Recommended testing algorithms for NTRK gene fusions in pediatric and selected adult cancers: Consensus of a
Kiat Hon Tony Lim1, Hwai Loong Kong2, Kenneth Tou En Chang3
1Division of Pathology, Department of Anatomical Pathology, Singapore General Hospital, Singapore.
Abstract:
The occurrence of neurotrophic tyrosine receptor kinase (NTRK) gene fusions in a wide range of tumor types presents an attractive opportunity for using a tropomyosin receptor kinase (TRK) inhibitor as cancer therapy. Recent clinical studies have demonstrated highly efficacious outcomes associated with the use of TRK inhibitors, such as larotrectinib and entrectinib in NTRK fusion-bearing cancers, in both adult and pediatric populations. While NTRK gene fusions are commonly found in some uncommon adult and pediatric malignancies, they are also found, albeit rarely, in a wide range of more common malignancies. The potential value of testing for NTRK gene fusions in practically all advanced malignancies is underpinned by the remarkable therapeutic outcomes that TRK inhibitors offer. This requirement presents practical and financial challenges in real-world oncological practice. Furthermore, different testing platforms exist to detect NTRK gene fusions, each with its advantages and disadvantages. It is, therefore, imperative to develop strategies for NTRK gene fusion testing in an attempt to optimize the use of limited tissue specimen and financial resources, and to minimize the turnaround time. A multidisciplinary task force of Singapore medical experts in both public and private sectors was convened in late 2020 to propose testing algorithms for adult colorectal tumors, sarcomas, non-small cell lung cancer, and pediatric cancers, with particular adaptation to the Singapore oncological practice. The recommendations presented here highlight the heterogeneity of NTRK-fusion positive cancers, and emphasize the need to customize the testing methods to each tumor type to optimize the workflow.
Insights
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions can be targeted with TRK inhibitors for cancer therapy. Developing optimal testing strategies is crucial for efficient resource utilization and timely treatment in diverse cancers.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are present in various cancers, offering a therapeutic target for tropomyosin receptor kinase (TRK) inhibitors.
- TRK inhibitors like larotrectinib and entrectinib have shown significant efficacy in NTRK fusion-positive adult and pediatric cancers.
- While NTRK fusions are rare in common malignancies, their presence in diverse tumor types suggests broad applicability of TRK inhibitor therapy.
Purpose of the Study:
- To propose optimized testing algorithms for NTRK gene fusions in specific adult and pediatric cancers.
- To address the practical and financial challenges of NTRK gene fusion testing in real-world oncology.
- To guide the selection of appropriate testing platforms and strategies for efficient resource management.
Main Methods:
- Convening a multidisciplinary task force of Singaporean medical experts.
- Developing testing algorithms tailored to specific cancer types, including colorectal tumors, sarcomas, non-small cell lung cancer, and pediatric cancers.
- Considering the heterogeneity of NTRK-fusion positive cancers and optimizing testing workflows.
Main Results:
- The recommendations highlight the diverse range of cancers harboring NTRK gene fusions.
- The proposed algorithms aim to optimize the use of limited tissue and financial resources.
- Customizing testing methods for each tumor type is emphasized to improve workflow efficiency.
Conclusions:
- TRK inhibitors represent a promising targeted therapy for NTRK fusion-positive cancers.
- Strategic NTRK gene fusion testing is essential to identify eligible patients and optimize treatment outcomes.
- Tailored testing approaches are necessary to overcome resource limitations and improve diagnostic turnaround times.
