doi:10.1016/j.ijrobp.2005.07.969 CLINICAL INVESTIGATION Rectum PREOPERATIVE CHEMORADIATION OF LOCALLY ADVANCED T3 RECTAL CANCER COMBINED WITH AN ENDORECTAL BOOST ANDERS JAKOBSEN, D.M.SC., JOHN P. MORTENSEN, M.D., CLAUS BISGAARD, M.D., JAN LINDEBJERG, M.D., JOHNNY W. HANSEN, M.SC., PH.D., AND SØREN R. RAFAELSEN, M.D. Danish Colorectal Cancer Group South, University of Southern Denmark, Vejle Hospital, Vejle, Denmark Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. Methods and Materials: The study included 50 patients with rectal adenocarcinoma. All patients had T3 tumor with a circumferential margin 0 –5 mm on a magnetic resonance imaging scan. The radiotherapy was delivered by a technique including two planning target volumes. Clinical target volume 1 (CTV1) received 60 Gy/30 fractions, and CTV2 received 48.6 Gy/27 fractions. The tumor dose was raised to 65 Gy with endorectal brachytherapy 5 Gy/1 fraction to the tumor bed. On treatment days, the patients received uracil and tegafur 300 mg/m2 concurrently with radiotherapy. Results: Forty-eight patients underwent operation. Histopathologic tumor regression was assessed by the Tumor Regression Grade (TRG) system. TRG1 was recorded in 27% of the patients, and a further 27% were classified as TRG2. TRG3 was found in 40%, and 6% had TRG4. The toxicity was low. Conclusion: The results indicate that high-dose radiation with concurrent chemotherapy and endorectal brachy- therapy is feasible with a high rate of complete response, but further trials are needed to define its possible role as treatment option. © 2006 Elsevier Inc. Rectal adenocarcinoma, Brachytherapy, Concurrent radiation. INTRODUCTION Preoperative radiation of rectal cancer reduces the risk of local recurrence, and it seems advantageous compared with postop- erative radiation, as shown in a recent randomized trial indi- cating improved local control and reduced toxicity in patients receiving preoperative radiotherapy vs. postoperative treatment (1). The risk of local recurrence is reduced by approximately 50% in patients receiving a biologic effective dose of 30 Gy (2), but the overall survival is improved only by approximately 4%. Furthermore, radiation has early as well as late side effects, and preoperative radiation should therefore be reserved for the group of patients with primary inoperable tumors or high risk of recurrence after radical surgery. The current literature indicates that preoperative radiation of inoperable T4 tumors renders the major part of the patients operable, and the combination of irradiation with concurrent chemotherapy seems to improve the effect (3). Patients with T3 tumors and close circumferential margin have a high risk of local recurrence (4), and a short course of preoperative che- motherapy does not reduce the risk significantly (5). This category of patients is likely to benefit from preoperative chemoradiation, but reliable preoperative selection criteria are necessary. At present, magnetic resonance imaging (MRI) appears to be the best method. A comparative study (6) has shown a close correlation between the circumferential margin on the MRI scan and the one measured by conventional his- topathologic examination. The optimal dose of preoperative radiation remains to be elucidated. There are a few studies suggesting a clear dose– effect relationship. Ahmad et al. (7) found a decrease in local failure rate from 20% to 8% by increasing the dose from 45 Gy to 55 Gy, and Fortier et al. (8) demonstrated decrease from 33% with 40 Gy to 9% with 50 Gy (7). A new randomized trial (9) investigating the effect of contact X-ray in combination with external radiation showed a rate of complete clinical response of 24% in the group receiving the combination of external radiation and contact X-ray vs. 2% in the group receiving external radiation only. There was no significant difference in toxicity between the two arms. The objective of the present study was to investigate the effect and feasibility of chemoradiation combined with endo- rectal brachytherapy in advanced T3 rectal tumors with com- plete pathologic remission (CPR) as the primary end point. METHODS AND MATERIALS The study enrolled 50 patients. Pretreatment evaluation included a complete history and physical examination, sigmoidoscopy or colonoscopy with biopsy, MRI scan, and transrectal ultrasound. The classification into T category was based on both MRI and Reprint requests to: Anders Jakobsen, D.M.Sc., Department of Oncology, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Den- mark. Tel: (+45) 7940-6010; Fax: (+45) 7940-6907; E-mail: andjac@vgs.vejleamt.dk Received June 17, 2005, and in revised form July 21, 2005. Accepted for publication July 25, 2005. Int. J. Radiation Oncology Biol. Phys., Vol. 64, No. 2, pp. 461– 465, 2006 Copyright © 2006 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/06/$–see front matter 461