Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial

2012 ◽  
Vol 30 (17) ◽  
pp. 2119-2127 ◽  
Author(s):  
Eric Van Cutsem ◽  
Sanne de Haas ◽  
Yoon-Koo Kang ◽  
Atsushi Ohtsu ◽  
Niall C. Tebbutt ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Locally Advanced ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Neuropilin 1

Purpose The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival. To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer, AVAGAST included a prospective, mandatory biomarker program. Patients and Methods Patients with previously untreated, locally advanced or metastatic gastric cancer were randomly assigned to bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Blood and tumor tissue samples were collected at baseline. Prespecified biomarkers included plasma vascular endothelial growth factor-A (VEGF-A), protein expression of neuropilin-1, and VEGF receptors-1 and -2 (VEGFR-1 and VEGFR-2). Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model. Results Plasma was available from 712 patients (92%), and tumor samples were available from 727 patients (94%). Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy. Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (hazard ratio [HR], 0.72; 95% CI, 0.57 to 0.93) versus patients with low VEGF-A levels (HR, 1.01; 95% CI, 0.77 to 1.31; interaction P = .07). Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival (HR, 0.75; 95% CI, 0.59 to 0.97) versus patients with high neuropilin-1 expression (HR, 1.07; 95% CI, 0.81 to 1.40; interaction P = .06). For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions. Conclusion Plasma VEGF-A and tumor neuropilin-1 are strong biomarker candidates for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab.

Association of radiation therapy with overall survival in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 528-528
Author(s):  
David Mitchell Marcus ◽  
Dana Nickleach ◽  
Bassel F. El-Rayes ◽  
Jerome Carl Landry
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Entire Cohort ◽  
The Impact

528 Background: The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiation followed by surgery, but many physicians question the benefit of multimodality therapy in patients with stage T3N0M0 disease. We aimed to determine the impact of radiation therapy (RT) on overall survival (OS) in this group of patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum from 2004 to 2010. The Kaplan-Meier method was used to compare OS for patients receiving RT vs. no RT, along with for pre-op vs. post-op RT among patients that received RT. Multivariable analysis (MVA) using a Cox proportional hazards model was performed to assess the association of RT with OS after adjusting for patient age, gender, race, tumor grade, carcinoembryonic antigen, type of surgery, and circumferential margin status. The analysis was repeated separately on patients that underwent total colectomy (TC) vs. sphincter-sparing surgery. Results: The cohort included 8,679 patients, including 4,705 who received RT and 3,974 who did not. Median age was 66 years. Five year OS was 76.5% in patients who received RT, compared to 60.0% in patients who did not receive RT (p <0.001). Five year OS was 76.9% for patients receiving pre-op RT vs. 75.7% in patients receiving post-op RT (p = 0.247). In patients undergoing TC, five year OS was 74.7% for patients receiving RT, compared to 47.5% in patients not receiving RT (p <0.001). In patients undergoing sphincter-sparing surgery, five year OS was 77.7% in patients receiving RT, compared to 62.9% in patients not receiving RT (p <0.001). Use of RT was significantly associated with OS on MVA, both in the entire cohort (HR 0.70 [95% CI 0.60-0.81]; p<0.001) and in subsets of patients undergoing TC (HR 0.55 [95% CI 0.38-0.79]; p=0.001) and sphincter-sparing surgery (HR 0.70 [95% CI 0.59-0.84]; p<0.001). Conclusions: The use of RT is associated with superior OS in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum. This benefit is demonstrated in both the pre-op and post-op settings and applies to patients undergoing both TC and sphincter-sparing surgery.

scholarly journals A novel nomogram to predict the overall survival in esthesinoeroblastoma

2020 ◽  
Author(s):  
Lijie Jiang ◽  
Tengjiao Lin ◽  
Yu Zhang ◽  
Wenxiang Gao ◽  
Jie Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Validation Cohort ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
P Value ◽  
Training Cohort

Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

Long-Term Survivors of Gastric Cancer: A California Population-Based Study

2012 ◽  
Vol 30 (28) ◽  
pp. 3507-3515 ◽  
Author(s):  
Pamela L. Kunz ◽  
Matthew Gubens ◽  
George A. Fisher ◽  
James M. Ford ◽  
Daphne Y. Lichtensztajn ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Gastroesophageal Junction ◽  
The United States ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Intestinal Histology ◽  
Hospital Size

Purpose In the United States, gastric cancer is rapidly fatal with a 25% 5-year survival. Of the few patients who survive, little is known about their demographic, clinical, and tumor characteristics. Patients and Methods Data regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed in California between 1988 and 2005 were obtained from the California Cancer Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. A Cox proportional hazards model was constructed to understand the independent relationships of patient demographic, disease, and treatment factors with survival. Results We identified 47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%) survived at least 3 years. Variables associated with longer survival were localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85), fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease-specific survival (DSS) in patients with tumors originating in the fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months). Intestinal histology had significantly longer median DSS (28.9 months) compared with other (11.0 months) or diffuse (10.1 months) histology. Conclusion Patients who survive gastric and GEJ cancer more than 3 years after diagnosis have demographic and pathologic characteristics distinct from those who do not survive.

Final overall survival and updated biomarker analysis results from the randomized phase III ICOGEN trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7559-7559 ◽  
Author(s):  
Yan Sun ◽  
Yuankai Shi ◽  
Li Zhang ◽  
Xiaoqing Liu ◽  
Caicun Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Significant Difference ◽  
Biomarker Analysis ◽  
Nsclc Patients

7559 Background: A total of 399 pretreated patients with advanced NSCLC were randomly assigned to receive gefitinib or icotinib in the phase III ICOGEN trial, the first head-to-head phase III trial of EGFR-TKIs. The results of the primary endpoint, PFS, have been reported previously. This report represents the final OS and biomarker analysis results. Methods: EGFR mutation was evaluated by using Scorpion ARMS (QIAGEN, n=152). Overall survival was analyzed by Cox proportional-hazards model analysis at 82% maturity. Results: Median OS was 13.3 months for icotinib and 13.9 months for gefitinib (hazard ratio [HR] = 0.90; 95% CI, 0.79 to 1.02; P = .109). The EGFR mutation rate was 43% in the icotinib group and 59% in the gefitinib group. Compared to wild type patients, patients with EGFR mutation had longer PFS (median, 6.2m vs. 2.3m; P=.00001) as well as OS (median, 20.5m vs. 7.7m; P=.00001). There were no significant differences in PFS or OS between the two treatment groups in EGFR mutation-positive subgroup (median PFS, 7.8m vs. 5.3m for icotinib and gefitinib, respectively, P =.3162; median OS, 20.9m vs. 20.2m for icotinib and gefitinib, respectively, P =.7611.) or in EGFR mutation-negative subgroup (median PFS, 2.3m vs. 2.2m for icotinib and gefitinib, respectively, P =.1531; median OS, 7.8m vs. 6.9m for icotinib and gefitinib, respectively, P =.7885.). Conclusions: There is no statistically significant difference between icotinib and gefitinib in PFS or OS when given to NSCLC patients. This suggests that icotinib can provide similar OS benefits to gefitinib in advanced NSCLC patients. Moreover, EGFR mutation status is the strongest predictor in identifying which patients are most likely to benefit from icotinib.

Survival and prognosticators of gastric cancer patients with only positive peritoneal lavage cytology.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 16-16
Author(s):  
Kazuki Kano ◽  
Tsutomu Sato ◽  
Yukio Maezawa ◽  
Kenki Segami ◽  
Tetsushi Nakajima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Proportional Hazards Model ◽  
Peritoneal Lavage ◽  
Multivariate Analyses ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Peritoneal Cytology ◽  
Peritoneal Lavage Cytology ◽  
Lavage Cytology

16 Background: Treatment strategies for only positive peritoneal lavage cytology findings have not yet been established. The objective of this retrospective study was to clarify the survival and prognosticators in these patients. Methods: Overall survival (OS) rates were examined in 39 patients with gastric cancer who underwent a curative resection and had positive peritoneal cytology in the absence of overt peritoneal metastases between January 2000 and June 2015. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. Results: A total of 39 patients were evaluated. The median overall survival was significantly longer in the 34 patients who received chemotherapy after surgery than that in the 5 who did not (19.1 vs 5.9 months, p < 0.01). Among the patients who received chemotherapy after surgery, univariate and multivariate analyses showed that pN3b was an independent significant prognosticator (hazard ratio of 4.169 with 95% CI: 1.108-15.684, p = 0.035). The median OS was 15.8 months when the patients diagnosed with N3b was 33.1 months when the patients diagnosed with N3a or lower. Conclusions: The prognosis of gastric carcinoma with positive peritoneal lavage cytology without peritoneal metastasis is still poor and need more aggressive treatment. The lymph node metastasis was a significant prognosticator in these patients.

scholarly journals Impact of Prior Cancer History on Outcomes in Thymoma

2020 ◽  
Author(s):  
Shilong Wu ◽  
Mengyang Liu ◽  
Weixue Cui ◽  
Guilin Peng ◽  
Jianxing He
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer History ◽  
Treatment Methods ◽  
Hazards Model ◽  
Kaplan Meier ◽  
The Impact

Abstract Background Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research. Method The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not. Results A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However, adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036). Conclusions Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.

scholarly journals A novel nomogram to predict the overall survival in esthesinoeroblastoma

2020 ◽  
Author(s):  
Lijie Jiang ◽  
Tengjiao Lin ◽  
Yu Zhang ◽  
Wenxiang Gao ◽  
Jie Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Validation Cohort ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Training Cohort ◽  
Chi Squared ◽  
Set Up

Abstract BackgroundIncreasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established.MethodsThis study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram.ResultsThe c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups.ConclusionsThe nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.# Co-first authors: Lijie Jiang and Tengjiao Lin contributed equally to this article.

MULTIMODALITY TREATMENT OF GLIOBLASTOMA PATIENTS USING DIFFERENT TEMOZOLOMIDE REGIMENS IN POSTOPERATIVE CHEMORADIOTHERAPY

2017 ◽  
Vol 63 (6) ◽  
pp. 915-919
Author(s):  
Edvard Zhavrid ◽  
Pavel Demeshko ◽  
Nataliya Artemova ◽  
V. Sinayko
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Patient Survival ◽  
Radiation Treatment ◽  
Multimodality Treatment ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model

The outcomes of multimodality treatment of 227 glioblastoma (grade IV) patients were evaluated in relation to the postoperative chemoradiotherapy (ChRT) regimen. No statistically significant differences were found in groups with conventional ChRT (temozolomide 75 mg/m2 per os 1 hour before the radiation treatment during the whole course of radiotherapy, n=111) and modified ChRT (temozolomide 75 mg/m2 per os 5 days a week 1 hour before the radiation treatment in the first and last two weeks of radiotherapy, n=116), the median overall survival being 16 months and 16 months respectively (P=0,889). The Cox proportional hazards model demonstrated that the postoperative ChRT regimen was not a prognostic factor affecting patient survival.

Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
R. M. Bukowski ◽  
T. Eisen ◽  
C. Szczylik ◽  
W. M. Stadler ◽  
R. Simantov ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Vegf Signaling ◽  
Hazards Model ◽  
Biomarker Analysis ◽  
Tumor Biopsies

5023 Background: Based on the significant PFS benefit of sorafenib (SOR) vs placebo (P) in a Phase III advanced RCC trial, P patients were unblinded and crossed over to SOR in May 2005. Final OS and biomarker data are reported. Methods: Final OS analysis was planned at ∼540 events (a=0.037 after adjusting for previous analyses). To minimize effect of crossover on OS, a secondary analysis was planned censoring P data on June 30, 2005 (a=0.037). Plasma VEGF and sVEGFR2 were measured by ELISA at baseline (BL), cycle (C) 1 day (D) 21, and C3D1. pERK was assayed by IHC. Results: 903 patients were randomized (SOR, 451; P, 452). The only OS analysis before crossover (May 2005) showed an estimated 39% OS improvement for SOR vs P (HR=0.72; p=0.018) (ECCO 2005); 216 P patients had crossed to SOR. OS analysis 6 months after crossover (Nov 2005) showed a 30% improvement in OS for SOR vs P (HR=0.77, p=0.015) (ASCO 2006). These OS differences did not reach prespecified O’Brien-Fleming statistical boundaries. Final OS (Sep 2006) at 561 deaths showed an improvement of 13.5% for SOR vs P and was not significant (median 17.8 vs 15.2 months; HR=0.88; p=0.146; a=0.037). Secondary analysis censoring P data (June 2005) showed a significant OS benefit for SOR vs P (HR=0.78, 95% CI: 0.62, 0.97; p=0.0287; a=0.037), suggesting crossover had confounded OS. Changes in VEGF (n=712) and sVEGFR2 (n=717) were observed after SOR treatment (AACR 2006); VEGF increased 32% (n=279) at C1D21 and 47% (n=203) at C3D1, and sVEGFR2 decreased 18% (n=282) and 24% (n=206). Using a COX proportional hazards model, BL VEGF was an independent prognostic factor (p=0.014); patients with high BL VEGF (>131 pg/ml) had poorer prognosis and a trend towards greater PFS benefit with SOR (SOR vs P, HR=0.48 vs 0.64 for high vs low VEGF, p=0.096). BL sVEGFR2, changes in VEGF or sVEGFR2 at C1D21, and pERK levels in limited diagnostic tumor biopsies were not predictive of SOR response. Conclusion: SOR demonstrated a PFS benefit in advanced RCC, although ITT final OS analysis showed a confounding effect of crossover. Significant OS benefit of SOR was seen in a planned secondary analysis adjusting for crossover. VEGF levels have prognostic importance, and SOR-associated changes in VEGF and sVEGFR2 are consistent with inhibition of VEGF signaling. No significant financial relationships to disclose.

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