White, J.Douglas

Abstract BACKGROUND Pineoblastoma is an aggressive, rare tumor of the pineal gland. Due to rarity of pineoblastoma, no large-scale prospective clinical trial data is available to guide clinical practice. Patients often receive treatment based on approaches to other high-grade embryonal central nervous system (CNS) tumors such as medulloblastoma. Multimodality treatment typically consists of maximal surgical resection followed by radiation therapy and chemotherapy. Despite treatment, recurrence is common and five-year survival rate is 60-70%. Pineoblastoma can disseminate through the leptomeninges, which is associated with poor survival. No therapy is known to confer a survival benefit in the setting of leptomeningeal disease (LMD) related to pineoblastoma. MATERIAL AND METHODS We report radiographic response and longer than expected survival for a patient with LMD related to pineoblastoma treated with single-agent temozolomide chemotherapy. RESULTS A 22-year-old male with a history of pineoblastoma presented with periodic headaches and leptomeningeal enhancement on surveillance imaging. 5 years prior to presentation (age 17), he was initially diagnosed with pineoblastoma after gross total resection followed by treatment with proton craniospinal radiation and adjuvant carboplatin/vincristine chemotherapy. Surveillance craniospinal MRIs identified diffuse leptomeningeal enhancement involving the posterior fossa and diffusely throughout the spine and lumbosacral nerve roots. While cerebrospinal fluid (CSF) cytology was negative for tumor cells on three separate occasions, CSF cell-free DNA (cfDNA) analysis isolated tumor DNA. He was started on temozolomide chemotherapy with near complete resolution of leptomeningeal enhancement on MRI after 2 cycles and complete resolution after 6 cycles. Treatment was well-tolerated with grade 1 fatigue as the only toxicity. Patient remains alive 20 months after initial diagnosis of LMD with resolution of headaches and durable radiographic response. CONCLUSION This case highlights utility of CSF cfDNA as a companion tool for diagnosis of LMD. Durable clinical and radiographic response achieved suggests temozolomide can be considered as a salvage treatment option for recurrent pineoblastoma with LMD.