doi:10.1016/j.ijrobp.2006.12.052 CLINICAL INVESTIGATION Anal Canal PREDICTORS AND PATTERNS OF RECURRENCE AFTER DEFINITIVE CHEMORADIATION FOR ANAL CANCER PRAJNAN DAS, M.D., M.S., M.P.H.,* SUMITA BHATIA, M.D.,* CATHY ENG, M.D., † JAFFER A. AJANI, M.D., † JOHN M. SKIBBER, M.D., ‡ MIGUEL A. RODRIGUEZ-BIGAS, M.D., ‡ GEORGE J. CHANG, M.D., ‡ PRIYA BHOSALE, M.D., § MARC E. DELCLOS, M.D.,* SUNIL KRISHNAN, M.D.,* NORA A. JANJAN, M.D., M.P.S.A.,* AND CHRISTOPHER H. CRANE, M.D.,* *Department of Radiation Oncology, † Department of Gastrointestinal Medical Oncology, ‡ Department of Surgical Oncology, and § Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX Purpose: To evaluate patterns of locoregional failure, and predictors of recurrence and survival in patients treated with chemoradiation for anal cancer. Methods and Materials: Between September 1992 and August 2004, 167 patients with nonmetastatic squamous cell anal carcinoma were treated with definitive chemoradiation. The median dose of radiotherapy was 5500 cGy. Concurrent chemotherapy was given with 5-fluorouracil and cisplatin in 117 patients, 5-fluorouracil and mitomycin C in 24 patients, and other regimens in 26 patients. Results: The estimated 3-year rates of locoregional control, distant control, disease-free survival, and overall survival were 81%, 88%, 67%, and 84%, respectively. Multivariate analysis showed that higher T stage and N stage independently predicted for a higher rate of locoregional failure; higher N stage and basaloid subtype independently predicted for a higher rate of distant metastasis; and higher N stage and positive human immunodeficiency virus status independently predicted for a lower rate of overall survival. Among the patients who had locoregional failure, 18 (75%) had failure involving the anus or rectum, 5 (21%) had other pelvic recurrences, and 1 (4%) had inguinal recurrence. The 5 pelvic recurrences all occurred in patients with the superior border of the radiotherapy field at the bottom of the sacroiliac joint. Conclusions: Trials of more aggressive and innovative locoregional and systemic therapies are warranted in high-risk patients, based on their T and N stages. The majority of locoregional failures involve the anus and rectum, whereas inguinal recurrences occur rarely. Placing the superior border of the radiotherapy field at L5/S1 could potentially reduce pelvic recurrences. © 2007 Elsevier Inc. Anal cancer, Chemoradiation, Radiation therapy, Recurrence, Predictive factors. INTRODUCTION Definitive chemoradiation serves as the standard of care for patients with locoregional squamous cell carcinoma of the anal canal. Nigro et al. first reported high rates of pathologic com- plete response with chemoradiation and demonstrated that definitive chemoradiation could act as a sphincter-sparing al- ternative to abdominoperineal resection for anal cancer (1). Subsequently, 2 randomized trials showed that chemoradiation improves local control compared with radiotherapy alone (2, 3). A randomized Intergroup trial also showed that chemora- diation with 5-fluorouracil (5-FU) and mitomycin C improved rates of disease-free survival and colostomy-free survival com- pared with chemoradiation with 5-FU (4). Although most patients treated with definitive chemora- diation for anal cancer have excellent outcomes, locore- gional and distant recurrences occur in some patients. In randomized multi-institutional trials on anal cancer, patients treated with definitive chemoradiation had locoregional fail- ure rates around 30%, with disease-free survival rates of 50%–70% (2–5). A better understanding of predictors and patterns of recurrence may help improve current treatments for these patients. Therefore, the goal of this study was to identify predictors of locoregional failure, distant metasta- sis, and overall survival and evaluate patterns of locore- gional failure in patients treated with definitive chemoradia- tion for anal cancer. Reprint requests to: Prajnan Das, M.D., M.S., M.P.H., Depart- ment of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 97, Houston, TX 77030. Tel: (713) 563-2300; Fax: (713) 563-2366; E-mail: PrajDas@mdanderson.org Acknowledgments—We thank Joan Zampieri, PA-C, for excellent assistance with data collection. Conflict of interest: none. Received Sept 13, 2006, and in revised form Dec 20, 2006. Accepted for publication Dec 22, 2006. Int. J. Radiation Oncology Biol. Phys., Vol. 68, No. 3, pp. 794 – 800, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter 794