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Clinical Trial
. 2012 Feb 1;82(2):809-16.
doi: 10.1016/j.ijrobp.2010.11.039. Epub 2011 Feb 1.

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

Ross A Abrams  1 , Kathryn A Winter, William F Regine, Howard Safran, John P Hoffman, Robert Lustig, Andre A Konski, Al B Benson, John S Macdonald, Tyvin A Rich, Christopher G Willett
Affiliations
Clinical Trial

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

Ross A Abrams et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: In Radiation Therapy Oncology Group 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 after therapy but before 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 nonhematologic toxicity (p = 0.065).

Conclusions: This is the first Phase III, multicenter, 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 nonhematologic toxicity.

Trial registration: ClinicalTrials.gov NCT00003216.

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Figures

Figure 1A
Figure 1A
Treatment Schema For RTOG Protocol 9704
Figure 1B
Figure 1B
Consort Diagram
Figure 2
Figure 2
Survival Results 2A. Survival Results By Randomization Between Treatment Arms. There is no significant difference in survival between the two treatment arms. Median Survivals: 5FU arm = 1.43 years; gemcitabine arm =1.55 years (p=0.51) 2B. Survival Results By Radiotherapy Quality (RTQA) Score as Per Protocol (PP) or less than Per Protocol (Head of Pancreas Patients By Treatment Arm. There is a trend towards improved survival (p=0.12) favoring the gemcitabine arm for head of pancreas patients. (median survivals: 5FU arm=1.43 years, gemcitabine arm=1.71 years). 2D. Survival Results For Head of Pancreas Patients By RTQA Score. Patients with RTQA score of PP had significantly better survival; 1.74 years vs.1.48 years (p =0.026).
Figure 2
Figure 2
Survival Results 2A. Survival Results By Randomization Between Treatment Arms. There is no significant difference in survival between the two treatment arms. Median Survivals: 5FU arm = 1.43 years; gemcitabine arm =1.55 years (p=0.51) 2B. Survival Results By Radiotherapy Quality (RTQA) Score as Per Protocol (PP) or less than Per Protocol (Head of Pancreas Patients By Treatment Arm. There is a trend towards improved survival (p=0.12) favoring the gemcitabine arm for head of pancreas patients. (median survivals: 5FU arm=1.43 years, gemcitabine arm=1.71 years). 2D. Survival Results For Head of Pancreas Patients By RTQA Score. Patients with RTQA score of PP had significantly better survival; 1.74 years vs.1.48 years (p =0.026).
Figure 2
Figure 2
Survival Results 2A. Survival Results By Randomization Between Treatment Arms. There is no significant difference in survival between the two treatment arms. Median Survivals: 5FU arm = 1.43 years; gemcitabine arm =1.55 years (p=0.51) 2B. Survival Results By Radiotherapy Quality (RTQA) Score as Per Protocol (PP) or less than Per Protocol (Head of Pancreas Patients By Treatment Arm. There is a trend towards improved survival (p=0.12) favoring the gemcitabine arm for head of pancreas patients. (median survivals: 5FU arm=1.43 years, gemcitabine arm=1.71 years). 2D. Survival Results For Head of Pancreas Patients By RTQA Score. Patients with RTQA score of PP had significantly better survival; 1.74 years vs.1.48 years (p =0.026).
Figure 2
Figure 2
Survival Results 2A. Survival Results By Randomization Between Treatment Arms. There is no significant difference in survival between the two treatment arms. Median Survivals: 5FU arm = 1.43 years; gemcitabine arm =1.55 years (p=0.51) 2B. Survival Results By Radiotherapy Quality (RTQA) Score as Per Protocol (PP) or less than Per Protocol (Head of Pancreas Patients By Treatment Arm. There is a trend towards improved survival (p=0.12) favoring the gemcitabine arm for head of pancreas patients. (median survivals: 5FU arm=1.43 years, gemcitabine arm=1.71 years). 2D. Survival Results For Head of Pancreas Patients By RTQA Score. Patients with RTQA score of PP had significantly better survival; 1.74 years vs.1.48 years (p =0.026).
Figure 3
Figure 3
Survival Results for head of pancreas patients by treatment when the results of factors significant in multivariate analysis are considered (RTQA Score and nodal involvement).
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