title: Intensified intensity-modulated radiotherapy in anal cancer with prevalent HPV p16 positivity.
abstract: OBJECTIVE
  To investigate the toxicity and response of intensity-modulated radiotherapy schedule intensified with a simultaneous integrated boost in anal canal cancer.
  
  
  METHODS
  From March 2009 to March 2014, we retrospectively analyzed 41 consecutive patients treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for anal canal squamous cell carcinoma at our center. Radiotherapy was delivered via simultaneous integrated boost (SIB) technique by helical tomotherapy, and doses were adapted to two clinical target volumes according to the tumor-node-metastasis (TNM) stage: 50.6 Gy and 41.4 Gy in 23 fractions in T1N0, 52.8 Gy and 43.2 Gy in 24 fractions in T2N0, and 55 Gy and 45 Gy in 25 fractions in all patients with N positive and/or ≥ T3, respectively, to planning target volumes 1 and 2. The most common chemotherapy regimen was 5-fluorouracil and mitomycin-based. Human papilloma virus (HPV) p16 expression was performed by immunohistochemistry and evaluated in the majority of patients. Acute and late toxicity was scored according to CTCAe v 3.0 and RTOG scales.
  
  
  RESULTS
  The median follow-up was 30 mo (range: 12-71). Median age was 63 years (range 32-84). The stage of disease was: stage I in 2 patients, stage II in 13 patients, stage IIIA in 12 patients, and stage IIIB in 14 patients, respectively. Two patients were known to be HIV positive (4.9%). HPV p16 expression status was positive in 29/34 (85.3%) patients. The 4-year progression-free survival and overall survival in HPV-positive patients were 78% and 92%, respectively. Acute grade 3 skin and gastrointestinal toxicities were reported in 5% and 7.3% of patients, respectively; patients' compliance to the treatment was good due to a low occurrence of severe acute toxicity, although treatment interruptions due to toxicity were required in 7.3% of patients. At 6 mo from end of treatment, 36/40 (90%) patients obtained complete response; during follow-up, 5 (13.8%) patients presented with disease progression (local or systemic).
  
  
  CONCLUSIONS
  In our experience, intensified SIB-IMRT with chemotherapy is very feasible in clinical practice, with excellent results in terms of overall survival and local control.
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Belgioia
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vagge
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Agnese
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Garelli
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Murialdo
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fornarini
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Chiara
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gallo
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Almalina
authors.initials: A
authors.lastname: Bacigalupo
authors.affiliation: Liliana Belgioia, Stefano Vagge, Dario Agnese, Almalina Bacigalupo, Renzo Corvò, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Corvò
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000532:radiotherapy* / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000821:virology*; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000532:radiotherapy*; D011878:Radiotherapy; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016685:Mitomycin; D005472:Fluorouracil
keywords: Anal canal cancer; HPV; Helical tomotherapy; Intensity-modulated radiotherapy; Simultaneous integrated boost