Work

Ogct-05 a Multi-center Phase Ii Trial of Hippocampal Avoidance in Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumors

Year: 2025

Type: conference-abstract

Abstract: In a phase II randomized trial, Yang et al. compared proton craniospinal irradiation (CSI) with standard of care involved field irradiation (IFRT) in patients with leptomeningeal disease (LMD) that is metastatic from non-small cell lung cancer (NSCLC) or breast cancer. Proton CSI was associated with significant improvement in CNS-progression free survival (PFS) and overall survival (OS) without increased toxicity. With improving survival rates, it is important to preserve patients’ neurocognitive function as much as possible which impacts quality of life. Past trials have shown that decreasing the radiation dose to the subgranular zone of the hippocampal dentate gyrus in the setting of whole brain irradiation preserves neurocognitive function, however this has not been studied in CSI for LMD. In a multi-center phase II clinical trial (NCT06518057; opened to accrual in Jan 2025), we are testing hippocampal avoidance (HA-CSI) for the first time. We will include 22 adult patients with NSCLC or breast cancer and good performance status (KPS ≥ 60) who have LMD established radiographically (brain and total spine MRI) and/or through CSF cytology. Patients with major neurologic deficits, extensive systemic disease, untreated metastases within 5 mm of the hippocampi and gross ventricular disease are excluded. The primary endpoint is CNS-PFS. Secondary endpoints are neurocognitive function, OS and toxicity. Patients receive proton HA-CSI at the University of Washington/Fred Hutch and Volumetric Modulated Arc Therapy photon HA-CSI at UCSF to a total dose of 30 Gray (Gy/ relative biological effect (RBE)] in 3 Gy (RBE) fractions. As an exploratory endpoint, the outcomes will be compared between the 2 techniques. A neurocognitive test battery and MRI are performed prior to CSI and at each follow up visit (every 3 months for 1 year). Patients complete self-reported mood and fatigue scales along with neurocognitive tests. We have enrolled 3 patients to date.

Source: Neuro-Oncology Advances

DOI: 10.1093/noajnl/vdaf123.080