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1.
Mol Diagn Ther ; 27(1): 87-103, 2023 01.
Article in English | MEDLINE | ID: mdl-36194351

ABSTRACT

INTRODUCTION: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions occur in ~ 0.3% of all solid tumours but are enriched in some rare tumour types. Tropomyosin receptor kinase (TRK) inhibitors larotrectinib and entrectinib are approved as tumour-agnostic therapies for solid tumours harbouring NTRK fusions. METHODS: This study investigated the prevalence of NTRK fusions in Canadian patients and also aimed to help guide NTRK testing paradigms through analysis of data reported from a national clinical diagnostic testing program between September 2019 and July 2021. RESULTS: Of 1,687 patients included in the final analysis, NTRK fusions were detected in 0.71% (n = 12) of patients representing salivary gland carcinoma (n = 3), soft tissue sarcoma (n = 3), CNS (n = 3), and one in each of melanoma, lung, and colorectal cancer. All three salivary gland carcinomas contained ETV6-NTRK3 fusions. Thirteen (0.77%) clinically actionable incidental findings were also detected. Two of the 13 samples containing incidental findings were NTRK fusion-positive (GFOD1-NTRK2, FGFR3-TACC3 in a glioblastoma and AFAP1-NTRK2, BRAF c.1799T>A in a glioma). The testing algorithm screened most patient samples via pan-TRK immunohistochemistry (IHC), whereas samples from the central nervous system (CNS), pathognomonic cancers, and confirmed/ putative NTRK fusion-positive samples identified under research protocols were reflexed straight to next-generation sequencing (NGS). CONCLUSION: These findings highlight the benefit and practicality of a diagnostic testing program to identify patients suitable for tumour-agnostic TRK inhibitor therapies, as well as other targeted therapies, due to clinically actionable incidental findings identified. Collectively, these findings may inform future guidance on selecting the appropriate testing approach per tumour type and on optimal NTRK testing algorithms.


Subject(s)
Oncogene Proteins, Fusion , Receptor, trkA , Sarcoma , Humans , Canada/epidemiology , Microtubule-Associated Proteins , Neoplasms/genetics , Neoplasms/metabolism , Oncogene Proteins, Fusion/genetics , Receptor, trkA/genetics , Sarcoma/diagnosis , Sarcoma/genetics
2.
J Environ Manage ; 140: 102-10, 2014 Jul 01.
Article in English | MEDLINE | ID: mdl-24726971

ABSTRACT

Viewing bears along roadside habitats is a popular recreational activity in certain national parks throughout the United States. However, safely managing visitors during traffic jams that result from this activity often requires the use of limited park resources. Using unique visitor survey data, this study quantifies economic values associated with roadside bear viewing in Yellowstone National Park, monetary values that could be used to determine whether this continued use of park resources is warranted on economic grounds. Based on visitor expenditure data and results of a contingent visitation question, it is estimated that summer Park visitation would decrease if bears were no longer allowed to stay along roadside habitats, resulting in a loss of 155 jobs in the local economy. Results from a nonmarket valuation survey question indicate that on average, visitors to Yellowstone National Park are willing to pay around $41 more in Park entrance fees to ensure that bears are allowed to remain along roads within the Park. Generalizing this value to the relevant population of visitors indicates that the economic benefits of allowing this wildlife viewing opportunity to continue could outweigh the costs of using additional resources to effectively manage these traffic jams.


Subject(s)
Recreation/economics , Ursidae , Animals , Data Collection , Humans , Wyoming
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