Clinical correlates of circulating cell-free DNA tumor fraction

被引:44
作者
Bredno, Joerg [1 ]
Lipson, Jafi [1 ,2 ]
Venn, Oliver [1 ]
Aravanis, Alexander M. [1 ,3 ]
Jamshidi, Arash [1 ]
机构
[1] GRAIL Inc, Menlo Pk, CA 94025 USA
[2] Genentech Inc, San Francisco, CA 94080 USA
[3] Illumina Inc, San Diego, CA USA
关键词
BREAST-CANCER PATIENTS; COLORECTAL-CANCER; FDG-PET; BLOOD; PLASMA; GROWTH; SIZE; OVERDIAGNOSIS; ANGIOGENESIS; MAMMOGRAPHY;
D O I
10.1371/journal.pone.0256436
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated. Methods and findings Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test. Conclusions Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.
引用
收藏
页数:26
相关论文
共 71 条
[1]   Engineered immune cells as highly sensitive cancer diagnostics [J].
Aalipour, Amin ;
Chuang, Hui-Yen ;
Murty, Surya ;
D'Souza, Aloma L. ;
Park, Seung-min ;
Gulati, Gunsagar S. ;
Patel, Chirag B. ;
Beinat, Corinne ;
Simonetta, Federico ;
Martinic, Ivana ;
Gowrishankar, Gayatri ;
Robinson, Elise R. ;
Aalipour, Eamon ;
Zhian, Zahra ;
Gambhir, Sanjiv S. .
NATURE BIOTECHNOLOGY, 2019, 37 (05) :531-+
[2]   Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].
Abbosh, Christopher ;
Birkbak, Nicolai J. ;
Wilson, Gareth A. ;
Jamal-Hanjani, Mariam ;
Constantin, Tudor ;
Salari, Raheleh ;
Le Quesne, John ;
Moore, David A. ;
Veeriah, Selvaraju ;
Rosenthal, Rachel ;
Marafioti, Teresa ;
Kirkizlar, Eser ;
Watkins, Thomas B. K. ;
McGranahan, Nicholas ;
Ward, Sophia ;
Martinson, Luke ;
Riley, Joan ;
Fraioli, Francesco ;
Al Bakir, Maise ;
Gronroos, Eva ;
Zambrana, Francisco ;
Endozo, Raymondo ;
Bi, Wenya Linda ;
Fennessy, Fiona M. ;
Sponer, Nicole ;
Johnson, Diana ;
Laycock, Joanne ;
Shafi, Seema ;
Czyzewska-Khan, Justyna ;
Rowan, Andrew ;
Chambers, Tim ;
Matthews, Nik ;
Turajlic, Samra ;
Hiley, Crispin ;
Lee, Siow Ming ;
Forster, Martin D. ;
Ahmad, Tanya ;
Falzon, Mary ;
Borg, Elaine ;
Lawrence, David ;
Hayward, Martin ;
Kolvekar, Shyam ;
Panagiotopoulos, Nikolaos ;
Janes, Sam M. ;
Thakrar, Ricky ;
Ahmed, Asia ;
Blackhall, Fiona ;
Summers, Yvonne ;
Hafez, Dina ;
Naik, Ashwini .
NATURE, 2017, 545 (7655) :446-+
[3]   The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging [J].
Amin, Mahul B. ;
Greene, Frederick L. ;
Edge, Stephen B. ;
Compton, Carolyn C. ;
Gershenwald, Jeffrey E. ;
Brookland, Robert K. ;
Meyer, Laura ;
Gress, Donna M. ;
Byrd, David R. ;
Winchester, David P. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2017, 67 (02) :93-99
[4]   A mathematical model of ctDNA shedding predicts tumor detection size [J].
Avanzini, Stefano ;
Kurtz, David M. ;
Chabon, Jacob J. ;
Moding, Everett J. ;
Hori, Sharon Seiko ;
Gambhir, Sanjiv Sam ;
Alizadeh, Ash A. ;
Diehn, Maximilian ;
Reiter, Johannes G. .
SCIENCE ADVANCES, 2020, 6 (50)
[5]   Supplemental MRI Screening for Women with Extremely Dense Breast Tissue [J].
Bakker, Marije F. ;
de Lange, Stephanie V. ;
Pijnappel, Ruud M. ;
Mann, Ritse M. ;
Peeters, Petra H. M. ;
Monninkhof, Evelyn M. ;
Emaus, Marleen J. ;
Loo, Claudette E. ;
Bisschops, Robertus H. C. ;
Lobbes, Marc B. I. ;
de Jong, Matthijn D. F. ;
Duvivier, Katya M. ;
Veltman, Jeroen ;
Karssemeijer, Nico ;
de Koning, Harry J. ;
van Diest, Paul J. ;
Mali, Willem P. T. M. ;
van den Bosch, Maurice A. A. J. ;
Veldhuis, Wouter B. ;
van Gils, Carla H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2019, 381 (22) :2091-2102
[6]   Interim results of PATHFINDER, a clinical use study using a methylation-based multi-cancer early detection test. [J].
Beer, Tomasz M. ;
McDonnell, Charles H. ;
Nadauld, Lincoln ;
Liu, Minetta C. ;
Klein, Eric A. ;
Reid, Robert Lawrence ;
Marinac, Catherine ;
Chung, Karen ;
Lopatin, Margarita ;
Fung, Eric T. ;
Schrag, Deborah .
JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (15)
[7]   Primary tumor standardized uptake value (SUVmax) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) is of prognostic value for survival in non-small cell lung cancer (NSCLC) -: A systematic review and meta-analysis (MA) by the European lung cancer working party for the IASLC lung cancer staging project [J].
Berghmans, Thierry ;
Dusart, Michele ;
Paesmans, Marianne ;
Hossein-Foucher, Claude ;
Buvat, Irene ;
Castaigne, Catherine ;
Scherpereel, Arnaud ;
Mascaux, Celine ;
Moreau, Michel ;
Roelandts, Martine ;
Alard, Stphane ;
Meert, Anne-Pascale ;
Patz, Edward F., Jr. ;
Lafitte, Jean-Jacques ;
Sculier, Jean-Paul .
JOURNAL OF THORACIC ONCOLOGY, 2008, 3 (01) :6-12
[8]   Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].
Bettegowda, Chetan ;
Sausen, Mark ;
Leary, Rebecca J. ;
Kinde, Isaac ;
Wang, Yuxuan ;
Agrawal, Nishant ;
Bartlett, Bjarne R. ;
Wang, Hao ;
Luber, Brandon ;
Alani, Rhoda M. ;
Antonarakis, Emmanuel S. ;
Azad, Nilofer S. ;
Bardelli, Alberto ;
Brem, Henry ;
Cameron, John L. ;
Lee, Clarence C. ;
Fecher, Leslie A. ;
Gallia, Gary L. ;
Gibbs, Peter ;
Le, Dung ;
Giuntoli, Robert L. ;
Goggins, Michael ;
Hogarty, Michael D. ;
Holdhoff, Matthias ;
Hong, Seung-Mo ;
Jiao, Yuchen ;
Juhl, Hartmut H. ;
Kim, Jenny J. ;
Siravegna, Giulia ;
Laheru, Daniel A. ;
Lauricella, Calogero ;
Lim, Michael ;
Lipson, Evan J. ;
Marie, Suely Kazue Nagahashi ;
Netto, George J. ;
Oliner, Kelly S. ;
Olivi, Alessandro ;
Olsson, Louise ;
Riggins, Gregory J. ;
Sartore-Bianchi, Andrea ;
Schmidt, Kerstin ;
Shih, Ie-Ming ;
Oba-Shinjo, Sueli Mieko ;
Siena, Salvatore ;
Theodorescu, Dan ;
Tie, Jeanne ;
Harkins, Timothy T. ;
Veronese, Silvio ;
Wang, Tian-Li ;
Weingart, Jon D. .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)
[9]  
Bredno J, 2020, J CLIN ONCOL, V38
[10]   Characterization of the cell-free DNA released by cultured cancer cells [J].
Bronkhorst, Abel Jacobus ;
Wentzel, Johannes F. ;
Aucamp, Janine ;
van Dyk, Etresia ;
du Plessis, Lissinda ;
Pretorius, Piet J. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2016, 1863 (01) :157-165