Journal article
Tumor fraction in cell-free DNA as a biomarker in prostate cancer
JCI insight, Vol.3(21), 122109
11/02/2018
DOI: 10.1172/jci.insight.122109
PMID: 30385733
Abstract
BACKGROUND. Tumor content in circulating cell-free DNA (cfDNA) is a promising biomarker, but longitudinal dynamics of tumor-derived and non-tumor-derived cfDNA through multiple courses of therapy have not been well described.
METHODS. CfDNA from 663 plasma samples from 140 patients with castration-resistant prostate cancer (CRPC) was subject to sparse whole genome sequencing. Tumor fraction (TFx) estimated using the computational tool ichorCNA was correlated with clinical features and responses to therapy.
RESULTS. TFx associated with the number of bone metastases (median TFx = 0.014 with no bone metastases, 0.047 with 1-3 bone metastases, 0.190 for 4+ bone metastases; P < 0.0001) and with visceral metastases (P < 0.0001). In multivariable analysis, TFx remained associated with metastasis location (P = 0.042); TFx was positively correlated with alkaline phosphatase (P = 0.0227) and negatively correlated with hemoglobin (Hgb) (P < 0.001), but it was not correlated with prostate specific antigen (PSA) (P = 0.75). Tumor-derived and non-tumor-derived cfDNA track together and do not increase with generalized tissue damage from chemotherapy or radiation at the time scales examined. All new treatments that led to = 30% PSA decline at 6 weeks were associated with TFx decline when baseline TFx was > 7%; however, TFx in patients being subsequently maintained on secondary hormonal therapy was quite dynamic.
CONCLUSION. TFx correlates with clinical features associated with overall survival in CRPC, and TFx decline is a promising biomarker for initial therapeutic response.
Details
- Title: Subtitle
- Tumor fraction in cell-free DNA as a biomarker in prostate cancer
- Creators
- Atish D. Choudhury - Broad InstituteLillian Werner - Harvard UniversityEdoardo Francini - Dana-Farber Cancer InstituteXiao X. Wei - Dana-Farber Cancer InstituteGavin Ha - Broad InstituteSamuel S. Freeman - Broad InstituteJustin Rhoades - Broad InstituteSarah C. Reed - Broad InstituteGregory Gydush - Broad InstituteDenisse Rotem - Broad InstituteChristopher Lo - Broad InstituteMary-Ellen Taplin - Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USALauren C. Harshman - Dana-Farber Cancer InstituteZhenwei Zhang - Dana-Farber Cancer InstituteEdward P. O'Connor - Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USADaniel G. Stover - The Ohio State UniversityHeather A. Parsons - Broad InstituteGad Getz - Broad InstituteMatthew Meyerson - Broad InstituteJ. Christopher Love - Broad InstituteWilliam C. Hahn - Broad InstituteViktor A. Adalsteinsson - Broad Institute
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.3(21), 122109
- DOI
- 10.1172/jci.insight.122109
- PMID
- 30385733
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 13
- Grant note
- Janssen Pharmaceuticals Inc.; Johnson & Johnson; Johnson & Johnson USA; Janssen Biotech Inc P30-CA14051 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Prostate Cancer Foundation Young Investigator Award Department of Defense Physician Scientist Training Award; United States Department of Defense Dana-Farber Cancer Institute Medical Oncology grant Gerstner Family Foundation Wong Family Award in Translational Oncology SU2C-AACR-DT0712 / Entertainment Industry Foundation
- Language
- English
- Date published
- 11/02/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985221143302771
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