Brainstem Toxicity in Pediatric Patients Receiving Posterior Fossa Photon Radiation

Abstract

Brainstem injury is a rare but significant complication of radiation therapy, and with increasing use of proton radiation therapy, comparative data have begun to emerge to determine the incidence of brainstem toxicity in both proton- and photon-treated patient cohorts. We report the results of a large multi-institutional study evaluating the incidence of brainstem toxicity in pediatric patients receiving photon therapy for tumors involving the posterior fossa. Clinical characteristics, including brainstem toxicity, preoperative characteristics, and dosimetric parameters, were recorded in 120 pediatric patients who received posterior fossa photon radiation for non-primary brainstem tumors from 2000-2016 at Dana-Farber Cancer Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and University of California, San Francisco. Patients with brainstem invasion by the primary tumor were excluded. All MR imaging was reviewed by a pediatric neuroradiologist at each institution. Post-radiation therapy imaging findings were recorded including new FLAIR/T2 lesions in the brainstem and radiation necrosis (ring enhancement within brainstem lesions). Brainstem toxicity was graded using the NCI Common Terminology Criteria for Adverse Events v5.0. Seventy-four patients (61.7%) were male and median age at diagnosis was 8.2 years (range: 0.8–20.6 years). The most common histologies were medulloblastoma (59.2%) and ependymoma (18.3%). Sixty-five of 119 (54.6%) patients underwent gross total resection, 51.3% (61/119) had hydrocephalus at diagnosis, 23.5% (28/119) received pre-radiation therapy chemotherapy, and 54.6% (65/119) received concurrent chemoradiation. Median prescribed dose was 55.8 Gy (range 23.4–64.0 Gy) with 95.8% (115/120) receiving ≥50.4 Gy. Seventy-nine patients (65.8%) received craniospinal irradiation and the majority of patients received involved field (38.3%) or whole posterior fossa (39.2%) boost (median: 19.8 Gy, range: 5.4-36 Gy). Median clinical and imaging follow-up durations were 50.2 months (range: 0.03–201.6 months) and 41.5 months (range: 0.6–203.7 months), respectively. The cumulative incidence of grade 1 brainstem necrosis was 1.7% (2 of 120 patients), and no grade ≥2 toxicities were observed. Both patients with grade 1 brainstem necrosis were by definition asymptomatic and experienced resolution on imaging, one after 5.3 months, and the other after 25.3 months. Risk of brainstem injury was minimal in this multi-institutional study of pediatric patients treated with photon radiation therapy to tumors involving the posterior fossa. In this large study, there were no cases of symptomatic brainstem injury. Further research is needed to determine if a difference exists in brainstem injury risk between photon and proton therapy.