Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer

The aim of this study was to investigate the worldwide evidence of the roles of adjuvant chemoradiation and adjuvant chemotherapy on survival in potentially curative resected pancreatic cancer. Five randomised controlled trials of adjuvant treatment in patients with histologically proven pancreatic ductal adenocarcinoma were identified, of which the four most recent trials provided individual patient data (875 patients). This meta-analysis includes previously unpublished follow-up data on 261 patients. The pooled estimate of the hazard ratio (HR) indicated a 25% significant reduction in the risk of death with chemotherapy (HR=0.75, 95% confidence interval (CI): 0.64, 0.90, P-valuesstratified (Pstrat)=0.001) with median survival estimated at 19.0 (95% CI: 16.4, 21.1) months with chemotherapy and 13.5 (95% CI: 12.2, 15.8) without. The 2- and 5-year survival rates were estimated at 38 and 19%, respectively, with chemotherapy and 28 and 12% without. The pooled estimate of the HR indicated no significant difference in the risk of death with chemoradiation (HR=1.09, 95% CI: 0.89, 1.32, Pstrat=0.43) with median survivals estimated at 15.8 (95% CI: 13.9, 18.1) months with chemoradiation and 15.2 (95% CI: 13.1, 18.2) without. The 2- and 5-year survival rates were estimated at 30 and 12%, respectively, with chemoradiation and 34 and 17% without. Subgroup analyses estimated that chemoradiation was more effective and chemotherapy less effective in patients with positive resection margins. These results show that chemotherapy is effective adjuvant treatment in pancreatic cancer but not chemoradiation. Further studies with chemoradiation are warranted in patients with positive resection margins, as chemotherapy appeared relatively ineffective in this patient subgroup

Pooling of prognostic studies in cancer of the pancreatic head and periampullary region: The Triple-P study

Objective: Development of a prognostic tool for patients with unresectable pancreatic cancer to distinguish between with low or high probabilities of survival 3 to 9 months after diagnosis. Design: Data about individual patients from five studies were pooled. A multivariate proportional hazards model with time-dependent covariates was developed, including age, sex, and metastases. An extended model was developed on a subset of patients, including weight loss, pain, and jaundice at diagnosis. Setting: Multicentre study, The Netherlands; Norway, USA, UK, and Canada. Subjects: 1020 patients with unresectable pancreatic cancer. Main outcome measures: Prediction of prognosis. Results: Patients with metastases, pain, or weight loss at diagnosis had a significantly poorer prognosis than the others. Older men had a worse prognosis than younger men, while older women had a better prognosis than younger ones. Patients with jaundice had a relatively good prognosis. Differences in survival among the studies were incorporated in a prognostic score chart. Conclusion: The prognostic score chart can be used to select patients with relatively low expectation of survival for endoscopic palliation, and patients with relatively high expectation for surgical palliation

Increase in serum bilirubin levels in obstructive jaundice secondary to pancreatic and periampullary malignancy – implications for timing of resectional surgery and use of biliary drainage

Background. Routine preoperative biliary drainage in cases of jaundice secondary to pancreatobiliary malignancy is associated with a significant risk of complications, failure and stent occlusion. It may be possible to avoid biliary drainage in those patients who are not deeply jaundiced. Aims. To measure presenting serum bilirubin and its rate of increase in patients with malignant obstructive jaundice. To predict the urgency with which surgery should be performed to avoid preoperative biliary drainage. Patients and methods. Prospective data collection for all pancreatic and periampullary malignancies over a period of 18 months was carried out. Serum bilirubin levels before successful drainage were recorded. Rates of increase in bilirubin and the number of days for bilirubin to reach different thresholds were calculated. Results. Of 111 patients, 66 (59%) had resectable disease on imaging investigations. Median serum bilirubin on presentation was 160 µmol/l. Median increase was 13.1 µmol/l/day or approximately 100 µmol/l/week. The predicted number of days for bilirubin levels to reach a variety of thresholds varied significantly. For a patient presenting with a serum bilirubin of 160 µmol/l, the mean number of days for it to rise to 200 µmol/l, 300 µmol/l, 400 µmol/l and 500 µmol/l was 3, 13, 22 and 31 days, respectively. Conclusions. There is a variable window of opportunity in jaundiced patients with pancreatic and periampullary malignancy during which surgery may be performed to avoid biliary drainage procedures, depending on the threshold for operating on the jaundiced patient