Prospective Feasibility Trial of Vertebral Body Sparing Pencil Beam Scanning Proton Craniospinal Irradiation in Growing Children

Abstract

Advanced proton therapy techniques now allow for delivery of craniospinal irradiation (CSI) to the entire brain and thecal sac while sparing many of the anterior vertebral bodies from doses expected to inhibit growth, though this technique has not been prospectively studied. The purpose of this trial is to test the feasibility and robustness of vertebral body sparing (VBS) CSI in children with standard image guidance, to assess the dosimetric and toxicity benefits of this approach, and to report early clinical outcomes. Children 3-18 years old requiring CSI treatment were eligible for this IRB approved prospective clinical trial. The CSI clinical target volume (CTV) included the brain, entire thecal sac and neural foramina with no expansion. Select anterior vertebral bodies (AVB) could be included at the physician's discretion. The spinal portion of the CTV was treated with PA beam(s) with robust optimization (+/-3.5% range, 5mm positional uncertainty). Daily image guidance included kV/kV imaging. Cone beam CT (CBCT) was acquired weekly after final positioning and a virtual CT (vCT) was created for quality assurance (QA) analysis. Acute toxicity was prospectively assessed weekly during treatment and 1 month after per CTCAE v5.0. Ten children with a median patient age and CSI dose of 9 years (range 3-16) and 36 Gy (RBE) (range 15-36 Gy (RBE)) were enrolled. Common diagnoses were medulloblastoma (n = 4) and non-germinomatous germ cell tumor (n = 3). Seven patients received prior chemotherapy; 2 patients were treated with palliative intent. Dose statistics for the anterior vertebral body varied according to age, CSI dose and portion of the spine, with the greatest sparing in the lower thoracic and lumbar vertebrae for all patients. Nine patients completed all QA CTs; one patient required a replan due to weight gain. For all remaining patients the treatment was highly robust: CTV V95 reduction at the C-spine, T-spine, and L-spine was 0.0±0.1%, 0.6±1.3%, and 0.8±1.1%, respectively. The highest grade non-hematologic acute toxicity was grade 2 alopecia (n = 9) and grade 2 nausea/vomiting (n = 5). One patient reported transient grade 1 esophagitis during treatment. Hematologic toxicity included >/ = grade 3 lymphopenia in 7 patients, >/ = grade 3 leukopenia in 1 patient, >/ = grade 2 anemia in 6 patients, and >/ = grade 1 thrombocytopenia in 3 patients. Median follow-up is 16.6 months (range 10-36 months). Three patients experience intracranial disease progression: 2 local and 1 distant intracranial failure. There were no failures within the spine. Proton vertebral body sparing CSI targeting the thecal sac only is a highly robust treatment technique and is well tolerated. Weekly CBCT to assess changes in soft tissue posterior to the spine is recommended. Further follow-up is required to assess long-term growth outcomes.