Dosimetric predictors of temporal lobe injury after intensity-modulated radiotherapy for T4 nasopharyngeal carcinoma: a competing risk study

BACKGROUND: In patients with T4 nasopharyngeal carcinoma (NPC), death may occur prior to the occurrence of temporal lobe injury (TLI). Because such competing risk death precludes the occurrence of TLI and thus the competing risk analysis should be applied to TLI research. The aim was to investigate the incidence and predictive factors of TLI after intensity-modulated radiotherapy (IMRT) among T4 NPC patients. METHODS: From March 2008 to December 2014, T4 NPC patients treated with full-course radical IMRT at our center were reviewed retrospectively. A nested case-control study was designed for this cohort of patients. The cases were patients with TLI diagnosed by MRI during the follow-up period, and the controls were patients without TLI after IMRT matched 1:1 to each case by gender, age at diagnosis, intercranial involvement, and follow-up time. The end point was time to TLI or death without prior TLI. We analyzed the cumulative incidence function (CIF) and performed a competing risk regression model to identify the predictors of TLI. RESULTS: With a median follow-up of 40.1 months, 63 patients (63/506, 12.5%) developed TLI as diagnosed by MRI, and 136 deaths occurred during the period. The cumulative incidence of TLI at 5 years was 13.2%, while 26.7% died without prior TLI. The univariate analysis showed that all selected dosimetric parameters were associated with the occurrence of TLI. On multivariate analysis, D1cc and V20 remained statistically significant. Based on the area-under-the-curve (AUC) values, D1cc was considered the most predictive. The patients with D1cc > 71.14 Gy had a 7.920-fold increased risk of TLI compared with those with D1cc ≤71.14 Gy (P < 0.05). Similarly, V20 > 42.22 cc was found to result in a statistically significant higher risk of TLI (subdistribution hazard ratio [sHR] =3.123, P < 0.05). CONCLUSIONS: TL D1cc and V20 were predictive of TLI after IMRT for T4 NPC. They should be considered as first and second priorities of dose constraints of the TL. D1cc ≤71.14 Gy and V20 ≤ 42.22 cc could be useful dose-volume constraints for reducing the occurrence of TLI during IMRT treatment planning without obviously compromising the tumor coverage.