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Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene

Significant improvements in the survival rates of paediatric cancer have been achieved over the past decade owing to recent advances in therapeutic and diagnostic strategies. However, disease progression and relapse remain a major challenge for the clinical management of paediatric angiosarcoma. Com...

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Autores principales: Cervi, Catherine, Sápi, Zoltán, Bedics, Gábor, Zajta, Erik, Hegyi, Lajos, Pápay, Judit, Dezső, Katalin, Varga, Edit, Mudra, Katalin, Bödör, Csaba, Csóka, Monika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997097/
https://www.ncbi.nlm.nih.gov/pubmed/36910630
http://dx.doi.org/10.3389/fonc.2023.999810
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author Cervi, Catherine
Sápi, Zoltán
Bedics, Gábor
Zajta, Erik
Hegyi, Lajos
Pápay, Judit
Dezső, Katalin
Varga, Edit
Mudra, Katalin
Bödör, Csaba
Csóka, Monika
author_facet Cervi, Catherine
Sápi, Zoltán
Bedics, Gábor
Zajta, Erik
Hegyi, Lajos
Pápay, Judit
Dezső, Katalin
Varga, Edit
Mudra, Katalin
Bödör, Csaba
Csóka, Monika
author_sort Cervi, Catherine
collection PubMed
description Significant improvements in the survival rates of paediatric cancer have been achieved over the past decade owing to recent advances in therapeutic and diagnostic strategies. However, disease progression and relapse remain a major challenge for the clinical management of paediatric angiosarcoma. Comprehensive genomic profiling of these rare tumours using high-throughput sequencing technologies may improve patient stratification and identify actionable biomarkers for therapeutic intervention. Here, we describe the clinical, histopathological, immunohistochemical and molecular profile of a novel and precision medicine-informed case where a KHDRBS1-NTRK3 fusion determined by next-generation sequencing-based comprehensive genomic profiling led to complete and sustained remission (clinical and radiological response) in an otherwise incurable disease. Our patient represents the first paediatric angiosarcoma harbouring a targetable NTRK3 fusion in the literature and demonstrates the first example of targeting this alteration in angiosarcoma using larotrectinib, an NTRK inhibitor. Clinical and radiological remission was achieved in under two months of therapy, and the patient is currently in complete remission, 4 month after stopping larotrectinib therapy, which was given over 17 months with only mild side effects reported. Therefore, this remarkable case exemplifies the true essence of precision-based care by incorporating conventional pathology with the why, when, and how to test for rare oncogenic drivers and agnostic biomarkers in paediatric angiosarcoma.
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spelling pubmed-99970972023-03-10 Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene Cervi, Catherine Sápi, Zoltán Bedics, Gábor Zajta, Erik Hegyi, Lajos Pápay, Judit Dezső, Katalin Varga, Edit Mudra, Katalin Bödör, Csaba Csóka, Monika Front Oncol Oncology Significant improvements in the survival rates of paediatric cancer have been achieved over the past decade owing to recent advances in therapeutic and diagnostic strategies. However, disease progression and relapse remain a major challenge for the clinical management of paediatric angiosarcoma. Comprehensive genomic profiling of these rare tumours using high-throughput sequencing technologies may improve patient stratification and identify actionable biomarkers for therapeutic intervention. Here, we describe the clinical, histopathological, immunohistochemical and molecular profile of a novel and precision medicine-informed case where a KHDRBS1-NTRK3 fusion determined by next-generation sequencing-based comprehensive genomic profiling led to complete and sustained remission (clinical and radiological response) in an otherwise incurable disease. Our patient represents the first paediatric angiosarcoma harbouring a targetable NTRK3 fusion in the literature and demonstrates the first example of targeting this alteration in angiosarcoma using larotrectinib, an NTRK inhibitor. Clinical and radiological remission was achieved in under two months of therapy, and the patient is currently in complete remission, 4 month after stopping larotrectinib therapy, which was given over 17 months with only mild side effects reported. Therefore, this remarkable case exemplifies the true essence of precision-based care by incorporating conventional pathology with the why, when, and how to test for rare oncogenic drivers and agnostic biomarkers in paediatric angiosarcoma. Frontiers Media S.A. 2023-02-23 /pmc/articles/PMC9997097/ /pubmed/36910630 http://dx.doi.org/10.3389/fonc.2023.999810 Text en Copyright © 2023 Cervi, Sápi, Bedics, Zajta, Hegyi, Pápay, Dezső, Varga, Mudra, Bödör and Csóka https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Cervi, Catherine
Sápi, Zoltán
Bedics, Gábor
Zajta, Erik
Hegyi, Lajos
Pápay, Judit
Dezső, Katalin
Varga, Edit
Mudra, Katalin
Bödör, Csaba
Csóka, Monika
Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
title Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
title_full Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
title_fullStr Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
title_full_unstemmed Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
title_short Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
title_sort case report: complete and durable response to larotrectinib (trk inhibitor) in an infant diagnosed with angiosarcoma harbouring a khdrbs1-ntrk3 fusion gene
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997097/
https://www.ncbi.nlm.nih.gov/pubmed/36910630
http://dx.doi.org/10.3389/fonc.2023.999810
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