Citations

Abstract Background Patients with Crohn’s disease (CD) who have ileal or any small bowel (SB) involvement are at increased risk of developing SB cancer. Due to the rarity of this complication of CD, we aimed to describe the clinical features, presentation, and of small bowel neoplasms (SBN) in patients with CD. Methods A case-control study was performed to include patients ≥18 years old with a diagnosis of CD with or without SBN at a single large referral center from January 1992 to May 2023. Patients were identified using bioinformatics and natural language processing tools, as well as anatomic pathology records. Two age- and sex-matched controls were identified for each case. Results In total, 54 patients with CD and SBN and 108 patients with CD without SBN were identified. Of the cases, most had ileal CD (55.6%) with stricturing (59.3%) phenotype. Median duration of CD prior to SBN diagnosis was 19.5 years. Nonpenetrating/nonstricturing behavior (odds ratio [OR], 9.23; 95% CI, 2.91-29.32; P = .0008) was significantly associated with an increased odds of SBN. History of tobacco use (OR, 0.27; 95% CI, 0.13-0.60; P = .0011) and IBD-associated colonic neoplasia (OR, 0.18; 95%, CI 0.4-0.85; P = .0303) were protective in development of SBN. Conclusions Nonpenetrating/nonstricturing CD appeared to raise SBN risk. History of tobacco use and colonic IBD-associated neoplasia are associated with reduced risk of SBN. Further studies with large sample sizes are needed to determine true incidence and risk factors associated with SBN in CD and assess potentially protective effects of early surgery.

Abstract Background and Aims Patients with inflammatory bowel disease (IBD) face increased risk of colorectal cancer (CRC). While the natural history of conventional dysplastic precursor lesions has been well-studied, the neoplastic potential of recently described nonconventional (NC) IBD-associated colonic mucosal lesions is unclear. We aimed to assess the incidence of antecedent NC lesions in patients with IBD who developed CRC. Methods A case-cohort study was performed to include patients with a diagnosis of IBD with or without CRC who underwent at least 2 surveillance endoscopic procedures at our institution between 1/1/2007 and 5/31/2023. NC lesions included serrated change and indefinite for dysplasia. Detection rates pre- and post-introduction of high-definition (HD) surveillance colonoscopy were compared. Results In total, 87 patients with IBD and CRC and 200 patients with IBD without CRC were identified. Of the cases, a majority had ulcerative colitis (n = 52, 60%), most commonly with extensive involvement (n = 46, 89%). Conventional (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.34-3.52) and NC (HR 2.28, 95% CI 1.59-3.26) lesions were associated with increased risk of CRC. Conventional lesions in the post-HD era appeared to have a stronger association with CRC (HR 2.79, 95% CI 1.62-4.77) than NC lesions (HR 1.62, 95% CI 0.86-3.06). Conclusions Both conventional and NC lesions seem to be associated with increased risk of CRC. Conventional lesions are more strongly associated with CRC than NC lesions in the post-HD era, but misclassifications in the pre-HD era may have resulted in a biased increased risk estimate for NC lesions.

89 Background: With estimates of over 150,000 incident and 50,000 fatal colorectal cancer (CRC) cases in 2024, efforts are ongoing to improve the national screening performance and engagement in the US. The Centers for Medicare & Medicaid Services (CMS) have established criteria for covering new blood-based CRC screening tests if minimum CRC sensitivity and specificity thresholds are met. However, the current blood-based tests are challenged by their relative inability to detect advanced precancerous lesions (APLs). At present, the importance of APL versus CRC sensitivity on screening outcomes remains undetermined. To address this knowledge gap, we conducted a simulation study to compare the screening effectiveness and outcomes of a hypothetical blood-based test across a range of sensitivities for CRC and APL detection. Methods: Outcomes were simulated using the CRC-AIM microsimulation model, which has been previously calibrated and validated. Predicted outcomes were calculated for average-risk individuals screened triennially with a blood-based test between ages 45-75 years, assuming perfect adherence. Base-case screening sensitivity and specificity inputs were based on CMS minimum thresholds (74% CRC sensitivity, 90% specificity) with assumed 10% APL sensitivity. Additional scenarios considered an increase in either APL or CRC sensitivity. Outcomes of interest included life years-gained (LYG), CRC incidence, and mortality reductions. Results: Compared to the CMS minimum performance (Table), increasing APL sensitivity by 1% (from 10% to 11%) resulted in a similar increase in LYG as compared to increasing CRC sensitivity by 11% (from 74% to 85%). Additionally, increasing APL sensitivity by 1% resulted in greater reductions in CRC cases and deaths (3% decrease) as compared to increasing CRC sensitivity by 11% (0% and 1% reductions, respectively). Conclusions: Data from this study show that increased APL sensitivity is a key determinant of screening-related outcomes, such as LYG, derived from a blood-based strategy, and that similar results would require much larger increases in CRC sensitivity. With the current CMS minimum performance threshold, blood-based tests that are designed to have high APL sensitivity can outperform tests with higher CRC sensitivity and little to no APL sensitivity. Comparison of CRC screening health outcomes with CMS proposed minimum threshold blood-test versus hypothetical tests with either increased APL and CRC sensitivity. APL Sensitivity CRC Sensitivity CRC Specificity Follow-up Colonoscopies CRC Cases (% reduction) CRC Deaths (% reduction) Life-Years Gained (LYG) (% increase) 10% 74% 90% 809 50 (ref) 18 (ref) 220 (ref) 11% 74% 90% 813 48 (-3%) 17 (-3%) 226 (3%) 10% 85% 90% 809 50 (0%) 18 (-1%) 227 (3%) APL: Advanced precancerous lesions; CRC: Colorectal cancer.

88 Background: There are an estimated 60 million individuals in the US who are not up-to-date with average-risk colorectal cancer (CRC) screening, as screening rates and adherence have remained stubbornly below the national target of 80%. Efforts are ongoing to improve CRC screening performance and participation, including the development of new blood-based tests. Despite high expectations for these tests, performance remains lower than other guideline-recommended strategies, particularly with respect to advanced precancerous lesion (APL) sensitivity. We conducted a simulation study of estimated clinical and economical outcomes for CRC screening with a blood-based test (at perfect adherence) compared to the multi-target stool-DNA (mt-sDNA) test (at published adherence rates). Methods: Utilizing CRC-AIM, a calibrated and validated microsimulation model, CRC screening outcomes were calculated for 1 million average-risk individuals screened between ages 45-75 years with triennial blood-based versus mt-sDNA testing. CRC and APL sensitivity and specificity inputs were derived from two large clinical validation studies for these screening modalities: ECLIPSE (NCT04136002) and DeeP-C (NCT01397747), respectively. To demonstrate the maximum benefits and burdens of blood-based screening, adherence to initial screening and follow-up colonoscopy after a positive blood test was modeled at 100%, while real-world adherence estimates of 65.6% were used for the mt-sDNA test. Outcomes of interest included life years-gained (LYG) and CRC cases missed by the blood-based test compared to the stool-based test, additional treatment costs imposed by theblood-based test, and additional CRC-related deaths per 1 million screened. Results: Compared to triennial screening with mt-sDNA at real-world adherence, blood-based screening at perfect adherence resulted in a higher number of incident (n=18,464) and fatal (n=6,483) CRC cases that would been avoided with the mt-sDNA test. Over a lifetime, screening with blood-based tests required 1,276,310 more tests (21% more) and 52,942 additional follow-up colonoscopies (7% more) compared to mt-sDNA screening. This increased testing burden did not generate additional benefits and instead reduced life-years gained by 67,645 per 1 million screened, resulting in an additional $1.6 billion in treatment costs compared to the mt-sDNA strategy. Conclusions: Data from this CRC-AIM modeling study show that even with perfect adherence, blood-based screening yields inferior clinical and economic benefits compared to mt-sDNA screening, due to suboptimal APL detection with the former test.

The Alaska Tribal Health System is increasing colorectal cancer (CRC) screening among Alaska Native (AN) peoples, who experience the highest CRC rate in the world. Through a clinical trial (NCT04336397), AN people living in rural/remote Alaska were offered either the previously unavailable multi-target stool DNA test (mt-sDNA; Cologuard®) or colonoscopy. From April 2022 to August 2024, 113 (59%) people who completed mt-sDNA testing and 51 (39%) who completed a colonoscopy procedure participated in a survey on factors influencing their screening test choice. The majority of mt-sDNA participants (79%) were aware of the colonoscopy option, while most colonoscopy participants (72%) reported being unaware of the mt-sDNA option. Key mt-sDNA preference themes included not having to travel, less time commitment, childcare and work responsibilities, physical limitations, greater convenience, and the test being less invasive and dangerous than a colonoscopy. In contrast, colonoscopy preference themes included wanting to adhere to screening recommendations, be proactive about preventative health, family history of cancer, awareness of the higher CRC risk among AN peoples, as well as the belief that colonoscopy is more reliable and accurate since it is performed by medical providers. These findings underscore the complex factors influencing CRC screening preferences among rural and remote AN people. Limited access to medical facilities, financial burdens, and personal commitments, along with personal factors, have a substantial bearing on the screening decision-making process. Recognizing and addressing these multifaceted influences can help CRC screening programs better meet community member needs and preferences, ultimately improving screening rates and colorectal health outcomes.

Objectives: To describe member adherence to a mail-based, health insurer-sponsored gap closure program for colorectal cancer (CRC) screening using multi-target stool DNA (mt-sDNA; Cologuard ® ) tests. Methods: Combined patient data from Exact Sciences Laboratories LLC and data from mass-mailed mt-sDNA orders placed by a large Medicare Advantage Insurance Plan were analyzed (03/01/2023-06/30/2023). Adherence and time to test return were the primary and secondary outcomes, respectively. Their association with patient characteristics was evaluated using multivariable regression. Results: Among the 3201 member-patients included (86.6% aged 65-75 years; 58.7% female), adherence rate was 49.4%, and mean time to test return was 25.5 days. After multivariable adjustment, the odds of test return were significantly higher among 65- to 75-year-olds (odds ratio [OR] = 1.59 relative to 45- to 64-year-olds), those living in small towns (OR = 1.43 relative to metropolitan-located individuals), and with digital outreach via both SMS and email (OR = 4.31 relative to no digital outreach). Time to test return was shorter in 65- to 75-year-olds than in 45- to 64-year-olds and was not associated with other patient characteristics. Conclusions: Mass-mailed mt-sDNA tests for CRC screening were associated with an overall adherence rate of about 50% in this Medicare Advantage population, with higher likelihood of test return among patients receiving digital outreach.

ABSTRACT Lymphoma is one of the leading causes of cancer and cancer deaths and yet has not been amenable to population screening. The role of methylated DNA markers (MDMs) in the detection of lymphoma has not been extensively studied. We aimed to discover, validate, and test tissue–derived MDMs of lymphoma in archival plasma specimens. Reduced representation bisulfite sequencing (RRBS) was performed on a discovery set of frozen tissues. MDMs identified were converted to methylation–specific PCR assays and validated on independent formalin–fixed, paraffin‐embedded (FFPE) tissues. Target enrichment long–probe quantitative‐amplified signal (TELQAS) assays were developed and assayed in plasma–extracted, bisulfite‐converted DNA from independent treatment‐naïve lymphoma patients and healthy controls. Prediction of cancer status was modeled using random forest model with in silico cross‐validation. After discovery and validation in tissue, 16 TELQAS assays ( ZNF503 , VWA5B1 , HOXA9 , GABRG3 , ITGA5 , MAX.chr17.7190 , BNC1 , CDK20 , MAX.chr4.4069 , TPBG , DNAH14 , SYT6 , CACNG8 , FAM110B , ADRA1D , and NRN1 ) were selected for testing in plasma. These detected 78% (95% CI, 74%–82%) of lymphoma cases at 90% specificity. Excluding marginal zone and T‐cell lymphomas, sensitivity increased to 84% (80%–88%). MDMs in plasma show promise to detect lymphoma and are candidates for inclusion in multi‐cancer detection studies.

Abstract Introduction: Blood-based tests represent a compelling option for early detection and management of cancers and other chronic diseases. While blood-based tests may offer potential to increase patient engagement, the assumption of greater adherence in clinical practice requires further evaluation. This systematic review aimed to evaluate the real-world adherence to established blood-based tests for commonly recommended screening indications, to better inform expectations for proposed application to average-risk colorectal cancer (CRC) screening. Methods: A systematic search of PubMed, Embase, and citations was performed to identify literature published from 2010 to 2023. Studies examined adherence to routine blood-based laboratory tests with a Grade A or B recommendation per the United States Preventive Services Task Force (USPSTF) for diabetes, dyslipidemia, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) in an average-risk patient population were included. In addition, prostate-specific antigen (PSA) testing adherence for prostate cancer screening (Grade-C USPSTF recommendation), the only commonly accessible blood-based single-cancer screening test for average-risk adults, was also included. Studies without venipuncture-derived blood were excluded. Results: Of 53,067 articles screened, 69 were included in the analysis. Overall, adherence rates of blood-based tests were highly variable, with median values (interquartile range, IQR) of 66.3% (11.8%), 67.8% (18.0%), 34% (28.7%), and 36.8% (30%) for diabetes, dyslipidemia, HCV, and HIV, respectively. PSA testing adherence was 37.2% (18.4%). Beyond disease type, adherence varied by study design, data source, patient characteristics, clinical setting, and study country. Information and selection bias were the most common risks of bias. Conclusions: Based on data from this comprehensive systematic review, real-world adherence to currently recommended, blood-based screening strategies is suboptimal. Future research is needed to identify the extent to which these data are generalizable to blood-based CRC screening, and to determine if/how this candidate strategy would impact clinical, economic, and health equity outcomes. Citation Format: Quang A. Le, Takako Kiener, Heather A. Johnson, Rukaiyya S. Khan, Joyce Kong, Kevin H. Li, Gina Thompson, A. Burak Ozbay, Mallik Greene, Paul J. Limburg, A. Mark Fendrick, John B. Kisiel, Derek W. Ebner. Systematic review of real-world adherence to blood-based laboratory tests for average-risk disease screening: potential implications for emerging colorectal cancer screening modalities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A027.