Durable response to serial tyrosine kinase inhibitors (TKIs) in an adolescent with metastatic TFG-ROS1 fusion positive Inflammatory Myofibroblastic Tumor (IMT). (August 2021)

• Record Type: Journal Article
• Authors: Ingley, Katrina M.; Hughes, Debbie; Hubank, Michael; Lindsay, Daniel; Plumb, Andrew; Cox, Rachel; Chesler, Louis; Strauss, Sandra J.
• Is Part Of: Lung cancer. Volume 158(2021)
• Page Start: 151
• Page End: 155
• Publication Date: 2021-08
• Subjects: IMT Inflammatory myofibroblastic tumor -- TKIs tyrosine kinase inhibitors -- NGS next generation sequencing -- ATP adenosine triphosphate -- NSCLC non-small cell lung cancer -- FISH fluorescent in-situ hybridization -- IHC immunohistochemistry -- EORTC European Organisation for Research and Treatment of Cancer -- DNA deoxyribonucleic acid -- RNA ribonucleic acid -- FFPE formalin-fixed paraffin-embedded -- EpSSG European pediatric Soft Tissue Sarcoma Study Group; Inflammatory myofibroblastic tumor (IMT) -- Tyrosine kinase inhibitors (TKI) -- Crizotinib -- Lorlatinib -- RNA sequencing -- ROS1; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.05.024
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Inflammatory myofibroblastic tumors (IMTs) are rare and can affect adolescents. This case report of an adolescent with ALK negative metastatic thoracic IMT demonstrates how diagnosis of IMT can be challenging due to a variable morphologic spectrum. Targeted RNA sequencing detected a TFG-ROS1 fusion on progression of the primary thoracic tumor which was retrospectively found on the diagnostic primary tumor. There is no standard of care for management of unresectable IMT, this disease responded to serial challenge with TKIs including 3rd generation ALK/ ROS1 inhibitor lorlatinib which led to resection of the ROS1 rearranged primary thoracic tumor. Detailed molecular analysis and repeat biopsy at progression should be considered in ALK negative IMTs to detect rare gene rearrangements and optimise ongoing therapy. Abstract: Here, we present the case of an adolescent with a rare metastatic Inflammatory myofibroblastic tumor (IMT) harboring a TFG-ROS1 fusion initially detected on tumor progression and retrospectively identified in the primary tumor after targeted RNA sequencing. The patient benefitted from sequential TKIs over a 5-year period with response to the third generation ALK/ROS inhibitor, lorlatinib leading to resection of the primary tumor. Detailed molecular analysis can identify targetable oncogenic kinase fusions that alters management in patients with unresectable disease and should be considered in all patients.