doi:10.1016/j.ijrobp.2003.10.025 CLINICAL INVESTIGATION Cervix CLINICAL COMPARISON OF TWO LINEAR-QUADRATIC MODEL-BASED ISOEFFECT FRACTIONATION SCHEMES OF HIGH-DOSE-RATE INTRACAVITARY BRACHYTHERAPY FOR CERVICAL CANCER CHONG-JONG WANG, M.D.,* ENG-YEN HUANG, M.D.,* LI-MIN SUN, M.D.,* HUI-CHUN CHEN, M.D.,* FU-MIN FANG, M.D.,* HSUAN-CHIH HSU, M.D.,* CHAN-CHAO CHANGCHIEN, M.D., † AND STEPHEN WAN LEUNG, M.S., M.D. ‡ Departments of *Radiation Oncology and † Gynecology Oncology, Kaohsiung Chang Gung Memorial Hospital; ‡ Department of Radiation Oncology, Yuan’s General Hospital, Kaohsiung, Taiwan Purpose: Two linear-quadratic model– based isoeffect fractionation schemes of high-dose-rate intracavitary brachytherapy (HDR-IC) were used to treat cervical cancer in two consecutive periods. Patient outcomes and complications were analyzed and compared. Methods and Materials: Between November 1987 and December 1996, a total of 541 women diagnosed with cervical cancer were treated with curative-intent radiotherapy. Patients were categorized into two groups according to the two isoeffect schemes used. Group 1 consisted of 254 patients treated with external beam radiotherapy (EBRT) plus 7.2 Gy HDR-IC to Point A for three fractions in the first period. Group 2 consisted of 284 patients treated with EBRT plus 4.8 Gy HDR-IC for five fractions in the second period. The goal of the new scheme for the latter group was to deliver an isoeffect dose that maintained similar tumor control but reduced normal tissue complications. The calculated biologically effective dose (BED 10 , assuming an / ratio  10) of EBRT plus HDR-IC for tumor and acute responding tissue in Groups 1 and 2 was 90 Gy 10 (52.8  37.2 Gy) and 88.6 Gy 10 (53.1  35.5 Gy), respectively. The corresponding BED 3 for late responding tissue (assuming an / ratio  3) in Groups 1 and 2 was 146.7 Gy 3 (73.3  73.4 Gy) and 134.4 Gy 3 (72  62.4 Gy), respectively. Patients were followed for 6.1–15.2 years (median, 9.8 years). Results: Overall, 66 patients (12.2%) developed pelvic recurrence. Of these, 53 patients had central recurrence. Of the 53 patients with central recurrence, 24 (9.4%) were in Group 1 and 29 (10.1%) in Group 2 (p  0.722). The actuarial pelvic control rate for Groups 1 and 2 was 88.2% and 86.3% at 5 years and 87.3% and 85.5% at 10 years, respectively (p  0.504). The actuarial overall survival rate for Groups 1 and 2 was 63.5% and 56.1% at 5 years and 47.8% and 49.3% at 10 years, respectively (p  0.734). The actuarial proctitis rate for Groups 1 and 2 was 49.7% and 32.7% at 5 years and 50.5% and 32.7% at 10 years, respectively (p <0.001). Most of the decrease in the rate of proctitis was a result of a decrease in the incidence of low-grade proctitis (38% vs. 22%). The incidence of high-grade complications remained unchanged, 8% vs. 7%. The actuarial cystitis rate for Groups 1 and 2 was 14.3% vs. 11.4% at 5 years and 24.1% vs. 15% at 10 years, respectively (p  0.134). Multivariate analysis revealed that the fractionation scheme (three fractions vs. five fractions) was a significant factor influencing the proctitis rate (p  0.004, hazard ratio  0.807; 95% confidence interval, 0.697– 0.934), but not the local pelvic control rate, overall survival rate, or cystitis rate. Conclusion: The treatment results of the two groups maintained similar outcomes, while the complications decreased. The linear-quadratic model correctly predicted this outcome. Biologically, the manipulation of the fraction size in our study suggested that the sensitivity of the late responding tissue to the fractional change from 7.2 Gy to 4.8 Gy in HDR-IC is high and detectable clinically. The success, however, had its limitations, and the improvement was confined to low-grade complications. © 2004 Elsevier Inc. Cervical carcinoma, Linear-quadratic model, High-dose-rate, Fractionation scheme, Brachytherapy. Reprint requests to: Chong-Jong Wang, M.D., Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Rd., Niao-Sung Hsian, Kaohsiung Hsien, Taiwan. Tel: (+886) 7-7317123, ext. 2600; Fax: (+886) 7-7322813; E-mail: cjw1010@adm.cgmh.org.tw Acknowledgments—We thank Dr. Yeh-Chi Lo, whose visit to our Department in 1993 and help in formulation substantiated the change in the fractionation scheme used in this report. Dr. Lo was then a medical physicist at the Memorial Sloan-Kettering Cancer Center in New York, and is now at Mount Sinai Hospital, New York. Received Jul 17, 2003, and in revised form Sep 29, 2003. Accepted for publication Oct 15, 2003. Int. J. Radiation Oncology Biol. Phys., Vol. 59, No. 1, pp. 179 –189, 2004 Copyright © 2004 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/04/$–see front matter 179