Prediction of the benefits from dose-escalated hypofractionated intensity-modulated radiotherapy for prostate cancer.
OBJECTIVE
To estimate the benefits of dose escalation in hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer, using radiobiologic modeling and incorporating positional uncertainties of organs.


METHODS
Biologically based mathematical models for describing the relationships between tumor control probability (TCP) and normal-tissue complication probability (NTCP) vs. dose were used to describe some of the results available in the literature. The values of the model parameters were then used together with the value of 1.5 Gy for the prostate cancer alpha/beta ratio to predict the responses in a hypofractionated 3 Gy/fraction IMRT trial at the Christie Hospital, taking into account patient movement characteristics between dose fractions.


RESULTS
Compared with the current three-dimensional conformal radiotherapy technique (total dose of 50 Gy to the planning target volume in 16 fractions), the use of IMRT to escalate the dose to the prostate was predicted to increase the TCP by 5%, 16%, and 22% for the three dose levels, respectively, of 54, 57, and 60 Gy delivered using 3 Gy per fraction while keeping the late rectal complications (>/=Grade 2 RTOG scale) at about the same level of 5%. Further increases in TCP could be achieved by reducing the uncertainty in daily target position, especially for the last stage of the trial, where up to 6% further increase in TCP should be gained.


CONCLUSIONS
Dose escalation to the prostate using IMRT to deliver daily doses of 3 Gy was predicted to significantly increase tumor control without increasing late rectal complications, and currently this prediction is being tested in a clinical trial.
Amer
Ali M
AM
North Western Medical Physics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, England, Manchester, UK. ali.amer@physics.cr.man.ac.uk
Mott
Judith
J
Mackay
Ranald I
RI
Williams
Peter C
PC
Livsey
Jacqueline
J
Logue
John P
JP
Hendry
Jolyon H
JH
D000230:Adenocarcinoma / Q000532:radiotherapy*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008962:Models, Theoretical; D009038:Motion; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D012007:Rectum / Q000293:injuries / Q000528:radiation effects; D016896:Treatment Outcome