A Phase II trial of arc-based hypofractionated intensity-modulated radiotherapy in localized prostate cancer.
OBJECTIVE
To evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image-guided (fiducial markers or ultrasound guidance), simplified intensity-modulated arc therapy for localized prostate cancer.


METHODS
This Phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2 Gy in 20 fractions over 4 weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.


RESULTS
Median follow-up was 36 months. Acute Phase Grade 2 and 3 toxicity was 34% and 9% for GU vs. 25% and 10% for GI symptoms. One Grade 4 acute GI toxicity occurred in a patient with unrecognized Crohn's disease. Late Grade 2 and 3 toxicity for GU was 14% and 5%, and GI toxicity was 25% and 3%. One late GI Grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity ≥ Grade 2 was shown to be a predictor for late toxicity Grade ≥ 2 (p < 0.001). The biochemical disease-free survival at 3 years was 95%.


CONCLUSIONS
Hypofractionated simplified intensity-modulated arc therapy radiotherapy given as 63.2 Gy in 20 fractions demonstrated promising biochemical control rates; however, higher rates of acute Grade 3 GU and GI toxicity and higher late Grade 2 GU and GI toxicity were noted. Ongoing randomized controlled trials should ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy.
Lock
Michael
M
Department of Oncology, University of Western Ontario and London Regional Cancer Program, London Health Sciences Centre, London, ON, Canada.
Best
Lara
L
Wong
Eugene
E
Bauman
Glenn
G
D'Souza
David
D
Venkatesan
Varagur
V
Sexton
Tracy
T
Ahmad
Belal
B
Izawa
Jonathan
J
Rodrigues
George
G
D000368:Aged; D000369:Aged, 80 and over; D001003:Anal Canal / Q000000981:diagnostic imaging / Q000528:radiation effects; D003967:Diarrhea / Q000209:etiology; D019583:Dose Fractionation, Radiation; D057918:Fiducial Markers; D005500:Follow-Up Studies; D006046:Gold; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011467:Prostate / Q000000981:diagnostic imaging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012007:Rectum / Q000000981:diagnostic imaging / Q000528:radiation effects; D012669:Seminal Vesicles / Q000000981:diagnostic imaging / Q000528:radiation effects; D047368:Tumor Burden; D018084:Ultrasonography, Interventional / Q000379:methods; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000528:radiation effects; D014555:Urination Disorders / Q000209:etiology
D006046:Gold; D017430:Prostate-Specific Antigen