Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: evidence from MRC RT01 Trial ISRCTN 47772397.
OBJECTIVE
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
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<or=80%, V40<or=65%, V50<or=55%, V60<or=40%, V65<or=30%, V70<or=15%, and V75<or=3%.


CONCLUSIONS
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.
Gulliford
Sarah L
SL
Joint Department of Physics, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, Sutton, United Kingdom.
Foo
Kerwyn
K
Morgan
Rachel C
RC
Aird
Edwin G
EG
Bidmead
A Margaret
AM
Critchley
Helen
H
Evans
Philip M
PM
Gianolini
Stefano
S
Mayles
W Philip
WP
Moore
A Rollo
AR
Sánchez-Nieto
Beatriz
B
Partridge
Mike
M
Sydes
Matthew R
MR
Webb
Steve
S
Dearnaley
David P
DP
D004307:Dose-Response Relationship, Radiation; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000150:complications / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D012002:Rectal Diseases / Q000209:etiology; D012007:Rectum / Q000473:pathology / Q000528:radiation effects*