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^*

^*Tämän työn vastaava kirjoittaja

Tays Syöpäkeskus

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

144 Sitaatiot (Scopus)

22 Lataukset (Pure)

Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	184
Julkaisu	Nature Communications
Vuosikerta	12
Numero	1
DOI - pysyväislinkit	https://doi.org/10.1038/s41467-020-20493-6
Tila	Julkaistu - 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

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. 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.

YK:n kestävän kehityksen tavoitteet

Tämä tuotos edistää seuraavia kestävän kehityksen tavoitteita:

SDG 3 – Hyvä terveys ja hyvinvointi

Julkaisufoorumi-taso

Jufo-taso 3

!!ASJC Scopus subject areas

Yleinen kemia
Yleinen biokemia, genetiikka ja molekyylibiologia
Yleinen fysiikka ja tähtitiede

Pääsy asiakirjaan

10.1038/s41467-020-20493-6Lisenssi: CC BY

plasma_ctDNA_is_a_tumor_2021
CC BY
Final published version, 1,81 MBLisenssi: CC BY

http://urn.fi/URN:NBN:fi:tuni-202102041929Lisenssi: CC BY

Siteeraa tätä

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), Artikkeli 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, Vuosikerta 12, Nro 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

Abstrakti

Rahoitus

YK:n kestävän kehityksen tavoitteet

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

Pääsy asiakirjaan

Sormenjälki

Siteeraa tätä