Prognostic Significance of Blood-Based Multi-cancer Detection in Plasma Cell-Free DNA

Chen, Xiaoji; Zhao, Dong; Hubbell, Earl; Kurtzman, Kathryn N.; Oxnard, Geoffrey R.; Venn, Oliver; Melton, Collin; Clarke, Christina A.; Shaknovich, Rita; Ma, Tianzhou; Meixiong, Gerry; Seiden, Michael V.; Klein, Eric A.; Fung, Eric T.; Liu, Minetta C.

doi:10.1158/1078-0432.ccr-21-0417

Cited by 75 publications

(74 citation statements)

References 46 publications

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“…However, more clinical trials are required for verifying these findings and for providing the standard operation procedure. Moreover, ctDNA testing has attracted great attention in early tumor detection of several common cancer types (57,(85)(86)(87), although it is still a long way to apply ctDNA testing in the clinical routine.…”

Section: Discussionmentioning

confidence: 99%

Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

et al. 2021

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BackgroundNon-small cell lung cancer (NSCLC) is one of the most prevalent causes of cancer-related death worldwide. Recently, there are many important medical advancements on NSCLC, such as therapies based on tyrosine kinase inhibitors and immune checkpoint inhibitors. Most of these therapies require tumor molecular testing for selecting patients who would benefit most from them. As invasive biopsy is highly risky, NSCLC molecular testing based on liquid biopsy has received more and more attention recently.ObjectiveWe aimed to introduce liquid biopsy and its potential clinical applications in NSCLC patients, including cancer diagnosis, treatment plan prioritization, minimal residual disease detection, and dynamic monitoring on the response to cancer treatment.MethodWe reviewed recent studies on circulating tumor DNA (ctDNA) testing, which is a minimally invasive approach to identify the presence of tumor-related mutations. In addition, we evaluated potential clinical applications of ctDNA as blood biomarkers for advanced NSCLC patients.ResultsMost studies have indicated that ctDNA testing is critical in diagnosing NSCLC, predicting clinical outcomes, monitoring response to targeted therapies and immunotherapies, and detecting cancer recurrence. Moreover, the changes of ctDNA levels are associated with tumor mutation burden and cancer progression.ConclusionThe ctDNA testing is promising in guiding the therapies on NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

et al. 2021

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“…Biological factors associated with tumor DNA shedding include tumor volume and tumor surface area, vascularization, tumor cell growth and death rates, mitotic and metabolic activity, and cell morphology. Furthermore, cancer signal detection is associated with active proliferation and explains why more aggressive cancers tend to shed more DNA into the bloodstream [ 135 ]. In fact, longitudinal follow-up data to evaluate the prognostic significance of a multi-cancer early detection (MCED) test has suggested that this test detected more clinically significant cancers and that detection was prognostic beyond clinical stage and method of clinical diagnosis.…”

Section: Current Status Of Clinical Use Of Ctdna Testing In Patients ...mentioning

confidence: 99%

“…In fact, longitudinal follow-up data to evaluate the prognostic significance of a multi-cancer early detection (MCED) test has suggested that this test detected more clinically significant cancers and that detection was prognostic beyond clinical stage and method of clinical diagnosis. Accordingly, cancers not detected by the MCED test tended to be less aggressive [ 135 ]. Hence, biological differences in shedding rates may explain the differences in sensitivity between various tumors and high ctDNA levels may be an indication for more aggressive cancers.…”

Section: Current Status Of Clinical Use Of Ctdna Testing In Patients ...mentioning

confidence: 99%

A clinician’s handbook for using ctDNA throughout the patient journey

Hasenleithner

Speicher

2022

Mol Cancer

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Background The promise of precision cancer medicine presently centers around the genomic sequence of a patient’s tumor being translated into timely, actionable information to inform clinical care. The analysis of cell-free DNA from liquid biopsy, which contains circulating tumor DNA (ctDNA) in patients with cancer, has proven to be amenable to various settings in oncology. However, open questions surrounding the clinical validity and utility of plasma-based analyses have hindered widespread clinical adoption. Main body Owing to the rapid evolution of the field, studies supporting the use of ctDNA as a biomarker throughout a patient’s journey with cancer have accumulated in the last few years, warranting a review of the latest status for clinicians who may employ ctDNA in their precision oncology programs. In this work, we take a step back from the intricate coverage of detection approaches described extensively elsewhere and cover basic concepts around the practical implementation of next generation sequencing (NGS)-guided liquid biopsy. We compare relevant targeted and untargeted approaches to plasma DNA analysis, describe the latest evidence for clinical validity and utility, and highlight the value of genome-wide ctDNA analysis, particularly as it relates to early detection strategies and discovery applications harnessing the non-coding genome. Conclusions The maturation of liquid biopsy for clinical application will require interdisciplinary efforts to address current challenges. However, patients and clinicians alike may greatly benefit in the future from its incorporation into routine oncology care.

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“…However, more than 90% of those who were negative for ctDNA did not relapse [ 13 ]. Since then, the prognostic value of ctDNA was repeatedly confirmed [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 ]. Similar to other tumor markers, ctDNA can also be used to monitor disease progression.…”

Section: Clinical Applications Of Ctdnamentioning

confidence: 99%

“…Importantly, it is well-established that the amount of ctDNA is proportional to tumor size (tumor burden) and is related to other clinicopathological parameters such as stage, lymph node infiltration, local and distant metastasis, and disease-free and overall survival [ 8 , 9 ]. Thus, ctDNA carries strong prognostic information [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Can Circulating Tumor DNA Support a Successful Screening Test for Early Cancer Detection? The Grail Paradigm

2021

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Circulating tumor DNA (ctDNA) is a new pan-cancer tumor marker with important applications for patient prognosis, monitoring progression, and assessing the success of the therapeutic response. Another important goal is an early cancer diagnosis. There is currently a debate if ctDNA can be used for early cancer detection due to the small tumor burden and low mutant allele fraction (MAF). We compare our previous calculations on the size of detectable cancers by ctDNA analysis with the latest experimental data from Grail’s clinical trial. Current ctDNA-based diagnostic methods could predictably detect tumors of sizes greater than 10–15 mm in diameter. When tumors are of this size or smaller, their MAF is about 0.01% (one tumor DNA molecule admixed with 10,000 normal DNA molecules). The use of 10 mL of blood (4 mL of plasma) will likely contain less than a complete cancer genome, thus rendering the diagnosis of cancer impossible. Grail’s new data confirm the low sensitivity for early cancer detection (<30% for Stage I–II tumors, <20% for Stage I tumors), but specificity was high at 99.5%. According to these latest data, the sensitivity of the Grail test is less than 20% in Stage I disease, casting doubt if this test could become a viable pan-cancer clinical screening tool.

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Prognostic Significance of Blood-Based Multi-cancer Detection in Plasma Cell-Free DNA

Cited by 75 publications

References 46 publications

Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

A clinician’s handbook for using ctDNA throughout the patient journey

Can Circulating Tumor DNA Support a Successful Screening Test for Early Cancer Detection? The Grail Paradigm

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