Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting):study protocol for a randomized controlled trial

Background: The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. Methods/Design: The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients’ motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients’ experiences of each trial arm. Discussion: The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on patient-reported, rather than disease-orientated, outcomes. Exploration of patient experience and health economic analyses will be integral to the assessment of benefit for patients and the NHS

1685TiP Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3):A multicenter randomized controlled trial

BackgroundSurgical resection followed by adjuvant mFOLFIRINOX is the current standard of care for patients with resectable pancreatic cancer. The main concern with adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.Trial designThis is a multicentre, phase III, RCT that will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centres and three centres in Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 hours continuous infusion of 5-fluorouracil 2400 g/m2) followed by surgery and 4 cycles of adjuvant mFOLFIRINOX. Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Accrual started on September 7, 2021, and as of May 10, 2023, all centres are open for inclusion and 138 patients have been randomized

1685TiP Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3):A multicenter randomized controlled trial

BackgroundSurgical resection followed by adjuvant mFOLFIRINOX is the current standard of care for patients with resectable pancreatic cancer. The main concern with adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.Trial designThis is a multicentre, phase III, RCT that will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centres and three centres in Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 hours continuous infusion of 5-fluorouracil 2400 g/m2) followed by surgery and 4 cycles of adjuvant mFOLFIRINOX. Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Accrual started on September 7, 2021, and as of May 10, 2023, all centres are open for inclusion and 138 patients have been randomized

Sex, Gender and Age Differences in Treatment Allocation and Survival of Patients With Metastatic Pancreatic Cancer: A Nationwide Study.

Biological sex, gender and age have an impact on the incidence and outcome in patients with metastatic pancreatic cancer. The aim of this study is to investigate whether biological sex, gender and age are associated with treatment allocation and overall survival (OS) of patients with metastatic pancreatic cancer in a nationwide cohort. Patients with synchronous metastatic pancreatic cancer diagnosed between 2015 and 2019 were selected from the Netherlands Cancer Registry (NCR). The association between biological sex and the probability of receiving systemic treatment were examined with multivariable logistic regression analyses. Kaplan Meier analyses with log-rank test were used to describe OS. A total of 7470 patients with metastatic pancreatic cancer were included in this study. Fourty-eight percent of patients were women. Women received less often systemic treatment (26% vs. 28%, P=0.03), as compared to men. Multivariable logistic regression analyses with adjustment for confounders showed that women ≤55 years of age, received more often systemic treatment (OR 1.82, 95% CI 1.24-2.68) compared to men of the same age group. In contrast, women at >55 years of age had a comparable probability to receive systemic treatment compared to men of the same age groups. After adjustment for confounders, women had longer OS compared to men (HR 0.89, 95% CI 0.84-0.93). This study found that women in general had a lower probability of receiving systemic treatment compared to men, but this can mainly be explained by age differences. Women had better OS compared to men after adjustment for confounders

Neoadjuvant chemotherapy with FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy for borderline resectable and resectable pancreatic cancer (PREOPANC-2):A multicenter randomized controlled trial

BackgroundThe PREOPANC trial demonstrated an overall survival (OS) benefit of neoadjuvant gemcitabine-based chemoradiotherapy compared with upfront surgery in patients with borderline resectable and resectable pancreatic cancer (PDAC). FOLFIRINOX may further improve OS in the neoadjuvant setting.MethodsThis multicenter, phase 3, randomized trial included patients with borderline resectable and resectable PDAC from 19 Dutch centers. Patients received FOLFIRINOX every 14 days for 8 cycles followed by surgery without adjuvant treatment (FFX arm) versus 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions during the second cycle), followed by surgery and 4 cycles of adjuvant gemcitabine (CRT arm). Randomization was stratified by center and resectability status. Primary endpoint was OS. Secondary endpoints included resection rate and serious adverse event (SAE) rate. To demonstrate a hazard ratio (HR) of 0.70 with two-sided α = 0.05 and 80% power, 368 patients (252 events) were needed. HR and 95% CI were estimated using a stratified Cox model.ResultsBetween June 2018 and January 2021, 375 patients were randomized to the FFX arm (n=188) or the CRT arm (n=187). Six patients (3 per arm) were excluded because of ineligibility (n=4) or withdrawal of informed consent immediately after randomization (n=2). After a median follow-up of 41.7 months with 254 events, median OS was 21.9 months in the FFX arm and 21.3 months in the CRT arm (HR 0.87; 95% CI 0.68-1.12, p=0.28). Resection rates were 77% in the FFX arm and 75% in the CRT arm (p=0.69). SAE rates were 49% in the FFX arm and 43% in the CRT arm (p=0.26).ConclusionsNeoadjuvant chemotherapy with FOLFIRINOX did not improve OS compared with neoadjuvant gemcitabine-based chemoradiotherapy in patients with borderline resectable and resectable PDAC

Neoadjuvant chemotherapy with FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy for borderline resectable and resectable pancreatic cancer (PREOPANC-2):A multicenter randomized controlled trial

BackgroundThe PREOPANC trial demonstrated an overall survival (OS) benefit of neoadjuvant gemcitabine-based chemoradiotherapy compared with upfront surgery in patients with borderline resectable and resectable pancreatic cancer (PDAC). FOLFIRINOX may further improve OS in the neoadjuvant setting.MethodsThis multicenter, phase 3, randomized trial included patients with borderline resectable and resectable PDAC from 19 Dutch centers. Patients received FOLFIRINOX every 14 days for 8 cycles followed by surgery without adjuvant treatment (FFX arm) versus 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions during the second cycle), followed by surgery and 4 cycles of adjuvant gemcitabine (CRT arm). Randomization was stratified by center and resectability status. Primary endpoint was OS. Secondary endpoints included resection rate and serious adverse event (SAE) rate. To demonstrate a hazard ratio (HR) of 0.70 with two-sided α = 0.05 and 80% power, 368 patients (252 events) were needed. HR and 95% CI were estimated using a stratified Cox model.ResultsBetween June 2018 and January 2021, 375 patients were randomized to the FFX arm (n=188) or the CRT arm (n=187). Six patients (3 per arm) were excluded because of ineligibility (n=4) or withdrawal of informed consent immediately after randomization (n=2). After a median follow-up of 41.7 months with 254 events, median OS was 21.9 months in the FFX arm and 21.3 months in the CRT arm (HR 0.87; 95% CI 0.68-1.12, p=0.28). Resection rates were 77% in the FFX arm and 75% in the CRT arm (p=0.69). SAE rates were 49% in the FFX arm and 43% in the CRT arm (p=0.26).ConclusionsNeoadjuvant chemotherapy with FOLFIRINOX did not improve OS compared with neoadjuvant gemcitabine-based chemoradiotherapy in patients with borderline resectable and resectable PDAC