title: Prospective multi-institutional study of definitive radiotherapy with high-dose-rate intracavitary brachytherapy in patients with nonbulky (<4-cm) stage I and II uterine cervical cancer (JAROG0401/JROSG04-2).
abstract: OBJECTIVE
  To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study.
  
  
  METHODS
  Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy(10) (α/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review.
  
  
  RESULTS
  Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥ 1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade ≥ 3 cases were observed for genitourinary/gastrointestinal late complications.
  
  
  CONCLUSIONS
  These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy(10) at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer.
authors.affiliation: Department of Radiology, Graduate School of Medical Science, University of Ryukyus, Okinawa, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Toita
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Niibe
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kazumoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kodaira
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kataoka
authors.forename: Naoto
authors.initials: N
authors.lastname: Shikama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kenjo
authors.forename: Sunao
authors.initials: S
authors.lastname: Tokumaru
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamauchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Suzuki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Hodaka
authors.initials: H
authors.lastname: Numasaki
authors.forename: Teruki
authors.initials: T
authors.lastname: Teshima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Oguchi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kagami
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Norio
authors.initials: N
authors.lastname: Mitsuhashi
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011446:Prospective Studies; D012007:Rectum / Q000528:radiation effects; D012062:Relative Biological Effectiveness; D047368:Tumor Burden; D001743:Urinary Bladder / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D055815:Young Adult