Emerging stool-based and blood-based non-invasive DNA tests for colorectal cancer screening: the importance of cancer prevention in addition to cancer detection

Pickhardt, Perry J.

doi:10.1007/s00261-016-0798-4

Cited by 42 publications

(32 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…cfDNA refers to circulating DNA fragments that originate from tumor cells, thus representing a form of liquid biopsy that carries the mutations and methylomic abnormalities present in the tumor [41]. The first FDA-approved assay, Epi proColon®, became available to the market in 2016 and is used to assess promoter hypermethylation in the SEPT9 gene [40,42]. The assay demonstrates high sensitivity and specificity for CRC, but its ability to detect precancerous lesions is low [40,42], indicating that early detection should be done in combination with other methods.…”

Section: Screening For Accelerated Biological Aging To Assess Colorecmentioning

confidence: 99%

Should we invest in biological age predictors to treat colorectal cancer in older adults?

Hägg

Jylhävä

2020

European Journal of Surgical Oncology

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a chronic disease of the old population with slow development progressing into clinical signs and symptoms. Biological aging is characterized by e.g. mitochondrial dysfunction and epigenetic alterations (e.g. methylation)-mechanisms that are also important in cancer development. For CRC, specific types of tumors are distinguishable by their methylation patterns and several detection methods using different epigenetic marks have been developed as signatures for the disease. Biological age assessed by DNA methylation patterns from blood, i.e. the epigenetic clock, is higher in CRC patients compared to controls, and may be a tool for identifying individuals at increased risk for CRC. Other types of biomarkers of aging are useful to calculate biological age, such as metabolites, protein levels, inflammatory markers and clinical biomarkers, where composite scores of biomarkers have been used to assess the risk of CRC and colorectal adenomas. Clinical assessments of biological aging includes frailty, which is a geriatric syndrome characterized by increased vulnerability to adverse outcomes. More than half of the CRC patients are estimated to be frail or pre-frail, and these individuals are at increased risk of postoperative complications, poorer prognosis, treatment intolerance and death. Hence, considering frailty as part of biological age in CRC patients may help identifying those at need of close monitoring. In summary, future screening programs for CRC may make use of biological age assessments, e.g. by epigenetic clock or composite scores. Monitoring disease relapse and treatment response should be enhanced in frail individuals for better prognosis.

show abstract

Section: Screening For Accelerated Biological Aging To Assess Colorecmentioning

confidence: 99%

Should we invest in biological age predictors to treat colorectal cancer in older adults?

Hägg

Jylhävä

2020

European Journal of Surgical Oncology

View full text Add to dashboard Cite

show abstract

“…Early screening tests for cancer are not novel to the medical system; existing tests provide a benchmark for the costs that payers are willing to tolerate for screening in the general population. As an example, in the USA, Medicare agreed to reimburse the Cologuard fecal screening test for colorectal cancer at $502 every three years [Pickhardt2016]. Assuming the physical limitation of sample volume and interpretive limitations of somatic heterogeneity could be successfully overcome, reimbursement may still pose a fundamental economic threat to the viability of mutation-based ctDNA assays for early detection.…”

Section: Health Economics Of Mutation Calling For Early Detectionmentioning

confidence: 99%

Challenges in Using ctDNA to Achieve Early Detection of Cancer

Haque

Elemento

2017

Preprint

View full text Add to dashboard Cite

Early detection of cancer is a significant unmet clinical need. Improved technical ability to detect circulating tumor-derived DNA (ctDNA) in the cell-free DNA (cfDNA) component of blood plasma via next-generation sequencing and established correlations between ctDNA load and tumor burden in cancer patients have spurred excitement about the possibilities of detecting cancer early by performing ctDNA mutation detection.We reanalyze published data on the expected ctDNA allele fraction in early-stage cancer and the population statistics of cfDNA concentration to show that under conservative technical assumptions, high-sensitivity cancer detection by ctDNA mutation detection will require either more blood volume (150-300mL) than practical for a routine screen or variant filtering that may be impossible given our knowledge of cancer evolution, and will likely remain out of economic reach for routine population screening without multiple-order-of-magnitude decreases in sequencing cost. Instead, new approaches that integrate ctDNA mutations with multiple other blood-based analytes (such as exosomes, circulating tumor cells, ctDNA epigenetics, metabolites) as well as integration of these signals over time for each individual may be needed.

show abstract

“…1 As such, preventive tests such as optical colonoscopy (OC) and CT colonography (CTC) were favored over the stool-based tests (fecal occult blood test, fecal immunochemical test, and stool DNA testing) which are primarily used for detection. 2,3 This revised guideline actually referred only to adults at average and low-risk, because no new consideration or changes were made with regard to recommendations for patients at high risk. Rather, tables were provided for patients at high risk that were simply carryovers of older guidelines from 2001 to 2003, before quality data existed on CTC screening.…”

Section: Introductionmentioning

confidence: 99%

CT Colonographic Screening of Patients With a Family History of Colorectal Cancer: Comparison With Adults at Average Risk and Implications for Guidelines

Pickhardt

Mbah

Pooler

et al. 2017

American Journal of Roentgenology

Self Cite

View full text Add to dashboard Cite

Objective The purposes of this study were to compare rates of lesion detection at CT colonographic (CTC) screening of adults without symptoms who had and did not have a family history of colorectal cancer according to American Cancer Society (ACS) guidelines and to consider the clinical implications. Materials and Methods Over 134 months, consecutively registered CTC cohorts of adults without symptoms who had (n=156; 88 [56.4%] women; 68 [43.6%] men; mean age, 56.3 years) and who did not have (n=8857; 4757 [53.7%] women; 4100 [46.3%] men; mean age, 56.6 years) an American Cancer Society-defined family history of colorectal cancer (first-degree relative with diagnosis before age 60 years or two first-degree relatives with diagnosis at any age) were compared for relevant colorectal findings. Results For the family history versus no family history cohorts, the frequency of all nondiminutive polyps (≥6 mm) reported at CTC was 23.7 % versus 15.5% (p = 0.007); small polyps (6-9 mm), 13.5% versus 9.1% (p = 0.068); and large polyps (≥10 mm), 10.2% versus 6.5% (p = 0.068). The rate of referral for colonoscopy was greater for the family history cohort (16.0% vs 10.5%; p=0.035). However, the frequencies of proven advanced adenoma (4.5% vs 3.2%; p=0.357), nonadvanced adenoma (5.1% vs 2.6%; p=0.070), and cancer (0.0% vs 0.4%; p=0.999) were not significantly increased. The difference in positive rates between the two cohorts (11.5% vs 4.3%; p<0.001) was primarily due to nonneoplastic findings of no colorectal cancer relevance, such as small hyperplastic polyps, diverticular disease, and false-positive CTC findings. Conclusion Although the overall CTC-positive and colonoscopy referral rates were higher in the family history cohort, the clinically relevant frequencies of advanced neoplasia and cancer were not significantly increased to preclude CTC screening. These findings support the use of CTC as a front-line screening option in adults with a positive family history of colorectal cancer.

show abstract

Emerging stool-based and blood-based non-invasive DNA tests for colorectal cancer screening: the importance of cancer prevention in addition to cancer detection

Cited by 42 publications

References 29 publications

Should we invest in biological age predictors to treat colorectal cancer in older adults?

Should we invest in biological age predictors to treat colorectal cancer in older adults?

Challenges in Using ctDNA to Achieve Early Detection of Cancer

CT Colonographic Screening of Patients With a Family History of Colorectal Cancer: Comparison With Adults at Average Risk and Implications for Guidelines

Contact Info

Product

Resources

About