A national study to assess outcomes of definitive chemoradiation regimens in proximal esophageal cancer

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens. Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model. Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9–77.2 months). Median OS (21.9 months; 95% CI: 16.9–27.0 months) was comparable between treatment groups (logrank p = .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3–5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31–10.87; p = .01). The occurrence of grades 3–5 late toxicities was not different between treatment groups. Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC

Lifestyle changes and reduction of colon cancer incidence in Europe: A scenario study of physical activity promotion and weight reduction.

BACKGROUND: Across Europe, there are over 300,000 new cases of colorectal cancer annually. Major risk factors include excess body weight (usually expressed by a high body mass index, BMI) and physical inactivity (PA). In this study we modelled the potential long-term effects on colon cancer incidence of changes in prevalence of excess body weight and physical inactivity in seven European countries across Europe with adequate data. METHODS: We addressed the impact of interventions aimed at preventing weight gain and increasing physical activity on colon cancer incidence using the Prevent model as refined in the FP-6 Eurocadet project. Relative risk (RR) estimates were derived from meta-analyses; sex- and country-specific prevalences of BMI and PA were determined from survey data. Models were made for Czech Republic, Denmark, France, Latvia, the Netherlands, Spain and the United Kingdom. RESULTS: In a hypothetical scenario in which a whole population had obtained an ideal weight distribution in the year 2009, up to 11 new cases per 100,000 person-years would be avoided by 2040. The population attributable fractions (PAF) for excess weight were much higher for males (between 13.5% and 18.2%) than for females (2.3-4.6%). In contrast, using the optimum scenario where everybody in Europe would adhere to the recommended guideline of at least 30 min of moderate PA 5d per week, the PAFs for PA in various countries were substantially greater in women (4.4-21.2%) than in men (3.2-11.6%). Sensitivity analyses were performed assuming underreporting of BMI by using self-reports (difference of 5 and 0.8 percent-points in males and females, respectively), using different risk estimates (between 5.8 and 11.5 percent-points difference for BMI for men and women, respectively, and up to 11.6 percent-points difference for PA for women). INTERPRETATION: Changes in lifestyle can indeed result in large health benefits, including for colon cancer. Two interesting patterns emerged: for colon cancer, achieving optimum BMI levels in the population appears to offer the greatest health benefits in population attributable fractions in males, while increased physical activity might offer the greatest fraction of avoidable cancers in females. These observations suggest a sex-specific strategy to colon cancer prevention

Gender Differences in Treatment Allocation and Survival of Advanced Gastroesophageal Cancer: A Population-Based Study.

Biological sex and gender have been reported to affect incidence and overall survival (OS) of curatively treated gastroesophageal cancer. The aim of this study was to compare palliative treatment allocation and OS between women and men with advanced gastroesophageal cancer. Patients with an unresectable or metastatic esophageal (including cardia) adenocarcinoma (EAC) or squamous cell carcinoma (ESCC) or gastric adenocarcinoma (GAC) diagnosed in 2015-2018 were identified in the Netherlands Cancer Registry. Treatment allocation was compared using χ2 tests and multivariable logistic regression analyses, and OS using the Kaplan-Meier method with log-rank test and Cox proportional hazards analysis. All statistical tests were 2-sided. Of patients with EAC (n = 3077), ESCC (n = 794), and GAC (n = 1836), 18.0%, 39.4%, and 39.1% were women, respectively. Women less often received systemic treatment compared with men for EAC (42.7% vs 47.4%, P = .045) and GAC (33.8% vs 38.8%, P = .03) but not for ESCC (33.2% vs 39.5%, P = .07). Women had a lower probability of receiving systemic treatment for GAC in multivariable analyses (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.62 to 1.00) but not for EAC (OR = 0.86, 95% CI = 0.69 to 1.06) and ESCC (OR = 0.81, 95% CI = 0.57 to 1.14). Median OS was lower in women with EAC (4.4 vs 5.2 months, P = .04) but did not differ after adjustment for patient and tumor characteristics and systemic treatment administration. We observed statistically significant and clinically relevant gender differences in systemic treatment administration and OS in advanced gastroesophageal cancer. Causes of these disparities may be sex based (ie, related to tumor biology) as well as gender based (eg, related to differences in treatment choices)