Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Nicolette M. Fonseca; Corinne Maurice-Dror; Cameron Herberts; Wilson Tu; William Fan; Andrew J. Murtha; Catarina Kollmannsberger; Edmond M. Kwan; Karan Parekh; Elena Schönlau; Cecily Q. Bernales; Gráinne Donnellan; Sarah W.S. Ng; Takayuki Sumiyoshi; Joanna Vergidis; Krista Noonan; Daygen L. Finch; Muhammad Zulfiqar; Stacy Miller; Sunil Parimi; Jean Michel Lavoie; Edward Hardy; Maryam Soleimani; Lucia Nappi; Bernhard J. Eigl; Christian Kollmannsberger; Sinja Taavitsainen; Matti Nykter; Sofie H. Tolmeijer; Emmy Boerrigter; Niven Mehra; Nielka P. van Erp; Bram De Laere; Johan Lindberg; Henrik Grönberg; Daniel J. Khalaf; Matti Annala; Kim N. Chi; Alexander W. Wyatt

doi:10.1038/s41467-024-45475-w

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Nicolette M. Fonseca, Corinne Maurice-Dror, Cameron Herberts, Wilson Tu, William Fan, Andrew J. Murtha, Catarina Kollmannsberger, Edmond M. Kwan, Karan Parekh, Elena Schönlau, Cecily Q. Bernales, Gráinne Donnellan, Sarah W.S. Ng, Takayuki Sumiyoshi, Joanna Vergidis, Krista Noonan, Daygen L. Finch, Muhammad Zulfiqar, Stacy Miller, Sunil ParimiJean Michel Lavoie, Edward Hardy, Maryam Soleimani, Lucia Nappi, Bernhard J. Eigl, Christian Kollmannsberger, Sinja Taavitsainen, Matti Nykter, Sofie H. Tolmeijer, Emmy Boerrigter, Niven Mehra, Nielka P. van Erp, Bram De Laere, Johan Lindberg, Henrik Grönberg, Daniel J. Khalaf, Matti Annala, Kim N. Chi, Alexander W. Wyatt

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Abstract

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

Original language	English
Article number	1828
Number of pages	16
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-45475-w
Publication status	Published - 2024
Publication type	A1 Journal article-refereed

Publication forum classification

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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s41467-024-45475-wFinal published version, 20.9 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202407197683Licence: CC BY

Cite this

Fonseca, N. M., Maurice-Dror, C., Herberts, C., Tu, W., Fan, W., Murtha, A. J., Kollmannsberger, C., Kwan, E. M., Parekh, K., Schönlau, E., Bernales, C. Q., Donnellan, G., Ng, S. W. S., Sumiyoshi, T., Vergidis, J., Noonan, K., Finch, D. L., Zulfiqar, M., Miller, S., ... Wyatt, A. W. (2024). Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer. Nature Communications, 15(1), Article 1828. https://doi.org/10.1038/s41467-024-45475-w

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title = "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer",

abstract = "No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.",

author = "Fonseca, {Nicolette M.} and Corinne Maurice-Dror and Cameron Herberts and Wilson Tu and William Fan and Murtha, {Andrew J.} and Catarina Kollmannsberger and Kwan, {Edmond M.} and Karan Parekh and Elena Sch{\"o}nlau and Bernales, {Cecily Q.} and Gr{\'a}inne Donnellan and Ng, {Sarah W.S.} and Takayuki Sumiyoshi and Joanna Vergidis and Krista Noonan and Finch, {Daygen L.} and Muhammad Zulfiqar and Stacy Miller and Sunil Parimi and Lavoie, {Jean Michel} and Edward Hardy and Maryam Soleimani and Lucia Nappi and Eigl, {Bernhard J.} and Christian Kollmannsberger and Sinja Taavitsainen and Matti Nykter and Tolmeijer, {Sofie H.} and Emmy Boerrigter and Niven Mehra and {van Erp}, {Nielka P.} and {De Laere}, Bram and Johan Lindberg and Henrik Gr{\"o}nberg and Khalaf, {Daniel J.} and Matti Annala and Chi, {Kim N.} and Wyatt, {Alexander W.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

doi = "10.1038/s41467-024-45475-w",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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Fonseca, NM, Maurice-Dror, C, Herberts, C, Tu, W, Fan, W, Murtha, AJ, Kollmannsberger, C, Kwan, EM, Parekh, K, Schönlau, E, Bernales, CQ, Donnellan, G, Ng, SWS, Sumiyoshi, T, Vergidis, J, Noonan, K, Finch, DL, Zulfiqar, M, Miller, S, Parimi, S, Lavoie, JM, Hardy, E, Soleimani, M, Nappi, L, Eigl, BJ, Kollmannsberger, C, Taavitsainen, S , Nykter, M, Tolmeijer, SH, Boerrigter, E, Mehra, N, van Erp, NP, De Laere, B, Lindberg, J, Grönberg, H, Khalaf, DJ, Annala, M, Chi, KN & Wyatt, AW 2024, 'Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer', Nature Communications, vol. 15, no. 1, 1828. https://doi.org/10.1038/s41467-024-45475-w

TY - JOUR

T1 - Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

AU - Fonseca, Nicolette M.

AU - Maurice-Dror, Corinne

AU - Herberts, Cameron

AU - Tu, Wilson

AU - Fan, William

AU - Murtha, Andrew J.

AU - Kollmannsberger, Catarina

AU - Kwan, Edmond M.

AU - Parekh, Karan

AU - Schönlau, Elena

AU - Bernales, Cecily Q.

AU - Donnellan, Gráinne

AU - Ng, Sarah W.S.

AU - Sumiyoshi, Takayuki

AU - Vergidis, Joanna

AU - Noonan, Krista

AU - Finch, Daygen L.

AU - Zulfiqar, Muhammad

AU - Miller, Stacy

AU - Parimi, Sunil

AU - Lavoie, Jean Michel

AU - Hardy, Edward

AU - Soleimani, Maryam

AU - Nappi, Lucia

AU - Eigl, Bernhard J.

AU - Kollmannsberger, Christian

AU - Taavitsainen, Sinja

AU - Nykter, Matti

AU - Tolmeijer, Sofie H.

AU - Boerrigter, Emmy

AU - Mehra, Niven

AU - van Erp, Nielka P.

AU - De Laere, Bram

AU - Lindberg, Johan

AU - Grönberg, Henrik

AU - Khalaf, Daniel J.

AU - Annala, Matti

AU - Chi, Kim N.

AU - Wyatt, Alexander W.

PY - 2024

Y1 - 2024

N2 - No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

AB - No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

U2 - 10.1038/s41467-024-45475-w

DO - 10.1038/s41467-024-45475-w

M3 - Article

C2 - 38418825

AN - SCOPUS:85186222605

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1828

ER -

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Abstract

Publication forum classification

ASJC Scopus subject areas

UN SDGs

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