NTRK (Neurotrophic receptor tyrosine kinase)

Pan-TRK IHC has a false-positive rate of ∼4%, particularly in squamous cell carcinomas, underscoring the need for confirmatory NGS to validate IHC findings and assess fusion functionality. Functional NTRK1/2/3 fusions remain exceedingly rare in NSCLC, with a detection rate of 0.03% across our combined cohorts.

However, NTRK gene aberrations are rare, necessitating FISH or next-generation sequencing confirmation for pan-TRK-positive cases to identify candidates for TRK-targeted therapy. Further studies are needed to clarify the biological role of non-fusion-mediated pan-TRK overexpression in meningioma progression.

In conclusion, this work consolidates practical recommendations for integrating optimized gene fusion detection into routine clinical workflows. These include guidance on assay design, quality control measures, and method validation, to ensure the delivery of reliable results to support personalized treatment strategies in NSCLC.

This case provides critical clinical evidence of the "driver versus passenger" phenomenon in precision oncology. It demonstrates that the epigenetic dominance of the SS18::SSX fusion can override the therapeutic relevance of a concurrent NTRK fusion. Our findings serve as a cautionary note: actionable targets detected via next-generation sequencing must be interpreted within the tumor's canonical biological context, as lineage-defining translocations may render secondary kinase alterations therapeutically inert.

P1/2, N=77, Suspended, University of California, Davis | Trial completion date: Jan 2030 --> Jan 2034 | Recruiting --> Suspended | Trial primary completion date: Jan 2026 --> Dec 2030

Larotrectinib shows meaningful efficacy and favorable tolerance across NTRK fusion-positive malignancies beyond IFS. These real-world data support early molecular testing, highlight histology-dependent outcomes, and inform clinical management strategies.

Eratrectinib demonstrated manageable safety profile and promising efficacy in patients with NTRK fusion positive solid tumors, representing a new treatment option for this patient population. Further studies to confirm the efficacy and safety of eratrectinib are ongoing. Trial registration NCT04614740 (ClinicalTrials.gov).

This comprehensive molecular profiling study illustrates the real-world utility and limitations of targeted next-generation sequencing of BTC and affirms the use of precision medicine in patients with these diseases. Characterization of genomic heterogeneity and therapeutic resistance has the potential to inform ongoing drug development efforts for BTC.

These observed frequencies should be interpreted as case-level implementation signals surfaced through routine CGP rather than assay superiority evidence, biological prevalence estimates, or treatment-benefit data. This nationwide, platform-aware benchmark supports practical interpretation of tumor-agnostic eligibility signals in routine CGP practice in Japan.

Rare actionable genomic alterations are recurrently identified in NGS-assessed NSCLC cohorts. These findings support the clinical value of broad genomic profiling, provide realistic expectations for diagnostic yield in routine practice, and may inform precision oncology implementation, molecular-testing pathways, and resource allocation.

This observation highlights the potential clinical benefit of repeating NGS even in late stages of breast cancer treatment. Furthermore, NGS may expand our ability to utilize targeted agents in not only early phase but also later phase breast cancer treatment.

P1/2, N=358, Recruiting, Xilio Development, Inc. | Trial completion date: Feb 2027 --> Sep 2028 | Trial primary completion date: Feb 2027 --> Sep 2028