Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion

Abstract

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

Uterine inflammatory myofibroblastic tumor: First report of a ROS1 fusion

“…Details regarding myogenic marker expression are limited in previous reports of ROS1-rearranged IMTs, but desmin, smooth muscle actin, and/or caldesmon appear to show variable expression. 2,15,19,22,24,25 However, it is not mentioned as to whether they are positive only in the compact areas, like seen in our case, or also in the myxoid (and hyalinized) foci. Akin to the association between ALK immunohistochemistry and ALK-rearrangement, 10 there is also evidence of a ROS1 immunohistochemical and molecular correlation, with only 2/18 (11%) ROS1rearranged IMTs being negative by immunohistochemistry.…”

“…Outside of the gynecologic tract, ROS1-rearranged IMTs account for approximately 10% 1,2,14 of tumors, with 37 cases reported to date. [1][2][3]9,[13][14][15][16][17][18][19][20][21][22][23][24] Most occur in the thoracic cavity (n = 14), gastrointestinal tract/liver (n = 10), or soft tissues (n = 10), with very rare (n = 8) are reported as being at least focally collagenized (hyalinized pattern), 3,13,15,17,19,24 which is a very rare morphologic feature in uterine IMTs, and only very focally present in the current case. Details regarding myogenic marker expression are limited in previous reports of ROS1-rearranged IMTs, but desmin, smooth muscle actin, and/or caldesmon appear to show variable expression.…”

Spitz nevus with a novel TFG‐NTRK2 fusion: The first case report of NTRK2‐rearranged Spitz/Reed nevus

“…TFG is mapped on chromosome 3q12.2, initially identified as a partner gene of TFG ‐ NTRK1 oncogenic fusion of thyroid carcinoma 24 . Subsequently, TFG was also reported to be a fusion partner of ALK , ROS1 , MET , TEC , NOR , and RARA in various tumor types 25‐33 . The present case is the first example in which TFG is reported as a fusion partner of NTRK2 .…”

Outstanding Response in a Patient With ROS1-Rearranged Inflammatory Myofibroblastic Tumor of Soft Tissues Treated With Crizotinib: Case Report

“…At disease progression, after therapy discontinuation, we decided to resume crizotinib because, as reported in the literature, new responses are still possible and, moreover, in this rare disease other effective therapies are still not approved and difficult to get the access ( 25 – 29 , 32 , 33 , 42 – 45 ).…”

“…In fact, in ALK-positive IMT patients, after progression to crizotinib, different ALK inhibitors, such as ceritinib, alectinib and lorlatinib, have been investigated reporting promising responses ( 25 – 29 , 32 , 33 , 42 – 45 ).…”