title: Intensity-modulated radiation therapy with simultaneous integrated boost combined with concurrent chemotherapy for the treatment of anal cancer patients: 4-year results of a consecutive case series.
abstract: OBJECTIVE
  To report the 4-year outcomes of a consecutive series of anal cancer patients treated with concurrent chemo-radiation delivered with intensity-modulated radiotherapy (IMRT), employing a simultaneous integrated boost (SIB) approach.
  
  
  METHODS
  A consecutive series of 54 patients was enrolled between 2007 and 2013. Treatment schedule consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to the gross tumor volume, while the elective nodal volumes were prescribed 42 Gy/28 fractions (1.5 Gy/daily) for patients having a cT2N0 disease. Patients with cT3-T4/N0-N3 tumors were prescribed 54 (T3) or 60 (T4) Gy/30 fractions (1.8-2 Gy daily) to the gross tumor volume; gross nodal volumes were prescribed 50.4 Gy/30 fr (1.68 Gy daily) if sized ≤ 3 cm or 54 Gy/30 fr (1.8 Gy daily) if > 3 cm; elective nodal regions were given 45 Gy/30 fractions (1.5 Gy daily). Chemotherapy was administered concurrently according to the Nigro's regimen. Primary endpoint was colostomy-free survival (CFS). Secondary endpoints were local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and toxicity profile.
  
  
  RESULTS
  Median follow up was 32.6 months (range 12-84). The actuarial probability of being alive at 4 years without a colostomy (CFS) was 68.9% (95% CI: 50.3%-84.7%). Actuarial 4-year OS, CSS, DFS, and LC were 77.7% (95% CI: 60.7-88.1%), 81.5% (95% CI: 64%-91%), 65.5% (95% CI: 47.7%-78.5%), and 84.6% (95% CI: 71.6%-92%). Actuarial 4-year metastasis-free survival was 74.4% (95% CI: 55.5%-86.2%). Maximum detected acute toxicities were as follows: dermatologic -G3: 13%; GI-G3: 8%; GU-G3: 2%; anemia-G3: 2%; neutropenia-G3:11%; G4: 2%; thrombocytopenia- G3:2%. Four-year G2 chronic toxicity rates were 2.5% (95% CI: 3.6-16.4) for GU, 14.4% (95% CI: 7.1-28) for GI, 3.9% (95% CI: 1%-14.5%) for skin, and 4.2% (95% CI: 1.1-15.9) for genitalia.
  
  
  CONCLUSIONS
  Our study shows the feasibility of IMRT in the combined modality treatment of anal cancer, with comparable results to the literature with respect to LC, sphincter preservation and survival. Acute toxicity is lower if compared to series employing standard techniques. Our results support the use of IMRT on a routine basis for the treatment of anal cancer.
authors.affiliation: Department of Oncology, Radiation Oncology 1.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Franco
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mistrangelo
authors.forename: Francesca
authors.initials: F
authors.lastname: Arcadipane
authors.forename: Fernando
authors.initials: F
authors.lastname: Munoz
authors.forename: Piera
authors.initials: P
authors.lastname: Sciacero
authors.forename: Rosella
authors.initials: R
authors.lastname: Spadi
authors.forename: Fernanda
authors.initials: F
authors.lastname: Migliaccio
authors.forename: Veronica
authors.initials: V
authors.lastname: Angelini
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Bombaci
authors.forename: Nadia
authors.initials: N
authors.lastname: Rondi
authors.forename: Gianmauro
authors.initials: G
authors.lastname: Numico
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ragona
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.forename: Mario
authors.initials: M
authors.lastname: Morino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Racca
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000379:methods*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016016:Proportional Hazards Models; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012673:Semustine / Q000008:administration & dosage
chemical_list: D012673:Semustine; D003520:Cyclophosphamide; D008558:Melphalan; D005472:Fluorouracil
keywords: Acute toxicity; Anal cancer; Concomitant radiochemotherapy; IMRT; Late toxicity; Radiation; Radiotherapy