Mo1599 HIGH-RISK SERRATED LESION DETECTION AT CRC SCREENING: MULTITARGET STOOL DNA VERSUS CT COLONOGRAPHY

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

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The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis

Cancers ◽

10.3390/cancers13071575 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1575

Author(s):

Lucia Zanoni ◽

Riccardo Mei ◽

Lorenzo Bianchi ◽

Francesca Giunchi ◽

Lorenzo Maltoni ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Malignant Lesion ◽

Lesion Detection ◽

Histopathological Analysis ◽

Choline Pet ◽

Primary Prostate Cancer ◽

Pet Ct

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

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Cross-sectional adherence with the multi-target stool DNA test for colorectal cancer screening in a large, nationally insured cohort

International Journal of Colorectal Disease ◽

10.1007/s00384-021-03956-0 ◽

2021 ◽

Author(s):

Lesley-Ann Miller-Wilson ◽

Lila J Finney Rutten ◽

Jack Van Thomme ◽

A Burak Ozbay ◽

Paul J Limburg

Keyword(s):

Colorectal Cancer ◽

National Sample ◽

Adherence Rate ◽

Average Risk ◽

Cross Sectional ◽

Commercial Insurance ◽

Dna Test ◽

Crc Screening ◽

Stool Dna ◽

Insured Patients

Abstract Purpose Colorectal cancer (CRC) is the second most deadly cancer in the USA. Early detection can improve CRC outcomes, but recent national screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test. We evaluated cross-sectional mt-sDNA test completion in a population of commercially and Medicare-insured patients. Methods Participants included individuals ages 50 years and older with commercial insurance or Medicare, with a valid mt-sDNA test shipped by Exact Sciences Laboratories LLC between January 1, 2018, and December 31, 2018 (n = 1,420,460). In 2020, we analyzed cross-sectional adherence, as the percent of successfully completed tests within 365 days of shipment date. Results Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance. Adherence increased with age: 60.8% for ages 50–64, 71.3% for ages 65–75, and 74.7% for ages 76 + years. Participants with mt-sDNA tests ordered by gastroenterologists had a higher adherence rate (78.3%) than those with orders by primary care clinicians (67.2%). Geographically, adherence rates were highest among highly rural patients (70.8%) and ordering providers in the Pacific region (71.4%). Conclusions Data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test, supporting its role as an accepted, noninvasive option for average-risk CRC screening. Attributes of mt-sDNA screening, including home-based convenience and accompanying navigation support, likely contributed to high completion rates.

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Estimation of Impact of American College of Radiology Recommendations on CT Colonography Reporting for Resection of High-Risk Adenoma Findings

The American Journal of Gastroenterology ◽

10.1038/ajg.2008.35 ◽

2008 ◽

Vol 104 (1) ◽

pp. 149-153 ◽

Cited By ~ 90

Author(s):

Douglas K Rex ◽

Andrew J Overhiser ◽

Shawn C Chen ◽

Oscar W Cummings ◽

Thomas M Ulbright

Keyword(s):

High Risk ◽

Ct Colonography

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Patient and Physician Factors Associated with Adenoma and Sessile Serrated Lesion Detection Rates

Digestive Diseases and Sciences ◽

10.1007/s10620-020-06419-8 ◽

2020 ◽

Vol 65 (11) ◽

pp. 3123-3131 ◽

Cited By ~ 1

Author(s):

Margaret J. Zhou ◽

Benjamin Lebwohl ◽

Anna Krigel

Keyword(s):

Lesion Detection ◽

Detection Rates ◽

Factors Associated ◽

Serrated Lesion

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High-risk human papillomavirus messenger RNA testing in wet- and dry- self-collected specimens for high-grade cervical lesion detection in Mombasa, Kenya

Sexually Transmitted Diseases ◽

10.1097/olq.0000000000001167 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Jessica Yasmine Islam ◽

Michael M. Mutua ◽

Emmanuel Kabare ◽

Griffins Manguro ◽

Michael G. Hudgens ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Messenger Rna ◽

Lesion Detection ◽

Cervical Lesion ◽

High Grade

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Fecal DNA Testing for Colorectal Cancer Screening

Annual Review of Medicine ◽

10.1146/annurev-med-103018-123125 ◽

2020 ◽

Vol 71 (1) ◽

pp. 59-69 ◽

Cited By ~ 5

Author(s):

John M. Carethers

Keyword(s):

Colorectal Cancer ◽

Average Risk ◽

Fecal Dna ◽

Polyp Detection ◽

Serrated Polyps ◽

Crc Screening ◽

Epigenetic Biomarkers ◽

Life Years ◽

Screening Strategies ◽

Stool Dna

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies’ assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80–90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.

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