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Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma

SIMPLE SUMMARY: Leiomyosarcomas are the most common soft tissue sarcomas (STS) subtype characterized by increased aggressiveness and early relapse. Current surveillance includes physical exam and imaging which may be inconclusive, confounding and pose radiation risk with repeat imaging. Given the di...

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Autores principales: Zhou, Maggie, Bui, Nam, Rathore, Richa, Sudhaman, Sumedha, George, Giby V., Malashevich, Allyson K., Malhotra, Meenakshi, Liu, Minetta C., Aleshin, Alexey, Ganjoo, Kristen N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818540/
https://www.ncbi.nlm.nih.gov/pubmed/36612153
http://dx.doi.org/10.3390/cancers15010157
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author Zhou, Maggie
Bui, Nam
Rathore, Richa
Sudhaman, Sumedha
George, Giby V.
Malashevich, Allyson K.
Malhotra, Meenakshi
Liu, Minetta C.
Aleshin, Alexey
Ganjoo, Kristen N.
author_facet Zhou, Maggie
Bui, Nam
Rathore, Richa
Sudhaman, Sumedha
George, Giby V.
Malashevich, Allyson K.
Malhotra, Meenakshi
Liu, Minetta C.
Aleshin, Alexey
Ganjoo, Kristen N.
author_sort Zhou, Maggie
collection PubMed
description SIMPLE SUMMARY: Leiomyosarcomas are the most common soft tissue sarcomas (STS) subtype characterized by increased aggressiveness and early relapse. Current surveillance includes physical exam and imaging which may be inconclusive, confounding and pose radiation risk with repeat imaging. Given the disease severity and aggressiveness, non-invasive biomarkers are needed to monitor disease progression and treatment response to facilitate prompt clinical decision-making. Circulating tumor DNA (ctDNA) is a minimally invasive blood-based biomarker that has shown to be prognostic of disease outcomes in patients with solid tumors. Herein, we investigated the potential utility of ctDNA for longitudinal monitoring of patients with LMS. Our data suggests that longitudinal ctDNA surveillance may be useful for monitoring treatment response in patients with LMS. ABSTRACT: Background: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4–6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression. Methods: We performed a retrospective review of patients with LMS who underwent treatment at Stanford Cancer Center between September 2019 and May 2022. ctDNA detection was performed using a personalized, tumor-informed ctDNA assay. Genomic analysis was conducted to characterize tumor mutation burden (TMB) and known driver mutations. Results: A total of 148 plasma samples were obtained from 34 patients with uterine (N = 21) and extrauterine (N = 13) LMS (median follow-up: 67.2 (19–346.3) weeks] and analyzed for ctDNA presence. Nineteen patients had metastatic disease. The most frequently mutated driver genes across sub-cohorts were TP53, RB1, and PTEN. Patients were stratified into four sub-cohorts (A-D) based on ctDNA kinetics. ctDNA levels tracked longitudinally with progression of disease and response to therapy. Conclusion: Our results indicate that while undetectable ctDNA may suggest a lower likelihood of relapse, ctDNA positivity may indicate progressive disease, enabling closer monitoring of patients for early clinical intervention.
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spelling pubmed-98185402023-01-07 Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma Zhou, Maggie Bui, Nam Rathore, Richa Sudhaman, Sumedha George, Giby V. Malashevich, Allyson K. Malhotra, Meenakshi Liu, Minetta C. Aleshin, Alexey Ganjoo, Kristen N. Cancers (Basel) Article SIMPLE SUMMARY: Leiomyosarcomas are the most common soft tissue sarcomas (STS) subtype characterized by increased aggressiveness and early relapse. Current surveillance includes physical exam and imaging which may be inconclusive, confounding and pose radiation risk with repeat imaging. Given the disease severity and aggressiveness, non-invasive biomarkers are needed to monitor disease progression and treatment response to facilitate prompt clinical decision-making. Circulating tumor DNA (ctDNA) is a minimally invasive blood-based biomarker that has shown to be prognostic of disease outcomes in patients with solid tumors. Herein, we investigated the potential utility of ctDNA for longitudinal monitoring of patients with LMS. Our data suggests that longitudinal ctDNA surveillance may be useful for monitoring treatment response in patients with LMS. ABSTRACT: Background: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4–6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression. Methods: We performed a retrospective review of patients with LMS who underwent treatment at Stanford Cancer Center between September 2019 and May 2022. ctDNA detection was performed using a personalized, tumor-informed ctDNA assay. Genomic analysis was conducted to characterize tumor mutation burden (TMB) and known driver mutations. Results: A total of 148 plasma samples were obtained from 34 patients with uterine (N = 21) and extrauterine (N = 13) LMS (median follow-up: 67.2 (19–346.3) weeks] and analyzed for ctDNA presence. Nineteen patients had metastatic disease. The most frequently mutated driver genes across sub-cohorts were TP53, RB1, and PTEN. Patients were stratified into four sub-cohorts (A-D) based on ctDNA kinetics. ctDNA levels tracked longitudinally with progression of disease and response to therapy. Conclusion: Our results indicate that while undetectable ctDNA may suggest a lower likelihood of relapse, ctDNA positivity may indicate progressive disease, enabling closer monitoring of patients for early clinical intervention. MDPI 2022-12-27 /pmc/articles/PMC9818540/ /pubmed/36612153 http://dx.doi.org/10.3390/cancers15010157 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
Zhou, Maggie
Bui, Nam
Rathore, Richa
Sudhaman, Sumedha
George, Giby V.
Malashevich, Allyson K.
Malhotra, Meenakshi
Liu, Minetta C.
Aleshin, Alexey
Ganjoo, Kristen N.
Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma
title Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma
title_full Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma
title_fullStr Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma
title_full_unstemmed Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma
title_short Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma
title_sort feasibility of longitudinal ctdna assessment in patients with uterine and extra-uterine leiomyosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818540/
https://www.ncbi.nlm.nih.gov/pubmed/36612153
http://dx.doi.org/10.3390/cancers15010157
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