The contemporary spectrum of radiotherapy for hematologic malignancies involving the central nervous system: From focal therapy to craniospinal

Abstract

The contemporary landscape of systemic therapy options for hematologic malignancies involving the central nervous system (CNS-HM) is rapidly evolving; a key question is how radiotherapy (RT) can be optimally integrated to improve patient outcomes. Historically, use of RT to treat CNS-HM was defined by broad fields and high doses. While effective, this approach raised concerns of potential neurotoxicity which significantly decreased RT utilization. RT was replaced by high-dose, CNS-penetrant, systemic therapies that offered durable control with lower perceived neurotoxic risk. But, as the therapeutic toolbox for CNS-HM expands, so too does the complexity and diversity of potential clinical scenarios where RT should be considered. In this review, we describe both well-established and emerging opportunities for RT integration, emphasizing how dose selection and field design could balance neurotoxicity risk and disease control. We propose an anatomical framework that captures the diverse utilization of RT for CNS-HM and serves as a practical guide for RT volume and dose design.

Figure 1.. General Framework to approach CNS-HM Patient who is a candidate for RT.

(A) There are four broad steps to CNS-HM workup, which include: 1) workup to define involved sites of disease in the CNS, 2) determine the active sites of CNS disease (if any), 3) assess clinical factors, and 4) determine the treatment intent. (B) An anatomic framework to approach CNS-RT. The field and dose will depend on the anatomic sites of CNS involvement (y-axis), as well as treatment intent and disease state (x-axis). For patients who have cleared all CNS sites of active disease and who are being treated with curative intent (left column) the RT field will typically encompass all sites of prior involvement. PCNSL is typically consolidated with whole brain radiotherapy (WBRT). For patients with ocular lymphoma, the field can include just the orbits for primary intraocular lymphoma (PIOL) or the orbits and whole brain for patients with PCNSL with ocular involvement. Reduced dose (≤ 24 Gy) is recommended for consolidation RT. For patients with active CNS disease who are being treated with curative intent (middle column), the RT field will typically encompass the involved compartments. That is, the whole brain is targeted for parenchymal involvement and the craniospinal axis is targeted for leptomeningeal involvement. However, if RT is being integrated into a larger therapeutic strategy (e.g., systemic therapy or cellular therapy), then it is reasonable to consider focal RT to sites of radiographic gross disease. Standard doses (24 – 36 Gy) are typically used. For patients with active CNS disease who are treated with palliative intent (right column), the RT field is focused on the sites of symptomatic disease, for example the cauda equina, skull base, or a symptomatic parenchymal lesion. If there is widespread parenchymal or meningeal involvement around the brain, then WBRT may be favored over focal RT. CNS: Central nervous system; CNS-HM: CNS hematologic malignancy; CNS-RT: CNS directed radiotherapy; WBRT: whole brain radiotherapy; CSI: craniospinal irradiation; PIOL: primary intraocular lymphoma; PCNSL: primary CNS lymphoma; RT: radiotherapy.

Figure 2.. Examples of Field Design.

(A) WBRT field with isocenter bisecting the bony canthi to reduce anterior divergence. (B) Focal RT field showing contours that define the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). The CTV is a 1cm expansion on the GTV. (C) Bilateral orbit field with isocenter set at the optic chiasm to reduce posterior divergence.