Outcomes Following Proton Therapy for Non-Metastatic Central Nervous System Germinoma in Children and Adolescents

Abstract

Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Compared to photons, proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects, but there are sparse data on long-term patient outcomes. Herein, we present the largest reported single institution experience utilizing PT for the management of PG. We performed an IRB-approved retrospective review of a prospective database containing 35 patients with non-metastatic PG treated with PT between July 2007 and September 2021. The median age at treatment was 13 years. All patients had > 6 months of follow up. Two patients were diagnosed based on cerebral spinal fluid B-HCG levels and the remaining 33 patients through histopathology. Eleven patients had bifocal or multifocal intracranial disease. Most patients (n = 31, 88.6%) received induction chemotherapy with carboplatin + etoposide (n = 25, 80.6%) with all demonstrating a radiographic response to neoadjuvant therapy. Twenty-nine were treated with whole ventricular irradiation (WVI) with an involved field (IF) boost, 2 with craniospinal irradiation + WVI + IF, 2 with IF, 1 with CSI + IF, and 1 with whole brain + IF. Among this subgroup, the most common total dose was 30 GyRBE (n = 18, 51.4%). Of the 4 patients that did not receive chemotherapy, 3 received WVI + IF and 1 was treated with CSI + WVI + IF. The total dose in the patients not receiving chemotherapy was 45 GyRBE. Twenty-nine patients were treated with double scattered PT (DS) and 6 patients with pencil beam scanning PT (PBS). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed according to the CTCAEv5. Median follow up was 6.2 years (Range: 0.9-15.2 years). The 10-year KM estimates for LC, FFDM, FFP, and OS were 100%, 100%, 100%, and 97% respectively. One patient developed acute lymphocytic leukemia 8 months after treatment and died. The sole ³ grade 3 radiation-related toxicity was a cavernoma with hemorrhage 3.6 years post treatment requiring surgical resection. The most common adverse events were hearing impairment requiring hearing aids (n = 3), hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 22 evaluable patients ³18 years old at last follow up, 7 were high school graduates/in college, 8 college graduates, and 5 others gainfully employed. The use of proton therapy in the multi-modality approach to non-metastatic PG does not compromise local control. Although serious side effects are rare and treatment has minimal impact on survivors' early educational/career trajectory, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.