Targeted treatment in inflammatory myofibroblastic tumors in children.

10046 Background: Inflammatory myofibroblastic tumors (IMTs) and epithelioid inflammatory myofibroblastic sarcoma (EIMS)-a variant of IMT, are rare mesenchymal neoplasms in children. Surgical resection has been the mainstay of treatment, however it may cause morbidities due to the size, location, invasiveness of the tumor. With the identification of targetable molecular alterations, targeted treatment has begun to be used in inoperable/relapsed/refractory cases. Methods: Files of children with IMT diagnosed and treated between 1990-2023 were retrospectively evaluated for demographic, clinical, molecular characteristics, treatment and outcome. Results: The mean age of 8 patients (5 male, 3 female) at diagnosis was 9 years (8 months-17 years). Six had IMT and two EMS. Tumor localization was intestine, retroperitoneum, lower extremity in two patients each; liver and back in one each. None had metastatic at diagnosis. Three of the six patients (one EMS) who underwent only surgical resection had negative surgical margins (one after re-resection) and are under follow-up with no evidence of disease (NED). Molecular analysis was performed in six patients. ALK was positive in the tumor tissue of five patients. One patient with an inoperable local recurrence received chemotherapy, had a life-threatening infection and resistant hypercalcemia. The molecular analysis by next-generation sequencing revealed a YWHAE-ROS fusion and she was treated by ceritinib, after which a significant (>90%) tumor shrinkage occurred and hypercalcemia resolved. She is currently in remission and continuing treatment. The patient with a positive surgical margin experienced local and metastatic (lung, liver) recurrences during follow-up and was treated with chemotherapy containing vincristine, actinomycin-D, and cyclophosphamide, the patient died due to progressive disease. In a patient with an unresectable tumor and ALK positivity, crizotinib treatment was initiated. After a treatment duration of seven months with crizotinib, the tumor completely regressed and treatment was stopped. On follow-up, local recurrence was detected after two months of cessation of crizotinib, crizotinib was restarted, considering the infiltrative appearance of the tumor and possible morbidities if operated. Two months after readministering crizotinib, complete response was achieved once again. The patient is continuing treatment with crizotinib. Thus, 7/8 patients are alive with NED for a median of 99 (9-174) months. Conclusions: Inflammatory myofibroblastic tumor and epithelioid inflammatory myofibroblastic sarcoma are rare in children. Surgery is the mainstay of treatment. The effectiveness of chemotherapy is yet unclear despite its use in inoperable cases. Molecular analysis of tumor tissue is highly recommended as targets such as ALK rearrangements or ROS fusions may enable the use of targeted treatments with fewer side effects.