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Modern Hodgkin lymphoma treatments to reduce second cancer risks: Influence of risk-adapted screening.

7053 Background: Second primary malignancies (SPMs) are the leading cause of long-term treatment-related mortality in Hodgkin Lymphoma (HL). Although substantial improvements have been made to treatments over recent decades, few studies have demonstrated reduced SPM risk, particularly following modern treatments, and how risks should inform screening. Methods: We assembled a national cohort of 7,428 women treated for HL aged <36 across England & Wales 1954-2010, with 99% complete follow-up until 2018. We analyzed SPM incidence from national cancer registry linkage. Treatment data were collated from >250 treatment centers. Standardized incidence ratios (SIRs) and Absolute Excess Risks (AERs) for SPMs were calculated, and multivariable analyses (Hazard Ratios, HR) were undertaken to assess the impact of changes in treatment and assess changing incidence trends over time. Results: Twelve hundred women (16%) developed 1,467 SPMs with mean follow-up of 22 years (range 0-62 years). Overall SIR to develop any SPM was 3.3 (95% CI 3.1-3.5), with breast cancer contributing the greatest excess risk (AER 30.8 95% CI 27.7-34.1). Radiotherapy use halved from 1954-1980 to 2000-2010 (98% to 47%) and mean dose dropped from 48Gy to 33Gy. Conversely chemotherapy use doubled from 55% to 97%, with anthracyclines used in 94% and classic alkylators in 31% of treatments in the most recent period compared with 6% and 48% respectively pre-1980. Radiotherapy conferred the greatest treatment-specific risk factor for SPMs, (SIR 3.5 95% 3.3-3.7), with a strong dose-response relationship trend (HR 1.01/Gy p<0.001), and highest relative risks seen in those treated with radiotherapy aged <15years (SIR 7.4 (95% CI 5.7-9.1). There was a 25% reduction in SPM risk from the earliest treatment period (<1990) to most recent (2000-2010) and 34% reduction in solid SPM risk (Table). The decrease in risk for SPMs became smaller and non-significant after adjusting for reduced radiotherapy use and dose (HR 0.89, p trend 0.11). There was no attenuation after adjustment for chemotherapy. Despite declining risks, risks remained significantly elevated beyond 40 years after treatment. Conclusions: Modern HL treatments are associated with a substantial reduction in SPM risks, which appears to be largely attributable to decreased radiotherapy use and dose. However large persistent excess risks, particularly for breast and lung cancers, underscore the need for targeted screening in high-risk survivors treated in more recent eras. Risk of SPMs by treatment era. SPMs & treatments Treated <1990HR (ref) Treated 1990-1999HR (95% CI) Treated 2000-2010HR (95% CI) p trend All SPMs Any treatment 1.0 0.77 (0.65-0.90 0.75 (0.57-0.99) 0.001 Adjusted for radiotherapy & dose 1.0 0.83 (0.69-1.00) 0.90 (0.63-1.28) 0.11 Solid SPMs Any treatment 1.0 0.71 (0.60-0.85) 0.66 (0.48-0.90) <0.001 Adjusted for radiotherapy & dose 1.0 0.79 (0.65-0.96) 0.81 (0.55-1.20) 0.03

Nutritional anemia and risk of critical illness among hospitalized patients with head and neck cancer.

e18131 Background: Patients with head and neck cancer frequently experience nutritional compromise related to tumor location, disease burden, and treatment effects, including dysphagia, mucositis, and decreased oral intake. These factors often coexist with systemic inflammation and chronic illness, contributing to impaired physiologic reserve during hospitalization. Nutritional anemia may capture this vulnerability, yet its relationship with inpatient clinical outcomes has not been well described in nationally representative data. Methods: We performed a retrospective cohort study using the National Inpatient Sample from 2016 to 2022. We reviewed adult hospitalizations with a principal diagnosis of head and neck cancer and coexisting nutritional anemia were identified using ICD-10 codes. The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation, length of stay, and total hospital charges adjusted to 2022 US dollars. Multivariable regression models adjusted for demographic factors, insurance status, neighborhood income quartile, comorbidity burden, and hospital characteristics. Acute in-hospital complications were not included in primary models given their likely role as intermediates along the causal pathway. Survey weights were applied to generate national estimates. Results: An estimated 189,320 hospitalizations for head and neck cancer were identified, of which 1.2 percent involved nutritional anemia. In unadjusted analyses, nutritional anemia was associated with higher in-hospital mortality. After adjustment for demographic, socioeconomic, comorbidity, and hospital characteristics, nutritional anemia was no longer independently associated with mortality. Nutritional anemia did, however, remain associated with higher odds of mechanical ventilation, longer hospital stays, and increased hospital charges. The attenuation of the mortality association after adjustment suggests that excess risk may be mediated through downstream clinical deterioration. Conclusions: Among adults hospitalized with head and neck cancer, nutritional anemia identifies patients with greater illness complexity and higher inpatient resource use. Although it was not independently associated with mortality after multivariable adjustment, nutritional anemia was associated with markers of critical illness and prolonged hospitalization. These findings support the role of nutritional anemia as a clinically meaningful marker of vulnerability and highlight the importance of early nutritional evaluation and supportive care during hospitalization.

Association between pre-diagnostic upper endoscopy and metastatic gastric cancer at diagnosis among patients from high-risk groups.

e23446 Background: Gastric cancer is frequently diagnosed at advanced stages in the United States. Although select high-risk populations may undergo upper endoscopic (EGD) evaluation prior to diagnosis, these procedures are often performed for non-surveillance indications. The relationship between pre-diagnostic EGD exposure and metastatic status at presentation remains incompletely characterized. Understanding this association may clarify real-world diagnostic pathways and inform future risk-based screening strategies. Methods: A retrospective cohort study using Epic SlicerDicer identified adults ≥18 years diagnosed with gastric adenocarcinoma at Tufts Medical Center between January 2021 and January 2026, excluding patients with prior gastric cancer. Patients with one or more risk factors for gastric cancer as defined by the 2025 AGA Clinical Practice Update were included: Asian race, Hispanic ethnicity, interpreter requirement, and prior diagnoses of Helicobacter pylori infection, gastric intestinal metaplasia, or chronic atrophic gastritis. Pre-diagnostic EGD exposure was defined as EGD performed 6–36 months before the index cancer diagnosis; procedures within 6 months were excluded to distinguish diagnostic from antecedent evaluation. Metastatic disease at diagnosis was defined by ICD-10 codes for secondary malignancy or malignant ascites. Associations were assessed using chi-square testing with calculation of odds ratios (OR) and 95% confidence intervals (CI). Results: Among 147 patients with gastric cancer and ≥1 risk factor for gastric cancer, 69 underwent EGD 6–36 months prior to diagnosis. Metastatic disease at diagnosis occurred in 19 patients (27.5%) with prior EGD exposure compared with 28 patients (35.9%) without prior EGD. Pre-diagnostic endoscopy was associated with numerically lower rates of metastatic disease, although this difference was not statistically significant (OR 0.68, 95% CI 0.34–1.35; p = 0.27). Conclusions: Among patients with gastric cancer from recognized high-risk groups, antecedent EGD exposure was associated with a lower proportion of metastatic disease at diagnosis, though statistical significance was not observed. Because endoscopy indication could not be determined, findings likely reflect a combination of symptom-driven evaluation and surveillance-related follow-up, and lead-time bias cannot be excluded. These results characterize real-world pathways preceding gastric cancer diagnosis and highlight potential opportunities to improve targeted evaluation in high-risk populations. Association between pre-diagnostic upper endoscopy exposure and metastatic status at diagnosis. Pre-diagnostic EGD (6–36 mo) Metastatic, n (%) Non-metastatic, n (%) Total Yes 19 (27.5%) 50 (72.5%) 69 No 28 (35.9%) 50 (64.1%) 78 Total 47 100 147 OR 0.68 (95% CI 0.34–1.35); p = 0.27.

Impact of immunotherapy on sotorasib toxicity in NSCLC: A real-world matched analysis.

e16184 Background: Sotorasib is a standard targeted therapy for KRAS G12C-mutated advanced NSCLC. Emerging real-world evidence suggests that sequential treatment following immune checkpoint inhibitors (ICIs) potentiates severe hepatotoxicity. We sought to quantify the specific risk of prior ICI exposure and determine if extending the washout interval reduces toxicity. Methods: We conducted a retrospective cohort study of patients with NSCLC treated with sotorasib following ICI therapy. Patients were required to have baseline AST/ALT ≤120 U/L. 1:1 propensity score matching (PSM) was done for age at index, race, gender, liver metastasis, alcohol-related disorders, liver disease, obesity, and statin use. We performed 3 parallel analyses: (1) Impact of Exposure: Any ICI exposure within 1 year (n = 458) vs. ICI-naïve patients (n = 458) (2) Impact of 6-week Washout: Sotorasib initiation < 6 weeks (n = 242) vs. > 6 weeks (n = 198) post-ICI. (3) Impact of 12-week Washout: Sotorasib < 12 weeks (n = 311) vs. > 12 weeks (n = 129) post-ICI. Outcomes were Grade ≥3 hepatotoxicity (AST/ALT > 3x ULN or Total Bilirubin > 3 mg/dL) and risk of diarrhea/colitis within 90 days. Results: In matched cohorts (n = 386/arm), prior ICI exposure significantly increased the rates of Grade ≥3 hepatotoxicity compared to ICI-naïve patients [RR 3.0; p < 0.001]. No significant difference was observed in GI toxicity rate. Among ICI-exposed patients, washout duration did not significantly alter hepatotoxicity. 6-week washout (n = 171/arm) showed no significant difference in hepatotoxicity as did the 12-week analysis (n = 113/arm). Conversely, acute initiation of sotorasib ( < 6 weeks) significantly increased diarrhea/colitis rates [RR 1.78; p = 0.03]. This signal was not significant in the 12-week analysis. Conclusions: Prior immunotherapy confers a near three-fold increase in sotorasib-induced hepatotoxicity risk, which was noted to be independent of washout interval (contrasting from prior reports) suggesting that 3-month rule for liver safety may be conservative. However, initiating sotorasib within 6 weeks of ICI was associated with a two-fold increase in the risk of colitis/diarrhea clinically justifying a 6-week washout to minimize severe gastrointestinal adverse events. Sensitivity analyses with extended follow-up (6 months) showed increased hepatotoxicity only in hyper-acute (3-week) settings, likely confounded by rapid disease progression than delayed toxicity onset. Sotorasib toxicity risks by ICI exposure and timing. Comparison Event Rate (%) RR (95% CI) p-value Prior ICI in 1year vs ICI naive Hepatotoxicity 13.2% vs. 4.4% 3 (1.76 - 5.1) <0.001 GI toxicity 14.2% vs 11.1% 1.28 (0.88 – 1.86) 0.20 <6 vs ≥6wk washout Hepatotoxicity 11.7% vs 10.5% 1.11 (0.61-2.03) 0.73 GI toxicity 18.7% vs 10.5% 1.78 (1.04 - 3.04) 0.03 <12 vs ≥12wk washout Hepatotoxicity 11.5% vs 10.6% 1.08 (0.52 - 2.27) 0.83 GI toxicity 13.3% vs 12.4% 1.07 (0.54 - 2.12) 0.84

Induction chemoimmunotherapy followed by hypofractionated radiotherapy and consolidation immunotherapy for locally advanced unresectable non–small cell lung cancer: A prospective phase II study.

8037 Background: Concurrent chemoradiotherapy followed by consolidation immunotherapy is the standard treatment for unresectable stage III LA-NSCLC; however, many patients in real-world practice are unable to complete concurrent therapy, and locoregional failure remains common. This phase II study evaluated induction chemoimmunotherapy followed by hypofractionated radiotherapy (hypo-RT) and consolidation immunotherapy to improve feasibility and disease control. Methods: Patients with newly diagnosed unresectable stage III NSCLC received 3-4 cycles of immune checkpoint inhibitors combined with platinum-based doublet chemotherapy. Patients without progression or grade ≥2 pneumonitis underwent eligibility assessment for hypo-RT based on anatomical suitability and organ-at-risk constraints. Eligible patients received definitive sequential hypo-RT (48–60 Gy in 12–15 fractions based on tumor regression) and consolidation immunotherapy when appropriate. The primary endpoint was progression-free survival (PFS) with secondary endpoints of safety and overall survival (OS). Results: Between October 2022 and October 2025, 132 patients received induction chemoimmunotherapy, and 55 underdoing hypo-RT. Median age was 70 years (range, 47–85), and 42 patients (76.4%) had squamous cell carcinoma. Programmed death-ligand 1 (PD-L1) expression ≥1% was observed in 17 patients (30.9%), with unknown PD-L1 status in 14 patients (25.5%). With a median follow-up of 20.1 (95%CI, 17.3-22.9) months, median PFS and OS were not reached. The 1- and 2-year PFS rates were 88.1% (95% CI, 78.8%–98.5%) and 58.5% (95% CI, 43.6%–77.7%), respectively; the 1- and 2-year OS rates were 100% and 77% (95% CI, 61.5%–93.7%), respectively. Isolated in-field recurrence occurred in 4 patients (7.3%). Pneumonitis was the most common acute nonhematologic toxicity, with grade 3 in 4 patients (7.3%) and grade 4 in 1 patient (1.8%). Grade 3 atelectasis occurred in 4 patients (7.3%), and grade 3 radiation esophagitis in 2 patients (3.6%). No grade 5 toxicities were observed. Conclusions: Induction chemoimmunotherapy followed by eligibility-adapted hypofractionated radiotherapy showed promising survival and locoregional control with acceptable toxicity in unresectable locally advanced NSCLC, supporting its feasibility as an alternative strategy for selected patients. Clinical trial information: NCT05784142 .

Why Is Methanol Formation Suppressed in CO ₂ Reduction Over Copper Electrocatalysts?

ABSTRACT Electrocatalytic CO 2 reduction (CO 2 RR) to produce methanol (CH 3 OH) provides a sustainable alternative to its energy‐intensive industrial synthesis. However, C 2+ species and CH 4 are typically the dominant products on prototypical Cu catalysts, with no CH 3 OH formation. Herein, employing constant‐potential explicit solvent methods, we systematically compared the thermodynamics and kinetics of C 2+ products (covering 21 possible C–C coupling paths), CH 4 , and CH 3 OH formation to uncover the origin of intrinsic suppression of CH 3 OH. Nine C–C coupling pathways exhibit significantly lower barriers than C 1 products, underscoring the facile formation of C 2+ products via multiple accessible routes beyond conventional CO–CO coupling. For C 1 products, the selectivity‐determining intermediate *CH 2 OH favors C–O bond cleavage toward CH 4 rather than hydrogenation to CH 3 OH, placing CH 3 OH formation at a kinetic disadvantage. This mechanism remains valid irrespective of Cu surface structures or applied potentials, and simulated Faradaic efficiencies (FE) align well with experimental trends, further validating our theoretical insight. Building on this, we propose a strategy that involves redirecting the pathway from *COOH to *HCOO and selectively stabilizing *CH 2 OH to steer its hydrogenation toward CH 3 OH. These findings establish a foundation for selective CH 3 OH production and highlight its synthesis as a key direction in electrocatalytic CO 2 conversion.

Nanotechnology-driven therapeutic strategies for lambert–eaton myasthenic syndrome: Emerging drug delivery and immunomodulatory approaches

Flexible Perovskite/Silicon Tandem Solar Cells Exceeding 30% Efficiency at Scale

ABSTRACT Flexible perovskite/silicon tandem solar cells (FTSCs) represent a frontier for high‐power‐density, conformable electronics, yet their commercial viability is hindered by the dual challenges of interfacial carrier recombination and mechanical delamination at the perovskite/C 60 interface. Here, we demonstrate a bimolecular piperazine‐derived interface engineering strategy that simultaneously optimizes interfacial photophysics and structural integrity. By applying a synergistic combination of piperazine dihydrochloride (PDCl) and 1‐(4‐chlorophenyl) piperazine hydrochloride ( p ‐ClPh‐PCl), we achieve complementary field‐effect passivation and in situ formation of a stabilizing low‐dimensional template. While PDCl effectively suppresses interfacial trap states and modulates band alignment for accelerated electron extraction, the p ‐ClPh‐PCl facilitates uniform C 60 growth, preventing fullerene aggregation and reinforcing interfacial adhesion. This unified molecular design enables us to reach a power conversion efficiency of 31.51% (1 cm 2 ) and a 30.31% for large‐area (17.64 cm 2 ) FTSCs, surpassing 30% PCE for the first time in FTSCs exceeding 10 cm 2 in device area. Furthermore, these devices exhibit exceptional durability, retaining 95% of their initial efficiency after 20,000 bending cycles and 650 h of continuous illumination.

Precise Microstructural and Stoichiometric Control Advances Flexible Ag ₂ Te Thin‐Film Thermoelectrics for Wearable Energy Harvesting

ABSTRACT Ag 2 Te has emerged as a promising n‐type flexible thermoelectric material for harvesting body heat in wearable electronics. However, previously reported thin films have suffered from low carrier mobility and limited power factor of < 10 µW cm −1 K −2 . Here, we present a two‐step evaporation strategy on polyimide substrates at 280°C, followed by post‐annealing at 250°C, enabling precise microstructural and stoichiometric control. This approach yields Ag 2 Te films with an exceptional room‐temperature carrier mobility of 4756 cm 2 V −1 s −1 and a power factor of 17.9 µW cm −1 K −2 , outperforming both prior thin‐film and bulk counterparts. The resulting devices exhibit excellent flexibility and rapid transient voltage response across temperature differences of 10–40 K, delivering power density up to 11 W m −2 . Integrated into robotic systems and light emitting diode arrays, these films enable thermally triggered actuation and sensing, underscoring their potential for efficient, adaptable, and self‐powered applications in next‐generation Internet of Things devices and sensor networks.

Development of HAUP-based method for measuring simultaneously linear birefringence and dichroism near diagonal position in anisotropic media

Association of acute kidney injury with in-hospital mortality and resource utilization among U.S. solid tumor hospitalizations: A National Inpatient Sample analysis, 2018–2022.

e23163 Background: Acute kidney injury (AKI) is a common and clinically significant complication among patients hospitalized with cancer. Despite its known impact on outcomes, contemporary national data evaluating the association between AKI, inpatient mortality, and healthcare resource utilization among hospitalizations primarily for solid tumors remain limited. This study aimed to assess the relationship between AKI and in-hospital mortality, length of stay, and resource utilization in cancer-related hospitalizations at a national level. Methods: A retrospective, hospitalization-level cohort study was conducted using the Healthcare Cost and Utilization Project National Inpatient Sample (NIS) from 2018 to 2022. Adult hospitalizations with a principal diagnosis of solid tumor malignancy were identified using ICD-10-CM diagnosis codes, excluding hematologic malignancies. AKI was defined by the presence of ICD-10-CM code N17* in any diagnosis position. Analyses accounted for the complex NIS survey design using discharge-level weights, hospital clustering, and stratification variables to generate nationally representative estimates. Primary outcomes included in-hospital mortality, length of stay (LOS), and total hospitalization charges. Results: An estimated 4,298,089 hospitalizations with a principal diagnosis of solid tumor malignancy were identified (95% CI 4,197,740–4,398,438), of which 13.49% (95% CI 13.35%–13.62%) were complicated by AKI. In-hospital mortality was higher among hospitalizations with AKI compared with those without AKI (12.30% [95% CI 12.08%–12.53%] vs 2.78% [95% CI 2.65%–2.91%]; absolute difference 9.52%). Hospitalizations complicated by AKI had longer mean LOS (9.71 days [95% CI 9.63–9.79]) than those without AKI (5.58 days [95% CI 5.54–5.61]; difference 4.13 days). Mean total hospitalization charges were also higher in the AKI group ($138,994 [95% CI $136,177–$141,811]) compared with hospitalizations without AKI ($93,009 [95% CI $91,489–$94,529]; difference $45,985). Conclusions: In a nationally representative sample of U.S. hospitalizations primarily for solid tumors, AKI was common and was associated with higher in-hospital mortality, longer hospitalization, and substantially greater resource utilization. These findings underscore the significant inpatient burden associated with AKI in oncology populations and support the importance of hospitalization-level risk stratification and system-based strategies aimed at mitigating kidney-related complications during cancer care.

Early indicators of prostate cancer risk in a community-based screening program in Lagos, Nigeria.

e22503 Background: Community-based prostate health screening programs are important for early identification of men at risk of prostate cancer, particularly in low- and middle-income countries. This study describes clinical findings and prostate-specific antigen (PSA) profiles from a prostate health outreach in sub-Saharan Africa. Methods: This was a cross-sectional analysis of data obtained from a community prostate screening outreach conducted in Lekki Local Council Development Area, Lagos, Nigeria. Following informed consent, 190 participants were enrolled. Prostate-specific antigen levels were analyzed and categorized as normal (<4 ng/mL) or elevated (≥4 ng/mL). Descriptive statistics were used to summarize all variables. Results: A total of 190 men were included in this study. The mean age was 52.1 ± 10.7 years. The age distribution of participants was: <50 years (46.8%), 50–59 years (30.5%), 60–69 years (12.6%), 70–79 years (7.4%), and ≥80 years (2.6%). Overall, 21 participants (11.1%) had an elevated PSA level. PSA levels were distributed as follows: <0.5–2.4 ng/mL (77.4%), 2.5–3.9 ng/mL (11.6%), 4.0–9.9 ng/mL (7.9%), and ≥10.0 ng/mL (3.1%). Participants with elevated PSA were older (median age 65 vs. 49 years) and reported more lower urinary tract symptoms (LUTS) (57.1% vs. 3%). Among participants with elevated PSA who have one or more LUTS, the most common symptoms were incomplete voiding (33.3%), straining during urination (33.3%), and intermittent urinary stream (25%). Conclusions: Approximately one in nine men screened had an elevated PSA, with higher levels occurring predominantly among older age groups. These findings support the value of community-based prostate screening initiatives for early identification of men at increased risk of prostate cancer and highlight the importance of targeting older men for prostate health interventions in urban Nigerian settings.

Evaluation and appraisal of quality indicators for end-of-life cancer care in an African context.

1517 Background: Population-based quality indicators (QIs) for end-of-life (EoL) cancer care are used to monitor and improve care delivery. Most QIs measure overuse of anticancer therapy or acute care near death and underuse of palliative care. This enables optimization of patient-centered care and healthcare resource utilization, which is especially critical in low-resource settings. Yet, QIs developed in U.S. may not be directly transferable in Africa. We evaluated EoL cancer care in Rwanda using existing QIs and appraised their relevance and feasibility in Rwanda. Methods: We conducted a retrospective chart review of all patients who died or were referred for EoL care (i.e., hospice) in 2022 in a Rwandan cancer center. Missing death dates were sought from family and community health workers. Relevance and feasibility of established QIs were appraised by the study team. QI performance was compared with published U.S. benchmarks. Results: Of 297 patients (median age 43; 16% pediatric; 61% female), the most common cancers were breast (19%), cervical (9%), acute lymphoid leukemia (9%), gastric (8%), lymphoma (7%), rectal (5%). Nearly half (46%) were stage IV at diagnosis. Most (72%) received treatment; 61% had chemotherapy. After outreach, death dates were available for 95%. Of 18 QIs validated in U.S., 5 were retained or adapted for Rwanda and 13 excluded due to contextual irrelevance or inadequate documentation. Length of stay in EoL care achieved its benchmark, while performance on other QIs was suboptimal (see Table). Conclusions: This study is among the first to evaluate and appraise established EoL cancer care QIs in Africa and highlights opportunities to reduce overuse of non-beneficial chemotherapy near death, increase use of palliative care and hospice, and adapt or develop novel EoL QIs to best fit African contexts. Comparison of EoL Care in Rwanda with published benchmarks. Rwanda Benchmark % referred for EoL care before death (n=297) 45% >55% % with length of stay in EoL care 3 days (n=114) 5% <8% % who died in a hospital (n=281) 48% <17% % starting new chemo within 30 days of death (n=297) 12% <2% % receiving chemo within 14 days of death (n=297) 17% <10% % receiving chemo within 30 days of death (n=297) 24% N/A* *Not a published benchmark; 45% in a published report from Uganda.

Intratumoral heterogeneity and genetic testing utilization in glioblastoma patients: A retrospective study at the University of Vermont Medical Center.

e14091 Background: Glioblastoma (GBM) is a primary malignant tumor characterized by intratumoral heterogeneity. Key biomarkers including isocitrate dehydrogenase (IDH) mutation status and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, as well as expanded molecular profiling, are critical to diagnosis, prognosis, and therapeutic decision-making. This study aims to investigate the number of patients who received standard and expanded genetic testing at the University of Vermont Medical Center (UVMMC) and explore differences in testing by gender and geographic residence. The study sought to identify the frequency of key mutations involving oncogenic signaling pathways, tumor suppressor function, and cell cycle regulation. Methods: A retrospective review was undertaken of electronic health records of 90 patients with GBM from 2021 to 2023 followed at UVMMC. We assessed all patients offered basic genetic testing, specifically IDH and MGMT promoter methylation, and the subset of patients who proceeded to receive expanded genetic testing. Demographic factors, including gender and geographic residence by zip code, were also assessed, with a focus on frequency of testing between patients residing in Chittenden County versus rural and New York-bordering regions. Results: Amongst 90 patients diagnosed with GBM at UVMMC, 97% of patients were offered basic genetic testing. Approximately 2% of patients demonstrated IDH mutations, consistent with predominantly IDH-wildtype GBM, while MGMT promoter methylation was observed in 39% of patients. 45% of patients proceeded to receive expanded testing, revealing TERT promoter mutations (56%) and CDKN2A/B loss (46%) as the most prevalent alterations. EGFR (39%), PTEN (33%), and TP53 alterations (33%) were also commonly identified. Less frequent mutations included MET (18%), FGFR (15%), PDGFRA/KIT/KDR (13%), NF1 (13%), and major chromosomal mutations (13%). Demographic analysis demonstrated males and females underwent standard and expanded testing at comparable rates. While basic genetic testing was performed nearly universally across urban (100%) and rural (96%) patients, those in urban settings received additional genetic testing at a significantly higher rate (58%) compared to rural patients (38%). Conclusions: Comprehensive molecular profiling in patients with GBM at UVMMC identified TERT promoter mutations and CDKN2A/B loss amongst the most common alterations. Testing rates were similar between males and females, while patients in urban areas were more likely to undergo expanded testing, likely driven by a difference in socioeconomic status and proximity to a medical center. Our findings highlight diverse genetic mutations and demographic factors influencing testing, providing opportunity to guide targeted therapies and optimize access to precision oncology.

Development of an online bone marrow transplant (BMT) unit medical education platform for internal medicine (IM) residents: A pilot study.

e21000 Background: Studies demonstrate that less than 50% of Internal Medicine (IM) residents feel comfortable caring for cancer patients. Research to address this education gap is ongoing and prior use of education modules is limited. To the best of our knowledge, this is the first standardized online education platform for IM residents rotating on a busy, metropolitan city hospital’s Bone Marrow Transplant (BMT) service. Methods: Eight online modules were created utilizing a ready accessible free online platform (i.e. Google Drive). Modules focused on high yield diagnoses, complications, and medications commonly managed on the BMT unit. Topics included: Multiple Myeloma, Acute Myeloid Leukemia/Acute Promyelocytic Leukemia, Allogeneic and Autologous Stem Cell Transplant, CAR-T therapy, Cytokine release Syndrome/Immune Effector Cell Associated Neurotoxicity, hematologic emergencies, infections in immunocompromised host, and chemotherapy basics. Prior to the start of the rotation, IM residents were emailed a 10-question pre-test. Only after completion of the pre-test were the education modules available to be reviewed at their own leisure. On the last day of their rotation, they were provided the same 10-question post-test. Knowledge assessments were created and stored in RedCap. Analysis was conducted using RedCap. Results: From January 10, 2025, to January 4, 2026, IM residents scheduled to rotate through the BMT service were recruited via email to participate in this pilot study. 76.2% of residents (n=48/63) completed the pre-test and 54% (n=34/63) completed the post test. 83.3% were PGY-2 (n=40/63) and 16.7% PGY-3 (n=8/63). 60.4% (n=29/63) reported rotating on service for the first time in their training and 39.6% (n=19) reported this was not their first time. The average pre-test score was 60.6% and improved to 67.6% on the post test. 97.1% of residents reported that this method of education was helpful. Conclusions: We present a novel standardized education curriculum for IM residents rotating on the BMT service. These data suggest an improvement in knowledge utilizing an online, readily accessible platform. Though only a modest improvement in knowledge, it is important to note that data could be confounded by clinical practice and prior experience. Given the high satisfaction ratings on this method of independent education, adaptation of this readily available learning platform into the IM residents' BMT curriculum is being implemented at our institution and can be considered for adoption by other institutions.

Racial disparities in molecular testing among patients with early-onset metastatic pancreatic ductal adenocarcinoma.

e13752 Background: Germline and somatic genetic testing are considered standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) per NCCN guidelines. Early-onset PDAC in particular has a higher likelihood of an underlying hereditary predisposition, warranting genetic evaluation as part of the diagnostic workup to inform therapeutic selection, clinical trial eligibility, and familial risk assessment. However, disparities in access to and completion of molecular testing among patients with early-onset PDAC remain understudied. Methods: We conducted a retrospective cohort study of all patients diagnosed with early-onset PDAC with metastatic disease between January 2015 and December 2025 at a single academic center. Patients were identified using ICD-10 codes, with pathologically confirmed PDAC and documented staging. Clinical, demographic, molecular, and treatment data were abstracted from the electronic health record and entered into a secure REDCap database. The primary outcomes were completion of germline and somatic tumor testing. Results: Among 95 patients with early-onset metastatic PDAC, black patients demonstrated substantially lower rates of molecular testing compared with non-black patients. Germline testing was completed in 20.0% of black patients versus 67.8% of non-black patients (OR 0.12; Fisher’s exact p = 0.048). Somatic tumor testing was also less frequent among black patients (20.0% vs 66.7%; OR 0.13; Fisher’s exact p = 0.054). When considering either germline or somatic testing, black patients were less likely to receive any molecular testing compared with non-black patients (40.0% vs 78.9%; OR 0.18; Fisher’s exact p = 0.080). Notably, no black patients received both germline and somatic testing compared with 55.6% of non-black patients (0% vs 55.6%; Fisher’s exact p = 0.021), highlighting a significant disparity in completion of comprehensive precision oncology evaluation. Conclusions: Despite NCCN guideline recommendations, black patients experienced significantly lower completion of comprehensive molecular testing in early-onset metastatic PDAC, suggesting potential gaps in delivery of precision oncology care. Although limited by sample size, these findings support efforts to standardize and more equitably deliver molecular testing for patients with early-onset PDAC. Molecular testing for early-onset pancreatic ductal adenocarcinoma, stratified by race. Race N Germline testing (%) Somatic testing (%) Both (%) White 39 69.2% 71.8% 59.0% Asian 25 52.0% 68.0% 52.0% Hispanic/Latinx 16 75.0% 50.0% 50.0% Black 5 20.0% 20.0% 0% Other 9 88.9% 77.8% 66.7%

Functional binding of PD-1 ligands: Overcoming PD-L1 staining limitations to predict therapy response.

2581 Background: Immune-checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis has improved outcomes across multiple malignancies, yet response prediction remains unreliable due to fundamental limitations of PD-L1 immunohistochemistry (IHC). As a static expression assay, PD-L1 IHC does not capture functional ligand engagement, does not account for PD-L2 contributions to PD-1 signaling, and is confounded by N-glycosylation that masks epitopes and distorts measurable abundance. These mechanistic gaps undermine biomarker accuracy and impede appropriate patient selection. To overcome these limitations, we established IcAR-PD1, a functional reporter system designed to quantify the true biological availability of PD-L1 and PD-L2 for therapeutic blockade by anti-PD-1/PD-L1 ICBs. Methods: We conducted a double-blinded retrospective study spanning multiple tumor types. IcAR-PD1 scores from patient-derived samples were correlated with clinical outcomes to anti-PD1 therapy and benchmarked against PD-L1 IHC, evaluating predictive accuracy, response probability, and duration-of-response. To define how PD-L1 N-glycosylation modulates inhibitory signaling and drug susceptibility, IcAR-PD1 was combined with a full four-site glycosylation mutation array and validated using primary CD8⁺ T-cell cytotoxicity assays. Results: IcAR-PD1 demonstrated markedly superior predictive power compared with PD-L1 IHC, achieving AUCs of 0.87–0.92 versus 0.55–0.62. High IcAR-PD1 scores aligned with >90% response probability and >3-fold longer median duration-of-response (p<0.01). Incorporation of PD-L2 activity and direct measurement of functional ligand availability explained the improved performance across tumor types. Glycosylation analysis showed that fully glycosylated PD-L1 reduced blockade efficiency, with anti-PD1 treatments markedly more sensitive to glycan status than anti-PDL1. Loss of the N35 site diminished anti-PD1 efficacy by increasing release of functional soluble PD-L1, partially affecting anti-PDL1 activity. The non-glycosylated Nx4 variant displayed enhanced susceptibility to both therapies, with a disproportionately greater improvement for anti-PD1 blockade. Conclusions: IcAR-PD1 resolves the major limitations of PD-L1 IHC by quantifying functional ligand activity, incorporating PD-L2 contribution, and revealing glycosylation-driven resistance mechanisms. These findings support IcAR-PD1 as a precise, mechanism-based biomarker for selecting patients most likely to benefit from anti-PD1 therapy.

Real-world outcomes in gastrointestinal cancer patients with targetable genomic alterations identified on serial liquid biopsy.

4238 Background: Precision oncology in gastrointestinal (GI) cancers relies on identifying targetable genomic alterations (TGA) to guide therapy. Liquid biopsy (LB) using circulating tumor DNA (ctDNA) enables minimally invasive molecular profiling and serial monitoring. As targeted therapies for GI cancers expand, repeat LB is increasingly used to detect emergent alterations. However, the clinical relevance of TGA not previously identified, particularly when detected at low variant allele fraction (VAF) where clonal burden is difficult to infer, remains unclear. Methods: GI cancer patients (pts) with >1 LB were identified from the Guardant Health InfinityAI Data Library, a real-world database of insurance claims and de-identified clinical Guardant360 records. Pts without TGA on initial LB, but gained TGA on subsequent LB were included. TGA were defined as biomarkers with cancer-type specific or pan-tumor matched targeted therapy (MTT) approvals: KRAS G12C, ERBB2 amplification (amp), BRAF V600E, IDH1, MSI-H, and NTRK/RET/FGFR2 fusions or with select approved MTT in non-GI cancers: PIK3CA and ERBB2 mutation (mut). When available, methylation-derived tumor fraction (TF), a measure of overall ctDNA burden independent of variant-specific effects, was compared with emergent TGA VAFs, excluding MSI-H and ERBB2 amp. Pts with multiple cancers or prior MTT were excluded. Cox proportional hazards model assessed associations between MTT and real-world overall survival (rwOS), adjusting for age, gender, cancer type, MSI-H status, and number of gained TGA. Results: Among 16,435 GI cancer pts with >1 LB and no initial TGA, 2,072 (12.6%) gained TGA on serial LB and were included in the overall cohort. For the survival analysis, 804 pts with gained TGA had treatment and survival data; 13.4% (108/804) received MTT. Colorectal cancer pts had the highest rate of emergent TGA with approved MTT (17%). The most common gained TGA across the overall cohort were PIK3CA mut (62%), ERBB2 mut (11.7%), BRAF V600E (9.5%), KRAS G12C (8.6%), ERBB2 amp (7%), MSI-H (4.4%), FGFR fusions (3%), and NTRK fusions (1.9%). Gained TGA were often detected at low VAF (median 0.2%; 0.01% - 41.4%), and below the TF, suggesting potential subclonal emergence. Cholangiocarcinoma and gastroesophageal cancers had the highest MTT rates (14.2% and 10%, respectively), whereas no anal cancer pts received MTT. Including pts who gained MSI-H status, 12-and 60-month rwOS from LB-detected TGA was 67% and 25% without MTT versus 78% and 44% with MTT, p<10-4; excluding MSI-H, rwOS with MTT was 82% and 34%, p=0.00025. Conclusions: Repeat LB identified TGA in a subset of GI cancer pts lacking baseline TGA, many detected at low VAF. MTT receipt for emergent TGA was associated with improved rwOS, supporting serial LB in later-line decision making. Further studies are needed to assess outcomes by TGA type, therapy, clonality, and GI cancer.

Do all patients really need hormonal screening before an adrenal biopsy?

e23070 Background: Timely tissue diagnosis is critical in patients with suspected advanced cancer, particularly as many deteriorate rapidly and may not reach treatment. Current guidelines, including NCCN, mandate exclusion of pheochromocytoma/paraganglioma (PH/PG) through hormonal screening prior to adrenal biopsy, due to concern for catecholamine-related complications. In patients with a low pretest probability of PH/PG, this requirement may introduce clinically meaningful delays that conflict with the urgency of oncologic care. We evaluated the safety of adrenal biopsy without prior hormonal screening and its impact on time to biopsy within a rapid cancer diagnostic pathway. Methods: Using the Sheba Medical Center Institutional Data Lab, OncoMind RWD, we identified patients seen at the Rapid Cancer Diagnostic Unit (2018–2025) with suspected advanced cancer and an adrenal mass considered a metastatic lesion who underwent CT-guided adrenal biopsy. Time from diagnostic intake to biopsy, diagnostic yield, and complications were recorded. To contextualize the risk of inadvertent PH/PG biopsy, we identified patients diagnosed with PH/PG at our institution outside the rapid diagnostic pathway who underwent CT-guided biopsy without documented hormonal screening. Results: Forty patients underwent adrenal biopsy within the Rapid Cancer Diagnostic Unit; 33 did not undergo hormonal screening and seven underwent screening prior to biopsy. Median age was 69 years, and 75% were male. Adrenal biopsy yielded the definitive diagnosis in 94%. Among the 33 cases without hormonal screening, 20 cases (63%) were deemed urgent due to severe symptoms, most commonly symptomatic brain metastases (n=9), severe respiratory symptoms (n=4), superior vena cava syndrome (n=3) and impending spinal cord compression (n=2). The most frequent diagnoses were non–small cell lung cancer (73%), small cell lung cancer (9%), and lymphoma (6%). No patient in either group was diagnosed with PH/PG, and no biopsy-related complications occurred. Time to biopsy was significantly longer in patients who underwent hormonal screening compared with those who did not (median 13 vs 3 days; p=0.001). Outside the rapid diagnostic unit, five patients with PH/PG underwent CT-guided biopsy (1 lung, 1 adrenal and 3 retroperitoneal) without documented hormonal screening; one experienced a hormonal-related complication. Conclusions: In patients with suspected advanced cancer and a low pretest probability of pheochromocytoma, adrenal biopsy without prior hormonal screening appears safe and substantially shortens time to diagnosis. Current guideline requirements may not fully reflect real-world oncologic urgency. In carefully selected patients managed in experienced centers, guidelines dictating for hormonal exclusion of pheochromocytoma may be over-cautious and warrant reconsideration.

Representation of rural oncology practices in quality certification programs: Insights from QOPI and CoC data.

e23291 Background: Quality certification programs like the ASCO Quality Oncology Practice Initiative (QOPI), focused on chemotherapy quality, and the American College of Surgeons Commission on Cancer (CoC) accreditation enhance cancer care standards. Rural areas, comprising ~19% of the US population, face barriers to quality oncology services due to limited resources and access. This study assesses rural practice representation in these programs to highlight opportunities for improving cancer care delivery in rural America. Methods: Data from QOPI-certified practices (n=217) and CoC-accredited programs (n=1093, after deduplication) were analyzed. Practices were categorized by Rural-Urban Commuting Area (RUCA) codes: Urban (1-3 or unclassified urban tracts), Micropolitan (4-6), Small Town (7-9), and Rural (10). Counts and percentages were calculated for each category in both datasets. Results: Rural practices were underrepresented in both programs. In QOPI, 185 (85.3%) were urban, 27 (12.4%) micropolitan, 1 (0.5%) small town, and 4 (1.8%) rural. In CoC, 947 (86.6%) were urban, 128 (11.7%) micropolitan, 8 (0.7%) small town, and 10 (0.9%) rural. Conclusions: The underrepresentation of rural oncology practices in QOPI and CoC certifications could potentially exacerbate quality disparities in cancer care. Opportunities include targeted ASCO outreach, resource support (e.g., tele-oncology, training grants), and streamlined certification processes to encourage rural participation, ultimately enhancing equitable care delivery in rural America. RUCA classification of quality-certified oncology practices. RUCA Category Description QOPI Practices n (%) CoC-Accredited Programs n (%) Urban Metropolitan core & high/low commuting (1-3) 185 (85.3) 947 (86.6) Micropolitan Micropolitan core & high/low commuting (4-6) 27 (12.4) 128 (11.7) Small Town Small town core & high/low commuting (7-9) 1 (0.5) 8 (0.7) Rural Primary flow to rural tracts (10) 4 (1.8) 10 (0.9) Total 217 (100) 1,093 (100)