Urgent and Emergent Radiotherapy for Hematologic Malignancies of the Central Nervous System: A Review of the Literature and Practical Approach

Kathryn Tringale ^1* Brandon Imber ² Gustav Cederquist ² Joachim Yahalom ² Zachary R Moore ² Richard T Hoppe ³ Michael S Binkley ³ Jason B Ross ³ Neil Wijetunga ⁴ Parag Sanghvi ¹ Dana Casey ⁴ Susan M Hiniker ³

• ¹ University of California, San Diego, La Jolla, United States
• ² Memorial Sloan Kettering Cancer Center, New York, New York, United States
• ³ Stanford University, Stanford, California, United States
• ⁴ University of North Carolina at Charlotte, Charlotte, North Carolina, United States

Hematologic malignancies, including leukemias, lymphomas, and myeloma, can involve the central nervous system (CNS) at the time of diagnosis or later in relapse. CNS involvement can lead to acute neurologic symptoms or signs that need prompt evaluation and treatment. Radiotherapy (RT) can lead to quick disease response, but how it can best be incorporated early into multi-modality treatment in the urgent clinical setting is often unclear.Here, we outline a practical approach to planning and incorporating urgent RT in patients with hematologic malignancies involving the CNS. We provide a review of the literature to inform RT indications, timing, dosing, and treatment volumes by histology and clinical scenario. We also highlight evolving controversies in this field and growing indications for RT in conjunction with novel therapeutics.RT is often the quickest-acting, most reliable tool to salvage cranial neuropathies or neurologic deficits and should be considered early. If systemic or intrathecal therapy are expected to achieve swift response as upfront treatment, simulation should still be planned in the event response is delayed and RT is needed. RT in combination with certain systemic or intrathecal therapies can lead to unacceptable neurotoxicity; therefore, early multidisciplinary discussion to appropriately sequence therapies is critical. Thorough work-up with systemic imaging, complete neuroaxis MRI, ophthalmologic exam, and cerebrospinal fluid sampling can dictate target volumes from focal RT to comprehensive craniospinal irradiation (CSI). Dosing can range from as low as 4 Gray (Gy) for indolent disease to 36-50 Gy for more aggressive or refractory disease. Often, mid-treatment replanning can be considered to address swift volume reduction to improve the therapeutic window. RT plays a promising role of bridging symptomatic patients to novel therapeutics (e.g., CAR T-cell therapy), but optimal dosing and treatment volumes are an evolving topic that requires further prospective evaluation.RT is a powerful tool for achieving rapid responses in hematologic malignancies and therefore should be considered early in urgent neurologic settings. Thorough workup and discussions with the multi-disciplinary team are critical to best incorporate RT in the context of other CNSpenetrating therapies. Further work is warranted on defining RT target volumes in the context of novel therapeutics.