Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps

Cock, Charles; Anwar, Shahzaib; Byrne, Susan E; Meng, Rosie; Pedersen, Susanne K.; Fraser, Robert; Young, Graeme P.; Symonds, Erin L.

doi:10.1007/s10620-019-05569-8

Cited by 27 publications

(26 citation statements)

References 35 publications

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“…Furthermore, age (≥ 70 years) and cell free DNA yield were significant independent factors associated with the detection of methylated BCAT1/IKZF1 in the patients with no CRC [ 54 ]. Another study showed low sensitivity of BCAT1/IKZF1 in detecting sessile serrated adenomas/polyps (SSP) (8.8%) and when combined with FIT, it remained low (26.5%) but still higher than FIT alone (16.3%) [ 55 ].…”

Section: Methodsmentioning

confidence: 99%

Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction

et al. 2021

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Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancers though its incidence ranks third. Early CRC detection is key and is associated with improved survival outcomes. However, existing tests for CRC diagnosis have several weaknesses thus rendering them inefficient. Moreover, reliable prognostic tests that can predict the overall cancer outcome and recurrence of the disease as well as predictive markers that can assess effectiveness of therapy are still lacking. Thus, shifting to noninvasive liquid biopsy or blood-based biomarkers is vital to improving CRC diagnosis, prognosis, and prediction. Methylated circulating tumor DNA (ctDNA) has gained increased attention as a type of liquid biopsy that is tumor-derived fragmented DNA with epigenetic alterations. Methylated ctDNA are more consistently present in blood of cancer patients as compared to mutated ctDNA. Hence, methylated ctDNA serves as a potential biomarker for CRC that is worth investigating. In this review, we explore what has been reported about methylated ctDNA as a biomarker for CRC diagnosis that can distinguish between CRC patients or those having adenoma and healthy controls as validated specifically through ROC curves. We also examine methylated ctDNA as a biomarker for CRC prognosis and prediction as confirmed through robust statistical analyses. Finally, we discuss the major technical challenges that limits the use of methylated ctDNA for clinical application and suggest possible recommendations to enhance its usage.

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Section: Methodsmentioning

confidence: 99%

Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction

et al. 2021

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“…These findings are unsurprising because f-Hb is related to severity of colorectal disease and higher f-Hb is found in HRA than LRA, large (> 10 mm) compared with small adenoma, and also adenoma displaying high-grade compared with low-grade dysplasia. [10] Our data would add to the observations that, in comparison to adenomas, SSA are found less frequently at colonoscopy and, for the various reasons elicited by Cock et al, [1] may not be associated with significant f-Hb. Moreover, our data suggest that their findings on SSA/SSP are likely to be transferable between clinical settings, over geography, and with different FIT systems.…”

mentioning

confidence: 50%

“…We were interested to read the study of Cock et al [1] on the clinical sensitivity of fecal immunochemical tests (FIT) for the detection of sessile serrated adenomas/polyps (SSA/SSP), and their conclusion that FIT have low sensitivity for their detection.…”

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confidence: 99%

Low Sensitivity of Fecal Immunochemical Tests (FIT) for Detection of Sessile Serrated Adenomas/Polyps Confirmed Over Clinical Setting, Geography, and FIT System

et al. 2019

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“…Cost-effectiveness analysis showed that FIT10 (10 µg Hb/g feces) would be the most optimal cut-off level in the average risk population, with a high sensitivity for CRC [33]. The FIT10 sensitivity for detecting AN was low in HL survivors, around 40%, but comparable with sensitivity data in average risk and above-average risk populations [27,[34][35][36].…”

Section: Discussionmentioning

confidence: 75%

“…Due to the increased risk of CRC, other criteria for optimal performance of stool tests should be used compared to an average-risk population-based screening [31][32][33][34][35][36]. In this high-risk-group, it can be argued that detection of precursor colorectal neoplasia is extra important due to the higher prevalence of these lesions and CRC.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Stool Tests for Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors

Ykema

Rigter

Spaander

et al. 2020

JCM

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Background: Hodgkin lymphoma (HL) survivors have an increased colorectal cancer (CRC) risk. Diagnostic accuracy of quantitative fecal immunochemical testing (FIT, OC Sensor) and/or a multi-target stool DNA test (mt-sDNA, Cologuard®) for advanced neoplasia (AN) was evaluated. Methods: 101 HL survivors underwent a surveillance colonoscopy and were asked to perform two stool tests (FIT and mt-sDNA). Advanced adenoma (AA), advanced serrated lesion (ASL), and AN (AA, ASL, CRC) were evaluated. Sensitivity, specificity, and area under the curve (AUC) for AN were calculated for different FIT cut-offs and mt-sDNA with colonoscopy as reference. Results: FIT and mt-sDNA were analyzed in 73 (72%) and 82 (81%) participants, respectively. AN was detected in 19 (26%) and 22 (27%), respectively. AN sensitivities for FIT cut-off of 10 ug Hb/g feces (FIT10) and mt-sDNA were 37% (95% confidence interval (CI): 16–62) and 68% (95% CI: 45–86), with corresponding specificities of 91% (95% CI: 80–97) and 70% (95% CI: 57–86), respectively. AUC for FIT was 0.68 (95% CI: 0.54–0.82) and for mt-sDNA 0.76 (95% CI: 0.63–0.89). Conclusions: In HL survivors, mt-sDNA showed highest sensitivity but with relatively low specificity for AN. Cost-effectiveness analyses is necessary to determine the optimal surveillance strategy.

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Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps

Cited by 27 publications

References 35 publications

Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction

Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction

Low Sensitivity of Fecal Immunochemical Tests (FIT) for Detection of Sessile Serrated Adenomas/Polyps Confirmed Over Clinical Setting, Geography, and FIT System

Diagnostic Accuracy of Stool Tests for Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors

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