Phase III Trial Compares Proton Therapy to Standard Radiation for Leptomeningeal Metastasis from Breast and Lung Cancers
Key Insights
The NRG-BN014 "RADIATE-LM" trial is testing proton craniospinal radiation therapy (search) versus standard involved-field radiation therapy (search) for patients with leptomeningeal metastasis (search) from breast cancer (search) or non-small cell lung cancer (search).
Leptomeningeal metastasis (search) patients typically have poor prognosis with average overall survival of 4-6 months using current standard approaches.
Proton craniospinal radiation therapy (search) shows potential for improved survival outcomes and reduced high-grade toxicities due to its more targeted radiation delivery.
A new Phase III clinical trial is investigating whether proton craniospinal radiation therapy (search) can improve outcomes for patients with leptomeningeal metastasis (search) from breast cancer (search) or non-small cell lung cancer (search). The NRG-BN014 study, known as "RADIATE-LM," activated for patient enrollment in November 2025 and represents a significant shift from current treatment approaches for this challenging condition.
Current Treatment Challenges
Leptomeningeal metastasis (search) occurs when breast cancer (search) or non-small cell lung cancer (search) spreads to the cerebrospinal fluid (search)-filled space around the brain and spinal cord. The condition carries a particularly poor prognosis, with patients typically experiencing multiple debilitating neurological dysfunctions that can be life-threatening due to the disease's dissemination through the central nervous system (search).
"Currently, IFRT is the usual radiation treatment approach to patients with LM and prognosis for this population is often poor. The average overall survival for patients being treated for LM is approximately 4-6 months with standard approaches," stated Jonathan T. Yang, MD, PhD, of the New York University School of Medicine and Perlmutter Cancer Center (search), who serves as the Principal Investigator of the RADIATE-LM Trial.
Rising Incidence and Treatment Innovation
The incidence of leptomeningeal metastasis (search) is rising, likely due to improved imaging techniques and systemic disease control. This trend has intensified the need for more effective treatment strategies. The current standard approach employs x-rays to treat the brain and specific areas of the spine through involved-field radiation therapy (search) (IFRT) to relieve or prevent symptoms.
The experimental approach being tested uses proton craniospinal irradiation (pCSI), which employs proton radiation to comprehensively treat the entire central nervous system (search) space, including the cerebrospinal fluid (search), brain, and spinal cord.
"Proton craniospinal radiation therapy (search) has showed potential promise in improving survival outcomes for this population as well as limited high-grade toxicities due to its more targeted delivery of radiation," Dr. Yang added.
Trial Design and Objectives
After receiving clearance for proton therapy, patients enrolled in the RADIATE-LM study will be registered and stratified by several factors: histology (breast cancer (search) or non-small cell lung cancer (search)), systemic disease status, and use of intrathecal therapy, immunotherapy, or targeted therapy including antibody-drug conjugates either 4 weeks prior or planned 4 weeks following completion of radiotherapy.
Patients will then be randomly assigned to either Treatment Arm 1 receiving IFRT or Treatment Arm 2 receiving pCSI. The primary aim of this trial is to determine if pCSI improves overall survival outcomes when compared to the usual IFRT.
Secondary Endpoints and Patient Eligibility
Additional objectives of the RADIATE-LM study include comparing CNS progression-free survival, CNS progression rates, treatment-related adverse events, radiation-induced CNS necrosis rates, and patient-reported outcomes between treatment arms.
To join this study, patients must have newly diagnosed leptomeningeal metastasis (search) from breast cancer (search) or non-small cell lung cancer (search), be able to walk and do routine activities for more than half the time they are awake, and be age 18 or older.