NTRK positive

Owing to the presence of neural tissue, NTRKs are highly positive in IHC, making these genes unsuitable as biomarkers for assessing NTRK inhibitor sensitivity and resistance, which are tissue-agnostic drugs. The observed low fusion rate is consistent with the literature, and the significance of the numerous point mutations identified as agnostic markers warrants further investigation. NTRK expression, fusion, and point mutations were not associated with clinical parameters or survival.

Inhibitors such as larotrectinib, entrectinib and repotrectinib are used when cancer cells harbor NTRK1, NTRK2 or NTRK3 fusion...Short courses of prednisone for the former and dexamethasone for the latter were initiated after failure of standard analgesia... For patients experiencing TRK inhibitor withdrawal pain, especially when tapering down the inhibitor is not an available strategy, a short course of corticosteroids can provide lasting relief. These cases emphasize the importance of better understanding the mechanism underlying the relationship between NRTK, NGF and nociception.

NCI-MATCH subprotocol Z1E demonstrates that larotrectinib offers clinically significant benefit with marked ORR across NTRK fusion-positive tumors with no clinically significant toxicities. These findings support the rationale for the US Food and Drug Administration's tissue-agnostic approval of larotrectinib for NTRK fusion-positive tumors. Our findings demonstrate the necessity of including NTRK1, NTRK2, and NTRK3 within comprehensive molecular assays of cancer to navigate patients to an easily administered and highly effective therapy.

These results support the use of repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .

Concurrent comprehensive genome profiling (FoundationOne® CDx) confirmed the LMNA-NTRK1 fusion, and treatment with the TRK inhibitor larotrectinib was started. With larotrectinib treatment, the tumor shrank in size at an early stage, and the response has been maintained for > 2 years.

This study suggests that pan-TRK immunostaining may be useful for confirming neural differentiation in MPNST. However, whether its positivity reflects NTRK rearrangements or neural differentiation must be carefully assessed in combination with various immunohistochemical and molecular tests.

Clinical and preclinical signals collectively support testing neurotrophin-targeted strategies to recalibrate myeloid composition, enhance antigen presentation, and restore T-cell access to tumor beds. The purpose of this review is to synthesize current evidence and propose a translational roadmap for targeting NGF/TrkA and BDNF/TrkB to remodel antitumor immunity in osteosarcoma.

According to our research, this case represents the first reported successful surgical resection of a pediatric scalp tumor with NTRK rearrangement. This finding suggests that clinicians should pay attention to early diagnosis through molecular testing and recognize the feasible value of surgical resection in the treatment of this type of tumor.

Pediatric STS are rare and biologically heterogeneous. Genomic advances have refined risk stratification and uncovered therapeutic targets; further progress relies on international collaboration and trials.

Immunohistochemistry and genetic analysis are important tools to differentiate MASC from its morphological mimickers. The treatment approach for MASC has not been well defined or standardised, necessitating further studies to develop evidence-based guidelines.

Larotrectinib was used in 142 patients, demonstrating an 83.80% response rate, with low mortality (2.82%) and recurrence (2.11%) rates. Entrectinib had a lower response rate of 63.64%. We confirm the rarity of NTRK1-3 fusions in sarcomas. TRK inhibitors show high efficacy in sarcomas, emphasizing the necessity of genomic testing in all cases.Protocol registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024563594.