Circulating tumor DNA – A potential aid in the management of chordomas

Chordomas are a locally invasive, low-grade, CNS malignancy that are primarily found in the skull base, spine, and sacrum. They are thought to be derived from notochordal remnants and remain a significant clinical challenge due to their local invasiveness, resistance to chemoradiation, and difficult...

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Main Authors: Stephen C. Frederico, Corbin Darling, Xiaoran Zhang, Sakibul Huq, Sameer Agnihotri, Paul A. Gardner, Carl H. Snyderman, Eric W. Wang, Georgios A. Zenonos
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1016385/full
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author Stephen C. Frederico
Stephen C. Frederico
Corbin Darling
Corbin Darling
Xiaoran Zhang
Sakibul Huq
Sameer Agnihotri
Paul A. Gardner
Carl H. Snyderman
Carl H. Snyderman
Eric W. Wang
Georgios A. Zenonos
author_facet Stephen C. Frederico
Stephen C. Frederico
Corbin Darling
Corbin Darling
Xiaoran Zhang
Sakibul Huq
Sameer Agnihotri
Paul A. Gardner
Carl H. Snyderman
Carl H. Snyderman
Eric W. Wang
Georgios A. Zenonos
author_sort Stephen C. Frederico
collection DOAJ
description Chordomas are a locally invasive, low-grade, CNS malignancy that are primarily found in the skull base, spine, and sacrum. They are thought to be derived from notochordal remnants and remain a significant clinical challenge due to their local invasiveness, resistance to chemoradiation, and difficulty in achieving a complete resection. Adjuvant therapy such as proton beam therapy is critical in preventing recurrence in patients who are at high risk, however this treatment is associated with increased risk of complication. Currently, intraoperative observation and imaging findings are used to determine recurrence and success of gross total resection. These methods can be unreliable due to limited operative view, bony and soft tissue involvement, and complex post-operative changes on MRI. Earlier detection of incomplete resection or recurrence will allow for earlier ability to intervene and potentially improve patient outcomes. Circulating-tumor DNA (ctDNA) is cell-free DNA that is released by tumor cells as they undergo cellular turn-over. Monitoring ctDNA has been shown to be more sensitive at predicting residual tumor than imaging in numerous solid malignancies. Furthermore, ctDNA could be detected earlier in peripheral blood as opposed to imaging changes, allowing for earlier intervention. In this review, we intend to give a brief overview of the current state of molecular diagnosis for skull base chordomas. We will then discuss current advances in the utilization of ctDNA for the management of CNS pathologies such as glioblastoma (GBM) and brain metastases. We will also discuss the role ctDNA has in the management of non-CNS pathologies such as osteosarcoma and Ewing sarcoma (EWS). Finally, we will discuss potential implications of ctDNA monitoring for chordoma management.
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spelling doaj.art-e973ba811cf14695b673db241e7e2d512022-12-22T02:34:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10163851016385Circulating tumor DNA – A potential aid in the management of chordomasStephen C. Frederico0Stephen C. Frederico1Corbin Darling2Corbin Darling3Xiaoran Zhang4Sakibul Huq5Sameer Agnihotri6Paul A. Gardner7Carl H. Snyderman8Carl H. Snyderman9Eric W. Wang10Georgios A. Zenonos11School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesSchool of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesChordomas are a locally invasive, low-grade, CNS malignancy that are primarily found in the skull base, spine, and sacrum. They are thought to be derived from notochordal remnants and remain a significant clinical challenge due to their local invasiveness, resistance to chemoradiation, and difficulty in achieving a complete resection. Adjuvant therapy such as proton beam therapy is critical in preventing recurrence in patients who are at high risk, however this treatment is associated with increased risk of complication. Currently, intraoperative observation and imaging findings are used to determine recurrence and success of gross total resection. These methods can be unreliable due to limited operative view, bony and soft tissue involvement, and complex post-operative changes on MRI. Earlier detection of incomplete resection or recurrence will allow for earlier ability to intervene and potentially improve patient outcomes. Circulating-tumor DNA (ctDNA) is cell-free DNA that is released by tumor cells as they undergo cellular turn-over. Monitoring ctDNA has been shown to be more sensitive at predicting residual tumor than imaging in numerous solid malignancies. Furthermore, ctDNA could be detected earlier in peripheral blood as opposed to imaging changes, allowing for earlier intervention. In this review, we intend to give a brief overview of the current state of molecular diagnosis for skull base chordomas. We will then discuss current advances in the utilization of ctDNA for the management of CNS pathologies such as glioblastoma (GBM) and brain metastases. We will also discuss the role ctDNA has in the management of non-CNS pathologies such as osteosarcoma and Ewing sarcoma (EWS). Finally, we will discuss potential implications of ctDNA monitoring for chordoma management.https://www.frontiersin.org/articles/10.3389/fonc.2022.1016385/fullclivusctDNADNAtumorskull basechordoma
spellingShingle Stephen C. Frederico
Stephen C. Frederico
Corbin Darling
Corbin Darling
Xiaoran Zhang
Sakibul Huq
Sameer Agnihotri
Paul A. Gardner
Carl H. Snyderman
Carl H. Snyderman
Eric W. Wang
Georgios A. Zenonos
Circulating tumor DNA – A potential aid in the management of chordomas
Frontiers in Oncology
clivus
ctDNA
DNA
tumor
skull base
chordoma
title Circulating tumor DNA – A potential aid in the management of chordomas
title_full Circulating tumor DNA – A potential aid in the management of chordomas
title_fullStr Circulating tumor DNA – A potential aid in the management of chordomas
title_full_unstemmed Circulating tumor DNA – A potential aid in the management of chordomas
title_short Circulating tumor DNA – A potential aid in the management of chordomas
title_sort circulating tumor dna a potential aid in the management of chordomas
topic clivus
ctDNA
DNA
tumor
skull base
chordoma
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1016385/full
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