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Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer.
Fonseca, Nicolette M; Maurice-Dror, Corinne; Herberts, Cameron; Tu, Wilson; Fan, William; Murtha, Andrew J; Kollmannsberger, Catarina; Kwan, Edmond M; Parekh, Karan; Schönlau, Elena; Bernales, Cecily Q; Donnellan, Gráinne; Ng, Sarah W S; Sumiyoshi, Takayuki; Vergidis, Joanna; Noonan, Krista; Finch, Daygen L; Zulfiqar, Muhammad; Miller, Stacy; Parimi, Sunil; Lavoie, Jean-Michel; Hardy, Edward; Soleimani, Maryam; Nappi, Lucia; Eigl, Bernhard J; Kollmannsberger, Christian; Taavitsainen, Sinja; Nykter, Matti; Tolmeijer, Sofie H; Boerrigter, Emmy; Mehra, Niven; van Erp, Nielka P; De Laere, Bram; Lindberg, Johan; Grönberg, Henrik; Khalaf, Daniel J; Annala, Matti; Chi, Kim N; Wyatt, Alexander W.
Affiliation
  • Fonseca NM; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Maurice-Dror C; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Herberts C; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Tu W; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Fan W; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Murtha AJ; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Kollmannsberger C; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Kwan EM; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Parekh K; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Schönlau E; Department of Medicine, School of Clinical Sciences; Monash University, Melbourne, VIC, Australia.
  • Bernales CQ; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Donnellan G; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Ng SWS; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Sumiyoshi T; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Vergidis J; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Noonan K; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Finch DL; Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Zulfiqar M; Department of Medical Oncology, BC Cancer, Victoria, BC, Canada.
  • Miller S; Department of Medical Oncology, BC Cancer, Surrey, BC, Canada.
  • Parimi S; Department of Medical Oncology, BC Cancer, Kelowna, BC, Canada.
  • Lavoie JM; Department of Medical Oncology, BC Cancer, Abbotsford, BC, Canada.
  • Hardy E; Department of Radiation Oncology, BC Cancer, Prince George, BC, Canada.
  • Soleimani M; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Nappi L; Department of Medical Oncology, BC Cancer, Victoria, BC, Canada.
  • Eigl BJ; Tom McMurtry & Peter Baerg Cancer Centre, Vernon Jubilee Hospital, Vernon, BC, Canada.
  • Kollmannsberger C; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Taavitsainen S; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Nykter M; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Tolmeijer SH; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Boerrigter E; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Mehra N; Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
  • van Erp NP; Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
  • De Laere B; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Lindberg J; Department of Medical Oncology, Research Institute for Medical Innovation, Radboud University, Nijmegen, The Netherlands.
  • Grönberg H; Department of Pharmacy, Research Institute for Medical Innovation, Radboud University, Nijmegen, The Netherlands.
  • Khalaf DJ; Department of Medical Oncology, Research Institute for Medical Innovation, Radboud University, Nijmegen, The Netherlands.
  • Annala M; Department of Pharmacy, Research Institute for Medical Innovation, Radboud University, Nijmegen, The Netherlands.
  • Chi KN; Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
  • Wyatt AW; Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
Nat Commun ; 15(1): 1828, 2024 Feb 28.
Article in En | MEDLINE | ID: mdl-38418825
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms, Castration-Resistant Limits: Humans / Male Language: En Journal: Nat Commun / Nature communications Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Canadá Country of publication: Reino Unido
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms, Castration-Resistant Limits: Humans / Male Language: En Journal: Nat Commun / Nature communications Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Canadá Country of publication: Reino Unido