title: Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study.
abstract: OBJECTIVE
  The purpose of this prospective study was to investigate the toxicity and efficacy of integrating extended-field para-aortic and pelvic external radiation, high-dose-rate intracavity brachytherapy, and concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer.
  
  
  METHODS
  A phase I/II study was performed from 1998 to 2003 including sixty-three patients with both clinical FIGO and MRI/CT-based TNM stage IIB-IVA cervical cancer. Patients were treated with extended-field external radiation to the para-aortic and pelvic regions with 45 Gy in 25 fractions, and an additional boost to the gross nodes to 50.4 Gy and the parametrium to 59.4 Gy. Patients also received a high-dose-rate (HDR) intracavity brachytherapy with doses of 22-31 Gy to point A in 4-6 fractions. Concurrently, two cycles of cisplatin (50-80 mg/m(2)) were administered in weeks 1 and 5 during radiotherapy, as well as two cycles of cisplatin (60-80 mg/m(2)) for 1 day and 5-fluorouracil (600-800 mg/m(2)) for 4 days at 1 and 2 months after completion of radiotherapy. The treatment-related acute and late side effects were evaluated using RTOG criteria, and the disease control and survival rate were calculated using the Kaplan-Meier method. The median follow-up interval was 36 months.
  
  
  RESULTS
  All sixty-three patients completed the planned extended-field radiotherapy and high-dose-rate brachytherapy with 2 concurrent cycles of cisplatin. Fifty-eight (92%) patients received 2 cycles of the post-radiation adjuvant chemotherapy of cisplatin and 5-fluorouracil. RTOG grade III acute toxicity was gastrointestinal (2%) and hematological (10%). No patient had grade IV acute toxicity. Late grades III-IV morbidity actuarial risk of 6% at 6.5 years primarily involved the injuries to the bowels requiring surgical intervention for intestinal obstruction or fistula formation. Initial sites of recurrence were locoregional failure alone (pelvic and para-aortic regions within the radiation field), 3%; distant metastases only, 8%; and locoregional failure plus distant metastases, 8%. The observed rates at 3-year and 5-year of locoregional control, freedom from distant metastasis, and overall survival were 86% and 86%, 81% and 81%, and 81% and 77%, respectively.
  
  
  CONCLUSIONS
  Incorporating HDR brachytherapy into a regimen including concurrent chemotherapy and extended radiation appears safe and effective.
authors.affiliation: Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, No. 125, Lih-Der Road, Taipei 112, Taiwan. ylchung@mail.kfcc.org.tw
authors.forename: Yih-Lin
authors.initials: YL
authors.lastname: Chung
authors.forename: James Jer-Min
authors.initials: JJ
authors.lastname: Jian
authors.forename: Skye Hongiun
authors.initials: SH
authors.lastname: Cheng
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Hsieh
authors.forename: Tran-Der
authors.initials: TD
authors.lastname: Tan
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Chang
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Hung
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Horng
authors.forename: Thomas
authors.initials: T
authors.lastname: Soong
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Tsou
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D007496:Iridium Radioisotopes; D002945:Cisplatin