PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Background Implementation of screening modalities has led to a decreased incidence of colorectal malignancies. Unfortunately, overall incidence has remained unchanged as cases have increased in patients below the suggested screening age. Therefore, we evaluated characteristics and oncological outcomes of malignancies in patients ≤40 years of age. Methods Single-center retrospective analysis of prospectively collected data of malignancies in patients ≤40 years evaluated in our institution between 2010 and 2016. Basic descriptors for demographic, clinical, histologic, and genetic data were collected. Disease-free survival (DFS) and 5-year overall survival (OS) were compared for patients between 30-40 years and <30 years. Results Fifty-six patients ≤40 years were identified, 44 of whom (96.5%) had adenocarcinomas. Most common malignancy location was the rectum (64.3%). Despite aggressive tumor characteristics such as moderate/poor differentiation (88.6%), lymphovascular invasion (26.8%), perineural invasion (21.4%), and advanced tumor stage T3/T4 (60.7%), OS rate was 94.6%. Both age groups had similar oncologic characteristics. There was a trend toward worse OS (2/11 and 1/45, P = .06) but not for DFS (7/11 and 15/43, P = .18) in patients <30 years of age compared to 30-40 years. There were no differences in OS (3/44 vs 0/88, P = .44) or DFS (17/42 vs 3/8, P = .80) between sporadic vs non-sporadic malignancies, respectively. Conclusions Patients ≤40 years of age with malignancy have advanced tumor stages and aggressive tumor characteristics at diagnosis. Although there is higher OS risk for patients <30 compared to those aged 30-40 years, no differences were found for DFS between these two groups.

PURPOSE Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome and inconsistent both in childhood cancers and in determining germline MMRD. PATIENTS AND METHODS We developed and analyzed a functional Low-pass Genomic Instability Characterization (LOGIC) assay to detect MMRD. The diagnostic performance of LOGIC was compared with that of current established assays including tumor mutational burden, immunohistochemistry, and the microsatellite instability panel. LOGIC was then applied to various normal tissues of patients with CMMRD with comprehensive clinical data including age of cancer presentation. RESULTS Overall, LOGIC was 100% sensitive and specific in detecting MMRD in childhood cancers (N = 376). It was more sensitive than the microsatellite instability panel (14%, P = 4.3 × 10−12), immunohistochemistry (86%, P = 4.6 × 10−3), or tumor mutational burden (80%, P = 9.1 × 10−4). LOGIC was able to distinguish CMMRD from other cancer predisposition syndromes using blood and saliva DNA ( P < .0001, n = 277). In normal cells, MMRDness scores differed between tissues (GI > blood > brain), increased over time in the same individual, and revealed genotype-phenotype associations within the mismatch repair genes. Importantly, increased MMRDness score was associated with younger age of first cancer presentation in individuals with CMMRD ( P = 2.2 × 10−5). CONCLUSION LOGIC was a robust tool for the diagnosis of MMRD in multiple cancer types and in normal tissues. LOGIC may inform therapeutic cancer decisions, provide rapid diagnosis of germline MMRD, and support tailored surveillance for individuals with CMMRD.

Our university, based data center has curated statewide data on short-term, involuntary examinations for mental illness/co-occurring disorders for over two decades. We recently began receiving petitions and orders for longer-term civil commitment from Clerks of Court. We are currently developing a system to curate data on involuntary assessments/treatment for substance use disorders. The involuntary examination data have been used to produce 100+ ad hoc reports for a variety of stakeholders, a statutorily required annual report, as well as to inform the state legislature, advocates, agencies, and several statewide taskforces relating to criminal justice and mental health initiatives. Data from documents are currently received and entered in a) hard copy via the mail, b) securely scanned and transferred either via SFTP or with secure transfer to our University's Box.com account, or c) direct provider entry into a secure web portal. Our University's IT environment has evolved, with an escalation of organizational and policy changes related to the merging of two IT units. While this merging has led to innovation, it has also presented operational, organizational and logistical challenges. Discussed in this presentation will be a) these IT challenges, b) the pros and cons of form submission methods, c) how choice of submission method is informed by the capabilities of those submitting the documents in addition to, the resources and capabilities of our center within the context of current funding, as well as d) how this impacts choices made about data entry, data quality and use of the data for analyses.

OBJECTIVES/GOALS: The purpose of this group is to foster professional and personal growth as leaders, provide peer mentoring, integrate the roles of scientist, woman, and mother, and build a self-sustaining network of peers for ongoing support throughout their careers in an academic setting. METHODS/STUDY POPULATION: - Study population: 12 Health sciences research faculty (50% protected research time); identify as female; mother of school-age and/or younger children Methods: Year-long program; including a 2-day retreat based on Brene Brown's Dare to Lead RESULTS/ANTICIPATED RESULTS: - Despite the pandemic, 100% of participants continued in the program over the one-year duration and met the attendance requirement of 75% - Screening for burnout was effective - facilitator was able to intervene when severe burnout was noted.