Development of an Electronic Health Record-Based Clinical Decision Support Tool for Patients With Lynch Syndrome.

PURPOSE: To develop an electronic health record (EHR)-based clinical decision support (CDS) tool to promote guideline-recommended cancer risk management among patients with Lynch syndrome (LS), an inherited cancer syndrome that confers an increased risk of colorectal and other cancer types. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the baseline prevalence and predictors of guideline-recommended colonic surveillance and annual genetics program visits among patients with LS. Multivariable log-binomial regressions estimated prevalence ratios (PRs) of cancer risk management adherence by baseline sociodemographic and clinical characteristics. These analyses provided rationale for the development of an EHR-based CDS tool to support patients and clinicians with LS-related endoscopic surveillance and annual genetics program visits. The CDS leverages an EHR platform linking discrete genetic data to LS Genomic Indicators, in turn driving downstream clinician- and patient-facing CDS. RESULTS: Among 323 patients with LS, cross-sectional adherence to colonic surveillance and annual genetics program visits was 69.3% and 55.4%, respectively. Patients with recent electronic patient portal use were more likely to be adherent to colonic surveillance (PR, 1.67; 95% CI, 1.11 to 2.52). Patients more recently diagnosed with LS were more likely to be adherent to annual genetics program visits (PR, 0.58; 95% CI, 0.44 to 0.76 for 2-4 years; PR, 0.62; 95% CI, 0.51 to 0.75 for ≥4 compared with <2 years). Our EHR-based CDS tool is now active for 421 patients with LS throughout our health system. CONCLUSION: We have successfully developed an EHR-based CDS tool to promote guideline-recommended cancer risk management among patients with LS.

COVID-19 Disruptions to Endoscopic Surveillance in Lynch Syndrome.

Disruptions in cancer screening due to the COVID-19 pandemic may disproportionally affect patients with inherited cancer predisposition syndromes, including Lynch syndrome. Herein, we study the effect of the COVID-19 pandemic on endoscopic surveillance in Lynch syndrome through a prospective study of patients with Lynch syndrome at a tertiary referral center who were scheduled for endoscopic surveillance during the COVID-19 pandemic shutdown between March 16, 2020 and June 4, 2020. Of our cohort of 302 individuals with Lynch syndrome, 34 (11%) had endoscopic procedures scheduled during the COVID-19 pandemic shutdown. Of the 27 patients whose endoscopic surveillance was canceled during this period, 85% rescheduled procedures within 6 months with a median delay of 72 days [interquartile range (IQR), 55-84 days], with identification of an advanced adenoma or gastrointestinal cancer in 13%. Individuals who did not have a rescheduled endoscopic procedure were significantly younger than those with a rescheduled procedure [age 35 (IQR, 26-43) vs. age 55 (IQR, 43-63), P = 0.018]. Male sex was also suggestive of increasing likelihood of not having a rescheduled procedure. Taken together, our study demonstrates that the COVID-19 pandemic shutdown led to delayed endoscopic surveillance in Lynch syndrome, with potentially impactful delays among young patients. These data also emphasize the importance of timely surveillance in Lynch syndrome during this current, as well as potential future, global pandemics. PREVENTION RELEVANCE: The COVID-19 pandemic has led to unprecedented disruptions in cancer screening, which may have disproportionate effects on individuals at increased cancer risk, including those with Lynch syndrome. Herein, we show that the COVID-19 pandemic led to significant disruptions in Lynch syndrome surveillance with potentially impactful delays, thus highlighting the importance of ensuring timely surveillance among this high-risk cohort.

Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers. While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines, there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS, including small intestinal cancer (SIC) and urinary tract cancer (UTC). Given the limited evidence, guidelines do not consistently recommend surveillance for SIC and UTC, and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance recommendations. AIM: To study factors associated with SIC and UTC surveillance uptake and outcomes in LS. METHODS: This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral center. Included individuals had a pathogenic or likely pathogenic variant in MLH1, MSH2, MSH6, PMS2, or EPCAM, or were a confirmed obligate carrier, and had at least one documented visit to our center. Information regarding SIC and UTC surveillance was captured for each individual, and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center's dedicated high-risk LS clinic between January 1, 2017 and October 29, 2020. During these initial management visits, all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC surveillance. Statistical analysis using Pearson's chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance, and a P value below 0.05 was deemed statistically significant. RESULTS: Of 317 individuals with LS, 86 (27%) underwent a total of 105 SIC surveillance examinations, with 5 leading to additional work-up and no SICs diagnosed. Additionally, 99 (31%) patients underwent a total of 303 UTC surveillance examinations, with 19 requiring further evaluation and 1 UTC identified. Of 155 individuals who had an initial LS management visit between January 1, 2017 and October 29, 2020, 63 (41%) chose to undergo SIC surveillance and 58 (37%) chose to undergo UTC surveillance. However, only 26 (41%) and 32 (55%) of those who initially chose to undergo SIC or UTC surveillance, respectively, successfully completed their surveillance examinations. Individuals with a pathogenic variant in MSH2 or EPCAM were more likely to initially choose to undergo SIC surveillance (P = 0.034), and older individuals were more likely to complete SIC surveillance (P = 0.007). Choosing to pursue UTC surveillance was more frequent among older individuals (P = 0.018), and females more frequently completed UTC surveillance (P = 0.002). Personal history of cancer and family history of SIC or UTC were not significantly associated with electing nor completing surveillance. Lastly, the provider discussing SIC/UTC surveillance was significantly associated with subsequent surveillance choices. CONCLUSION: Pursuing and completing SIC/UTC surveillance in LS is influenced by several factors, however broad incorporation in LS management is likely unhelpful due to low yield and frequent false positive results.

EUS-based Pancreatic Cancer Surveillance in BRCA1/BRCA2/PALB2/ATM Carriers Without a Family History of Pancreatic Cancer.

Carriers of a pathogenic/likely pathogenic (P/LP) BRCA1/BRCA2/ATM/PALB2 variant are at increased risk of pancreatic ductal adenocarcinoma (PDAC), yet current guidelines recommend surveillance only for those with a family history of PDAC. We aimed to investigate outcomes of endoscopic ultrasound (EUS)-based PDAC surveillance in BRCA1/BRCA2/ATM/PALB2 carriers without a family history of PDAC. We performed a retrospective analysis of all P/LP BRCA1/BRCA2/ATM/PALB2 carriers who underwent EUS at a tertiary care center. Of 194 P/LP BRCA1/BRCA2/ATM/PALB2 carriers who underwent EUS, 64 (33%) had no family history of PDAC and had at least 1 EUS for PDAC surveillance. These individuals underwent 143 total EUSs, were predominantly female (72%), and BRCA2 carriers (73%), with the majority having a personal history of cancer other than PDAC (67%). The median age at time of first EUS was 62 years [interquartile range (IQR), 53-67 years] and a median of 2 EUSs (IQR 1-3) were performed per patient, with a median of 3 years (IQR 2-4.5 years) between the first and last EUS for those with more than 1 EUS. Pancreatic abnormalities were detected in 44%, including cysts in 27%, and incidental luminal abnormalities in 41%. Eight percent developed a new pancreatic mass or cyst during surveillance, 2 individuals developed PDAC, and no serious complications resulted from surveillance. After discussion of the risks, limitations, and potential benefits, PDAC surveillance can be considered in BRCA1/BRCA2/ATM/PALB2 carriers without a family history of PDAC; however, the effectiveness of PDAC surveillance in this population requires further study. PREVENTION RELEVANCE: BRCA1/BRCA2/ATM/PALB2 carriers have increased pancreatic ductal adenocarcinoma (PDAC) risk, yet are typically not eligible for PDAC surveillance in the absence of PDAC family history. Herein we describe outcomes of PDAC surveillance in BRCA1/BRCA2/ATM/PALB2 carriers without a family history of PDAC, showing that PDAC surveillance can be considered in this high-risk group.

Upper Endoscopic Surveillance in Lynch Syndrome Detects Gastric and Duodenal Adenocarcinomas.

Lynch syndrome is a prevalent hereditary cancer predisposition syndrome. While colorectal cancer is the most common gastrointestinal (GI) cancer in Lynch syndrome, there is also increased risk of gastric and small intestinal cancers. Recommendations for upper GI cancer surveillance in Lynch syndrome vary widely with limited data supporting effectiveness. Herein, we collected data on individuals with a diagnosis of Lynch syndrome seen at our tertiary care referral center. We identified individuals who underwent upper endoscopy and those with upper GI cancers, and associated demographics, genetic testing results, and endoscopic information. Standard statistical analyses were performed. Among 295 individuals with Lynch syndrome seen at our center, 217 (73.6%) underwent 660 total upper endoscopies. Of these 217, precancerous upper endoscopy findings included Barrett's esophagus (7, 3.2%), gastric intestinal metaplasia (18, 8.3%), and duodenal adenomas (4, 1.8%), and Helicobacter pylori was identified in 6 (2.8%). Upper GI cancers were diagnosed in 11 individuals (3.7%), including esophageal in 1, gastric in 6, and duodenal in 4. Five (1.7%) of these upper GI cancers were identified on surveillance. Individuals with upper GI cancers identified on surveillance were older at first surveillance endoscopy, with median age 63.3 versus 44.9 years (P < 0.001). Of the upper GI cancers detected on surveillance, 80% (4/5) occurred within 2 years of last upper endoscopy and 80% were stage I. In conclusion, upper endoscopy surveillance in Lynch syndrome identifies upper GI cancers. For individuals with Lynch syndrome who undergo upper GI surveillance, a short surveillance interval may be warranted.