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Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS...

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Autores principales: Braig, David, Runkel, Alexander, Eisenhardt, Anja E., Schmid, Adrian, Zeller, Johannes, Pauli, Thomas, Lausch, Ute, Wehrle, Julius, Bronsert, Peter, Jung, Matthias, Kiefer, Jurij, Boerries, Melanie, Eisenhardt, Steffen U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499617/
https://www.ncbi.nlm.nih.gov/pubmed/36142126
http://dx.doi.org/10.3390/ijms231810215
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author Braig, David
Runkel, Alexander
Eisenhardt, Anja E.
Schmid, Adrian
Zeller, Johannes
Pauli, Thomas
Lausch, Ute
Wehrle, Julius
Bronsert, Peter
Jung, Matthias
Kiefer, Jurij
Boerries, Melanie
Eisenhardt, Steffen U.
author_facet Braig, David
Runkel, Alexander
Eisenhardt, Anja E.
Schmid, Adrian
Zeller, Johannes
Pauli, Thomas
Lausch, Ute
Wehrle, Julius
Bronsert, Peter
Jung, Matthias
Kiefer, Jurij
Boerries, Melanie
Eisenhardt, Steffen U.
author_sort Braig, David
collection PubMed
description Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS, only limited inferences can be drawn from imaging data regarding therapy response. To date there are no established and evidence-based diagnostic biomarkers for STS due to their rarity and diversity. In a proof-of-concept study, circulating tumor DNA (ctDNA) was quantified in (n = 25) plasma samples obtained from (n = 3) patients with complex karyotype STS collected over three years. Genotyping of tumor tissue was performed by exome sequencing. Patient-individual mini-panels for targeted next-generation sequencing were designed encompassing up to 30 mutated regions of interest. Circulating free DNA (cfDNA) was purified from plasma and ctDNA quantified therein. ctDNA values were correlated with clinical parameters. ctDNA concentrations correlated with the tumor burden. In case of full remission, no ctDNA was detectable. Patients with a recurrence at a later stage showed low levels of ctDNA during clinical remission, indicating minimal residual disease. In active disease (primary tumor or metastatic disease), ctDNA was highly elevated. We observed direct response to treatment, with a ctDNA decline after tumor resections, radiotherapy, and chemotherapy. Quantification of ctDNA allows for the early detection of recurrence or metastases and can be used to monitor treatment response in STS. Therapeutic decisions can be made earlier, such as the continuation of a targeted adjuvant therapy or the implementation of extended imaging to detect recurrences. In metastatic disease, therapy can be adjusted promptly in case of no response. These advantages may lead to a survival benefit for patients in the future.
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spelling pubmed-94996172022-09-23 Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas Braig, David Runkel, Alexander Eisenhardt, Anja E. Schmid, Adrian Zeller, Johannes Pauli, Thomas Lausch, Ute Wehrle, Julius Bronsert, Peter Jung, Matthias Kiefer, Jurij Boerries, Melanie Eisenhardt, Steffen U. Int J Mol Sci Article Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS, only limited inferences can be drawn from imaging data regarding therapy response. To date there are no established and evidence-based diagnostic biomarkers for STS due to their rarity and diversity. In a proof-of-concept study, circulating tumor DNA (ctDNA) was quantified in (n = 25) plasma samples obtained from (n = 3) patients with complex karyotype STS collected over three years. Genotyping of tumor tissue was performed by exome sequencing. Patient-individual mini-panels for targeted next-generation sequencing were designed encompassing up to 30 mutated regions of interest. Circulating free DNA (cfDNA) was purified from plasma and ctDNA quantified therein. ctDNA values were correlated with clinical parameters. ctDNA concentrations correlated with the tumor burden. In case of full remission, no ctDNA was detectable. Patients with a recurrence at a later stage showed low levels of ctDNA during clinical remission, indicating minimal residual disease. In active disease (primary tumor or metastatic disease), ctDNA was highly elevated. We observed direct response to treatment, with a ctDNA decline after tumor resections, radiotherapy, and chemotherapy. Quantification of ctDNA allows for the early detection of recurrence or metastases and can be used to monitor treatment response in STS. Therapeutic decisions can be made earlier, such as the continuation of a targeted adjuvant therapy or the implementation of extended imaging to detect recurrences. In metastatic disease, therapy can be adjusted promptly in case of no response. These advantages may lead to a survival benefit for patients in the future. MDPI 2022-09-06 /pmc/articles/PMC9499617/ /pubmed/36142126 http://dx.doi.org/10.3390/ijms231810215 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Braig, David
Runkel, Alexander
Eisenhardt, Anja E.
Schmid, Adrian
Zeller, Johannes
Pauli, Thomas
Lausch, Ute
Wehrle, Julius
Bronsert, Peter
Jung, Matthias
Kiefer, Jurij
Boerries, Melanie
Eisenhardt, Steffen U.
Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas
title Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas
title_full Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas
title_fullStr Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas
title_full_unstemmed Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas
title_short Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas
title_sort individualized mini-panel sequencing of ctdna allows tumor monitoring in complex karyotype sarcomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499617/
https://www.ncbi.nlm.nih.gov/pubmed/36142126
http://dx.doi.org/10.3390/ijms231810215
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