Pediatric Cancer

SS 14 - Pediatrics 2

102 - Brainstem Toxicity in Pediatric Patients Receiving Posterior Fossa Photon Radiation

Monday, October 22
11:15 AM - 11:25 AM
Location: Room 008

Brainstem Toxicity in Pediatric Patients Receiving Posterior Fossa Photon Radiation
C. A. Devine1, K. X. Liu1, M. Ioakeim-Ioannidou2, M. S. Susko3, T. Y. Poussaint4, T. A. G. M. Huisman5, M. Aboian6, D. Brown4, C. Zaslowe-Dude7, A. D. Rao2, L. T. Orlina8, B. Rawal9, S. Mueller10, K. J. Marcus11, S. A. Terezakis12, S. E. Braunstein10, and D. A. Haas-Kogan8; 1Harvard Medical School, Boston, MA, 2Department of Radiation and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine, Baltimore, MD, 3Department of Radiation Oncology University of California, San Francisco, San Francisco, CA, 4Department of Radiology, Boston Children's Hospital, Boston, MA, 5Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, 6Department of Radiology, University of California San Francisco, San Francisco, CA, 7Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, 8Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, 9Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 10University of California, San Francisco, San Francisco, CA, 11Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, 12The Johns Hopkins Hospital, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD

Purpose/Objective(s): 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.

Materials/Methods: 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.

Results: 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.

Conclusion: 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.

Author Disclosure: C.A. Devine: None. K.X. Liu: None. M. Ioakeim-Ioannidou: None. M.S. Susko: None. T.Y. Poussaint: None. T.A. Huisman: None. M. Aboian: None. D. Brown: Employee; Don Orione. C. Zaslowe-Dude: None. A.D. Rao: Employee; Johns Hopkins School of Medicine. S. Mueller: Research Grant; Novartis, Midatech, Regneron, Genentech. K.J. Marcus: Editorial Board Member; PDQ. S.A. Terezakis: Research Grant; Elekta. Honoraria; Elekta. Travel Expenses; Elekta. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC. D. Haas-Kogan: Research Grant; Novartis. Clinical Advisory Board; Cellworks.

Christopher Devine, MPhil

Disclosure:
Employment
Harvard Medical School: Employee: Employee

Biography:
Chris Devine is a joint MD/MBA candidate at Harvard Medical School and Harvard Business School working at the Dana-Farber/Brigham and Women's Cancer Center. He holds an MPhil from the University of Cambridge and an AB from Harvard College, and is expected to graduate from medical school in 2019. His research is focused on outcomes in pediatric radiation oncology, and his primary mentor is Professor Daphne Haas-Kogan.

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