Proton Beam Therapy for Pediatric Tumors of the Central Nervous System—Experiences of Clinical Outcome and Feasibility from the KiProReg Study

Abstract

As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT.

Deep-learning-based deformable image registration of head CT and MRI scans

“…The clinical protocol requires a planning MRI if the most recent diagnostic MRI is older than 30 days or if anatomical changes were likely in this period. For the 25 patients, who were part of a cohort of the KiProReg register study (DRKS00005363) [20], the acquisition of the planning scans was performed subsequent to the respective X-ray CT scan. In addition, the testing data set with 14 paediatric patients was used to assess the workflow with the most suitable parameter setting.…”

Chemotherapy in pediatric brain tumor and the challenge of the blood–brain barrier

“…Improvement in gross total resection (GTR) or subtotal resection (STR) of PBT has resulted in the targeted removal of the tumor and enhanced radiological treatment 6 . For example, proton beam treatment is one promising radiation therapy as it allows targeted dosing at high levels with reduced surrounding tissue damage 7 . Unfortunately, despite advancements, radiation therapy can cause hearing loss, impaired neurocognition, and alteration in neuroendocrine function, among other adverse events 8–10 .…”

“… 6 For example, proton beam treatment is one promising radiation therapy as it allows targeted dosing at high levels with reduced surrounding tissue damage. 7 Unfortunately, despite advancements, radiation therapy can cause hearing loss, impaired neurocognition, and alteration in neuroendocrine function, among other adverse events. 8 , 9 , 10 The detrimental effect of radiotherapy in the modulation of BBB integrity was examined in immunocompetent and immunocompromised mice, and it was found that 12‐h irradiation in immunocompetent mice caused alteration of efflux transporter activity compared to immunocompromised mice indicating a role of proinflammatory molecules in BBB structural changes.…”