Orusa, Ahauve

Background: Southeast Asian Americans (SEAAs) experience a disproportionately high burden of hepatocellular carcinoma (HCC), with incidence in several subgroups (i.e., Cambodian, Laotian, and Vietnamese individuals) reaching up to nine times that of non-Hispanic Whites. HCC in SEAAs is largely driven by chronic hepatitis B (HBV), hepatitis C (HCV), metabolic dysfunction–associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). Despite established screening guidelines, under-detection and delayed diagnosis remain common. Objective: To summarize epidemiologic patterns, risk factors, screening challenges, and potential interventions aimed at reducing HCC disparities among SEAAs. Design and Methods: This narrative review synthesized evidence from population based epidemiologic studies, community-based interventions, health services research, and policy analyses. Attention was given to studies reporting disaggregated SEAA subgroup data. Findings derived from SEAA specific studies were distinguished from evidence drawn from broader Asian American or general cirrhosis populations, with inferential steps explicitly noted where subgroup specific data were limited. Key Findings: HCC incidence varies widely across SEAA subgroups, with elevated HBV- and HCV-related HCC in Vietnamese, Cambodian, and Laotian communities, and increasing MASLD-related HCC including among lean individuals who fall outside many surveillance frameworks. Screening and surveillance remain suboptimal, with fewer than 30% of patients with cirrhosis receiving recommended semiannual HCC surveillance and even lower uptake among SEAAs. Barriers include low HBV/HCV screening rates, limited disease awareness, language barriers, underinsurance, provider knowledge gaps, and lack of automated EHR-based reminders. Structural challenges such as poverty, transportation barriers, and limited access to specialty care further delay diagnosis. Proposed Interventions: Culturally tailored outreach programs, bilingual navigators, and community-based screening initiatives have demonstrated improved HBV/HCV testing and linkage to care. AI-enabled EHR tools may enhance identification of high-risk patients, streamline follow-up, and increase surveillance adherence. Expanded use of non-invasive fibrosis assessment and recognition of MASLD-related risk in non-obese individuals may support earlier detection. Policy priorities include mandatory Asian subgroup data disaggregation, expanded insurance coverage, and strengthened community-level healthcare infrastructure. Conclusions: SEAAs face a substantial and preventable HCC burden. A coordinated approach combining culturally tailored community engagement, improved provider support systems, and policy reforms is essential to improving early detection and reducing HCC disparities in this diverse population.

Abstract BACKGROUND Tumor Treating Field (TTF) therapy exerts antineoplastic effects through application of alternating electrical fields that disrupt mitotic machinery and induce DNA damage and activation of cell cycle checkpoints. However, despite extensive utilization in clinical practice for the management of glioblastoma, molecular markers for TTF sensitivity have proven elusive. METHODS To assess impact of molecular alterations on TTF response, we evaluated our institutional cohort of IDH wild type glioblastomas (n=449) for whom chromosomal microarray data was available. RESULTS A total of 142 patients were found to have undergone TTF treatment (31.6%) with improved overall survival (OS) (p=0.0049, univariate analysis). We assessed TTF treatment responses when stratified by alterations in the MDM2/4-TP53 axis, as well as the CDK4/6-RB1 axis, given well-described roles for these pathways on cellular responses to DNA damage and mitotic stressors. On univariate analysis, MDM2/4 amplified tumors treated with TTFs demonstrated significantly improved OS compared to untreated tumors (p=0.0012), and while MDM2/4-unaltered, TP53 intact tumors showed OS benefit from TTFs (p=0.0192), TP53-altered tumors did not demonstrate such benefit (p=0.6591). We confirmed these findings with multivariate Cox regression after adjusting for age and sex, where TTF therapy improved OS in MDM2/4 amplified tumors (HR 0.3881, p=0.0062) and a signal towards improved OS was seen in TP53 intact tumors (HR 0.7552, p=0.0509) but no such benefit was seen in TP53-altered tumors (HR 1.0025, p=0.9916). TTF therapy appeared to demonstrate improved OS in CDK4/6 amplified tumors (p=0.0116) on univariate analysis, with continued signal towards this effect on multivariate Cox regression (HR 0.5975, p=0.0870). CONCLUSIONS TP53 intact status and MDM2/4 amplification may represent previously unappreciated molecular markers for sensitivity to TTF therapy in IDH wild type glioblastoma. Confirmatory work with multi-institutional collaborations and evaluation of other potential prognostic factors are currently underway.

Abstract BACKGROUND Chromosomal instability is a well-recognized hallmark of tumorigenesis. However, it is not known how markers for chromosomal instability, such as total distance of DNA altered or total copy number variations (CNV), affect survival, particularly in IDH wild type glioblastoma. Additionally, whether alterations in pathways that impact cellular responses to chromosomal instability, such as the TP53 or RB1 axis, influence survival, similarly remain poorly understood. METHODS To better characterize potential prognostic impact of markers of chromosomal instability on patient outcomes, we assessed the Mayo Clinic cohort of IDH wild type glioblastomas (n=449) for whom chromosomal microarray data was available. RESULTS We found that while total distance of DNA altered on microarray analysis was not associated with overall survival (OS) (p=0.4030, univariate analysis), the least altered tumors (stratified by quartiles) when assessed by numbers of CNVs demonstrated improved OS (p=0.0057, univariate analysis). We next evaluated alterations in the MDM2/4-TP53 signaling axis, as well as the CDKN2A/B-CDK4/6-RB1 axis, as both amplifications and losses impacting these pathways have been well characterized in adult diffuse gliomas. While TP53 status was not predictive of OS (p=0.1504, univariate analysis), amplification of MDM2 or MDM4 was predictive of decreased OS (p=0.0071, univariate analysis). We also found that tumors without alterations in the CDKN2A/B-CDK4/6-RB1 axis had improved OS when compared to altered tumors (p<0.0001, univariate analysis). Multivariate Cox regression analysis, adjusting for age and sex, confirmed prognostic impact of MDM2/4 amplification status (HR 1.4090, p=0.0370) and CNV status (HR 0.6798, p=0.00312) on OS. CONCLUSIONS CNV status and MDM2/4 amplification represent previously unappreciated molecular markers for prognostication in IDH wild type glioblastoma. Further work is underway to confirm our findings through multi-institutional collaborations and to account for additional potential prognostic factors.

e13718 Background: Oncology has evolved in the cyber era of medicine. The 21 st Century Cures Act mandated patient access to medical data (tests, provider notes) via patient portals connected to EHRs in order to facilitate patient engagement. Furthermore, the COVID-19 pandemic rapidly transformed patients’ interactions with portals by increasing reliance on telehealth and portal messaging. This shift has been well-documented in primary care, and emerging research suggests similar trends in oncology. More information is needed regarding how this has evolved post-pandemic. We present single academic institution real-world data (RWD) describing ongoing changes in patient messages and telephone calls in oncology. Methods: We quantified the changes (2019-2024) within oncology at Mayo Clinic Rochester campus including all care team, provider, nursing, and pharmacist visits, patient portal medical advice requests, patient calls, and messages sent to patients per year using Epic's SlicerDicer™ tool. Results: Patient visits/year dipped (-0.2%) from 2019 to 2020, but increased steadily from 2021 forward (Table 1). Patient portal advice requests increased significantly faster (Table 1); from 2019 to 2024, visits /year increased by 40%, while the number of advice requests increased by 131%. Patient calls/year increased more modestly (64%), while the number of messages sent to patients increased by 163% over this time. Conclusions: The transparency allowed by the Cures Act coupled with the impact of the pandemic has empowered patients to engage in their oncology care more proactively through the EHR. Patient-initiated portal messaging is increasing, with messages sent to patients from the oncology department similarly rising. Patient call volumes are also growing despite EHR messaging. Further research is necessary to better understand patterns of EHR use in oncology and explore ways to reduce clinician burnout that may arise from responding to this increased communication volume, as well as to understand the impact on patient satisfaction and outcomes. Changes in patient volume compared to patient calls and EHR messaging over time. Year Total Patient Visits Change in Patient Visits from Prior Year (%) Total Patient Medical Advice Messages Change in Patient Medical Advice Message Volume from Prior Year (%) Total Patient Calls Change in Patient Call Volume from Prior Year (%) Messages Sent to Patients Change in Patient Messages Sent to Patients from Prior Year (%) 2019 62,440 n/a 173,177 n/a 195,143 n/a 99,974 n/a 2020 61,959 -0.7 218,976 +26.5 240,833 +23.4 135,044 +35.1 2021 70,950 +14.5 276,561 +26.3 267,395 +11.0 165,293 +22.4 2022 74,961 +5.7 325,580 +17.7 263,732 -1.4 206,043 +24.7 2023 80,672 +7.6 349,756 +7.4 274,446 +4.0 214,257 +4.0 2024 87,605 +8.6 399,740 +14.3 319,963 +16.6 263,271 +22.9