title: Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: analysis of dose and fractionation schedule.
abstract: OBJECTIVE
  To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer.
  
  
  METHODS
  Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy(10) (range: 48-76.8 Gy(10)) for early disease, and 76.8 Gy(10) (range: 38.4-86.4 Gy(10)) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy(3) (range: 59.1-134.4 Gy(3)) at the rectum, 97.8 Gy(3) (range: 54.6-130.4 Gy(3)) at the bladder, and 324 Gy(3) (range: 185.5-618 Gy(3)) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED.
  
  
  RESULTS
  The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose-response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade > or =1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis (p < 0.0001) and enterocolitis (p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy(10) at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013).
  
  
  CONCLUSIONS
  In view of the therapeutic ratio, cumulative BED 70-80 Gy(10) at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100-120 Gy(3) to prevent late rectal complication.
authors.affiliation: Department of Radiology, University of the Ryukyus School of Medicine, Okinawa, Japan. b983255@med.u-ryukyu.ac.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Toita
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kakinohana
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Genki
authors.initials: G
authors.lastname: Adachi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Moromizato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maehama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sakumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Kanazawa
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Murayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*