Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis

Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compare...

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Bibliographic Details
Published in:	Journal of clinical oncology Vol. 40; no. 33; pp. 3858 - 3867
Main Authors:	Yang, Jonathan T, Wijetunga, N Ari, Pentsova, Elena, Wolden, Suzanne, Young, Robert J, Correa, Denise, Zhang, Zhigang, Zheng, Junting, Steckler, Alexa, Bucwinska, Weronika, Bernstein, Ashley, Betof Warner, Allison, Yu, Helena, Kris, Mark G, Seidman, Andrew D, Wilcox, Jessica A, Malani, Rachna, Lin, Andrew, DeAngelis, Lisa M, Lee, Nancy Y, Powell, Simon N, Boire, Adrienne
Format:	Journal Article
Language:	English
Published:	United States 20-11-2022
Subjects:	Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carcinoma, Non-Small-Cell Lung - drug therapy Craniospinal Irradiation - adverse effects Humans Lung Neoplasms - drug therapy Meningeal Carcinomatosis - drug therapy Meningeal Carcinomatosis - radiotherapy Proton Therapy - adverse effects Protons
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Summary:	Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT. We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non-small-cell lung cancer and breast cancers with LM. We enrolled patients with other solid tumors to an exploratory pCSI group. For the randomized groups, patients were assigned (2:1), stratified by histology and systemic disease status, to pCSI or IFRT. The primary end point was CNS PFS. Secondary end points included overall survival (OS) and treatment-related adverse events (TAEs). Between April 16, 2020, and October 11, 2021, 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. At planned interim analysis, a significant benefit in CNS PFS was observed with pCSI (median 7.5 months; 95% CI, 6.6 months to not reached) compared with IFRT (2.3 months; 95% CI, 1.2 to 5.8 months; < .001). We also observed OS benefit with pCSI (9.9 months; 95% CI, 7.5 months to not reached) versus IFRT (6.0 months; 95% CI, 3.9 months to not reached; = .029). There was no difference in the rate of grade 3 and 4 TAEs ( = .19). In the exploratory pCSI group, 35 patients enrolled, the median CNS PFS was 5.8 months (95% CI, 4.4 to 9.1 months) and OS was 6.6 months (95% CI, 5.4 to 11 months). Compared with photon IFRT, we found pCSI improved CNS PFS and OS for patients with non-small-cell lung cancer and breast cancer with LM with no increase in serious TAEs.
ISSN:	0732-183X 1527-7755
DOI:	10.1200/JCO.22.01148