Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer

Williams, Scott G., Taylor, Jeremy M. G., Liu, Ning, Tra, Yolande, Duchesne, Gillian M., Kestin, Larry L., Martinez, Alvaro, Pratt, Gary R. and Sandler, Howard (2007) Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer. International Journal of Radiation:Oncology-Biology-Physics, 68 1: 24-33. doi:10.1016/j.ijrobp.2006.12.036


Author Williams, Scott G.
Taylor, Jeremy M. G.
Liu, Ning
Tra, Yolande
Duchesne, Gillian M.
Kestin, Larry L.
Martinez, Alvaro
Pratt, Gary R.
Sandler, Howard
Title Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer
Journal name International Journal of Radiation:Oncology-Biology-Physics   Check publisher's open access policy
ISSN 0360-3016
1879-355X
Publication date 2007-01-01
Sub-type Article (original research)
DOI 10.1016/j.ijrobp.2006.12.036
Volume 68
Issue 1
Start page 24
End page 33
Total pages 10
Editor J. D. Cox
Place of publication New York, U.S.A.
Publisher Elsever
Collection year 2008
Language eng
Subject 321023 Radiotherapy and Nuclear Medicine
730108 Cancer and related disorders
C1
Formatted 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 α/β ratios were estimated via a proportional hazards model stratified by risk severity and institution.

Results


The α/β ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, ∞ 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; α/β 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 α/β 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.

Keyword Dose Fractionation
Humans
Male
*Neoplasm Recurrence, Local/blood
Proportional Hazards Models
Prostate-Specific Antigen/blood
Prostatic Neoplasms/blood/*radiotherapy
Radiobiology
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Mon, 03 Mar 2008, 21:31:37 EST