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

Tutkimustuotos: ArtikkeliTieteellinenvertaisarvioitu

10 Sitaatiot (Scopus)
4 Lataukset (Pure)

Abstrakti

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.

AlkuperäiskieliEnglanti
Artikkeli1828
Sivumäärä16
JulkaisuNature Communications
Vuosikerta15
Numero1
DOI - pysyväislinkit
TilaJulkaistu - 2024
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

This work was primarily funded by a Canadian Cancer Society Challenge Grant (grant #707339) to A.W.W., K.N.C., and N.M.F. Other funding support was provided by the Canadian Institutes of Health Research, Prostate Cancer Canada, Movember Foundation, Prostate Cancer Foundation, Jane and Aatos Erkko Foundation, Academy of Finland Center of Excellence program (project no. 312043), a Terry Fox New Frontiers Program Project Grant, the BC Cancer Foundation, and Kom op tegen Kanker (Stand Up To Cancer - Flemish Cancer Society) [grant numbers STI.VLK.2020.0006.01; STI.VLK.2022.0005.01]. No funding sources were involved in the design or execution of the study. The authors are grateful to all participating patients and their families.

RahoittajatRahoittajan numero
Flemish Cancer SocietySTI.VLK.2022.0005.01, STI.VLK.2020.0006.01
Movember Foundation
Canadian Institutes of Health Research
Prostate Cancer Canada /Movember
Canadian Cancer Society707339
Academy of Finland312043
Jane ja Aatos Erkon Säätiö
Kom op tegen Kanker
BC Cancer Foundation
Prostate Cancer Fight Foundation

    Julkaisufoorumi-taso

    • Jufo-taso 3

    !!ASJC Scopus subject areas

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

    Sormenjälki

    Sukella tutkimusaiheisiin 'Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer'. Ne muodostavat yhdessä ainutlaatuisen sormenjäljen.

    Siteeraa tätä