NTRK1 positive

The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

Case Presentation and We report two cases with RAI-resistant lung metastases treated with larotrectinib: 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation)...In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of -0.060. As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

Three patients recurred after first-line therapy: 1 with BRAF mutated GBM, 1 with GBM harboring FGFR3-TACC3 fusion, and 1 with NTRK1 fusion positive glioneuronal tumor received specific BRAF/MEK inhibitor (dabrafenib/trametinib), FGFR inhibitor (pemigatinib), and NTRK inhibitor (larotrectinib), respectively. The incidence of actionable molecular alterations in IDH wt gliomas and glioneuronal/neuronal tumors was low. However, the use of targeted therapies may lead to significant impact on the outcome.

NTRK expression is common in JXG or AXG and associated with localized rather than disseminated disease. We speculate that the potential importance of this in JXG and AXG has not been previously appreciated due to the tendency to focus sequencing studies on disseminated disease. We confirm the presence of an NTRK1 fusion in two positive cases by NGS, however, additional genetic studies are necessary to further explore this.

However, ORR was the lowest among entrectinib-treated NTRK+ CRC (20%, 2/10) and selpercatinib treated RET+ CRC (20%, 2/10)...Thus, NTRK+ and RET+ CRC patients may benefit more from FDA approved immunotherapy (single agent pembrolizumab or dostarlimab) than TKIs in NTRK+ and RET+ CRC. We surveyed all 58 human RTKs to identify RTK fusions in CRC using AACR GENIE cBioPortal public version 13.0... In this comprehensive survey of human RTK fusions in CRC, NRTK1+ and RET+ CRC harbor significantly higher mean co-occurring genomic alterations compared to other RTK+ CRC consistent with previous reports. Hypothesis-generating randomized trials comparing pembrolizumab versus target-specific TKIs should be performed to address optimal treatment of NTRK1/3/RET+ CRC.

Regarding break-apart FISH, NTRK detection is difficult because of the diversity of signal patterns. Further research is warranted to identify the characteristics of NTRK-fusion CRCs.

This study provides new insights and facilitates our current understanding of clinicopathological features and survival outcomes of different fusion oncogenes in PTCs. It may help clinicians better counsel the patients and tailor appropriate treatment decisions.

In 2020, UK NICE approved a histology-independent TRK-inhibitor drug, larotrectinib, for treatment of such tumours in both children and adults.Methodology: We present the case of a 49-year old female who presented with recurrence of an NTRK1-TPM3 fusion positive cervical sarcoma nine months following primary total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). The patient was initially referred with a large cervical mass measuring 9cm on imaging...Although four cycles of doxorubicin were administered, the pulmonary masses continued to progress... Excellent durable response and improved survival was achieved. Testing for NTRK should be done and NTRK inhibitors considered for advanced gynaecological sarcomas. Future research will further assess the efficacy of TRK-inhibition therapy as primary, neoadjuvant and adjuvant treatment.

The capability of AZD4547 to inhibit TRKA, TRKB and clinically relevant mutants (TRKA G595R, G667S, G667C and G667A) was also evaluated using Ba/F3 cells harboring the ETV6-NTRKs fusion gene. The combined observations demonstrate the potential application of AZD4547 for treatment of NTRK fusion driven cancers.

"In our series, 20% (1/5) of MSI-H KRAS/NRAS/BRAF wt CRC were NTRK rearranged. All methodologies were optimal to detect NTRK rearrangements. Different methodologies provide complementary information about rear- rangements, being NGS the most specific."