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*, Kathryn A. Winter, William F. Regine, Howard Safran, John P. Hoffman, Robert Lustig, Andre A. Konski, Al B Benson III, John S. MacDonald, Tyvin A. Rich, Christopher G. Willett

*Corresponding author for this work

Research output: Contribution to journalArticle

136 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)809-816
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume82
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Adjuvant Chemoradiotherapy
gemcitabine
pancreas
chemotherapy
Adjuvant Chemotherapy
Pancreas
radiation therapy
Adenocarcinoma
Radiotherapy
Guidelines
Survival
Fluorouracil
toxicity
tumors
scoring
trends
Neoplasms
Radiation Oncology
Therapeutics
set theory

Keywords

  • Adjuvant therapy
  • Chemoradiotherapy
  • Pancreatic adenocarcinoma
  • Quality assurance
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Abrams, Ross A. ; Winter, Kathryn A. ; Regine, William F. ; Safran, Howard ; Hoffman, John P. ; Lustig, Robert ; Konski, Andre A. ; Benson III, Al B ; MacDonald, John S. ; Rich, Tyvin A. ; Willett, Christopher G. / 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. In: International Journal of Radiation Oncology Biology Physics. 2012 ; Vol. 82, No. 2. pp. 809-816.
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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.",
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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. / Abrams, Ross A.; Winter, Kathryn A.; Regine, William F.; Safran, Howard; Hoffman, John P.; Lustig, Robert; Konski, Andre A.; Benson III, Al B; MacDonald, John S.; Rich, Tyvin A.; Willett, Christopher G.

In: International Journal of Radiation Oncology Biology Physics, Vol. 82, No. 2, 01.02.2012, p. 809-816.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Abrams, Ross A.

AU - Winter, Kathryn A.

AU - Regine, William F.

AU - Safran, Howard

AU - Hoffman, John P.

AU - Lustig, Robert

AU - Konski, Andre A.

AU - Benson III, Al B

AU - MacDonald, John S.

AU - Rich, Tyvin A.

AU - Willett, Christopher G.

PY - 2012/2/1

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N2 - 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.

AB - 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.

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