NTRK fusion

RET fusions and genetic alteration combination are independent prognostic markers for tumor recurrence of PTC, integrating tumors' genetic status into the 2025 ATA RSS system improves the accuracy of risk stratification for PTC.

P2, N=152, Not yet recruiting, The Third Xiangya Hospital of Central South University

The approach emphasizes (i) selecting a thyroid-appropriate molecular assay from the outset whenever feasible, (ii) explicitly documenting residual suspicion and the scope of the performed assay in pathology reports, (iii) using pan-TRK immunohistochemistry only as an optional triage tool rather than a rule-out test, and (iv) considering RNA-based or other fusion-optimized assays only when the original clinical question remains unresolved and the result is clinically relevant. This framework is intended to reduce false reassurance from negative limited panels while reinforcing the need for appropriate molecular testing in the correct clinical scenario.

Across both diseases, circulating tumor DNA is emerging as a promising tool for prognostication, minimal residual disease assessment, response monitoring, and early resistance detection. Contemporary care increasingly depends on early molecular profiling, individualized treatment sequencing, and integration of targeted therapies, biomarker-guided immunotherapy, and clinical trials.

In this cohort, the DNA+RNA-based panel showed a higher detection rate for TK fusions, although the panels were applied to different patient groups and the sensitivity and specificity could not be determined. Future studies evaluating different test types on the same tumor specimens are warranted to clarify whether the dual-sequencing approaches can improve the identification of actionable genetic events.

P1, N=14, Not yet recruiting, Jecho Biopharmaceuticals Co., Ltd.

FISH may represent a useful intermediate diagnostic tool when NGS is unavailable but requires cautious interpretation particularly in cases with atypical or isolated signals. NGS-based molecular confirmation remains essential for the definitive identification of NTRK fusions.

The results from this study can support healthcare planning and budget forecasts, including for different potential government treatment subsidy scenarios.

P2, N=78, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | N=42 --> 78 | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Sep 2025 --> Sep 2026

P2/3, N=82, Active, not recruiting, SWOG Cancer Research Network | Trial primary completion date: Feb 2027 --> Jun 2027

TRK inhibitors (larotrectinib, entrectinib, repotrectinib) are FDA/EMA-approved for pediatric and adult solid tumors with NTRK fusions and have demonstrated high and durable response rates. The identification of ETV6-NTRK3 provides diagnostic specificity and offers a precision oncology option in the event of relapse. Long-term surveillance and multidisciplinary follow-up remain essential for optimal care.

Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.