Radiation Therapy in the Management of Leptomeningeal Disease From Solid Tumors

Andrew B Barbour; Rupesh Kotecha; Stanislav Lazarev; Joshua D Palmer; Timothy Robinson; Divya Yerramilli; Jonathan T Yang

doi:10.1016/j.adro.2023.101377

Radiation Therapy in the Management of Leptomeningeal Disease From Solid Tumors

Adv Radiat Oncol. 2023 Sep 15;9(2):101377. doi: 10.1016/j.adro.2023.101377. eCollection 2024 Feb.

Authors

Andrew B Barbour¹, Rupesh Kotecha², Stanislav Lazarev³, Joshua D Palmer⁴, Timothy Robinson⁵, Divya Yerramilli⁶, Jonathan T Yang¹

Affiliations

¹ Department of Radiation Oncology, University of Washington - Fred Hutchinson Cancer Center, Seattle, Washington.
² Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida.
³ Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ Department of Radiation Oncology, The James Cancer Hospital, The Ohio State University Wexner Medical Center, Columbus, Ohio.
⁵ Department of Therapeutic Radiology, Yale University, New Haven, Connecticut.
⁶ Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Abstract

Purpose: Leptomeningeal disease (LMD) is clinically detected in 5% to 10% of patients with solid tumors and is a source of substantial morbidity and mortality. Prognosis for this entity remains poor and treatments are palliative. Radiation therapy (RT) is an essential tool in the management of LMD, and a recent randomized trial demonstrated a survival benefit for proton craniospinal irradiation (CSI) in select patients. In the setting of this recent advance, we conducted a review of the role of RT in LMD from solid tumors to evaluate the evidence basis for RT recommendations.

Methods and materials: In November 2022, we conducted a comprehensive literature search in PubMed, as well as a review of ongoing clinical trials listed on ClinicalTrials.gov, to inform a discussion on the role of RT in solid tumor LMD. Because of the paucity of high-quality published evidence, discussion was informed more by expert consensus and opinion, including a review of societal guidelines, than evidence from clinical trials.

Results: Only 1 prospective randomized trial has evaluated RT for LMD, demonstrating improved central nervous system progression-free survival for patients with breast and lung cancer treated with proton CSI compared with involved-field RT. Modern photon CSI techniques have improved upon historical rates of acute hematologic toxicity, but the overall benefit of this modality has not been prospectively evaluated. Multiple retrospective studies have explored the use of involved-field RT or the combination of RT with chemotherapy, but clear evidence of survival benefit is lacking.

Conclusions: Optimal management of LMD with RT remains reliant upon expert opinion, with proton CSI indicated in patients with good performance status and extra-central nervous system disease that is either well-controlled or for which effective treatment options are available. Photon-based CSI traditionally has been associated with increased marrow and gastrointestinal toxicities, though intensity modulated RT/volumetric-modulated arc therapy based photon CSI may have reduced the toxicity profile. Further work is needed to understand the role of radioisotopes as well as combined modality treatment with intrathecal or central nervous system penetrating systemic therapies.

Publication types

Review

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States