(P 202) INFLAMMATORY MYOFIBROBLASTIC TUMOUR WITH ROS1 GENE FUSIONS IN CHILDREN AND YOUNG ADOLESCENTS

Objective: Inflammatory Myofibroblastic Tumours (IMTs) are very rare tumours that may occur in children, adolescents, and adults. Although IMTs are of intermediate malignancy, they may be locally aggressive and difficult to resect. IMTs are often driven by ALK fusions and less frequently by alternative fusions such as ROS1. As a result, targeted treatments (ALK/ROS1 inhibitors) have become available for these patients. We describe the clinical characteristics, treatment approach and outcome for a series of young patients with IMTs and ROS1 alterations.

Methods: Retrospective, international, multi-centre study analysing young patients ( < 21 years) with ROS1 altered IMTs, treated in ten European referral centres between 2014 and 2022. Patients were included in the EpSSG NRSTS-2005 protocol or registered in the SoTiSaR registry. Primary surgery was recommended if a microscopic radical resection was feasible without mutilation. No standard systemic treatment protocol was available, but several medical options were recommended.

Results: A total of 19 patients (median age 8.3 years) were included. Most patients had a biopsy at diagnosis (IRS I; n=2, IRS II; n=1, IRS III biopsy; n=11, IRS III resection; n=3, IRS IV; n=2). Twelve patients received neo-adjuvant systemic therapy in first line (four received multiple treatments): high dose steroids (n=2), vinorelbine/vinblastine with methotrexate (n=6), or ROS1 inhibitors (n=8). After a median follow-up of 2.8 years (range, 0.2-13.4), seven patients developed an event. Two patients developed loco-regional progression, three had a loco-regional relapse, one developed both progression of the primary tumour and of a metastatic lesion in the central nervous system, and one patient had persistent disease with systemic symptoms. The 3-year event free survival was 41% (95% confidence interval 11-71%) and 3-year overall survival 100%.

Conclusion: Outcome for ROS1 altered IMTs appears excellent. A complete resection at diagnosis was often considered not feasible and most patients needed neo-adjuvant therapy. Patients that developed a tumour event could be cured with re-initiation of systemic therapy and/or surgery. This approach illustrates a switch in treatment philosophy moving from immediate, often mutilating, surgery to systemic (targeted) therapy as a bridge to more conservative surgery later in the treatment course.