scholarly journals Excision Repair Cross-Complementation Group 6 Gene Polymorphism Is Associated with the Response to FOLFIRINOX Chemotherapy in Asian Patients with Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1196
Author(s):  
Young Hoon Choi ◽  
Younggyun Lim ◽  
Ji Kon Ryu ◽  
Woo Hyun Paik ◽  
Sang Hyub Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Excision Repair ◽  
Cox Model ◽  
Progression Free Survival ◽  
Complementation Group ◽  
Cox Regression Analysis ◽  
Asian Patients ◽  
Damage Repair

FOLFIRINOX is currently one of the standard chemotherapy regimens for pancreatic cancer patients, but little is known about the factors that can predict a response to it. We performed a study to discover novel DNA damage repair (DDR) gene variants associated with the response to FOLFIRINOX chemotherapy in patients with pancreatic cancer. We queried a cohort of pancreatic cancer patients who received FOLFIRINOX chemotherapy as the first treatment and who had tissue obtained through an endoscopic ultrasound-guided biopsy that was suitable for DNA sequencing. We explored variants of 148 DDR genes based on whole exome sequencing and performed multivariate Cox regression to find genetic variants associated with progression-free survival (PFS). Overall, 103 patients were included. Among 2384 variants of 141 DDR genes, 612 non-synonymous variants of 123 genes were selected for Cox regression analysis. The multivariate Cox model showed that rs2228528 in ERCC6 was significantly associated with improved PFS (hazard ratio 0.54, p = 0.001). The median PFS was significantly longer in patients with rs2228528 genotype AA vs. genotype GA and GG (23.5 vs. 16.2 and 8.6 months; log-rank p < 0.001). This study suggests that rs2228528 in ERCC6 could be a potential predictor of response to FOLFIRINOX chemotherapy in patients with pancreatic cancer.

scholarly journals Alternative splicing acts as an independent prognosticator in ovarian carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Ouyang ◽  
Kaide Xia ◽  
Xue Yang ◽  
Shichao Zhang ◽  
Li Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Alternative Splicing ◽  
Ovarian Carcinoma ◽  
Cancer Patients ◽  
Cox Regression ◽  
Excision Repair ◽  
Splicing Factors ◽  
Prognostic Signature ◽  
Cox Regression Analysis

AbstractAlternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma. There are no reliable features to predict survival outcomes for ovarian cancer patients. In this study, comprehensive profiling of AS events was conducted by integrating AS data and clinical information of ovarian serous cystadenocarcinoma (OV). Survival-related AS events were identified by Univariate Cox regression analysis. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to construct the prognostic signatures within each AS type. Furthermore, we established a splicing-related network to reveal the potential regulatory mechanisms between splicing factors and candidate AS events. A total of 730 AS events were identified as survival-associated splicing events, and the final prognostic signature based on all seven types of AS events could serve as an independent prognostic indicator and had powerful efficiency in distinguishing patient outcomes. In addition, survival-related AS events might be involved in tumor-related pathways including base excision repair and pyrimidine metabolism pathways, and some splicing factors might be correlated with prognosis-related AS events, including SPEN, SF3B5, RNPC3, LUC7L3, SRSF11 and PRPF38B. Our study constructs an independent prognostic signature for predicting ovarian cancer patients’ survival outcome and contributes to elucidating the underlying mechanism of AS in tumor development.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

The efficacy of first-line chemotherapy in recurrent pancreatic cancer after S-1 adjuvant chemotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 475-475
Author(s):  
Ryo Kanata ◽  
Masato Ozaka ◽  
Seita Kataoka ◽  
Kazunaga Ishigaki ◽  
Ikuhiro Yamada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Cancer Recurrence ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Recurrent Pancreatic Cancer ◽  
Line Chemotherapy

475 Background: In Japan, adjuvant chemotherapy with S-1 for 6 months is standard care for resected pancreatic cancer. However, the efficacy of chemotherapy for recurrent pancreatic cancer(RPC) after adjuvant S-1 chemotherapy is not well evaluated. Methods: Medical records were retrospectively reviewed for consecutive patients who had RPC after adjuvant S-1 treatment and received chemotherapy between April 2013 and July 2016. Recurrence free interval (RFI) was defined as the interval from adjuvant S-1 initiation to cancer recurrence. Overall survival (OS) and progression free survival (PFS) after 1st line chemotherapy for RPC were compared between patients with RFIs of shorter than 6 month (Group S) and longer than 6 months (Group L). Results: In the 53 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 5.1 months, and the median RFI was 8.3 months. After recurrence, they received Gemcitabine alone (20 patients), Gemcitabine+nab-paclitaxel (28 patients), modified FOLFIRINOX (one patient), and other regimen (4 patients). In all patients, the median PFS was 7.3 months and the median OS was 14.8 months. When compered in two groups (group S and group L), median OS in group S and group L was 6.7 months (95% confidence interval(CI): 4.2-12.9) and NA (95% CI: 13 months-NA) , respectively (p < 0.001), and median PFS was 3.8 months (95%CI: 2.5-9.1) and 7.3 months (95%CI: 3.9-15.3), respectively (p = 0.11). Multivariate Cox regression analysis revealed CEA < 4.0 mg/dl before chemotherapy and an RFI of ≥ 6 months were significantly associated with longer survival. Conclusions: These data suggest that RFI < 6 months is a surrogate marker for a poor prognosis in patients with RPC.

Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 3-3
Author(s):  
Grace Lee ◽  
Daniel W. Kim ◽  
Vinayak Muralidhar ◽  
Devarati Mitra ◽  
Nora Horick ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Anal Cancer ◽  
Cox Regression ◽  
Cox Model ◽  
Rank Test ◽  
Anal Squamous Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.

scholarly journals Identification of a Ubiquitination-Related Gene Risk Model for Predicting Survival in Patients With Pancreatic Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Hao Zuo ◽  
Luojun Chen ◽  
Na Li ◽  
Qibin Song
Keyword(s):  
Pancreatic Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Risk Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Transcriptional Level ◽  
Cox Regression Analysis

Pancreatic cancer is known as “the king of cancer,” and ubiquitination/deubiquitination-related genes are key contributors to its development. Our study aimed to identify ubiquitination/deubiquitination-related genes associated with the prognosis of pancreatic cancer patients by the bioinformatics method and then construct a risk model. In this study, the gene expression profiles and clinical data of pancreatic cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database and the Genotype-tissue Expression (GTEx) database. Ubiquitination/deubiquitination-related genes were obtained from the gene set enrichment analysis (GSEA). Univariate Cox regression analysis was used to identify differentially expressed ubiquitination-related genes selected from GSEA which were associated with the prognosis of pancreatic cancer patients. Using multivariate Cox regression analysis, we detected eight optimal ubiquitination-related genes (RNF7, NPEPPS, NCCRP1, BRCA1, TRIM37, RNF25, CDC27, and UBE2H) and then used them to construct a risk model to predict the prognosis of pancreatic cancer patients. Finally, the eight risk genes were validated by the Human Protein Atlas (HPA) database, the results showed that the protein expression level of the eight genes was generally consistent with those at the transcriptional level. Our findings suggest the risk model constructed from these eight ubiquitination-related genes can accurately and reliably predict the prognosis of pancreatic cancer patients. These eight genes have the potential to be further studied as new biomarkers or therapeutic targets for pancreatic cancer.

Pancreatic cancer: Assessment of neoadjuvant chemotherapy outcome based on radiomics of pretreatment computed tomography.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15767-e15767
Author(s):  
Xiang Li ◽  
Tianyu Tang ◽  
Xueli Bai ◽  
Tingbo Liang
Keyword(s):  
Computed Tomography ◽  
Pancreatic Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Size ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Histopathologic Response

e15767 Background: The objective response rate to neoadjuvant chemotherapy (NAC) was limited to around 35% in pancreatic cancer and as more as 30% patients show no benefit to NAC. In this instance, predicting the response to NAC may play an important role in individual treatment for pancreatic cancer patients. We aim to evaluate contrast enhanced-computed tomography (CE-CT) features in predicting treatment response and survival after neoadjuvant chemotherapy (NAC) for patients with borderline resectable and locally advanced pancreatic cancer. Methods: Sixty-one pancreatic cancer patients receiving NAC were enrolled and underwent abdominal CE-CT before treatment. All patients were divided into groups according to the changes of tumor size after treatment. 396 radiomics features were extracted from three-dimensional ROIs (region of interest) based on pretreatment CE-CT images of each patient. The optimal features were selected and three supervised machine learning classifiers were developed. Finally, univariate and multivariate analyses were performed to evaluate the capability of the selected features in predicting histopathologic response and outcomes. Results: Nine, seven and five radiomics features were selected as optimal features for three experiments respectively. Two features, Haralick Entropy and Histogram Entropy, were found consistent in experiments and were both higher in patients with tumor enlargement. Moreover, lower Histogram Entropy was significantly associated with a better histopathologic response (p = 0.008) and smaller tumor size (p = 0.041) in patients with tumor resection. In univariate Cox regression analysis, lower Histogram Entropy (P = 0.006) and lower Haralick Entropy (P = 0.001) predicted a better prognosis. Meanwhile, lower Haralick Entropy (p = 0.048) was independent predictor for longer survival time in multivariate Cox regression analysis. Conclusions: Radiomics features are strongly correlated with NAC treatment response and prognosis in pancreatic cancer, suggesting the great potential of imaging radiomics to help tailoring the treatment into the era of personalized medicine

Real-life results from the prospective QoliXane trial of the platform for outcome, quality of life, and translational research on pancreatic cancer (PARAGON) registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4625-4625
Author(s):  
Salah-Eddin Al-Batran ◽  
Ralf Dieter Hofheinz ◽  
Alexander Reichart ◽  
Claudia Pauligk ◽  
Rudolf Schlag ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Pancreatic Cancer ◽  
Cox Regression ◽  
Real Life ◽  
Progression Free Survival ◽  
Response Analysis ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Therapy

4625 Background: Gemcitabine and nab-paclitaxel (NPG) is standard first-line therapy for metastatic pancreatic cancer (mPC), but the pivotal study did not include quality of life (QoL) analyses. Methods: The QOLIXANE-PARAGON study started as a prospective, non-interventional, multicenter study conducted in Germany and transitioned into a permanent registry for pancreatic cancer patients (pts) considering all types of treatments. This report focuses on the pts enrolled into the QOLIXANE portion of the study. Pts were recruited from 95 German centers. QoL was prospectively measured via EORTC-C30 questionnaires (prior to and every month thereafter): therapy and efficacy parameters were prospectively collected. QoL and efficacy endpoints were analyzed in the intention-to-treat population (ITT). The primary endpoint was the rate of pts without deterioration of QoL/Global Health Score (QoL/GHS) at 3 months. Results: 600 pts were enrolled. Mean GHS/QoL score at baseline was low and was 46.2 (SD 22.8). Median progression-free survival was 5.85 months (95% CI, 5.23 to 6.25). Median overall survival (OS) was 8.91 months (95% CI, 7.89 to 10.19). The KM-analysis showed that 61% and 41% of pts had maintained QoL/GHS after 3 and 6 months, respectively. Median time to deterioration of QoL/GHS was 4.68 months (95% CI, 4.04 to 5.59). Mean QoL/GHS improved from 46.1 (SD 22.7) at baseline to 52.8 (SD 21.3) after 6 months. In the QoL response analysis, 34.6%, 37.4% and 28% of evaluable pts had improved, stable and worse QoL/GHS after 3 months, respectively. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a HR of 0.86 (p < 0.0001). Conclusions: QoliXane the largest study on QoL of mPC. It shows that time to deterioration of QoL is short but that a relevant group of mPC in first line have improved or maintained QoL after 3 and 6 months and that QoL is a predictor of pts outcome. Clinical trial information: NCT02691052 .

Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients

2012 ◽  
Vol 393 (5) ◽  
pp. 391-401 ◽  
Author(s):  
Lina Seiz ◽  
Julia Dorn ◽  
Matthias Kotzsch ◽  
Axel Walch ◽  
Nicolai I. Grebenchtchikov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cancer Patients ◽  
Stromal Cell ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Cancer Tissue ◽  
Cox Regression Analysis

Abstract Several members of the human kallikrein-related peptidase family, including KLK6, are up-regulated in ovarian cancer. High KLK6 mRNA or protein expression, measured by quantitative polymerase chain reaction and enzyme-linked immunoassay, respectively, was previously found to be associated with a shortened overall and progression-free survival (OS and PFS, respectively). In the present study, we aimed at analyzing KLK6 protein expression in ovarian cancer tissue by immunohistochemistry. Using a newly developed monospecific polyclonal antibody, KLK6 immunoexpression was initially evaluated in normal tissues. We observed strong staining in the brain and moderate staining in the kidney, liver, and ovary, whereas the pancreas and the skeletal muscle were unreactive, which is in line with previously published results. Next, both tumor cell- and stromal cell-associated KLK6 immunoexpression were analyzed in tumor tissue specimens of 118 ovarian cancer patients. In multivariate Cox regression analysis, only stromal cell-associated expression, besides the established clinical parameters FIGO stage and residual tumor mass, was found to be statistically significant for OS and PFS [high vs. low KLK6 expression; hazard ratio (HR), 1.92; p=0.017; HR, 1.80; p=0.042, respectively]. These results indicate that KLK6 expressed by stromal cells may considerably contribute to the aggressiveness of ovarian cancer.

DNA repair functionality modulates the clinical outcome of patients with advanced sarcoma treated with trabectedin (ET-743)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9522-9522 ◽  
Author(s):  
P. Schöffski ◽  
P. G. Casali ◽  
M. Taron ◽  
A. T. Van Oosterom ◽  
I. R. Judson ◽  
...  
Keyword(s):  
Median Survival ◽  
Cox Regression ◽  
Excision Repair ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Expression ◽  
Brca1 And Brca2 ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Low Expression

9522 Background and Methods: The sensitivity to trabectedin (Yondelis, ET-743) in experimental cancer models correlates with functional transcription-coupled nucleotide excision repair (TC-NER) and with deficient homologous recombination repair (HRR) activity. In order to assess the clinical relevance of this observation we have characterized the mRNA expression levels of ERCC1, XPD, BRCA1 and BRCA2 by RT-PCR in historical tumor samples from 92 sarcoma patients (pts) treated with the agent. Results: The overall objective response (CR+PR) rate to Yondelis in this group was 9%, which confirms the previous clinical experience with the compound in unselected, pre-treated patients with sarcoma. The Kaplan-Meier estimates for progression-free survival at 6 months (PFS6) was 23% and for median survival 8 months (mo). 26% of pts were alive at 24 mo. Correlative Study: Pts with high expression levels (> median) of ERCC1 had better PFS6 (32% vs 15%, p = 0.07) and better median survival (12 vs 7 mo) as compared to pts with low expression ( ≤ to median). Pts with low expression levels of BRCA1 had better PFS6 (33 vs 11%, p = 0.02) and superior median survival (15 vs 5 mo, p = 0.0003) than pts with high expression. Expression levels of XPD and BRCA2 (58 pts) had no significant impact on PFS and survival. The analysis of co-expression of ERCC1-BRCA1 identified a highly sensitive group of pts, characterized by high ERCC1 and low BRCA1 expression levels, with a PFS6 of 50% (p=0.0003) and median survival of 20.4 mo (p = 0.0005). A Cox regression analysis demonstrated that ERCC1 (HR=0.52, p = 0.02) and BRCA1 (HR=2.73, p = 0.0006) are independent variables for PFS, while BRCA1 (HR= 2.57, p = 0.0005) is also an independent variable for survival. Conclusion: This exploratory retrospective study supports the hypothesis that the sensitivity to Yondelis in pts with sarcoma correlates with a functional TC-NER and with deficient HRR. Prospective studies in sarcoma and other potentially sensitive tumor types are required to confirm and validate these findings. [Table: see text]

scholarly journals Effects of marital status on overall and cancer-specific survival in laryngeal cancer patients: a population-based study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ding ◽  
Deshun Yu ◽  
Hefeng Li ◽  
Yueming Ding
Keyword(s):  
Marital Status ◽  
Cancer Patients ◽  
Laryngeal Cancer ◽  
Cox Regression ◽  
Group Analysis ◽  
Population Based ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
The Difference

AbstractMarital status has long been recognized as an important prognostic factor for many cancers, however its’ prognostic effect for patients with laryngeal cancer has not been fully examined. We retrospectively analyzed 8834 laryngeal cancer patients in the Surveillance Epidemiology and End Results database from 2004 to 2010. Patients were divided into four groups: married, widowed, single, and divorced/separated. The difference in overall survival (OS) and cancer-specific survival (CSS) of the various marital subgroups were calculated using the Kaplan–Meier curve. Multivariate Cox regression analysis screened for independent prognostic factors. Propensity score matching (PSM) was also conducted to minimize selection bias. We included 8834 eligible patients (4817 married, 894 widowed, 1732 single and 1391 divorced/separated) with laryngeal cancer. The 5-year OS and CSS of married, widowed, single, and separated/divorced patients were examined. Univariate and multivariate analyses found marital status to be an independent predictor of survival. Subgroup survival analysis showed that the OS and CSS rates in widowed patients were always the lowest in the various American Joint Committee on Cancer stages, irrespective of sex. Widowed patients demonstrated worse OS and CSS in the 1:1 matched group analysis. Among patients with laryngeal cancer, widowed patients represented the highest-risk group, with the lowest OS and CSS.

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