doi:10.1016/j.ijrobp.2005.02.030 CLINICAL INVESTIGATION Anus INTENSITY-MODULATED RADIATION THERAPY (IMRT) IN THE TREATMENT OF ANAL CANCER: TOXICITY AND CLINICAL OUTCOME MICHAEL T. MILANO, M.D., PH.D.,* ASHESH B. JANI, M.D.,* KARL J. FARREY, M.S.,* CARLA RASH, C.M.D.,* RUTH HEIMANN, M.D., PH.D., † AND STEVEN J. CHMURA, M.D., PH.D.* *Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL; † Division of Radiation Oncology, University of Vermont, Burlington, VT Purpose: To assess survival, local control, and toxicity of intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the anal canal. Methods and Materials: Seventeen patients were treated with nine-field IMRT plans. Thirteen received concurrent 5-fluorouracil and mitomycin C, whereas 1 patient received 5-fluorouracil alone. Seven patients were planned with three-dimensional anteroposterior/posterior-anterior (AP/PA) fields for dosimetric comparison to IMRT. Results: Compared with AP/PA, IMRT reduced the mean and threshold doses to small bowel, bladder, and genitalia. Treatment was well tolerated, with no Grade >3 acute nonhematologic toxicity. There were no treatment breaks attributable to gastrointestinal or skin toxicity. Of patients who received mitomycin C, 38% experienced Grade 4 hematologic toxicity. IMRT did not afford bone marrow sparing, possibly resulting from the clinical decision to prescribe 45 Gy to the whole pelvis in most patients, vs. the Radiation Therapy Oncology Group–recommended 30.6 Gy whole pelvic dose. Three of 17 patients, who did not achieve a complete response, proceeded to an abdominoperineal resection and colostomy. At a median follow-up of 20.3 months, there were no other local failures. Two-year overall survival, disease-free survival, and colostomy-free survival are: 91%, 65%, and 82% respectively. Conclusions: In this hypothesis-generating analysis, the acute toxicity and clinical outcome with IMRT in the treatment of anal cancer is encouraging. Compared with historical controls, local control is not compromised despite efforts to increase conformality and reduce normal structure dose. © 2005 Elsevier Inc. Anal cancer, Chemoradiation, Intensity-modulated radiation therapy. INTRODUCTION The standard of care for carcinoma of the anal canal has been evolving over the past 30 years from abdominoperi- neal resection, resulting in subsequent lifelong colostomy, to organ preservation therapy employing combined chemo- therapy and radiation. Although chemoradiotherapy results in 70% colostomy-free survival rates, acute and late mor- bidity remain substantial. Acute toxicities, including proc- titis, dysuria, dermatitis (especially in perineal structures), coupled to reported long-term sequelae of perineal skin atrophy, fibrosis, dyspareunia, and impotence, has prompted investigations into alternatives to both the chemotherapeutic regimen and radiation delivery techniques. Intensity-modulated radiation therapy (IMRT) is an emerging technology that allows delivery of radiation dose in a more conformal manner than conventional two- or three-dimensional radiation therapy by varying the radiation beams spatially or temporally (1). The physician contours targets to treat and regions to avoid on axial computed tomography (CT) slices. In contrast to conventional radio- therapy, IMRT uses inverse planning, with the field modu- lation optimized by planning software. To our knowledge, there are no other published series on the use of IMRT in anal cancer. At the University of Chicago, IMRT was im- plemented in 1998, and results have been published in gynecologic (2–6), prostate (7–9), advanced head-and-neck (10), and pancreatic and bile duct (11) malignancies. Anal cancer is well suited for IMRT because avoidance structures such as small bowel, bladder, genitalia, and bone marrow can potentially be spared. Normal tissue tolerance doses form the basis for IMRT dose–volume constraints, though concurrent chemotherapy likely lowers the threshold doses. The present article details our single institution ex- perience of 17 patients with squamous cell cancer of the anal canal treated with IMRT. We hypothesized that IMRT would minimize acute and late toxicity by virtue of sparing Reprint requests to: Steven Chmura, M.D., Ph.D., University of Chicago, Department of Cellular and Radiation Oncology, 5841 S. Maryland Ave., MC 9006, Chicago, IL 60637; Tel: (773) 702-5976; Fax: (773) 834-7340; E-mail: schmura@radonc.uchicago.edu. The dosimetric comparison of IMRT to AP/PA was presented at the 2002 American Society of Clinical Oncology meeting, whereas the clinical outcome in treated patients was initially reported at the 2003 American Society of Clinical Oncology meeting. Received Nov 29, 2004, and in revised form Jan 20, 2005. Accepted for publication Feb 1, 2005. Int. J. Radiation Oncology Biol. Phys., Vol. 63, No. 2, pp. 354 –361, 2005 Copyright © 2005 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/05/$–see front matter 354