Kuhlman, Justin J.

9021 Background: An escape room is a team-based activity in which participants collaborate to solve puzzles within a fixed time limit and escape. Prior studies demonstrate high learner satisfaction and improved teamwork and communication with medical education escape rooms. To date, no published reports describe an escape room designed specifically for hematology/oncology (hem/onc) fellows. As part of Hem/Onc Curriculum, we designed and implemented a hem/onc-focused escape room and evaluated learner satisfaction and perceived learning impact. Methods: The escape room was designed using evidence-based learning science principles (Table 1). Teams worked to solve sequential puzzles, centered on a patient case, addressing key hem/onc concepts, including transfusion medicine, peripheral blood smears, lymphoma classification, and coagulation disorders. Each solved puzzle revealed additional patient laboratory and pathology data. Successful completion required teams to diagnose the patient and select appropriate treatment. Following the activity, teams participated in a facilitator-led debrief focused on team dynamics, communication, and problem solving. Teams observed each other and shared feedback. A larger group debrief co-led by chief fellows and faculty reviewed learning objectives and key takeaways. Learner outcomes were assessed using a post-activity survey evaluating satisfaction, engagement, and impact on learning. Results: Eighteen learners participated, including 14 hem/onc fellows, 1 APP hem/onc fellow, and 3 internal medicine residents. Three of four teams escaped within 1 hour (mean completion time, 52 minutes). All participants provided positive verbal feedback. Fifteen learners completed the post-activity survey, and all respondents reported satisfaction with the activity and would recommend it for future fellows. One-word descriptors included “engaging,” “fun,” and “challenging.” Most respondents (93.3%) agreed that the activity reinforced key hem/onc concepts and improved confidence in clinical problem-solving. All learners felt the activity supported learning, and 93.3% reported that collaboration enhanced the learning experience. Participants identified team-based problem solving, clinical application, and interactive puzzles as the most effective components. Conclusions: A hem/onc escape room resulted in high learner satisfaction and reinforced hem/onc knowledge and clinical problem-solving. This feasible, fun, and innovative activity complements traditional fellowship education by leveraging adult learning principles through gamified, team-based learning and should be incorporated into training programs’ curriculum. Learning science principles applied in a hem/onc escape room. Active Learning Belonging Contrasting Cases Debriefing Deliberate Practice Elaboration Generation Listening and Sharing Reward Worked Examples

8545 Background: Brain metastases (BM) correlate with poor prognosis, occurring in 10% of non-small cell lung cancer (NSCLC) patients (pts) at diagnosis and up to 40% over the disease course. Immunotherapy (IO) with or without chemotherapy has become the new standard of care for stage IV NSCLC. However, the survival benefit of IO in pts with BM remains unclear as most studies are limited to small sample sizes or highly selected pts with asymptomatic or treated BMs. This study represents the largest real-world data analysis evaluating the survival benefits of IO in stage IV NSCLC pts with BM. Methods: Demographics, clinical features, and survival were analyzed in stage IV NSCLC pts with BM from the National Cancer Database (NCDB) from 2014-2020. A multivariate Cox proportional hazards modeling assessed factors impacting mortality. Results: Of 204,249 pts with stage IV NSCLC, 30% had BM. The mean age was 68 years, with 54% male. Most pts were White (82%), followed by Black (12%) and Asian (3.1%). Government insurance covered 70% of pts, and 26% had private insurance. Adenocarcinoma was the predominant histology (62%), followed by squamous cell carcinoma (SCC) (20%). Liver and bone metastases were observed in 19% and 42% of pts, respectively. Among pts with BM, 18% received immunotherapy, 53% received chemotherapy, 66% received whole-brain radiation, and 18% received limited-brain radiation. Multivariate Cox analysis showed that pts receiving IO had a 46% lower mortality risk compared to not receiving IO (HR: 0.54, 95% CI: 0.51–0.56, p < 0.001), demonstrating the independent benefit of IO in pts with BM, regardless of brain radiation or chemotherapy. Females had a lower mortality risk than males (HR: 0.88, 95% CI: 0.85–0.91, p < 0.001). Asian (HR: 0.71, 95% CI: 0.64–0.79), Hispanic (HR: 0.76, 95% CI: 0.65–0.89), and Black pts (HR: 0.88, 95% CI: 0.84–0.93) had improved survival as compared to White. Pts with private insurance have lower mortality risk (HR: 0.94, 95% CI: 0.90–0.98), compared to lack of insurance (HR: 1.19, 95% CI: 1.08–1.31). SCC was linked to worse survival (HR: 1.28, 95% CI: 1.22–1.35). Conclusions: IO significantly improves survival in pts with NSCLC with BM, regardless of brain radiation therapy or chemotherapy. However, survival disparities based on histology, insurance status, and demographic factors persist, highlighting the need for more equitable treatment strategies.

e16610 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 1-2 per million per year. The optimal treatment remains unclear as does the benefit of chemotherapy (chemo) in patients (pts) with resectable ACC. Methods: The SEER database (2000–2021) was used to identify ACC pts > 18 years. Variables of interest included age, race, household income, rural-urban classification, stage, chemo, radiation therapy (RT), and surgery. Statistical analyses were conducted using ANOVA, Kruskal-Wallis, and Kaplan-Meier methods to compare survival outcomes according to variables of interest. Results: Of the 2,598 pts identified, 1,564 (60%) were female. The majority of pts (85%) were white, followed by black (9%). Most pts (87%) resided in metropolitan areas. Pts with localized, regional, or distant metastatic disease comprised 25%, 17% and 36% of the group, respectively. 40% of pts underwent radical or total surgical removal of the primary site disease while 9%, 2%, and 1% underwent partial surgical removal, excision, or debulking surgery, respectively, and 30% did not undergo surgery. 34% of pts received chemo and 8% received RT. The median overall survival (mOS) for the entire cohort was 15 months (m) (95% CI: 14–17 m). No significant differences in OS were observed among pts of different races or household incomes. Distant metastatic disease was significantly associated with worse mortality when compared with regional or localized diseases (mOS: 5 m vs. 20 m vs 60.6 m, respectively, p < 0.001). Surgical intervention of any kind was associated with longer survival when compared to those who did not undergo surgery (18 m vs. 3 m, HR 0.33, p < 0.0001). Among the 971 pts with distant metastatic disease, pts who received chemo had a superior mOS compared to those who did not receive chemo or with unknown chemo status (8 m vs. 2 m, p < 0.0001). This OS advantage remained significant even after excluding pts who underwent surgery (5 m vs. 2 m, p < 0.0001). While chemo was also associated with longer mOS (29 m vs. 27 m, p < 0.0001) in localized disease, this survival advantage was not present in pts with localized disease managed with surgery (27 m vs. 27 m, p = 0.061). Although chemo was associated with numerically longer mOS in pts with regional disease, the difference was not significant. Conclusions: ACC with distant metastatic disease carries a poor prognosis yet demonstrates superior survival in pts who receive chemo. Surgery is associated with better survival outcomes, but there is no additive benefit from chemo in those with localized disease managed with surgical resection.

The emergence of immunotherapy has ushered in a new era in the management of non-small cell lung cancer (NSCLC). Various immune check point inhibitors have demonstrated significant benefit in the management of locally advanced NSCLC that are treated with either surgery or concurrent chemoradiation. We provide a comprehensive and up-to-date review of data from key studies, discuss the challenging clinical issue regarding the timing and duration of immunotherapy in patients undergoing surgery, and highlight the unmet needs and future directions of immunotherapy in NSCLC.

Abstract Extramedullary disease in acute myeloid leukemia (AML), also known as myeloid sarcoma (MS), is an uncommon presentation of de novo AML. We analyzed medical records of patients in the Mayo Clinic database spanning between 1996 and 2021 who were diagnosed with de novo extramedullary AML. Survival outcomes were analyzed using Kaplan-Meier and Cox-proportional hazard models for univariate and multivariate analysis, respectively. With a median follow-up of 20.7 months, 83 patients with de novo MS were identified; 49 presented with synchronous MS and 34 with isolated MS. Next generation sequencing (NGS) revealed RTK-RAS pathway mutations in 44% of patients. Median overall survival (OS) was 25.3 months and 17.8 months in isolated and synchronous MS, respectively (p = 0.49). Variables associated with improved OS on univariate analysis included treatment with intensive chemotherapy (p < 0.001), normal or favorable risk karyotype (p = 0.001), age less than 60 years (p = 0.001), and a complete response to treatment at extramedullary sites (p < 0.0001). On multivariate analysis, normal or favorable risk karyotype (p = 0.001), age less than 60 (p = 0.01), and a complete extramedullary response (p = 0.001) were associated with improved OS. Localized therapy did not provide added survival benefit in isolated MS. Genomic stratification, age, and extramedullary site response are predictive of survival outcomes.

Abstract Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x10 9 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

e19002 Background: Extramedullary disease in acute myeloid leukemia (AML), also known as myeloid sarcoma (MS), is an uncommon presentation of de novo AML. Clinicopathologic characteristics and optimal treatment strategies of de novo MS remain unclear in both isolated MS without bone marrow (BM) involvement and synchronous MS with BM involvement. Methods: In a single-site retrospective study, medical records of patients with de novo extramedullary AML who received oncological care at any Mayo Clinic site between 1996 and 2021 were analyzed. Using BlueSky Statistics software, survival outcomes were analyzed using Kaplan-Meier and Cox-proportional hazard models for univariate and multivariate analysis, respectively. Results: 83 patients with de novo MS were identified; 49 (59%) presented with synchronous MS and 34 (41%) exhibited isolated MS. Median age at diagnosis was 56 years (range, 17-89); 63% were male. Next-generation sequencing of the blood +/- BM revealed abnormalities in 24/27 (88%) analyzed patients; aberrations included mutations in RTK-RAS pathways (12/27), NPM1 (10/27), TET2 (6/27), and IDH2 (4/27). Median length of follow-up was 1.73 years (95% CI; 0.03-3.0); 53 patients (64%) had expired. Median event free survival was 0.64 years and 0.61 years in isolated and synchronous MS, respectively (p = 0.5). Median overall survival (mOS) in isolated and synchronous MS was 2.1 years and 1.5 years, respectively (p = 0.5). Induction treatment with intensive chemotherapy (IC) was administered in 70 patients (84%). IC regimens included 7+3, MEC, CLAG-M, and hyper-CVAD. Variables associated with improved survival in both groups included treatment with IC +/- allogenic stem cell transplant (alloSCT) (p < 0.001), normal or favorable risk karyotype (p = 0.001), and age less than 60 (p = 0.001). Localized therapy (LT) did not provide an added survival benefit. Patients with synchronous MS were more likely to relapse in the BM and blood than isolated MS (p = 0.02). Conclusions: Enriched with RTK-RAS mutations, de novo MS remains an aggressive form of AML, particularly in patients with intermediate or high-risk genomics or those with skin, soft tissue, or lymphatic involvement. IC should be employed with consideration of alloSCT in eligible patients, particularly in synchronous MS due to a heightened risk for medullary and leukemic relapse.[Table: see text]

e19552 Background: Leukemic involvement (LI) in diffuse large B cell lymphoma (L-DLBCL) is very rare and has been sparsely reported. We report our experience with this entity in a large academic multi-center setting. Methods: Medical records of patients with DLBCL who received care at Mayo Clinic between 1/2003 and 6/2020 were reviewed. DLBCL patients with LI were identified. LI was defined as increased white blood cell counts and the presence of clonal B cells on peripheral blood flow-cytometry. Kaplan-Meier method was used for survival analysis. Results: Twenty patients with L-DLBCL were identified with a median follow-up of 32.5 months (CI95%, 32.5-NR). Median age at initial diagnosis was 62 (45-80) years. 60% (12/20) were male; 90% (18/20) were Caucasian. Pathologically, 90% (18/20) had DLBCL and 10% (2/20) had high-grade B cell lymphoma (HGBCL) with intermediate features between DLBCL and Burkitt lymphoma. By Hans criteria, 58% (11/19) had germinal center B-cell DLBCL (GCB-DLBCL) and 42% (8/19) had non-germinal center B-cell DLBCL (non-GCB-DLBCL). 40% (8/20) had transformed DLBCL (t-DLBCL); 36% (5/14) had double-hit lymphoma (DHL) by FISH analysis. LI was present in 55% (11/20) at initial diagnosis and 45% (9/20) at relapse. Median WBC was 39.5/ul (range, 4.3-121) with median absolute lymphocyte count of 25 k/ul (range, 0.7-117). Immunophenotypically, the leukemic lymphoma cells expressed CD19, CD20, and CD79a. Bone marrow involvement and pancytopenia were documented in all patients with a median bone marrow cellularity of 80%. Other extranodal sites of involvement with LI included spleen (65%;13/20), liver (20%;4/20), breast and soft tissue (20%;4/20), bladder or kidneys (10%;2/20), skeleton (10%;2/20), and myocardium (5%;1/20). 65% (13/20) had B-symptoms. All patients had LDH elevation (UNL 222 U/L) with a median of 2125 U/L (range, 308-10,760). 45% (5/11) of patients with LI at initial diagnosis had CNS involvement on relapse/progression. All patients with LI at initial diagnosis received anthracycline-based chemoimmunotherapy with or without CNS prophylaxis. Patients with LI at relapse had had a median of 2 prior treatments (range, 1-5) before LI. Median overall survival (OS) for the whole group was 9 months (CI 95%; 5.8-11.8). There were no long-term survivors. Median progression free survival after LI was 4.7 months (CI95%; 0.8-7.6) in the newly diagnosed group and 3 months (CI95%; 0.9-20) in the relapsed group. 90% (18/20) died due to their progressive disease. Cell of origin, DHL status, or newly diagnosed vs. relapsed status did not have a significant impact on OS in patients with L-DLBCL. Conclusions: Leukemic involvement at any time during the course of DLBCL is associated with poor prognosis. It also appears to be a major risk factor for CNS relapse. It is most frequently associated with DHL and t-DLBCL. Novel therapeutic approaches at the time of initial therapy need to be developed for L-DLBCL.

We report a male patient who developed eight different cancers between ages 57 and 64. BRAF p.V600E mutation was detected in Langerhans cell histiocytosis, chronic lymphocytic leukemia, histiocytic sarcoma, melanoma, and adenocarcinoma of the lung. It was not detected in multiple myeloma, basal cell carcinoma, and papillary thyroid cancer. BRAF p.V600E was not detected in normal skin tissue biopsy indicating that BRAF V600E was a somatic mutation affecting cancer cells. The presence of eight different cancers with five of them positive for BRAF p.V600E in a single patient is unprecedented. This type of BRAF p.V600E-associated poly-neoplastic syndrome has never been reported in the medical literature.

AbstractEBV‐positive HHV8‐negative EBL is part of the spectrum of EBV‐positive diffuse large B‐cell lymphoma NOS. This entity can be labeled as primary age‐related EBV‐associated EBL and appears to respond well to rituximab and thoracentesis.