doi:10.1016/j.ijrobp.2006.06.026 CLINICAL INVESTIGATION Head and Neck COMBINED-MODALITY TREATMENT FOR ADVANCED ORAL TONGUE SQUAMOUS CELL CARCINOMA KANG-HSING FAN, M.D.,* § CHEN-YU LIN, M.D.,* § CHUNG-JAN KANG, M.D., †§ SHIANG-FU HUANG, M.D., †§ HUNG-MING WANG, M.D., ‡§ ERIC YEN-CHAO CHEN, M.D.,* § I-HOW CHEN, M.D., †§ CHUN-TA LIAO, M.D., †§ ANN-JOY CHENG,PH.D., § AND JOSEPH TUNG-CHIEH CHANG, M.D. M.H.A.* §¶ *Department of Radiation Oncology, † Department of ENT, ‡ Division of Hematology/Oncology, Department of Internal Medicine; § Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan;  Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; and ¶ Department of Nursing, Chang Gung Institute of Technology, Taiwan Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8 –72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT signifi- cantly improved survival (3-year RFS with ECS and with CCRT  48.2% vs. without CCRT  15%, p  0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present. © 2007 Elsevier Inc. Tongue neoplasms, Combined modality therapy, Radiotherapy, Concurrent chemotherapy. INTRODUCTION Squamous cell carcinoma of the oral tongue usually presents differently from other cancers in the oral cavity. In particular, metastatic disease rather than local recurrence usually poses a great challenge. Occult metastasis may be present in 20% to 34% of patients, and nodal metastasis often predicts treatment failure, especially when extracapsular spread (ECS) is present (1–3). Many factors are recognized as predictors of a poor prognosis, such as stage, status of the surgical margin, extent of nodal metastasis, ECS, perineural invasion, and lymphovascu- lar permeation (4–6). Among these, some studies suggest that the extent of nodal metastasis is one of the strongest factors predicting failure of regional control and thus shorter recur- rence-free survival (RFS) (3, 7). If ECS is added to nodal metastasis, the prognosis is extremely grave (2). Adjuvant radiotherapy reduces tumor recurrence and pro- longs survival (8 –11). The more intense the treatment, the better the locoregional control and survival (12, 13). Recently, two large-scale randomized trials from the United States and Europe have demonstrated the benefits of adjuvant concurrent chemoradiotherapy (CCRT) after radical surgery in high-risk head-and-neck cancer patients (14, 15). Combining the data from these two studies suggested that adjuvant CCRT should be used whenever ECS or microscopically unclear margins or Reprint requests to: Joseph Tung-Chieh Chang, M.D., M.H.A., Department of Radiation Oncology, Chang Gung Institute of Tech- nology, No. 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan. Tel: (+886) 3-3281200-2613; Fax: (+886) 3-3280797; E-mail: jtchang@adm.cgmh.org.tw Supported by Grant Nos. CMRPG32038 from the Chang Gung Memorial Hospital and University and NSC-91-2314-B-182A-165 from National Science Council of Taiwan Government. Acknowledgment—The authors thank Mary Jean Buttery, M.D., for critical reading and correction of the manuscript. Conflict of interest: none. Received March 15, 2006, and in revised form June 14, 2006. Accepted for publication June 16, 2006. Int. J. Radiation Oncology Biol. Phys., Vol. 67, No. 2, pp. 453– 461, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter 453