Cancer Research UK.

for the European Study Group for Pancreatic Cancer IMPORTANCE The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear. OBJECTIVE To define patterns of recurrence after adjuvant chemotherapy and the association with survival. DESIGN, SETTING, AND PARTICIPANTS Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019. INTERVENTIONS Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine. MAIN OUTCOMES AND MEASURES Overall survival, recurrence, and sites of recurrence. RESULTSOf the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03). CONCLUSIONS AND RELEVANCEThere were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.

Research in Context Panel:Evidence before this study: Preclinical data, epidemiological studies, and meta-analyses of randomised data from cardiovascular trials support the hypothesis that aspirin could be an effective adjuvant cancer therapy (Langley R, et al. Br J Cancer 2011;105(8):1107-13; Algra AM et al. Lancet Oncol 2012;13(5):518-27 ). Globally, several phase III studies are ongoing to assess this, though debate continues about the safety profile of aspirin particularly after radical therapy for gastrointestinal malignancies.Added value of this study: The Add-Aspirin trial (encompassing 4 individually powered phase III studies in gastro-oesophageal, colorectal, prostate and breast cancer) is the largest of the ongoing trials and includes a pre-defined feasibility analysis to assess the acceptability of randomisation, tolerability and toxicity based on an open label run-in phase prior to double-blind randomisation. The data show that aspirin is well tolerated after radical cancer therapy, acceptable to patients, and there is no evidence to suggest there is increased toxicity in the gastro-oesophageal cohort over other tumour-specific cohorts.Implications of all the available evidence: Aspirin is a low cost generic drug with the potential to have a large impact on cancer outcomes globally. Outcomes from gastro-oesophageal cancer remain poor and there is an imperative to complete recruitment to the ongoing trials as quickly as possible. The rationale and supporting evidence for evaluating aspirin as a potential anti-cancer therapy remains strong. More generally, a run-in approach may be useful in adjuvant (or prevention) studies for reducing the risk of non-adherence and participant attrition at a later date. ABSTRACT Background: Pre-clinical, epidemiological and randomised data indicate aspirin prevents tumour development and metastases leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. To address concerns about toxicity particularly bleeding after radical treatment for gastro-oesophageal cancer, a pre-planned feasibility analysis was incorporated into the ongoing Add-Aspirin trial. Method: The Add-Aspirin protocol includes 4 phase III randomised-controlled trials evaluating the effect of aspirin on recurrence/survival after radical therapy in 4 tumour cohorts: gastro-oesophageal (GO), colorectal (CRC), breast and prostate. An open-label run-in phase (aspirin 100mg daily for 8 weeks) precedes double-blind randomisation (1:1:1 aspirin 300mg: aspirin 100mg: matched placebo). A preplanned analysis of feasibility, including recruitment, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648), and remains open to recruitment. Findings: After two years of recruitment (October 2015-October 2017), 3494 participants were registered on the trial (gastro-oesophageal 115, colorectal 950, breast...

ObjectivesTo investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).DesignCross-sectional study.SettingUniversity Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence.ParticipantsPatients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities.Main outcome measureTo identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment.ResultsMUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients.ConclusionsGiven the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.

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