Case Report: Adult NTRK-Rearranged Spindle Cell Neoplasm: Early Tumor Shrinkage in a Case With Bone and Visceral Metastases Treated With Targeted Therapy

Abstract

BackgroundNTRK (neurotrophic tyrosine receptor kinase)-rearranged spindle cell neoplasms are a new group of tumors included in the new 5th edition of the World Health Organization (WHO) classification of soft Tissue and Bone Sarcomas. These tumors are characterized by NTRK gene fusions and show a wide spectrum of histologies and clinical behavior. Several targeted therapies have recently been approved for tumors harboring NTRK fusions, including STS.Case PresentationA 26-year-old male with advanced, pretreated NTRK rearranged spindle cell neoplasm and liver, lung and bone metastases was treated with larotrectinib on a continuous 28-day schedule, at a dose of 100 mg twice daily. An 18FDG-PET/CT scan performed after 7 days of treatment showed tumor shrinkage in both visceral and bone lesions. There was no drug-related toxicity. Subsequent evaluations confirmed continued tumor regression in disease sites. The patient is well and continues treatment.ConclusionThe clinical and radiological response of our patient with an uncommon TPM4 (exon 7)-NTRK1 (exon 12) gene fusion tumor treated with a first-generation TRK inhibitor could contribute to a better understanding of the biology of this new STS entity and help to improve patient management.

Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma

“…Antibody-drug conjugate (ADC) drugs against NY-ESO-1 have already demonstrated evidence of activity. 38 Additionally, some new biomarkers such as neurotrophic tyrosine receptor kinase (NTRK), 11 RANK-L, 12 and corresponding drugs larotrectinib, denosumab have also been shown to affect certain sarcomas dramatically.…”

NTRK Fusions in 1113 Solid Tumors in a Single Institution

“…IMTs are genetically heterogeneous, and most of them harbor gene rearrangements of receptor tyrosine kinases, including ALK (approximately 50–60%), ROS1 (approximately 5–10%), and NTRK3 (approximately 5%) but rarely RET and PDGFRβ fusion [ 27 , 28 , 29 , 30 , 31 ]. Recent translational studies provided evidence of the potential activity of TKIs in sarcoma, including larotrectenib [ 32 , 33 , 34 ]…”

IntestinalLMNA::NTRK1-fused spindle cell neoplasm with S100 and CD34 coexpression: a new case

“… 2 3 Responses in NTRK-SCNs have also been reported. 19 Pan-TRK (clone EPR17341) immunohistochemistry, which detects the C-terminal region of TRK A, B and C proteins, has been shown to be a reliable surrogate marker for the presence of an NTRK fusion. However, molecular testing for NTRK fusions by NGS or fluorescence in situ hybridization (FISH) is usually recommended for verification due to observed limitations in sensitivity and specificity of the pan-TRK immunostaining.…”

“…The actionable NTRK fusions appear to predict response to TRK inhibitors, such as larotrectinib and entrectinib, across multiple tumour types and histologies, necessitating their detection 2 3. Responses in NTRK-SCNs have also been reported 19. Pan-TRK (clone EPR17341) immunohistochemistry, which detects the C-terminal region of TRK A, B and C proteins, has been shown to be a reliable surrogate marker for the presence of an NTRK fusion.…”