Integrated response analysis of pediatric low-grade gliomas during and after targeted therapy treatment


 
 
 Pediatric low grade gliomas (pLGGs) are the most common central nervous system tumor in children, characterized by RAS/MAPK pathway driver alterations. Genomic advances have facilitated use of molecular targeted therapies, however their long-term impact on tumor behavior remains critically unanswered.
 
 
 
 We performed an IRB-approved, retrospective chart and imaging review of pLGGs treated with off-label targeted therapy at Dana-Farber/Boston Children’s from 2010 to 2020. Response analysis was performed for BRAFV600E and BRAF fusion/duplication driven pLGG subsets.
 
 
 
 Fifty-five patients were identified (dabrafenib n = 15, everolimus n = 26, trametinib n = 11, vemurafenib n = 3). Median duration of targeted therapy was 9.48 months (0.12 – 58.44). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation were 62.1%, 38.2%, and 31.8%, respectively. Mean volumetric change for BRAFV600E mutated pLGG on BRAF inhibitors was -54.11%; median time to best volumetric response was 8.28 months with 9 of 12 (75%) objective RAPNO response . Median time to largest volume post-treatment was 2.86 months (+13.49%); mean volume by last follow-up was -14.02%. Mean volumetric change for BRAF fusion/duplication pLGG on trametinib was +7.34%; median time to best volumetric response was 6.71 months with 3 of 7 (43%) objective RAPNO response . Median time to largest volume post-treatment was 2.38 months (+71.86%); mean volume by last follow up was +39.41%.
 
 
 
 Our integrated analysis suggests variability in response by pLGG molecular subgroup and targeted therapy, as well as the transience of some tumor growth following targeted therapy cessation.
