Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704—A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients With Resected Adenocarcinoma of the Pancreas

Abstract

Purpose In RTOG 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (<PP). Scoring occurred following therapy but prior to trial analysis and without knowledge of individual patient treatment outcomes. Scoring was done for all tumor locations and for the subset of pancreatic head location. Results RT was scored for 416 patients: 216 PP and 200 <PP. For all pancreatic sites (head, body/tail) median survival (MS) for PP vs. <PP was 1.74 vs. 1.46 years (log-rank p=0.0077). In multivariate analysis, PP vs. <PP score correlated more strongly with MS than assigned treatment arm (p=0.014, p=NS, respectively); for patients with pancreatic head tumors, both PP score and gemcitabine treatment correlated with improved MS (p=0.016, p=0.043, respectively). For all tumor locations PP score was associated with decreased risk of failure (p=0.016) and, for gemcitabine patients, a trend toward reduced grade 4/5 non-hematologic toxicity (p=0.065). Conclusions This is the first phase III, multi-center, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased non-hematologic toxicity.

Executive summary of AAPM Report Task Group 113: Guidance for the physics aspects of clinical trials

“…It has been shown that the quality and consistency of the trial impacts patient outcomes 1, 2, 3, 4, 5. This report identifies physics and other team member practices that specifically improve the treatment planning and delivery data for clinical trials.…”

“…The importance of compliance in trials and the impact on detecting changes in outcome have been demonstrated in a number of trials,1, 2, 3, 4, 6 such as TROG 02.02 on advanced head and neck cancer (Fig. 1), and in meta‐analyses of other trials.…”

“…There is growing evidence1, 2, 3, 4, 5 on the need for standardization of treatment planning and delivery methods to ensure quality in clinical trials to help support the investigation of new safe and effective treatments and/or assessment methods in multi‐institutional settings. Such standardization will improve the consistency of the radiotherapy received by patients and the radiotherapy data submitted for a given clinical trial.…”

The Controversial Role of Chemoradiation for Patients With Locally Advanced Pancreatic Cancer

“…This latter study did not include a review of patients who did not receive chemoradiation. Several small phase II trials have demonstrated survival of 9.6 -17 months with induction chemotherapy followed by radiation [10].…”

“…We must obtain data from an optimally designed, randomized phase III trial before using an across-the-board approach with potential toxicities and implications for systemic therapy in our treatment of patients with locally advanced pancreatic cancer. analysis based on quality assurance of radiation treatment fields [10].…”