title: Reduction in acute morbidity using hypofractionated intensity-modulated radiation therapy assisted with a fluoroscopic real-time tumor-tracking system for prostate cancer: preliminary results of a phase I/II study.
abstract: OBJECTIVE
  The positioning of the prostate is improved with the use of the fluoroscopic real-time tumor-tracking radiation therapy system for prostate cancer. The acute radiation reaction and preliminary tumor response of prostate cancer to hypofractionated intensity-modulated radiation therapy assisted with real-time tumor-tracking radiation therapy were investigated in this study.
  
  
  METHODS
  Patients were classified into prognostic risk groups on the basis of the presence of the pretreatment prostate-specific antigen, clinical stage, and histologic differentiation. Neoadjuvant hormonal therapy was administered to patients in the high-risk group for 6 months before radiation therapy commenced. The intensity-modulated radiation therapy employed a segmental multileaf collimator, which generated a field made up of two or more shaped subfields using forward planning. Real-time tumor-tracking radiation therapy was used for the precise positioning of the prostate to minimize geometric uncertainties, while the dose was escalated in increments of 5 Gy from 65 Gy using a daily dose of 2.5 Gy (65 Gy/2.5 Gy), following the dose-escalation rules. Acute and late gastrointestinal and genitourinary morbidities due to radiation therapy were scored according to the toxicity criteria of Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer.
  
  
  RESULTS
  Thirty-one patients were enrolled in this study between 1998 and 2001. Eighteen patients were classified as being members of the high-risk group. Total dose was escalated, with 65 Gy/2.5 Gy being administered to 12 patients and 70 Gy/2.5 Gy to 19 patients. The median follow-up period was 37 months (range, 30-43 months), and 19 months (range, 10-27 months), for the 65-Gy and 70-Gy arms, respectively. Patients experienced no acute toxicity and grade 1 late gastrointestinal toxicity (8.3%) in the 65-Gy/2.5-Gy arm. Patients in the 70-Gy/2.5-Gy arm experienced grade 1 acute gastrointestinal toxicity (5.3%) and grade 1 and 2 acute genitourinarytoxicities (15.8%). No patients experienced dose-limiting toxicity (defined as a grade 3 or higher acute toxicity) or a grade 2 or higher late complication in this study period. One and two prostate-specific antigen relapses were observed in the 65-Gy and 70-Gy arms, respectively.
  
  
  CONCLUSIONS
  Up to 70 Gy/2.5 Gy, equivalent to 80 Gy with a daily dose of 2.0 Gy, assuming alpha/beta ratio of 1.5, intensity-modulated radiation therapy assisted with real-time tumor-tracking radiation therapy was administered safely with a reasonable biochemical control rate. A further dose-escalation study using this system is justifiable.
authors.affiliation: Department of Radiology, Hokkaido University School of Medicine, Sapporo, Japan. ktmr@radi.med.hokudai.ac.jp
authors.forename: Kei
authors.initials: K
authors.lastname: Kitamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.forename: Toru
authors.initials: T
authors.lastname: Harabayashi
authors.forename: Rikiya
authors.initials: R
authors.lastname: Onimaru
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Fujita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Koyanagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Miyasaka
mesh_terms: D000208:Acute Disease; D000230:Adenocarcinoma / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D003199:Computer Systems; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005471:Fluoroscopy; D005767:Gastrointestinal Diseases / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D052801:Male Urogenital Diseases / Q000453:epidemiology; D008875:Middle Aged; D009017:Morbidity; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology* / Q000209:etiology; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome