Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma

Purpose: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) and to explore whether a combination of high -dose-rate (HDR) intracavitary brachytherapy and external beam radiation th erapy (ERT) could improve the therapeutic ratio. Methods and Materials: Ninety-one patients with nonmetastatic locally recur rent NPC who were treated,vith curative intent during the years 1990-1999 w ere retrospectively analyzed. Eighty-two patients had histologically proven carcinoma. The remaining 9 had clinical and imaging features suggestive of local recurrence. The Ho's T-stage distribution at recurrence (rT) was as follows: rT1-37, rT2-14, rT3-40. Total equivalent dose (TED) was calculated by the linear-quadratic formula without a time factor correction. For thos e treated by combined-modality treatment (CMT), the TED was taken as the su mmation of the equivalent dose by ERT and the absolute dose delivered to fl oor of the sphenoid by brachytherapy. Eight patients were treated solely wi th brachytherapy, all receiving 24-45 Gy in 3-10 sessions. Forty-one patien ts were treated with ERT alone receiving a median TED of 57.3 Gy (range, 49 .8-62.5 Gy). Forty-two patients were treated by CMT with a median equivalen t dose of 50 Gy (range, 40-60 Gy) given by ERT and 14.8 Gy by brachytherapy (range, 3-29.6 Gy). Multivariate analyses were performed using the Cox reg ression proportional hazards model. Results: The 5-year actuarial overall survival rate, disease specific survi val rate and local failure-free survival (LFFS) rate for the whole group we re 30%, 33.3% and 37.8%, respectively. The 3-year LFFS rates of rT1, rT2, a nd rT3 diseases were 64%, 61.5%, and 18.4%, respectively (p = 0.001). Of the 8 patients treated with brachytherapy alone, 4 failed locally. Furth er analyses were concentrated on the ERT (41 patients) and CMT (42 patients ) groups. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 66.7%, 6 6.7%, and 18.4%, respectively (p = 0.0008). Better local control for patien ts who received a TED of 60 Gy or greater was shown. The corresponding 3-ye ar LFFS rates were 29% and 60% (p = 0.0004). Subgroup analysis on the ERT a nd CMT groups showed a 3-year LFFS rate of 33.5% and 57% (p = 0.003). ERT g roup had an excess of patients with rT3 disease. Further analysis was perfo rmed on the rT1-2 patients showing a trend toward improvement in local cont rol in favor of the CMT group (3-year LFFS rates: CMT, 71.7%; ERT, 54%; p = 0.13). Multivariate analyses showed that rT stage (p = 0.002) and TED (p = 0.01; HR, 0.93; 95% confidence interval, 0.88-0.98) remained significant. The 5-year major and central nervous system (CNS) complication-free rates w ere 26.7% and 47.8%. The following factors were found to be significant on univariate analyses for both complications in the ERT and CMT groups: (I) M odality of treatment: more complications with ERT group; and (2) rT stage. Multivariate analyses showed that the rT stage was significant for predicti ng the occurrence of major (p = 0.004) and CNS complications (p = 0.04). Conclusion: For rT1-2 local recurrences, CMT with at least 60 Gy TED is rec ommended. The high incidence of major late complications is of serious conc ern. Ways of improving the local control of Ho's rT3 disease and reducing t he risk of late complications should be explored. (C) 2000 Elsevier Science Inc.