INNV-57. Using circulating tumor DNA testing to diagnose and guide treatment for brainstem glioma

Diagnosis and treatment of brainstem tumors is challenging due to increased risks associated with surgical biopsy. Recent advances in circulating tumor DNA (ctDNA) testing of cerebrospinal fluid (CSF) offers a promising non-invasive alternative by providing molecular sequencing that can aid in diagnosis and guide potential treatment options. This case report presents a patient with a presumed brainstem glioma who underwent CSF analysis with the Belay SummitTM assay and demonstrated confirmation of diagnosis along with actionable mutations. The patient initially presented with diplopia, with imaging showing a heterogeneously enhancing mass in the brainstem, consistent with a presumed high-grade glioma. Due to the inaccessibility of the lesion, biopsy was not performed. He was empirically treated with concurrent chemoradiation followed by 12 cycles of adjuvant temozolomide. Upon disease progression, he enrolled in a phase I clinical trial but progressed after five cycles. He subsequently enrolled in a phase II clinical trial involving a targeted agent, which he remains on. Due to worsening neurologic symptoms concerning for increased intracranial pressure or subclinical tumor progression not evident on imaging, a lumbar puncture was performed. CSF was sent for ctDNA analysis, which identified clinically significant genomic variants, including IDH1 R132H, TP53, and KRAS mutations. Institutional cytology was negative for malignant cells. The molecular findings informed potential future use of IDH inhibitor therapy and trial considerations on disease progression. This case report highlights the diagnostic and therapeutic utility of CSF ctDNA testing in brainstem gliomas where tissue biopsy is not feasible. Large prospective clinical trials are needed to validate the clinical utility of CSF ctDNA in the diagnosis, monitoring, and treatment planning of brain tumors that have historically relied on imaging alone.