Evolution and Dosimetric Analysis of Magnetic Resonance Imaging–Detected Brain Stem Injury After Intensity Modulated Radiation Therapy in Nasopharyngeal Carcinoma

Abstract

To evaluate the evolution of radiation-induced brain stem injury (BSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) and to identify the critical dosimetric predictors of BSI. A total of 6288 NPC patients treated with IMRT between 2009 and 2015 were retrospectively reviewed. Among these 6288 patients, 24 had radiation-induced BSI, which manifested as edematous lesions and contrast-enhanced lesions (CLs) on magnetic resonance imaging. Latency, symptoms, and evolution of BSI were assessed. Critical dosimetric predictors of BSI were identified using a penalized regression model with performance evaluated by receiver operating characteristic curve analysis. Median BSI latency was 14.5 months (range, 7.6-37.5 months), and 9 out of 24 patients (37.5%) were clinically symptomatic. Edematous lesions and CLs were both present in all patients. Necrosis was significantly more common in larger CLs (P = .007). After median follow-up of 12.5 months, 13 out of 24 patients (54.2%) had complete remission, and 5 out of 24 patients (20.8%) had partial remission. Remission was unaffected by whether or not symptomatic treatment was given. Maximum point dose (Dmax) was identified as the critical predictor of BSI (area under the receiver operating curve = 0.898), with the optimal cutoff equivalent dose in 2-Gy fractions (D2) being 67.4 Gy (sensitivity = 0.833, 20 out of 24; specificity = 0.835, 5234 out of 6264). Patients with Dmax ≥67.4 Gy (D2) were significantly more likely to develop BSI (odds ratio = 25.29; 95% CI, 8.63-74.14; P < .001) than those with Dmax <67.4 Gy (D2). In patients with NPC treated with IMRT, BSI generally tends to improve over time. Dmax = 67.4 Gy (D2) appears to be the dose constraint for brain stem, potentially providing clinicians with greater choice and flexibility when balancing the tumor target coverage and brain stem protection. Further studies are needed to validate our findings.