cannie, M M; Rodó, C; Fabietti, I; Persico, N; Saada, J; Carreras, E; Senat, M-V; Benachi, A

    2015-08-01

    To investigate the value of fetal stomach position in predicting postnatal outcome in left-sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO). This was a retrospective review of CDH cases that were expectantly managed or treated with FETO, assessed from May 2008 to October 2013, in which we graded, on a scale of 1-4, stomach position on the four-chamber view of the heart with respect to thoracic structures. Logistic regression analysis was used to investigate the effect of management center (Paris, Brussels, Barcelona, Milan), stomach grading, observed-to-expected lung area-to-head circumference ratio (O/E-LHR), gestational age at delivery, birth weight in expectantly managed CDH, gestational ages at FETO and at removal and period of tracheal occlusion, on postnatal survival in CDH cases treated with FETO. We identified 67 expectantly managed CDH cases and 47 CDH cases that were treated with FETO. In expectantly managed CDH, stomach position and O/E-LHR predicted postnatal survival independently. In CDH treated with FETO, stomach position and gestational age at delivery predicted postnatal survival independently. In left-sided CDH with or without FETO, stomach position is predictive of postnatal survival. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  18. Health-related quality of life predicts long-term survival in patients with peripheral artery disease

    DEFF Research Database (Denmark)

    Issa, Samson M; Hoeks, Sanne E; Scholte op Reimer, Wilma J M;

    2010-01-01

    We examined whether health-related quality of life (HRQoL) predicts long-term survival in patients with peripheral artery disease (PAD) independent of established prognostic risk factors. In 2004, data on 711 consecutive patients with PAD undergoing vascular surgery were collected from 11 hospita...

  19. Niclosamide, an anti-helminthic molecule, downregulates the retroviral oncoprotein Tax and pro-survival Bcl-2 proteins in HTLV-1-transformed T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Di [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Yuan, Yunsheng [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai (China); Chen, Li [Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou (China); Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Liu, Xin; Belani, Chandra [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Cheng, Hua, E-mail: hcheng@ihv.umaryland.edu [Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2015-08-14

    Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancy and is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein, Tax, which plays a key role in transactivating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival, proliferation and transformation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis. We here show that niclosamide, an anti-helminthic molecule, induced apoptosis of HTLV-1-transformed T cells. Niclosamide facilitated degradation of the Tax protein in proteasome. Consistent with niclosamide-mediated Tax degradation, this compound inhibited activities of MAPK/ERK1/2 and IκB kinases. In addition, niclosamide downregulated Stat3 and pro-survival Bcl-2 family members such as Mcl-1 and repressed the viral gene transcription of HTLV-1 through induction of Tax degradation. Since Tax, Stat3 and Mcl-1 are crucial molecules for promoting survival and growth of HTLV-1-transformed T cells, our findings demonstrate a novel mechanism of niclosamide in inducing Tax degradation and downregulating various cellular pro-survival molecules, thereby promoting apoptosis of HTLV-1-associated leukemia cells. - Highlights: • Niclosamide is a promising therapeutic candidate for adult T cell leukemia. • Niclosamide employs a novel mechanism through proteasomal degradation of Tax. • Niclosamide downregulates certain cellular pro-survival molecules.

  20. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage

    DEFF Research Database (Denmark)

    Hagmar, L; Brøgger, A; Hansteen, I L;

    1994-01-01

    Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target...... tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange.......0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk....

  1. The absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles is not significantly impacted by the use of myeloid growth factors and predicts clinical outcomes in classical Hodgkin lymphoma regardless of their use

    Directory of Open Access Journals (Sweden)

    Kaufman GP

    2014-07-01

    Full Text Available Gregory P Kaufman,1 Kay M Ristow,1,2 Svetomir N Markovic,1,2 Luis F Porrata1,2 1Department of Internal Medicine, 2Division of Hematology, Mayo Clinic, Rochester, MN, USA Abstract: Risk stratification of patients with classical Hodgkin lymphoma (cHL remains suboptimal. The ratio of the absolute lymphocyte count (ALC to absolute monocyte count (AMC both at diagnosis and during subsequent recovery from serial cycles of chemotherapy predicts survival in cHL, and possesses advantages over other commonly used prognostic markers. Myeloid growth factors (MGFs, while not strongly recommended for use in adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD treatment cycles, are not uncommonly used to prevent the negative consequences of neutropenia. The effect that MGFs have on the ALC/AMC ratio during ABVD treatment cycles, if any, remains unclear. We retrospectively evaluated 208 patients with cHL, who were diagnosed, treated, and followed at Mayo Clinic Rochester between 1990 and 2014, and who had quantifiable records for the use of MGFs during ABVD treatment cycles. Having an ALC/AMC ratio <1.1 during all treatment cycles was confirmed as being a negative predictor of overall and progression free survival (hazard ratio [HR] 0.06, 95% confidence interval [CI] 0.03–0.14 and HR 0.08, 95% CI 0.04–0.17, respectively. Data on both the ALC/AMC ratio and use of MGFs were available for 1,979 half treatment cycles. When stratified to whether or not MGFs were given, the change in the ALC/AMC ratio as compared to the prior half cycle was found to be statistically insignificant (P=0.3445. No survival advantage was found with the administration of MGFs in any cycle of therapy (log rank P=0.5713. Our data validate the prognostic significance of having an ALC/AMC ratio of ≥1.1 regardless of the use of MGFs. Keywords: myeloid growth factors, classical Hodgkin lymphoma, survival ALC/AMC ratio, ABVD chemotherapy

  2. Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

    Directory of Open Access Journals (Sweden)

    Wickramarachchi RE

    2010-09-01

    Full Text Available Abstract Objectives This study compares clinico-pathological features in young (50 years with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. Materials and methods A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. Results Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05. In both groups, the majority presented without bowel obstruction (young - 81%, older - 94%. Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p Conclusion If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.

  3. Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert E. Page

    2007-01-01

    Full Text Available Background: Proprotein convertases (PCs are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and angiogenic factors. Although the expression of several PCs is increased in many tumors, their expression in primary ovarian tumors has not been studied in detail. We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression. Methods: We assessed their expression by RT-PCR, Real-time PCR, Western blot, and immunohistochemistry using cells derived from normal human ovarian surface epithelium (HOSE and cancer cell lines as well as ovarian epithelial cancer specimens (45 RT-PCR/Real-time PCR, and 120 archival specimens for Immunohistochemistry. Results: We found that furin expression was restricted to the cancer cell lines. In contrast, PACE-4 and PC-7 showed expression only in normal HOSE cells lines. Furthermore, furin was predominantly expressed in primary tumors from patients who survived for less than five years. The other PCs are either expressed in the group of survivors (PC-7 and PACE4 or expressed in low amounts (PC-5. Conclusions: Our studies point to a clear relationship between furin and ovarian cancer. In addition, these results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. In summary, furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease.

  4. IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide.

    NARCIS (Netherlands)

    Dubbink, H.J.; Taal, W.; Marion, R. van; Kros, J.M.; Heuvel, I. van; Bromberg, J.E.; Zonnenberg, B.A.; Zonnenberg, C.B.; Postma, T.J.; Gijtenbeek, J.M.M.; Boogerd, W.; Groenendijk, F.H.; Smitt, P.A.; Dinjens, W.N.; Bent, M.J. van den

    2009-01-01

    BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade

  5. IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide

    NARCIS (Netherlands)

    Dubbink, H. J.; Taal, W.; van Marion, R.; Kros, J. M.; van Heuvel, I.; Bromberg, J. E.; Zonnenberg, B. A.; Zonnenberg, C. B. L.; Postma, T. J.; Gijtenbeek, J. M. M.; Boogerd, W.; Groenendijk, F. H.; Smitt, P. A. E. Sillevis; Dinjens, W. N. M.; van den Bent, M. J.

    2009-01-01

    Background: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade

  6. An easy tool to predict survival in patients receiving radiation therapy for painful bone metastases

    NARCIS (Netherlands)

    Westhoff, P.G.; Graeff, A. de; Monninkhof, E.M.; Bollen, L.; Dijkstra, S.P.; Steen-Banasik, E.M. van der; Vulpen, M. van; Leer, J.W.H.; Marijnen, C.A.; Linden, Y.M. van der; Study, G.

    2014-01-01

    PURPOSE: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and p

  7. Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival.

    Science.gov (United States)

    Sevinc, M; Stamp, S; Ling, J; Carter, N; Talbot, D; Sheerin, N

    2016-12-01

    Ex vivo perfusion is used in our unit for kidneys donated after cardiac death (DCD). Perfusion flow index (PFI), resistance, and perfusate glutathione S-transferase (GST) can be measured to assess graft viability. We assessed whether measurements taken during perfusion could predict long-term outcome after transplantation. All DCD kidney transplants performed from 2002 to 2014 were included in this study. The exclusion criteria were: incomplete data, kidneys not machine perfused, kidneys perfused in continuous mode, and dual transplantation. There were 155 kidney transplantations included in the final analysis. Demographic data, ischemia times, donor hypertension, graft function, survival and machine perfusion parameters after 3 hours were analyzed. Each perfusion parameter was divided into 3 groups as high, medium, and low. Estimated glomerular filtration rate was calculated at 12 months and then yearly after transplantation. There was a significant association between graft survival and PFI and GST (P values, .020 and .022, respectively). PFI was the only independent parameter to predict graft survival. A low PFI during ex vivo hypothermic perfusion is associated with inferior graft survival after DCD kidney transplantation. We propose that PFI is a measure of the health of the graft vasculature and that a low PFI indicates vascular disease and therefore predicts a worse long-term outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. CD69 expression potentially predicts response to bendamustine and its modulation by ibrutinib or idelalisib enhances cytotoxic effect in chronic lymphocytic leukemia

    Science.gov (United States)

    Roldán, Jocabed; Jiménez, Laura; Cabezas, Sandra; Clot, Guillem; Pinyol, Magda; Xargay-Torrent, Sílvia; Rosich, Laia; Arimany-Nardí, Cristina; Aymerich, Marta; Villamor, Neus; López-Guillermo, Armando; Pérez-Galán, Patricia; Roué, Gaël; Pastor-Anglada, Marçal; Campo, Elías; López-Guerra, Mónica; Colomer, Dolors

    2016-01-01

    Clinical responses to bendamustine in chronic lymphocytic leukemia (CLL) are highly heterogeneous and no specific markers to predict sensitivity to this drug have been reported. In order to identify biomarkers of response, we analyzed the in vitro activity of bendamustine and the gene expression profile in primary CLL cells. We observed that mRNA expression of CD69 (CD69) and ITGAM (CD11b) constitute the most powerful predictor of response to bendamustine. When we interrogated the predictive value of the corresponding cell surface proteins, the expression of the activation marker CD69 was the most reliable predictor of sensitivity to bendamustine. Importantly, a multivariate analysis revealed that the predictive value of CD69 expression was independent from other clinico-biological CLL features. We also showed that when CLL cells were co-cultured with distinct subtypes of stromal cells, an upregulation of CD69 was accompanied by a reduced sensitivity to bendamustine. In agreement with this, tumor cells derived from lymphoid tumor niches harbored higher CD69 expression and were less sensitive to bendamustine than their peripheral blood counterparts. Furthermore, pretreatment of CD69 high CLL cases with the B-cell receptor (BCR) pathway inhibitors ibrutinib and idelalisib decreased CD69 levels and enhanced bendamustine cytotoxic effect. Collectively, our findings indicate that CD69 could be a predictor of bendamustine response in CLL patients and the combination of clinically-tested BCR signaling inhibitors with bendamustine may represent a promising strategy for bendamustine low responsive CLL cases. PMID:26701728

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

    Science.gov (United States)

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

    2011-10-01

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

  10. Validation of the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) pulmonary hypertension prediction model in a unique population and utility in the prediction of long-term survival.

    Science.gov (United States)

    Cogswell, Rebecca; Kobashigawa, Erin; McGlothlin, Dana; Shaw, Robin; De Marco, Teresa

    2012-11-01

    The Registry to Evaluate Early and Long-Term Pulmonary Arterial (PAH) Hypertension Disease Management (REVEAL) model was designed to predict 1-year survival in patients with PAH. Multivariate prediction models need to be evaluated in cohorts distinct from the derivation set to determine external validity. In addition, limited data exist on the utility of this model in the prediction of long-term survival. REVEAL model performance was assessed to predict 1-year and 5-year outcomes, defined as survival or composite survival or freedom from lung transplant, in 140 patients with PAH. The validation cohort had a higher proportion of human immunodeficiency virus (7.9% vs 1.9%, p model to predict survival was 0.765 at 1 year and 0.712 at 5 years of follow-up. The C-index of the model to predict composite survival or freedom from lung transplant was 0.805 and 0.724 at 1 and 5 years of follow-up, respectively. Prediction by the model, however, was weakest among patients with intermediate-risk predicted survival. The REVEAL model had adequate discrimination to predict 1-year survival in this small but clinically distinct validation cohort. Although the model also had predictive ability out to 5 years, prediction was limited among patients of intermediate risk, suggesting our prediction methods can still be improved. Copyright © 2012. Published by Elsevier Inc.

  11. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation.

    Science.gov (United States)

    Ting, Stephen M S; Iqbal, Hasan; Kanji, Hemali; Hamborg, Thomas; Aldridge, Nicolas; Krishnan, Nithya; Imray, Chris H E; Banerjee, Prithwish; Bland, Rosemary; Higgins, Robert; Zehnder, Daniel

    2014-01-01

    Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

  12. Endobronchial mucosa invasion predicts survival in patients with small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Pai-Chien Chou

    Full Text Available BACKGROUND: Current staging system for small cell lung cancer (SCLC categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion. METHODS: We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated. RESULTS: 84% (364/432 of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30-3.10, age (HR, 1.04; 95% CI, 1.03-1.06, and extensive stage (HR, 1.39; 95% CI, 1.06-1.84 were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25-0.42 was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001. Among SCLC patients of either limited (median 180 vs. 460, p<0.0001 or extensive (median 125 vs. 207, p<0.0001 stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively. CONCLUSION: Endobronchial mucosal involvement is an independent prognostic factor for SCLC

  13. High Percentage of ADAM-10 Positive Melanoma Cells Correlates with Paucity of Tumor-Infiltrating Lymphocytes but Does Not Predict Prognosis in Cutaneous Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Piotr Donizy

    2015-01-01

    Full Text Available ADAM-10 (CDw156, CD156c, and kuzbanian is a protein belonging to a superfamily of metalloproteases, enzymes capable of degrading the extracellular matrix. ADAMs have also been shown to be primarily involved in ectodomain cleavage. The aim of the study was to assess the expression and intracellular location of ADAM-10 in 104 primary skin melanomas and 16 metastatic lesions from regional lymph nodes. Also, prognostic significance of ADAM-10 expression in primary tumor cells and metastatic lesion cells was evaluated during 5-year observation. It was revealed that high expression of ADAM-10 positive cells was strictly related with lower intensity of tumor-infiltrating lymphocytes (P=0.037, which suggests that ADAM-10 regulates immunoresponse in melanoma initiation and progression. No statistically significant correlations were found between ADAM-10 expression in primary tumor cells and nodal metastases and other histopathological parameters analyzed. Decreased immunoreactivity of ADAM-10 in cancer cells from regional lymph nodes was correlated with worse prognosis; however this correlation was statistically nonsignificant (P=0.065. Review of the literature shows that our study is the first one ever to describe the significance of ADAM-10 expression in correlation with detailed histopathological parameters of the primary tumor and data on long-term survival of cutaneous melanoma patients.

  14. Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission.

    Science.gov (United States)

    Nishiwaki, Satoshi; Inamoto, Yoshihiro; Sakamaki, Hisashi; Kurokawa, Mineo; Iida, Hiroatsu; Ogawa, Hiroyasu; Fukuda, Takahiro; Ozawa, Yukiyasu; Kobayashi, Naoki; Kasai, Masanobu; Mori, Takehiko; Iwato, Koji; Yoshida, Takashi; Onizuka, Makoto; Kawa, Keisei; Morishima, Yasuo; Suzuki, Ritsuro; Atsuta, Yoshiko; Miyamura, Koichi

    2010-11-18

    To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph(-) ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph(-) ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph(-) ALL in CR1 could be improved.

  15. Platelet indices and platelet-to-lymphocyte ratio predict coronary chronic total occlusion in patients with acute ST-elevation myocardial infarction

    Directory of Open Access Journals (Sweden)

    Hadadi Laszlo

    2015-12-01

    Full Text Available Coronary chronic total occlusion (CTO is caused by organized thrombi or atherosclerotic plaque progression. The presence of a CTO is an independent predictor of mortality in patients presenting with ST-segment elevation myocardial infarction (STEMI. Platelets have a crucial role in the pathophysiology of atherosclerosis. The aim of this retrospective study was to investigate platelet indices as predictors of CTO in patients with STEMI treated with primary percutaneous coronary intervention (pPCI. A total number of 334 patients admitted for STEMI between January 2011 and December 2013 were included and divided in two groups based on the presence of CTO (48 patients in CTO+ group, 286 patients in CTO-group. Platelet count, mean platelet volume (MPV, platelet distribution width (PDW, platelet-large cell ratio (P-LCR, lymphocyte and neutrophil count determined on admission were analyzed. MPV was larger in patients with CTO compared with patients without CTO (p=0.02, as were PDW (p=0.03 and P-LCR (p=0.01. Platelet-to-lymphocyte ratio (PLT/LYM was lower in patients with CTO: 105.2 (75.86-159.1 compared to 137 (97-188.1, p<0.01. Receiver-operator characteristic curve analysis identified an area under the curve of 0.61 (95%CI=0.57-0.67, p< 0.01 for PLT/LYM in predicting the presence of a CTO, with a cut-off value at 97.73. Lower values than this were independent predictors of a CTO in multivariate logistic regression analysis, with an Odds Ratio of 2.2 (95%CI=1.15-4.20, p=0.02. Our results support the use of platelet indices and PLT/LYM as predictors of CTO in patients presenting with STEMI.

  16. Predicting short-term survival after liver transplantation on eight score systems: a national report from China Liver Transplant Registry.

    Science.gov (United States)

    Ling, Qi; Dai, Haojiang; Zhuang, Runzhou; Shen, Tian; Wang, Weilin; Xu, Xiao; Zheng, Shusen

    2017-02-13

    To compare the performance of eight score systems (MELD, uMELD, MELD-Na. iMELD, UKELD, MELD-AS, CTP, and mCTP) in predicting the post-transplant mortality, we analyzed the data of 6,014 adult cirrhotic patients who underwent liver transplantation between January 2003 and December 2010 from the China Liver Transplant Registry database. In hepatitis B virus (HBV) group, MELD, uMELD and MELD-AS showed good predictive accuracies at 3-month mortality after liver transplantation; by comparison with other five models, MELD presented the best ability in predicting 3-month, 6-month and 1-year mortality, showing a significantly better predictive ability than UKELD and iMELD. In hepatitis C virus and Alcohol groups, the predictive ability did not differ significantly between MELD and other models. Patient survivals in different MELD categories were of statistically significant difference. Among patients with MELD score >35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one. In conclusion, MELD is superior to other score systems in predicting short-term post-transplant survival in patients with HBV-related liver disease. Among patients with MELD score >35, a new prognostic model can identify the sickest patients who should be excluded from waiting list to prevent wasteful transplantation.

  17. Impact of tumour volume on prediction of progression-free survival in sinonasal cancer

    Directory of Open Access Journals (Sweden)

    Hennersdorf Florian

    2015-09-01

    Full Text Available Background. The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS for malignancies of the nasal cavity and the paranasal sinuses.

  18. The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients

    National Research Council Canada - National Science Library

    Malyszko, Jolanta; Zbroch, Edyta; Malyszko, Jacek; Mysliwiec, Michal; Iaina, Adrian

    2010-01-01

    .... The correction of anaemia was effective in the amelioration of both cardiac and renal failure. We studied the relationship between the severity of CRA syndrome in peritoneally dialyzed patients and their survival probability...

  19. Development of a Summarized Health Index (SHI) for use in predicting survival in sea turtles.

    Science.gov (United States)

    Li, Tsung-Hsien; Chang, Chao-Chin; Cheng, I-Jiunn; Lin, Suen-Chuain

    2015-01-01

    Veterinary care plays an influential role in sea turtle rehabilitation, especially in endangered species. Physiological characteristics, hematological and plasma biochemistry profiles, are useful references for clinical management in animals, especially when animals are during the convalescence period. In this study, these factors associated with sea turtle surviving were analyzed. The blood samples were collected when sea turtles remained alive, and then animals were followed up for surviving status. The results indicated that significantly negative correlation was found between buoyancy disorders (BD) and sea turtle surviving (p sea turtles had significantly higher levels of aspartate aminotranspherase (AST), creatinine kinase (CK), creatinine and uric acid (UA) than surviving sea turtles (all p sea turtles and to improve veterinary care at rehabilitation facilities.

  20. Quality of life predicts overall survival in women with platinum-resistant ovarian cancer: an AURELIA substudy.

    Science.gov (United States)

    Roncolato, F T; Gibbs, E; Lee, C K; Asher, R; Davies, L C; Gebski, V J; Friedlander, M; Hilpert, F; Wenzel, L; Stockler, M R; King, M; Pujade-Lauraine, E

    2017-08-01

    Women with platinum-resistant ovarian cancer are a heterogeneous group whose median overall survival is 12 months. We hypothesized that their quality of life (QoL) scores would be prognostic. Data from AURELIA (n = 326), a randomized trial of chemotherapy with or without bevacizumab, were used to identify baseline QoL domains [EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 and OV28] that were significantly associated with overall survival in multivariable Cox regression analyses. Patients were classified as having good, medium, or poor risk. Cutpoints were validated in an independent dataset, CARTAXHY (n = 136). Multivariable analyses of significant QoL domains on survival were adjusted for clinicopathological prognostic factors. The additional QoL information was assessed using C statistic. In AURELIA, all domains, except cognitive function, predicted overall survival in univariable analyses. Physical function (P 93) risk categories for physical function, median overall survival was 11.0, 14.7, and 19.3 months, respectively (P 44), medium- (13-44), and low- (AURELIA (P < 0.001) and 10.5, 19.6, and 24.1 months in CARTAXHY (P = 0.02). Physical function (P = 0.02) and abdominal/gastrointestinal symptoms (P = 0.03) remained independent prognostic factors after adjustment for clinicopathological factors. The C statistic of the full model was 0.71. For QoL factors alone, patient factors alone and disease factors alone, the C statistics were 0.61, 0.61, and 0.67 respectively. Physical function and abdominal/gastrointestinal symptom scores improved predictions of overall survival over clinicopathological factors alone in platinum-resistant ovarian cancer. This additional prognostic information could improve trial stratification, patient-doctor communication about prognosis, and clinical decision-making. NCT00976911.

  1. Pretransplant prediction of posttransplant survival for liver recipients with benign end-stage liver diseases: a nonlinear model.

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    Full Text Available BACKGROUND: The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients' survival with benign end-stage liver diseases (BESLD by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD and a general-illness severity model (the sequential organ failure assessment score, or SOFA score. METHODOLOGY/PRINCIPAL FINDINGS: With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na(+; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P<0.001 in one-year and 0.88 (P<0.001 in two-year prediction. The performances of SOFA and MELD were fairly poor in prognostic assessment, with c-statistics of 0.70 and 0.66, respectively, in one-year prediction, and 0.67 and 0.65 in two-year prediction. CONCLUSIONS/SIGNIFICANCE: The posttransplant prognosis is a multidimensional nonlinear

  2. Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    Eduardo Vilar Gomez; Luis Calzadilla Bertot; Bienvenido Gra Oramas; Enrique Arus Soler; Raimundo Llanio Navarro; Javier Diaz Elias; Oscar Villa Jiménez; Maria del Rosario Abreu Vazquez

    2009-01-01

    AIM:To investigate the capability of a biochemical and clinical model,BioCliM,in predicting the survival of cirrhotic patients.METHODS:We prospectively evaluated the survival of 172 cirrhotic patients.The model was constructed using clinical (ascites,encephalopathy and variceal bleeding) and biochemical (serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model.It was applied to estimate 12-,52- and 104-wk survival.The model's calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset.Finally,the model's validity was tested among an independent set of 85 patients who were stratified into 2 risk groups (low risk ≤8 and high risk>8).RESULTS:In the validation cohort,all measures of fit,discrimination and calibration were improved when the biochemical and clinical model was used.The proposed model had better predictive values (c-statistic:0.90,0.91,0.91) than the Model for End-stage Liver Disease (MELD) and Child-Pugh (CP) scores for 12-,52- and 104-wk mortality,respectively.In addition,the Hosmer-Lemeshow (H-L) statistic revealed that the biochemical and clinical model (H-L,4.69) is better calibrated than MELD (H-L,17.06) and CP (H-L,14.23).There were no significant differences between the observed and expected survival curves in the stratified risk groups (low risk,P=0.61;high risk,P=0.77).CONCLUSION:Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients.

  3. Polymorphisms in MicroRNA Binding Sites Predict Colorectal Cancer Survival

    Science.gov (United States)

    Yang, Ying-Pi; Ting, Wen-Chien; Chen, Lu-Min; Lu, Te-Ling; Bao, Bo-Ying

    2017-01-01

    Background: MicroRNAs (miRNAs) mediate negative regulation of target genes through base pairing, and aberrant miRNA expression has been described in cancers. We hypothesized that single nucleotide polymorphisms (SNPs) within miRNA target sites might influence clinical outcomes in patients with colorectal cancer. Methods: Sixteen common SNPs within miRNA target sites were identified, and the association between these SNPs and overall survival was assessed in colorectal cancer patients using Kaplan-Meier analysis, Cox regression model, and survival tree analysis. Results: Survival tree analysis identified a higher-order genetic interaction profile consisting of the RPS6KB1 rs1051424 and ZNF839 rs11704 that was significantly associated with overall survival. The 5-year survival rates were 74.6%, 62.7%, and 57.1% for the low-, medium-, and high-risk genetic profiles, respectively (P = 0.006). The genetic interaction profile remained significant even after adjusting for potential risk factors. Additional in silico analysis provided evidence that rs1051424 and rs11704 affect RPS6KB1 and ZNF839 expressions, which in turn is significantly correlated with prognosis in colorectal cancer. Conclusion: Our results suggest that the genetic interaction profiles among SNPs within miRNA target sites might be prognostic markers for colorectal cancer survival. PMID:28138309

  4. Multi-objective evolutionary algorithms for fuzzy classification in survival prediction.

    Science.gov (United States)

    Jiménez, Fernando; Sánchez, Gracia; Juárez, José M

    2014-03-01

    This paper presents a novel rule-based fuzzy classification methodology for survival/mortality prediction in severe burnt patients. Due to the ethical aspects involved in this medical scenario, physicians tend not to accept a computer-based evaluation unless they understand why and how such a recommendation is given. Therefore, any fuzzy classifier model must be both accurate and interpretable. The proposed methodology is a three-step process: (1) multi-objective constrained optimization of a patient's data set, using Pareto-based elitist multi-objective evolutionary algorithms to maximize accuracy and minimize the complexity (number of rules) of classifiers, subject to interpretability constraints; this step produces a set of alternative (Pareto) classifiers; (2) linguistic labeling, which assigns a linguistic label to each fuzzy set of the classifiers; this step is essential to the interpretability of the classifiers; (3) decision making, whereby a classifier is chosen, if it is satisfactory, according to the preferences of the decision maker. If no classifier is satisfactory for the decision maker, the process starts again in step (1) with a different input parameter set. The performance of three multi-objective evolutionary algorithms, niched pre-selection multi-objective algorithm, elitist Pareto-based multi-objective evolutionary algorithm for diversity reinforcement (ENORA) and the non-dominated sorting genetic algorithm (NSGA-II), was tested using a patient's data set from an intensive care burn unit and a standard machine learning data set from an standard machine learning repository. The results are compared using the hypervolume multi-objective metric. Besides, the results have been compared with other non-evolutionary techniques and validated with a multi-objective cross-validation technique. Our proposal improves the classification rate obtained by other non-evolutionary techniques (decision trees, artificial neural networks, Naive Bayes, and case

  5. Social affiliation matters: both same-sex and opposite-sex relationships predict survival in wild female baboons.

    Science.gov (United States)

    Archie, Elizabeth A; Tung, Jenny; Clark, Michael; Altmann, Jeanne; Alberts, Susan C

    2014-10-22

    Social integration and support can have profound effects on human survival. The extent of this phenomenon in non-human animals is largely unknown, but such knowledge is important to understanding the evolution of both lifespan and sociality. Here, we report evidence that levels of affiliative social behaviour (i.e. 'social connectedness') with both same-sex and opposite-sex conspecifics predict adult survival in wild female baboons. In the Amboseli ecosystem in Kenya, adult female baboons that were socially connected to either adult males or adult females lived longer than females who were socially isolated from both sexes--females with strong connectedness to individuals of both sexes lived the longest. Female social connectedness to males was predicted by high dominance rank, indicating that males are a limited resource for females, and females compete for access to male social partners. To date, only a handful of animal studies have found that social relationships may affect survival. This study extends those findings by examining relationships to both sexes in by far the largest dataset yet examined for any animal. Our results support the idea that social effects on survival are evolutionarily conserved in social mammals.

  6. Use of "one-pot, mix-and-read" peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

    DEFF Research Database (Denmark)

    Svitek, Nicholas; Hansen, Andreas Martin; Steinaa, Lucilla

    2014-01-01

    Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8(+) cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA....... parva CTL epitopes. Using an ELISA assay to measure peptide-BoLA monomer formation and p-MHC class I tetramers of new specificity, we demonstrate that a predicted alternative epitope Tp2(29-37) rather than the previously reported Tp2(27-37) epitope is the correct Tp2 epitope presented by BoLA-6......*04101. We also verified the prediction by NetMHCpan that the Tp5(87-95) epitope reported as BoLA-T5 restricted can also be presented by BoLA-1*02301, a molecule similar in sequence to BoLA-T5. In addition, Tp5(87-95) specific bovine CTL were simultaneously stained by Tp5-BoLA-1*02301 and Tp5-BoLA-T5...

  7. {sup 18}F-FDG PET/CT predicts survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Carkaci, Selin [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); The Ohio State University, Department of Radiology, Columbus, OH (United States); Sherman, Christopher T.; Ozkan, Efe; Adrada, Beatriz E.; Yang, Wei T. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Wei, Wei [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Rohren, Eric M. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Mawlawi, Osama R. [The University of Texas MD Anderson Cancer Center, Department of Imaging Physics, Houston, TX (United States); Ueno, Naoto T. [The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology, Houston, TX (United States); Buchholz, Thomas A. [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States)

    2013-12-15

    The objective of this study was to evaluate the role of {sup 18}F-FDG PET/CT in predicting overall survival in inflammatory breast cancer patients undergoing neoadjuvant chemotherapy. Included in this retrospective study were 53 patients with inflammatory breast cancer who had at least two PET/CT studies including a baseline study before the start of neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to assess the effects on survival of the following factors: tumor maximum standardized uptake value (SUVmax) at baseline, preoperatively and at follow-up, decrease in tumor SUVmax, histological tumor type, grade, estrogen, progesterone, HER2/neu receptor status, and extent of disease at presentation including axillary nodal and distant metastases. By univariate analysis, survival was significantly associated with decrease in tumor SUVmax and tumor receptor status. Patients with decrease in tumor SUVmax had better survival (P = 0.02). Patients with a triple-negative tumor (P = 0.0006), a Her2/neu-negative tumor (P = 0.038) or an ER-negative tumor (P = 0.039) had worse survival. Multivariate analysis confirmed decrease in tumor SUVmax and triple-negative receptor status as significant predictors of survival. Every 10 % decrease in tumor SUVmax from baseline translated to a 15 % lower probability of death, and complete resolution of tumor FDG uptake translated to 80 % lower probability of death (P = 0.014). Patients with a triple-negative tumor had 4.11 times higher probability of death (P = 0.004). Decrease in tumor SUVmax is an independent predictor of survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy. Further investigation with prospective studies is warranted to clarify its role in assessing response and altering therapy. (orig.)

  8. Comparative study of joint analysis of microarray gene expression data in survival prediction and risk assessment of breast cancer patients.

    Science.gov (United States)

    Yasrebi, Haleh

    2016-09-01

    Microarray gene expression data sets are jointly analyzed to increase statistical power. They could either be merged together or analyzed by meta-analysis. For a given ensemble of data sets, it cannot be foreseen which of these paradigms, merging or meta-analysis, works better. In this article, three joint analysis methods, Z-score normalization, ComBat and the inverse normal method (meta-analysis) were selected for survival prognosis and risk assessment of breast cancer patients. The methods were applied to eight microarray gene expression data sets, totaling 1324 patients with two clinical endpoints, overall survival and relapse-free survival. The performance derived from the joint analysis methods was evaluated using Cox regression for survival analysis and independent validation used as bias estimation. Overall, Z-score normalization had a better performance than ComBat and meta-analysis. Higher Area Under the Receiver Operating Characteristic curve and hazard ratio were also obtained when independent validation was used as bias estimation. With a lower time and memory complexity, Z-score normalization is a simple method for joint analysis of microarray gene expression data sets. The derived findings suggest further assessment of this method in future survival prediction and cancer classification applications.

  9. High-sensitivity C-reactive protein levels predict survival and are related to haemodynamics in alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Mortensen, Christian; Andersen, Ove; Krag, Aleksander;

    2012-01-01

    Inflammation may be implicated in the haemodynamic deterioration and in the development of complications in patients with cirrhosis. High-sensitivity C-reactive protein (hsCRP) is a marker of low-grade inflammation, and predicts outcomes in patients at risk of ischaemic heart disease....... Proinflammatory cytokines reflect immune activation and have been found to be elevated in cirrhosis. We investigated a possible association between markers of inflammation and splanchnic and systemic haemodynamics, complications and survival in patients with cirrhosis....

  10. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    OpenAIRE

    Fleischmann, Achim; Thalmann, George; Perren, Aurel; Seiler,Roland

    2014-01-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumor...

  11. A graded prognostic assessment scale to predict overall survival in patients diagnosed with brain metastases undergoing Gamma-knife radiosurgery

    OpenAIRE

    Shahzadi, Sohrab; Azimi, Parisa; Bitaraf, Mohammad Ali; Azar, Maziar; Alikhani, Mazdak; Zali, Alireza; Sadeghi, Sohrab; Salmanian, Soraya

    2012-01-01

    Abstract: Background: The present study aims to evaluate the Graded Prognostic Assessment (GPA) score for predicting overall survival in patients diagnosed with brain metastases undergoing Gamma-knife radiosurgery. Methods: This was a cross sectional study conducted on the patients diagnosed with brain metastases undergoing Gamma-knife radiosurgery during 2003 to 2011. Clinical and radiological parameters were evaluated, and the GPA score were determined. Kaplan–Meier and log-rank tests were ...

  12. Using weather indices to predict survival of winter wheat in a cool temperate environment

    Science.gov (United States)

    Hayhoe, H. N.; Lapen, D. R.; Andrews, C. J.

    2002-10-01

    Seven years of winter survival data for winter wheat (Triticum aestivum L.) were collected on a loam soil located on the Central Experimental Farm at Ottawa, Ontario (45°23'N, 75°43'W). The site was low-lying and subject to frequent winter flooding and ice-sheet formation. Two cultivars, a soft white and a hard red winter wheat, were planted in September. Crop establishment was measured in late fall and the percentage survival was measured in April of the following year. Meteorological data, which were available from the nearby weather site, were used to develop a large set of monthly weather indices that were felt to be important for winter survival. The objective of the study was to use genetic selection algorithms and artificial neural networks to select a subset of critical weather factors and topographic features and to model winter survival. The six weather indices selected were the total rain depth for December (mm), the total rain depth for February (mm), the number of days of the month with snow on the ground for January, the extreme minimum observed daily air temperature for March (°C), the number of days of the month with snow on the ground for March, and the number of days of April with a daily maximum air temperature greater than 0 °C. It was found 89% of the variation in winter survival could be explained by these six weather indices, the cultivar, elevation and plot location.

  13. Cognitive performance and functional status are the major factors predicting survival of centenarians in Poland.

    Science.gov (United States)

    Mossakowska, Malgorzata; Broczek, Katarzyna; Wieczorowska-Tobis, Katarzyna; Klich-Rączka, Alicja; Jonas, Marta; Pawlik-Pachucka, Eliza; Safranow, Krzysztof; Kuznicki, Jacek; Puzianowska-Kuznicka, Monika

    2014-10-01

    Clinical and biochemical predictors of extreme longevity would be useful in geriatric practice but have still not been clearly defined. To identify the best nongenetic predictors of survival in centenarians, we examined 340 individuals aged 100+ years. A detailed questionnaire was completed, and comprehensive geriatric assessment and blood analyses were performed. Survival of study participants was checked annually over the period of 10 years. In the univariate Cox proportional hazards model, a longer survival of centenarians was correlated with a higher adjusted Mini-Mental State Examination (MMSE(adj)) score (p HR = 0.978 per each MMSE(adj) point, 95% CI: 0.964-0.993, p = .004; HR = 0.900 per each ADL point, 95% CI: 0.842-0.962, p = .002, respectively). In multivariate analysis with the ADL score substituted by the IADL(adj) score, the only predictor of survival was MMSE(adj) (HR = 0.973 per each MMSE(adj) point, 95% CI: 0.958-0.988, p = .0006). Cognitive and functional performances are predictors of survival in centenarians. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Integration of Chinese Herbal Medicine Therapy Improves Survival of Patients With Chronic Lymphocytic Leukemia: A Nationwide Population-Based Cohort Study.

    Science.gov (United States)

    Fleischer, Tom; Chang, Tung-Ti; Chiang, Jen-Huai; Hsieh, Ching-Yun; Sun, Mao-Feng; Yen, Hung-Rong

    2016-05-01

    Utilization of Chinese Medicine (CM) is not uncommon in patients with chronic lymphocytic leukemia (CLL). However, the current knowledge of the usage and efficacy of CM among CLL patients is limited. The aim of this study was to determine the impact of integrative Chinese Herbal Medicine (CHM) on the disease course of CLL and ascertain the herbal products most commonly prescribed to patients with CLL.A Taiwanese nationwide population-based study involving the use of Western medicine and CM services provided by the National Health Insurance (NHI) was conducted.An NHI Research Database-based cohort study was performed; the timeframe of the study was January 2000 to December 2010. The end of the follow-up period was defined as December 31, 2011.A total of 808 patients were diagnosed with CLL in Taiwan within the defined study period. After randomly matching for age and sex and excluding patients younger than 18 years of age, data from 616 patients were analyzed.The 2 study groups both received standard of care treatment. In addition, 1 group also received CHM. Patients who were registered as receiving other forms of CM, such as acupuncture, were excluded.Hazard ratios of mortality were used to determine the influence of CHM and the therapeutic potential of herbal products.In total, 616 CLL patients were included in the analyses. We found that the HR associated with the adjunctive use of CHM was less than half when compared to the non-CHM group (0.43, 95% CI 0.33-0.55, P < 0.0001) and that treatment-naive patients who used CHM had the lowest HR. We also established that this association between reduction in HR and CHM was dose-dependent, and the longer CHM users received prescriptions, the lower the HR (P < 0.001).We supplied data from a relatively large population that spanned a significant amount of time. Our data suggests that the treatment of CLL with adjunctive CHM may have a substantial positive impact on mortality, especially for treatment-naive patients

  15. High-dose survival in the lymphocytic choriomeningitis virus infection is accompanied by suppressed DTH but unaffected T-cell cytotoxicity

    DEFF Research Database (Denmark)

    Marker, O; Thomsen, Allan Randrup; Volkert, M

    1985-01-01

    cells and infected sensitive targets in the central nervous system. On the other hand, high doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). In addition, when splenocytes from high-dose animals were transferred either intravenously or locally...... in mice infected with these doses of virus. In the high-dose mice we found generally higher organ virus titres and serum interferon titres than in the low-dose mice. Since we could demonstrate that virus-specific T-cell cytotoxicity in spleen, peripheral blood, and meningeal exudate was similar after...... intracerebral infection with large and small virus doses, and since the LCMV infection in the brain qualitatively and quantitatively was independent of the size of virus inoculum, the explanation for the survival of the high-dose animals is obviously not lack of possibilities for interaction between cytotoxic T...

  16. Pregnancy estrogen drives the changes of T-lymphocyte subsets and cytokines and prolongs the survival of H-Y skin graft in murine model

    Institute of Scientific and Technical Information of China (English)

    LIN Xing-guang; ZHOU Qi; WANG Li; GAO Ying; ZHANG Wei-na; LUO Zhen-long; CHEN Bi-cheng; CHEN Zhong-hua; CHANG Sheng

    2010-01-01

    Background Estrogen as well as CD4+Foxp3+ regulatory T cells were shown to have a protective role not only in maintaining maternal-fetal tolerance but also against autoimmune diseases. We aimed to investigate whether the pregnancy levels of estrogen are enough to induce transplant tolerance as to maintain fetal-maternal tolerance.Methods We established H-Y skin graft transplantation in C57BL/6 ovariectomized mice that reconstituted with estrogen. Subsequently, consecutive daily estrogen injection was administrated. Tregs and the cytokines in the peripheral blood were detected by flow cytometry and ELISA pre- and post-transplant.Results The results indicated that pregnancy levels of estrogen could promote Tregs in secondary lymphoid organs and peripheral blood (P0.05). The estrogen-treated recipients accepted H-Y skin grafts for more than 35 days (median survival time (MST): (44.0±1.2) days) compared with estrogen-untreated mice (MST:(23.0±1.6) days) (P <0.05). It was also observed that estrogen up-regulated the expression of Foxp3, but did not affect CD3+CD8+ effector T-cells in non-transplant mice. While in the presence of H-Y antigens, the expression of Foxp3 was more significant and CD3+CD8+ effector T cells were decreased significantly (P <0.05). Meanwhile, the up-regulated IL-10 and IL-4, and down-regulated IFN-Y could be observed (P <0.05).Conclusions Pregnancy levels of estrogen may promote the conversion of peripheral Tregs in secondary lymphoid organs, but show no effect on the natural Tregs production, differentiation and maturity in central lymphoid organs.Furthermore, pregnancy levels of estrogen could significantly prolong the survivals of H-Y skin grafts by the expansion of Tregs, suppression of CD3+CD8+ effector T-cells and immune shift towards Th2 cytokines.

  17. Predicting the Survival Time for Bladder Cancer Using an Addi-tive Hazards Model in Microarray Data

    Directory of Open Access Journals (Sweden)

    Leili TAPAK

    2016-02-01

    Full Text Available Background: One substantial part of microarray studies is to predict patients’ survival based on their gene expression profile. Variable selection techniques are powerful tools to handle high dimensionality in analysis of microarray data. However, these techniques have not been investigated in competing risks setting. This study aimed to investigate the performance of four sparse variable selection methods in estimating the survival time.Methods: The data included 1381 gene expression measurements and clinical information from 301 patients with bladder cancer operated in the years 1987 to 2000 in hospitals in Denmark, Sweden, Spain, France, and England. Four methods of the least absolute shrinkage and selection operator, smoothly clipped absolute deviation, the smooth integration of counting and absolute deviation and elastic net were utilized for simultaneous variable selection and estimation under an additive hazards model. The criteria of area under ROC curve, Brier score and c-index were used to compare the methods.Results: The median follow-up time for all patients was 47 months. The elastic net approach was indicated to outperform other methods. The elastic net had the lowest integrated Brier score (0.137±0.07 and the greatest median of the over-time AUC and C-index (0.803±0.06 and 0.779±0.13, respectively. Five out of 19 selected genes by the elastic net were significant (P<0.05 under an additive hazards model. It was indicated that the expression of RTN4, SON, IGF1R and CDC20 decrease the survival time, while the expression of SMARCAD1 increase it.Conclusion: The elastic net had higher capability than the other methods for the prediction of survival time in patients with bladder cancer in the presence of competing risks base on additive hazards model.Keywords: Survival analysis, Microarray data, Additive hazards model, Variable selection, Bladder cancer 

  18. Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma.

    Science.gov (United States)

    Shen, Sipeng; Wang, Guanrong; Shi, Qianwen; Zhang, Ruyang; Zhao, Yang; Wei, Yongyue; Chen, Feng; Christiani, David C

    2017-01-01

    DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO). The correlation between DNA methylation and corresponding gene expression and the prognostic value of the gene expression were explored as well. The seven DNA methylation CpG sites were identified which were significantly associated with OSCC overall survival. Prognostic signature, a weighted linear combination of the seven CpG sites, successfully distinguished the overall survival of OSCC patients and had a moderate predictive ability for survival [training set: hazard ratio (HR) = 3.23, P = 5.52 × 10(-10), area under the curve (AUC) = 0.76; validation set 1: HR = 2.79, P = 0.010, AUC = 0.67; validation set 2: HR = 3.69, P = 0.011, AUC = 0.66]. Stratification analysis by human papillomavirus status, clinical stage, age, gender, smoking status, and grade retained statistical significance. Expression of genes corresponding to candidate CpG sites (AJAP1, SHANK2, FOXA2, MT1A, ZNF570, HOXC4, and HOXB4) was also significantly associated with patient's survival. Signature integrating of DNA methylation, gene expression, and clinical information showed a superior ability for prognostic prediction (AUC = 0.78). Prognostic signature integrated of DNA methylation, gene expression, and clinical information provides a better prognostic prediction value for OSCC patients than that with clinical information only.

  19. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    Science.gov (United States)

    Shi, Mingguang; He, Jianmin

    2016-04-01

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

  20. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  1. HIF1-Alpha Expression Predicts Survival of Patients with Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    dos Santos, Marcelo; Mercante, Ana Maria da Cunha; Louro, Iúri Drumond; Gonçalves, Antônio José; de Carvalho, Marcos Brasilino; da Silva, Eloiza Helena Tajara; da Silva, Adriana Madeira Álvares

    2012-01-01

    Background Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood. Patients and Methods In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth. Results Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse. Conclusion These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient. PMID:23028863

  2. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    DEFF Research Database (Denmark)

    Loeve, Martine; Hop, Wim C. J.; de Bruijne, Marleen

    2012-01-01

    /inflammation" (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR) and bulla/cysts (BUL). The volume of each component was computed using semi-automated software. Survival analysis included Kaplan-Meier curves, and Cox-regression models. Measurements and main results: 366 (186 males) out of 411...

  3. Retransplantation of the liver in adults : outcome and predictive factors for survival

    NARCIS (Netherlands)

    Postma, R; Haagsma, EB; Peeters, PMJG; van den Berg, AP; Slooff, MJH

    2004-01-01

    Hepatic retransplantation is considered to carry a higher risk than primary transplantation. Survival might improve with more experience and better immunosuppression. We studied all 55 patients who were adults at the time of their first retransplantation and who underwent retransplantation between 1

  4.  Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

    Science.gov (United States)

    Begini, Paola; Gigante, Elia; Antonelli, Giulio; Carbonetti, Francesco; Iannicelli, Elsa; Anania, Giulia; Imperatrice, Barbara; Pellicelli, Adriano Maria; Fave, Gianfranco Delle; Marignani, Massimo

     Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

  5. Prediction of Survival for Preterm Births by Weight and Gestational Age: Retrospective Population Based Study

    National Research Council Canada - National Science Library

    Elizabeth S. Draper; Bradley Manktelow; David J. Field; David James

    1999-01-01

    ... (a) known to be alive at the onset of labour, and (b) admitted for neonatal care. Results 738 deaths occurred in 3760 infants born between 22 and 32 weeks' gestation during the study period, giving an overall survival rate of 80.4...

  6. Are Breast Cancer Molecular Classes Predictive of Survival in Patients with Long Follow-Up?

    Directory of Open Access Journals (Sweden)

    Danae Pracella

    2013-01-01

    Full Text Available In this study we investigate the clinical outcomes of 305 breast cancer (BC patients, aged 55 years or younger, with long follow-up and according to intrinsic subtypes. The cohort included 151 lymph node negative (LN− and 154 lymph node positive (LN+ patients. Luminal A tumors were mainly LN−, well differentiated, and of stage I; among them AR was an indicator of good prognosis. Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and nodal metastases as well as higher proliferation status and stage. Among luminal tumors, those PR positive and vimentin negative showed a longer survival. HER2-positive nonluminal and TN patients showed a poorer outcome, with BC-specific death mostly occurring within 5 and 10 years. Only luminal tumor patients underwent BC death over 10 years. When patients were divided in to LN− and LN+ no differences in survival were observed in the luminal subgroups. LN− patients have good survival even after 20 years of follow-up (about 75%, while for LN+ patients survival at 20 years (around 40% was comparable to HER2-positive nonluminal and TN groups. In conclusion, in our experience ER-positive breast tumors are better divided by classical clinical stage than molecular classification, and they need longer clinical follow-up especially in cases with lymph node involvement.

  7. Predicting Secondary School Dropout among South African Adolescents: A Survival Analysis Approach

    Science.gov (United States)

    Weybright, Elizabeth H.; Caldwell, Linda L.; Xie, Hui; Wegner, Lisa; Smith, Edward A.

    2017-01-01

    Education is one of the strongest predictors of health worldwide. In South Africa, school dropout is a crisis where by Grade 12, only 52% of the age appropriate population remain enrolled. Survival analysis was used to identify the risk of dropping out of secondary school for male and female adolescents and examine the influence of substance use…

  8. 139 Clinically Applicable and Biologically Validated MRI Radiomic Test Method Predicts Glioblastoma Genomic Landscape and Survival.

    Science.gov (United States)

    Zinn, Pascal O; Singh, Sanjay K; Kotrotsou, Aikaterini; Zandi, Faramak; Thomas, Ginu; Hatami, Masumeh; Luedi, Markus M; Elakkad, Ahmed; Hassan, Islam; Gumin, Joy; Sulman, Erik P; Lang, Frederick F; Colen, Rivka R

    2016-08-01

    Imaging is the modality of choice for noninvasive characterization of biological tissue and organ systems; imaging serves as early diagnostic tool for most disease processes and is rapidly evolving, thus transforming the way we diagnose and follow patients over time. A vast number of cancer imaging characteristics have been correlated to underlying genomics; however, none have established causality. Therefore, our objectives were to test if there is a causal relationship between imaging and genomic information; and to develop a clinically relevant radiomic pipeline for glioblastoma molecular characterization. Functional validation was performed using a prototypic in vivo RNA-interference-based orthotopic xenograft mouse model. The automated pipeline collects 4800 MRI-derived texture features per tumor. Using univariate feature selection and boosted tree predictive modeling, a patient-specific genomic probability map was derived and patient survival predicted (The Cancer Genome Atlas/MD Anderson data sets). Data demonstrated a significant xenograft to human association (area under the curve [AUC] 84%, P applicable analytical imaging method termed Radiome Sequencing to allow for automated image analysis, prediction of key genomic events, and survival. This method is scalable and applicable to any type of medical imaging. Further, it allows for human-mouse matched coclinical trials, in-depth end point analysis, and upfront noninvasive high-resolution radiomics-based diagnostic, prognostic, and predictive biomarker development.

  9. SU-E-T-131: Artificial Neural Networks Applied to Overall Survival Prediction for Patients with Periampullary Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Y; Yu, J; Yeung, V; Palmer, J; Yu, Y; Lu, B; Babinsky, L; Burkhart, R; Leiby, B; Siow, V; Lavu, H; Rosato, E; Winter, J; Lewis, N; Sama, A; Mitchell, E; Anne, P; Hurwitz, M; Yeo, C; Bar-Ad, V [Thomas Jefferson University Hospital, Philadelphia, PA (United States); and others

    2015-06-15

    Purpose: Artificial neural networks (ANN) can be used to discover complex relations within datasets to help with medical decision making. This study aimed to develop an ANN method to predict two-year overall survival of patients with peri-ampullary cancer (PAC) following resection. Methods: Data were collected from 334 patients with PAC following resection treated in our institutional pancreatic tumor registry between 2006 and 2012. The dataset contains 14 variables including age, gender, T-stage, tumor differentiation, positive-lymph-node ratio, positive resection margins, chemotherapy, radiation therapy, and tumor histology.After censoring for two-year survival analysis, 309 patients were left, of which 44 patients (∼15%) were randomly selected to form testing set. The remaining 265 cases were randomly divided into training set (211 cases, ∼80% of 265) and validation set (54 cases, ∼20% of 265) for 20 times to build 20 ANN models. Each ANN has one hidden layer with 5 units. The 20 ANN models were ranked according to their concordance index (c-index) of prediction on validation sets. To further improve prediction, the top 10% of ANN models were selected, and their outputs averaged for prediction on testing set. Results: By random division, 44 cases in testing set and the remaining 265 cases have approximately equal two-year survival rates, 36.4% and 35.5% respectively. The 20 ANN models, which were trained and validated on the 265 cases, yielded mean c-indexes as 0.59 and 0.63 on validation sets and the testing set, respectively. C-index was 0.72 when the two best ANN models (top 10%) were used in prediction on testing set. The c-index of Cox regression analysis was 0.63. Conclusion: ANN improved survival prediction for patients with PAC. More patient data and further analysis of additional factors may be needed for a more robust model, which will help guide physicians in providing optimal post-operative care. This project was supported by PA CURE Grant.

  10. {sup 18}F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with {sup 90}Y microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Haug, Alexander R. [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany); Klinikum Grosshadern, Department of Nuclear Medicine, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University, Department of Internal Medicine III, Munich (Germany); Bruns, Christiane J. [Ludwig-Maximilians-University, Department of Surgery, Munich (Germany); Hoffmann, Ralf; Jakobs, Tobias [Ludwig-Maximilians-University, Institute of Clinical Radiology, Munich (Germany); Bartenstein, Peter; Hacker, Marcus [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

    2011-06-15

    {sup 90}Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with {sup 99m}Tc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization. The study group comprised 26 consecutive patients suffering from nonresectable ICC. Before treatment with radioembolization, all patients underwent MRI of the liver, as well as MAA scintigraphy, which was followed immediately by SPECT(/CT) to quantify the liver-lung shunt fraction. Using image fusion, regions of interest were drawn around the tumours and the entire liver, and the tumour-to-liver quotient was calculated. In addition, FDG PET/CT was performed at baseline and 3 months after radioembolization, and the percentage changes in peak ({delta}SUV{sub max}) and mean ({delta}SUV{sub mean}) FDG uptake and in metabolic tumour volume ({delta}Vol{sub 2SD}) relative to baseline were calculated. Treatment response at 3 months was also assessed using contrast-enhanced MRI and CT on the basis of standard criteria. Of 23 patients in whom follow-up MRI was available, 5 (22%) showed a partial response, 15 (65%) stable disease and 3 (13%) progressive disease. The change in all FDG values significantly predicted survival by Kaplan-Meier analysis after radioembolization; {delta}Vol{sub 2SD} responders had a median survival of 97 weeks versus 30 weeks in nonresponders (P = 0.02), whereas {delta}SUV{sub max} and {delta}SUV{sub mean} responders had a median survival of 114 weeks (responder) versus 19 weeks (nonresponder) and 69 weeks in patients with stable disease (P < 0.05). Pretherapeutic MAA scintigraphy or MRI did not predict survival, nor did the presence of extrahepatic metastases, or prior therapies. Only {delta}Vol{sub 2SD} was significantly associated with survival by univariate analysis (hazard ratio 0.25; P = 0.04) and multivariate analysis (hazard ratio 0.20, P = 0

  11. Integration of Multi-Modal Biomedical Data to Predict Cancer Grade and Patient Survival.

    Science.gov (United States)

    Phan, John H; Hoffman, Ryan; Kothari, Sonal; Wu, Po-Yen; Wang, May D

    2016-02-01

    The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization. Results indicate that integration of multiple data modalities improves prediction of cancer grade and outcome. Specifically, stacked generalization, a method that integrates multiple data modalities to produce a single prediction result, outperforms both single-data-modality prediction and majority vote. Moreover, stacked generalization reveals the contribution of each data modality (and specific features within each data modality) to the final prediction result and may provide biological insights to explain prediction performance.

  12. Absolute Monocyte Count and Lymphocyte-Monocyte Ratio Predict Outcome in Nodular Sclerosis Hodgkin Lymphoma: Evaluation Based on Data From 1450 Patients.

    Science.gov (United States)

    Tadmor, Tamar; Bari, Alessia; Marcheselli, Luigi; Sacchi, Stefano; Aviv, Ariel; Baldini, Luca; Gobbi, Paolo G; Pozzi, Samantha; Ferri, Paola; Cox, Maria Christina; Cascavilla, Nicola; Iannitto, Emilio; Federico, Massimo; Polliack, Aaron

    2015-06-01

    To verify whether absolute monocyte count (AMC) and lymphocyte- monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL). Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007. The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm(3), and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; PHR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3). This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  13. SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma.

    Science.gov (United States)

    Dhanda, J; Triantafyllou, A; Liloglou, T; Kalirai, H; Lloyd, B; Hanlon, R; Shaw, R J; Sibson, D R; Risk, J M

    2014-11-25

    Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available. In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis. Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (PSMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (PSMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%). A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.

  14. NFAT5 induction by the pre-T-cell receptor serves as a selective survival signal in T-lymphocyte development.

    Science.gov (United States)

    Berga-Bolaños, Rosa; Alberdi, Maria; Buxadé, Maria; Aramburu, José; López-Rodríguez, Cristina

    2013-10-01

    The Rel-like transcription factors nuclear factor kappa B (NF-κB) and the calcineurin-dependent nuclear factor of activated T cells (NFATc) control specific points of thymocyte maturation. Thymocytes also express a distinct member of the Rel family, the calcineurin-independent, osmostress response regulator NFAT5. Here we show that IKKβ regulates the expression of NFAT5 in thymocytes, which in turn contributes to the survival of T-cell receptor αβ thymocytes and the transition from the β-selection checkpoint to the double-positive stage in an osmostress-independent manner. NFAT5-deficient thymocytes had normal expression and proximal signaling of the pre-T-cell receptor but exhibited a partial defect in β-chain allelic exclusion and increased apoptosis. Further analysis showed that NFAT5 regulated the expression of the prosurvival factors A1 and Bcl2 and attenuated the proapoptotic p53/Noxa axis. These findings position NFAT5 as a target of the IKKβ/NF-κB pathway in thymocytes and as a downstream effector of the prosurvival role of the pre-T-cell receptor.

  15. NFAT5 induction by the pre–T-cell receptor serves as a selective survival signal in T-lymphocyte development

    Science.gov (United States)

    Berga-Bolaños, Rosa; Alberdi, Maria; Buxadé, Maria; Aramburu, José; López-Rodríguez, Cristina

    2013-01-01

    The Rel-like transcription factors nuclear factor kappa B (NF-κB) and the calcineurin-dependent nuclear factor of activated T cells (NFATc) control specific points of thymocyte maturation. Thymocytes also express a distinct member of the Rel family, the calcineurin-independent, osmostress response regulator NFAT5. Here we show that IKKβ regulates the expression of NFAT5 in thymocytes, which in turn contributes to the survival of T-cell receptor αβ thymocytes and the transition from the β-selection checkpoint to the double-positive stage in an osmostress-independent manner. NFAT5-deficient thymocytes had normal expression and proximal signaling of the pre–T-cell receptor but exhibited a partial defect in β-chain allelic exclusion and increased apoptosis. Further analysis showed that NFAT5 regulated the expression of the prosurvival factors A1 and Bcl2 and attenuated the proapoptotic p53/Noxa axis. These findings position NFAT5 as a target of the IKKβ/NF-κB pathway in thymocytes and as a downstream effector of the prosurvival role of the pre–T-cell receptor. PMID:24043824

  16. Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group.

    Directory of Open Access Journals (Sweden)

    João Pedreira Duprat

    Full Text Available The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs in sentinel lymph node (SLN metastasis.This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL were identified by multiple logistic regression.SLN metastasis was detected in 101 of 633 cases (16.1% and in 93 of 428 patients (21.7% when melanomas ≤ 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1-3.0, in addition to Breslow index (greater than 2.00 mm, lymph vascular invasion, and presence of mitosis.SLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists.

  17. Prediction of kidney survival in children with primary focal segmental glomerulosclerosis (a two-center study.

    Directory of Open Access Journals (Sweden)

    Alaleh Gheissari

    2007-07-01

    Full Text Available BACKGROUND: Focal segmental glomerulosclerosis (FSGS is one of the most common glomerulopathies in children leading to end stage renal disease (ESRD. Different values of median renal survival have been reported among different ethnicities and races. Many factors are assumed to be responsible for ESRD in these patients. In this study, we tried to determine median renal survival (MRS and also some clinical and histopathological features predisposing FSGS
    patients to ESRD in two referral hospitals in Tehran.
    METHODS: The study involved 103 FSGS patients (61 males and 42 females with a mean age of 7.08 ± 0.68 years. The diagnosis was made based on kidney biopsies. All kidney biopsies were studied by light and immunofluorescent microscopes. Ocular grids (counting squares were used as the standard method to calculate the percentage of cortical interstitial fibrosis (CIF. The percentage of glomerular sclerosis was presented as renal injury score. Glomerular filtration rate (GFR950 ml/min was considered as renal death or the end point. Patients were followed for 1 to 15 years, until occurrence of renal death.
    RESULTS: The MRS was 9.04 ± 1.8 yrs. The renal survival reached 72%, 47% and 17% after 5, 10 and 15 years, respectively. Univariate analysis showed significant reverse correlation (P<0.05 between renal survival and the following variables: hypertension, anemia, GFR at the time of first admission and also renal injury score >50%, peritubular fibrosis, periglomerular fibrosis, tubular atrophy and CIFC20%. However, multivariate analysis revealed only a reverse correlation between renal survival with CIFC20% and also hypertension (P<0.0001 and P<0.05, respectively.
    CONCLUSIONS: In our patients, FSGS showed a rapid course towards ESRD compared with patients of western countries. Perhaps some ethnic and genetic factors such as angiotensin converting enzyme genotypes

  18. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Gouel, Pierrick [Centre Henri Becquerel and Rouen University Hospital, Department of Nuclear Medicine, Rouen (France); Di Fiore, Frederic [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Centre Henri Becquerel, Department of Medical oncology, Rouen (France); Marre, Charline; Michel, Pierre [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Hapdey, Sebastien; Modzelewski, Romain; Vera, Pierre [Centre Henri Becquerel and Rouen University Hospital, Department of Nuclear Medicine, Rouen (France); University of Rouen, QuantIF (Litis EA 4108 - FR CNRS 3638), Rouen (France); Dubray, Bernard [University of Rouen, QuantIF (Litis EA 4108 - FR CNRS 3638), Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France)

    2014-11-15

    It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes. Included in the study were 67 patients with a histological diagnosis of oesophageal squamous cell carcinoma. Each patient underwent {sup 18}F-FDG PET (4.5 MBq/kg) before chemoradiotherapy. Quantitative analysis was performed using the following parameters: age, weight loss, location, N stage, OMS performance status, MTV{sub p} and MTV{sub p'} (metabolic tumour volume determined by two different physicians), MTV{sub 40%} (volume for a threshold of 40 % of SUVmax), MTV{sub a} (volume automatically determined with a contrast-based adaptive threshold method), SUVmax, SUVmean and TLG (total lesion glycolysis). MTV{sub p} and MTV{sub 40%} were highly correlated (Pearson's index 0.92). SUVmean{sub p} and SUVmean{sub 40%} were also correlated (Pearson's index 0.86), as were TLG{sub p} and TLG{sub 40%} (Pearson's index 0.98). Similarly, the parameters obtained with the adaptive threshold method (MTV{sub a}, SUVmean{sub a} and TLG{sub a}) were correlated with those obtained manually (MTV{sub p}, SUVmean{sub p} and TLG{sub p}). The manual metabolic tumour volume determination (MTV{sub p} and MTV{sub p'}) was reproducible. Multivariate analysis for disease-free survival (DFS) showed that a larger MTV{sub p} was associated with a shorter DFS (p = 0.004) and that a higher SUVmax was associated with a longer DFS (p = 0.02). Multivariate analysis for overall survival (OS) showed that a larger MTV{sub p} was associated with a shorter OS (p = 0.01) and that a tumour in the distal oesophagus was associated with a longer OS (p = 0.005). The associations among the other parameters were not statistically significant. Metabolic tumour volume is a major

  19. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites

    DEFF Research Database (Denmark)

    Krag, A; Bendtsen, F; Henriksen, J H;

    2010-01-01

    OBJECTIVES: Recent studies suggest that cardiac dysfunction precedes development of the hepatorenal syndrome. In this follow-up study, we aimed to investigate the relation between cardiac and renal function in patients with cirrhosis and ascites and the impact of cardiac systolic function...... on survival. Patients and DESIGN: Twenty-four patients with cirrhosis and ascites were included. Cardiac function was investigated by gated myocardial perfusion imaging (MPI) for assessment of cardiac index (CI) and cardiac volumes. The renal function was assessed by determination of glomerular filtration...... (130 (SD 46) vs 78 (SD 29) mumol/l, pdeveloped hepatorenal syndrome type 1 within 3 months was higher in the group with low CI than in the high CI group (43% vs 5%, p = 0.04). Patients with the lowest CI (N = 8) had significantly poorer survival at 3, 9, and 12 months...

  20. Visceral Obesity Predicts Fewer Lymph Node Metastases and Better Overall Survival in Colon Cancer

    OpenAIRE

    Park, Se Woo; Lee, Hang Lak; Doo, Eun Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Oh Young; Han, Dong Soo; Yoon, Byung Chul; Choi, Ho Soon; Lee, Kang Hong

    2015-01-01

    Background The relationship between visceral obesity and colon cancer outcome has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node (LN) metastasis and overall survival (OS) in colon cancer. Materials and Methods Metastatic LN ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected LNs. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume dist...

  1. Composition of symbiotic bacteria predicts survival in Panamanian golden frogs infected with a lethal fungus.

    Science.gov (United States)

    Becker, Matthew H; Walke, Jenifer B; Cikanek, Shawna; Savage, Anna E; Mattheus, Nichole; Santiago, Celina N; Minbiole, Kevin P C; Harris, Reid N; Belden, Lisa K; Gratwicke, Brian

    2015-04-22

    Symbiotic microbes can dramatically impact host health and fitness, and recent research in a diversity of systems suggests that different symbiont community structures may result in distinct outcomes for the host. In amphibians, some symbiotic skin bacteria produce metabolites that inhibit the growth of Batrachochytrium dendrobatidis (Bd), a cutaneous fungal pathogen that has caused many amphibian population declines and extinctions. Treatment with beneficial bacteria (probiotics) prevents Bd infection in some amphibian species and creates optimism for conservation of species that are highly susceptible to chytridiomycosis, the disease caused by Bd. In a laboratory experiment, we used Bd-inhibitory bacteria from Bd-tolerant Panamanian amphibians in a probiotic development trial with Panamanian golden frogs, Atelopus zeteki, a species currently surviving only in captive assurance colonies. Approximately 30% of infected golden frogs survived Bd exposure by either clearing infection or maintaining low Bd loads, but this was not associated with probiotic treatment. Survival was instead related to initial composition of the skin bacterial community and metabolites present on the skin. These results suggest a strong link between the structure of these symbiotic microbial communities and amphibian host health in the face of Bd exposure and also suggest a new approach for developing amphibian probiotics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. Loss of expression of BAP1 predicts longer survival in mesothelioma.

    Science.gov (United States)

    Farzin, Mahtab; Toon, Christopher W; Clarkson, Adele; Sioson, Loretta; Watson, Nicole; Andrici, Juliana; Gill, Anthony J

    2015-06-01

    BRCA1-associated protein 1 (BAP1) is a tumour suppressor gene frequently inactivated in mesothelioma, rarely also in association with germline mutation. BAP1 mutations have been associated with improved prognosis and distinct clinicopathological features. We sought to determine the clinicopathological significance of BAP1 immunohistochemistry (IHC) in mesothelioma.We performed IHC on a tissue microarray (TMA) cohort comprising all available thoracic mesotheliomas encountered during the period 1991-2014 at our institution (n = 229). All cases were independently reviewed to confirm the diagnosis and subclassify as epithelioid, sarcomatoid or biphasic. The median age at diagnosis was 72 years; 188 (82.1%) were male; 120 (52.4%) were epithelioid (median survival 13.0 months), 67 (29.3%) sarcomatoid (median survival 5.6 months) and 42 (18.3%) biphasic (median survival 10.6 months). Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in non-neoplastic cells) occurred in 106 (46.3%) mesotheliomas. There was complete interobserver concordance for BAP1 IHC status. BAP1 loss was strongly associated with younger age at onset (p mesothelioma.

  3. Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival

    Directory of Open Access Journals (Sweden)

    Tambasco Mauro

    2010-12-01

    Full Text Available Abstract Background Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade. There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity for invasive ductal carcinoma of the breast. Methods We applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA cores derived from 379 patients. Patients were categorized according to low (1.75, N = 90 fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status. Results Patients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p Conclusion Except for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.

  4. Can gene expression profiling predict survival for patients with squamous cell carcinoma of the lung?

    Directory of Open Access Journals (Sweden)

    Endo Chiaki

    2004-12-01

    Full Text Available Abstract Background Lung cancer remains to be the leading cause of cancer death worldwide. Patients with similar lung cancer may experience quite different clinical outcomes. Reliable molecular prognostic markers are needed to characterize the disparity. In order to identify the genes responsible for the aggressiveness of squamous cell carcinoma of the lung, we applied DNA microarray technology to a case control study. Fifteen patients with surgically treated stage I squamous cell lung cancer were selected. Ten were one-to-one matched on tumour size and grade, age, gender, and smoking status; five died of lung cancer recurrence within 24 months (high-aggressive group, and five survived more than 54 months after surgery (low-aggressive group. Five additional tissues were included as test samples. Unsupervised and supervised approaches were used to explore the relationship among samples and identify differentially expressed genes. We also evaluated the gene markers' accuracy in segregating samples to their respective group. Functional gene networks for the significant genes were retrieved, and their association with survival was tested. Results Unsupervised clustering did not group tumours based on survival experience. At p Conclusion The overall gene expression pattern between the high and low aggressive squamous cell carcinomas of the lung did not differ significantly with the control of confounding factors. A small subset of genes or genes in specific pathways may be responsible for the aggressive nature of a tumour and could potentially serve as panels of prognostic markers for stage I squamous cell lung cancer.

  5. Melanoma long non-coding RNA signature predicts prognostic survival and directs clinical risk-specific treatments.

    Science.gov (United States)

    Chen, Xijia; Guo, Wenna; Xu, Xin-Jian; Su, Fangchu; Wang, Yi; Zhang, Yingzheng; Wang, Qiang; Zhu, Liucun

    2017-03-01

    Various studies have demonstrated that the Breslow thickness, tumor ulceration and mitotic index could serve as prognostic markers in patients with cutaneous melanoma. Recently, however, as these clinicopathological biomarkers lack efficient interpretation of endogenous mechanism of melanoma, the emphasis on the prognosis of melanoma has transformed to molecular tumor markers. This study was designed to identify survival-related long non-coding RNAs (lncRNAs), and based on the different expressions of these lncRNAs, clinical risk-specific diagnosis and adjuvant therapy could be employed on melanoma patients, especially patients in the early course of disease or patients with a Breslow thickness no more than 2mm. The clinical information and corresponding RNA expression data were obtained from The Cancer Genome Atlas dataset and Gene Expression Omnibus dataset (GSE65904). All samples were categorized into one training dataset and two validation datasets. Cox proportional hazard regression analysis was then used to identify survival-related lncRNAs and risk assessment signature was constructed in training dataset. Kaplan-Meier method was used to estimate the utility of this signature in predicting the duration of survival of patients both in the training dataset and two validation datasets. Meanwhile receiver operating characteristic analyses were used to evaluate the predictive effectiveness of this signature in two validation datasets. It was found that the signature was effective while used for risk stratification, and Kaplan-Meier analyses indicated that the duration of survival of patients in high-risk groups were significantly shorter than that of low-risk groups. Moreover, areas under the receiver operating characteristic curve were 0.711 (95% confidence interval: 0.618-0.804) and 0.698 (95% confidence interval: 0.614-0.782) when this signature was used to predict the patients' duration of survival in two validation datasets respectively, indicating the

  6. Cumulative scores based onplasma D-dimer andserum albumin levels predict survival inesophageal squamous cell carcinoma patients treated withtransthoracic esophagectomy

    Institute of Scientific and Technical Information of China (English)

    DeQingLiu; FangFangLi; WeiHuaJia

    2016-01-01

    Background:Recently, studies have shown that plasma D‑dimer and serum albumin are prognostic markers for esophageal cancer. The purpose of this study was to evaluate a novel prognostic scoring system—DA score (combi‑nation of preoperative plasma D‑dimer and serum albumin levels)—and analyze the association between survival of patients with esophageal squamous cell carcinoma (ESCC) and their Glasgow prognostic score. Methods:In this retrospective study, preoperative biochemical markers and clinicopathologic factors in 260 ESCC patients treated with transthoracic esophagectomy were reviewed. According to receiver operating characteristic analysis, the cutoff values of D‑dimer and albumin were deifned as 0.5μg/mL and 43.8g/L, respectively. Patients with high D‑dimer levels (≥0.5μg/mL) and low albumin levels (<43.8g/L) were assigned a score of 2, those with only one of the two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were assigned a score of 0. Results:ESCC patients with a DA score of 0, 1, and 2 numbered 55, 116, and 89, respectively. Survival analysis showed that patients with a DA score of 2 had lower overall survival (OS) rates than those with DA scores of 1 and 0 (37.1% vs. 52.6% and 76.4%,P<0.001); similar ifndings were observed for disease‑free survival (DFS) rates (32.6% vs. 44.8% and 67.3%,P<0.001). In addition, the predictive value of the DA score was also signiifcant in patients with stages I–IIA and stages IIB–IV ESCC. Multivariate Cox regression analyses indicated that hazard ratios (HRs) for predicting OS of patients with DA scores 1 and 2 were 2.25 (P=0.010) and 3.14 (P<0.001), respectively, compared with those with a DA score of 0, and HRs for predicting DFS of patients with DA scores of 1 and 2 were 1.86 (P=0.023) and 2.68 (P<0.001), respectively, compared with those with a DA scores of 0. Conclusions:Our study suggests that preoperative DA scores are notably associated with

  7. Does adding risk-trends to survival models improve in-hospital mortality predictions? A cohort study

    Directory of Open Access Journals (Sweden)

    Forster Alan J

    2011-07-01

    Full Text Available Abstract Background Clinicians informally assess changes in patients' status over time to prognosticate their outcomes. The incorporation of trends in patient status into regression models could improve their ability to predict outcomes. In this study, we used a unique approach to measure trends in patient hospital death risk and determined whether the incorporation of these trend measures into a survival model improved the accuracy of its risk predictions. Methods We included all adult inpatient hospitalizations between 1 April 2004 and 31 March 2009 at our institution. We used the daily mortality risk scores from an existing time-dependent survival model to create five trend indicators: absolute and relative percent change in the risk score from the previous day; absolute and relative percent change in the risk score from the start of the trend; and number of days with a trend in the risk score. In the derivation set, we determined which trend indicators were associated with time to death in hospital, independent of the existing covariates. In the validation set, we compared the predictive performance of the existing model with and without the trend indicators. Results Three trend indicators were independently associated with time to hospital mortality: the absolute change in the risk score from the previous day; the absolute change in the risk score from the start of the trend; and the number of consecutive days with a trend in the risk score. However, adding these trend indicators to the existing model resulted in only small improvements in model discrimination and calibration. Conclusions We produced several indicators of trend in patient risk that were significantly associated with time to hospital death independent of the model used to create them. In other survival models, our approach of incorporating risk trends could be explored to improve their performance without the collection of additional data.

  8. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    Science.gov (United States)

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (Ptumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  9. New symptom-based predictive tool for survival at seven and thirty days developed by palliative home care teams.

    Science.gov (United States)

    Nabal, Maria; Bescos, Mar; Barcons, Miquel; Torrubia, Pilar; Trujillano, Javier; Requena, Antonio

    2014-10-01

    This study sought to develop models to predict survival at 7 and 30 days based on symptoms detected by palliative home care teams (PHCTs). This prospective analytic study included a 6-month recruitment period with patient monitoring until death or 180 days after recruitment. The inclusion criteria consisted of age greater than 18 years, advanced cancer, and treatment provided by participating PHCTs between April and July 2009. The study variables included death at 7 or 30 days, survival time, age, gender, place of residence, type of tumor and extension, presence of 11 signs and symptoms measured with a 0-3 Likert scale, functional and cognitive status, and use of a subcutaneous butterfly needle. The statistics applied included a descriptive analysis according to the percentage or mean±standard deviation. For symptom comparison between surviving and nonsurviving patients, the χ(2) test was used. Classification and regression tree (CART) methodology was used for model development. An internal validation system (cross-validation with 10 partitions) was used to ensure generalization of the models. The area under the receiver operating characteristics (ROC) curve was calculated (with a 95% confidence interval) to assess the validation of the models. A total of 698 patients were included. The mean age of the patients was 73.7±12 years, and 60.3% were male. The most frequent type of neoplasm was digestive (37.6%). The mean Karnofsky score was 51.8±14, the patients' cognitive status according to the Pfeiffer test was 2.6±4 errors, and 8.3% of patients required a subcutaneous butterfly needle. Each model provided 8 decision rules with a probability assignment range between 2.2% and 99.1%. The model used to predict the probability of death at 7 days included the presence of anorexia and dysphagia and the level of consciousness, and this model produced areas under the curve (AUCs) of 0.88 (0.86-0.90) and 0.81 (0.79-0.83). The model used to predict the probability of

  10. TIMP-3 expression associates with malignant behaviors and predicts favorable survival in HCC.

    Directory of Open Access Journals (Sweden)

    Xuefeng Gu

    Full Text Available The tissue inhibitors of metalloproteinases (TIMPs are proteins that specifically inhibit the proteolytic activity of the matrix metalloproteinases (MMPs. TIMP-3, the only member of the TIMPs that can tightly bind to the extracellular matrix, has been identified as a unique tumor suppressor that demonstrates the ability to inhibit tumor angiogenesis, invasion, and metastasis. This study aimed to detect the expression of TIMP-3 in hepatocellular carcinoma (HCC and investigate the association between TIMP-3 expression and its clinicopathological significance in HCC patients. In the current study, reverse transcription-polymerase chain reaction (RT-PCR and Western blotting of HCC cell lines and one-step quantitative reverse transcription PCR (qPCR and immunohistochemistry (IHC analyses in HCC tissues were performed, to characterize the TIMP-3 expression. Kaplan-Meier survival and Cox regression analyses were utilized to evaluate the prognosis of 101 HCC patients. The results showed that the expression of TIMP-3 in HCC was significantly decreased relative to that of non-cancerous cells and tissues. Furthermore, the TIMP-3 expression was statistically associated with malignant behaviors of HCC, including portal vein invasion (p = 0.036 and lymph node metastasis (p = 0.030. Cox regression analysis revealed that TIMP-3 expression was an independent prognostic factor for disease-free survival (p = 0.039 and overall survival (p = 0.049. These data indicate that TIMP-3 expression is a valuable prognostic biomarker for HCC and that TIMP-3 expression suggests a favorable prognosis for HCC patients.

  11. Can subjective global assessment of nutritional status predict survival in ovarian cancer?

    Directory of Open Access Journals (Sweden)

    Gupta Digant

    2008-10-01

    Full Text Available Abstract Background Malnutrition is a significant problem in patients with ovarian cancer. The goal of this study was to investigate the prognostic role of Subjective Global Assessment (SGA in patients with ovarian cancer treated in an integrative cancer treatment setting. Methods We evaluated a case series of 132 ovarian cancer patients treated at Cancer Treatment Centers of America® from Jan 2001 to May 2006. SGA was used to assess nutritional status at baseline. Using SGA, patients were classified as well nourished (SGA A, moderately malnourished (SGA B or severely malnourished (SGA C. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of SGA independent of other factors. Results Of 132 patients, 24 were newly diagnosed while 108 had received prior treatment. 15 had stage I disease at diagnosis, 8 stage II, 85 stage III and 17 stage IV. The median age at presentation was 54.4 years (range 25.5 – 82.5 years. 66 patients were well-nourished (SGA A, 35 moderately malnourished (SGA B and 31 severely malnourished (SGA C. Well nourished patients had a median survival of 19.3 months (95% CI: 14.1 to 24.5, moderately malnourished 15.5 months (95% CI: 5.8 to 25.1, and severely malnourished 6.7 months (95% CI: 4.1 to 9.3; the difference being statistically significant (p = 0.0003. Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that moderately malnourished and severely malnourished status were associated with a relative risk of 2.1 (95% CI: 1.2 to 3.6, p = 0.008 and 3.4 (95% CI: 1.9 to 5.8, p Conclusion Univariate and multivariate survival analyses found that low SGA scores (i.e. well-nourished status are associated with better survival outcomes. This study lends support to the role of aggressive nutritional intervention in improving patient outcomes in cancer care.

  12. More Accurate Prediction of Metastatic Pancreatic Cancer Patients' Survival with Prognostic Model Using Both Host Immunity and Tumor Metabolic Activity.

    Directory of Open Access Journals (Sweden)

    Younak Choi

    Full Text Available Neutrophil to lymphocyte ratio (NLR and standard uptake value (SUV by 18F-FDG PET represent host immunity and tumor metabolic activity, respectively. We investigated NLR and maximum SUV (SUVmax as prognostic markers in metastatic pancreatic cancer (MPC patients who receive palliative chemotherapy.We reviewed 396 MPC patients receiving palliative chemotherapy. NLR was obtained before and after the first cycle of chemotherapy. In 118 patients with PET prior to chemotherapy, SUVmax was collected. Cut-off values were determined by ROC curve.In multivariate analysis of all patients, NLR and change in NLR after the first cycle of chemotherapy (ΔNLR were independent prognostic factors for overall survival (OS. We scored the risk considering NLR and ΔNLR and identified 4 risk groups with different prognosis (risk score 0 vs 1 vs 2 vs 3: OS 9.7 vs 7.9 vs 5.7 vs 2.6 months, HR 1 vs 1.329 vs 2.137 vs 7.915, respectively; P<0.001. In PET cohort, NLR and SUVmax were independently prognostic for OS. Prognostication model using both NLR and SUVmax could define 4 risk groups with different OS (risk score 0 vs 1 vs 2 vs 3: OS 11.8 vs 9.8 vs 7.2 vs 4.6 months, HR 1 vs 1.536 vs 2.958 vs 5.336, respectively; P<0.001.NLR and SUVmax as simple parameters of host immunity and metabolic activity of tumor cell, respectively, are independent prognostic factors for OS in MPC patients undergoing palliative chemotherapy.

  13. Simple Clinical Score to Predict 24-Week Survival Times in Patients with Inoperable Malignant Distal Biliary Obstruction as a Tool for Selecting Palliative Metallic or Plastic Stents.

    Science.gov (United States)

    Sripongpun, Pimsiri; Attasaranya, Siriboon; Chamroonkul, Naichaya; Sookpaisal, Theerapong; Khow-Ean, Uthai; Siripun, Aroon; Kongkamol, Chanon; Piratvisuth, Teerha; Ovartlarnporn, Bancha

    2017-01-17

    Endoscopic biliary drainage (EBD) is the mainstay treatment for inoperable malignant distal biliary obstruction (MDBO). Some authorities suggest that metallic stents are more cost-effective than plastic stents in patients with expected survival of at least 6 months. However, studies attempting to define the predictive factors for such survival times are limited. This study aims to develop a scoring system for predicting a survival time of clinical, laboratory, and imaging data were retrieved. The survival time data were retrieved from the medical records and Thailand's civil registration database. Multivariate Cox regression model coefficients were used in the development of a survival time prediction scoring system. Ninety-eight patients were included. The overall median survival was 17.6 weeks. Fifty-seven (58.1%) survived Clinical Score (SCS) was calculated from (2× liver metastasis) + (1× pancreatic cancer) - (2× ampullary cancer) - (1× cholangiocarcinoma), when 1 and 0 were used for the presence and absence of each factor, respectively. The cutoff value of the score ≥0 had a sensitivity and specificity of 0.77 and 0.63, respectively, for predicting a survival time of system from this study may be beneficial for clinicians to select the appropriate stents in endoscopic biliary drainage in inoperable MDBO patients.

  14. Applied the additive hazard model to predict the survival time of patient with diffuse large B- cell lymphoma and determine the effective genes, using microarray data

    Directory of Open Access Journals (Sweden)

    Arefa Jafarzadeh Kohneloo

    2015-09-01

    Full Text Available Background: Recent studies have shown that effective genes on survival time of cancer patients play an important role as a risk factor or preventive factor. Present study was designed to determine effective genes on survival time for diffuse large B-cell lymphoma patients and predict the survival time using these selected genes. Materials & Methods: Present study is a cohort study was conducted on 40 patients with diffuse large B-cell lymphoma. For these patients, 2042 gene expression was measured. In order to predict the survival time, the composition of the semi-parametric additive survival model with two gene selection methods elastic net and lasso were used. Two methods were evaluated by plotting area under the ROC curve over time and calculating the integral of this curve. Results: Based on our findings, the elastic net method identified 10 genes, and Lasso-Cox method identified 7 genes. GENE3325X increased the survival time (P=0.006, Whereas GENE3980X and GENE377X reduced the survival time (P=0.004. These three genes were selected as important genes in both methods. Conclusion: This study showed that the elastic net method outperformed the common Lasso method in terms of predictive power. Moreover, apply the additive model instead Cox regression and using microarray data is usable way for predict the survival time of patients.

  15. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL)

    National Research Council Canada - National Science Library

    Benza, Raymond L; Miller, Dave P; Gomberg-Maitland, Mardi; Frantz, Robert P; Foreman, Aimee J; Coffey, Christopher S; Frost, Adaani; Barst, Robyn J; Badesch, David B; Elliott, C Gregory; Liou, Theodore G; McGoon, Michael D

    2010-01-01

    .... A quantitative survival prediction tool has not been established for research or clinical use. Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL...

  16. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas.

    Science.gov (United States)

    Gao, Ke; Li, Gang; Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-02-23

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.

  17. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    Science.gov (United States)

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma.

  18. Expression of Aurora-B and FOXM1 predict poor survival in patients with nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pei-Yu; Luo, Dong-Hua; Mai, Hai-Qiang [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Nasopharyngeal Carcinoma, Guangzhou (China); Li, Yan; Zeng, Ting-Ting; Li, Meng-Qing [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Hou, Xue; Zhang, Li [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Medical Oncology, Guangzhou (China)

    2015-08-15

    The purpose of this work was to investigate the relationship between Aurora-B, FOXM1, and clinical outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with a combination of induction chemotherapy and radiotherapy. The expression of Aurora-B and FOXM1 were investigated by immunohistochemistry using a tissue microarray (TMA) containing samples from 166 NPC patients who were treated with cisplatin (DDP) + fluorouracil (5-FU) induction chemotherapy and radiotherapy between 1999 and 2005. The relationship of Aurora-B, FOXM1, and survival of these NPC patients was analyzed. Informative TMA results were obtained in 91 tumor cases for Aurora-B and 93 tumor cases for FOXM1. The 8-year failure-free survival rate (FFS) for the Aurora-B-negative and Aurora-B-positive group was 65.6 and 37.3 %, respectively (p = 0.024), and the 8-year distant FFS (D-FFS) rate was 65.6 and 41.5 %, respectively (p = 0.047). The 8-year overall survival (OS) in the FOXM1-negative group was moderately higher than in the FOXM1-positive group (58.4 vs 39.1 %, p = 0.081). Cox regression analysis revealed that for FFS, Aurora-B expression was a significant prognostic factor (p = 0.025), while for D-FFS, Aurora-B expression was a marginally significant prognostic factor (p = 0.056). When FOXM1 expression was analyzed, the Cox regression analyses showed that FOXM1 expression was a marginally significant prognostic factor (p = 0.056) for OS. Correlation analysis showed that Aurora-B and FOXM1 expression had no significant correlation. Aurora-B and FOXM1 were both adverse prognostic markers for NPC patients treated with chemoradiotherapy. However, the two markers had no significant correlation. (orig.) [German] Ziel war die Untersuchung der Beziehung zwischen Aurora-B, FOXM1 und den klinischen Ergebnissen bei Patienten mit nasopharyngealem Karzinom (NPC), die mit einer Kombinationstherapie aus Induktionschemotherapie und Radiotherapie behandelt wurden. Die Expression von Aurora-B und

  19. A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study.

    Science.gov (United States)

    Sabbagh, Charles; Mauvais, François; Cosse, Cyril; Rebibo, Lionel; Joly, Jean-Paul; Dromer, Didier; Aubert, Christine; Carton, Sophie; Dron, Bernard; Dadamessi, Innocenti; Maes, Bernard; Perrier, Guillaume; Manaouil, David; Fontaine, Jean-François; Gozy, Michel; Panis, Xavier; Foncelle, Pierre Henri; de Fresnoy, Hugues; Leroux, Fabien; Vaneslander, Pierre; Ghighi, Caroline; Regimbeau, Jean-Marc

    2014-01-01

    Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive of survival in colon cancer. The aim of the present study was to validate the LNR as a prognostic factor and to determine the optimum LNR cutoff for distinguishing between "good prognosis" and "poor prognosis" colon cancer patients. From January 2003 to December 2007, patients with TNM stage III colon cancer operated on with at least of 3 years of follow-up and not lost to follow-up were included in this retrospective study. The two primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) as a function of the LNR groups and the cutoff. One hundred seventy-eight patients were included. There was no correlation between the LNR group and 3-year OS (P=0.06) and a significant correlation between the LNR group and 3-year DFS (P=0.03). The optimal LNR cutoff of 10% was significantly correlated with 3-year OS (P=0.02) and DFS (P=0.02). The LNR was not an accurate prognostic factor when fewer than 12 lymph nodes were sampled. Clarification and simplification of the LNR classification are prerequisites for use of this system in randomized control trials. An LNR of 10% appears to be the optimal cutoff.

  20. D-Dimer and Carcinoembryonic Antigen Levels: Useful Indicators for Predicting the Tumor Stage and Postoperative Survival

    Directory of Open Access Journals (Sweden)

    Kemal Tekeşin

    2016-01-01

    Full Text Available The purpose of this prospective study is to determine the preoperative plasma D-dimer and serum Carcinoembryonic Antigen (CEA levels of patients scheduled for curative surgical resection for colorectal cancer and to evaluate the significance of these levels on the prognosis and postoperative survival rate. One hundred sixty-five patients with colorectal cancer, who were scheduled to have elective resection between January 2008 and January 2011, were included in the study. A significant increase was observed in the D-dimer levels, particularly in poorly differentiated tumors. The distance covered by the tumor inside the walls of the colon and rectum (T-stage was significant for both D-dimer and CEA levels. As the T-stage increased, there was also a significant increase in the D-dimer and CEA levels. A high significance and correlation level was detected between the TNM staging and both D-dimer and CEA. A significant relationship was found between the advanced tumor stage and short postoperative survival rate of patients with colorectal cancer. Therefore, the analysis of preoperative D-dimer and CEA levels can be useful in predicting the stage and differentiation of the tumor and the postoperative survival rate.

  1. Long‐Term Post‐CABG Survival: Performance of Clinical Risk Models Versus Actuarial Predictions

    Science.gov (United States)

    Carr, Brendan M.; Romeiser, Jamie; Ruan, Joyce; Gupta, Sandeep; Seifert, Frank C.; Zhu, Wei

    2015-01-01

    Abstract Background/aim Clinical risk models are commonly used to predict short‐term coronary artery bypass grafting (CABG) mortality but are less commonly used to predict long‐term mortality. The added value of long‐term mortality clinical risk models over traditional actuarial models has not been evaluated. To address this, the predictive performance of a long‐term clinical risk model was compared with that of an actuarial model to identify the clinical variable(s) most responsible for any differences observed. Methods Long‐term mortality for 1028 CABG patients was estimated using the Hannan New York State clinical risk model and an actuarial model (based on age, gender, and race/ethnicity). Vital status was assessed using the Social Security Death Index. Observed/expected (O/E) ratios were calculated, and the models' predictive performances were compared using a nested c‐index approach. Linear regression analyses identified the subgroup of risk factors driving the differences observed. Results Mortality rates were 3%, 9%, and 17% at one‐, three‐, and five years, respectively (median follow‐up: five years). The clinical risk model provided more accurate predictions. Greater divergence between model estimates occurred with increasing long‐term mortality risk, with baseline renal dysfunction identified as a particularly important driver of these differences. Conclusions Long‐term mortality clinical risk models provide enhanced predictive power compared to actuarial models. Using the Hannan risk model, a patient's long‐term mortality risk can be accurately assessed and subgroups of higher‐risk patients can be identified for enhanced follow‐up care. More research appears warranted to refine long‐term CABG clinical risk models. doi: 10.1111/jocs.12665 (J Card Surg 2016;31:23–30) PMID:26543019

  2. The development of simple survival prediction models for blunt trauma victims treated at Asian emergency centers

    Directory of Open Access Journals (Sweden)

    Kimura Akio

    2012-02-01

    Full Text Available Abstract Background For real-time assessment of the probability of survival (Ps of blunt trauma victims at emergency centers, this study aimed to establish regression models for estimating Ps using simplified coefficients. Methods The data of 10,210 blunt trauma patients not missing both the binary outcome data about survival and the data necessary for Ps calculation by The Trauma and Injury Severity Score (TRISS method were extracted from the Japan Trauma Data Bank (2004-2007 and analyzed. Half (5,113 of the data was allocated to a derivation data set, with the other half (5,097 allocated to a validation data set. The data of 6,407 blunt trauma victims from the trauma registry of Khon Kaen Regional Hospital in Thailand were analyzed for validation. The logistic regression models included age, the Injury Severity Score (ISS, the Glasgow Coma Scale score (GCS, systolic blood pressure (SBP, respiratory rate (RR, and their coded values (cAGE, 0-1; cISS, 0-4; cSBP, 0-4; cGCS, 0-4; cRR, 0-4 as predictor variables. The coefficients were simplified by rounding off after the decimal point or choosing 0.5 if the coefficients varied across 0.5. The area under the receiver-operating characteristic curve (AUROCC was calculated for each model to measure discriminant ability. Results A group of formulas (log (Ps/1-Ps = logit (Ps = -9 + cISS - cAGE + cSBP + cGCS + cRR/2, where -9 becomes -7 if the predictor variable of cRR or cISS is missing was developed. Using these formulas, the AUROCCs were between 0.950 and 0.964. When these models were applied to the Khon Kean data, their AUROCCs were greater than 0.91. Conclusion: These equations allow physicians to perform real-time assessments of survival by easy mental calculations at Asian emergency centers, which are overcrowded with blunt injury victims of traffic accidents.

  3. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E

    2012-07-01

    Full Text Available Abstract Background Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS of brainstem metastases. Methods We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89. Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44% had received whole brain radiation therapy (WBRT prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%. The median tumor volume was 0.94 cm3 (range: 0.01-4.2 with a median prescription dose of 17 Gy (range: 12–24 delivered in 1–5 fractions. Results Median follow-up for the cohort was 3.2 months (range: 0.4-20.6. Nineteen patients (52% had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79% experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40% had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of

  4. The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.

    Science.gov (United States)

    Hsu, Tina; Speers, Caroline H; Kennecke, Hagen F; Cheung, Winson Y

    2017-05-15

    Patient-reported outcomes (PROs) are increasingly used in clinical settings. Prior research suggests that PROs collected at baseline may be associated with cancer survival, but most of those studies were conducted in patients with breast or lung cancer. The objective of this study was to determine the correlation between prospectively collected PROs and cancer-specific outcomes in patients with early stage colorectal cancer. Patients who had newly diagnosed stage II or III colorectal cancer from 2009 to 2010 and had a consultation at the British Columbia Cancer Agency completed the brief Psychosocial Screen for Cancer (PSSCAN) questionnaire, which collects data on patients' perceived social supports, quality of life (QOL), anxiety and depression, and general health. PROs from the PSSCAN were linked with the Gastrointestinal Cancers Outcomes Database, which contains information on patient and tumor characteristics, treatment details, and cancer outcomes. Cox regression models were constructed for overall survival (OS), and Fine and Gray regression models were developed for disease-specific survival (DSS). In total, 692 patients were included. The median patient age was 67 years (range, 26-95 years), and the majority had colon cancer (61%), were diagnosed with stage III disease (54%), and received chemotherapy (58%). In general, patients felt well supported and reported good overall health and QOL. On multivariate analysis, increased fatigue was associated with worse OS (hazard ratio [HR], 1.99; P = .00007) and DSS (HR, 1.63; P = .03), as was lack of emotional support (OS: HR, 4.36; P = .0003; DSS: HR, 1.92; P = .02). Although most patients described good overall health and QOL and indicated that they were generally well supported, patients who experienced more pronounced fatigue or lacked emotional support had a higher likelihood of worse OS and DSS. These findings suggest that abbreviated PROs can inform and assist clinicians to identify patients who have a worse

  5. Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study

    DEFF Research Database (Denmark)

    Ganly, Ian; Amit, Moran; Kou, Lei;

    2015-01-01

    BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METH...

  6. Nestling telomere shortening, but not telomere length, reflects developmental stress and predicts survival in wild birds

    NARCIS (Netherlands)

    Boonekamp, Jelle J.; Mulder, Ellis; Salomons, H. Martijn; Dijkstra, Cornelis; Verhulst, Simon

    2014-01-01

    Developmental stressors often have long-term fitness consequences, but linking offspring traits to fitness prospects has remained a challenge. Telomere length predicts mortality in adult birds, and may provide a link between developmental conditions and fitness prospects. Here, we examine the effect

  7. Can {sup 18}F-FDOPA PET/CT predict survival in patients with suspected recurrent glioma? A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam, E-mail: drsellam84@yahoo.co.in [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Sharma, Punit; Kumar, Abhishek [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Gupta, Deepak Kumar [Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi (India); Khangembam, Bangkim Chandra; Ballal, Sanjana; Kumar, Rakesh; Kumar, Rajeev [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Bal, Chandrasekhar, E-mail: csbal@hotmail.com [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India)

    2014-01-15

    Purpose of the present study was to evaluate the role of {sup 18}F-FDOPA PET/CT for predicting survival in patients with suspected recurrent glioma. Methods: A total of 33 previously treated, histopathologically proven glioma patients with clinical and contrast enhanced MRI findings suspicious for recurrence were enrolled in this prospective study. All patients underwent {sup 18}F-FDOPA PET/CT. Ratios of tumor uptake to normal tissue uptake were generated by dividing the tumor SUVmax with SUVmax of the contralateral normal brain tissue (T/N), normal striatum (T/S), normal white matter (T/W) and normal cerebellum (T/C). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was performed for the distributions of each variable and by multivariate analysis. Results: {sup 18}F-FDOPA PET/CT was positive for recurrence in 25 patients and negative in 8. Death occurred in nineteen patients. Median follow up period was 20.2 months. Median survival in this study was 39.2 months. In univariate analysis significant association of survival was noted with results of {sup 18}F-FDOPA PET/CT (P = 0.007) and {sup 18}F-FDOPA PET/CT quantitative parameters namely SUVmax (P = 0.001), T/S (P = 0.005), T/W (P = 0.0004), T/N (P = 0.001) and T/C (P = 0.003) were found to be significant. On multivariate analysis, only MRI size of the recurrent tumor (P = 0.002) and T/N ratio of {sup 18}F-FDOPA PET/CT (P = 0.005) were found to be independent predictors of survival. Conclusion: T/N ratio on {sup 18}F-FDOPA PET/CT is an independent predictor of survival in patients with suspected recurrent glioma, along with size of recurrent tumor on MRI.

  8. Automated digital volume measurement of melanoma metastases in sentinel nodes predicts disease recurrence and survival

    DEFF Research Database (Denmark)

    Riber-Hansen, Rikke; Nyengaard, Jens R; Hamilton-Dutoit, Stephen J

    2011-01-01

    aim was to investigate whether digital image analysis can estimate TMV accurately in melanoma SLNs. Methods and results: TMV was measured in 147 SLNs from 95 patients both manually and by automated digital image analysis. The results were compared by Bland-Altman plots (numerical data) and kappa......Aims: Total metastatic volume (TMV) is an important prognostic factor in melanoma sentinel lymph nodes (SLNs) that avoids both the interobserver variation and unidirectional upstaging seen when using semi-quantitative size estimates. However, it is somewhat laborious for routine application. Our...... statistics (categorical data). In addition, disease-free and melanoma-specific survivals were calculated. Mean metastatic volume per patient was 10.6 mm(3) (median 0.05 mm(3); range 0.0001-621.3 mm(3)) and 9.62 mm(3) (median 0.05 mm(3); range 0.00001-564.3 mm(3)) with manual and digital measurement...

  9. Factors predicting long-term survival in low-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2003-01-01

    population-based data from the Danish Lymphoma Group, we analyzed if prognostic clinical pretreatment factors could be identified in patients with low-risk DLBCL. One hundred seventy-seven patients, all with a prognostic profile as favorable as possible according to the IPI and treated with anthracycline-based...... combination chemotherapy (92%) or loco-regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow-up time was 11 years. Twenty-six patients relapsed, with a median time to relapse of 12.1 months. Overall survival...... at 5 years and 10 years was 85% and 75%, respectively. Stage II was associated with poor response to treatment (P=0.044). In a multivariate analysis, Stage II (P=0.001) and age >50 years (P=0.043) were independently associated with poor outcome. Patients without these adverse factors had an excellent...

  10. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Jakobsen, Annika Loft;

    2010-01-01

    -eight prospectively enrolled patients with NE tumors underwent FDG-PET imaging. FDG uptake was quantified by maximal standardized uptake value (SUVmax). The prognostic value of FDG uptake, proliferation index, chromogranin A, and liver metastases were assessed. RESULTS: During the 1-year follow-up, 14 patients died......PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors. EXPERIMENTAL DESIGN: Ninety...... was the only predictor of progression-free survival (HR, 8.4; P value of FDG-PET for NE tumors, which exceeds the prognostic value of traditional markers such as Ki67, chromogranin A, and liver metastases. FDG-PET may obtain an important role for NE...

  11. Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Karlsson Per

    2008-09-01

    Full Text Available Abstract Background It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. Methods 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. Results A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy, whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively. Conclusion The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. Trial

  12. Plasma levels of soluble HLA-E and HLA-F at diagnosis may predict overall survival of neuroblastoma patients.

    Science.gov (United States)

    Morandi, Fabio; Cangemi, Giuliana; Barco, Sebastiano; Amoroso, Loredana; Giuliano, Maria; Gigliotti, Anna Rita; Pistoia, Vito; Corrias, Maria Valeria

    2013-01-01

    The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS) of neuroblastoma (NB) patients. Concentration of soluble (s) biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3) or serum (calprotectin) samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient's outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS), whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  13. Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

    Directory of Open Access Journals (Sweden)

    Fabio Morandi

    2013-01-01

    Full Text Available The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS of neuroblastoma (NB patients. Concentration of soluble (s biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3 or serum (calprotectin samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient’s outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS, whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  14. VILIP-1 downregulation in non-small cell lung carcinomas: mechanisms and prediction of survival.

    Directory of Open Access Journals (Sweden)

    Jian Fu

    Full Text Available VILIP-1, a member of the neuronal Ca++ sensor protein family, acts as a tumor suppressor gene in an experimental animal model by inhibiting cell proliferation, adhesion and invasiveness of squamous cell carcinoma cells. Western Blot analysis of human tumor cells showed that VILIP-1 expression was undetectable in several types of human tumor cells, including 11 out of 12 non-small cell lung carcinoma (NSCLC cell lines. The down-regulation of VILIP-1 was due to loss of VILIP-1 mRNA transcripts. Rearrangements, large gene deletions or mutations were not found. Hypermethylation of the VILIP-1 promoter played an important role in gene silencing. In most VILIP-1-silent cells the VILIP-1 promoter was methylated. In vitro methylation of the VILIP-1 promoter reduced its activity in a promoter-reporter assay. Transcriptional activity of endogenous VILIP-1 promoter was recovered by treatment with 5'-aza-2'-deoxycytidine (5'-Aza-dC. Trichostatin A (TSA, a histone deacetylase inhibitor, potently induced VILIP-1 expression, indicating that histone deacetylation is an additional mechanism of VILIP-1 silencing. TSA increased histone H3 and H4 acetylation in the region of the VILIP-1 promoter. Furthermore, statistical analysis of expression and promoter methylation (n = 150 primary NSCLC samples showed a significant relationship between promoter methylation and protein expression downregulation as well as between survival and decreased or absent VILIP-1 expression in lung cancer tissues (p<0.0001. VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors and its clinical evaluation could have a role as a predictor of short-term survival in lung cancer patients.

  15. Thrombocytosis at secondary cytoreduction for recurrent ovarian cancer predicts suboptimal resection and poor survival.

    Science.gov (United States)

    Cohen, Joshua G; Tran, Arthur-Quan; Rimel, B J; Cass, Ilana; Walsh, Christine S; Karlan, Beth Y; Li, Andrew J

    2014-03-01

    A growing body of evidence supports a role for thrombocytosis in the promotion of epithelial ovarian cancer biology. However, studies have only linked preoperative platelet count at time of initial cytoreductive surgery to clinical outcome. Here, we sought to determine the impact of elevated platelet count at time of secondary cytoreductive surgery (SCS) for recurrent disease. Under an IRB-approved protocol, we identified 107 women with invasive epithelial ovarian cancer who underwent SCS between January 1997 and June 2012. We reviewed clinical, laboratory, and pathologic records from this retrospective cohort. The data was analyzed using the chi-squared, Fisher's exact, Cox proportional hazards, and Kaplan-Meier tests. We defined thrombocytosis as a platelet count ≥ 350 × 10(9)/L and optimal resection at SCS as microscopic residual disease. Thirteen of 107 women (12%) with recurrent ovarian cancer had thrombocytosis prior to SCS. Preoperative thrombocytosis at SCS was associated with failure to undergo optimal resection (p=0.0001). Women with preoperative thrombocytosis at time of SCS demonstrated shorter overall survival (33 months) compared to those with normal platelet counts (46 months, p=0.004). On multivariate analysis, only preoperative platelet count retained significance as an independent prognostic factor (p=0.025) after controlling for age at SCS (p=0.90), disease free interval from primary treatment (0.06), and initial stage of disease (0.66). Elevated platelet count at time of SCS is associated with suboptimal resection and shortened overall survival. These data provide further evidence supporting a plausible role for thrombocytosis in aggressive ovarian tumor biology. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas.

    Science.gov (United States)

    Pennington, Kathryn P; Walsh, Tom; Harrell, Maria I; Lee, Ming K; Pennil, Christopher C; Rendi, Mara H; Thornton, Anne; Norquist, Barbara M; Casadei, Silvia; Nord, Alexander S; Agnew, Kathy J; Pritchard, Colin C; Scroggins, Sheena; Garcia, Rochelle L; King, Mary-Claire; Swisher, Elizabeth M

    2014-02-01

    Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain. Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway. Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Nonserous ovarian carcinomas had similar rates of homologous recombination mutations to serous carcinomas (28% vs. 31%, P = 0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic homologous recombination mutations was highly predictive of primary platinum sensitivity (P = 0.0002) and improved overall survival (P = 0.0006), with a median overall survival of 66 months in germline homologous recombination mutation carriers, 59 months in cases with a somatic homologous recombination mutation, and 41 months for cases without a homologous recombination mutation. Germline or somatic mutations in homologous recombination genes are present in almost one third of ovarian carcinomas, including both serous and nonserous histologies. Somatic BRCA1/2 mutations and mutations in other homologous recombination genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of homologous recombination mutations in nonserous carcinomas supports their inclusion in PARP inhibitor clinical trials. ©2013 AACR.

  17. A modified TNM-7 staging system to better predict the survival in patients with hepatocellular carcinoma after hepatectomy.

    Science.gov (United States)

    Huang, Junting; Zhang, Yaojun; Peng, Zhenwei; Gao, Hengjun; Xu, Li; Jiao, Long R; Chen, Minshan

    2013-10-01

    To evaluate the accuracy of the 7th edition of the American Joint Committee on Cancer staging system (TNM-7) for patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and to propose a modified TNM system for better prediction of survival. Clinico-pathological data for 1,313 patients who underwent hepatectomy as initial treatment for HCC between 2000 and 2008 were retrieved from a prospective database. Overall survival (OS) and disease-free survival (DFS) were analyzed to evaluate the predictive value. The 1-, 3-, 5-year OS and DFS of 1,313 patients were 79.2, 55.4, 45.5 %, and 52.6, 36.1, 31.8 %, respectively. Multivariate analysis revealed that major vascular invasion was the most important prognostic factor for both OS and DFS, along with tumour number and size. Patients with pT1 and pT2 disease had significantly better OS and DFS than those with pT3 disease (P TNM system within the existing framework was proposed to combine the current pT3a and pT4 together as the new pT3 and to change pT3b to the new pT4. Analysis showed that this modified system had a better prognostic power than either TNM-6 or TNM-7. TNM-7 would seem to be inaccurate for staging advanced HCC. The modified system can improve both the prognostic accuracy and the hazard discrimination of disease to be consistent among subgroups of HCC.

  18. The Neutrophil-Platelet Score (NPS Predicts Survival in Primary Operable Colorectal Cancer and a Variety of Common Cancers.

    Directory of Open Access Journals (Sweden)

    David G Watt

    Full Text Available Recent in-vitro studies have suggested that a critical checkpoint early in the inflammatory process involves the interaction between neutrophils and platelets. This confirms the importance of the innate immune system in the elaboration of the systemic inflammatory response. The aim of the present study was to examine whether a combination of the neutrophil and platelet counts were predictive of survival in patients with cancer.Patients with histologically proven colorectal cancer who underwent potentially curative resection at a single centre between March 1999 and May 2013 (n = 796 and patients with cancer from the Glasgow Inflammation Outcome Study, who had a blood sample taken between January 2000 and December 2007 (n = 9649 were included in the analysis.In the colorectal cancer cohort, there were 173 cancer and 135 non-cancer deaths. In patients undergoing elective surgery, cancer-specific survival (CSS at 5 years ranged from 97% in patients with TNM I disease and NPS = 0 to 57% in patients with TNM III disease and NPS = 2 (p = 0.019 and in patients undergoing elective surgery for node-negative colon cancer from 98% (TNM I, NPS = 0 to 65% (TNM II, NPS = 2 (p = 0.004. In those with a variety of common cancers there were 5218 cancer and 929 non-cancer deaths. On multivariate analysis, adjusting for age and sex and stratified by tumour site, incremental increase in the NPS was significantly associated with poorer CSS (p<0.001.The neutrophil-platelet score predicted survival in a variety of common cancers and highlights the importance of the innate immune system in patients with cancer.

  19. Potential prognostic long non-coding RNA identification and their validation in predicting survival of patients with multiple myeloma.

    Science.gov (United States)

    Hu, Ai-Xin; Huang, Zhi-Yong; Zhang, Lin; Shen, Jian

    2017-04-01

    Multiple myeloma, a typical hematological malignancy, is characterized by malignant proliferation of plasma cells. This study was to identify differently expressed long non-coding RNAs to predict the survival of patients with multiple myeloma efficiently. Gene expressing profiles of diagnosed patients with multiple myeloma, GSE24080 (559 samples) and GSE57317 (55 samples), were downloaded from Gene Expression Omnibus database. After processing, survival-related long non-coding RNAs were identified by Cox regression analysis. The prognosis of multiple myeloma patients with differently expressed long non-coding RNAs was predicted by Kaplan-Meier analysis. Meanwhile, stratified analysis was performed based on the concentrations of serum beta 2-microglobulin (S-beta 2m), albumin, and lactate dehydrogenase of multiple myeloma patients. Gene set enrichment analysis was performed to further explore the functions of identified long non-coding RNAs. A total of 176 long non-coding RNAs significantly related to the survival of multiple myeloma patients (p multiple myeloma. Gene set enrichment analysis-identified pathways of cell cycle, focal adhesion, and G2-M checkpoint were associated with these long non-coding RNAs. A total of 176 long non-coding RNAs, especially RP1-286D6.1, AC008875.2, MTMR9L, AC069360.2, and AL512791.1, were potential biomarkers to evaluate the prognosis of multiple myeloma patients. These long non-coding RNAs participated indispensably in many pathways associated to the development of multiple myeloma; however, the molecular mechanisms need to be further studied.

  20. Child-Pugh-Turcott versus Meld score for predicting survival in a retrospective cohort of black African cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    KA Attia; KC Ackoundou-N'guessan; AT N'dri-yoman; AK Mahassadi; E Messou; YF Bathaix; YH Kissi

    2008-01-01

    AIM: To compare the performance of the Child-Pugh-Turcott (CPT) score to that of the model for end-stage liver disease (MELD) score in predicting survival of a retrospective cohort of 172 Black African patients with cirrhosis on a short and mid-term basis.METHODS: Univariate and multivariate (Cox model)analyses were used to identify factors related to mortality. Relationship between the two scores was appreciated by calculating the correlation coefficient.The Kaplan Meier method and the log rank test were used to elaborate and compare survival respectively.The Areas Under the Curves were used to compare the performance between scores at 3, 6 and 12 mo.RESULTS: The study population comprised 172 patients, of which 68.9% were male. The mean age of the patient was 47.5 ± 13 years. Hepatitis B virus infection was the cause of cirrhosis in 70% of the cases.The overall mortality was 31.4% over 11 years of follow up. Independent factors significantly associated with mortality were: CPT score (HR = 3.3, 95% CI [1.7-6.2])(P 1.5 mg/dL versus serum creatine 21 vs MELD < 21). The area under the curves (AUC)that predict survival was 0.72 and 0.75 at 3 mo (P = 0.68),0.64 and 0.62 at 6 mo (P = 0.67), 0.69 and 0.64 at 12 mo (P = 0.38) respectively for the CPT score and the MELD score.CONCLUSION: The CPT score displays the same prognostic significance as does the MELD score in black African patients with cirrhosis. Moreover, its handling appears less cumbersome in clinical practice as compared to the latter.

  1. Prognostic model for predicting survival of patients with metastatic urothelial cancer treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Apolo, Andrea B; Ostrovnaya, Irina; Halabi, Susan; Iasonos, Alexia; Philips, George K; Rosenberg, Jonathan E; Riches, Jamie; Small, Eric J; Milowsky, Matthew I; Bajorin, Dean F

    2013-04-03

    A prognostic model that predicts overall survival (OS) for metastatic urothelial cancer (MetUC) patients treated with cisplatin-based chemotherapy was developed, validated, and compared with a commonly used Memorial Sloan-Kettering Cancer Center (MSKCC) risk-score model. Data from 7 protocols that enrolled 308 patients with MetUC were pooled. An external multi-institutional dataset was used to validate the model. The primary measurement of predictive discrimination was Harrell's c-index, computed with 95% confidence interval (CI). The final model included four pretreatment variables to predict OS: visceral metastases, albumin, performance status, and hemoglobin. The Harrell's c-index was 0.67 for the four-variable model and 0.64 for the MSKCC risk-score model, with a prediction improvement for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .002). In the validation cohort, the c-indices for the four-variable and the MSKCC risk-score models were 0.63 (95% CI = 0.56 to 0.69) and 0.58 (95% CI = 0.52 to 0.65), respectively, with superiority of the four-variable model compared with the MSKCC risk-score model for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .02).

  2. Factors predicting survival for HIV-infected patients with respiratory failure.

    Science.gov (United States)

    van Leeuwen, H J; Boereboom, F T; Pols, M A; Hoepelman, A I; Savelkoul, J T

    2000-09-01

    Despite improved treatment modalities, the mortality of HIV infected patients admitted to the intensive care unit with respiratory failure remains high. To help ICU physicians in advising HIV infected patients whether to undergo mechanical ventilation, we retrospectively investigated prognostic factors predicting hospital outcome for HIV-infected patients, admitted to a medical intensive care unit with respiratory failure before the era of highly-active anti-retroviral therapy. A retrospective chart review was carried out of all HIV-infected patients with respiratory failure admitted to the medical ICU of a Dutch University Hospital between 1991 and 1997. In the six year period, 29 HIV-infected patients were admitted to the ICU for respiratory failure. Mechanical ventilation, CD4 cell count, APACHE II score, APACHE III score, ARDS and length of ICU stay all differed significantly between survivors and non-survivors. However, a multivariate analysis only showed the need for mechanical ventilation as an independent risk factor for mortality. The only combination of factors able to accurately predict mortality for the individual patient was the development of ARDS and the requirement of mechanical ventilation. The combination of mechanical ventilation and ARDS accurately predicts hospital outcome in HIV-infected patients presenting with respiratory failure before the HAART era.

  3. Improving the Prediction of Survival in Cancer Patients by Using Machine Learning Techniques: Experience of Gene Expression Data: A Narrative Review.

    Science.gov (United States)

    Bashiri, Azadeh; Ghazisaeedi, Marjan; Safdari, Reza; Shahmoradi, Leila; Ehtesham, Hamide

    2017-02-01

    Today, despite the many advances in early detection of diseases, cancer patients have a poor prognosis and the survival rates in them are low. Recently, microarray technologies have been used for gathering thousands data about the gene expression level of cancer cells. These types of data are the main indicators in survival prediction of cancer. This study highlights the improvement of survival prediction based on gene expression data by using machine learning techniques in cancer patients. This review article was conducted by searching articles between 2000 to 2016 in scientific databases and e-Journals. We used keywords such as machine learning, gene expression data, survival and cancer. Studies have shown the high accuracy and effectiveness of gene expression data in comparison with clinical data in survival prediction. Because of bewildering and high volume of such data, studies have highlighted the importance of machine learning algorithms such as Artificial Neural Networks (ANN) to find out the distinctive signatures of gene expression in cancer patients. These algorithms improve the efficiency of probing and analyzing gene expression in cancer profiles for survival prediction of cancer. By attention to the capabilities of machine learning techniques in proteomics and genomics applications, developing clinical decision support systems based on these methods for analyzing gene expression data can prevent potential errors in survival estimation, provide appropriate and individualized treatments to patients and improve the prognosis of cancers.

  4. Individualized Prediction of Overall Survival After Postoperative Radiation Therapy in Patients With Early-Stage Cervical Cancer: A Korean Radiation Oncology Group Study (KROG 13-03)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Jin [Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Han, Seungbong [Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Kim, Young Seok, E-mail: ysk@amc.seoul.kr [Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Nam, Joo-Hyun [Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae [Department of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Jae Weon [Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul (Korea, Republic of); Park, Won [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Byoung-Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jin Hee [Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Cha, Soon Do [Department of Obstetrics and Gynecology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Juree [Department of Radiation Oncology, Cheil General Hospital and Women' s Healthcare Center, Kwandong University, College of Medicine, Seoul (Korea, Republic of); Lee, Ki-Heon [Department of Obstetrics and Gynecology, Cheil General Hospital and Women' s Healthcare Center, Kwandong University, College of Medicine, Seoul (Korea, Republic of); Yoon, Mee Sun [Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Jeollanam-do (Korea, Republic of); and others

    2013-11-15

    Purpose: A nomogram is a predictive statistical model that generates the continuous probability of a clinical event such as death or recurrence. The aim of the study was to construct a nomogram to predict 5-year overall survival after postoperative radiation therapy for stage IB to IIA cervical cancer. Methods and Materials: The clinical data from 1702 patients with early-stage cervical cancer, treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop a prediction nomogram based on the Cox proportional hazards model. Demographic, clinical, and pathologic variables were included and analyzed to formulate the nomogram. The discrimination and calibration power of the model was measured using a concordance index (c-index) and calibration curve. Results: The median follow-up period for surviving patients was 75.6 months, and the 5-year overall survival probability was 87.1%. The final model was constructed using the following variables: age, number of positive pelvic lymph nodes, parametrial invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The nomogram predicted the 5-year overall survival with a c-index of 0.69, which was superior to the predictive power of the International Federation of Gynecology and Obstetrics (FIGO) staging system (c-index of 0.54). Conclusions: A survival-predicting nomogram that offers an accurate level of prediction and discrimination was developed based on a large multi-center study. The model may be more useful than the FIGO staging system for counseling individual patients regarding prognosis.

  5. High expression of HMGA2 predicts poor survival in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Na N

    2016-11-01

    Full Text Available Ning Na,1,* Tujie Si,2,* Zhengyu Huang,1,* Bin Miao,1 Liangqing Hong,1 Heng Li,1 Jiang Qiu,2 Jianguang Qiu3 1Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, 2Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, 3Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: High-mobility group AT-hook 2 (HMGA2 is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS of patients with non-metastatic clear cell renal cell carcinoma (ccRCC following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004. An IHC analysis revealed that HMGA2 was expressed in the nuclei of tumor cells in 146 (90.1% patients with ccRCC. The level of HMGA2 was positively correlated with tumor size, lymph node metastasis, and Fuhrman Grade. A Kaplan–Meier analysis with log-rank test found that patients with high HMGA2 expression had a poor outcome and that patients with low HMGA2 expression had better survival. Cox regression analysis showed that HMGA2 expression could serve as an independent prognostic factor for ccRCC patients. The efficacy of the following prognostic models was improved when HMGA2 expression was added: tumor node metastasis stage, UCLA Integrated Scoring System, Mayo Clinic stage, size, grade, and necrosis score. In summary, this study showed that HMGA2 expression is an independent prognostic factor for OS in patients with ccRCC. HMGA2 was found to be a valuable biomarker for ccRCC progression. Keywords: renal carcinoma, high-mobility group protein A

  6. Expression of IL-4 and IL-13 predicts recurrence and survival in localized clear-cell renal cell carcinoma.

    Science.gov (United States)

    Chang, Yuan; Xu, Le; An, Huimin; Fu, Qiang; Chen, Lian; Lin, Zongming; Xu, Jiejie

    2015-01-01

    Interleukin-4 (IL-4) and IL-13 are anti-inflammatory and immunoregulatory cytokines that can influence cancer-directed immunosurveillance. However, they are not evaluated as biomarkers for ccRCC outcomes. The aim of this study was to investigate the prognostic value of tumor-derived IL-4 and IL-13 in patients with localized ccRCC after surgery. Our study comprised 194 consecutive patients with localized ccRCC undergoing nephrectomy in a single center. Clinical characteristics, recurrence-free survival (RFS) and overall survival (OS) were recorded. We assessed IL-4 and IL-13 expression as continuous variables and dichotomized as low versus high by immunohistochemistry. For associations with RFS and OS, we used the Kaplan-Meier method and Cox regression models. Concordance index was calculated for predictive accuracy. We found that high expression levels of IL-4 and IL-13 were associated with increased recurrence (P IL-13 expression (IL-4/IL-13 signature) was an independent prognostic factor for RFS and OS (P = 0.009 and P = 0.016, respectively). When applied to UISS score, IL-4/IL-13 signature improved the predictive accuracy. Notably, this improvement in prediction was mainly observed in patients with low-risk disease. To conclude, IL-4/IL-13 signature is an independent predictor of outcomes in patients with localized ccRCC, and the prognostic value is more prominent among patients with low-risk disease. Evaluation of IL-4 and IL-13 expression provides the opportunity to optimize postsurgical management and develop novel targeted therapies for ccRCC patients.

  7. Visceral Obesity Predicts Fewer Lymph Node Metastases and Better Overall Survival in Colon Cancer.

    Science.gov (United States)

    Park, Se Woo; Lee, Hang Lak; Doo, Eun Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Oh Young; Han, Dong Soo; Yoon, Byung Chul; Choi, Ho Soon; Lee, Kang Hong

    2015-08-01

    The relationship between visceral obesity and colon cancer outcome has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node (LN) metastasis and overall survival (OS) in colon cancer. Metastatic LN ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected LNs. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume distribution via CT scan, and visceral obesity was defined as a VFA to total fat area ratio (V/T) > 0.29. In a multivariate analysis among 186 patients, there were inverse associations between V/T and MLR (OR = 0.413, 95% CI = 0.216-0.789, P = 0.007). Furthermore, patients with visceral obesity tended to have significantly better OS than patients with non-visceral obesity. Higher V/T ratios which indicate referring to visceral obesity was significantly associated with decreased MLR and better OS for CRC.

  8. Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome

    Science.gov (United States)

    Greenland, John R.; Jones, Kirk D.; Hays, Steve R.; Golden, Jeffrey A.; Urisman, Anatoly; Jewell, Nicholas P.; Caughey, George H.

    2013-01-01

    Rationale: Lung transplantation offers great promise for otherwise terminal lung diseases, but the development of bronchiolitis obliterans syndrome (BOS) continues to limit survival. Although acute rejection and lymphocytic bronchiolitis have been identified as risk factors for the development of BOS, it is unclear whether large-airway lymphocytic inflammation conveys the same risk. Objectives: We evaluated lymphocytic bronchitis on endobronchial biopsies as a risk factor for BOS and mortality. Methods: Endobronchial biopsies were collected and graded during surveillance after lung transplantation. We assessed samples with negative cultures collected in the first 90 days from 298 subjects and compared large-airway lymphocytic bronchitis assessed by a 0–2 “E-score” and with standard A and BR pathology scores for acute rejection and small-airway lymphocytic bronchiolitis, respectively. Measurements and Main Results: We found surprisingly little association between large- and small-airway lymphocytic inflammation scores from a given bronchoscopy. Endobronchial lymphocytic bronchitis was more prevalent in subjects in BOS stage 0p and BOS stages 1–3 at the time of biopsy. Within 90 days after transplantation, increasing maximum E-score was associated with greater risk of BOS (adjusted hazard ratio, 1.76; 95% confidence interval, 1.11–2.78; P = 0.02) and in this analysis 90-day maximum E-scores were the only score type predictive of BOS (P < 0.01). Conclusions: These results support a multicenter study to evaluate endoscopic biopsies for the identification of patients at increased risk for BOS. The association of endobronchial lymphocytic inflammation and BOS may have mechanistic implications. PMID:23239157

  9. Deep Feature Transfer Learning in Combination with Traditional Features Predicts Survival Among Patients with Lung Adenocarcinoma.

    Science.gov (United States)

    Paul, Rahul; Hawkins, Samuel H; Balagurunathan, Yoganand; Schabath, Matthew B; Gillies, Robert J; Hall, Lawrence O; Goldgof, Dmitry B

    2016-12-01

    Lung cancer is the most common cause of cancer-related deaths in the USA. It can be detected and diagnosed using computed tomography images. For an automated classifier, identifying predictive features from medical images is a key concern. Deep feature extraction using pretrained convolutional neural networks (CNNs) has recently been successfully applied in some image domains. Here, we applied a pretrained CNN to extract deep features from 40 computed tomography images, with contrast, of non-small cell adenocarcinoma lung cancer, and combined deep features with traditional image features and trained classifiers to predict short- and long-term survivors. We experimented with several pretrained CNNs and several feature selection strategies. The best previously reported accuracy when using traditional quantitative features was 77.5% (area under the curve [AUC], 0.712), which was achieved by a decision tree classifier. The best reported accuracy from transfer learning and deep features was 77.5% (AUC, 0.713) using a decision tree classifier. When extracted deep neural network features were combined with traditional quantitative features, we obtained an accuracy of 90% (AUC, 0.935) with the 5 best post-rectified linear unit features extracted from a vgg-f pretrained CNN and the 5 best traditional features. The best results were achieved with the symmetric uncertainty feature ranking algorithm followed by a random forests classifier.

  10. Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

    Directory of Open Access Journals (Sweden)

    Scalerta Romano

    2009-12-01

    Full Text Available Abstract Background The detection of circulating tumor cells (CTC is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR for the expression of four CTC related genes: carcinoembryonic antigen (CEA, cytokeratin-19 (CK19, vascular endothelial growth factor (VEGF and Survivin (BIRC5. Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.

  11. Predicting survival after curative colectomy for cancer: individualizing colon cancer staging.

    Science.gov (United States)

    Weiser, Martin R; Gönen, Mithat; Chou, Joanne F; Kattan, Michael W; Schrag, Deborah

    2011-12-20

    Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy. Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves. Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line. Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.

  12. Survival characteristics and the applicability of predictive mathematical modelling to Listeria monocytogenes growth in sous vide products.

    Science.gov (United States)

    Nyati, H

    2000-06-01

    Survival and growth of Listeria monocytogenes isolates during sous vide processing and storage, and the applicability of predictive modelling in determining the potential for growth of L. monocytogenes in broth models and in sous vide products was investigated. L. monocytogenes grew in anaerobic tryptose phosphate broth and in chicken and beef samples by 2 log cycles in 8 days at 3 degrees C and 4-5 log cycles in 6 days at 8 degrees C. However, heating to an internal temperature of 70 degrees C resulted in a 4-5 log reduction and 70 degrees C/2 min resulted in a reduction greater than 7 log cycles. Lowering the product pH to 5.0 was effective in inhibiting L. monocytogenes growth, whereas a sodium chloride concentration of 2% had a negligible effect on growth rates. The square root model (Ratkowsky et al., 1983) predicted L. monocytogenes growth rates at 0-25 degrees C with a coefficient of determination (R2 value) of 98.36-99.63% and a bias factor of 1.08 to 1.21 in beef, chicken and broth substrates of unmodified pH. In addition, the Response Surface Polynomial Model (Version 3.1, Buchanan et al., 1989) predicted generation times at 5-25 degrees C with a 0-17.4% difference between observed and expected generation times in tryptose phosphate broth at pH 7.3. There were however, large differences (25.5 vs. 5.3 h) between observed generation times at pH 5.6 (8 degrees C) and those predicted by the Pathogen Modelling Program in tryptose phosphate broth. A divergence from predicted values was also noted at lower temperatures (0-3.5 degrees C) in the square root model.

  13. Optimism and survival: does an optimistic outlook predict better survival at advanced ages? A twelve-year follow-up of Danish nonagenarians

    DEFF Research Database (Denmark)

    Engberg, Henriette; Jeune, Bernard; Andersen-Ranberg, Karen;

    2013-01-01

    BACKGROUND AND AIMS: Studies examining predictors of survival among the oldest-old have primarily focused on objective measures, such as physical function and health status. Only a few studies have examined the effect of personality traits on survival, such as optimism. The aim of this study...... physical and cognitive functioning and disease were taken into account the association between optimism and survival weakened in both sexes, but the general pattern persisted. Optimistic women were still at lower risk of death compared to neutral women [HR 0.85, 95 % CI (0.74-0.97)]. The risk of death...

  14. Ventricular mass index correlates with pulmonary artery pressure and predicts survival in suspected systemic sclerosis-associated pulmonary arterial hypertension.

    Science.gov (United States)

    Hagger, Dan; Condliffe, Robin; Woodhouse, Neil; Elliot, Charlie A; Armstrong, Iain J; Davies, Christine; Hill, Catherine; Akil, Mohammed; Wild, Jim M; Kiely, David G

    2009-09-01

    The ventricular mass index (VMI) has been proposed as a diagnostic tool for the assessment of patients with suspected pulmonary hypertension (PH). We hypothesized that in patients with SSc it may predict the presence or absence of PH. Details of all consecutive SSc patients undergoing MRI and right heart catheterization were collected prospectively. Subsequently, the VMI for all patients was calculated, and further baseline data were collected. Data for 40 patients, 28 of whom were diagnosed with PH at rest (PH(REST)), were analysed. VMI correlated strongly with mean pulmonary artery pressure (mPAP; r = 0.79). Using a VMI threshold of 0.56, positive predictive value (PPV) for PH(REST) was 88% and negative predictive value (NPV) was 100%. Using a threshold of 0.7, PPV was found to be 100% and NPV 53%. Echocardiographically obtained tricuspid gradient (TG) also demonstrated a strong correlation with mPAP. Two-year survival in patients with VMI or =0.7 was 91 and 43%, respectively (P VMI correlates well with mPAP in patients with SSc and may have a role in non-invasively excluding clinically significant PH in breathless SSc patients in whom echocardiographic screening has failed. Further study in larger groups of patients is justified.

  15. Predicting patient survival from microarray data by accelerated failure time modeling using partial least squares and LASSO.

    Science.gov (United States)

    Datta, Susmita; Le-Rademacher, Jennifer; Datta, Somnath

    2007-03-01

    We consider the problem of predicting survival times of cancer patients from the gene expression profiles of their tumor samples via linear regression modeling of log-transformed failure times. The partial least squares (PLS) and least absolute shrinkage and selection operator (LASSO) methodologies are used for this purpose where we first modify the data to account for censoring. Three approaches of handling right censored data-reweighting, mean imputation, and multiple imputation-are considered. Their performances are examined in a detailed simulation study and compared with that of full data PLS and LASSO had there been no censoring. A major objective of this article is to investigate the performances of PLS and LASSO in the context of microarray data where the number of covariates is very large and there are extremely few samples. We demonstrate that LASSO outperforms PLS in terms of prediction error when the list of covariates includes a moderate to large percentage of useless or noise variables; otherwise, PLS may outperform LASSO. For a moderate sample size (100 with 10,000 covariates), LASSO performed better than a no covariate model (or noise-based prediction). The mean imputation method appears to best track the performance of the full data PLS or LASSO. The mean imputation scheme is used on an existing data set on lung cancer. This reanalysis using the mean imputed PLS and LASSO identifies a number of genes that were known to be related to cancer or tumor activities from previous studies.

  16. Context-dependent survival, fecundity and predicted population-level consequences of brucellosis in African buffalo.

    Science.gov (United States)

    Gorsich, Erin E; Ezenwa, Vanessa O; Cross, Paul C; Bengis, Roy G; Jolles, Anna E

    2015-07-01

    Chronic infections may have negative impacts on wildlife populations, yet their effects are difficult to detect in the absence of long-term population monitoring. Brucella abortus, the bacteria responsible for bovine brucellosis, causes chronic infections and abortions in wild and domestic ungulates, but its impact on population dynamics is not well understood. We report infection patterns and fitness correlates of bovine brucellosis in African buffalo based on (1) 7 years of cross-sectional disease surveys and (2) a 4-year longitudinal study in Kruger National Park (KNP), South Africa. We then used a matrix population model to translate these observed patterns into predicted population-level effects. Annual brucellosis seroprevalence ranged from 8·7% (95% CI = 1·8-15·6) to 47·6% (95% CI = 35·1-60·1) increased with age until adulthood (>6) and varied by location within KNP. Animals were on average in worse condition after testing positive for brucellosis (F = -5·074, P brucellosis and pregnancy or being observed with a calf. For the range of body condition scores observed in the population, the model-predicted growth rate was λ = 1·11 (95% CI = 1·02-1·21) in herds without brucellosis and λ = 1·00 (95% CI = 0·85-1·16) when brucellosis seroprevalence was 30%. Our results suggest that brucellosis infection can potentially result in reduced population growth rates, but because these effects varied with demographic and environmental conditions, they may remain unseen without intensive, longitudinal monitoring.

  17. Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma

    Science.gov (United States)

    Maurer, Matthew J.; Jais, Jean-Philippe; Ghesquières, Hervé; Witzig, Thomas E.; Hong, Fangxin; Haioun, Corinne; Thompson, Carrie A.; Thieblemont, Catherine; Micallef, Ivana N.; Porrata, Luis F.; Ribrag, Vincent; Nowakowski, Gregorz S.; Casanovas, Olivier; Bologna, Serge; Morschhauser, Franck; Morrison, Vicki A.; Peterson, Bruce A.; Macon, William R.; Copie-Bergman, Christiane; Feldman, Andrew L.; Syrbu, Sergei I.; Kurtin, Paul J.; Gascoyne, Randy D.; Li, Hailun; Allmer, Cristine; Kahl, Brad S.; Ansell, Stephen M.; Slager, Susan L.; Link, Brian K.; Salles, Gilles; Habermann, Thomas M.; Tilly, Hervé; Cerhan, James R.

    2016-01-01

    We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps. PMID:26492520

  18. Late Release of Circulating Endothelial Cells and Endothelial Progenitor Cells after Chemotherapy Predicts Response and Survival in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jeanine M. Roodhart

    2010-01-01

    Full Text Available We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor cells (CE(PCs and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS. Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(PC by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(PCs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(PCs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(PC was found (P < .01, independent of the type of chemotherapy. Changes in CE(PC levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(PC is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.

  19. Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer.

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    Jie Chen

    Full Text Available BACKGROUND: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis. METHODOLOGY/PRINCIPAL FINDINGS: Examination of FOXO3a and phosphorylated-Akt (P-Akt expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052, poor prognosis (p = 0.014, and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway. CONCLUSIONS/SIGNIFICANCE: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell

  20. ERCC1 and ERCC2 variants predict survival in gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Yangkai Li

    Full Text Available PURPOSE: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore, functional single nucleotide polymorphisms (SNPs in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy. However, few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients. EXPERIMENTAL DESIGN: We genotyped by the TaqMan assay three common, potentially functional ERCC1 (rs3212986 and ERCC2 SNPs (rs13181 and rs1799793 in 360 gastric cancer patients. We used both Kaplan-Meier tests and Cox proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical outcomes. RESULTS: We found that, compared with ERCC2 rs1799793 GG+AG genotypes, the homozygous variant AA genotype was associated with significantly poorer overall survival (OS (AA vs. GG+AG, log-rank P=0.012 and significantly higher risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to 3.56; P=0.004. In combined analyses, patients with any one of the three unfavorable genotypes (i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793 AA had statistically significant hazards of poor prognosis (Adjusted HR, 1.54; 95% CI, 1.06 to 2.25; P=0.025, compared with those without any unfavorable genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986 had a significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011, compared with the common haplotype G-T-G. CONCLUSION: ERCC1 and ERCC2 functional SNPs may jointly affect OS in Caucasian gastric cancer patients. Additional large prospective studies are essential to confirm our findings.

  1. Combining Gait Speed and Recall Memory to Predict Survival in Late Life: Population-Based Study.

    Science.gov (United States)

    Marengoni, Alessandra; Bandinelli, Stefania; Maietti, Elisa; Guralnik, Jack; Zuliani, Giovanni; Ferrucci, Luigi; Volpato, Stefano

    2017-03-01

    To evaluate the relationship between gait speed, recall memory, and mortality. A cohort study (last follow-up December 2009). Tuscany, Italy. Individual data from 1,014 community-dwelling older adults aged 60 years or older with baseline gait speed and recall memory measurements and follow-up for a median time of 9.10 (IQR 7.1;9.3) years. Participants were a mean (SD) age of 73.9 (7.3) years, and 55.8% women. Participants walking faster than 0.8 m/s were defined as fast walkers; good recall memory was defined as a score of 2 or 3 in the 3-word delayed recall section of the Mini-Mental State Examination. All-cause mortality. There were 302 deaths and the overall 100 person-year death rate was 3.77 (95% CI: 3.37-4.22). Both low gait speed and poor recall memory were associated with mortality when analysed separately (HR = 2.47; 95% CI: 1.87-3.27 and HR = 1.47; 95% CI: 1.16-1.87, respectively). When we grouped participants according to both recall and gait speed, death rates (100 person-years) progressively increased from those with both good gait speed and memory (2.0; 95% CI: 1.6-2.5), to those with fast walk but poor memory (3.4; 95% CI: 2.8-4.2), to those with slow walk and good memory (8.8; 95% CI: 6.4-12.1), to those with both slow walk and poor memory (13.0; 95% CI: 10.6-16.1). In multivariate analysis, poor memory significantly increases mortality risk among persons with fast gait speed (HR = 1.40; 95% CI: 1.04-1.89). In older persons, gait speed and recall memory are independent predictors of expected survival. Information on memory function might better stratify mortality risk among persons with fast gait speed. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  2. The modified high-density survival assay is the useful tool to predict the effectiveness of fractionated radiation exposure.

    Science.gov (United States)

    Kuwahara, Yoshikazu; Mori, Miyuki; Oikawa, Toshiyuki; Shimura, Tsutomu; Ohtake, Yosuke; Mori, Shiro; Ohkubo, Yasuhito; Fukumoto, Manabu

    2010-01-01

    The high-density survival (HDS) assay was originally elaborated to assess cancer cell responses to therapeutic agents under the influence of intercellular communication. Here, we simplified the original HDS assay and studied its applicability for the detection of cellular radioresistance. We have recently defined clinically relevant radioresistant (CRR) cells, which continue to proliferate with daily exposure to 2 gray (Gy) of X-rays for more than 30 days in vitro. We established human CRR cell lines, HepG2-8960-R from HepG2, and SAS-R1 and -R2 from SAS, respectively. In an attempt to apply the HDS assay to detect radioresistance with clinical relevance, we simplified the original HDS assay by scoring the total number of surviving cells after exposure to X-rays. The modified HDS assay successfully detected radioresistance with clinical relevance. The modified HDS assay detected CRR phenotype, which is not always detectable by clonogenic assay. Therefore, we believe that the modified HDS assay presented in this study is a powerful tool to predict the effectiveness of fractionated radiotherapy against malignant tumors.

  3. Prediction of Relapse After Cognitive-Behavioral Treatment of Gambling Disorder in Individuals With Chronic Schizophrenia: A Survival Analysis.

    Science.gov (United States)

    Echeburúa, Enrique; Gómez, Montserrat; Freixa, Montserrat

    2017-01-01

    Gambling disorder (GD) in individuals with chronic schizophrenia is relevant because there are higher rates of GD in schizophrenic populations (10%) than in the nonschizophrenic population (1%-5%). In addition, these patients have more severe alcohol use disorder (i.e., meeting at least 6 of the DSM-5 11 criteria for diagnosis of this disorder), higher depression scores, a poor adherence to treatment, and more frequent use of outpatient mental health care. One of the main problems in GD is therapeutic failure (defined as three or more lapse episodes during treatment) or relapse (three or more lapse episodes in the follow-up period). Predicting a relapse of GD in individuals with chronic schizophrenia can be useful in targeting the patients for aftercare services. The main aim of this study was to estimate the time to a GD relapse (survival rate) and to evaluate some of the qualitative and quantitative variables related to a GD relapse by a survival analysis. The sample consisted of 35 patients with chronic schizophrenia and GD who were treated with pharmacological and cognitive-behavioral therapy. The therapeutic failure rate in the treatment period was 43%, and it was associated with the number of episodes of schizophrenia, the age of gambling onset, and the age of the patients. The relapse rate in the follow-up period was 32%, and it was associated with the patients' age, educational level, and weekly allowance. The implications of this study for future research are discussed. Copyright © 2016. Published by Elsevier Ltd.

  4. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

    Science.gov (United States)

    Dienstmann, R; Mason, M J; Sinicrope, F A; Phipps, A I; Tejpar, S; Nesbakken, A; Danielsen, S A; Sveen, A; Buchanan, D D; Clendenning, M; Rosty, C; Bot, B; Alberts, S R; Milburn Jessup, J; Lothe, R A; Delorenzi, M; Newcomb, P A; Sargent, D; Guinney, J

    2017-05-01

    TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include

  5. PPT and VES-13 in elderly patients with cancer: evaluation in multidimensional geriatric assessment and prediction of survival.

    Science.gov (United States)

    Augschoell, Julia; Kemmler, Georg; Hamaker, Marije E; Stauder, Reinhard

    2014-10-01

    The multidimensional geriatric assessment (MGA) detects impairments in the elderly and forms the basis for individualized treatment algorithms. Screening tools have been developed to detect patients in need of a full assessment. The aim of this pilot study was to evaluate the discriminative power and the prognostic impact of the screening scores for the Physical Performance Test (PPT) and the Vulnerable Elders Survey-13 (VES-13). In 77 patients with cancer aged ≥60years (median 74years) from the Department of Internal Medicine V, Innsbruck Medical University, VES-13 and PPT were performed and compared with data from MGA and clinical outcomes. Overall, of the 77 patients 70% was deemed impaired, as defined by impairments in two or more scores of the MGA. The VES-13 showed 42% to be impaired, the PPT 79%. Using a cut-off of ≤19, the PPT exhibited better discriminative power than did the standard PPT (≤20). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of VES-13, PPT≤20 and PPT≤19 in the detection of impairments were 56% (88%, 82%), 91% (45%, 75%), 94% (80%, 89%), and 45% (60%, 63%) respectively. The area under the curve was 0.73 (0.67, 0.79), respectively. Both impaired VES-13 and PPT significantly correlated with an unfavorable overall survival in both uni- and multivariate analysis. PPT (≤19) reveals favorable sensitivity, NPV and overall accuracy in elderly patients with cancer. Still, the NPV is too low to sufficiently discriminate between fit and frail patients. Both PPT and VES-13 are useful predictors for survival. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Independent external validation of radiotherapy and its impact on the accuracy of a nomogram for predicting survival of women with endometrial cancer.

    Science.gov (United States)

    Koskas, Martin; Bendifallah, Sofiane; Luton, Dominique; Darai, Emile; Rouzier, Roman

    2011-11-01

    To externally validate and assess the impact of radiotherapy on the accuracy of a nomogram for predicting overall survival of women with endometrial cancer. Using data from the Surveillance, Epidemiology, and End Results (SEER), we assessed the concordance indexes, the discrimination and the calibration provided by a nomogram for predicting overall survival. Patients were grouped into deciles based on their survival predictions, and the three-year overall survival in each group was compared with the mean predicted probability. Between 1988 and 2006, 64,023 patients were analyzed and divided into two groups: 14,323 patients with adjuvant radiotherapy and 49,700 patients without adjuvant radiotherapy. Among the whole population, predicted and observed three-year overall survivals were 85.2% and 85.6% (+/-0.1%) respectively. In patients with adjuvant radiotherapy, overall survivals were 81.0% and 83.1% (+/-0.3%) and in patients without adjuvant radiotherapy, they were 86.5% and 86.3% (+/-0.2%) respectively. The concordance indexes for the whole population, in patients with radiotherapy and in patients without radiotherapy were 0.811 (+/-0.004), 0.751 (+/-0.009) and 0.803 (+/-0.006) respectively. The mean and maximal errors in patients with radiotherapy were 2.1% and 4.0% and in patients without radiotherapy 2.3% and 8.1%. The nomogram can accurately predict three-year overall survival, whether patients undergo adjuvant radiotherapy or not. The nomogram has an improved individual discrimination when compared with the 1988 and the 2009 staging systems for endometrial cancer. It may be useful in the information processed for patients and in building surveillance timing. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Predicting population survival under future climate change: density dependence, drought and extraction in an insular bighorn sheep.

    Science.gov (United States)

    Colchero, Fernando; Medellin, Rodrigo A; Clark, James S; Lee, Raymond; Katul, Gabriel G

    2009-05-01

    1. Our understanding of the interplay between density dependence, climatic perturbations, and conservation practices on the dynamics of small populations is still limited. This can result in uninformed strategies that put endangered populations at risk. Moreover, the data available for a large number of populations in such circumstances are sparse and mined with missing data. Under the current climate change scenarios, it is essential to develop appropriate inferential methods that can make use of such data sets. 2. We studied a population of desert bighorn sheep introduced to Tiburon Island, Mexico in 1975 and subjected to irregular extractions for the last 10 years. The unique attributes of this population are absence of predation and disease, thereby permitting us to explore the combined effect of density dependence, environmental variability and extraction in a 'controlled setting.' Using a combination of nonlinear discrete models with long-term field data, we constructed three basic Bayesian state space models with increasing density dependence (DD), and the same three models with the addition of summer drought effects. 3. We subsequently used Monte Carlo simulations to evaluate the combined effect of drought, DD, and increasing extractions on the probability of population survival under two climate change scenarios (based on the Intergovernmental Panel on Climate Change predictions): (i) increase in drought variability; and (ii) increase in mean drought severity. 4. The population grew from 16 individuals introduced in 1975 to close to 700 by 1993. Our results show that the population's growth was dominated by DD, with drought having a secondary but still relevant effect on its dynamics. 5. Our predictions suggest that under climate change scenario (i), extraction dominates the fate of the population, while for scenario (ii), an increase in mean drought affects the population's probability of survival in an equivalent magnitude as extractions. Thus, for the

  8. An early-biomarker algorithm predicts lethal graft-versus-host disease and survival

    Science.gov (United States)

    Hartwell, Matthew J.; Özbek, Umut; Holler, Ernst; Major-Monfried, Hannah; Reddy, Pavan; Aziz, Mina; Hogan, William J.; Ayuk, Francis; Efebera, Yvonne A.; Hexner, Elizabeth O.; Bunworasate, Udomsak; Qayed, Muna; Ordemann, Rainer; Wölfl, Matthias; Mielke, Stephan; Chen, Yi-Bin; Devine, Steven; Jagasia, Madan; Kitko, Carrie L.; Litzow, Mark R.; Kröger, Nicolaus; Locatelli, Franco; Morales, George; Nakamura, Ryotaro; Reshef, Ran; Rösler, Wolf; Weber, Daniela; Yanik, Gregory A.; Levine, John E.; Ferrara, James L.M.

    2017-01-01

    BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set (n = 309) and validation set (n = 358). RESULTS. A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group (P < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, P < 0.001) and the multicenter validation set (26% vs. 10%, P < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, P < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, P < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. CONCLUSION. A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. FUNDING. The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation. PMID:28194439

  9. Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab

    Science.gov (United States)

    Salgado, Roberto; Denkert, Carsten; Campbell, Christine; Savas, Peter; Nuciforo, Paolo; Aura, Claudia; de Azambuja, Evandro; Eidtmann, Holger; Ellis, Catherine E.; Baselga, Jose; Piccart-Gebhart, Martine J.; Michiels, Stefan; Bradbury, Ian; Sotiriou, Christos; Loi, Sherene

    2017-01-01

    Importance The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved outcomes in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer treated with adjuvant trastuzumab and chemotherapy. The prognostic associations in the neoadjuvant setting of other anti-HER2 agents and combinations are unknown. Objective To determine associations between presence of TILs, pathological complete response (pCR), and event-free survival (EFS) end points in patients with early breast cancer treated with trastuzumab, lapatinib, or the combination. Design, Setting, and Participants The NeoALTTO trial (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) randomly assigned 455 women with HER2-positive early-stage breast cancer between January 5, 2008, and May 27, 2010, to 1 of 3 neoadjuvant treatment arms: trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The primary end point used in this study was pCR in the breast and lymph nodes, with a secondary end point of EFS. We evaluated levels of percentage of TILs using hematoxylin-eosin–stained core biopsy sections taken at diagnosis (prior to treatment) in a prospectively defined retrospective analysis. Main Outcomes and Measures Levels of TILs were examined for their associations with efficacy end points adjusted for prognostic clinicopathological factors including PIK3CA genotype. Results Of the 455 patients, 387 (85.1%) tumor samples were used for the present analysis. The median (interquartile range [IQR]) level of TILs was 12.5% (5.0%-30.0%), with levels lower in hormone receptor–positive (10.0% [5.0%-22.5%]) vs hormone receptor–negative (12.5% [3.0%-35.0%]) samples (P = .02). For the pCR end point, levels of TILs greater than 5% were associated with higher pCR rates independent of treatment group (adjusted odds ratio, 2

  10. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties

    Directory of Open Access Journals (Sweden)

    Christine Dorothee Schmeitz

    2013-09-01

    Full Text Available Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic or initiates apoptosis depends on extracellular triggers and intracellular signalling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modelling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.

  11. Validation of the memorial Sloan-Kettering Cancer Center nomogram to predict disease-specific survival after R0 resection in a Chinese gastric cancer population.

    Directory of Open Access Journals (Sweden)

    Donglai Chen

    Full Text Available BACKGROUND: Prediction of disease-specific survival (DSS for individual patient with gastric cancer after R0 resection remains a clinical concern. Since the clinicopathologic characteristics of gastric cancer vary widely between China and western countries, this study is to evaluate a nomogram from Memorial Sloan-Kettering Cancer Center (MSKCC for predicting the probability of DSS in patients with gastric cancer from a Chinese cohort. METHODS: From 1998 to 2007, clinical data of 979 patients with gastric cancer who underwent R0 resection were retrospectively collected from Peking University Cancer Hospital & Institute and used for external validation. The performance of the MSKCC nomogram in our population was assessed using concordance index (C-index and calibration plot. RESULTS: The C-index for the MSKCC predictive nomogram was 0.74 in the Chinese cohort, compared with 0.69 for American Joint Committee on Cancer (AJCC staging system (P<0.0001. This suggests that the discriminating value of MSKCC nomogram is superior to AJCC staging system for prognostic prediction in the Chinese population. Calibration plots showed that the actual survival of Chinese patients corresponded closely to the MSKCC nonogram-predicted survival probabilities. Moreover, MSKCC nomogram predictions demonstrated the heterogeneity of survival in stage IIA/IIB/IIIA/IIIB disease of the Chinese patients. CONCLUSION: In this study, we externally validated MSKCC nomogram for predicting the probability of 5- and 9-year DSS after R0 resection for gastric cancer in a Chinese population. The MSKCC nomogram performed well with good discrimination and calibration. The MSKCC nomogram improved individualized predictions of survival, and may assist Chinese clinicians and patients in individual follow-up scheduling, and decision making with regard to various treatment options.

  12. {sup 18}F-FDG PET/CT predicts survival after {sup 90}Y transarterial radioembolization in unresectable hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jreige, Mario; Mitsakis, Periklis; Gucht, Axel van der; Pomoni, Anastasia; Silva-Monteiro, Marina; Boubaker, Ariane; Nicod-Lalonde, Marie; Prior, John O.; Schaefer, Niklaus [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Gnesin, Silvano [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Duran, Rafael; Denys, Alban [Lausanne University Hospital, Department of Radiodiagnostic and Interventional Radiology, Lausanne (Switzerland)

    2017-07-15

    To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 ({sup 90}Y-TARE) for unresectable hepatocellular carcinoma (uHCC). We analysed data from 48 patients in our prospective database undergoing {sup 90}Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent {sup 18}F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and {sup 90}Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of {sup 18}F-FDG PET/CT metabolic parameters, including SUV{sub max}, tumour-to-liver (T/L) uptake ratio and SUV{sub mean} of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after {sup 90}Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUV{sub max} (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUV{sub max} and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUV{sub max} and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean

  13. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...... the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how...

  14. MELD vs Child-Pugh and creatinine-modified Child-Pugh score for predicting survival in patients with decompensated cirrhosis

    Institute of Scientific and Technical Information of China (English)

    George V. Papatheodoridis; Evangelos Cholongitas; Eleni Dimitriadou; Giota Touloumi; Vassilios Sevastianos; Athanasios J. Archimandritis

    2005-01-01

    AIM: Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the predictive values of MELD, Child-Pugh and creatinine modified Child-Pugh scores in decompensated cirrhosis. METHODS: A cohort of 102 patients with decompensated cirrhosis followed-up for a median of 6 mo was studied.Two types of modified Child-Pugh scores estimated by adding 0-4 points to the original score using creatinine levels as a sixth categorical variable were evaluated.RESULTS: The areas under the receiver operating characteristic curves did not differ significantly among the four scores, but none had excellent diagnostic accuracy (areas:0.71-0.79). Child-Pugh score appeared to be the worst, while the accuracy of MELD was almost identical with that of modified Child-Pugh in predicting short-term and slightly better in predicting medium-term survival. In Cox regression analysis, all four scores were significantly associated with survival, while MELD and creatinine-modified Child-Pugh scores had better predictive values (c-statistics: 0.73 and 0.69-0.70) than Child-Pugh score (c-statistics: 0.65). Adjustment for gamma-glutamate transpeptidase levels increased the predictive values of all systems (c-statistics: 0.77-0.81). Analysis of the expected and observed survival curves in patients subgroups according to their prognosis showed that all models fit the data reasonably well with MELD probably discriminating better the subgroups with worse prognosis. CONCLUSION: MELD compared to the old Child-Pugh and particularly to creatinine-modified Child-Pugh scores does not appear to offer a clear advantage in predicting survival in patients with decompensated cirrhosis in daily clinical practice.

  15. {sup 18}F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Salaun, Pierre-Yves; Robin, Philippe [University Hospital, Nuclear Medicine Department, Brest (France); Campion, Loic [ICO-Gauducheau Cancer Institute, Statistical Department, Nantes (France); Ansquer, Catherine; Mathieu, Cedric [University Hospital, Nuclear Medicine Department, Nantes (France); Frampas, Eric [University Hospital, Radiology Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); Bournaud, Claire [University Hospital, Nuclear Medicine Department, Lyon (France); Vuillez, Jean-Philippe [University Hospital, Nuclear Medicine Department, Grenoble (France); Taieb, David [University Hospital, Nuclear Medicine Department, Marseille (France); Rousseau, Caroline [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Drui, Delphine [University Hospital, Endocrinology Department, Nantes (France); Mirallie, Eric [University Hospital, Surgery Department, Nantes (France); Borson-Chazot, Francoise [University Hospital, Endocrinology Department, Lyon (France); Goldenberg, David M. [IBC Pharmaceuticals, Inc., and Immunomedics, Inc., Morris Plains, NJ (United States); Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ (United States); Chatal, Jean-Francois [GIP ARRONAX, Saint-Herblain (France); Barbet, Jacques [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); GIP ARRONAX, Saint-Herblain (France); Kraeber-Bodere, Francoise [University Hospital, Nuclear Medicine Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Hotel Dieu University Hospital, Nuclear Medicine Department, Nantes (France)

    2014-08-15

    PET is a powerful tool for assessing targeted therapy. Since {sup 18}F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated {sup 18}F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV{sub max}, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV{sub max} (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the

  16. Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Juana Dornbusch

    Full Text Available BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC are frequently treated with tyrosine kinase inhibitors (TKI such as sunitinib. It inhibits angiogenic pathways by mainly targeting the receptors of VEGF and PDGF. In ccRCC, angiogenesis is characterized by the inactivation of the von Hippel-Lindau gene (VHL which in turn leads to the induction of HIF1α target genes such as CA9 and VEGF. Furthermore, the angiogenic phenotype of ccRCC is also reflected by endothelial markers (CD31, CD34 or other tumor-promoting factors like Ki67 or survivin. METHODS: Tissue microarrays from primary tumor specimens of 42 patients with metastatic ccRCC under sunitinib therapy were immunohistochemically stained for selected markers related to angiogenesis. The prognostic and predictive potential of theses markers was assessed on the basis of the objective response rate which was evaluated according to the RECIST criteria after 3, 6, 9 months and after last report (12-54 months of sunitinib treatment. Additionally, VHL copy number and mutation analyses were performed on DNA from cryo-preserved tumor tissues of 20 ccRCC patients. RESULTS: Immunostaining of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -β was significantly associated with the sunitinib response after 6 and 9 months as well as last report under therapy. Furthermore, HIF-1α, CA9, CD34, VEGFR1 and -3 and PDGRFα showed significant associations with progression-free survival (PFS and overall survival (OS. In multivariate Cox proportional hazards regression analyses high CA9 membrane staining and a response after 9 months were independent prognostic factors for longer OS. Frequently observed copy number loss and mutation of VHL gene lead to altered expression of VHL, HIF-1α, CA9, and VEGF. CONCLUSIONS: Immunoexpression of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -β in the primary tumors of metastatic ccRCC patients might support the

  17. Recursive Partitioning Analysis Index Is Predictive for Overall Survival in Patients Undergoing Spine Stereotactic Body Radiation Therapy for Spinal Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Samuel T., E-mail: chaos@ccf.org [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Brain Tumor and Neuro-oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Koyfman, Shlomo A.; Woody, Neil [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Angelov, Lilyana [Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Brain Tumor and Neuro-oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Soeder, Sherry L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Brain Tumor and Neuro-oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Reddy, Chandana A. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Rybicki, Lisa A. [Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Djemil, Toufik [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Suh, John H. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Brain Tumor and Neuro-oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States); Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195 (United States)

    2012-04-01

    Purpose: To generate a prognostic index using recursive partitioning analysis (RPA) for patients undergoing spine stereotactic body radiation therapy (sSBRT) for spinal metastases (sMet). Methods and Materials: From an institutional review board-approved database, 174 patients were treated for sMet with sSBRT between February 2006 and August 2009. Median dose was 14 Gy (range, 8-24 Gy), typically in a single fraction (range, 1-5). Kaplan-Meier analysis was performed to detect any correlation between survival and histology. Histologies were divided into favorable (breast and prostate), radioresistant (renal cell, melanoma and sarcoma), and other (all other histologies). RPA was performed to identify any association of the following variables with overall survival (OS) following sSBRT: histology, gender, age, Karnofsky performance status (KPS), control of primary, extraosseous metastases, time from primary diagnosis (TPD), dose of sSBRT ({<=}14 Gy vs. >14 Gy), extent of spine disease (epidural only, bone and epidural, bone only), upfront or salvage treatment, presence of paraspinal extension, and previous surgery. Results: Median follow-up was 8.9 months. Median OS time from sSBRT was 10.7 months. Median OS intervals for favorable histologies were 14 months, 11.2 months for radioresistant histologies, and 7.3 months for other histologies (p = 0.02). RPA analysis resulted in three classes (p < 0.0001). Class 1 was defined as TPD of >30 months and KPS of >70; Class 2 was TPD of >30 months and KPS of {<=}70 or a TPD of {<=}30 months and age <70 years old; Class 3 was TPD of {<=}30 months and age {>=}70 years old. Median OS was 21.1 months for Class 1 (n = 59), 8.7 months for Class 2 (n = 104), and 2.4 months for Class 3 (n = 11). Conclusion: sSBRT patients treated for sMet have a wide variability in OS. We developed an RPA classification system that is predictive of OS. While many patients are treated for palliation of pain or to avoid symptomatic progression, this

  18. Predictive value of assessing diastolic strain rate on survival in cardiac amyloidosis patients with preserved ejection fraction.

    Directory of Open Access Journals (Sweden)

    Dan Liu

    Full Text Available Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA, we hypothesized that speckle-tracking-imaging (STI derived longitudinal early diastolic strain rate (LSRdias could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%.Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients.Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years. Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views.Nineteen (46% out of 41 CA patients died during a median of 16 months (quartiles 5-35 months follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6 ± 2 vs. 8 ± 3 mm, global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p < 0.05. NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17-3.26, P = 0.010, global LSRdias (HR = 7.30, 95% CI 2.08-25.65, P = 0.002, and E/LSRdias (HR = 2.98, 95% CI 1.54-5.79, P = 0.001 remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S-1 (sensitivity 68%, specificity 67%. Global LSRdias < 0.85 S-1 predicted a 4-fold increased mortality in CA patients with preserved LVEF.STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

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

    Energy Technology Data Exchange (ETDEWEB)

    Oh, J; Apte, A; Folkerts, M; Kohutek, Z; Wu, A; Rimmer, A; Lee, N; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

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

  20. MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.

    Science.gov (United States)

    Lu, Yan; Govindan, Ramaswamy; Wang, Liang; Liu, Peng-yuan; Goodgame, Boone; Wen, Weidong; Sezhiyan, Ananth; Pfeifer, John; Li, Ya-fei; Hua, Xing; Wang, Yian; Yang, Ping; You, Ming

    2012-05-01

    About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.

  1. Gene signatures derived from a c-MET-driven liver cancer mouse model predict survival of patients with hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Irena Ivanovska

    Full Text Available Biomarkers derived from gene expression profiling data may have a high false-positive rate and must be rigorously validated using independent clinical data sets, which are not always available. Although animal model systems could provide alternative data sets to formulate hypotheses and limit the number of signatures to be tested in clinical samples, the predictive power of such an approach is not yet proven. The present study aims to analyze the molecular signatures of liver cancer in a c-MET-transgenic mouse model and investigate its prognostic relevance to human hepatocellular carcinoma (HCC. Tissue samples were obtained from tumor (TU, adjacent non-tumor (AN and distant normal (DN liver in Tet-operator regulated (TRE human c-MET transgenic mice (n = 21 as well as from a Chinese cohort of 272 HBV- and 9 HCV-associated HCC patients. Whole genome microarray expression profiling was conducted in Affymetrix gene expression chips, and prognostic significances of gene expression signatures were evaluated across the two species. Our data revealed parallels between mouse and human liver tumors, including down-regulation of metabolic pathways and up-regulation of cell cycle processes. The mouse tumors were most similar to a subset of patient samples characterized by activation of the Wnt pathway, but distinctive in the p53 pathway signals. Of potential clinical utility, we identified a set of genes that were down regulated in both mouse tumors and human HCC having significant predictive power on overall and disease-free survival, which were highly enriched for metabolic functions. In conclusions, this study provides evidence that a disease model can serve as a possible platform for generating hypotheses to be tested in human tissues and highlights an efficient method for generating biomarker signatures before extensive clinical trials have been initiated.

  2. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  3. TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy.

    Science.gov (United States)

    Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos; Areškevičiūtė, Aušrinė; Brown, Peter; Girkov, Mia Seremet; Pedersen, Anja; Sjö, Lene D; Heegaard, Steffen; Broholm, Helle; Kristensen, Lasse S; Ralfkiaer, Elisabeth; Grønbæk, Kirsten

    2016-04-22

    Primary central nervous system lymphoma (PCNSL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) confined to the CNS. TP53 mutations (MUT-TP53) were investigated in the context of MIR34A/B/C- and DAPK promoter methylation status, and associated with clinical outcomes in PCNSL patients. In a total of 107 PCNSL patients clinical data were recorded, histopathology reassessed, and genetic and epigenetic aberrations of the p53-miR34-DAPK network studied. TP53 mutational status (exon 5-8), with structural classification of single nucleotide variations according to the IARC-TP53-Database, methylation status of MIR34A/B/C and DAPK, and p53-protein expression were assessed. The 57/107 (53.2 %) patients that were treated with combination chemotherapy +/- rituximab (CCT-treated) had a significantly better median overall survival (OS) (31.3 months) than patients treated with other regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P TP53 mutations were identified in 32/86 (37.2 %), among which 12 patients had hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL patients with no influence on survival. Combined MUT-TP53 and MIR34A methylation was associated with poor PFS (median 6.4 versus 38.0 months), P = 0.0070. This

  4. [{sup 11}C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Giovacchini, Giampiero [Stadtspital Triemli, Department of Radiology and Nuclear Medicine, Zurich (Switzerland); Incerti, Elena; Mapelli, Paola; Gianolli, Luigi; Picchio, Maria [IRCCS San Raffaele Scientific Institute, Department of Nuclear Medicine, Milano (Italy); Kirienko, Margarita [University of Milano-Bicocca, Milano (Italy); Briganti, Alberto; Gandaglia, Giorgio; Montorsi, Francesco [IRCCS San Raffaele Scientific Institute, Department of Urology, Milano (Italy)

    2015-05-01

    Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [{sup 11}C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [{sup 11}C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [{sup 11}C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. Median follow-up was 7.2 years (1.4 - 18.9 years). [{sup 11}C]Choline PET/CT was positive in 101 of 302 patients (33 %). Median PCa-specific survival after prostatectomy was 14.9 years (95 % CI 9.7 - 20.1 years) in patients with positive [{sup 11}C]choline PET/CT. Median survival was not achieved in patients with negative [{sup 11}C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4 % (95 % CI 31.7 - 53.1 %) in patients with positive [{sup 11}C]choline PET/CT and 95.5 % (95 % CI 93.5 - 97.5 %) in patients with negative [{sup 11}C]choline PET/CT. In multivariate analysis, [{sup 11}C]choline PET/CT (hazard ratio 6.36, 95 % CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95 % CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80 %. Positive [{sup 11}C]choline PET/CT after biochemical failure

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Baohua Wang

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

  7. hGBP-1 Expression Predicts Shorter Progression-Free Survival in Ovarian Cancers, While Contributing to Paclitaxel Resistance

    Science.gov (United States)

    Wadi, Suzan; Tipton, Aaron R.; Trendel, Jill A.; Khuder, Sadik A.; Vestal, Deborah J.

    2017-01-01

    Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance. hGBP-1 is expressed in 17% of ovarian tumors from patients that have not yet received treatment. However, at least 80% of the ovarian tumors that recurred after therapies that included a tax-ane, either paclitaxel or docetaxel, were positive for hGBP-1. In addition, hGBP-1 expression predicts a significantly shorter progression-free survival in ovarian cancers. Based on these studies, hGBP-1 could prove to be a potential biomarker for paclitaxel resistance in ovarian cancer. PMID:28090373

  8. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Ramaiya, Nikhil H.; Tirumani, Sree Harsha [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, MA (United States); Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  9. A score model for predicting post-liver trans-plantation survival in HBV cirrhosis-related hepatocellular carcinoma recipients:a single center 5-year experience

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Wang; Xin-Hua Chen; Tian-An Jiang; Fen Chen; Shu-Sen Zheng; Xiao Xu; Wei-Lin Wang; Jian Wu; Min Zhang; Yan Shen; Sheng Yan; Hai-Yang Xie

    2015-01-01

    BACKGROUND: The prognostic prediction of liver transplan-tation (LT) guides t