ATRT-05. Late intracranial metastatic recurrence of Atypical Teratoid Rhabdoid Tumor (ATRT) in an adolescent/young adult: Durable disease response to multimodal therapy containing tazemetostat

ATRT is notorious for its aggressive behavior and propensity to relapse despite multimodal treatment, with most recurrences reported within the first year from upfront therapy. Although most common in younger children (< 3 years), ATRT represents a clinically and biologically heterogeneous disease which can present in older adolescents, with similar recurrence patterns. In unique instances, ATRT can recur at later time points, potentially providing additional treatment opportunities. Herein we present a case of a late relapse in an 18-year-old male, originally diagnosed at 12 years with localized right frontal ATRT (SHH molecular subgroup) treated with gross total resection, focal proton radiation (50.4Gy), and 6 cycles of alternating cisplatin/etoposide and cyclophosphamide/etoposide. Surveillance imaging remained reassuring until 6 years later, when the patient became symptomatic, with MRI demonstrating a new large left temporal mass, for which he underwent resection; pathology was consistent with recurrent ATRT (conserved SHH subgroup) and germline whole exome sequencing was negative for tumor predisposition variants, confirming a late intracranial metastatic relapse (not second primary tumor). Within 3 weeks post resection, the tumor rapidly regrew. The patient received proton craniospinal radiation (CSI; 36 Gy with 19.8Gy boost), followed by second look surgery for residual tumor, with pathology confirming viable (albeit less proliferative) ATRT. Chemotherapy per ACNS0332 was administered for 3 cycles, though discontinued due to nephrotoxicity and mucositis. He subsequently completed 12 cycles of maintenance tazemetostat (oral EZH2 inhibitor) with minimal toxicity, aside from fatigue. This patient is now more than 1 year post-completion of tazemetostat therapy with no radiographic evidence of residual or recurrent disease. This case importantly illustrates the rare possibility of a very late metastatic intracranial recurrence in an adolescent patient who did not receive upfront CSI, and highlights potential utility of maintenance therapy with tazemetostat on the backbone of conventional re-resection, re-irradiation, and chemotherapy.