Ressler, Steven W.

10578 Background: Multicancer detection (MCD) testing using cell-free DNA methylation patterns is a novel blood-based approach to cancer screening. In 2022, Mayo Clinic implemented offering MCD testing into routine clinical practice. Prior real-world reports have been limited to single-site experiences. We evaluated enterprise-wide implementation of MCD testing across all three Mayo Clinic sites using the Mayo Clinic Platform. Methods: We performed a retrospective analysis of de-identified clinical data from Mayo Clinic Platform Discover, including GRAIL Galleri tests performed at Mayo Clinic sites in Rochester, MN; Scottsdale, AZ; and Jacksonville, FL. This activity did not require IRB review per 45 CFR 46.102. Demographics, test results, cancer diagnoses, and prior cancer history were extracted using a privacy-preserving protocol, with data de-identified by expert determination. ICD-10 diagnostic codes were used to identify subsequent cancer diagnoses. Results: A total of 8,201 Galleri tests were performed in 7,300 patients; some patients underwent repeat testing. Fifty-seven tests (0.7%) were positive. Among MCD-positive patients, cancer diagnostic codes were identified in 32 patients, yielding a positive predictive value (PPV) of 58.7%. The most common cancers identified were oropharyngeal (34.4%), lymphoid and hematopoietic (34.4%), and gastrointestinal malignancies (18.8%).Among 8,144 MCD-negative tests (99.3% of all testing performed), 423 patients (5.2%) subsequently received a cancer diagnostic code, yielding a negative predictive value of 92.5%. The most commonly identified cancers in this group were male genital organs (36.6%), urinary tract (10.6%), and thyroid or other endocrine glands (7.3%). Overall, 10.1% of patients had a prior cancer history, which was more common in MCD-positive than MCD-negative patients (22.6% vs 10.0%). Patients with positive tests were older (mean age 68.4 vs 61.5 years) and more often male (67% vs 62%). Race distribution was similar. Conclusions: Enterprise-wide implementation of MCD testing across diverse clinical settings is feasible within routine workflows. Over half of positive tests were associated with cancer diagnostic codes, supporting the clinical promise of MCD testing. Limitations include incomplete capture of externally diagnosed cancers and lack of cancer signal-of-origin data. The Mayo Clinic Platform enables scalable, secure analytics to support future cancer interception strategies.

Background/Objectives: Multi-cancer detection (MCD) tests have emerged as a promising tool to redefine the landscape of early cancer detection. Implementation of this novel technology will likely fall to primary care clinicians (PCC). The purpose of this study is to characterize and explore differences in PCCs perceptions and preferences towards MCD testing. Methods: Between March and May of 2023, this cross-sectional survey was administered to 281 PCCs, including physicians and advanced care providers practicing within an integrated healthcare system spanning five states. The survey collected data on self-reported characteristics, perceptions of MCD testing, and preferences for learning about MCD testing. Analysis was limited to those with no prior experience with MCD testing (N = 181, response rate 22.8%). Descriptive statistics summarized key variables and chi-square tests assessed differences in perceptions and preferences by key characteristics. Results: Most PCCs were interested in MCD testing (66.3%), but limited knowledge/awareness of MCD testing and confidence to manage patients with a positive test were observed, along with concerns around cost (76.7%) and misuse/poor implementation. The primary preferences for learning about MCD testing were online courses or classroom instruction (64.5%). Significant differences in perceptions and preferences for learning were observed by location, degree, and years in practice. Conclusions: PCCs in our study held positive views towards MCD testing, but gaps and variation in knowledge and confidence towards MCD testing and concerns around the cost and misuse/poor implementation were observed. While efforts to train and educate all PCCs on MCD testing is a critical first step, more research is needed to understand how best to support implementation tailored to individual and system-level needs and characteristics.

Objective: Multicancer Detection (MCD) tests, such as the GRAIL Galleri, offer a novel approach to cancer screening by detecting cancer-specific methylation patterns in cell-free DNA through a single blood sample. This study evaluated an 18-month implementation of MCD testing in a tertiary ambulatory internal medicine clinic. Patients and Methods: Between June 2022 and November 2023, 2244 asymptomatic (without symptoms attributed to cancer) patients underwent MCD testing. The study focused on operational workflows, patient and physician education, and diagnostic follow-up of positive results. Standardized materials, including electronic health record (EHR) workflows, FAQs, and diagnostic pathways, were developed to facilitate implementation. Challenges included managing false positives, patient anxiety, costs, and ethical considerations. Results: Of the 2244 patients tested, 17 (0.76%) had positive results, and 15 underwent further diagnostic evaluation. Cancer was confirmed in 11 (73.3%) patients, including cases of breast, colon, esophageal, lymphoma, ovarian, and pancreatic cancers. Four patients had no identifiable malignancy despite comprehensive work-up. Conclusions: MCD testing is feasible in routine clinical workflows, with 73% of positive cases yielding cancer diagnoses. While promising, further research is required to assess long-term outcomes, cost-effectiveness, and optimal implementation strategies of cancer interception in broader healthcare settings.

Introduction: The Undiagnosed Mass Clinic (UMC) at our institution is a clinical and research program created to address gaps in the early diagnostic phase of the cancer care continuum for patients with potential malignant neoplasms. All patients referred to the UMC are invited to participate in the UMC registry, which tracks operational and clinical metrics while maintaining a repository of blood and tissue specimens for future research. Methods: We conducted a retrospective cohort study of the first 100 patients enrolled in the UMC registry. We analyzed patient demographics, final diagnoses, and the time from initial consultation to final diagnosis. Results: Most participants were White (86%), non-Hispanic (93%), and married (72%). The mean (SD) age was 64 (13.9) years. The final diagnoses of the masses were categorized as malignant/neoplastic with malignant potential (n = 53), benign (n = 36), or requiring diagnostic surveillance (n = 10). The mean (SD) time from initial consultation to final diagnosis of malignant/neoplastic with malignant potential masses significantly improved from 37.4 (36.6) days for the first 50 participants to 17.3 (19.7) days for the next 50 participants ( P = .006). Conclusions: These initial insights from the UMC registry will help direct future efforts to improve the care of patients with potential malignant neoplasms.

Background: Angiosarcomas are rare tumors that can be difficult to diagnose due to subtle changes in the vascular endothelium. When there is evidence to suggest malignancy, such as a pathologic fracture, further investigation is needed, and a high suspicion for angiosarcoma needs to be present so that appropriate immunohistochemical stains are utilized on biopsied tissue. In situations where such suspicion is high and prior biopsies have been negative, performance of splenectomy, can be both diagnostic and therapeutic when splenomegaly is present. Case Report: This is a case of a 52-year-old woman with splenomegaly, initially attributed to infection, in the setting of upper respiratory symptoms and thrombocytopenia. Three months later, however, she presented with back pain. Imaging showed lytic bone lesions with pathologic vertebral fracture and numerous liver lesions that were too small to characterize further. Initial biopsies of the liver and bone did not reveal a pathologic process. Several months later, still without a unifying diagnosis, she presented to our institution. MRI of the brain was done for neurologic concerns and showed pathologic enhancement in the calvarium. A PET scan showed diffuse avidity of the skeleton and spleen. After discussing the case with a hematologist, splenectomy was performed for both diagnostic and therapeutic purposes. Angiosarcoma was identified in the spleen and in a PET-directed bone biopsy. With a definitive diagnosis, she returned home and subsequently elected to pursue hospice care. Conclusion: When there is a high clinical suspicion for malignant angiosarcoma, a multidisciplinary approach is necessary to direct both tissue acquisition and necessary histochemical staining.