doi:10.1016/j.ijrobp.2006.11.038 CLINICAL INVESTIGATION Anal Canal CONFORMAL THERAPY IMPROVES THE THERAPEUTIC INDEX OF PATIENTS WITH ANAL CANAL CANCER TREATED WITH COMBINED CHEMOTHERAPY AND EXTERNAL BEAM RADIOTHERAPY TÉ VUONG, M.D., F.R.C.P.C.,* NEIL KOPEK, M.D.,* THIERRY DUCRUET, M.SC., † LORRAINE PORTELANCE, M.D., F.R.C.P.C.,* SERGIO FARIA, M.D., PH.D.,* BORIS BAHORIC, M.D., F.R.C.P.C.,* AND SLOBODAN DEVIC,PH.D. ‡ Departments of *Radiation Oncology, † Statistics, and ‡ Medical Physics, McGill University Health Centre, Quebec, Canada Purpose: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. Methods and Materials: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45–58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. Results: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p  0.0056); the FFR rate was 70.2% and 46.1% (p  0.0166), and the OS rate was 80.7% and 53.9% (p  0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p  0.038), N status (p  0.011), and T status (p  0.012); and for FFR, 3D-CRT (p  0.024) and N status (p < 0.001). Conclusion: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS. © 2007 Elsevier Inc. Anal canal, 3D conformal therapy, Treatment-related toxicity, Treatment outcomes. INTRODUCTION In the era of advanced computerized tumor imaging and three-dimensional (3D) radiation treatment-planning sys- tems (1–3), 3D conformal radiotherapy (3D-CRT) was in- troduced in radiation institutions for better tumor identifi- cation and to protect organs at risk in individual patients. The dose to the target volume and normal tissues can be better defined, leading to reduced treatment morbidity. Three dimensional CRT has been extensively evaluated in the treatment of patients with prostate cancer (4–6), pedi- atric tumors (7, 8), brain tumors (7–11), and subsequently in other areas, such as Hodgkin’s lymphoma (12) and lung (13–15), head and neck (16, 17), gastric (18), and gyneco- logic tumors (19, 20). The concept was indeed appealing, leading to dose-escalation clinical trials (14, 16, 21) for improvement in tumor control. Combined chemotherapy and radiotherapy has been well established as the treatment for anal canal cancer (22–25). A variety of combined chemotherapy regimens and radiation techniques (external beam, interstitial implants) have been reported, with local control (LC) and survival rates equiv- alent to those reported for surgery. In addition, anal preser- vation has been possible in two third of patients (22–25). At present, rates of locoregional control have reached a thresh- old value for patients with advanced T 3–4 tumors. However, significant myelosuppression and severe skin toxicity have been observed with conventional external beam techniques and concurrent chemotherapy (26), leading to frequent treatment breaks, unique in a radical radiation regimen. Because overall treatment time has been suggested as an important factor in local tumor control (27–30), conformal therapy is definitely an avenue to explore. We have previ- ously reported preliminary acute toxicity results, technical Reprint requests to: Té Vuong, M.D., Montreal General Hospi- tal, 1650 Cedar Ave., Montreal, Québec H3G 1A4, Canada. Tel: (514) 934-8040; Fax: (514) 934-8392; E-mail: te.vuong@muhc. mcgill.ca Presented at the Annual Meeting of the American Society of Clinical Oncology, May 13–17, 2005, Orlando, FL. Conflict of interest: none. Acknowledgments—The authors thank Dr. Bernard Cummings for his comments and suggestions regarding revision of the manu- script. Received May 16, 2006 and in revised form Nov 2, 2006. Accepted for publication Nov 13, 2006. Int. J. Radiation Oncology Biol. Phys., Vol. 67, No. 5, pp. 1394 –1400, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter 1394