FRACTIONATED HIGH-DOSE-RATE BRACHYTHERAPY IN PRIMARY-CARCINOMA OF THENASOPHARYNX

Purpose: A growing body of data suggests that local control in nasopha ryngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These resu lts were analyzed together with data obtained from controls who did no t receive BT. Patients and Methods: The BT group comprised 42 consecut ive patients of whom 29 patients were staged according to the tumor, n ode, metastasis system as T1 through 3, 13 patients were T4, and 34 pa tients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumo rs comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with paraphary ngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fra ctions of 3 Gy BT. The no-BT group consisted of all patients treated f rom 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Co x proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease -free survival (DFS), cause-specific survival (CSS), and the prognosti c factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependenc e of local failure (LF) on the physical dose as well as the biologic e ffective dose (BED) corrected for the overall treatment time (OTT) (BE Dcor(10)) was studied. Results: The BT group had a superior 3-year loc al relapse-free rate (86% v 60%; univariate analysis, P=.004). Multiva riate analysis showed hazards ratios for BT versus no-BT of 0.24 for T TLF (P=.003), 0.35 for TTDF (P=.038), 0.31 for DFS (P<.001), and 0.44 for CSS (P=.01). The best prognostic group consisted of patients with T1 through 3, NO through 2b tumors treated with BT who attained a 5-ye ar TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group , ie, 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. Conclusion: Hi gh doses of radiation (73 to 95 Gy) can be administered to patients wi th NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patie nts with T1 through 3, NO through 2b disease. The steep dose-effect re lationship seen for the physical dose and the BEDcor(10) indicates tha t the results are dose related. The analysis has identified a poor pro gnostic group in whom treatment intensification with chemotherapy(CHT) is indicated. (C) 1998 by American Society of Clinical Oncology.