Individual patient data meta-analysis of neoadjuvant chemotherapy followed by surgery versus upfront surgery for carcinoma of the oesophagus or the gastro-oesophageal junction.

INTRODUCTION: Which neoadjuvant treatment for locally advanced thoracic oesophagus (TE) or gastro-oesophageal junction carcinoma is best remains an open question. Randomised controlled trials variously accrued patients with adenocarcinoma and squamous cell carcinoma, making strong conclusions hard to obtain. The primary objective of this individual participant data meta-analysis was to investigate the effect of neoadjuvant chemotherapy on overall survival (OS). PATIENTS AND METHODS: Eligible trials should have closed to accrual before 2016 and compared neoadjuvant chemotherapy and surgery (CS) to surgery alone. All relevant published and unpublished trials were identified via searches of electronic databases, conference proceedings and clinical trial registers. The main end-point was OS. Investigators were contacted to obtain the individual patient data, which was recorded, harmonised and checked. A random-effects Cox model, stratified by trial, was used for meta-analysis and subgroup analyses were preplanned. RESULTS: 16 trials were identified as eligible. Individual patient data were obtained from 12 trial and 2478 patients. CS was associated with an improved OS versus surgery, hazard ratio (HR) = 0.83 [0.72-0.96], p < 0.0001, translating to an absolute benefit of 5.7% at 5-years from 16.8% to 22.5%. Treatment effects did not vary substantially between adenocarcinoma (HR = 0.73 [0.62-0.87]) and squamous cell carcinoma (HR = 0.91 [0.76-1.08], interaction p = 0.26). A somewhat more pronounced effect was observed in gastro-oesophageal junction (HR = 0.68 [0.50-0.93]) versus TE (HR = 0.87 [0.75-1.00], interaction p = 0.07). CS was also associated with a greater disease-free survival (HR = 0.74 [0.64-0.85], p < 0.001). CONCLUSIONS: Neoadjuvant chemotherapy conferred a better OS than surgery alone and should be considered in all anatomical location and histological subtypes.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Concurrent coronary and carotid artery surgery: factors influencing perioperative outcome and long-term results.

AIMS: To assess risk factors for early and late outcome after concurrent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). METHODS AND RESULTS: Records of all 311 consecutive patients having concurrent CEA and CABG from 1989 to 2002 were reviewed, and follow-up obtained (100% complete). In the group (mean age 67 years; 74% males), 62% had triple-vessel disease, 57% unstable angina, 31% left main coronary stenosis, 19% congestive heart failure, and 35% either a history of vascular procedures or existing vasculopathies. Preoperative assessment revealed transient ischaemic attack in 16%, stroke in 7%, and bilateral carotid disease in 20%. There were 7% emergent and 19% urgent operations, and ascending aorta was described as atheromatous or calcified in 21%. Hospital death occurred in 19 patients, myocardial infarction in seven, and permanent stroke in 12. Significant multivariable predictors of hospital death were aortic calcifications, coexisting vasculopathy, and emergent procedure. Significant predictors of postoperative stroke were calcified or dilated aorta, and of prolonged hospital stay were advanced age, unstable angina, and coexisting vascular disease. For hospital survivors, 10-year actuarial late event-free rates were: death, 50%; myocardial infarction, 84%; stroke, 93%; percutaneous angioplasty, 95%; redo CABG, 98%; and all morbidity and mortality, 48%. Significant multivariable predictors of late deaths were coexisting vasculopathy, age, renal insufficiency, previous cardiac surgery, tobacco abuse, calcified or atheromatous aorta, and duration of intensive care unit stay. CONCLUSION: Concurrent CEA and CABG can be performed with acceptable operative mortality and morbidity, and good long-term freedom from coronary and neurologic events. Atheromatous aortic disease is a harbinger of poor operative and long-term outcome.