{"paper_id":"2da72bf4-67db-4566-a1c5-2e42f14e09d2","body_text":"This is a preprint and has not been peer reviewed. Data may be preliminary.\nTARGETED INHIBITION IN PEDIATRIC MET and ALK ALTERED PEDIATRIC HIGH GRADE GLIOMAS: OBJECTIVE RESPONSES FOLLOWED BY TREATMENT RESISTANCE\nAbstract\nPurpose : Pediatric-type Diffuse High Grade Gliomas (pHGG) tend to have a dismal prognosis. Some of these gliomas feature alterations in genes such as ROS1, ALK, MET, and NTRK1-3. Despite advances in categorization and development of targeted agents, the therapeutic application of these agents in pHGG is still unclear. The aim of this study is to report the outcome of two patients with pHGG who received targeted agents with initial response followed by treatment resistance. Methods : We present a retrospective case series of two patients diagnosed with pHGGs at Arkansas Children’s Hospital. Each diagnosis was determined based on histology, targeted tumor sequencing, and methylation profiling. Results : Both patients were treated with targeted therapies (Cabozantinib for a MET fusion in patient 1 and Lorlatinib for an ALK fusion in patient 2) with an objective disease response in both patients. In both cases, relapse occurred while on targeted inhibition. Recurrent tumor sequencing for patient 2 revealed a MET copy gain suggesting the mechanism of resistance in this patient. Conclusion : Pediatric high-grade gliomas with targetable alterations can show objective responses to pathway inhibition. Relapse after initial response may warrant additional surgical sample to identify new alterations which can lead to changes in therapy. Larger prospective cohorts are needed to study targeted agents in this population, and earlier integration of these agents may be beneficial.\nSupplementary Material\nFile (wilson pediatric high grade glioma case series.docx)\n- Download\n- 5.35 MB\nInformation & Authors\nInformation\nVersion history\nCopyright\nThis work is licensed under a Non Exclusive No Reuse License.\nKeywords\nAuthors\nMetrics & Citations\nMetrics\nArticle Usage\n249views\n117downloads\nCitations\nDownload citation\nDavid Wilson, Sateesh Jayappa, Lora Parker, et al.\nTARGETED INHIBITION IN PEDIATRIC MET and ALK ALTERED PEDIATRIC HIGH GRADE GLIOMAS: OBJECTIVE RESPONSES FOLLOWED BY TREATMENT RESISTANCE. Authorea. 12 July 2025.\nDOI: https://doi.org/10.22541/au.175231445.55763704/v1\nDOI: https://doi.org/10.22541/au.175231445.55763704/v1\nIf you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.\nFor more information or tips please see 'Downloading to a citation manager' in the Help menu.","source_license":"CC-BY-4.0","license_restricted":false}