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Title: Use of Individual Fraction Size Data from 3756 Patients to Directly Determine the {alpha}/{beta} Ratio of Prostate Cancer

Abstract

Purpose: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. Methods and Materials: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The {alpha}/{beta} ratios were estimated via a proportional hazards model stratified by risk severity and institution. Results: The {alpha}/{beta} ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, {infinity} Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; {alpha}/{beta} ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up maturedmore » (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. Conclusions: This study supports the concept that the {alpha}/{beta} ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.« less

Authors:
 [1];  [2];  [3];  [2];  [4];  [5];  [6];  [6];  [7];  [8]
  1. Division of Radiation Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria (Australia). E-mail: scott.williams@petermac.org
  2. Department of Biostatistics, University of Michigan, Ann Arbor, MI (United States)
  3. (United States)
  4. Department of Mathematics and Statistics, Rochester Institute of Technology, Rochester, NY (United States)
  5. Division of Radiation Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria (Australia)
  6. Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)
  7. Division of Radiation Oncology, Royal Brisbane Hospital, Brisbane, Queensland (Australia)
  8. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States)
Publication Date:
OSTI Identifier:
20951611
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.12.036; PII: S0360-3016(06)03670-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ACCURACY; BETA RATIO; BRACHYTHERAPY; CARCINOMAS; CORRECTIONS; DOSE RATES; FAILURES; HAZARDS; PATIENTS; PROSTATE; RADIATION DOSES; RADIOBIOLOGY

Citation Formats

Williams, Scott G., Taylor, Jeremy M.G., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, Liu Ning, Tra, Yolande, Duchesne, Gillian M., Kestin, Larry L., Martinez, Alvaro, Pratt, Gary R., and Sandler, Howard. Use of Individual Fraction Size Data from 3756 Patients to Directly Determine the {alpha}/{beta} Ratio of Prostate Cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.036.
Williams, Scott G., Taylor, Jeremy M.G., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, Liu Ning, Tra, Yolande, Duchesne, Gillian M., Kestin, Larry L., Martinez, Alvaro, Pratt, Gary R., & Sandler, Howard. Use of Individual Fraction Size Data from 3756 Patients to Directly Determine the {alpha}/{beta} Ratio of Prostate Cancer. United States. doi:10.1016/j.ijrobp.2006.12.036.
Williams, Scott G., Taylor, Jeremy M.G., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, Liu Ning, Tra, Yolande, Duchesne, Gillian M., Kestin, Larry L., Martinez, Alvaro, Pratt, Gary R., and Sandler, Howard. Tue . "Use of Individual Fraction Size Data from 3756 Patients to Directly Determine the {alpha}/{beta} Ratio of Prostate Cancer". United States. doi:10.1016/j.ijrobp.2006.12.036.
@article{osti_20951611,
title = {Use of Individual Fraction Size Data from 3756 Patients to Directly Determine the {alpha}/{beta} Ratio of Prostate Cancer},
author = {Williams, Scott G. and Taylor, Jeremy M.G. and Department of Radiation Oncology, University of Michigan, Ann Arbor, MI and Liu Ning and Tra, Yolande and Duchesne, Gillian M. and Kestin, Larry L. and Martinez, Alvaro and Pratt, Gary R. and Sandler, Howard},
abstractNote = {Purpose: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. Methods and Materials: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The {alpha}/{beta} ratios were estimated via a proportional hazards model stratified by risk severity and institution. Results: The {alpha}/{beta} ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, {infinity} Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; {alpha}/{beta} ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. Conclusions: This study supports the concept that the {alpha}/{beta} ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.},
doi = {10.1016/j.ijrobp.2006.12.036},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 68,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}