EFFECT OF TIME, DOSE, AND FRACTIONATION ON TEMPORAL-LOBE NECROSIS FOLLOWING RADIOTHERAPY FOR NASOPHARYNGEAL CARCINOMA

Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different b iological equivalent models. Methods and Materials: Consecutive patien ts (1008) treated radically with four different fractionation schedule s during 1976-1985 for T1 nasopharyngeal carcinoma were retrospectivel y analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18-84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5-4.2 Gy, total dose 45.6-60 Gy, and over all time 38-75 days. Results: Despite a lower total dose of 50.4 Gy, t he 621 patients irradiated with 4.2 Gy per fraction had a significantl y higher incidence of temporal lobe necrosis than the 320 patients tre ated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidenc e being 18.6% vs. 4.6%, p < 0.001. Multivariate survival analysis show ed that fractional effect (product of total dose and fractional dose) was the most significant factor: p = 0.0022, hazard ratio (HR) = 1.014 per Gy(2). Overall time and age were both insignificant. The alpha/be ta ratio calculated from our data was 2.9 Gy (95% CI: -1.8, 7.6 Gy). B iological effective dose (BEDGy3), neuret, and brain tolerance unit al l showed strongly significant correlation with the necrotic rate (p < 0.001), and gave similar predictions. The hazard of TLN increased by 1 4% per Gy(3), and it was estimated that 64 Gy (at conventional fractio nation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. No t only did the nominal standard dose (NSD) show the lowest value in te rms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates. Conclusion: Fraction al effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assumi ng an alpha/beta ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misle ading predictions. (C) 1998 Elsevier Science Inc.