Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention

Lennon, Anne Marie; Buchanan, Adam H.; Kinde, Isaac; Warren, Andrew; Honushefsky, Ashley; Cohain, Ariella; Ledbetter, David H.; Sanfilippo, Fred; Sheridan, Kathleen; Rosica, Dillenia; Adonizio, Christian S.; Hwang, Hee Jung; Lahouel, Kamel; Cohen, Joshua D.; Douville, Christopher; Patel, Aalpen A.; Hagmann, Leonardo N.; Rolston, David D.K.; Malani, Nirav; Zhou, Shibin; Bettegowda, Chetan; Diehl, David L.; Urban, Bobbi; Still, Christopher D.; Kann, Lisa; Woods, Julie; Salvati, Zachary; Vadakara, Joseph; Leeming, Rosemary; Bhattacharya, Prianka; Walter, Carroll; Parker, Alex; Lengauer, Christoph; Klein, Alison P.; Tomasetti, Cristian; Fishman, Elliot K.; Hruban, Ralph H.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas

doi:10.1126/science.abb9601

Cited by 428 publications

(408 citation statements)

References 48 publications

(59 reference statements)

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“…One recent study by Liu et al studied DNA methylation as a further hallmark of a cancer cell, beyond simply mutation [ 64 ]. Another major investigation combined the detection of oncogenic ctDNA mutations, protein markers, and PET-CT (positron emission tomography—computerized tomography) in order to increase the accuracy of cancer detection while specifying the tissue of origin [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Mutations in normal tissues—some diagnostic and clinical implications

Fiala

Diamandis

2020

BMC Med

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Background It has long been known that mutations are at the core of many diseases, most notably cancer. Mutational analysis of tissues and fluids is useful for cancer and other disease diagnosis and management. Main body The prevailing cancer development hypothesis posits that cancer originates from mutations in cancer-driving genes that accumulate in tissues over time. These mutations then confer special characteristics to cancer cells, known as the hallmarks of cancer. Mutations in specific driver genes can lead to the formation of cancerous subclones and mutation risk increases with age. New research has revealed an unexpectedly large number of mutations in normal tissues; these findings could have significant implications to the understanding of the pathobiology of cancer and for disease diagnosis and therapy. Here, we discuss how the prevalence of mutations in normal tissues provides novel and relevant insights about clonal development in cancer and other diseases. Specifically, this review will focus on discussing mutations in normal tissues in the context of developing specific, circulating tumor DNA (ctDNA) tests for cancer, and evaluating clonal hematopoiesis as a predictor of blood cancers and cardiovascular pathology, as well as their implications to the phenomena of neural mosaicism in the context of Alzheimer’s disease. Conclusions In view of these new findings, the fundamental differences between the accumulation of genetic alterations in healthy, aging tissues compared to cancer and cardiovascular or neural diseases will need to be better delineated in the future.

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Section: Discussionmentioning

confidence: 99%

Mutations in normal tissues—some diagnostic and clinical implications

Fiala

Diamandis

2020

BMC Med

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“…However, the cancer detection effectiveness of CancerSEEK ranges from 98% for ovarian cancer to only 33% for breast cancer. A feasibility study of CancerSEEK tests has been conducted on a general population of 10,000 women with no history of cancer [ 39 ]. The blood test detected 26 previously unknown cancers of different types with a sensitivity (26/96) of 27.1%, a specificity of 98.9% (9707/9815), and a positive predictive value of 19.4% (26/134) [ 39 ].…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

“…Among the participants, 27 breast cancers were identified. Among them, only one breast cancer was first detected by the blood test, 20 by standard-of-care screening and six by other imaging means [ 39 ]. Therefore, CancerSEEK tests only have a low sensitivity of 3.7% (1/27) in breast cancer detection.…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

“…The CancerSEEK test was developed from a case–control study, which introduced a possible bias in the utility of the assay [ 145 , 146 ]. Although a remolding of the CancerSEEK test, e.g., the CancerA1DE method, increased the sensitivity to 70% for breast cancer detection at a 99% specificity [ 40 ], it is unlikely that the CancerSEEK test will be effective in breast cancer detection [ 39 ].…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

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Non-Invasive Biomarkers for Early Detection of Breast Cancer

Guan

Fan

et al. 2020

Cancers

135

104

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Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of “omics” strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

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“…The DETECT-A study recently demonstrated that assessment of a combination of mutations in cfDNA and protein marker analysis with clinical imaging can safely detect cancer in a previously unaffected, unselected population. 51 The Circulating Cell-Free Genome Atlas Study (CCGA) and STRIVE studies have shown cancer detection and accurate tissue of origin determination using methylation-based approaches (NCT02889978 and NCT03085888). 52 An another recent study, It is important to acknowledge the many questions and challenges that need to be addressed by researchers and healthcare providers;…”

Section: Capp-seq 33mentioning

confidence: 99%

Considerations for the use of circulating tumor DNA sequencing as a screening tool in cancer predisposition syndromes

Paramathas

Guha

Pugh

et al. 2020

Pediatric Blood & Cancer

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Liquid biopsy, specifically circulating tumor DNA (ctDNA) detection, has started to revolutionize the clinical management of patients with cancer by surpassing many limitations of traditional tissue biopsies, particularly for serial testing. ctDNA sequencing has been successfully utilized for cancer detection, prognostication, and assessment of disease response and evolution. While the applications of ctDNA analysis are growing, the majority of studies to date have primarily evaluated its use as a tool for tracking a known cancer, and in most cases at advanced stage. Herein, we discuss the potential application of ctDNA for surveillance and early cancer detection in patients with a cancer predisposition syndrome.

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Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention

Cited by 428 publications

References 48 publications

Mutations in normal tissues—some diagnostic and clinical implications

Mutations in normal tissues—some diagnostic and clinical implications

Non-Invasive Biomarkers for Early Detection of Breast Cancer

Considerations for the use of circulating tumor DNA sequencing as a screening tool in cancer predisposition syndromes

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