Inflammatory Myofibroblastic Tumor With <i>ROS1</i> Gene Fusions in Children and Young Adolescents.

Abstract

Inflammatory myofibroblastic tumors (IMTs) are often driven by anaplastic lymphoma kinase fusions and less frequently by alternative fusions such as <i>ROS1</i>. We describe the clinical characteristics, treatment approach, and outcome for a series of young patients with IMTs and <i>ROS1</i> alterations. This was a retrospective, international, multicenter study analyzing young patients (younger than 21 years) with <i>ROS1</i>-altered IMTs treated in 10 European referral centers between 2014 and 2022. Patients were included in the European <i>pediatric</i> Soft tissue sarcoma Study Group NRSTS-2005 protocol or registered in the Soft Tissue Sarcoma 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. A total of 19 patients (median age 8.3 years) were included. Most patients had a biopsy at diagnosis (Intergroup Rhabdomyosarcoma Study [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 neoadjuvant systemic therapy in first line (four received multiple treatments): high-dose steroids (n = 2), vinorelbine/vinblastine with methotrexate (n = 6), or <i>ROS1</i> inhibitors (n = 8). After a median follow-up of 2.8 years (range, 0.2-13.4), seven patients developed an event. The 3-year event-free survival was 41% (95% CI, 11 to 71), and the 3-year overall survival was 100%. Outcome for <i>ROS1</i>-altered IMTs appears excellent. A complete resection at diagnosis was often not feasible, and most patients needed neoadjuvant therapy. Patients who developed a tumor event could be cured with reinitiation 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.