Lack of Significant Brainstem Toxicity is Observed Among Children Following Modern Era Posterior Fossa Tumor Radiation Therapy

Abstract

Radiation-induced brainstem toxicity after treatment for pediatric posterior fossa (PF) malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of and predictive factors for brainstem toxicity after photon radiation therapy (RT) for PF tumors were examined. After IRB approval, 40 pediatric patients treated at our institution for non-metastatic infratentorial ependymoma, medulloblastoma, and atypical rhabdoid/teratoid tumor with IMRT were included in this analysis. Dosimetric variables, including maximum dose to the brainstem, dose to 10 and 50% of the brainstem, and the volume of brainstem receiving 40, 45, 50, and 55 Gy were recorded from individual patient dose-volume histogram data. Age at diagnosis, extent of resection, use of chemotherapy, and PTV volumes were also examined for correlation. Acute (onset within 3 months) and late (onset 3 months to 2 years of RT) RT-induced brainstem toxicities (new or worsening brainstem symptoms during or after RT) were scored using CTCAE v4.0. Corresponding changes on posttreatment MRIs were also noted. Patients from ages 9 months to 19 years were treated using IMRT or VMAT postoperatively to the PTV covering the posterior fossa or postoperative bed. Median follow-up time was 4.0 years; median progression-free survival and overall survival were not reached. Acute grade 1-2 brainstem toxicities were noted in 10% of patients (n=4); late grade 1-2 toxicities were seen in 12.5% of patients (n=5). One late grade 3 toxicity was noted (2.5%) in a patient who required repeat surgery for residual disease prior to RT. Nine patients (22.5%) had post-RT brainstem changes on MRI, but without correlative symptoms. Age less than 3 years (P=.048) and subtotal resection (P=.04) predicted for more acute toxicity, but this did not translate to late toxicity. Independent t-tests found only maximum dose to the brainstem above 57.8 Gy to be a significant predictor of late brainstem toxicity (P=.02). Other aforementioned factors did not affect acute or late toxicities. This study provides a unique dosimetric and radiographic analysis of clinically significant brainstem toxicity related to photon-based conformal radiation therapy in the modern treatment-planning era. Current dosimetric guidelines, appear to allow safe delivery of doses 54- 59.4 Gy to the posterior fossa; however, careful attention should be given to maximum brainstem dose, especially in younger patients with subtotal resection to minimize risk of late brainstem toxicity, especially given long-term survival of these patients.