b'CLINICAL SCIENCENeed federal legislation for clinical trials andgenomic testing.RESEARCH: GAPS ANDNeed more pilot studies for novel therapies.NEEDS FOR RARENeed orphan drug designations of medications. Need PK analysis for pediatric dosing. LYMPHATIC DISEASES Need novel methods for drug delivery directly intoThere are big gaps in the collaborative collection affected tissue and cells to avoid the toxic side effect profile of existing and new drugs (with accompanying of data and biospecimens for rare lymphatic and animal models to test these methods).vascular anomalies.Need to be able to target mutant endothelialWe need natural history studies.cells and reduce toxic side effects of drugs usedWe need broader, more comprehensive, and for treatment. collaborative registries. Is trametinib a better treatment for RAS pathway Gaps in early diagnosis and therefore with delayed driven CLAs than sirolimus? What other MEK- diagnosis comes morbidity and mortality.inhibitors may be better with less side effects?How do mutations in genes that cause CLAs affect We need more non-invasive diagnostic tests and biomarkers for lymphatic and vascular anomalies. Drug mechanism studies: how does sirolimus or initial lymphatics and collecting lymphatics?Are there therapies besides obvious targeted any drug used currently for CLAs work (e.g., trametinib, apelesib). How do we assess pharma- therapies that would be effective at treating CLAs? Can the lymphatic disease be monitored bycokinetics response? How do we evaluate drug resistance (pathway investigation) with all imaging (e.g., FDG-PET, fMRI, or other novel of these drugs? techniques)?Why do mutations in PIK3CA cause different Do we need dual therapy, working on both thephenotypes?PIK3 and RAS pathways?Better evaluation of response (radiologically) andstandardized outcome measures. Development of validated patient reported outcomesand other clinical outcomes.Other assessments for genotype that are safer thanbiopsy (i.e.,circulating free DNA).|Gaps in the Field of Lymphatic Research|2024 Update|7'