In an interim analysis of a phase II trial reported in JAMA Oncology, Yang et al found that proton craniospinal irradiation (pCSI) improved central nervous system (CNS) progression-free survival vs photon involved-field radiotherapy (IFRT) in patients who have breast cancer or non–small cell lung cancer (NSCLC) with leptomeningeal metastasis.
Study Details
In the U.S. multicenter open-label trial, 63 patients (57% with NSCLC and 43% with breast cancer in each group) were randomly assigned 2:1 between April 2020 and October 2021 to receive pCSI (n = 42) or IFRT (n = 21). RT was given at 3 Gy × 10 daily fractions. pCSI was given as pencil beam scanning proton therapy to the entire CNS compartment. Patients who received photon IFRT for bulky or symptomatic disease underwent 3D photon planning. The primary outcome measure was CNS progression–free survival.
Key Findings
At the planned interim analysis (median follow-up = 26.8 months, 95% confidence interval [CI] = 18.5 months to not reached), the pCSI group had significantly better CNS progression–free survival, resulting in early discontinuation of the trial. Median CNS progression–free survival was 8.2 months (95% CI = 6.6–15.3 months) in the pCSI group vs 2.3 months (95% CI = 1.2–4.0 months) in the IFRT group (P < .001). The cumulative incidence of CNS disease progression at 6 months was 22% vs 88% (P < .001).
Median overall survival was 11.3 months (95% CI = 7.5–18.3 months) in the pCSI group vs 4.9 months (95% CI = 3.9–15.0 months) in the IFRT group (P = .04). The rate at 6 months was 72% vs 47%. On multivariate analysis, pCSI was independently associated with significantly improved CNS progression–free survival (HR = 0.14, 95% CI = 0.06–0.30, P < .001) and overall survival (HR = 0.50, 95% CI = 0.27–0.94, P = .03).
A trend toward improved self-reported daily function was observed in the pCSI group.
The investigators concluded: “This randomized clinical trial that assessed the optimal radiotherapy treatment for [leptomeningeal metastases] found improved CNS [progression-free survival] and [overall survival] with pCSI compared with IFRT. The results suggest that pCSI should be considered when available.”
Jonathan T. Yang, MD, PhD, of the Department of Radiation Oncology, NYU Grossman School of Medicine, New York, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by grants from the Cycle for Survival Equinox Innovation Initiative Award and the National Cancer Institute. For full disclosures of all study authors, visit jamanetwork.com.
