Presenter(s)
K. Schumacher1, E. Krzeminski2, H. Worrall2, A. Leow2, D. J. Indelicato3, A. Gajjar4, and T. E. Merchant2; 1State University of New York, Syracuse, NY, 2St. Jude Children's Research Hospital, Memphis, TN, 3University of Florida, Jacksonville, FL, 4Division of Neuro-Oncology, St. Jude Children’s Research Hospital, Memphis, TN
Purpose/Objective(s): Children with brain tumors under 3 years of age are vulnerable to radiotherapy-related toxicities. With the advent of conformal radiotherapy, a protocol was developed to administer focal radiotherapy after surgery and induction chemotherapy in children with CNS embryonal tumors and ependymoma using a novel clinical target volume margin of 0.5 cm. With long-term follow-up, this study reports the feasibility of this strategy and patterns of failure in selected patients.
Materials/Methods: Between 2007 and 2017, 75 children with atypical teratoid rhabdoid tumor (ATRT=18), ependymoma (EP=32), and medulloblastoma (MB=25) underwent definitive radiotherapy (54 Gy to the primary site) using proton (n=36) or photon (n=39) therapy after four cycles of intravenous cyclophosphamide, vincristine, cisplatin, and methotrexate. Post-irradiation maintenance was prescribed based on diagnosis and risk stratification. Radiotherapy volume was focal or craniospinal (CSI) based on post-induction staging. Low risk (LR) was assigned to MB based on histology, intermediate risk (IR) to localized tumors, and high risk (HR) to neuroaxis metastases. Radiotherapy was initially planned for IR patients and deferred for LR and HR patients. Progression-free survival (PFS) and overall survival (OS) were calculated from radiotherapy start to progression and death, respectively. Patterns of failure were evaluated by registration of progression imaging to the original treatment plan.
Results: With a median follow-up of 13 years among survivors, the 10-year PFS and OS rates were 44.4% and 50.0% for ATRT, 69.0% and 80.5% for EP, and 60.0% and 76.0% for MB, respectively. All ATRT and EP patients were initially classified as IR and received focal radiotherapy. Six LR MB patients experienced progression after induction chemotherapy and were successfully salvaged, resulting in a 100% PFS; five of these patients required CSI. Progression occurred in 8 of 14 initially IR MB patients; however, long-term survival was achieved in 10 of 14 patients following a second course of therapy that included CSI. Among the five initially HR MB patients, three achieved long-term PFS and OS. Progression occurred in 11 of 32 EP patients, of whom eight received a second course of treatment. Median overall survival after a second treatment course was 5.5 years (range, 2.0–8.3 years). The 10-year cumulative incidences of local and distant progression in EP patients were 14.8% and 16.8%, respectively. In contrast, no cases of local progression were observed in the MB subgroup, and only one case of local progression occurred in the ATRT subgroup. No marginal failures were observed overall.
Conclusion: Focal radiotherapy using a reduced 0.5 cm clinical target volume margin is feasible in selected young children with brain tumors with no observed marginal failures. Long-term disease control was achieved in a substantial proportion of patients supporting this risk-adapted approach to minimize radiotherapy exposure in very young children.