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The impact of high body-mass index on cancer mortality in the United States: An emerging public health challenge.

10626 Background: Obesity prevalence has increased markedly in the United States, yet the contribution of high body-mass index (BMI) to age-standardized mortality rates (ASMR) across cancer types, sex, and age groups over three decades remains poorly defined. We evaluated temporal trends in BMI-associated ASMR to identify cancers and populations most affected and inform prevention and equity-focused strategies. Methods: Using Global Burden of Disease (GBD) 2023 data, we extracted U.S. mortality estimates attributable to high BMI for neoplasms overall and selected cancer types from 1990-2023. BMI-associated ASMRs were compared by cancer type and sex, alongside age-specific rates for adults aged 20–54 years and all-age estimates. Age-standardized rates were used to distinguish changes in risk from demographic aging, while age-specific analyses assessed early-onset burden. Results: Between 1990-2023, BMI-attributable cancer mortality among adults aged 20–54 years increased by 44% (1.79 to 2.58), indicating a shift in the population-level burden toward earlier life. Overall BMI-attributable ASMR increased from 7.28 to 7.87, while all-age mortality increased from 9.15 to 14.15. Among evaluated cancers, liver, pancreatic, and uterine cancers demonstrated the largest increases in BMI-attributable ASMR. Liver cancer ASMR increased from 0.29 to 1.02 (~250%), pancreatic cancer from 0.13 to 0.40 (~200%), and uterine cancer from 1.02 to 1.74 (~70%). Early-onset BMI-attributable mortality also increased for liver (0.11 to 0.33), pancreatic (0.04 to 0.12), and colon cancer (0.53 to 0.90). Male predominance was observed for liver, pancreatic, kidney, and colon cancers, whereas uterine cancer accounted for the highest BMI-attributable burden among women. Marked geographic heterogeneity was observed, with the highest-to-lowest state BMI-attributable ASMR ratio of approximately 2.36 in 1990 (District of Columbia vs Hawaii) and 1.75 in 2023 (West Virginia vs Hawaii), indicating persistent but shifting geographic disparities. These patterns suggest amplification of existing cancer inequities at the population level over time. Conclusions: High BMI represents an increasingly important population-level contributor to cancer mortality burden in the U.S., with rising BMI-attributable ASMRs for metabolically associated malignancies and emerging early-onset burden. These findings underscore the importance of obesity prevention and metabolic risk reduction earlier in life as potential strategies to mitigate future cancer mortality and reduce inequities. BMI-associated cancer mortality rates by age group and sex, United States, 1990–2023. Age group / Metric Sex 1990 2023 20-54 Both 1.79 2.58 Female 1.67 2.62 Male 1.91 2.54 All ages Both 9.15 14.15 Female 11.41 16.44 Male 6.77 11.82 Age-standardized Both 7.28 7.87 Female 8.00 8.43 Male 6.29 7.20

Rates of metachronous colorectal cancer or secondary Lynch syndrome–related cancers in patients with non-metastatic colorectal cancer.

3648 Background: Lynch syndrome (LS) increases metachronous colorectal cancer (CRC) risk up to 5-fold, while extended resection surgery after initial CRC can reduce this risk. Prior work showed that pre-surgical germline genetic testing (GGT) was more likely to result in extended resections, especially for MLH1 / MSH2 carriers. We evaluated the rates of metachronous CRC following surgery, along with rates of other LS cancers following CRC diagnosis. Methods: GGT and insurance claims (Komodo Healthcare Map) data for adults with non-metastatic colon (CC) or rectal (RC) cancer and CRC surgery from 2015-25, ≥6 months of cancer-free claims pre-CRC diagnosis, ≥6 months of claims post-CRC surgery, and EPCAM / MLH1 / MSH2 / MSH6 / PMS2 GGT. Statistical tests compared metachronous CRC rates (new CRC ≥6 months post-surgery) following partial (partial/segmental colectomy or proctectomy) or extended (total colectomy or total proctocolectomy) resections by GGT result. Multivariable logistic regression modeled variables associated with metachronous CRC or other LS cancers. Results: Of 4,050 CRC patients (3,905 CC, 145 RC), 530 (13.1%) were LS-positive. 3,860 (95.3%) had partial (12.2% LS-positive) and 190 (4.7%) had extended resections (32.1% LS-positive). Post-surgery claims were available for a mean (standard deviation) of 47.7 (28.0) months. 251 (6.2%) patients with CRC had metachronous CRC post-surgery (6.1% partial vs. 8.9% extended resection, p=0.145). 282 (7.0%) patients with CRC were diagnosed with other LS cancers (54 [10.2%] LS-positive vs. 228 [6.5%] negative/variant of unknown significance (LS-negative), p=0.002). Patients with other LS cancers were diagnosed an average of 31.6 (23.9) months after initial CRC diagnosis (LS-positive: 29.0 [26.7], LS-negative: 32.2 [23.2]). The most common other LS cancer was prostate for men (80/1,822, 4.4%) and endometrial/uterine for women (55/2,228, 2.5%). Increased odds of metachronous CRC were associated with RC (compared to CC) (odds ratio [OR]: 5.1, 95% confidence interval [CI]: 3.3-8.0) and more months of available post-surgery claims (OR: 1.02, CI: 1.01-1.02). Increased odds of other LS cancers were associated with MLH1/MSH2/EPCAM carriers (compared to LS-negative) (OR: 2.0, CI: 1.3-3.1), older age (1.04, 1.03-1.05), male sex (1.6, 1.3-2.1), physician-reported Black race (1.6, 1.0-2.4) (compared to White), and more months of available post-surgery claims (1.02, 1.02-1.03). Conclusions: Patients with pathogenic variants in MLH1 / MSH2 / EPCAM had 2x higher odds of a second LS cancer diagnosis. 1 out of 10 patients with CRC and LS had a second LS cancer, and more than half (55.6%) of second diagnoses were within 2 years of initial CRC diagnosis. These findings highlight the importance of integrating genetic testing and comprehensive Lynch syndrome surveillance into patient care at the time of initial CRC diagnosis.

SWOG S2107: Randomized phase II trial of encorafenib and cetuximab with or without nivolumab for patients with previously treated MSS, <i> BRAF ^V600E </i> metastatic colorectal cancer (mCRC).

3504 Background: BRAF V600E mutations are associated with poor survival yet increased immune activation among patients (pts) with microsatellite stable (MSS) mCRC. A prior single-institution trial of the BRAF inhibitor encorafenib (E) with the anti-EGFR antibody cetuximab (C) and the anti-PD-1 antibody nivolumab (N) reported an overall response rate (ORR) of 50% and median progression-free survival (PFS) of 7.2 months in pts with MSS, BRAF V600E mCRC, promising findings relative to historical controls with E+C. Methods: In this phase II SWOG/NCTN study (NCT05308446), pts with previously treated, MSS BRAF V600E mCRC were randomized 2:1 to receive E (300 mg PO daily) + C (500 mg/m 2 IV every 2 weeks) + N (480 mg IV every 4 weeks) vs E+C only. No prior exposure to BRAF, EGFR, or immune checkpoint therapies were allowed. The primary endpoint was PFS and targeted a hazard ratio (HR) of 0.57 with a 1-sided α=0.10 and 80% power. Randomization was stratified by prior lines of therapy (1 vs 2) and Zubrod PS (0 vs 1). Treatment response was assessed every 8 weeks radiographically (RECIST 1.1). Secondary endpoints were overall survival (OS), ORR, and treatment-related adverse events (TRAE) according to CTCAE v5. Differences in PFS by treatment arm were assessed via stratified log-rank test. Results: Of 88 pts enrolled, 85 were eligible and evaluable (57 E+C+N, 28 E+C). Participant characteristics are listed in Table. Median PFS was 5.8 months (95% CI 4.0-7.8) with E+C+N and 6.3 months (95% CI 5.0-11.4; p=0.64) with E+C; HR 1.10 (95% CI 0.65-1.86). ORR was 35% for E+C+N and 32% for E+C. OS was similar between E+C+N and E+C: median 13.5 months (95% CI 11.0-18.9) vs. 11.6 months (95% CI 9.2-15.6; p=0.29); HR 0.85 (95% CI 0.47-1.52). 31 out of 57 pts (54%) had grade 3-4 TRAEs for E+C+N, vs 10 out of 28 (36%; p=0.11) for E+C; Grade 3 TRAEs occurring in &gt;10% pts treated with E+C+N included fatigue (14%) and arthralgia (11%). Conclusions: The addition of N to E+C did not improve survival outcomes in this study population of pts with pretreated MSS, BRAF V600E mCRC. Ongoing correlative studies seek to identify biomarkers associated with treatment benefit that may be applied to future efforts seeking to personalize treatment approaches for this biologically heterogeneous population. Clinical trial information: NCT05308446 . Patient demographics. E+C+N(N=57) E+C(N=28) AGE  Median 64.3 66.1 SEX (%)  Male 27 (47) 19 (68)  Females 30 (53) 9 (32) PRIOR LINES SYSTEMIC THERAPY (%)  1 40 (70) 18 (64)  2 17 (30) 10 (36) PERFORMANCE STATUS (%)  0 32 (56) 16 (57)  1 25 (44) 12 (43)

Enhanced financial assistance intervention for unmet essential needs: A prospective pilot study to improve timely cancer treatment completion.

11078 Background: Unmet essential needs, such as food, transportation, and housing insecurity, can create barriers to timely cancer treatment. Delayed or prolonged courses of definitive radiotherapy (RT) can compromise cancer outcomes like recurrence and survival. There are limited prospective data testing interventions to improve timely cancer treatment completion by meeting essential needs. Methods: We conducted a pragmatic single-arm pilot study testing an enhanced financial assistance intervention for unmet needs during RT. Eligibility criteria included adults with a cancer diagnosis and unmet social needs (via social risk screening and/or social worker evaluation) who were prescribed or undergoing a course of RT with &gt; 10 fractions remaining. Participants received standard institutional assistance (e.g., limited support for travel/lodging with strict eligibility criteria) plus the enhanced assistance intervention, including needs assessments prior to and during RT and up to $2000/patient of tailored unconditional monetary transfer via gift cards for all essential needs identified. The primary outcome was delay-free completion of RT (DFC: completing all prescribed RT fractions and delaying &lt; 5 fractions). The study was powered (power = 80%, 1-sided alpha = 0.2 for this pilot study) to detect a 10-percentage point increase in % DFC relative to a historic benchmark of 83% (based on similar patients from our institution), with required sample size of N = 33. Due to delays in gift card administration (on average ~2 weeks after consent), we also present per protocol analysis, limited to patients who had &gt; 10 fractions remaining after first receiving financial assistance. Post-hoc analyses using generalized linear mixed models evaluated percentages of delayed fractions prior to and after an individual’s receipt of financial assistance. Results: 35 met inclusion criteria and were approached, 33/35 enrolled. Participants received median assistance of $1800 ($700-2000) and had a median of 27 RT fractions after consent (range: 12-35) and 17 (3-34) after receiving assistance. In the overall cohort, 1 patient did not complete RT and 2 patients had ≥5 delayed fractions, leading to 30/33 achieving DFC (90.9%, 80% CI = 83.9 – 100), significantly higher than the 83% benchmark. In the per protocol analysis, 27/28 achieved DFC (96.4%, 80% CI = 89.7–100, P = .037). Among the 27 patients who started RT prior to receiving assistance, mixed model analysis showed more delayed fractions prior to (7.1%) vs. after (3.0%) receiving assistance (OR 2.84, 95% CI = 1.43-5.80, P = .003). Conclusions: In this prospective pilot study, a tailored enhanced financial assistance intervention for unmet essential needs led to improved delay-free completion of RT over a historic benchmark. Further analysis on patient-reported quality of life and financial toxicity will be reported in the future. Clinical trial information: NCT06582849 .

PACT-chemo: Improving chemotherapy flow, safety, and value through physician–pharmacist EHR activation at SSMC, a tertiary hospital in the Middle East.

e23317 Background: Chemotherapy order activation is a major ambulatory infusion bottleneck and a key point to intercept high-risk medication errors. Scalable physician oncology hematology clinical pharmacist partnership policy backed model for Day 2+ activation with international benchmarking remain limited. The structure aimed to achieve universal visit coverage for chemotherapy activation days, reduce infusion center delays, and quantify clinical and economic impact. Methods: Prospective quality improvement program at a tertiary oncology center (Abu Dhabi, UAE), January 2022–December 2025. PACT CHEMO implemented a standardized multistep activation workflow multi-day chemoactivation formally delegated to Oncology clinical pharmacist while Most Responsible Physician retained responsibility for future initiation and Day-1 activation, as well as multistep oncology pharmacist verification protocol, and electronic health record integration to enable parallel processing, semi-automated lab-to-pharmacy alerts, nurse to pharmacy communications, and conditional physician escalation for protocol deviations/complexity. Clinical pharmacists prospectively reviewed and activated 100% of systemic therapy visits on treatment Day 2 Plus cycles . Primary outcome was mean time from order activation to drug preparation. Secondary outcomes included prescriber acceptance, intervention clinical significance, medication error rate, cost avoidance (70–130% sensitivity), and equity. Intervention-level analysis used 10,687 interventions (Oct 2024–Oct 2025) across 10 high-risk agents; results were benchmarked against internationally reported QOPI. Results: Mean activation-to-preparation time decreased from 83.5 minutes (2022) to 40.6 minutes (2025), a 56.4% reduction, with improved reliability (SD 8.2→2.1; 74% reduction). Prescriber acceptance was 99.4% (10,623/10,687); 92.9% of accepted interventions were rated major/severe. Medication error rate declined from 6.8% to 1.7% (75% relative reduction; p &lt; 0.01). Year-3 cost avoidance was AED 2,044,650 (US$557,000), representing 48.7% of baseline operational risk, yielding +46.0% ROI and a 2.3-year payback. Acceptance did not differ by age (p = 0.98), sex (p = 0.76), or ethnicity (p = 0.84). Compared with Singapore NCCS, activation time was 40.6 vs 55 minutes and acceptance 99.4% vs 93% (p &lt; 0.001). ASCO QOPI targets across seven quality domains were met or exceeded. Sustained annual gains reduced waiting-time inequity without demographic disparities in daily care. Conclusions: An EHR-enabled physician–pharmacist activation partnership achieved sustained improvements in chemotherapy flow, safety, value, and equity, meeting or exceeding international benchmarks and supporting broader adoption across ambulatory infusion services.

BCG at home: A first-in-kind pilot trial of home-based intravesical Bacillus Calmette-Guérin delivery for high-risk non-muscle-invasive bladder cancer.

e13615 Background: Bacillus Calmette-Guérin (BCG) remains the standard intravesical therapy for high-risk non-muscle-invasive bladder cancer (NMIBC), but weekly clinic-based instillations create substantial travel, time, and indirect costs that may threaten adherence. Therefore, we proposed a pilot trial of delivering BCG at Home as a prospective, single-center pilot testing a pharmacy-to-home pathway with digital patient-reported outcome (PRO) monitoring. Methods: BCG at Home is a prospective, single-center pilot evaluating feasibility and safety of home delivery of induction BCG for treatment-naïve, high-grade T1 and/or carcinoma in situ NMIBC. Dose 1 is administered in clinic to confirm tolerability and catheterization feasibility; doses 2-6 are administered at home by Penn Medicine at Home nurses after a 3 month training and proctorship program in intravesical therapy and exposure precautions. To enable transport beyond conventional short post-preparation windows, the pharmacy prepares BCG using a closed system transfer device (CSTD); bench testing demonstrated stability and sterility for 24 hours after connection. A medical courier delivers the prepared medication to the patient’s home, where the nurse receives the delivery and performs the instillation. The primary endpoint is induction adherence (completion of all recommended doses). Secondary endpoints include PROs (EORTC QLQ-C30/QLQ-NMIBC24), satisfaction, and acute care utilization. PROs are captured before and after treatment using a conversational chatbot; domain summaries are assessed at baseline, 6 weeks, and 12 weeks. Results: The pilot began enrollment in June 2025 (planned sample size: 20). To date, eight participants have enrolled and completed induction. Median age was 76 years (range 41-88); 50% were female and 25% were Black/African American. Participants lived a mean of 30 miles from the treating facility. Forty home instillations were delivered, and all participants completed all recommended induction doses (100% adherence). Median nurse time in the home was 40 minutes. Five episodes of hematuria were self-limited; one urinary tract infection resolved with antibiotics. Self-efficacy improved from a median of 3 pre-treatment to 7 post-treatment. The median COST-FACIT score was 30 (scale 1-44). Mean EORTC QLQ-C30 global health status was 71 (0-100). EORTC QLQ-NMIBC24 averages showed urinary symptoms rising during induction (23 at baseline to 30 at 6 weeks) with improvement by 12 weeks (18) and future worries decreasing (33 to 25); intravesical treatment issues remained low (5 to 2). Conclusions: BCG at Home is, to our knowledge, the first prospective trial to administer intravesical BCG in the home setting using a standardized pharmacy-to-home pathway. Early results support feasibility, complete adherence, and an acceptable short-term safety profile. Clinical trial information: 07048496 .

Survival outcomes with modern first-line systemic therapy in advanced hepatocellular carcinoma: A systematic review and meta-analysis.

e16218 Background: First-line systemic therapy for advanced hepatocellular carcinoma (HCC) has evolved from tyrosine kinase inhibitor (TKI) monotherapy to immune checkpoint inhibitor (ICI)–based strategies, including PD-1/PD-L1 inhibitors combined with anti-VEGF therapy and dual checkpoint blockade. We conducted a systematic review and meta-analysis to evaluate survival outcomes across contemporary first-line systemic regimens for advanced HCC. Methods: PubMed, Scopus, and Web of Science were searched for phase II–III studies evaluating first-line systemic therapy in advanced or unresectable HCC. Regimens included PD-1/PD-L1 inhibitors, CTLA-4 blockade, TKIs, anti-VEGF therapy, and investigational immunotherapy combinations, including TIGIT-based approaches. The primary endpoint was overall survival (OS); progression-free survival (PFS) was a secondary endpoint. Comparative outcomes were summarized as hazard ratios (HRs) with 95% confidence intervals (CIs), and pooled using random-effects models when available. Prespecified subgroup analyses were performed by regimen class. Single-arm studies and indirect comparisons were included in qualitative synthesis but excluded from pooled analyses. Heterogeneity was assessed using the I² statistic. Results: Fourteen studies met inclusion criteria, encompassing IO–VEGF combinations, dual checkpoint blockade, PD-1/PD-L1 monotherapy, TKIs, VEGF/EGFR-targeted strategies, and emerging investigational TIGIT-containing regimens. Comparative randomized trials contributed to pooled OS estimates, which favored experimental therapy over control within defined regimen classes, with heterogeneity reflecting treatment and design variability. PFS outcomes were synthesized using comparative HRs when available and summarized descriptively otherwise. Among single-arm studies, median PFS ranged from 4.0 months (pembrolizumab; 95% CI, 2–8) to 9.4 months (envafolimab plus lenvatinib; 95% CI, 1.6–15.6), with a 6-month PFS rate of 56.7% for envafolimab plus lenvatinib. In the ALTER-0802 phase II study of anlotinib, 24-week PFS rates were 54.2% (95% CI, 32.4–71.7) in TKI-naïve patients and 46.6% (95% CI, 24.4–66.2) in previously treated patients. Conclusions: Modern first-line systemic therapies for advanced HCC demonstrate favorable survival outcomes compared with control treatments within specific regimen classes, particularly among combination strategies. Variability across therapeutic approaches highlights the importance of biomarker-informed treatment selection and optimized sequencing. Together, these findings support a personalized first-line treatment approach informed by clinical and emerging biomarker data, while highlighting the need for biomarker-driven trials to optimize sequencing of combination therapies.

Neurological adverse events related to immune checkpoint inhibitors in cancer treatment: A systematic review and meta-analysis of clinical trials.

e14569 Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment with significant improvements in survival and recurrence rates among several cancer types. However, their increasing use was accompanied by several case reports and series describing their neurological adverse events. We conducted this systematic review and meta-analysis to estimate the prevalence of neurological adverse events (NAEs) among ICI clinical trials. Methods: We searched PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) on 11/25/2025 using ICI and clinical trial as keywords along with their related MeSH terms. The inclusion criteria involved clinical trials investigating the efficacy or safety of any ICI as the only systemic therapy among never treated patients with cancer. To eliminate the impact of other systemic therapy, trials that used ICI as an adjuvant to another systemic treatment or included patients previously treated with any systemic therapy other than ICI were excluded. Prevalence of NAEs and 95% confidence intervals (95%CI) were used as the effect measures in the analysis. Subgroup analyses were performed by type of cancer and number of ICIs used in the trial. Results: We included a total of 8,826 patients with cancer from 31 clinical trials. The pooled prevalence of neurological adverse events was 1.78 ×10 -3 % (95%CI: 1.06×10 -3 %-2.78 ×10 -3 %). There was no significant difference in the prevalence of neurological side effects between trials that used one ICI (1.83×10 -3 % ; 95%CI: 0.81×10 -3 %-3.22 ×10 -3 %) compared to those that used two ICIs (0.90×10 -3 % ; 95%CI: 0.01×10 -3 %-2.64×10 -3 %). Furthermore, no significant difference was found in the prevalence among patients with hepatocellular carcinoma (1.20; 95%CI: 0.01-3.67), non-small cell lung carcinoma (1.83×10 -3 %; 95%CI: 0.01x10 -3 %-6.0×10 -3 %), or melanoma (1.16×10 -3 %; 95%CI: 0.22×10 -3 %-2.71×10 -3 %). The most common neurological adverse events were peripheral neuropathy (1.34×10 -3 %; 95%CI: 0.61 ×10 -3 %-2.3×10 -3 %), myositis (0.78 ×10 -3 %; 95%CI: 0.29×10 -3 %-1.49 ×10 -3 %), aseptic meningitis (0.71×10 -3 %; 95%CI: 0.25×10 -3 %-1.40×10 -3 %), autoimmune demyelinating polyneuropathy (0.66×10 -3 %; 95%CI: 0.21×10 -3 %-1.32×10 -3 %), epilepsy (0.66 ×10 -3 %; 95%CI: 0.21×10 -3 %-1.32×10 -3 %) and myasthenia gravis (0.66×10 -3 %; 95%CI: 0.21×10 -3 %-1.32×10 -3 %). Conclusions: All in all, the prevalence of ICI related neurological adverse events among patients with cancer is low and estimated at 1 in 5000 patients. Individual data analysis of ICI clinical trials is needed to elucidate the factors associated with ICI related neurological adverse events.

Ultrasensitive ctDNA detection for relapse and response prediction in melanoma patients treated with immunotherapy.

9572 Background: Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in melanoma and are now standard of care in advanced and adjuvant settings. However, substantial toxicities remain, and up to 50% of patients derive no clinical benefit. Conventional clinicopathological factors lack sufficient precision for risk stratification, resulting in under- and overtreatment. Circulating tumor DNA (ctDNA) has emerged as a highly specific biomarker for molecular residual disease (MRD) detection, enabling real-time, minimally invasive monitoring to guide personalized ICI strategies. Methods: We analyzed 847 plasma timepoints from 98 melanoma patients treated with ICI in either the unresectable advanced (metastatic) setting (25 patients) or adjuvant setting following complete resection of the primary and/or loco-regional metastases (73 patients). Plasma samples were analyzed using NeXT Personal, a whole-genome-sequencing-based tumor-informed assay designed to track up to 1,800 patient-specific variants. This ultrasensitive liquid biopsy approach achieves detection limits of down to ~1 part per million (PPM) at high specificity (&gt;99.9%), enabling identification of MRD and early molecular relapse that may inform timely therapeutic intervention. Results: Baseline ctDNA was detected in 100% of 25 patients with unresectable melanoma. Within this group, an early molecular response defined by a ≥30% decrease in ctDNA by cycle 3 predicted an 80% reduction in the risk of progression or death (PFS HR 0.2, P=0.01; OS HR 0.2, P=0.03). In the adjuvant cohort, landmark ctDNA positivity at 3 months post-surgery prior to immunotherapy, was 35% and identified patients with significantly inferior outcomes, with a &gt;3-fold increase for the risk of distant metastasis or death (DMFS HR 3.8, P=4.9510−3; OS HR 4.1, P=3.61×10−3). Longitudinal monitoring further established that any ≥20% increase in ctDNA during adjuvant treatment was highly prognostic of poor survival (DMFS HR 3.0, P=0.01; OS HR 3.5, P=0.02). These molecular increases identified recurrences a median of 212 days prior to radiographic detection. The clinical necessity of ultrasensitive assays was underscored by the fact that 71% of these early detections occurred at ultra-low levels below 100 PPM. Real-time variant tracking revealed mutations druggable mutations such as BRAF V600E. Conclusions: Detection of MRD with PPM sensitivity represents a major advance in treatment monitoring for both unresectable and completely resected melanoma. Early on-treatment ctDNA decreases identify responders in advanced disease, while postoperative ctDNA positivity identifies adjuvant patients at highest relapse risk. Early MRD-based detection of loco-regional or distant relapse enables timely adaptation of therapeutic strategies.

Terminal admission phenotype in acute myeloid leukemia: A national analysis of inpatient care intensity (NIS 2016–2023).

e23207 Background: Inpatient mortality among patients with acute myeloid leukemia (AML) remains substantial; however, terminal hospitalizations are poorly characterized in administrative data. Inpatient death alone does not distinguish expected end-of-life trajectories from potentially avoidable, high-intensity care. This study aims to define and evaluate a terminal hospitalization phenotype in AML based on inpatient death with markers of high-intensity, life-sustaining care. Methods: A retrospective, survey-weighted analysis of the National Inpatient Sample (2016–2023) was performed. Adult AML hospitalizations were identified using ICD-10-CM C92.0*. Terminal admission was defined as inpatient death with ICU-level care proxies, including invasive mechanical ventilation, dialysis, or shock. Primary outcome was terminal admission prevalence. Secondary outcomes included care intensity, length of stay (LOS), and costs. Multivariable survey-weighted logistic regression evaluated factors associated with terminal admissions. Results: Among 484,550 national AML hospitalizations, 8.7% resulted in in-hospital death. Notably, 43.7% of these deaths occurred in the setting in the ICU level of life-sustaining care, defining a terminal admission phenotype. Although terminal admissions accounted for only 3.8% of all AML hospitalizations, they represented a disproportionate concentration of care intensity. Across all AML hospitalizations, mechanical ventilation occurred in 4.9%, dialysis in 2.1%, and shock in 2.0%. Among the high-risk subgroup of patients who died, care intensity was markedly concentrated: 37.9% received mechanical ventilation, 9.7% dialysis, and 10.9% experienced shock during the terminal hospitalization. Mean LOS was 11.7 days overall (95% CI 11.5–11.9) and 13.4 days among deaths (95% CI 12.9–13.9). Mean hospitalization cost was $47,114 overall (95% CI $44,611–$49,618) and $73,562 among deaths (95% CI $67,115–$80,009). Mean charges among deaths reached $255,771 (95% CI $239,769–$271,773). After adjustment, terminal admissions were independently associated with weekend admission (adjusted odds ratio [aOR] 1.34, 95% CI 1.22–1.46) and urban teaching hospitals (aOR 2.20, 95% CI 1.65–2.93). Increasing age (aOR 1.01 per year, 95% CI 1.00–1.01) and male sex were also associated with higher odds of terminal admission. Conclusions: Over two in five inpatient AML deaths occur in the setting of high-intensity life-sustaining care, defining a distinct terminal phenotype requiring substantial resources. This nationally representative analysis moves beyond mortality alone to identify a reproducible marker of end-of-life care intensity in AML. The terminal admission phenotype provides a scalable framework for evaluating care delivery patterns, hospital variation, and opportunities to better align inpatient AML care with prognosis and goals.

Learning under uncertainty—Conservation of populations and persistence of dynamic resources through adaptive switching feedback controllers

In the context of conservation under uncertainty, the problem of designing and analysing adaptive switching feedback control schemes for systems of positive difference equations is considered. The aim is to ensure persistence of the population, corresponding to the zero equilibrium of the closed-loop control system being unstable in a certain sense. A robust control approach is adopted, where multiple discrete control actions are available, corresponding to different management strategies or policies. However, the exact effect of each strategy is assumed to be uncertain. Based on principles from both positive dynamical systems and simple adaptive feedback control, a suite of control schemes is proposed from which a destabilising (persistent) strategy is selected based on a switching process, should such a strategy exist. We demonstrate that the switching rules can be augmented with several variations, altering the transient behaviour and thus tailoring them to the particular requirements of the user. The current work substantially builds upon and enhances earlier results of the authors, by establishing key and quite general hypotheses of the underlying model and control scheme to ensure persistence, so that the results are applicable to a wide range of model types. The proposed control schemes are illustrated with examples.

Harnessing Antiaromatic Perturbation in Multiple‑Resonance TADF Emitter for Simultaneous Bathochromic Shift and Spectral Narrowing

ABSTRACT Narrowband multiple‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters are pivotal for wide‐color‐gamut displays, yet they often encounter an inherent trade‐off between emission redshift and spectral broadening. In this study, we present a molecular design strategy that incorporates antiaromatic four‐membered rings into a boron‐ and nitrogen‐embedded MR framework to achieve aromaticity localization. This approach enhances the aromaticity localization within the MR skeleton, effectively suppressing vibrational coupling and narrowing the emission spectrum, while simultaneously extending the π‐conjugation to induce a bathochromic shift—thereby counteracting the typical broadening that accompanies redshift. Relative to the DABNA‐1 parent molecule, the designed emitter exhibits a substantially redshifted emission maximum from 460 to 523 nm, along with a narrowed full‐width at half‐maximum (FWHM) from 27 to 16 nm. The corresponding organic light‐emitting diode (OLED) achieves a narrow FWHM of 21.5 nm with CIE coordinates of (0.26, 0.70), a maximum external quantum efficiency (EQE max ) of 36.1%, and a significantly low efficiency roll‐off. Remarkably, the device demonstrates superior operational stability with an LT90 lifetime of 1469 h at an initial luminance of 1000 cd m −2 . This work establishes a novel paradigm in molecular design for realizing long‐wavelength MR‐TADF emitters that concurrently achieve high color purity and excellent electroluminescence performance.

Design principles for high-performance hybrid solar cells: Achieving 17.13% efficiency through advanced interface engineering

Human umbilical cord mesenchymal stem cells derived exosomes enhance the therapeutic efficacy of anti-miR-10b in glioblastoma

Disruption of GxxxG motifs in pATOM36 impairs biogenesis of the mitochondrial protein translocase of the outer membrane in Trypanosoma brucei

Embedding patient priorities into clinical research: Co-developing access, drug navigation, and communication of results within a provincial precision oncology program.

e23174 Background: Patient partners in the Personalized Onco-Genomics (POG) Program’s Patient Working Group identified three priorities: equitable access to precision oncology across British Columbia (BC), improved navigation to POG-informed therapies, and patient-centered communication of genomic results. Patients cited travel, limited regional access, and tissue requirements as key barriers, especially in remote areas, and emphasized the need for understandable results, navigation support, and a centralized information hub. This initiative aimed to integrate patient-defined priorities into POG through a patient-engaged implementation model. Methods: POG established a Patient Working Group within program governance. Members completed a priority-setting survey and ranked themes by importance. In 2025, quarterly meetings with patients, clinicians, nurses, analysts, and trainees discussed lived-experience barriers and co-developed next steps with clinical and genomics teams. Discussions focused on access, therapy navigation, communication, and peer support. Patient-identified priorities were refined into action items, tracked through shared documentation, and iteratively reviewed to align patient goals with program implementation. Results: Patient-driven priorities informed several program changes. To reduce geographic inequities, POG expanded participation beyond Vancouver to additional hospital sites in BC. Workflow updates enabling use of archival tissue samples reduced new biopsy and travel needs, benefiting patients in remote and underserved regions. To improve navigation to POG-informed therapies, the Chemotherapy Resource and Information Specialist (CHRIS) role was established to link genomic findings to drug access, support clinicians, and compile real-world cases for funding advocacy. To address communication and education gaps, patients co-developed requirements for accessible, plain-language resources. Implemented tools include automated patient-specific genomic summaries, educational videos, written materials, and an updated POG website featuring multimedia content and curated links, enhancing a centralized public information hub. Conclusions: Embedding a patient working group within POG translated patient-ranked priorities—equitable access, therapy navigation, and communication of genomic results—into measurable changes across sites, workflows, and communication tools. This co-development model shows how patient-driven governance can improve precision oncology, reduce access barriers, and ensure program evolution aligns with patient needs while supporting sustainable, system-level advocacy.

Prognostic impact of digitally quantified tumor-infiltrating lymphocytes in HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitors.

1112 Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors plus endocrine therapy are the first-line treatment for hormone receptor (HR)-positive/HER2-negative metastatic breast cancer(MBC). Prognostic biomarkers are needed to guide treatment decisions. Although Tumor-infiltrating lymphocytes (TILs) have been studied in breast cancer, their prognostic value in HR+/HER2- MBC remains unclear. Therefore, we aimed to assess the prognostic value of TILs in this patient population. Methods: We retrospectively analyzed patients with HR+/HER2- MBC receiving CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) plus endocrine therapy at Gangnam Severance Hospital, Seoul, Republic of Korea, from 2017 to 2025. We included 180 of 326 treated patients who met prespecified criteria. TILs were assessed according to the International Immuno-Oncology Biomarker Working Group guidelines using the digital pathology software QuPath (v0.6.0). Stromal TILs were quantified in two representative regions of interest (ROIs; each approximately 1,000 µm wide) using the formula TIL (%) = [immune cell area / (annotation area – tumor cell area)] × 100, and the values were averaged across ROIs. Patients were classified into high- and low-TIL groups using the median TIL as the cutoff. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan-Meier analyses and log-rank tests. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Results: Among 180 patients, the median age was 53.9 years (range, 28.0–87.5) and the median follow-up was 32.4 months (range, 4.6–104.4). Median PFS was 23.2 months (98 progression events) and median OS was 32.4 months (28 death events). Using a median TIL cutoff of 7.31%, 90 patients were classified into each group. The high-TIL group showed numerically longer PFS than the low-TIL group (median 35.2 vs. 28.1 months, 95% confidence interval [CI] 25.6–not reached[NR] vs. 22.7–42.0; log-rank p=0.15; HR 0.75, 95% CI 0.50–1.12; Cox p=0.154). For OS, the high-TIL group had significantly longer survival (median NR in both groups; log-rank p=0.028; HR 0.41, 95% CI 0.18–0.93; Cox p=0.033). In the primary breast tumor subset (n=111), similar trends were observed for PFS (median 42.2 vs 27.6 months; 95% CI 24.8–NR vs 19.3–61.4; log-rank p=0.072; HR 0.62, 95% CI 0.36–1.05; Cox p=0.075) and OS (median NR in both groups; log-rank p=0.073; HR 0.41, 95% CI 0.15–1.13; Cox p=0.083). Conclusions: Higher TIL levels may be associated with more favorable outcomes in patients with HR+/HER2- MBC treated with CDK4/6 inhibitor-based therapy. In contrast, patients with low TILs, who may derive less benefit, could be considered for alternative targeted therapies or chemotherapy. These findings suggest TILs may have prognostic value in this setting and warrant confirmation in further prospective, multicenter studies.

Comparative effectiveness and healthcare utilization of atezolizumab plus bevacizumab versus durvalumab plus tremelimumab in older patients with advanced hepatocellular carcinoma.

e16232 Background: Older adults constitute an increasing proportion of patients with advanced hepatocellular carcinoma (HCC) but remain underrepresented in pivotal clinical trials. Treatment selection in this population is influenced by bleeding risk, frailty, cardiovascular comorbidities, and concerns regarding immune-related toxicity. Although Atezolizumab plus Bevacizumab (AtezoBev) and Durvalumab plus Tremelimumab (DurvaTreme) are established first-line regimens, comparative real-world data in older patients are not well defined. We compared survival, tolerability, and healthcare utilization between these regimens in patients aged ≥65 years. Methods: We conducted a retrospective cohort study using the TriNetX Research Network. Patients aged ≥65 years with advanced HCC who initiated first-line AtezoBev or DurvaTreme were identified. The index date was treatment initiation. The primary outcome was overall survival (OS). Secondary outcomes included hospitalization, emergency department (ED) visits, systemic corticosteroid exposure, and gastrointestinal bleeding. Cohorts were matched 1:1 using propensity scores adjusting for age, sex, and baseline comorbidities. Kaplan–Meier methods and Cox proportional hazards models were used for survival analysis. Results: We identified 4,926 patients treated with AtezoBev and 793 treated with DurvaTreme. After propensity score matching, balanced cohorts of approximately 650 patients per group were analyzed. At 3 months, survival was higher with AtezoBev compared with DurvaTreme (84.7% vs 78.4%; HR 0.67, 95% CI 0.51–0.87, p &lt; 0.01). No significant difference in long-term OS was observed (HR 0.95, 95% CI 0.80–1.13; p = 0.55). Hospitalization occurred in 41.3% versus 38.0% (RR 1.09, 95% CI 0.83–1.43; p = 0.56). ED visits occurred in 13.4% versus 15.7% (RR 0.86, 95% CI 0.61–1.21; p = 0.37). Systemic corticosteroid exposure within 1 year was higher with DurvaTreme (50.0% vs 38.5%; p &lt; 0.01). Conclusions: Among older adults with advanced HCC, AtezoBev and DurvaTreme demonstrated comparable long-term survival in real-world practice. AtezoBev demonstrated improved early survival and numerically lower ED utilization, whereas DurvaTreme was associated with higher corticosteroid exposure. These findings highlight the importance of individualized treatment selection in older patients, incorporating clinical risk factors, toxicity profiles, and patient preferences. Limitations include the retrospective design, potential residual confounding despite matching, and limited detail in electronic health record data.

Microbiome-derived bile acids and association with dietary fiber intake to anti-tumor responses in patients with melanoma receiving immune checkpoint blockade (ICB).

9575 Background: Multiple studies have now linked high fiber diet (HFD) and outcomes with ICBs, however, the clinical actionability and mechanistic basis of this association remain incompletely defined. We investigated whether microbiome-derived metabolites may function as potentially actionable mediators of this interaction. Methods: Blood samples from two studies in patients (pts) with melanoma starting ICB were utilized: (1) longitudinal samples from the prospective Phase II DIET clinical trial (NCT04645680), in which pts with melanoma starting ICBs were randomized (2:1) to a HFD [up to 50 g fiber/day (d)] or a healthy control diet (HCD, 20 g/d) and (2) baseline samples from an observational prospective diet/microbiome ICB-treated melanoma cohort. Untargeted and targeted metabolome analysis of bile acids and tryptophan-metabolites were performed via liquid chromatography (LC)- and short-chain fatty acids (SCFAs) via gas chromatography (GC)-mass spectrometry. Circulating metabolite levels were compared between pre- and on-treatment samples in DIET trial by arm and between pts with response (R, assessed by RECIST 1.1) and no response (NR) in the observational cohort. Results: A total of 110 pts were included: 45 DIET study pts randomized to HFDI (n=30) vs HCD (n=15), and 65 pts in the observational cohort. As previously reported, response rates were numerically improved in HFD (77% vs 29% in HCD (p=0.06), in the DIET study. Untargeted metabolomics yielded 38 metabolites with statistically significant differences (nominal p&lt;0.05) in change over time in the HFD arm vs in the HCD arm, with notable reductions in glycine conjugated bile acids with HFD. Bile acid biosynthesis metabolite sets were the most significantly differentially enriched (p&lt;0.01, enrichment ratio &gt;5.0). Targeted metabolomics showed that HFD reduced secondary-to-primary bile acid ratios (deoxycholic acid [DCA] to cholic acid [CA], p=0.02) as well as glycine- and taurine-conjugated to unconjugated bile acid ratios (glycocholic acid [GCA] to CA, taurocholic acid [TCA] to CA, both p=0.03). In the observational cohort, GCA/CA and TCA/CA ratios were significantly lower in R vs NR (p=0.03 and p=0.04, respectively) whereas no difference was seen in DCA/CA ratios. SCFAs and tryptophan metabolites showed neither temporal changes in DIET trial nor response associations in the observational cohort. Conclusions: We observed that bile acid deconjugation, a key microbiome-mediated step, was reduced by an HFD intervention and inversely associated with response to ICB in an observational cohort. Building on prior work demonstrating that additional HFD-mediated secondary bile acids can impair T cell function, microbial bile acid metabolism emerges as a potential determinant of anti-tumor response targetable through HFD. Clinical trial information: NCT04645680 .

Early toxicity, healthcare utilization, and survival after CAR T-cell therapy versus bispecific antibodies in DLBCL: A propensity-matched real-world analysis.

7041 Background: CD20×CD3 bispecific antibodies and CD19-directed CAR T-cell therapies are increasingly used in relapsed/refractory DLBCL. CAR T therapy is associated with higher rates of CRS,ICANS, and cytopenias, whereas bispecific antibodies are often perceived as less toxic and more outpatient-friendly. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with DLBCL treated with bispecific antibodies (glofitamab, epcoritamab) were compared with those receiving commercial CAR T-cell therapy (tisa, liso, axi). Propensity score matching was performed on demographics, comorbidities, baseline laboratory values, and corticosteroid exposure, yielding 468 patients per cohort. Outcomes included CRS, ICANS, severe neutropenia (ANC &lt;500/µL), and thrombocytopenia (platelets &lt;50×10³/µL), as well as hospitalization and ICU admission at 1, 3, 6, and 12 months. Overall survival (OS) was assessed using Kaplan–Meier analysis with log-rank testing. Results: After matching, CAR T therapy was associated with significantly higher immune-mediated toxicity. CRS occurred more frequently with CAR T at 1 month (37.4% vs 22.4%), 3 months (39.3% vs 27.6%), 6 months (40.6% vs 28.8%), and 12 months (41.2% vs 29.7%) (all p&lt;0.001). ICANS was also more common with CAR T across all timepoints (1 month: 10.5% vs 4.9%; 12 months: 12.6% vs 7.5%). Severe neutropenia and thrombocytopenia were markedly more frequent in the CAR T cohort, with neutropenia affecting 66.7% vs 12.8% at 1 month and 71.6% vs 32.7% at 12 months (all p&lt;0.001). Despite higher toxicity, healthcare utilization was comparable. Hospitalization rates were similar between groups at 1 and 3 months (61.8% vs 66.7% and 67.1% vs 75.9%), and ICU admission rates did not differ meaningfully at any timepoint. Importantly, overall survival consistently favored CAR T therapy. Survival differences emerged early and persisted over time, with lower mortality in the CAR T cohort at 1 month (2.1% vs 9.0%), 3 months (7.7% vs 18.6%), 6 months (15.8% vs 26.7%), and 12 months (26.5% vs 35.3%), corresponding to significantly improved OS by log-rank testing at all timepoints (p&lt;0.001). Conclusions: In this large, real-world, propensity-matched analysis of relapsed/refractory DLBCL, CAR T-cell therapy was associated with substantially higher rates of CRS, ICANS, and severe cytopenias compared with bispecific antibodies. However, these toxicities did not translate into higher hospitalization or ICU utilization. Despite a less favorable early toxicity profile, CAR T therapy conferred a consistent and clinically meaningful survival advantage from early to late follow-up. Early toxicity alone should not preclude CAR T referral in appropriate candidates, underscoring the need for optimized patient selection, sequencing strategies, and supportive care.