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Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC

BACKGROUND: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical si...

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Autores principales: MacManus, Michael, Kirby, Laura, Blyth, Benjamin, Banks, Owen, Martin, Olga A., Yeung, Miriam M., Plumridge, Nikki, Shaw, Mark, Hegi-Johnson, Fiona, Siva, Shankar, Ball, David, Wong, Stephen Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551836/
https://www.ncbi.nlm.nih.gov/pubmed/37808452
http://dx.doi.org/10.1016/j.ctro.2023.100682
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author MacManus, Michael
Kirby, Laura
Blyth, Benjamin
Banks, Owen
Martin, Olga A.
Yeung, Miriam M.
Plumridge, Nikki
Shaw, Mark
Hegi-Johnson, Fiona
Siva, Shankar
Ball, David
Wong, Stephen Q.
author_facet MacManus, Michael
Kirby, Laura
Blyth, Benjamin
Banks, Owen
Martin, Olga A.
Yeung, Miriam M.
Plumridge, Nikki
Shaw, Mark
Hegi-Johnson, Fiona
Siva, Shankar
Ball, David
Wong, Stephen Q.
author_sort MacManus, Michael
collection PubMed
description BACKGROUND: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance. MATERIALS AND METHODS: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy. Blood was collected at predefined intervals before, during (including 24 h after fraction 1 of radiotherapy) and after radiotherapy/chemoradiotherapy. Mutation-specific droplet digital PCR assays used to track ctDNA levels during and after treatment. RESULTS: Sequential ctDNA results are available for 14 patients with known tumor-based mutations, including in EGFR, KRAS and TP53, with a median follow-up of 723 days (range 152 to 1110). Treatments delivered were fractionated radiotherapy/chemoradiotherapy, in 2–2.75 Gy fractions (n = 12), or stereotactic ablative body radiotherapy (SABR, n = 2). An increase in ctDNA was observed after fraction 1 in 3/12 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable. Neither SABR patient had detectable ctDNA immediately before or after radiotherapy, but one of these later relapsed systemically with a high detected ctDNA concentration. CONCLUSIONS: A rapid increase in ctDNA levels was observed after one fraction of fractionated radiotherapy in three cases. Further molecular characterization will be required to understand if a “spike” in ctDNA levels could represent rapid initial tumor cell destruction and could have clinical value as a surrogate for early treatment response and/or as a means of enriching ctDNA for mutational profiling.
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spelling pubmed-105518362023-10-06 Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC MacManus, Michael Kirby, Laura Blyth, Benjamin Banks, Owen Martin, Olga A. Yeung, Miriam M. Plumridge, Nikki Shaw, Mark Hegi-Johnson, Fiona Siva, Shankar Ball, David Wong, Stephen Q. Clin Transl Radiat Oncol Case Report BACKGROUND: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance. MATERIALS AND METHODS: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy. Blood was collected at predefined intervals before, during (including 24 h after fraction 1 of radiotherapy) and after radiotherapy/chemoradiotherapy. Mutation-specific droplet digital PCR assays used to track ctDNA levels during and after treatment. RESULTS: Sequential ctDNA results are available for 14 patients with known tumor-based mutations, including in EGFR, KRAS and TP53, with a median follow-up of 723 days (range 152 to 1110). Treatments delivered were fractionated radiotherapy/chemoradiotherapy, in 2–2.75 Gy fractions (n = 12), or stereotactic ablative body radiotherapy (SABR, n = 2). An increase in ctDNA was observed after fraction 1 in 3/12 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable. Neither SABR patient had detectable ctDNA immediately before or after radiotherapy, but one of these later relapsed systemically with a high detected ctDNA concentration. CONCLUSIONS: A rapid increase in ctDNA levels was observed after one fraction of fractionated radiotherapy in three cases. Further molecular characterization will be required to understand if a “spike” in ctDNA levels could represent rapid initial tumor cell destruction and could have clinical value as a surrogate for early treatment response and/or as a means of enriching ctDNA for mutational profiling. Elsevier 2023-09-22 /pmc/articles/PMC10551836/ /pubmed/37808452 http://dx.doi.org/10.1016/j.ctro.2023.100682 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Case Report
MacManus, Michael
Kirby, Laura
Blyth, Benjamin
Banks, Owen
Martin, Olga A.
Yeung, Miriam M.
Plumridge, Nikki
Shaw, Mark
Hegi-Johnson, Fiona
Siva, Shankar
Ball, David
Wong, Stephen Q.
Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC
title Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC
title_full Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC
title_fullStr Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC
title_full_unstemmed Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC
title_short Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC
title_sort early circulating tumor dna dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for nsclc
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551836/
https://www.ncbi.nlm.nih.gov/pubmed/37808452
http://dx.doi.org/10.1016/j.ctro.2023.100682
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