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Abdul Rehman Syed University of Calgary, Calgary, Alberta, Canada

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Aakash Gorana Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada

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Erik Nohr Alberta Precision Laboratories, Molecular Pathology Program, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Xiaoli-Kat Yuan Precision Oncology Hub Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada

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Parthiv Amin MASc Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary Alberta, Canada

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Sana Ghaznavi Arnie Charbonneau Cancer Institute, Department of Medicine, Section of Endocrinology, University of Calgary, Calgary, Alberta, Canada

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Debbie Lamb Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada

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John McIntyre Precision Oncology Hub Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada

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Markus Eszlinger Department of Oncology, Cumming School of Medicine, and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada

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Ralf Paschke Departments of Medicine, Section of Endocrinology, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Context

Two-thirds of metastatic differentiated thyroid cancer (DTC) patients have radioiodine (RAI)-resistant disease, resulting in poor prognosis and high mortality. For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, variable success of re-induction of RAI avidity during treatment with NTRK or RET inhibitors has been reported.

Case presentation and results

We report two cases with RAI-resistant lung metastases treated with larotrectinib: an 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation). Post larotrectinib treatment, diagnostic I-123 whole body scan revealed unsuccessful RAI-uptake re-induction in the TERT-positive tumor, with a thyroid differentiation score (TDS) of −0.287. In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of −0.060.

Conclusion

As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

Open access