Volumetric Modulated Arc Therapy Craniospinal Irradiation Utilizing a Vertebral Body Sparing Approach: A Toxicity Analysis

Abstract

Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral-body-sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. A recent phase II trial (Yang et al, JCO 2022) has shown efficacy of proton-based CSI to treat non-small cell lung and breast cancer with LMD. We hypothesize that VBS-CSI utilizing volumetric modulated arc therapy (VMAT) could also effectively reduce dose to vertebral bodies and surrounding organs-at-risk (OARs), minimizing toxicity for adult patients with LMD and comparing favorably to proton-based CSI. Consecutive patients with leptomeningeal disease received VMAT VBS-CSI, 30 Gy in 10 fractions, as a part of a prospective registry. Full VMAT arcs for the brain fields matched to two spine isocenters for the upper and lower spine were created utilizing limited posterior arcs. The PTV was created with margins of 3mm uniformly around the brain contour and 7mm around the spinal canal. To further decrease the vertebral body dose, an avoid entry and exit contour was created. This structure was a margin on the PTV anteriorly designed to carve dose out of the vertebral bodies while still maintaining coverage to the PTV. Acute toxicity data were collected using Common Terminology Criteria for Adverse Events (CTCAE) v5 and was defined as toxicity occurring within 30 days of treatment conclusion. Ten adult patients were treated in this cohort. All patients completed radiation treatment. One patient experienced Grade 2 neutropenia with the remaining nine experiencing Grade 1 hematologic toxicity (three Grade 1 pancytopenia, six Grade 1 thrombocytopenia). Three patients experienced Grade 2 gastrointestinal toxicity (Grade 2 nausea, Grade 2 esophagitis, Grade 2 esophagitis/Grade 2 diverticulitis) with the remaining seven experiencing Grade 1 nausea. No patient experienced Grade 3+ toxicities in this cohort. One patient experienced a 5-day delay in systemic therapy initiation due to neutropenia; otherwise, all patients planned for systemic therapy started without delay. VMAT VBS-CSI is an effective technique to reduce dose to surrounding OARs and vertebral bodies. In this study, VMAT VBS-CSI led to acceptable toxicity compared to patients treated with proton CSI on a phase 2 clinical trial. An NRG phase 3 clinical trial may be developed to evaluate the efficacy of proton-based CSI for patients with LMD. However, these data show how VMAT VBS-CSI may be an acceptable alternative for centers without proton therapy capabilities. Given its promising early results, future prospective evaluation of the technique is warranted.