Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

Gillian Vandekerkhove; Jean Michel Lavoie; Matti Annala; Andrew J. Murtha; Nora Sundahl; Simon Walz; Takeshi Sano; Sinja Taavitsainen; Elie Ritch; Ladan Fazli; Antonio Hurtado-Coll; Gang Wang; Matti Nykter; Peter C. Black; Tilman Todenhöfer; Piet Ost; Ewan A. Gibb; Kim N. Chi; Bernhard J. Eigl; Alexander W. Wyatt

doi:10.1038/s41467-020-20493-6

Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

Gillian Vandekerkhove, Jean Michel Lavoie, Matti Annala, Andrew J. Murtha, Nora Sundahl, Simon Walz, Takeshi Sano, Sinja Taavitsainen, Elie Ritch, Ladan Fazli, Antonio Hurtado-Coll, Gang Wang, Matti Nykter, Peter C. Black, Tilman Todenhöfer, Piet Ost, Ewan A. Gibb, Kim N. Chi, Bernhard J. Eigl, Alexander W. Wyatt

TAYS Cancer Centre

Research output: Contribution to journal › Article › Scientific › peer-review

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Abstract

Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.

Original language	English
Article number	184
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20493-6
Publication status	Published - 2021
Publication type	A1 Journal article-refereed

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Publication forum level 3

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Vandekerkhove, G., Lavoie, J. M., Annala, M., Murtha, A. J., Sundahl, N., Walz, S., Sano, T., Taavitsainen, S., Ritch, E., Fazli, L., Hurtado-Coll, A., Wang, G., Nykter, M., Black, P. C., Todenhöfer, T., Ost, P., Gibb, E. A., Chi, K. N., Eigl, B. J., & Wyatt, A. W. (2021). Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer. Nature Communications, 12(1), Article 184. https://doi.org/10.1038/s41467-020-20493-6

@article{d90a7ab761f24432b5640c2f987b5950,

title = "Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer",

abstract = "Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.",

author = "Gillian Vandekerkhove and Lavoie, {Jean Michel} and Matti Annala and Murtha, {Andrew J.} and Nora Sundahl and Simon Walz and Takeshi Sano and Sinja Taavitsainen and Elie Ritch and Ladan Fazli and Antonio Hurtado-Coll and Gang Wang and Matti Nykter and Black, {Peter C.} and Tilman Todenh{\"o}fer and Piet Ost and Gibb, {Ewan A.} and Chi, {Kim N.} and Eigl, {Bernhard J.} and Wyatt, {Alexander W.}",

note = "Funding Information: This work was supported by the Canadian Institutes of Health Research (CIHR), Bladder Cancer Canada, the Jane and Aatos Erkko Foundation, and the Adolf Leuze Foundation. We are thankful to all contributing patients and their families. Funding Information: J.-M.L. reports honoraria from Pfizer, Astellas, and Ipsen. N.S. reports travel grants from Bayer, MSD, Bristol-Myers Squibb, and Astellas. T.T. reports speaker/consultant roles with Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, MSD, Roche, and Sanofi. E.A.G. is an employee of Decipher Biosciences, Inc. K.N.C. reports receiving commercial research grants and honorarium from Astellas, AstraZeneca, Constellation Pharmaceuticals, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, and Sanofi. A.W.W. reports receiving a commercial research grant from Janssen, and honorarium from AstraZeneca, Astellas, Janssen, and Merck. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

doi = "10.1038/s41467-020-20493-6",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Vandekerkhove, G, Lavoie, JM, Annala, M, Murtha, AJ, Sundahl, N, Walz, S, Sano, T, Taavitsainen, S, Ritch, E, Fazli, L, Hurtado-Coll, A, Wang, G, Nykter, M, Black, PC, Todenhöfer, T, Ost, P, Gibb, EA, Chi, KN, Eigl, BJ & Wyatt, AW 2021, 'Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer', Nature Communications, vol. 12, no. 1, 184. https://doi.org/10.1038/s41467-020-20493-6

TY - JOUR

T1 - Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

AU - Vandekerkhove, Gillian

AU - Lavoie, Jean Michel

AU - Annala, Matti

AU - Murtha, Andrew J.

AU - Sundahl, Nora

AU - Walz, Simon

AU - Sano, Takeshi

AU - Taavitsainen, Sinja

AU - Ritch, Elie

AU - Fazli, Ladan

AU - Hurtado-Coll, Antonio

AU - Wang, Gang

AU - Nykter, Matti

AU - Black, Peter C.

AU - Todenhöfer, Tilman

AU - Ost, Piet

AU - Gibb, Ewan A.

AU - Chi, Kim N.

AU - Eigl, Bernhard J.

AU - Wyatt, Alexander W.

N1 - Funding Information: This work was supported by the Canadian Institutes of Health Research (CIHR), Bladder Cancer Canada, the Jane and Aatos Erkko Foundation, and the Adolf Leuze Foundation. We are thankful to all contributing patients and their families. Funding Information: J.-M.L. reports honoraria from Pfizer, Astellas, and Ipsen. N.S. reports travel grants from Bayer, MSD, Bristol-Myers Squibb, and Astellas. T.T. reports speaker/consultant roles with Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, MSD, Roche, and Sanofi. E.A.G. is an employee of Decipher Biosciences, Inc. K.N.C. reports receiving commercial research grants and honorarium from Astellas, AstraZeneca, Constellation Pharmaceuticals, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, and Sanofi. A.W.W. reports receiving a commercial research grant from Janssen, and honorarium from AstraZeneca, Astellas, Janssen, and Merck. The remaining authors declare no competing interests. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021

Y1 - 2021

N2 - Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.

AB - Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.

U2 - 10.1038/s41467-020-20493-6

DO - 10.1038/s41467-020-20493-6

M3 - Article

AN - SCOPUS:85098944842

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 184

ER -

Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

Abstract

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UN SDGs

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