Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
ObjectiveTo assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study.
Summary Background DataPancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies.
MethodsESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status.
ResultsOf 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups.
ConclusionsResection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.
In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.
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