title: Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity.
abstract: OBJECTIVE
  Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy.
  
  
  METHODS
  Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria.
  
  
  RESULTS
  The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05).
  
  
  CONCLUSIONS
  It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. takimoto@showa.gunma-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Akimoto
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ito
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Saitoh
authors.forename: Shin-ei
authors.initials: SE
authors.lastname: Noda
authors.forename: Koichi
authors.initials: K
authors.lastname: Harashima
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Hideo
authors.initials: H
authors.lastname: Niibe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D014521:Urethra / Q000528:radiation effects*; D014555:Urination Disorders / Q000209:etiology*
chemical_list: D007496:Iridium Radioisotopes