title: Chemoradiation with concomitant boosts followed by radical surgery in locally advanced cervical cancer: long-term results of the ROMA-2 prospective phase 2 study.
abstract: OBJECTIVE
  This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer.
  
  
  METHODS
  Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m(2), days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m(2)/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1).
  
  
  RESULTS
  pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2.
  
  
  CONCLUSIONS
  Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity.
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy. Electronic address: gabriella.ferrandina@libero.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Division of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Gambacorta
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Gallotta
authors.affiliation: Division of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Smaniotto
authors.affiliation: Gynecologic Surgery, University of Perugia, Terni, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Fagotti
authors.affiliation: Division of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tagliaferri
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Foti
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fanfani
authors.affiliation: Division of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Autorino
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Division of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008875:Middle Aged; D010388:Pelvis; D011446:Prospective Studies; D020266:Radiotherapy, Conformal / Q000379:methods; D013534:Survival; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil