Received: 21 August 2017 Revised: 15 December 2017 Accepted: 29 December 2017 DOI: 10.1002/pbc.26997 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology RESEARCH ARTICLE Early outcomes and patterns of failure following proton therapy for nonmetastatic intracranial nongerminomatous germ cell tumors Meriem Mokhtech 1 Ronny L. Rotondo 1 Julie A. Bradley 1 Eric S. Sandler 2 Ronica Nanda 1 Natalie Logie 1 Philipp R. Aldana 3 Christopher G. Morris 1 Daniel J. Indelicato 1 1 Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida 2 Department of Pediatrics, University of Florida College of Medicine, Jacksonville, Florida 3 Department of Neurosurgery, University of Florida College of Medicine, Jacksonville, Florida Correspondence Daniel J. Indelicato, University of Florida College of Medicine, Department of Radiation Oncol- ogy, 2015 North Jefferson Street,Jacksonville, FL 32206. Email: dindelicato@floridaproton.org Abstract Background: Although dosimetric comparisons demonstrate the advantage of proton therapy (PT) over conventional radiotherapy for nongerminomatous germ cell tumors (NGGCT), clinical outcome data for this rare tumor are lacking. We sought to evaluate outcomes for children with NGGCT treated with PT. Methods: Between 2007 and 2016, 14 children (median age 11, range, 5–19 years) with non- metastatic NGGCT were treated with PT after induction chemotherapy. Most (8/14) were mixed germ cell. Five of 14 patients had complete resection of their primary tumor before radiation. Off study, eight patients received 36 Gy (RBE [relative biological effectiveness]) craniospinal irradi- ation (CSI). On study, two patients received 30.6 Gy (RBE) whole-ventricle irradiation and four received focal radiation alone. All patients received a total dose of 54 Gy (RBE) to the tumor/tumor bed. Results: At a median follow-up of 2.8 years, all patients were alive with no local recurrences. Three-year progression-free survival was 86%. Both metastatic recurrences occurred in patients treated with focal radiation alone; one with an immature teratoma developed an isolated spinal recurrence 5 months after treatment. Another with a mixed germ cell tumor developed a multifo- cal ventricular and shunt tract recurrence 7 months after treatment. Serious toxicity was minimal, including cataracts and hormone deficiency, and limited to children who received CSI. Conclusion: Early outcomes in children treated for NGGCT suggest the high conformality of PT does not compromise disease control and yields low toxicity. This pattern of failure data adds to growing evidence suggesting chemotherapy followed by focal radiotherapy alone is inadequate in controlling localized NGGCT. KEYWORDS central nervous system, choriocarcinoma, embryonal carcinoma, germ cell, neoplasms, pediatric, proton therapy, radiation oncology, teratoma, yolk sac tumor 1 INTRODUCTION Central nervous system (CNS) germ cell tumors (GCT) account for approximately 3% of pediatric brain tumors. 1 Historically, GCT Abbreviations: CNS, central nervous system; COG, Children's Oncology Group; CSI, craniospinal irradiation; GCT, germ cell tumors; GTR, gross total resection; HRQoL, health-related quality of life; NGGCTs, nongerminomatous germ cell tumors; SIOP, Societe Internationale d'Oncologie Pediatrique; STR, subtotal resection have been classified into germinomas and nongerminomatous GCT (NGGCTs), with NGGCTs accounting for approximately one-third of GCTs. 2 The classification is based on histology and the degree of differentiation. NGGCTs can be further classified into embryonal carcinomas, yolk sac tumors, choriocarcinomas, teratomas, and mixed GCTs. 3,4 Adequately classifying a GCT as either germinomatous or nongerminomatous can help determine proper treatment. 5 The prognosis of NGGCTs is generally less favorable than germino- mas. The overall survival rate for NGGCTs treated with radiation alone Pediatr Blood Cancer. 2018;e26997. c  2018 Wiley Periodicals, Inc. 1 of 6 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.26997