The current RTOG trial (RTOG 0848) After resected head of pancreas cancer randomizes postOp chemo first (5 cycles of Gemzar alone or Gemzar plus Tarceva) then if there is no progression has a second randomization (one more cycle of chemo or one more cycle then chemoradiation (50.4Gy combined with either 5FU or Xeloda)

Some of the studies using radiation and chemotherapy after a surgical resection are noted below.

Adjuvant therapy for pancreatic cancer.

Ghaneh P, Slavin J, Sutton R, Neoptolemos JP.Swiss Surg 2000;6(5):289-95

Department of Surgery, University of Liverpool, UK.

For 15 years only the GITSG had tested adjuvant therapy in a randomised controlled trial. This small study of only 43 patients suggested a survival benefit for post-operative chemoradiotherapy combined with follow-on chemotherapy. Recently two large trials of over 800 patients, one from the EORTC and the other from ESPAC, have shown no benefit from chemoradiotherapy alone. Results from a Norwegian and from ESPAC suggest that adjuvant chemotherapy (without chemoradiotherapy) prolongs survival.

Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group .Cancer 1987 Jun 15;59(12):2006-10

The Gastrointestinal Tumor Study Group (GITSG) previously demonstrated a significant survival advantage for patients who receive adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Median survival in the group randomized to control was 10.9 months, compared with 21.0 months for those randomized to treatment. GITSG registered 30 additional patients, who received the adjuvant therapy to demonstrate that the results of the randomized trial could be replicated. Characteristics of registered patients were similar to those of patients in the randomized phase, with the exception of an improved performance status. The registered patients had median survival time of 18 months. Ten patients were alive at 18.9 to 42.4 months (median, 25.0.). Two-year actuarial survival was 46% (95% confidence interval [CI], 0.28, 0.65) compared with 43% (95% CI, 0.25, 0.63) for 21 patients randomized to treatment and 18% (95% CI, 0.08, 0.36) for 22 patients randomized to control. Based on the original study and the confirmatory findings, the combined use of radiation therapy and fluorouracil as adjuvant therapy after curative resection is effective and is preferred to no adjuvant therapy.

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, Zahurak ML, Dooley WC, Coleman J, Sauter PK, Pitt HA, Lillemoe KD, Cameron JLAnn Surg 1997 May;225(5):621-33; discussion 633-6

Department of Surgery, Johns Hopkins Medical Institution, Baltimore, Maryland, USA.

From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.

Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

Klinkenbijl JH,  Ann Surg 1999 Dec;230(6):776-82; discussion 782-4

Department of Surgery, University Hospital Rotterdam-Dijkzigt, The Netherlands.

Eligible patients with T1-2N0-1aM0 pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically proven adenocarcinoma were randomized after resection. RESULTS: Between 1987 and 1995, 218 patients were randomized (108 patients in the observation group, 110 patients in the treatment group). Eleven patients were ineligible (five in the observation group and six in the treatment group). Baseline characteristics were comparable between the two groups. One hundred fourteen patients (55%) had pancreatic cancer (54 in the observation group and 60 in the treatment group). In the treatment arm, 21 patients (20%) received no treatment because of postoperative complications or patient refusal. In the treatment group, only minor toxicity was observed. The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group (log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %, respectively. The results when stratifying for tumor location showed a 2-year survival rate of 26% in the observation group and 34% in the treatment group (log-rank, p = 0.099) in pancreatic head cancer; in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the treatment group

Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma.

Pendurthi TK, Am Surg 1998 Jul;64(7):686-92

Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Two groups of patients with adenocarcinoma of the pancreas treated with either preoperative chemoradiation (preop CTRT) or postoperative chemoradiation (postop CTRT) were retrospectively analyzed for various treatment-related parameters. Between November 1986 and October 1996, a total of 70 patients with pancreatic adenocarcinoma were enrolled into preop CTRT protocols at our institution. Twenty-five patients with adenocarcinoma of the head of the pancreas underwent pancreaticoduodenectomy with curative intent. After the closure of the preop CTRT protocols, we had the opportunity to perform 23 pancreatic resections without preop CTRT. After surgery, these patients were advised to undergo CTRT. These two groups of patients were therefore selected consecutively, dependent only on the time of referral and no other bias. These two cohorts of patients are compared for various intraoperative parameters, length of hospital stay, pathologic findings, time to recurrence, and survival. There were no significant survival differences observed (median 20 months vs 25 months; P = 0.48), in follow-up that ranged from 4 to 76 months (median 44 months for surviving patients) for the preop group and 4 to 40 months (median 16 months for surviving patients) for those with postop CTRT. Local failure either alone or as a component of distant failure occurred in 16 per cent (4 of 25 patients) with preop CTRT and 16.6 per cent (3 of 18) with postop CTRT. Analysis of differences between those treated with preoperative and postoperative CTRT demonstrates similarity in toxicity and effects. However, 22 per cent of patients intended for postoperative therapy did not receive treatment.

Adjuvant therapy of resected adenocarcinoma of the pancreas.

Whittington R, Int J Radiat Oncol Biol Phys 1991 Oct;21(5):1137-43

Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia.

Seventy-two patients underwent resections of pancreatic carcinomas between 1981 and 1989 at the Hospital of the University of Pennsylvania and were evaluable for follow-up. There were three treatment groups as treatment policies evolved. Initially, patients were observed after surgery without adjuvant treatment (Group 1-33 patients). Beginning in 1984, patients were offered adjuvant radiation therapy postoperatively (Group 2-19 patients) and eight of these patients also received 5-FU as an IV bolus on the first 3 days of the first and fifth weeks of treatment. Twenty patients were treated with chemosensitized radiation therapy following surgery using 96-hour 5-FU infusions during the first and fifth weeks of treatment. There were four postoperative deaths, which are excluded from the analysis, and sites of failure could not be determined for five other patients. Among evaluable patients, local recurrences occurred in 85% of the patients in group 1, 55% of the patients in group 2, and 25% of the patients in group 3. The 2-year survival was 35% in group 1, 30% in group 2, and 43% in group 3. Patients with involved surgical margins had a poor survival; only 2 of these 16 patients survived longer than 18 months. Among patients with negative margins, the 2-year survival is 41% in group 1, 33% in group 2, and 59% in group 3. Although the number of patients is smaller, the 3-year survival is 22% in group 1, 11% in group 2, and 47% in group 3. Chemosensitized irradiation is well tolerated in these patients. The major challenge in this group of patients is nutritional maintenance. There was no other significant toxicity. The trend in these observations suggests that survival following pancreatic resection is substantially improved with the addition of adjuvant chemosensitized radiation therapy.

Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas.

Spitz FR, J Clin Oncol 1997 Mar;15(3):928-37

Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

From July 1990 to July 1995, 142 patients with localized adenocarcinoma of the pancreatic head deemed resectable on the basis of radiographic images were treated with curative intent using a multimodality approach involving either preoperative or postoperative chemoradiation. Patients with biopsy confirmation of adenocarcinoma and a low-density mass in the pancreatic head identified by computed tomography (CT) received preoperative chemoradiation. Patients without a mass on CT or in whom the preoperative biopsy was negative underwent pancreaticoduodenectomy with planned postoperative chemoradiation. Protocol-based preoperative chemoradiation consisted of external-beam irradiation at a dose of 50.4 Gy (standard fractionation; 1.8 Gy/d, 5 d/wk) or 30 Gy (rapid fractionation; 3 Gy/d, 5 d/wk) combined with continuous infusion 5-FU (300 mg/m2/d, 5 d/wk). Postoperative chemoradiation combined 50.4 Gy of external-beam irradiation (standard fractionation) with continuous-infusion 5-FU.  At a median followup of 19 months, no significant differences in survival were observed between treatment groups. No patient who received preoperative chemoradiation and pancreaticoduodenectomy experienced a local recurrence; peritoneal (regional) recurrence occurred in 10% of these patients. Local or regional recurrence occurred in 21% of patients who received pancreaticoduodenectomy and postoperative chemoradiation.