Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2015; 21(37): 10688-10696
Published online Oct 7, 2015. doi: 10.3748/wjg.v21.i37.10688
Intensified intensity-modulated radiotherapy in anal cancer with prevalent HPV p16 positivity
Liliana Belgioia, Stefano Vagge, Dario Agnese, Stefania Garelli, Roberto Murialdo, Giuseppe Fornarini, Silvana Chiara, Fabio Gallo, Almalina Bacigalupo, Renzo Corvò
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
Stefania Garelli, Department of Medical Physics, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy
Roberto Murialdo, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
Giuseppe Fornarini, Silvana Chiara, Department of Medical Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy
Fabio Gallo, Section of Biostatistics, Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Author contributions: Belgioia L, Agnese D and Bacigalupo A performed the literature search and wrote the manuscript; Vagge S, Garelli S, Murialdo R, Fornarini G, Chiara S and Corvò R participated in drafting the paper and performing critical revision for important intellectual content; Vagge S and Gallo F performed the statistical analysis.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no actual or potential conflicts of interest to declare.
Data sharing statement: No additional data is available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Liliana Belgioia, MD, University Research, Department of Radiation Oncology, AOU IRCCS San Martino - IST National Cancer Research Institute and University, 16132 Genoa, Italy. liliana.belgioia@unige.it
Telephone: +39-328-4833384 Fax: +39-010-5556393
Received: March 2, 2015
Peer-review started: March 4, 2015
First decision: April 24, 2015
Revised: May 12, 2015
Accepted: July 18, 2015
Article in press: July 18, 2015
Published online: October 7, 2015
Abstract

AIM: 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).

CONCLUSION: 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.

Keywords: Anal canal cancer, Intensity-modulated radiotherapy, Simultaneous integrated boost, Helical tomotherapy, HPV

Core tip: This study evaluated intensity-modulated radiotherapy with simultaneous integrated boost in anal canal cancer of prevalent Human papilloma virus (HPV)-positive patients. The results show excellent outcomes in HPV-positive tumors, and suggest that an intensified radiotherapy schedule associated with chemotherapy is safe and allows the obtaining of oncologic results comparable to the standard schedule without an increase in acute toxicity.