Citations

9029 Background: Addressing guideline concordant FP and TPP with cancer is challenging, especially for OT. SIM, a well-known education tool, has not been traditionally used to teach these topics. As part of the hematology/oncology fellowship curriculum, we designed a SIM applying LSP to bridge this educational gap. Methods: Applying LSP of contrasting cases, elaboration, feedback, generation and just-in-time telling, chief OTs and faculty designed a SIM with 3 clinical scenarios (CS) and 3 standardized pts (SP): FP for a female pt hospitalized for acute lymphoblastic leukemia tx, FP for a male pt in clinic for germ cell tumor tx, and breast cancer tx for a pregnant pt in 2 nd trimester. OT received written educational materials (WEM) and attended a lecture 1 week and 1 day pre SIM, respectively. OT were split into 2 groups; 1 started in the FP CS and 1 in the TPP CS, and then they switched. To reduce cognitive overload, each OT participated in 1 of 2 FP CS: half in the female FP CS and half in the male. Faculty and chiefs led debriefing sessions after all CS. The FP debrief ended with a special “learner as a teacher” part, where OT who attended the female CS taught those from the male CS about their topic and vice versa. The SIM concluded with "take-home" points. Pre (after having WEM) and post SIM anonymous surveys and verbal feedback assessed OT comfort, perceptions, and knowledge. Results: A 3 hour SIM with 14 OT and 5 faculty was completed successfully. SIM ended with all OT verbally sharing a learning point and positive feedback. All OT filled pre and post SIM surveys. Pre SIM, 17% reported having prior FP education, and 42% had prior TPP education. However, only 8% and 25% felt adequately prepared for FP and TPP discussions, respectively. Post SIM survey showed major improvement in comfort and knowledge about FP and TPP (see table 1). 75% of OT favored a combination of SIM and learning by teaching over other SIM formats. 83% supported having a TPP lecture before SIM. 100% reported satisfaction with FP and TPP SIM’s quality and wanted similar activities in the future. 92% were satisfied with the learner as a teacher tool. 100% felt education about FP and TPP with cancer should be part of fellowship training. Moral/cultural concerns were discussed as possible challenges in FP education. Conclusions: The application of LSP through SIM significantly increased OTs’ comfort discussing FP and TPP with cancer, and objectively enhanced their knowledge on these topics compared to after reading WEM. The SIM was largely perceived as a successful activity to educate about challenging topics and should become part of fellowship curriculum. Pre SIM % Post SIM % Comfortable addressing FP 17 92 Comfortable addressing TPP 8 100 Correct answers about female FP 63 83 Correct answers about male FP 67 94 Correct answers about TPP with cancer 68 98

10587 Background: The American Society of Clinical Oncology (ASCO) and NCCN recommend germline testing for patients (pts) with biliary tract cancers (BTC), particularly those diagnosed at a young age. Prior studies estimate that approximately 15% of pts with BTC harbor pathogenic germline alterations. Germline testing can identify hereditary cancer syndromes, guide targeted therapy, and inform family counseling. This study aimed to further characterize and describe the prevalence of pathogenic germline variants (PGVs) in patients with young-onset BTC (YO-BTC). Methods: We conducted a retrospective review of medical records for pts diagnosed with YO-BTC (ages 18–55) across all Mayo Clinic tri-sites from January 2014 to October 2024. Data collected included results from germline DNA sequencing, tumor genetic testing, demographics, history of other malignancies, and family history of cancer. The primary outcome was the identification of pathogenic germline mutations associated with cancer predisposition. Results: Among 239 pts with YO-BTC, the median age at diagnosis was 43 years (range 19–55), with 62% female and 65.2% identifying as white. Clinical germline testing (e.g., Invitae, Ambry, Myriad) was performed in 123 pts (51.5%), revealing PGVs in 15 pts (12.1%), variants of uncertain significance (VUS) in 30 pts (24.3%), and likely benign variants in 4 pts (3.2%). Among those with PGVs, DNA repair mutations were the most common findings (10/15), including ATM (4), CHEK2 (2), BRCA2 (2), BAP1 (1), and PALB2 (1). One pt had a Lynch syndrome-associated mutation (MSH6), and four had mutations in other cancer-related genes (MUTYH, HOXB13, RMRP, and PIK3CA). Tumor genomic profiling (via CARIS, TEMPUS, or FoundationOne) was performed in 9 pts with PGVs, detecting the variant in 4 (44%), while liquid biopsy (Guardant) identified the PGV in 4 of 6 cases (66.6%).The majority of PGV carriers had advanced BTC (14/15), with intrahepatic cholangiocarcinoma being the most prevalent (11/15), while 4 had extrahepatic cholangiocarcinoma. Additionally, most PGV carriers had a first- or second-degree relative with a prior history of malignancy (14/15), and 3 pts had a second malignancy. Of the 15 pts with PGVs, 4 had BTC associated with primary sclerosing cholangitis. Conclusions: In this large institutional series of YO-BTC, PGVs were identified in 12.1% of pts, demonstrating a significant yield from germline testing in this population. Notably, tissue and liquid biopsies demonstrated different detection rates for PGVs, underscoring the variability in PGVs reporting across platforms. Germline testing through CLIA-approved methods should remain the standard of care. DNA repair pathway mutations, particularly ATM, CHEK2, and BRCA2, were the most frequently identified PGVs, highlighting their role in the pathogenesis of YO-BTC and their potential to guide treatment decisions.

163 Background: CRC with PM has a poor prognosis and limited treatment options. Immunotherapy has shown promise in improving outcomes for patients with microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), and high tumor mutational burden (TMB-H) tumors. However the peritoneal niche has a unique microenvironment, which can influence the effectiveness of immune check point inhibitors (ICIs). We assessed the impact of ICI on progression-free survival (PFS) and overall survival (OS) in CRC patients (pts) and PM, considering key clinical and molecular characteristics. Methods: A retrospective review aiming to identify CRC pts with MSI-H/dMMR and PM treated with immunotherapy between 2015 and 2023 was performed. Data collected included pt demographics, tumor characteristics, and treatment details. Responses were evaluated using RECIST v1.1 criteria. Results: 37 pts were included, 9 (24%) had Lynch syndrome. The median age of diagnosis was 61 years and most pts were females (65%). Most pts had MSI-H/dMMR tumors, while one pt was treated based on ultra-hypermutated phenotype (TMB 202) and POLE mutation. Among those with available TMB data, the median TMB was 52 mutations/Mb (0-202). Common mutations were PMS2 (51%), MLH1 (38%), MSH6 (16.2%), and MSH2 (16.2%). Right-sided tumors were in 54%, mucinous histology in 62%, and ascites in 54%. Pts received a median of 11 cycles of ICI (2-52). Pembrolizumab was the most frequently used ICI (78%), while Nivolumab was used either alone (11%) or in combination with Ipilimumab (11%). Median PFS in our cohort was 7.8 months and median OS was 29.9 months. The disease control rate (DCR) was 81%, with an objective response rate (ORR) of 51.3% (9 complete responses, 12 partial responses). At the time of data collection, 30% of pts were off systemic therapy and 5-FU-based chemotherapy combined with a biologic agent was the most common subsequent treatment in 32% who had PD. Univariate analysis showed no significant differences in PFS or OS based on tumor sidedness, isolated PM, liver metastases, mucinous vs. non mucinous histology or BRAF / RAS status (WT vs mutant). Malignant ascites was associated with worse OS(HR 0.3; p= 0.03). Conclusions: Treatment with ICIs in pts with MSI-H/dMMR and/or TMB-H CRC and PM improved disease control in CRC pts with PM, however, as compared to historical controls for patients with MSI-H/d-MMR disease treated with ICI, this group showed less favorable outcomes. Malignant ascites was associated with poorer overall survival. Further research of the immune response and tumor microenvironment in the peritoneal cavity is warranted.