Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer

W. Robert Lee, James J. Dignam, Mahul Amin, Deborah W. Bruner, Daniel Low, Gregory P. Swanson, Amit B. Shah, David P. D'Souza, Jeff M. Michalski, Ian S. Dayes, Samantha A. Seaward, William A. Hall, Paul L. Nguyen, Thomas M. Pisansky, Sergio L. Faria, Yuhchyau Chen, Bridget F. Koontz, Rebecca Paulus, Howard M. Sandler

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Abstract

Purpose: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). Results: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95%CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.

Original languageEnglish (US)
Pages (from-to)2325-2332
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number20
DOIs
StatePublished - Jul 10 2016

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Prostatic Neoplasms
Appointments and Schedules
Radiotherapy
Disease-Free Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. / Lee, W. Robert; Dignam, James J.; Amin, Mahul; Bruner, Deborah W.; Low, Daniel; Swanson, Gregory P.; Shah, Amit B.; D'Souza, David P.; Michalski, Jeff M.; Dayes, Ian S.; Seaward, Samantha A.; Hall, William A.; Nguyen, Paul L.; Pisansky, Thomas M.; Faria, Sergio L.; Chen, Yuhchyau; Koontz, Bridget F.; Paulus, Rebecca; Sandler, Howard M.

In: Journal of Clinical Oncology, Vol. 34, No. 20, 10.07.2016, p. 2325-2332.

Research output: Contribution to journalArticle

Lee, WR, Dignam, JJ, Amin, M, Bruner, DW, Low, D, Swanson, GP, Shah, AB, D'Souza, DP, Michalski, JM, Dayes, IS, Seaward, SA, Hall, WA, Nguyen, PL, Pisansky, TM, Faria, SL, Chen, Y, Koontz, BF, Paulus, R & Sandler, HM 2016, 'Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer', Journal of Clinical Oncology, vol. 34, no. 20, pp. 2325-2332. https://doi.org/10.1200/JCO.2016.67.0448
Lee, W. Robert ; Dignam, James J. ; Amin, Mahul ; Bruner, Deborah W. ; Low, Daniel ; Swanson, Gregory P. ; Shah, Amit B. ; D'Souza, David P. ; Michalski, Jeff M. ; Dayes, Ian S. ; Seaward, Samantha A. ; Hall, William A. ; Nguyen, Paul L. ; Pisansky, Thomas M. ; Faria, Sergio L. ; Chen, Yuhchyau ; Koontz, Bridget F. ; Paulus, Rebecca ; Sandler, Howard M. / Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 20. pp. 2325-2332.
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abstract = "Purpose: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90{\%} power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65{\%} (H-RT/C-RT hazard ratio [HR] < 1.52). Results: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3{\%} (95{\%} CI, 81.9 to 88.1) in the C-RT arm and 86.3{\%} (95{\%}CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95{\%} CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.",
author = "Lee, {W. Robert} and Dignam, {James J.} and Mahul Amin and Bruner, {Deborah W.} and Daniel Low and Swanson, {Gregory P.} and Shah, {Amit B.} and D'Souza, {David P.} and Michalski, {Jeff M.} and Dayes, {Ian S.} and Seaward, {Samantha A.} and Hall, {William A.} and Nguyen, {Paul L.} and Pisansky, {Thomas M.} and Faria, {Sergio L.} and Yuhchyau Chen and Koontz, {Bridget F.} and Rebecca Paulus and Sandler, {Howard M.}",
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T1 - Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer

AU - Lee, W. Robert

AU - Dignam, James J.

AU - Amin, Mahul

AU - Bruner, Deborah W.

AU - Low, Daniel

AU - Swanson, Gregory P.

AU - Shah, Amit B.

AU - D'Souza, David P.

AU - Michalski, Jeff M.

AU - Dayes, Ian S.

AU - Seaward, Samantha A.

AU - Hall, William A.

AU - Nguyen, Paul L.

AU - Pisansky, Thomas M.

AU - Faria, Sergio L.

AU - Chen, Yuhchyau

AU - Koontz, Bridget F.

AU - Paulus, Rebecca

AU - Sandler, Howard M.

PY - 2016/7/10

Y1 - 2016/7/10

N2 - Purpose: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). Results: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95%CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.

AB - Purpose: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). Results: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95%CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.

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