Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT).

Autor: Sommer S; Department of Hematology and Oncology, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Schmutz M; Department of Hematology and Oncology, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Schaller T; General Pathology and Molecular Diagnostics, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Mayr P; Department of Hematology and Oncology, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Dintner S; General Pathology and Molecular Diagnostics, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Märkl B; General Pathology and Molecular Diagnostics, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Huss R; General Pathology and Molecular Diagnostics, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Golas MM; Department of Hematology and Oncology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.; Human Genetics, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Kuhlen M; Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.; Swabian Children's Cancer Center, University Medical Center Augsburg, Augsburg, Germany., Jordan F; Department of Hematology and Oncology, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Claus R; General Pathology and Molecular Diagnostics, Faculty of Medicine, University of Augsburg, Augsburg, Germany.; Comprehensive Cancer Center Augsburg (CCCA), Faculty of Medicine, University of Augsburg, Augsburg, Germany., Heinrich B; Heinrich/Bangerter, Hämatologie-Onkologie im Zentrum MVZ, Augsburg, Germany.
Jazyk: angličtina
Zdroj: Cancer reports (Hoboken, N.J.) [Cancer Rep (Hoboken)] 2024 Jan; Vol. 7 (1), pp. e1916. Date of Electronic Publication: 2023 Nov 11.
DOI: 10.1002/cnr2.1916
Abstrakt: Background: Inflammatory myofibroblastic tumor (IMTs) are rare mesenchymal neoplasms with slow growth. Resection is considered as therapeutic standard, with chemotherapy being insufficiently effective in advanced disease. ALK translocations are present in 50% of cases, ROS1 fusions (YWHAE::ROS1, TFG::ROS1) are extremely rare. Here, we present a case with TFG::ROS1 fusion and highlight the significance of molecular tumor boards (MTBs) in clinical precision oncology for post-last-line therapy.
Case Presentation: A 32-year-old woman presented with IMT diagnosed at age 27 for biopsy and treatment evaluation. Previous treatments included multiple resections and systemic therapy with vinblastine, cyclophosphamide, and methotrexate. A computed tomography scan showed extensive tumor infiltration of the psoas muscles and the posterior abdomen. Next generation sequencing revealed an actionable ROS1 fusion (TFG::ROS1) with breakpoints at exon 4/35 including the kinase domain and activating the RAS-pathway. TFG, the Trk-fused gene, exerts functions such as intracellular trafficking and exhibits high sequence homology between species. Based on single reports about efficacy of ROS1-targeting in ROS1 translocation positive IMTs the patient was started on crizotinib, an ATP-competitive small molecule c-MET, ALK and ROS1-inhibitor. With a follow-up of more than 9 months, the patient continues to show a profound response with major tumor regression, improved quality of life and no evidence for severe adverse events.
Conclusion: This case underscores the importance of the availability of modern molecular diagnostics and interdisciplinarity in precision oncology to identify rare, disease-defining genotypes that make an otherwise difficult-to-treat disease targetable.
(© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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