Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

PURPOSE: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. METHOD: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). CONCLUSION: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

A phase III randomized trial evaluating the quality of life impact of a tailored versus systematic use of defunctioning ileostomy following total mesorectal excision for rectal cancer-GRECCAR 17 trial protocol.

AIM: The systematic use of a defunctioning ileostomy for 2-3 months postoperatively to protect low colorectal anastomosis (<7 cm from the anal verge) has been the standard practice after total mesorectal excision (TME). However, stoma-related complications can occur in 20%-60% of cases, which may lead to prolonged inpatient care, urgent reoperation and long-term definitive stoma. A negative impact on quality of life (QoL) and increased healthcare expenses are also observed. Conversely, it has been reported that patients without a defunctioning stoma or following early stoma closure (days 8-12 after TME) have a better functional outcome than patients with systematic defunctioning stoma in situ for 2-3 months. METHOD: The main objective of this trial is to compare the QoL impact of a tailored versus systematic use of a defunctioning stoma after TME for rectal cancer. The primary outcome is QoL at 12 months postoperatively using the European Organization for. Research and Treatment of Cancer QoL questionnaire QLQ-C30. Among 29 centres of the French GRECCAR network, 200 patients will be recruited over 18 months, with follow-up at 1, 4, 8 and 12 months postoperatively, in an open-label, randomized, two-parallel arm, phase III superiority clinical trial. The experimental arm (arm A) will undergo a tailored use of defunctioning stoma after TME based on a two-step process: (i) to perform or not a defunctioning stoma according to the personalized risk of anastomotic leak (defunctioning stoma only if modified anastomotic failure observed risk score ≥2) and (ii) if a stoma is fashioned, whether to perform an early stoma closure at days 8-12, according to clinical (fever), biochemical (C-reactive protein level on days 2 and 4 postoperatively) and radiological postoperative assessment (CT scan with retrograde contrast enema at days 7-8 postoperatively). The control arm (arm B) will undergo systematic use of a defunctioning stoma for 2-3 months after TME for all patients, in keeping with French national and international guidelines. Secondary outcomes will include comprehensive analysis of functional outcomes (including bowel, urinary and sexual function) again up to 12 months postoperatively and a cost analysis. Regular assessments of anastomotic leak rates in both arms (every 50 randomized patients) will be performed and an independent data monitoring committee will recommend trial cessation if this rate is excessive in arm A compared to arm B. CONCLUSION: The GRECCAR 17 trial is the first randomized trial to assess a tailored, patient-specific approach to decisions regarding defunctioning stoma use and closure after TME according to personalized risk of anastomotic leak. The results of this trial will describe, for the first time, the QoL and morbidity impact of selective use of a defunctioning ileostomy and the potential health economic effect of such an approach.

A New Paradigm in Managing Advanced Ovarian Cancer: Differentiating Patients Requiring Neoadjuvant Treatment from Primary Cytoreduction.

Our study aims to evaluate the comparability of primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) patients. This single-center retrospective study includes all patients treated for advanced stages high-grade serous ovarian carcinomas (HGSOC) between 2007 and 2017. Preoperative characteristics and postoperative outcomes were compared after a propensity score matching analysis. Of the 221 patients included, 38% underwent PDS, and 62% received NACT. There was no age difference at diagnosis; however, CA125 levels, PCI score levels, and rates of stage IV were higher in the NACT group. There were no differences concerning the rate and the severity of complications (p = 0.29). The propensity score distribution showed a broad distinction between PDS patients and NACT patients with no significant overlap. Survival analyses demonstrate, after a median follow-up of 66.5 months, an overall survival (OS) of 105.9 and progression-free survival (PFS) of 29.2 months in the PDS group, compared to OS of 52.8 and PFS of 18.9 months in the NACT group. Advanced HGSOC is a heterogeneous population, in which inoperable patients should be differentiated from PDS patients based on many factors, primarily tumor burden.

Prognostic value of the texture analysis parameters of the initial computed tomographic scan for response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

BACKGROUND AND PURPOSE: Baseline contrast-enhanced computed tomography (CT)-derived texture analysis in locally advanced rectal cancer could help offer the best personalized treatment. The purpose of this study was to determine the value of baseline-CT texture analysis in the prediction of downstaging in patients with locally advanced rectal cancer. PATIENTS AND METHODS: We retrospectively included all consecutive patients treated with neoadjuvant chemoradiation therapy (CRT) followed by surgery for locally advanced rectal cancer. Tumor texture analysis was performed on the baseline pre-CRT contrast-enhanced CT examination. Based on the selected model of downstaging with a penalized logistic regression in a training set, a radiomics score (Radscore) was calculated as a linear combination of selected features. A multivariable prognostic model that included Radscore and clinical factors was created. RESULTS: Of the 121 patients included in the study, 109 patients (90%) had T3-T4 cancer and 99 (82%) had N+ cancer. A downstaging response was observed in 96 patients (79%). In the training set (79 patients), the best model (ELASTIC-NET method) reduced the 36 texture features to a combination of 6 features. The multivariate analysis retained the Radscore (odds ratio [OR] = 13.25; 95% confidence interval [95% CI], 4.06-71.64; p < 0.001) and age (OR = 1.10/1 year; 1.03-1.20; p = 0.008) as independent factors. In the test set, the area under the curve was estimated to be 0.70 (95% CI, 0.48-0.92). CONCLUSION: This study presents a prognostic score for downstaging, from initial computed tomography-derived texture analysis in locally advanced rectal cancer, which may lead to a more personalized treatment for each patient.