2659 - Proton Craniospinal Radiation for Leptomeningeal Disease from Patients with Metastatic Solid Tumors: A Multi-Institutional Retrospective Analysis

Purpose/Objective(s): Phase II randomized data suggests that proton craniospinal radiation (pCSI) improves progression-free and overall survival compared with involved field radiation (IFRT). Detailed analyses of prognostic variables for patients treated with this technique are needed to inform management.

Materials/Methods: We conducted a multi-institutional retrospective cohort study that included patients with solid tumor malignancies with leptomeningeal disease, who were treated with proton craniospinal radiation. Overall survival (OS), central nervous system progression free survival (CNS PFS) were estimated using the Kaplan-Meier method. Multivariable analyses were performed using the Cox Proportional Hazards model. Median follow-up was determined using the reverse Kaplan-Meier method.

Results: From July 2014 – December 2024, 168 patients were treated with pCSI. Patients were heavily pre-treated. Patients received a median of 2.5 lines (range 0-12) of prior systemic therapy. 127 (76%) were female. The median age was 58 (range 25 – 79). The cohort included patients with EGFR / ALK / ROS driven non-small cell lung cancer (NSCLC, 41), non-driver mutation NSCLC (18), triple negative breast cancer (13), HER2+ breast cancer (11), other breast cancer (38), melanoma (9), gastrointestinal cancer (15), and other cancers (23). 18 (11%) of patients required ventriculoperitoneal shunt before RT. The median prescribed dose was 30 CGE / 10 fractions. Dose and field adjustments were performed for prior radiotherapy or age. With median follow-up of 2.1 years, the median CNS PFS was 5.2 months (4.1 – 6.6 months) and overall survival was 7.1 months (5.5 – 7.9 months). 1-year overall survival was 29% (CI 22 .4 – 37.8%). On univariable analysis, age > 70 (HR 2.01, CI 1.29 – 3.13, p = 0.002), Karnofsky Performance Status (HR 0.85 per 10 points, 0.74 – 0.97, p = 0.02), uncontrolled extracranial disease (HR 1.78, 1.22 – 2.59, p = 0.003), breast or lung histology (HR 0.61, 0.41 – 0.89, p = 0.01) and pCSI field modifications were associated with survival (HR 1.98, 1.11 – 3.5, p = 0.02). These findings remained significant after multivariable adjustment (Table 1).

Conclusion: To our knowledge, this is the largest multi-institutional series to date on proton craniospinal radiotherapy for patients with metastatic solid tumors and includes patients who were heavily pre-treated. The results confirm the findings from our previous phase II trial and provides prognostic information for counseling and decision making.