Temporal Lobe Radiation Necrosis after Re-Irradiation Involving the Skull Base With Proton Therapy: A Single-Institutional Experience

Abstract

To analyze clinical and dosimetric factors for the occurrence of temporal lobe necrosis (TLN) among patients who received proton therapy involving the skull base in the re-irradiation setting. We performed a retrospective analysis of 92 patients re-irradiated at our cancer center involving the skull base with proton therapy between 09/2013 and 03/2017. The most common primaries treated included the nasopharynx (n=21), paranasal cavity/sinuses (n=14), and major salivary gland (n=10); the most common histologies included squamous cell carcinoma (n=49), adenoid cystic carcinoma (n=12), sarcoma (n=5), and poorly differentiated carcinoma (n=4). Twelve (13.8%) patients had third-course radiation treatment. Follow up interval was defined from the beginning of proton therapy. Analyzed factors included prior radiation dose, composite mean dose to 2 cc and composite max pixel dose to the temporal lobe. Outcomes of interest included the grade of TLN, incidence as well as time to development of TLN among patients treated in the re-irradiation setting. Of the 92 patients analyzed, 84 (91%) were treated due to recurrent locoregional disease and 4 (4.3%) were treated due to metastatic disease. The median follow-up was 11.5 months (range 0-56) for the entire cohort and 15 months (range 1-44) for living patients; at time of analysis, 43 (47%) patients were still alive. The median prior irradiation dose to the skull base region was 6360 cGy for those without TLN and 6760 cGy for those with TLN (P=.055). Median re-irradiation proton dose was 60 CGE without TLN and 7 0CGE with TLN (P=.419). Twelve patients (13%) were found to have temporal lobe necrosis with median time to development of 8 months. Of these patients, 6 patients had right-sided TLN, 5 had left-sided, and 1 patient had bilateral TLN. The median total mean dose to 2 cc to the right temporal lobe was 51.87 CGE for those without TLN and 75.10 CGE for those with TLN (P=.057); median max pixel dose to the right was 68.80 CGE without TLN and 110.13 CGE with TLN (P=.040). On the left side, median total mean dose to 2 cc was 32.29 CGE with no TLN and 59 CGE with TLN (P=.211) and median max pixel dose was 55.19 CGE without TLN and 71.34 CGE with TLN (P=.560). All patients were determined to have grade 1 TLN per CTCAE 4.0 with only radiographic evidence and were clinically asymptomatic except for one patient with grade 2 toxicity requiring medical management with steroids. Among patients treated in the re-irradiation setting with proton therapy, 13% of patients developed TLN that was only apparent radiographically except for one who was treated medically. Analysis of more detailed dosimetric data with longer follow-up data are underway to better ascertain the significance of these findings.