308 Administration of targeted therapy in children with NTRK rearranged mesenchymal neoplasms

The aim of this report is to present 2 patients diagnosed with neoplasm of mesenchymal origin, in whom NTRK inhibitor entrectinib was succesfully administered. The first patient presented at the age of 9 months as reccurent chalazion. During subsequent clinical and radiological follow-up a diagnosis of right upper eyelid tumor was made. Taking into account tumor localization, surgical procedure of a maximum possible tumor reduction was performed, unfortunately with positive resection margins. Histopthological analysis confirmed the diagnosis of „NTRK-rearranged spindle cell neoplasm’ according to the new 2020 WHO classification of soft tissue tumors. The neoplasm was charachterized by increased cellularity and relatively low mitotic activity. The possibility of an aggressive clinical course could not be excluded. Molecular analysis (FusionPlex Sarcoma Kit SAR6) verified an LMNA-NTRK fusion and oral entrectinib therapy was initiated. The patient has tolerated the medication very well and is without the radiological signs of eventual local relapse (magnetic resonance imaging). The second patient is a 12-year-old boy presenting with a solid expansive lesion of the lesser pelvis extending towards the groin and anterior abdominal wall (locoregional disease). Tumor tissue sampling comfirmed malignant peripheral nerve sheath tumor. Neoadjuvant systemic chemotherapy according to the EpSSG-NRSTS protocol and radiotherapy accomplished only partial reduction of the tumor mass prompting next generation sequencing on formalin-fixed paraffin-embedded tissue blocks (FoundationOne®Heme) that confirmed LMNA-NTRK1 fusion. Oral entrectinib has been initiated leading to tumor shrinkage that enabled complete surgical resection. The adverse effects registered in this case are one forearm fracture and increased appetite accompanied by significant weight gain that are diminished after medication dose reduction. In conclusion, implementation of the targeted therapy has enabled avoidance of mutilating surgery and adverse effecets of conventional cytostatic agents in the first case. Excellent control of malignant mesenchymal tumor has been achieved in the second case.