title: Locally Advanced (T3-T4 or N+) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.
abstract: OBJECTIVE
  To report on clinical outcomes of a consecutive series of locally advanced (T3-T4N0-N3) anal cancer patients treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial.
  
  
  METHODS
  A cohort of 45 patients underwent SIB-IMRT employing a schedule consisting of 54 Gy/30 fractions to the macroscopic anal planning target volume (PTV), while clinical nodes were prescribed 50.4 Gy/30 fractions if sized ≤3 cm or 54 Gy/30 fractions if >3 cm. Elective nodal PTV was prescribed 45 Gy/30 fractions. Chemotherapy was administered concurrently following the Nigro regimen. Primary end-point was colostomy-free survival (CFS). Secondary end-points were locoregional control (LRC), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS).
  
  
  RESULTS
  Median follow-up was 39.7 months. The actuarial 3-year CFS was 63.4 % (95% confidence interval (CI=44.8-77.1%). Actuarial 3-year OS and CSS were 67.7% (95%CI=48.7-80.9%) and 72.9% (95%CI=53.8-85.1%), while DFS was 55.8% (95%CI=37.5.4-70.7%). Actuarial 3-year LRC was 74.1% (95%CI=56.7-85.4%). On multivariate analysis, male sex (hazard ratio (HR)=10.9; p=0.004; 95%CI=2.2-55.5%) had a significant impact on CFS, while higher clinical stage (Stage IIIB vs. others) had borderline significance (HR=2.7; p=0.062; 95%CI=1.8-5.9%). A shorter package time (HR=0.94; p=0.007; 95%CI=0.91-0.98%) predicted for higher CFS. Maximum detected events included: skin (G3): 13%; gastrointestinal (GI) (G3): 13%; genitourinary (GU) (G2): 38%; genitalia (G2): 45%; anemia (G2): 4%; leukopenia (G3): 24%, (G4):7%; neutropenia (G3): 16%; (G4): 11%; thrombocytopenia (G3): 9%, (G4): 2%.
  
  
  CONCLUSIONS
  Our clinical results support the use of SIB-IMRT in the combined modality treatment of locally advanced anal cancer patients.
authors.affiliation: Department of Oncology-Radiation Oncology, University of Turin, Turin, Italy pierfrancesco.franco@unito.it.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Franco
authors.affiliation: Department of Oncology-Radiation Oncology, University of Turin, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Arcadipane
authors.affiliation: Department of Oncology-Radiation Oncology, University of Turin, Turin, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ragona
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mistrangelo
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Department of Medical Imaging and Radiotherapy, Radiation Oncology, AOU Città della Salute e della Scienza, Turin, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rondi
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Morino
authors.affiliation: Oncological Centre for Gastrointestinal Neoplasm, Medical Oncology 1, AOU Città della Salute e della Scienza, Turin, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Racca
authors.affiliation: Department of Oncology-Radiation Oncology, University of Turin, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil
keywords: Anal cancer; IMRT; VMAT; acute toxicity; concomitant radiochemotherapy; radiation; radiotherapy; volumetric modulated arc-therapy