Dose–Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397
Received 15 October 2008; received in revised form 11 February 2009; accepted 11 February 2009. published online 19 June 2009.
Purpose
Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose–volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (≥50 Gy). Evidence is emerging that lower doses could also be important.
Methods and Materials
Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose–volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity.
Results
A statistically significant dose–volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30–70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose–volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose–volume constraints from the set of V30≤80%, V40≤65%, V50≤55%, V60≤40%, V65≤30%, V70≤15%, and V75≤3%.
Conclusion
Considering the entire dose distribution to the rectum by applying dose–volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.
#Department of Physics, Clatterbridge Centre for Oncology, Wirral, United Kingdom
∗∗Servicio de Radioterapia, Clinica Alemana de Santiago, Santiago, Chile
††Department of Academic Urology, Institute of Cancer Research and Royal Marsden Hospitals, Sutton, United Kingdom
Reprint requests to: Sarah L. Gulliford, Ph.D., Joint Department of Physics, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, Cotswold Rd., Sutton SM2 5NG United Kingdom. Tel: (+44) 208-661-3675; Fax: (+44) 208-643-3812
Note—An online CME test for this article can be taken at http://asro.astro.org under Continuing Education.
Supported and coordinated by the U.K. Medical Research Council, Institute of Cancer Research, and Cancer Research U.K. Section of Radiotherapy Grant C46/A2131.
Conflict of interest: M. Sydes and R. Morgan are employed by the trial sponsor (Medical Research Council United Kingdom).
ABSTRACT