Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk

Abstract We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients tr...

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Autores principales:	Mark Jesus M. Magbanua, Wen Li, Denise M. Wolf, Christina Yau, Gillian L. Hirst, Lamorna Brown Swigart, David C. Newitt, Jessica Gibbs, Amy L. Delson, Ekaterina Kalashnikova, Alexey Aleshin, Bernhard Zimmermann, A. Jo Chien, Debu Tripathy, Laura Esserman, Nola Hylton, Laura van ‘t Veer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fc14e93945954cfb88f54bbbdcc007fe
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spelling	oai:doaj.org-article:fc14e93945954cfb88f54bbbdcc007fe2021-12-02T17:03:56ZCirculating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk10.1038/s41523-021-00239-32374-4677https://doaj.org/article/fc14e93945954cfb88f54bbbdcc007fe2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00239-3https://doaj.org/toc/2374-4677Abstract We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). We examined correlations between ctDNA and FTV, evaluated the additive value of ctDNA to FTV-based predictors of pCR using area under the curve (AUC) analysis, and analyzed the impact of FTV and ctDNA on distant recurrence-free survival (DRFS) using Cox regressions. The levels of ctDNA (mean tumor molecules/mL plasma) were significantly correlated with FTV at all time points (p < 0.05). Median FTV in ctDNA-positive patients was significantly higher compared to those who were ctDNA-negative (p < 0.05). FTV and ctDNA trajectories in individual patients showed a general decrease during NAC. Exploratory analysis showed that adding ctDNA information early during treatment to FTV-based predictors resulted in numerical but not statistically significant improvements in performance for pCR prediction (e.g., AUC 0.59 vs. 0.69, p = 0.25). In contrast, ctDNA-positivity after NAC provided significant additive value to FTV in identifying patients with increased risk of metastatic recurrence and death (p = 0.004). In this pilot study, we demonstrate that ctDNA and FTV were correlated measures of tumor burden. Our preliminary findings based on a limited cohort suggest that ctDNA at surgery improves FTV as a predictor of metastatic recurrence and death. Validation in larger studies is warranted.Mark Jesus M. MagbanuaWen LiDenise M. WolfChristina YauGillian L. HirstLamorna Brown SwigartDavid C. NewittJessica GibbsAmy L. DelsonEkaterina KalashnikovaAlexey AleshinBernhard ZimmermannA. Jo ChienDebu TripathyLaura EssermanNola HyltonLaura van ‘t VeerNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mark Jesus M. Magbanua Wen Li Denise M. Wolf Christina Yau Gillian L. Hirst Lamorna Brown Swigart David C. Newitt Jessica Gibbs Amy L. Delson Ekaterina Kalashnikova Alexey Aleshin Bernhard Zimmermann A. Jo Chien Debu Tripathy Laura Esserman Nola Hylton Laura van ‘t Veer Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
description	Abstract We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). We examined correlations between ctDNA and FTV, evaluated the additive value of ctDNA to FTV-based predictors of pCR using area under the curve (AUC) analysis, and analyzed the impact of FTV and ctDNA on distant recurrence-free survival (DRFS) using Cox regressions. The levels of ctDNA (mean tumor molecules/mL plasma) were significantly correlated with FTV at all time points (p < 0.05). Median FTV in ctDNA-positive patients was significantly higher compared to those who were ctDNA-negative (p < 0.05). FTV and ctDNA trajectories in individual patients showed a general decrease during NAC. Exploratory analysis showed that adding ctDNA information early during treatment to FTV-based predictors resulted in numerical but not statistically significant improvements in performance for pCR prediction (e.g., AUC 0.59 vs. 0.69, p = 0.25). In contrast, ctDNA-positivity after NAC provided significant additive value to FTV in identifying patients with increased risk of metastatic recurrence and death (p = 0.004). In this pilot study, we demonstrate that ctDNA and FTV were correlated measures of tumor burden. Our preliminary findings based on a limited cohort suggest that ctDNA at surgery improves FTV as a predictor of metastatic recurrence and death. Validation in larger studies is warranted.
format	article
author	Mark Jesus M. Magbanua Wen Li Denise M. Wolf Christina Yau Gillian L. Hirst Lamorna Brown Swigart David C. Newitt Jessica Gibbs Amy L. Delson Ekaterina Kalashnikova Alexey Aleshin Bernhard Zimmermann A. Jo Chien Debu Tripathy Laura Esserman Nola Hylton Laura van ‘t Veer
author_facet	Mark Jesus M. Magbanua Wen Li Denise M. Wolf Christina Yau Gillian L. Hirst Lamorna Brown Swigart David C. Newitt Jessica Gibbs Amy L. Delson Ekaterina Kalashnikova Alexey Aleshin Bernhard Zimmermann A. Jo Chien Debu Tripathy Laura Esserman Nola Hylton Laura van ‘t Veer
author_sort	Mark Jesus M. Magbanua
title	Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
title_short	Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
title_full	Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
title_fullStr	Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
title_full_unstemmed	Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
title_sort	circulating tumor dna and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fc14e93945954cfb88f54bbbdcc007fe
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Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk

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