Single Institution Assessment of Compliance with Guideline Directed Aspirin Therapy in the Prevention of Colorectal Cancer in Lynch Syndrome

Single Institution Assessment of Compliance with Guideline Directed Aspirin Therapy in the Prevention of Colorectal Cancer in Lynch Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Single Institution Assessment of Compliance with Guideline Directed Aspirin Therapy in the Prevention of Colorectal Cancer in Lynch Syndrome Alexandra Yudiski, Heather Rocha, Edward Liu, Matthew Dzeda, Olivia Granja, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7189423/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Feb, 2026 Read the published version in Familial Cancer → Version 1 posted 9 You are reading this latest preprint version Abstract Background : Patients with Lynch syndrome (LS) have been shown to have up to an 80% lifetime risk of developing colorectal cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommend LS patients consider taking aspirin daily to reduce their risk of colorectal cancer, which is primarily based on the Cancer Prevention Project 2 (CAPP-2) study results. In this study, we evaluated the compliance of guideline directed aspirin therapy among LS patients at Geisinger Inherited Risk Gastrointestinal clinic (IRGI). Methods: Medical records of 177 patients were retrospectively reviewed from May 2016 to December 2022. After excluding those with missing data or lost to follow-up, our study cohort consisted of 167 patients. Demographics, affected genes, clinical history, and ASA use were collected. Chi-square test and unpaired T-test were used to evaluate the association between various parameters and aspirin use. Results: With a median annual follow up of 36 months and adjustment for patients with relative and absolute contraindications to ASA, 58.5% (83/142) of patients were compliant with ASA therapy. Nearly half 49.4% (41/83) of ASA users took 81 mg daily, 1.2% (1/83) took 250 mg daily, 42.2% (35/83) took 325 mg daily and only 7.2% (6/83) reported taking >600 mg daily. The difference of age on those taking ASA and those not taking ASA was found to be statistically significant (p-value = 0.025.) Conclusions: The adherence to guideline directed therapy likely stems from provider and patient education in addition to improved patient navigation strategies. Figures Figure 1 Introduction Lynch syndrome (LS) is a common inherited cancer syndrome characterized by germline mutations in genes involved in DNA mismatch repair (MMR) system including MLH1, MSH2/EPCAM, MSH6 and PMS2 [ 1 ]. Affected patients are at an increased risk of developing cancers in several organs. The mismatch DNA repair system corrects base substitution mismatches and insertion/deletion mismatches that occur during DNA replication. Defects in the mismatch repair system have been identified in 15% of colorectal cancers and result in a high tumor mutational burden secondary to microsatellite instability [ 2 ]. The risk of colon cancer varies based on the effect of MMR genes with a cumulative risk of diagnosis up to age 80 of 61% for patients with MLH1 mutations compared to 20% for patients with PMS2 mutations [ 3 ]. Regardless of risk, routine colonoscopy screenings are recommended for all LS patients to help detect premalignant polyps prior to transformation into cancer per NCCN guidelines. In 2016, the United States Preventive Services Task Force made recommendations supporting the use of low dose ASA for colorectal cancer prevention in the general population [ 4 ]. However, this recommendation was recently revised after assessing the data from the ARRIVE and ASPREE trials, where the beneficial role of low dose ASA in colorectal cancer prevention was deemed limited and highly variable [ 5 – 7 ]. The data for the role of ASA in LS patients is less controversial. In a recent analysis of the Colorectal Adenoma/Carcinoma Prevention Programme 2 (CAPP-2) trial of hereditary colorectal cancer patients taking 600 mg of ASA daily for 2 years with 10 years of follow-up, there was a significant reduction in the lifetime risk of developing colorectal cancer [ 8 ]. This benefit was seen after 5 years of randomization and persisted for up to 20 years. Based on this data, the NCCN recommends ASA for LS patients while accounting for individual risks, benefits, adverse effects, and childbearing plans [ 9 ]. There is an ongoing study, Cancer Prevention Project 3 (CAPP-3) investigating the optimal dosing for cancer prevention in LS patients while limiting adverse effects. There have been limited studies evaluating adherence to NCCN guideline-directed ASA therapy. Therefore, the aim of this study was to evaluate adherence to ASA use recommendation and recognize likely barriers to adherence and identify possible strategies to increase ASA use among LS patients. Methods Study Population Our institution has the IRGI clinic that is composed of a multidisciplinary team including genetic counselors, internists, gynecologists, gastroenterologists, and urologists. All patients presenting to the IRGI clinic from 2016 to 2022 were considered for this study. Throughout the study period, the clinicians provided in-person and telemedicine visits to patients who tested positive for a LS germline mutation and discussed the individualized NCCN guideline-based recommendations including ASA therapy. Patients were identified through any one of four sources: Geisinger Cancer Genetics program, MyCode Community Health Initiative (MyCode), Geisinger Autism and Developmental Medicine Institute (ADMI), or external referral by provider or self. The Cancer Genetics program identifies patients either through traditional evaluation of personal or family cancer history, as well as patients who underwent immunohistochemical testing of colon cancer and endometrial cancer surgical specimens showing loss of protein expression of MLH-1, MSH2, MSH6, or PMS-2 genes with absence of BRAF V600E mutation for patients with loss of expression of MLH-1/PMS-2 and subsequently found to have a corresponding germline mutation. The patients identified through the MyCode program represented the subset of MyCode participants who underwent exome sequencing through the DiscovEHR collaboration with Regeneron Genetics Center and incidentally found to have pathogenic or likely pathogenic variants in the LS genes. Likewise, a small subset of patients in the Geisinger ADMI program that underwent exome DNA sequence analysis were revealed to have likely pathogenic or pathogenic germline mutations in any one of the four LS genes. Aspirin Adherence Due to formulation differences of ASA in the U.S. compared to worldwide, patients were recommended to take either 81 mg, 325 mg, two 325 mg of ASA or 7–8 tablets of 81 mg daily to reach a dose close to the guideline recommended dose of 600 mg for a duration of 2 years. Adherence to ASA use was based on patient self-reporting during annual follow up visits. Those who refuse ASA without any documented contraindications to ASA were selected for repeat education and discussion at the annual follow up visits. Dosing, compliance, and all discussions about therapy are documented in the medical records for each patient. The data was retrospectively reviewed to assess both clinical provider education discussion and patient compliance with their recommendations. Reviewers followed the same standard of procedure instructions for initial review, and a quality control analysis was completed by randomly assigning 20% of charts to be re-reviewed by a different reviewer to ensure the accuracy and precision of the initial chart review. Statistical Methods Categorical variables were described using frequency and percentage. Pearson’s chi-square was used to determine whether gender, personal/family history of cancer, comorbidities or type of affected Lynch gene influenced ASA use. An unpaired T-test was used to determine whether age had significant difference in ASA use. All analyses were conducted using Excel statistical software (Microsoft, Redmond, WA). A p-value < 0.05 was considered statistically significant. Results A total of 167 patients were included in the data analysis after excluding the 10 patients that were lost to follow up Overall, 45.5% of patients were identified through Geisinger’s cancer genetic program and 42.5% were identified through population health screening program, or as a secondary finding through the MyCode program or ADMI.). The other 12% of patients had an external referral. Various factors that could influence the decision to take ASA were assessed including age, gender, personal and family history of cancer, specific mismatch repair variant (MLH1, MSH2/EPCAM, MSH6, PMS2), and medical comorbidities. Table one depicts the demographic data of the patients included in the study that accepted or declined ASA. The only significant statistical difference of those patient taking ASA compared to those not taking ASA was age (p-value = 0.025). Ages ranged from 20 to 81 with an average of 47.3 years. Patients assigned female at birth accounted for 69.5% of the study population. A family history of colon cancer was present in 70.1% of the study population. Within our overall study cohort, there were 19 (11.4%) patients with history of colorectal cancer, and 44 (29.7%) with a personal history of a non-colorectal malignancy. Table 1 Demographic data of the patients included within the study that accepted or declined ASA. Accepted ASA N (%) 1 Declined ASA N (%) 2 p-value 3 Sex 0.0575 Female 64 (55.2) 52 (44.8) Male 20 (39.2) 31 (60.8) Race 0.1573 Non-Hispanic White 82 (49.7) 83 (50.3) Blacks 2 (100) 0 (0) MMR gene 0.3122 MLH1 12 (52.2) 11 (47.8) MSH2 28 (60.9) 18 (39.1) MSH6 26 (42.6) 35 (57.4) PMS2 18 (48.6) 19 (51.4) Personal History of Cancer (Excluding Patients with History of Colorectal Cancer) 0.4719 Yes 24 (54.5) 20 (45.5) No 50 (48.1) 54 (51.9) Personal History of Colorectal Cancer 0.8290 Yes 10 (52.6) 9 (47.4) No 74 (50) 74 (50) Family History of Colorectal Cancer 0.2872 Yes 62 (53.0) 55 (47.0) No 22 (44.0) 28 (56.0) Both Personal and Family History of Colorectal Cancer 0.8054 Yes 8 (53.3) 7 (46.7) No 76 (50) 76 (50) Method of Ascertainment 0.0532 Cancer Genetics Clinic 46 (60.5) 30 (39.5) Genetic Screening program 30 (42.2) 41(57.7) External Referral 8 (40.0) 12 (60.0) BMI 0.0870 30 45 (48.9) 47 (51.1) Smoking History 0.3081 Yes 41 (54.7) 34 (45.3) No 43 (46.7) 49 (53.3) History of Coronary Artery Disease 0.7395 Yes 5 (45.5) 6 (54.5) No 79 (50.6) 77 (49.4) History of Cerebral Vascular Event 0.5531 Yes 1 (33.3) 2 (66.7) No 83 (50.6) 81 (49.4) History of Hypercoagulability 0.4794 Yes 5 (62.5) 3 (37.5) No 79 (49.7) 80 (50.3) 1 N representing number of patients and (%) indicating percentage of patients within the specific demographic group that accepted taking ASA therapy 2 N representing number of patients and (%) indicating percentage of patients within the specific demographic group that declined taking ASA therapy 3 p-value was determined using a Pearson’s chi-square analysis for all demographics listed within table with a p-value of < 0.05 considered statistically significant Overall, 49.7% of eligible patients agreed to take ASA with doses ranging between 81 mg to 650 mg. Among the ASA users, 41 (49.4%) took 81 mg of ASA daily and 35 (42.2%) took 325 mg daily, citing concerns for bleeding and ulcer at higher doses. Only 3 (3.6%) of all patients agreeable to ASA therapy took the recommended 650 mg dose, and 3 (3.6%) took approximately 600mg using a variety of pill combinations. One patient (1.2%) was taking 250 mg due to history of migraines prior to discussion. In addition, 2 patients, one with previous MI and the other with mitral valve disorder, were already taking 81 mg prior to discussion. Figure 1 shows recorded reasons for refusal and contraindications for ASA therapy. Of those who are not adhering to the ASA therapy, 4 (4.8%) reported allergy or prior intolerance, 7 (8.3%) had history of gastric ulcer, prior gastrointestinal bleeding, GERD and/or general gastrointestinal issues. Two (2.4%) were taking medications which when taken concomitantly with ASA would increase risk of bleeding. The rest had a variety of reasons for the lack of recommendation including total colectomy, anemia, lymphocytic colitis, gastric bypass, thrombocytopenia, fall risk, easy bleeding or bruising, and other contraindications. Out of the patients not taking ASA, 57 (67.8%) provided no reason. Only 2 patients (2.4%) did not have a discussion at the clinic about taking ASA. One patient’s chart stated that the clinician did not discuss ASA due to young age and the other provided no reason for the lack of discussion. Taking into account the 25 patients with ASA not recommended adjusted compliance was 58.5% for eligible patients. Discussion In this study, we evaluated adherence to ASA as a colorectal cancer chemopreventive agent as recommended in the NCCN guidelines. Despite the controversial role of ASA for colon cancer in the general population, there is level 1 data supporting its use in LS patients [ 9 ]. Based on this evidence, our multidisciplinary team have made ASA use equally important as adherence to colonoscopy screening to both reduce colon cancer development and facilitate early detection of disease, respectively. ASA use is routinely discussed with patients in a shared decision-making format by physicians (internist and gastroenterologist) and genetic counselors. Patients are educated about the CAPP-2 demonstrating a significant reduction in colorectal cancer risk among LS patients and their eligibility determined after a thorough review of their personal risk and medical contraindications. In this study, there was an overall compliance rate of 49.7% among all patients and 58.5% among eligible patients after an individualized discussion of any absolute or relative contraindications. There was one other published abstract at the 2022 American Society of Clinical Oncology annual meeting that evaluated ASA compliance in LS patients and showed an adherence rate of 25% among 127 patients [ 10 ]. The reasons for a higher compliance rate in our study are likely multifactorial and may be related to differences in prior provider awareness, patient knowledge, patient education, patient risk factors, ASA dosing, and routine follow-up efforts. Our clinic providers routinely review the NCCN guidelines and their updates at the start of each monthly multidisciplinary clinic meeting. LS gene-specific educational materials are provided and reviewed with all patients during their clinic visit. While we did not specifically access the role of physician and patient knowledge in ASA use adherence, its importance was recently highlighted in a national survey that found 62.5% percent of general practitioners reported never having seen a patient with LS and only 46.7% were aware of the use of ASA in cancer risk reduction [ 11 ]. Our ASA use compliance rate reflected any ASA use, however, only 8% of patient took approximately 600 mg based on United States available dosing which was the among utilized in the CAPP-2 trial. ASA compliance included any ASA dose taken as NCCN guidelines recommend basing dosing on an individualized level as there is no current standard for dosing. While a variety of ASA doses have been tested and found to potentially effective in the general population, the question about the optimal dosing in LS patients will have to await the results of the CAPP-3 trial [ 12 ]. In a systematic review of public, patient, and healthcare provider attitudes and adherence with ASA use for cancer prevention within clinical trials, ASA use adherence was > 90% for short term use ( 80% for long term use [ 13 ]. Though these high compliance rates are not surprising for clinical trial studies, they represent aspirational clinical benchmarks that could be attained during routine clinical care. Similar to our study, no association between gender with ASA adherence was identified in this systematic review when focusing on ASA use in reducing the risk of colorectal cancer in high-risk populations. That said, 50.3% of patients in this study refused ASA, of which only 29.8% have a documented medication relative or absolute contraindications and 2.4% have no documented discussion. This represents an opportunity for intervention in 70.2% of eligible patients. Several strategies have described for generalized medication adherence. For example, introducing clinical pharmacy consultations may provide patients with further information on ASA side effect profile and medication interactions to better allow them to make an informed decision about therapy. In one study assessing patient adherence to statin therapy, patients who received educational intervention had significantly higher adherence at 72% compared to 61% in the control group [ 14 ]. Secondly, increasing the frequency of follow-up visits to every 6 months or every 3 months can provide more opportunities for face-to-face time with providers and potentially increase medication adherence. Finally, writing a script for ASA rather than having patients buy directly over the counter may also be an effective measure. The automated refill of medications by the pharmacy may improve convenience and serve as a reminder for patients to pick up their medications. In another adherence to statin medications study, patients who receive a telephone reminder and personalized letter emphasizing importance of medication adherence as compared to the control group without these interventions showed that 17% more patients filled their prescription within two weeks of the reminder call [ 15 ]. In our study, we identified several barriers that influenced patient compliance including perceived personal risk, concern for ASA effectiveness, drug-drug interactions, and side effects of ASA use. Though our analysis showed that a small subset of our patients had documented intolerance to ASA therapy including history of gastric ulcer or prior bleeding, the potential side effects associated with regular ASA use in average risk individuals with no history of bleeding and not taking any other anticoagulant or antiplatelet medication are often overestimated. One meta-analysis evaluating ASA doses of 75–325 mg daily showed that the estimated occurrence of gastrointestinal bleeding events were only one to two events per 1000 person-years [ 16 ]. However, there should be an individualized risk discussion prior to initiation of therapy, particularly since the optimal dosing and duration of aspirin therapy for chemoprevention remains unknown, and studies have shown that hazards for bleeding tend to be higher in patients treated for longer periods of time, and with higher doses, 300–325 mg of aspirin compared to those treated with lower doses of 75-162.5 mg [ 16 ]. Thus, even with preexisting risk factors, patients may still be candidates for ASA therapy after a risks and benefits discussion and modifications such as dose adjustments. Until the CAPP-3 trial provides data on the lowest effective dosing for colorectal cancer risk reduction in LS patients, the optimal ASA dosing remains unclear. In addition, it is not easy to provide 600 mg dosing of ASA used within the CAPP-2 in the United States due to current available dosing of 81 mg and 325 mg. During a LS patient’s first introduction to ASA therapy, we can assess whether the patient has any medical contraindications to starting ASA therapy, such as a history of a bleeding disorder, taking any anticoagulation or other antiplatelet that would increase bleeding risk, or prior total colectomy. If the above criteria are met, then we can proceed with an individualized risk discussion on dosing and duration of therapy as further studies are required to solidify more universal recommendations. Patients in agreement with initiation therapy may then be started on 650 mg of ASA for two years based on the dosing in the CAPP-2 trial or a lower dosing based on individual discussion. For example, patients that have no absolute or relative contraindications, but have concerns about side effects of high dose ASA use, there should be a risk and benefits discussion about initiation of therapy given concerns of increased risk of bleeding and can first consider lower doses such as 81 mg and can potentially increase dosing based on patient preference and CAPP-3 study results once completed. Measures to ensure compliance may include electronic prescribing for ease of medication renewal and maintaining routine in-person or telephone visit follow up. Overall, assessing the underlying reason for declining ASA would aid the efforts to improve compliance. One study limitation is that the patient population only consists of a single center with patients that are predominantly Caucasian in rural areas which may hinder the generalizability of study when comparing to more diverse and larger populations. In future studies, it may be worthwhile to evaluate multidisciplinary clinics in multiple settings, such as rural, urban, and suburban, to denote any similarities or differences in adherence. Conclusion ASA serves as an effective and affordable therapy for the prevention of colorectal cancer in patients with LS. Establishing optimal ASA dosing and duration to limit adverse effects while lowering colorectal cancer risk remains an unmet need. Barriers to ASA use compliance do exist, but so are opportunities to both identify and mitigate their impact on colon cancer-specific outcomes in this patient population. Involvement of additional specialists including pharmacists and behavioral therapists may provide further resources to motivate and improve medication adherence. Declarations Ethics Approval: Ethical approval was waived by IRB of Geisinger in view of the retrospective nature of the study and all the interventions being performed were part of the routine care. Competing Interests No funding was received for conducting this study. Author Thomas Morland has received research support and has intellectual property interest from Tempus Labs, Inc. Author Thomas Morland also has an immediate family member that holds employment and is a shareholder of the United Therapeutics Corporation. Author Bradley Confer has been a consultant for Boston Scientific Corporation and participated in speaker’s bureau at Abbvie. Author Hannah Woolley has an immediate family member who owns stock in Alcon, Novartis, Gilead Sciences, Regeneron, Amgen, Pfizer, Vertex Pharmaceutical, Biogen, BioNTech, and Moderna Therapeutics. Author Heather Rocha has an immediate family member who is employed by New York Presbyterian Hospital. All other authors have no relevant financial or non-financial interests to disclose. Funding & Competing Interests: No funding was received for conducting this study. Author Thomas Morland has received research support and has intellectual property interest from Tempus Labs, Inc. Author Thomas Morland also has an immediate family member that holds employment and is a shareholder of the United Therapeutics Corporation. Author Bradley Confer has been a consultant for Boston Scientific Corporation and participated in speaker’s bureau at Abbvie. Author Hannah Woolley has an immediate family member who owns stock in Alcon, Novartis, Gilead Sciences, Regeneron, Amgen, Pfizer, Vertex Pharmaceutical, Biogen, BioNTech, and Moderna Therapeutics. Author Heather Rocha has an immediate family member who is employed by New York Presbyterian Hospital. All other authors have no relevant financial or non-financial interests to disclose. Author Contribution A.Y. wrote main manuscript text and prepared figures and tables.H.R, E.L., and B.C. edited initial manuscript draft and reviewed the manuscript.All other authors reviewed manuscript. Data Availability All data supporting the findings of this study are available within the paper and its supplementary information. References Bansidhar B, Silinsky J. History and Pathogenesis of Lynch Syndrome. Clin Colon Rectal Surg . 2012;25(02):063-066. doi:10.1055/s-0032-1313776 Buecher B, Cacheux W, Rouleau E, Dieumegard B, Mitry E, Lièvre A. Role of microsatellite instability in the management of colorectal cancers. Digestive and Liver Disease . 2013;45(6):441-449. doi:10.1016/j.dld.2012.10.006 Bonadona V, Bonaïti B, Olschwang S, et al. Cancer Risks Associated With Germline Mutations in MLH1 , MSH2 , and MSH6 Genes in Lynch Syndrome. JAMA . 2011;305(22):2304. doi:10.1001/jama.2011.743 Bibbins-Domingo K. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med . 2016;164(12):836-845. doi:10.7326/M16-0577 Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. The Lancet . 2018;392(10152):1036-1046. doi:10.1016/S0140-6736(18)31924-X McNeil JJ, Gibbs P, Orchard SG, et al. Effect of Aspirin on Cancer Incidence and Mortality in Older Adults. JNCI: Journal of the National Cancer Institute . 2021;113(3):258-265. doi:10.1093/jnci/djaa114 Guirguis-Blake JM, Evans C V., Perdue LA, Bean SI, Senger CA. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer. JAMA . 2022;327(16):1585. doi:10.1001/jama.2022.3337 Burn J, Sheth H, Elliott F, et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. The Lancet . 2020;395(10240):1855-1863. doi:10.1016/S0140-6736(20)30366-4 National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric (Version 1.2025). Available at: genetics_ceg.pdf (Accessed July 1, 2025) Hall MJ, Clapper M, Chang WCJ, Chertock Y, Nguyen MJ. Predictors of uptake of aspirin (ASA) chemoprevention in Lynch syndrome (LS). Journal of Clinical Oncology . 2021;39(3_suppl):49-49. doi:10.1200/JCO.2021.39.3_suppl.49 Smith SG, Foy R, McGowan J, et al. General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey. Fam Cancer . 2017;16(4):509-516. doi:10.1007/s10689-017-9986-9 Burn J, Mathers JC, Bishop DT. Chemoprevention in Lynch syndrome. Fam Cancer . 2013;12(4):707-718. doi:10.1007/s10689-013-9650-y Lloyd KE, Hall LH, King N, et al. Aspirin use for cancer prevention: A systematic review of public, patient and healthcare provider attitudes and adherence behaviours. Prev Med (Baltim) . 2022;154:106872. doi:10.1016/j.ypmed.2021.106872 Nieuwkerk PT, Nierman MC, Vissers MN, et al. Intervention to improve adherence to lipid-lowering medication and lipid-levels in patients with an increased cardiovascular risk. Am J Cardiol . 2012;110(5):666-672. doi:10.1016/j.amjcard.2012.04.045 Derose SF, Green K, Marrett E, et al. Automated outreach to increase primary adherence to cholesterol-lowering medications. JAMA Intern Med . 2013;173(1):38-43. doi:10.1001/2013.jamainternmed.717 Drew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer . 2016;16(3):173-186. doi:10.1038/nrc.2016.4 Additional Declarations Competing interest reported. No funding was received for conducting this study. Author Thomas Morland has received research support and has intellectual property interest from Tempus Labs, Inc. Author Thomas Morland also has an immediate family member that holds employment and is a shareholder of the United Therapeutics Corporation. Author Bradley Confer has been a consultant for Boston Scientific Corporation and participated in speaker’s bureau at Abbvie. Author Hannah Woolley has an immediate family member who owns stock in Alcon, Novartis, Gilead Sciences, Regeneron, Amgen, Pfizer, Vertex Pharmaceutical, Biogen, BioNTech, and Moderna Therapeutics. Author Heather Rocha has an immediate family member who is employed by New York Presbyterian Hospital. All other authors have no relevant financial or non-financial interests to disclose. Supplementary Files Supplementalmaterial.docx Cite Share Download PDF Status: Published Journal Publication published 09 Feb, 2026 Read the published version in Familial Cancer → Version 1 posted Editorial decision: Revision requested 05 Oct, 2025 Reviews received at journal 26 Sep, 2025 Reviews received at journal 23 Sep, 2025 Reviewers agreed at journal 16 Sep, 2025 Reviewers agreed at journal 02 Sep, 2025 Reviewers invited by journal 24 Jul, 2025 Editor assigned by journal 23 Jul, 2025 Submission checks completed at journal 23 Jul, 2025 First submitted to journal 22 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shane","middleName":"","lastName":"Conklin","suffix":""},{"id":491839803,"identity":"6d3683cb-6816-45c9-a226-2fb26dddd635","order_by":8,"name":"Gabrielle Shermanski","email":"","orcid":"","institution":"Geisinger Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Gabrielle","middleName":"","lastName":"Shermanski","suffix":""},{"id":491839804,"identity":"c2e786da-0f04-4d03-88ae-a4a7ccd46e79","order_by":9,"name":"Amanda Leicht","email":"","orcid":"","institution":"Geisinger Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Amanda","middleName":"","lastName":"Leicht","suffix":""},{"id":491839808,"identity":"8117986c-e795-462c-8cc5-b6c09cb075d6","order_by":10,"name":"Thomas Morland","email":"","orcid":"","institution":"Geisinger Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Morland","suffix":""},{"id":491839809,"identity":"2f6217ac-67a3-4096-bd5e-e34fbb950770","order_by":11,"name":"Kathie Wu","email":"","orcid":"","institution":"Geisinger Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Kathie","middleName":"","lastName":"Wu","suffix":""},{"id":491839810,"identity":"3ae88450-2d9d-4a19-b198-695b241c486c","order_by":12,"name":"Bradley Confer","email":"","orcid":"","institution":"Geisinger Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Bradley","middleName":"","lastName":"Confer","suffix":""}],"badges":[],"createdAt":"2025-07-22 17:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7189423/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7189423/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10689-026-00533-8","type":"published","date":"2026-02-09T15:59:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87897373,"identity":"a80e366d-3d9f-4068-ba08-f413add220d9","added_by":"auto","created_at":"2025-07-30 07:47:21","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":195076,"visible":true,"origin":"","legend":"\u003cp\u003eRelative and absolute contraindications provided by study subjects for refusal of ASA therapy\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7189423/v1/50fc5fff37332be7b035fbbc.jpeg"},{"id":102785405,"identity":"730f5c10-44b1-4fb9-b11a-3ab3a3d6c36f","added_by":"auto","created_at":"2026-02-16 16:06:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":936112,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7189423/v1/474eb092-31e9-4bcc-b3b3-19063a39c4c0.pdf"},{"id":87897372,"identity":"50e2febc-2ce3-490d-80fb-b689e8086ca9","added_by":"auto","created_at":"2025-07-30 07:47:21","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":57925,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalmaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7189423/v1/be6e816f98786ee3a1bcaa57.docx"}],"financialInterests":"Competing interest reported. No funding was received for conducting this study. Author Thomas Morland has received research support and has intellectual property interest from Tempus Labs, Inc. Author Thomas Morland also has an immediate family member that holds employment and is a shareholder of the United Therapeutics Corporation. Author Bradley Confer has been a consultant for Boston Scientific Corporation and participated in speaker’s bureau at Abbvie. Author Hannah Woolley has an immediate family member who owns stock in Alcon, Novartis, Gilead Sciences, Regeneron, Amgen, Pfizer, Vertex Pharmaceutical, Biogen, BioNTech, and Moderna Therapeutics. Author Heather Rocha has an immediate family member who is employed by New York Presbyterian Hospital. All other authors have no relevant financial or non-financial interests to disclose.","formattedTitle":"Single Institution Assessment of Compliance with Guideline Directed Aspirin Therapy in the Prevention of Colorectal Cancer in Lynch Syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLynch syndrome (LS) is a common inherited cancer syndrome characterized by germline mutations in genes involved in DNA mismatch repair (MMR) system including \u003cem\u003eMLH1, MSH2/EPCAM, MSH6\u003c/em\u003e and \u003cem\u003ePMS2\u003c/em\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Affected patients are at an increased risk of developing cancers in several organs. The mismatch DNA repair system corrects base substitution mismatches and insertion/deletion mismatches that occur during DNA replication. Defects in the mismatch repair system have been identified in 15% of colorectal cancers and result in a high tumor mutational burden secondary to microsatellite instability [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The risk of colon cancer varies based on the effect of MMR genes with a cumulative risk of diagnosis up to age 80 of 61% for patients with MLH1 mutations compared to 20% for patients with PMS2 mutations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Regardless of risk, routine colonoscopy screenings are recommended for all LS patients to help detect premalignant polyps prior to transformation into cancer per NCCN guidelines.\u003c/p\u003e\u003cp\u003eIn 2016, the United States Preventive Services Task Force made recommendations supporting the use of low dose ASA for colorectal cancer prevention in the general population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, this recommendation was recently revised after assessing the data from the ARRIVE and ASPREE trials, where the beneficial role of low dose ASA in colorectal cancer prevention was deemed limited and highly variable [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The data for the role of ASA in LS patients is less controversial. In a recent analysis of the Colorectal Adenoma/Carcinoma Prevention Programme 2 (CAPP-2) trial of hereditary colorectal cancer patients taking 600 mg of ASA daily for 2 years with 10 years of follow-up, there was a significant reduction in the lifetime risk of developing colorectal cancer [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This benefit was seen after 5 years of randomization and persisted for up to 20 years. Based on this data, the NCCN recommends ASA for LS patients while accounting for individual risks, benefits, adverse effects, and childbearing plans [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. There is an ongoing study, Cancer Prevention Project 3 (CAPP-3) investigating the optimal dosing for cancer prevention in LS patients while limiting adverse effects.\u003c/p\u003e\u003cp\u003e There have been limited studies evaluating adherence to NCCN guideline-directed ASA therapy. Therefore, the aim of this study was to evaluate adherence to ASA use recommendation and recognize likely barriers to adherence and identify possible strategies to increase ASA use among LS patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOur institution has the IRGI clinic that is composed of a multidisciplinary team including genetic counselors, internists, gynecologists, gastroenterologists, and urologists. All patients presenting to the IRGI clinic from 2016 to 2022 were considered for this study. Throughout the study period, the clinicians provided in-person and telemedicine visits to patients who tested positive for a LS germline mutation and discussed the individualized NCCN guideline-based recommendations including ASA therapy. Patients were identified through any one of four sources: Geisinger Cancer Genetics program, MyCode Community Health Initiative (MyCode), Geisinger Autism and Developmental Medicine Institute (ADMI), or external referral by provider or self. The Cancer Genetics program identifies patients either through traditional evaluation of personal or family cancer history, as well as patients who underwent immunohistochemical testing of colon cancer and endometrial cancer surgical specimens showing loss of protein expression of MLH-1, MSH2, MSH6, or PMS-2 genes with absence of \u003cem\u003eBRAF\u003c/em\u003e V600E mutation for patients with loss of expression of MLH-1/PMS-2 and subsequently found to have a corresponding germline mutation. The patients identified through the MyCode program represented the subset of MyCode participants who underwent exome sequencing through the DiscovEHR collaboration with Regeneron Genetics Center and incidentally found to have pathogenic or likely pathogenic variants in the LS genes. Likewise, a small subset of patients in the Geisinger ADMI program that underwent exome DNA sequence analysis were revealed to have likely pathogenic or pathogenic germline mutations in any one of the four LS genes.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAspirin Adherence\u003c/b\u003e\u003c/p\u003e\u003cp\u003e Due to formulation differences of ASA in the U.S. compared to worldwide, patients were recommended to take either 81 mg, 325 mg, two 325 mg of ASA or 7–8 tablets of 81 mg daily to reach a dose close to the guideline recommended dose of 600 mg for a duration of 2 years. Adherence to ASA use was based on patient self-reporting during annual follow up visits. Those who refuse ASA without any documented contraindications to ASA were selected for repeat education and discussion at the annual follow up visits. Dosing, compliance, and all discussions about therapy are documented in the medical records for each patient. The data was retrospectively reviewed to assess both clinical provider education discussion and patient compliance with their recommendations. Reviewers followed the same standard of procedure instructions for initial review, and a quality control analysis was completed by randomly assigning 20% of charts to be re-reviewed by a different reviewer to ensure the accuracy and precision of the initial chart review.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical Methods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCategorical variables were described using frequency and percentage. Pearson’s chi-square was used to determine whether gender, personal/family history of cancer, comorbidities or type of affected Lynch gene influenced ASA use. An unpaired T-test was used to determine whether age had significant difference in ASA use. All analyses were conducted using Excel statistical software (Microsoft, Redmond, WA). A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 167 patients were included in the data analysis after excluding the 10 patients that were lost to follow up Overall, 45.5% of patients were identified through Geisinger\u0026rsquo;s cancer genetic program and 42.5% were identified through population health screening program, or as a secondary finding through the MyCode program or ADMI.). The other 12% of patients had an external referral.\u003c/p\u003e\u003cp\u003eVarious factors that could influence the decision to take ASA were assessed including age, gender, personal and family history of cancer, specific mismatch repair variant (MLH1, MSH2/EPCAM, MSH6, PMS2), and medical comorbidities. Table one depicts the demographic data of the patients included in the study that accepted or declined ASA. The only significant statistical difference of those patient taking ASA compared to those not taking ASA was age (p-value\u0026thinsp;=\u0026thinsp;0.025). Ages ranged from 20 to 81 with an average of 47.3 years. Patients assigned female at birth accounted for 69.5% of the study population. A family history of colon cancer was present in 70.1% of the study population. Within our overall study cohort, there were 19 (11.4%) patients with history of colorectal cancer, and 44 (29.7%) with a personal history of a non-colorectal malignancy.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic data of the patients included within the study that accepted or declined ASA.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAccepted ASA N (%)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDeclined ASA N (%)\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0575\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64 (55.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (44.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (39.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (60.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRace\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.1573\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-Hispanic White\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82 (49.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83 (50.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlacks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMMR gene\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.3122\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMLH1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (52.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (47.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMSH2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (60.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (39.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMSH6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (42.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (57.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePMS2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (48.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (51.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePersonal History of Cancer (Excluding Patients with History of Colorectal Cancer)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.4719\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (54.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (45.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50 (48.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (51.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePersonal History of Colorectal Cancer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.8290\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (52.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (47.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFamily History of Colorectal Cancer\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.2872\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (53.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55 (47.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (44.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (56.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBoth Personal and Family History of Colorectal Cancer\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.8054\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e76 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMethod of Ascertainment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0532\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer Genetics Clinic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (60.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (39.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGenetic Screening program\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (42.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41(57.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExternal Referral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0870\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (69.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e25\u0026ndash;30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (42.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (57.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45 (48.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (51.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSmoking History\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.3081\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (54.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34 (45.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory of Coronary Artery Disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.7395\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (45.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (54.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 (50.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77 (49.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory of Cerebral Vascular Event\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.5531\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83 (50.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81 (49.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory of Hypercoagulability\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.4794\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 (49.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80 (50.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eN representing number of patients and (%) indicating percentage of patients within the specific demographic group that accepted taking ASA therapy\u003c/p\u003e\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eN representing number of patients and (%) indicating percentage of patients within the specific demographic group that declined taking ASA therapy\u003c/p\u003e\u003cp\u003e\u003csup\u003e3\u003c/sup\u003ep-value was determined using a Pearson\u0026rsquo;s chi-square analysis for all demographics listed within table with a p-value of \u0026lt;\u0026thinsp;0.05 considered statistically significant\u003c/p\u003e\u003cp\u003eOverall, 49.7% of eligible patients agreed to take ASA with doses ranging between 81 mg to 650 mg. Among the ASA users, 41 (49.4%) took 81 mg of ASA daily and 35 (42.2%) took 325 mg daily, citing concerns for bleeding and ulcer at higher doses. Only 3 (3.6%) of all patients agreeable to ASA therapy took the recommended 650 mg dose, and 3 (3.6%) took approximately 600mg using a variety of pill combinations. One patient (1.2%) was taking 250 mg due to history of migraines prior to discussion. In addition, 2 patients, one with previous MI and the other with mitral valve disorder, were already taking 81 mg prior to discussion.\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows recorded reasons for refusal and contraindications for ASA therapy. Of those who are not adhering to the ASA therapy, 4 (4.8%) reported allergy or prior intolerance, 7 (8.3%) had history of gastric ulcer, prior gastrointestinal bleeding, GERD and/or general gastrointestinal issues. Two (2.4%) were taking medications which when taken concomitantly with ASA would increase risk of bleeding. The rest had a variety of reasons for the lack of recommendation including total colectomy, anemia, lymphocytic colitis, gastric bypass, thrombocytopenia, fall risk, easy bleeding or bruising, and other contraindications. Out of the patients not taking ASA, 57 (67.8%) provided no reason. Only 2 patients (2.4%) did not have a discussion at the clinic about taking ASA. One patient\u0026rsquo;s chart stated that the clinician did not discuss ASA due to young age and the other provided no reason for the lack of discussion. Taking into account the 25 patients with ASA not recommended adjusted compliance was 58.5% for eligible patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e In this study, we evaluated adherence to ASA as a colorectal cancer chemopreventive agent as recommended in the NCCN guidelines. Despite the controversial role of ASA for colon cancer in the general population, there is level 1 data supporting its use in LS patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Based on this evidence, our multidisciplinary team have made ASA use equally important as adherence to colonoscopy screening to both reduce colon cancer development and facilitate early detection of disease, respectively.\u003c/p\u003e\u003cp\u003eASA use is routinely discussed with patients in a shared decision-making format by physicians (internist and gastroenterologist) and genetic counselors. Patients are educated about the CAPP-2 demonstrating a significant reduction in colorectal cancer risk among LS patients and their eligibility determined after a thorough review of their personal risk and medical contraindications. In this study, there was an overall compliance rate of 49.7% among all patients and 58.5% among eligible patients after an individualized discussion of any absolute or relative contraindications. There was one other published abstract at the 2022 American Society of Clinical Oncology annual meeting that evaluated ASA compliance in LS patients and showed an adherence rate of 25% among 127 patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The reasons for a higher compliance rate in our study are likely multifactorial and may be related to differences in prior provider awareness, patient knowledge, patient education, patient risk factors, ASA dosing, and routine follow-up efforts. Our clinic providers routinely review the NCCN guidelines and their updates at the start of each monthly multidisciplinary clinic meeting. LS gene-specific educational materials are provided and reviewed with all patients during their clinic visit. While we did not specifically access the role of physician and patient knowledge in ASA use adherence, its importance was recently highlighted in a national survey that found 62.5% percent of general practitioners reported never having seen a patient with LS and only 46.7% were aware of the use of ASA in cancer risk reduction [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur ASA use compliance rate reflected any ASA use, however, only 8% of patient took approximately 600 mg based on United States available dosing which was the among utilized in the CAPP-2 trial. ASA compliance included any ASA dose taken as NCCN guidelines recommend basing dosing on an individualized level as there is no current standard for dosing. While a variety of ASA doses have been tested and found to potentially effective in the general population, the question about the optimal dosing in LS patients will have to await the results of the CAPP-3 trial [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In a systematic review of public, patient, and healthcare provider attitudes and adherence with ASA use for cancer prevention within clinical trials, ASA use adherence was \u0026gt;\u0026thinsp;90% for short term use (\u0026lt;\u0026thinsp;1 year) and \u0026gt;\u0026thinsp;80% for long term use [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Though these high compliance rates are not surprising for clinical trial studies, they represent aspirational clinical benchmarks that could be attained during routine clinical care. Similar to our study, no association between gender with ASA adherence was identified in this systematic review when focusing on ASA use in reducing the risk of colorectal cancer in high-risk populations.\u003c/p\u003e\u003cp\u003eThat said, 50.3% of patients in this study refused ASA, of which only 29.8% have a documented medication relative or absolute contraindications and 2.4% have no documented discussion. This represents an opportunity for intervention in 70.2% of eligible patients. Several strategies have described for generalized medication adherence. For example, introducing clinical pharmacy consultations may provide patients with further information on ASA side effect profile and medication interactions to better allow them to make an informed decision about therapy. In one study assessing patient adherence to statin therapy, patients who received educational intervention had significantly higher adherence at 72% compared to 61% in the control group [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Secondly, increasing the frequency of follow-up visits to every 6 months or every 3 months can provide more opportunities for face-to-face time with providers and potentially increase medication adherence. Finally, writing a script for ASA rather than having patients buy directly over the counter may also be an effective measure. The automated refill of medications by the pharmacy may improve convenience and serve as a reminder for patients to pick up their medications. In another adherence to statin medications study, patients who receive a telephone reminder and personalized letter emphasizing importance of medication adherence as compared to the control group without these interventions showed that 17% more patients filled their prescription within two weeks of the reminder call [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our study, we identified several barriers that influenced patient compliance including perceived personal risk, concern for ASA effectiveness, drug-drug interactions, and side effects of ASA use. Though our analysis showed that a small subset of our patients had documented intolerance to ASA therapy including history of gastric ulcer or prior bleeding, the potential side effects associated with regular ASA use in average risk individuals with no history of bleeding and not taking any other anticoagulant or antiplatelet medication are often overestimated. One meta-analysis evaluating ASA doses of 75\u0026ndash;325 mg daily showed that the estimated occurrence of gastrointestinal bleeding events were only one to two events per 1000 person-years [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, there should be an individualized risk discussion prior to initiation of therapy, particularly since the optimal dosing and duration of aspirin therapy for chemoprevention remains unknown, and studies have shown that hazards for bleeding tend to be higher in patients treated for longer periods of time, and with higher doses, 300\u0026ndash;325 mg of aspirin compared to those treated with lower doses of 75-162.5 mg [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Thus, even with preexisting risk factors, patients may still be candidates for ASA therapy after a risks and benefits discussion and modifications such as dose adjustments.\u003c/p\u003e\u003cp\u003eUntil the CAPP-3 trial provides data on the lowest effective dosing for colorectal cancer risk reduction in LS patients, the optimal ASA dosing remains unclear. In addition, it is not easy to provide 600 mg dosing of ASA used within the CAPP-2 in the United States due to current available dosing of 81 mg and 325 mg. During a LS patient\u0026rsquo;s first introduction to ASA therapy, we can assess whether the patient has any medical contraindications to starting ASA therapy, such as a history of a bleeding disorder, taking any anticoagulation or other antiplatelet that would increase bleeding risk, or prior total colectomy. If the above criteria are met, then we can proceed with an individualized risk discussion on dosing and duration of therapy as further studies are required to solidify more universal recommendations. Patients in agreement with initiation therapy may then be started on 650 mg of ASA for two years based on the dosing in the CAPP-2 trial or a lower dosing based on individual discussion. For example, patients that have no absolute or relative contraindications, but have concerns about side effects of high dose ASA use, there should be a risk and benefits discussion about initiation of therapy given concerns of increased risk of bleeding and can first consider lower doses such as 81 mg and can potentially increase dosing based on patient preference and CAPP-3 study results once completed. Measures to ensure compliance may include electronic prescribing for ease of medication renewal and maintaining routine in-person or telephone visit follow up. Overall, assessing the underlying reason for declining ASA would aid the efforts to improve compliance.\u003c/p\u003e\u003cp\u003eOne study limitation is that the patient population only consists of a single center with patients that are predominantly Caucasian in rural areas which may hinder the generalizability of study when comparing to more diverse and larger populations. In future studies, it may be worthwhile to evaluate multidisciplinary clinics in multiple settings, such as rural, urban, and suburban, to denote any similarities or differences in adherence.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eASA serves as an effective and affordable therapy for the prevention of colorectal cancer in patients with LS. Establishing optimal ASA dosing and duration to limit adverse effects while lowering colorectal cancer risk remains an unmet need. Barriers to ASA use compliance do exist, but so are opportunities to both identify and mitigate their impact on colon cancer-specific outcomes in this patient population. Involvement of additional specialists including pharmacists and behavioral therapists may provide further resources to motivate and improve medication adherence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was waived by IRB of Geisinger in view of the retrospective nature of the study and all the interventions being performed were part of the routine care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study. Author Thomas Morland has received research support and has intellectual property interest from Tempus Labs, Inc. Author Thomas Morland also has an immediate family member that holds employment and is a shareholder of the United Therapeutics Corporation. Author Bradley Confer has been a consultant for Boston Scientific Corporation and participated in speaker\u0026rsquo;s bureau at Abbvie. Author Hannah Woolley has an immediate family member who owns stock in Alcon, Novartis, Gilead Sciences, Regeneron, Amgen, Pfizer, Vertex Pharmaceutical, Biogen, BioNTech, and Moderna Therapeutics. Author Heather Rocha has an immediate family member who is employed by New York Presbyterian Hospital. All other authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u0026amp; Competing Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study. Author Thomas Morland has received research support and has intellectual property interest from Tempus Labs, Inc. Author Thomas Morland also has an immediate family member that holds employment and is a shareholder of the United Therapeutics Corporation. Author Bradley Confer has been a consultant for Boston Scientific Corporation and participated in speaker\u0026rsquo;s bureau at Abbvie. Author Hannah Woolley has an immediate family member who owns stock in Alcon, Novartis, Gilead Sciences, Regeneron, Amgen, Pfizer, Vertex Pharmaceutical, Biogen, BioNTech, and Moderna Therapeutics. Author Heather Rocha has an immediate family member who is employed by New York Presbyterian Hospital. All other authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eA.Y. wrote main manuscript text and prepared figures and tables.H.R, E.L., and B.C. edited initial manuscript draft and reviewed the manuscript.All other authors reviewed manuscript.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eAll data supporting the findings of this study are available within the paper and its supplementary information.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBansidhar B, Silinsky J. History and Pathogenesis of Lynch Syndrome. \u003cem\u003eClin Colon Rectal Surg\u003c/em\u003e. 2012;25(02):063-066. doi:10.1055/s-0032-1313776 \u003c/li\u003e\n\u003cli\u003eBuecher B, Cacheux W, Rouleau E, Dieumegard B, Mitry E, Li\u0026egrave;vre A. Role of microsatellite instability in the management of colorectal cancers. \u003cem\u003eDigestive and Liver Disease\u003c/em\u003e. 2013;45(6):441-449. doi:10.1016/j.dld.2012.10.006 \u003c/li\u003e\n\u003cli\u003eBonadona V, Bona\u0026iuml;ti B, Olschwang S, et al. Cancer Risks Associated With Germline Mutations in \u003cem\u003eMLH1\u003c/em\u003e, \u003cem\u003eMSH2\u003c/em\u003e, and \u003cem\u003eMSH6\u003c/em\u003e Genes in Lynch Syndrome.\u003cem\u003eJAMA\u003c/em\u003e. 2011;305(22):2304. doi:10.1001/jama.2011.743 \u003c/li\u003e\n\u003cli\u003eBibbins-Domingo K. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. \u003cem\u003eAnn Intern Med\u003c/em\u003e. 2016;164(12):836-845. doi:10.7326/M16-0577 \u003c/li\u003e\n\u003cli\u003eGaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. \u003cem\u003eThe Lancet\u003c/em\u003e. 2018;392(10152):1036-1046. doi:10.1016/S0140-6736(18)31924-X \u003c/li\u003e\n\u003cli\u003eMcNeil JJ, Gibbs P, Orchard SG, et al. Effect of Aspirin on Cancer Incidence and Mortality in Older Adults. \u003cem\u003eJNCI: Journal of the National Cancer Institute\u003c/em\u003e. 2021;113(3):258-265. doi:10.1093/jnci/djaa114 \u003c/li\u003e\n\u003cli\u003eGuirguis-Blake JM, Evans C V., Perdue LA, Bean SI, Senger CA. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer. \u003cem\u003eJAMA\u003c/em\u003e. 2022;327(16):1585. doi:10.1001/jama.2022.3337 \u003c/li\u003e\n\u003cli\u003eBurn J, Sheth H, Elliott F, et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. \u003cem\u003eThe Lancet\u003c/em\u003e. 2020;395(10240):1855-1863. doi:10.1016/S0140-6736(20)30366-4 \u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric (Version 1.2025). Available at: genetics_ceg.pdf (Accessed July 1, 2025) \u003c/li\u003e\n\u003cli\u003eHall MJ, Clapper M, Chang WCJ, Chertock Y, Nguyen MJ. Predictors of uptake of aspirin (ASA) chemoprevention in Lynch syndrome (LS). \u003cem\u003eJournal of Clinical Oncology\u003c/em\u003e. 2021;39(3_suppl):49-49. doi:10.1200/JCO.2021.39.3_suppl.49 \u003c/li\u003e\n\u003cli\u003eSmith SG, Foy R, McGowan J, et al. General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey. \u003cem\u003eFam Cancer\u003c/em\u003e. 2017;16(4):509-516. doi:10.1007/s10689-017-9986-9 \u003c/li\u003e\n\u003cli\u003eBurn J, Mathers JC, Bishop DT. Chemoprevention in Lynch syndrome. \u003cem\u003eFam Cancer\u003c/em\u003e. 2013;12(4):707-718. doi:10.1007/s10689-013-9650-y \u003c/li\u003e\n\u003cli\u003eLloyd KE, Hall LH, King N, et al. Aspirin use for cancer prevention: A systematic review of public, patient and healthcare provider attitudes and adherence behaviours. \u003cem\u003ePrev Med (Baltim)\u003c/em\u003e. 2022;154:106872. doi:10.1016/j.ypmed.2021.106872 \u003c/li\u003e\n\u003cli\u003eNieuwkerk PT, Nierman MC, Vissers MN, et al. Intervention to improve adherence to lipid-lowering medication and lipid-levels in patients with an increased cardiovascular risk. \u003cem\u003eAm J Cardiol\u003c/em\u003e. 2012;110(5):666-672. doi:10.1016/j.amjcard.2012.04.045 \u003c/li\u003e\n\u003cli\u003eDerose SF, Green K, Marrett E, et al. Automated outreach to increase primary adherence to cholesterol-lowering medications. \u003cem\u003eJAMA Intern Med\u003c/em\u003e. 2013;173(1):38-43. doi:10.1001/2013.jamainternmed.717 \u003c/li\u003e\n\u003cli\u003eDrew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. \u003cem\u003eNat Rev Cancer\u003c/em\u003e. 2016;16(3):173-186. doi:10.1038/nrc.2016.4 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"familial-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"fame","sideBox":"Learn more about [Familial Cancer](http://link.springer.com/journal/10689)","snPcode":"10689","submissionUrl":"https://submission.nature.com/new-submission/10689/3","title":"Familial Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7189423/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7189423/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Patients with Lynch syndrome (LS) have been shown to have up to an 80% lifetime risk of developing colorectal cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommend LS patients consider taking aspirin daily to reduce their risk of colorectal cancer, which is primarily based on the Cancer Prevention Project 2 (CAPP-2) study results. In this study, we evaluated the compliance of guideline directed aspirin therapy among LS patients at Geisinger Inherited Risk Gastrointestinal clinic (IRGI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Medical records of 177 patients were retrospectively reviewed from May 2016 to December 2022. After excluding those with missing data or lost to follow-up, our study cohort consisted of 167 patients. \u0026nbsp;Demographics, affected genes, clinical history, and ASA use were collected. \u0026nbsp;Chi-square test and unpaired T-test were used to evaluate the association between various parameters and aspirin use.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e With a median annual follow up of 36 months and adjustment for patients with relative and absolute contraindications to ASA, 58.5% (83/142) of patients were compliant with ASA therapy. Nearly half 49.4% (41/83) of ASA users took 81 mg daily, 1.2% (1/83) took 250 mg daily, 42.2% (35/83) took 325 mg daily and only 7.2% (6/83) reported taking \u0026gt;600 mg daily. The difference of age on those taking ASA and those not taking ASA was found to be statistically significant (p-value = 0.025.)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eThe adherence to guideline directed therapy likely stems from provider and patient education in addition to improved patient navigation strategies.\u003c/p\u003e","manuscriptTitle":"Single Institution Assessment of Compliance with Guideline Directed Aspirin Therapy in the Prevention of Colorectal Cancer in Lynch Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-30 07:47:16","doi":"10.21203/rs.3.rs-7189423/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-05T08:34:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-26T11:03:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-23T23:39:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114912912825413325003495447892697400666","date":"2025-09-16T12:01:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217758411294524746119755520399445161806","date":"2025-09-02T12:16:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-24T06:19:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-23T06:24:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-23T06:21:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Familial Cancer","date":"2025-07-22T17:07:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"familial-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"fame","sideBox":"Learn more about [Familial Cancer](http://link.springer.com/journal/10689)","snPcode":"10689","submissionUrl":"https://submission.nature.com/new-submission/10689/3","title":"Familial Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"04c4f32c-af3b-456a-9209-cf3191534a1c","owner":[],"postedDate":"July 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T16:03:36+00:00","versionOfRecord":{"articleIdentity":"rs-7189423","link":"https://doi.org/10.1007/s10689-026-00533-8","journal":{"identity":"familial-cancer","isVorOnly":false,"title":"Familial Cancer"},"publishedOn":"2026-02-09 15:59:03","publishedOnDateReadable":"February 9th, 2026"},"versionCreatedAt":"2025-07-30 07:47:16","video":"","vorDoi":"10.1007/s10689-026-00533-8","vorDoiUrl":"https://doi.org/10.1007/s10689-026-00533-8","workflowStages":[]},"version":"v1","identity":"rs-7189423","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7189423","identity":"rs-7189423","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}