Postoperative chemoradiation therapy

Gastrointestinal Study Group (GITSG): A small randomized trial conducted by the GITSG in 1985 compared surgery alone with surgery followed by chemoradiation.[4][Level of evidence A1];[5][Level of evidence B4]

Gastrointestinal Study Group (GITSG): A small randomized trial conducted by the GITSG in 1985 compared surgery alone with surgery followed by chemoradiation.[4][Level of evidence A1];[5][Level of evidence B4]

The investigators reported a significant but modest improvement in median-term and long-term survival over resection alone with postoperative bolus 5-FU and regional split-course radiation given at a dose of 40 Gy.

European Organisation for the Research and Treatment of Cancer (EORTC): An attempt by the EORTC to reproduce the results of the GITSG trial failed to confirm a significant benefit for adjuvant chemoradiation therapy over resection alone;[6][Level of evidence A1] however, this trial treated patients with pancreatic and periampullary cancers (with a potentially better prognosis).

European Organisation for the Research and Treatment of Cancer (EORTC): An attempt by the EORTC to reproduce the results of the GITSG trial failed to confirm a significant benefit for adjuvant chemoradiation therapy over resection alone;[6][Level of evidence A1] however, this trial treated patients with pancreatic and periampullary cancers (with a potentially better prognosis).

A subset analysis of the patients with primary pancreatic tumors indicated a trend toward improved median, 2-year, and 5-year OS with adjuvant therapy (17.1 months, 37%, and 20%, respectively) compared with surgery alone (12.6 months, 23%, and 10%, respectively); P = .09 for median survival).

An updated analysis of a subsequent ESPAC-1 trial examined only patients who underwent strict randomization after pancreatic resection. The patients were assigned to one of four groups (observation, bolus 5-FU chemotherapy, bolus 5-FU chemoradiation therapy, or chemoradiation therapy followed by additional chemotherapy).[7,8,28][Level of evidence A1]

An updated analysis of a subsequent ESPAC-1 trial examined only patients who underwent strict randomization after pancreatic resection. The patients were assigned to one of four groups (observation, bolus 5-FU chemotherapy, bolus 5-FU chemoradiation therapy, or chemoradiation therapy followed by additional chemotherapy).[7,8,28][Level of evidence A1]

With a 2 × 2 factorial design reported at a median follow-up of 47 months, a median survival benefit was observed for only the patients who received postoperative 5-FU chemotherapy. However, these results were difficult to interpret because of a high rate of protocol nonadherence and the lack of a separate analysis for each of the four groups in the 2 × 2 design.

U.S. Gastrointestinal Intergroup: The U.S. Gastrointestinal Intergroup has reported the results of a randomized phase III trial (Radiation Therapy Oncology Group [RTOG]-9704) that included 451 patients with resected pancreatic cancers who were assigned to receive either postoperative infusional 5-FU plus infusional 5-FU and concurrent radiation or adjuvant gemcitabine plus infusional 5-FU and concurrent radiation.[29][Level of evidence A1] The primary end points were OS for all patients and OS for patients with pancreatic head tumors.

U.S. Gastrointestinal Intergroup: The U.S. Gastrointestinal Intergroup has reported the results of a randomized phase III trial (Radiation Therapy Oncology Group [RTOG]-9704) that included 451 patients with resected pancreatic cancers who were assigned to receive either postoperative infusional 5-FU plus infusional 5-FU and concurrent radiation or adjuvant gemcitabine plus infusional 5-FU and concurrent radiation.[29][Level of evidence A1] The primary end points were OS for all patients and OS for patients with pancreatic head tumors.

A 5-year update of RTOG-9704 reported that patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 5-year OS rate of 22% with gemcitabine, versus a median survival of 17.1 months and a 5-year OS rate of 18% with 5-FU (HR, 0.84; 95% CI, 0.67–1.05; P = .12).[30]

U.S. Gastrointestinal Intergroup: The U.S. Gastrointestinal Intergroup has reported the results of a randomized phase III trial (Radiation Therapy Oncology Group [RTOG]-9704) that included 451 patients with resected pancreatic cancers who were assigned to receive either postoperative infusional 5-FU plus infusional 5-FU and concurrent radiation or adjuvant gemcitabine plus infusional 5-FU and concurrent radiation.[29][Level of evidence A1] The primary end points were OS for all patients and OS for patients with pancreatic head tumors.

Univariate analysis showed no difference in OS. However, on multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = .08). Distant relapse remained the predominant site of first failure (78%).