title: Concomitant boost plus large-field preoperative chemoradiation in locally advanced uterine cervix carcinoma: Phase II clinical trial final results (LARA-CC-1).
abstract: OBJECTIVE
  To report the Phase II study final results in terms of pathological complete response (pCR) and complications in locally advanced cervical carcinoma (LACC) patients treated with chemoradiation (CT/RT) regimen based on accelerated fractionation, nodal extended fields and adjuvant radical surgery.
  
  
  METHODS
  The sample size was quantified according to published data which shows that CT/RT followed by radical surgery in LACC patients provides a pCR rate above 45%. The 2-stage design by Simon was used to test the null hypothesis that the true pCR would improve by above 20%. The chemoradiation regimen was considered active if >24/43 pCRs were recorded. 40 Gy/2 Gy fraction in 4 weeks was delivered to nodal volume extending up to L3 vertebra, concurrently with chemotherapy. 45 Gy in 20 fractions with a concomitant boost strategy was delivered to the macroscopic disease only.
  
  
  RESULTS
  47 patients were enrolled. Median follow-up was 26 months (3-52 months). Pathological response was assessed in 44/47 patients: 17/44 (38.6%) showed a pCR to treatment, and 9/44 cases (20.5%) showed microscopic disease. Pelvic nodal metastases were documented in 9/44 cases (20.5%). 87.5% of recurrences were extra pelvic. Five patients (11%) developed acute severe gastrointestinal toxicity. The actuarial cumulative 2-year incidence of G ≥ 2 late cutaneous, gastrointestinal, and genitourinary toxicity was 10.3%, 8.3% and 24.9%, respectively. The 3-year DFS was 77.1%, while the 3-year OS was 80.5%.
  
  
  CONCLUSIONS
  Our results confirm the high tolerability and efficacy of this accelerated regimen. However, based on the study design, 45 Gy as a concomitant boost CT/RT delivered by a 3D technique does not seem sufficient to increase pCR rate.
authors.affiliation: Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy. gmacchia@rm.unicatt.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Savino
authors.initials: S
authors.lastname: Cilla
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lucidi
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaccesi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Numa
authors.initials: N
authors.lastname: Cellini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D002945:Cisplatin; D005472:Fluorouracil