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Homoleptic and Heteroleptic Carbones L1‐C‐L2
ABSTRACT Quantum chemical calculations using density functional theory at the BP86‐D3(BJ)/def2‐TZVPP level and ab initio theory at the CCSD(T)/def2‐TZVPP level have been carried out for the heteroleptic carbones L1‐C‐L2 with the ligands L1, L2 = PPh 3 , SPh 2 , CO, CS, NHC Me , CAAC Me . The complexes L1‐C‐L2 have bent equilibrium structures, with the exception of N 2 ‐C‐CS and OC‐C‐CS, which have a linear geometry. Calculations of the bond dissociation energy suggest that all heteroleptic carbones, which are considered in this work, are stable enough to be experimentally observed. A comparison of the change of the bond strength and the bond length of the heteroleptic complexes compared with the homoleptic species shows that there is no direct correlation between the changes of the bond length and the carbon‐ligand BDE, which is influenced by several factors. The detailed analysis of the carbon‐ligand interactions using the EDA‐NOCV approach shows that the Pauli repulsion often has a stronger effect on the carbon‐ligand interactions than the attractive orbital interactions. In general, weaker carbon‐ligand bonds in homoleptic complexes L1‐C‐L1 are strengthened in heteroleptic carbons L1─C─L2, while stronger bonds L2─C─L2 are weakened. However, the extent of bond weakening/bond strengthening is not quantitatively correlated, and mutual strengthening of the bonds may even occur.
Super–Foldable Glass–Like Plastic
ABSTRACT Fatigue–free foldability is required for next–generation flexible electronics. For the essential protective films, ultrathin glass is susceptible to brittle fractures, whereas plastic films have inadequate hardness and tend to crease under dynamic loading conditions. We report a glass–like plastic featuring a nano–hybrid interpenetrating network comprising a plastic nanofibrous scaffold interpenetrated by an organic–inorganic silsesquioxane@nanosilica composite, which effectively inhibits fatigue relaxation. This hybrid material possesses glass–like transparency and hardness yet exhibits plastic–like elongation and impact resistance, and rubber–like resilience. When manufactured as thin films (5–30 µm), they can withstand extreme folding cycles (500,000 cycles at a radius of curvature of 0.5 mm) without macroscopic creasing/cracking or microscopic structure/morphology changes. The superior dynamic foldability of these glass–like plastics makes them promising for future device applications.
Biosynthesized Silk‐Amyloid‐Mussel Proteins as Dissolution Recyclable Materials With Tunable Supercontraction
ABSTRACT Dissolution recycling represents a promising and potentially cost‐effective strategy for material regeneration and greenhouse gas reduction. Yet, very few polymers are practically recyclable by dissolution because strong intermolecular interactions, essential for mechanical performance, are typically incompatible with solvent disruption during dissolution. Here, we present a rational material engineering approach that balances these competing requirements to create high‐performance, dissolution‐recyclable protein‐based materials (PBMs). Using protein engineering and synthetic biology, we designed silk‐amyloid‐mussel (SAM) protein hybrids whose amorphous domains control solvent ingress, while crystalline domains maintain load‐bearing intermolecular interactions. The engineered SAM fibers, SAM HY , exhibited exceptional tensile strength (401 ± 40 MPa), toughness (124 ± 38 MJ/m −3 ), and minimal supercontraction (2.2% ± 1.9%) under high humidity (>90%), alongside full recyclability through a rapid (<1 h), energy‐efficient dissolution process using aqueous formic acid. Recycled fibers retained both structural integrity and mechanical performance over multiple recycling cycles. Moreover, the recycled SAM HY protein was reprocessed into hydrogels with strong underwater adhesion and mechanical robustness even after further recycling. These findings establish fundamental design principles for recyclable PBMs and demonstrate the feasibility of producing versatile, high‐performance, sustainable, and recyclable protein materials for a broad range of applications.
Age-stratified outcomes and racial disparities in hospitalized patients with endometrial cancer: A national analysis.
e17648 Background: The incidence of endometrial cancer is increasing in both younger and older populations, yet national age-specific data on outcomes, comorbidities and racial disparities remain limited. Methods: We performed a retrospective analysis of adult endometrial cancer hospitalizations using the National Inpatient Sample. Weighted estimates were used to generate national trends. Patients were stratified by age <50 vs >50 years. Data were queried in Google BigQuery and analyzed in R. Multivariable regression adjusted for demographic, hospital, and clinical factors; race–age interactions were assessed. Results: The cohort represented approximately 1.29 million hospitalizations, predominantly among patients aged >50 years. In-hospital mortality was higher in patients >50 than £50 years (4.98% vs 3.56%), with increased adjusted odds of death (AOR 1.44, 95% CI 1.22–1.69). Length of stay was modestly longer among older patients, while adjusted hospital charges were similar. Racial disparities varied by age (interaction p=0.020). Black patients had higher mortality than White patients in both age groups (£50: AOR 1.73; >50: AOR 1.62). Among younger patients, Asian/Pacific Islander race was associated with increased mortality (AOR 1.44), while among older patients, Hispanic ethnicity was associated with modestly higher mortality (AOR 1.09). Older patients had substantially higher cardiovascular and renal comorbidity burden (all p<0.001). Obesity was more prevalent in younger patients and inversely associated with older age (AOR 0.66). Older patients were less likely to receive inpatient chemotherapy (AOR 0.77) or blood transfusion (AOR 0.79). Conclusions: Age is a major determinant of in-hospital mortality, comorbidity burden, and treatment patterns among patients hospitalized with endometrial cancer. Persistent age-specific racial disparities underscore inequities not explained by age alone and highlight the need for age-adapted, equity-focused strategies to improve outcomes.
Impact of recent chemotherapy exposure on overall survival in patients with diffuse large B-cell lymphoma receiving bispecific antibody therapy.
e19093 Background: Diffuse large B-cell lymphoma (DLBCL) is cured with first-line chemoimmunotherapy, yet nearly 40% of patients develop relapsed/refractory (R/R) disease. Bispecific antibodies (BsAbs) such as glofitamab and epcoritamab improve outcomes in heavily pretreated R/R DLBCL and are being investigated with chemotherapy in earlier lines. The impact of chemotherapy combined with BsAbs on survival and immune toxicities is not well defined. Methods: Retrospective cohort study using de-identified electronic medical record data from the TriNetX network (data through Jan 2026). Adults ≥18, who were diagnosed with DLBCL identified via ICD-10-CM or ICD-O codes (C85.80, C83.30, 9680/3), receiving glofitamab and/or epcoritamab were grouped by receipt of chemotherapy within 90 days (index event), controlled for number of prior lines of therapy (LOT). To minimize confounding, 1:1 propensity score matching (PSM) greedy nearest neighbor, (0.1 caliper) was performed on demographics and key comorbidities. Primary endpoint was overall survival (OS) through 3 years. Secondary endpoints included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), as defined and graded per the ASTCT criteria. Results: A total of 763 patients met the inclusion criteria; including 284 who received chemotherapy within 90 days of the index event and 479 who did not. After PSM: n=252 per cohort with balanced covariates. Patients in the recent chemotherapy cohort demonstrated a significantly inferior 3-year survival probability compared to the non-chemotherapy cohort (35.7% vs. 46.3%; p = 0.0102). Recent chemotherapy was also associated with higher absolute risk of CRS grade 1–2 (8.7%; p=0.028), and grade >3 CRS (11.5%; p=0.006), as well as ICANS grade 1–2 (5.2%; p=0.038); whereas there was no difference in ICANS grade >3 (5.6% vs 4.4%; p=0.54) [Table 1]. Conclusions: Among adults with DLBCL treated with glofitamab/epcoritamab, chemotherapy within 90 days of BsAb initiation was associated with inferior 3-year OS and increased risk of CRS and ICANS. These findings potentially inform practice, optimal therapy sequencing, and pave the way for future BsAb clinical trials. Overview of recent chemotherapy vs. no chemotherapy prior to bispecific antibody therapy analysis. Category Parameter Chemotherapy Cohort Non-Chemotherapy Cohort Hazard Ratio Absolute Risk Difference p-value Cohort Before Matching 284 479 - - - Cohort After Matching 252 252 - - - Overall Survival (OS) 3-Year Survival Probability 35.67% 46.34% 1.425 - 0.0102 Safety CRS (grades 1-2) 31.75% 23.02% - 8.73% 0.0280 CRS (grades 3-5) 40.08% 28.57% - 11.5% 0.0065 ICANS (grades 1-2) 11.11% 5.95% - 5.16% 0.0382 ICANS (grades 3-5) 5.56% 4.36% - 1.19% 0.5383
CONVERGE-01 part 3: Ac-225 rosopatamab tetraxetan (CONV01-α) in Lu-PSMA-pretreated metastatic castration-resistant prostate cancer (mCRPC).
5011 Background: Ac-225 rosopatamab tetraxetan (CONV01-α, Convergent Therapeutics, Cambridge, MA), an alpha-emitting radionuclide conjugated to a PSMA-targeting monoclonal antibody, has demonstrated safety and encouraging activity in prior investigator-initiated trials (Tagawa et al. JCO 2024, Nauseef et al. AACR 2023). This phase 2 Convergent Therapeutics-sponsored multi-center CONVERGE-01 trial is evaluating the safety and efficacy of CONV01-α in pts with mCRPC, including those previously treated with Lu-PSMA-617 or -I&T (Lu-PSMA), in a dose-escalation (DE) and in an Initial Expansion (IE) cohort. Methods: Eligible pts had PSMA PET-positive (VISION criteria) mCRPC with previous exposure to ≥1 ARPI, 0-1 taxane regimens, and 1-6 cycles of Lu-PSMA. CONV01-α was administered in a single cycle of two doses (D1 & D15). Dose escalation used a BOIN design protocol (dose levels [DLs]: 45 and 55 kBq/kg, with optional IE). Primary endpoints: safety (CTCAE v5, all pts) and proportion of patients with decline in PSA of 50% or greater (PSA50) (at recommended phase 2 dose [RP2D]). Secondary endpoints: biodistribution and pharmacokinetic profile. Exploratory endpoints: bPFS, rPFS, genomic and imaging biomarkers. Enrollment into DE and IE cohorts of Part 3 was conducted between 8/2024 and 12/2025. Data within reflect current status and are subject to change with continued follow up and analysis. Results: DE was completed without DLTs in all evaluable pts (n=3 at DL45, n=6 at DL55). This was followed by an IE at both DLs (total n=22, incl pts in DE; DL45: n=12, DL55: n=10). ECOG: PS 0 - 12/22, PS 1 - 10/22. 21/22 pts were taxane exposed (19 for CRPC). Common grade (Gr) ≥3 treatment emergent adverse events (TEAEs) (occurring in >1 pt) are in shown Table. Among all TEAE at DL45: thrombocytopenia occurred in 5/12 patients (Gr 1 3/12, Gr 2 2/12), without clinical sequelae. Dry mouth was limited to Gr 1 (5/12) and Gr 2 (1/12). Among pts at who were evaluable for PSA change, 45.4% (5/11) achieved a PSA50 at DL45, with several pts experiencing ongoing PSA declines including pts who were primarily refractory to Lu-PSMA. Based on the combined safety and activity profile, DL45 was chosen as RP2D and Subsequent Expansion is underway. Conclusions: CONV01-α at the RP2D of DL45 is well-tolerated and shows promising activity in a heavily pretreated and Lu-PSMA-exposed population where there are limited therapeutic options available. Subsequent Expansion continues for pts exposed to Lu-PSMA (Part 3) at RP2D of DL45. A pivotal study is planned. Clinical trial information: NCT06549465 . Grade ≥3 TEAE. Overall n=22 DL45Grade 3 DL45Grade 4 DL55Grade 3 DL55Grade 4 n (%) n (%) n (%) n (%) n (%) Lymphopenia 8 (36) 3 (25) 0 3 (30) 2 (20) Thrombocytopenia 5 (23) 0 0 5 (50) 0 Neutropenia 4 (18) 2 (16) 0 2 (20) 0 Anemia 3 (14) 1 (8) 0 2 (20) 0 Hypotension 2 (9) 1 (8) 0 1 (10) 0
Fatal infection–associated adverse events with B-cell maturation antigen–directed therapies in multiple myeloma: A FAERS pharmacovigilance study.
e19552 Background: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies have transformed the treatment landscape for relapsed or refractory multiple myeloma. However, infectious complications remain a major source of morbidity and mortality, particularly in heavily pretreated patients. Real-world patterns of fatal infection-associated adverse events across BCMA-directed platforms have not been systematically characterized in post-marketing surveillance. Methods: We performed a retrospective pharmacovigilance analysis of the U.S. FDA Adverse Event Reporting System (FAERS) to evaluate FDA-approved BCMA-directed therapies (idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), teclistamab, elranatamab, and talquetamab) from approval through the end of 2024. Primary or secondary suspected drug reports (PS+SS) were included, with sensitivity analyses restricted to primary suspect reports. Fatal infection–associated events were defined as death with concurrent infection-related MedDRA preferred terms; secondary endpoints included fatal cytopenia, fatal cytokine release syndrome (CRS), and a serious adverse event composite. Duplicate reports were excluded using standard FAERS de-duplication methods, with primary approval-aligned analyses and calendar-window sensitivity analyses. Results: Across approval-aligned windows, 7,280 BCMA-directed adverse event reports were identified. Fatal infection–associated events were most frequently reported with teclistamab (187/2,397 reports; 612 deaths), followed by cilta-cel (71/2,366; 301 deaths), elranatamab (45/792; 157 deaths), ide-cel (23/972; 125 deaths), and talquetamab (21/753; 73 deaths). Fatal CRS-associated events were observed across agents, most commonly with cilta-cel (83) and teclistamab (74). Calendar-window sensitivity analyses (2022–2024) demonstrated consistent relative ranking, and primary-suspect-only analyses showed similar directional patterns. Conclusions: In this real-world FAERS analysis, BCMA-directed therapies exhibited distinct post-marketing safety profiles, with a substantial burden of infection-associated fatal events, particularly among bispecific antibodies. CRS- and cytopenia-associated fatalities were observed across agents, and serious non-fatal adverse events were common. These findings highlight heterogeneity in safety signals across BCMA platforms and underscore the need for continued post-marketing surveillance and agent-specific infection risk mitigation strategies in heavily pretreated multiple myeloma populations.
Variations in postoperative patient-reported outcomes (PROs) attributed to patients, surgeons, or surgical centers.
e23277 Background: Postoperative PROs reflect patients’ subjective experiences and are influenced by numerous factors, including disease severity, surgery type and complexity, duration of hospitalization, and perioperative support. By measuring variation in postoperative PROs after cancer surgery, we sought to gain insight into potentially modifiable factors at the patient, surgeon and surgical center levels that might inform interventions to improve outcomes. Methods: We studied patients who had colectomy, hysterectomy, lobectomy, or pancreaticoduodenectomy at 6 centers participating in the SIMPRO study who completed ≥1 ePRO survey. For each surgical procedure, we fit a multilevel mixed-effects regression model with random effects for patient, surgeon, and center to partition the variance in total symptom scores. The total symptom score is the summation of 12 frequently reported postoperative symptoms (range 0-34), with higher scores indicating greater symptom burden. The fixed-effects covariates in the model included patient age, sex, race, ethnicity, comorbidities, primary language, poverty, insurance, marital status and time since surgical discharge. Coefficients were estimated for fixed effects. Intraclass correlation coefficients (ICCs) were calculated from the estimated variance components to quantify the proportion of variance attributable to patients, surgeons and centers (Table). Results: A total of 3808 patients had surgery (1316 hysterectomy, 1072 colectomy, 590 lobectomy, 198 pancreaticoduodenectomy) performed by 35, 52, 23, and 13 surgeons respectively across 6 centers. Most variation in PROs was attributable to patients (75% to 78%). The proportion of variation attributable to surgeons and centers was below 3% for hysterectomy, colectomy and lobectomy. Unexplained variation was less than 26% across procedures. Conclusions: Across surgeries for four common cancers, most variation in postoperative symptoms occurred at the patient level. The unexplained (residual) variation could be due to cancer stage, postoperative complications, supportive care programs, or unmeasured confounders. Identifying and incorporating potentially modifiable factors may enable targeted interventions to reduce the postoperative symptom burden. Clinical trial information: NCT03850912 . Decomposition of variance in postoperative PROs: intraclass correlation coefficients attributable to patients, surgeons, and centers ( ICC, %) . Hysterectomy Colectomy Lobectomy Pancreaticoduodenectomy Patients 75.00% 77.67% 76.10% 77.75% Surgeons 1.90% 0.55% 2.40% Center 1.10% 1.21% 2.00% Unexplained 22.00% 20.57% 19.50% 22.25%
Phase 1 first-in-human trial of AG01, a recombinant humanized monoclonal antibody to progranulin/glycoprotein 88 (GP88) to determine the safety, tolerability, pharmacokinetics, and preliminary antitumor activity in subjects with advanced solid tumor malignancies.
TPS2669 Background: Progranulin also called GP88/PGRN plays a major role as an autocrine growth & survival factor associated with resistance to standard of care (SOC) targeted and chemo therapies in several cancers including breast cancer (BC) & non-small cell lung carcinoma (NSCLC): 1) GP88 is expressed in 80% breast invasive ductal carcinomas & is negative in normal mammary tissue; 2) GP88 tumor expression is a prognostic indicator of recurrence & survival in BC, NSCLC & prostate cancer patients (pts) 4) Elevated serum GP88 levels are present in several cancers including metastatic breast cancer (MBC), lung & prostate cancer pts compared to healthy subjects; 5) Elevated/rising GP88 serum levels in MBC pts are associated with disease progression & inferior survival. These results make GP88 an ideal therapeutic & diagnostic target in solid tumors. An anti-human PGRN/GP88 monoclonal antibody inhibiting PGRN/GP88 action was developed & expressed in CHO cells. Pharmacology, GMP manufacturing, formulation, stability studies & GLP toxicology studies in non-human primates were done. The IND application cleared by the US FDA led to the FIH AG01 study in adults with advanced solid tumors lacking effective therapies. Methods: A Phase 1 FIH dose-escalation study was designed in pts with advanced solid tumor malignancies, the study is approved by the University of Maryland IRB. AG01 monoclonal antibody is administered intravenously (IV) over 90 minutes every 14 days +/- 1 day; DLT observation period is the 1st cycle=28days, with AGO1 Dose levels of,1mg/kg, 2mg/kg, 4mg/kg, 6mg/kg, 8 mg/kg. Initially accelerated titration design (1pt/dose level) was followed by 3+3 design). Eligibility criteria include pathologically confirmed diagnosis of advanced/relapsed/refractory solid tumor malignancy; failed >=1 SOC therapy or not a candidate/declines SOC therapy, ECOG <=2, adequate organ/bone marrow function, at least 1 RECIST 1.1 measurable and/or evaluable lesion. Tumor imaging-every 2 cycles (8 weeks) is used for response assessment. Primary objective is to determine the maximum tolerated dose MTD and/or maximum administered dose MAD of AG01 in the target population. Secondary objectives are to determine the RP2D, safety, tolerability, PKs, immunogenicity (ADA) & the preliminary anti-tumor activity of AG01 in pts with advanced solid tumors. Exploratory objectives will determine PGRN/GP88 expression in tumor tissue & PGRN/ GP88 blood levels (A&G’s IHC & ELISA test). The study is ongoing; & pts are currently enrolled. A parallel prospective study investigates the association of serum GP88 in MBC pts with response to SOC therapy and progression of disease based on RECIST 1.1 criteria. These studies are supported by NCI grants R44CA224718 and CA210817. Clinical trial information: NCT05627960 .
Genetic testing in endometrial cancer (GenEC): A study on the patient experience with MSK-IMPACT.
e22635 Background: Guidelines recommend consideration of genetic testing (GT) for patients with endometrial cancer (EC); however, real-world uptake varies, and data are limited on the patient experience. We aimed to measure uptake of GT in EC and survey patient perspectives. Methods: All patients with newly diagnosed EC eligible for tumor-normal targeted sequencing via MSK-IMPACT were prospectively tracked and invited to complete surveys, regardless of GT acceptance. Clinical and demographic data were abstracted. Surveys included investigator-designed items assessing GT knowledge, GT information sources, and experiences with GT decision-making, and a validated 7-item Medical Mistrust Index (MMI). This study was approved under MSK IRB X25-012. Results: We identified 50 patients with newly diagnosed EC between 09/25/2025 – 12/5/2025. Median age was 65 years (range, 29 – 86) and 22 (44%) patients had stage I disease. Patients identified as White (n=29, 58%), Black (n=7, 14%), Asian (n=5, 10%), and other/missing (n=9, 18%), and 47 (94%) patients selected English as primary language. Overall, 43 (86%) patients consented to MSK-IMPACT GT, 4 (8%) declined, and 3 (6%) were undecided. Of 50 patients, 15 (30%) completed the survey, and all consented to GT. All patients had high school level or above education, and 2 patients reported a history of anxiety/depression. Of the 15 patients, 67% reported being somewhat or very knowledgeable about GT prior to their visit, while 33% had no prior knowledge. Patients reported getting information on GT from multiple sources, including another provider (n=7, 47%), online (n=6, 40%), family/friends (n=3, 27%), other (n=3, 20%), and social media (n=1, 7%). After the medical visit, 67% patients reported improved understanding of GT and 53% felt hopeful. Most patients felt they received enough information to decide on GT (n=11, 73%) and that GT discussions were understandable (n=11, 73%). Of the 15 respondents, 3 (20%) reported some difficulty trusting healthcare providers in a single question regarding mistrust, and the median MMI score was 2.3, indicating a low level of medical mistrust overall. MMI questions with the highest mistrust rates were about “patients have sometimes been deceived or misled by healthcare organizations” (8 patients agreed, 53%) and “healthcare organizations have sometimes done harmful experiments on patients without their knowledge” (8 patients agreed, 53%). Conclusions: There was high uptake of GT among patients with newly diagnosed EC. Most patients reported prior knowledge of GT and felt adequately informed by their provider to make decisions on GT. Although there was a low level of medical mistrust among patients who answered surveys, this represented a small group who all consented to GT. Further surveys and semi-structured interviews are ongoing to better characterize the patient experience, particularly among those who decline GT.
Differences in the receipt of recommended cardiovascular assessment among cancer survivors in the United States by atherosclerotic cardiovascular disease status.
12027 Background: Cardio-oncology guidelines recommend annual cardiovascular (CV) assessment among cancer survivors, particularly those with pre-existing atherosclerotic cardiovascular disease (ASCVD). Despite this, little is known regarding the proportion of cancer survivors receiving comprehensive CV assessment and whether certain subgroups experience suboptimal uptake. We investigated the prevalence and predictors of receiving recommended comprehensive CV assessment (i.e., cholesterol, blood pressure, blood glucose) among cancer survivors in the United States. Methods: We used self-reported, cross-sectional data from the National Health Interview Survey (2012-2018), an annual, weighted survey that uses multistage sampling and interviews to produce nationally representative estimates of the noninstitutionalized U.S. population. Adults with cancer and complete information on ASCVD status (defined as a history of myocardial infarction, stroke, coronary heart disease, or angina) were included. To examine the association between sociodemographic characteristics and lack of recommended CV assessment within the past year, adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression stratified by ASCVD status. Results: Among 16,420 cancer survivors (median age: 65.4 years; 20.1% with ASCVD), representing approximately 15.4 million survivors annually, 38.2% did not receive recommended CV assessment in the past year. Approximately 3.7% of cancer survivors (representing 566,043 individuals annually) received none of the CV assessments. Among cancer survivors with ASCVD, factors associated with increased odds of not receiving recommended CV assessment included lower (vs higher) level of education (aOR, 1.30 [95% CI, 1.01-1.65]). In cancer survivors without ASCVD, these factors included age 18-44 years (vs ≥75 years) (aOR, 1.82 [95% CI, 1.39-2.39]), low/lowest (vs high/middle) income (aOR, 1.23 [95% CI, 1.06-1.44]), uninsured (vs insured) status (aOR, 1.94 [95% CI, 1.37-2.74]), South (vs Northeast) region (aOR, 1.31 [95% CI, 1.05-1.62]), and no (vs yes) usual source of care (aOR, 2.42 [95% CI, 1.66-3.53]). Among all cancer survivors, there was a stepwise increase in receipt of CV assessment with increasing age at initial cancer diagnosis ranging from 52.7% among those aged 18-44 years at diagnosis to 68.5% among those aged 65-74 years at diagnosis (p < 0.001). Conclusions: More than 1 in 3 cancer survivors did not receive recommended annual CV assessment with several subgroups having even lower screening rates, including by age, socioeconomic status, and access to care. Improving awareness of contemporary cardio-oncology guidelines and targeting interventions during cancer survivorship are needed to increase uptake of optimal CV assessment.
Patterns of prostate-specific antigen levels for early detection of prostate cancer in sub-Saharan Africa.
e22501 Background: Prostate cancer remains a major cause of morbidity and mortality among men in sub-Saharan Africa, largely due to late presentation and limited access to screening. Prostate-specific antigen (PSA) testing is widely used for early detection; however, community-based data on PSA patterns in the region are limited. This study investigates the pattern of PSA in a community-based screening program in sub-Saharan Africa. Methods: This descriptive cross-sectional study evaluated PSA levels among men in Ilesa West, Osun State, Nigeria. Following informed consent, 81 participants were enrolled. Serum PSA levels were measured and categorized, while demographic data and lower urinary tract symptoms (LUTS) were recorded. Data were analyzed using descriptive statistics and t-tests in SPSS, with statistical significance set at p<0.05. Results: Elevated PSA levels (≥4 ng/mL) were observed in 17 men (21%). Prostate-specific antigen levels were distributed as follows: 0.5–2.4 ng/mL (65.4%), 2.5–3.9 ng/mL (13.6%), 4.0–9.9 ng/mL (18.5%), and ≥10.0 ng/mL (2.5%). The age-specific distribution of mean PSA levels was: <50 years (1.86 ± 0.31 ng/mL), 50–59 years (2.35 ± 0.46 ng/mL), 60–69 years (3.14 ± 0.50 ng/mL), 70–79 years (3.44 ± 1.37 ng/mL), and ≥80 years (8.40 ± 1.54 ng/mL). Prostate-specific antigen levels were significantly higher among men aged ≥50 years (p<0.05). Additionally, men with lower urinary tract symptoms (LUTS) had significantly higher PSA levels compared with those without symptoms (p<0.05). Conclusions: Prostate-specific antigen levels increased with age and the presence of LUTS, with over one-fifth of participants exhibiting elevated values. These findings support targeted community-based PSA screening to enhance early detection of prostate cancer in Nigeria and similar resource-limited settings.
Spatial multi-omics profiling of the primary lung microenvironment to elucidate the mechanism of osseous metastasis in advanced NSCLC through imaging mass cytometry.
e20546 Background: Non-small cell lung cancer (NSCLC) is one of the world's deadliest cancers, including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) . Osseous metastasis (OM) is common metastatic event and represents one of the direst consequences of NSCLC, portending a grim prognosis. Therefore, it’s vital to explore and improve the understanding of the etiology and pathogenesis of OM in NSCLC. Anatomizing tumor microenvironment (TME) can provide new insights into the mechanisms of osseous metastases. And the TME distinctions of advanced NSCLC with or without OM at the single-cell protein level have not been fully explored. Methods: We collected 32 tissues biopsy samples and clinical characteristics from advanced NSCLC patients with or without OM. 32 tissues were divided in to 4 groups (n = 8, each group): LUAD-NC, LUAD-OM, LUSC-NC and LUSC-OM. Then, we used imaging mass cytometry (IMC) to explore the spatial proteomic features and the factors influencing the therapeutic effect. Results: A total of 193,246 cells with spatial information revealed by IMC depicted the differences in the TME. Compared to LUSC-NC, CAFs and LYVE1 + epithelial cells showed higher abundance in LUSC-OM, while CD8 + T cells, CX3CR1 + CD4 + T cells, CX3CR1 + M1 like macrophage and E-cad - Ki67 + proliferating epithelial cells showed lower abundance. Among all CAFs, mCAFs, vCAFs, tCAFs and LYVE1 + CAFs were higher infiltration in LUSC-OM. Compared to LUAD-NC, B cells, memory CD4 + T cells, TCF1 + CD4 + T cells, memory CD8 + T cells and EMT epithelial cells showed higher abundance in LUAD-OM, while CAFs showed lower abundance. In our study, 4 LUSC-OM , 4 LUSC-NC, 2 LUAD-OM and 1 LUAD-NC received the immunotherapy plus chemotherapy treatment. The efficacy assessment of LUSC-OM is 3 SD, 1 PD, while 4 PR in LUSC-NC and 3 PR in LUAD. The main reasons for treatment failure in LUSC-OM were the low abundance of PD-L1 + , HLA-DR + and E-cad + Ki67 + proliferating epithelial cells. In patients with effective treatment, the main positive factor influencing drug efficacy was the low abundance of CX3CR1 + CD8 + T cells. Moreover, the low abundance CD8 + TRM and Treg in preoperative TME were the high-risk factors for 1-year postoperative recurrence in LUSC-NC. Conclusions: This study determines the spatial multi-omics profiling of TME components at a single-cell resolution in NSCLC with OM. The TME in LUSC-OM presents an oligoimmune state, in which CAFs and LYVE1 + epithelial cells are high risk factors for OM. And the TME in LUAD-OM presents an immune-enrichment state with EMT epithelial cells paling important role in OM. Moreover, the complex TME affect the treatment efficacy and postoperative recurrence. In a word, the comprehensive analysis may contribute to the early identification of OM in NSCLC and the development of therapeutic options.
Examining the impact of community, knowledge, and shared support on the <i>EGFR</i> -mutated lung cancer care journey: Results from the first annual EGFR Resisters Patient and Caregiver Summit.
e13781 Background: Social isolation, loneliness, and lack of shared support networks are associated with increased psychosocial burden, diminished quality of life, and suboptimal clinical outcomes in patients with cancer. Among patients with EGFR -mutated lung cancer, which comprises 10-15% of NSCLC cases diagnosed annually in the US, the need for community and shared purpose is accentuated by the niche nature of the diagnosis, pervasive societal stigma, and the uncertainty associated with a rapidly evolving paradigm. Thus, even as novel therapeutics improve survival, it is imperative that all clinical and humanistic patient needs are addressed to optimize the quality of patient-centered care. This is a principal mission of the EGFR Resisters lung cancer patient advocacy group. Methods: We conducted an informal survey of the EGFR Resisters patient and caregiver community to identify topics of greatest interest and unmet need. Based on survey themes, we designed and executed an inaugural multi-day summit, comprised of prominent keynote addresses, expert plenaries, breakouts, and dedicated opportunities for networking and community-building, in Chicago, IL from November 14-16, 2025. A total of 149 patients and caregivers attended (105 in-person, 44 virtually), as did 14 faculty members with expertise in thoracic medical oncology, surgery, radiation, research, palliative care, social work, and psychosocial wellness. We asked participants to complete a post-Summit evaluation, which employed both Likert scale and open response formats, to assess satisfaction and interest in future Summits. Results: Evaluation responses revealed the impact of the inaugural Summit and the exigent need for prospective efforts. Attendees rated their satisfaction with the Summit at 4.8 (on a 5.0 Likert scale) and indicated that the most meaningful aspects of the experience were ‘access to experts’ (39%), ‘community’ (34%), and ‘hope’ (14%). When asked to choose one word to describe the importance of the Summit, the most common responses were ‘community’ and ‘informative.’ As for areas of improvement or increased emphasis in future Summits, respondents expressed a desire for ‘more expert access,’ ‘more information on the latest data and therapeutic hot topics,’ and ‘greater opportunities for social interaction with fellow patients and caregivers.’ Conclusions: The 1 st Annual EGFR Resisters Patient and Caregiver Summit was highly rated by attendees and achieved demonstrable impact for patients living with EGFR -mutated lung cancer and their caregivers, headlined by the provision of access to experts, a summary of the latest data and treatment advances, and perhaps most profoundly, by opportunities to build community and establish shared hope. Attendee feedback will be utilized to design, develop, and deliver the 2 nd Annual Summit in 2026.
Oncological safety of oncoplastic breast conservation surgery: Experience of over a decade in early and locally advanced breast cancer from a tertiary care cancer center in India.
584 Background: Oncoplastic breast conservation surgery (O-BCS) is the norm. O-BCS improves cosmetic outcomes by restoring the shape, size, contour and symmetry of the breast and hence, quality of life. Carefully selected patients with locally advanced breast cancers (LABC) can be offered O-BCS after systemic therapy. We retrospectively evaluated our prospective dataset for oncological outcomes of patients who had O-BCS. Methods: Patients undergoing O-BCS between January 2013 and December 2023 were included. They received (neo)adjuvant chemotherapy, targeted and radiotherapy along with endocrine treatment as per standard institutional protocol and decision of Breast Cancer-Disease Management Group (BC-DMG). Clinico-pathological characteristics, type of oncoplastic procedure and follow-up details were updated from Electronic Medical Records. Data was collected and analyzed in SPSS-V29. Results: A total 1483 patients underwent O-BCS during the study period. The median age of the cohort was 45 (21- 86) years. Of 1483, 670 (45.2%) were operated upfront and 573 (38.6%) post-chemotherapy whereas 240 (16.2%) had had prior excision biopsy elsewhere. Clinically, 939 (63.3%) were early (EBC-T1/2, N0/1), 518 (34.9%) locally advanced (LABC-T3/4, N2/3) and 26 (1.8%) oligometastatic breast cancers. 1016 (68.5%) were HR+, 289 (19.5) TN and 396 (26.7%) HER2+. Median pT in upfront versus post-chemotherapy operated patients was 3 cm (0.1–8.5) and 2.7 cm (1-10) respectively. Upfront, 45.8% patients were node positive (median-2 {1-54}) and post-chemotherapy 38.3% (median-3 {1-38}). The median specimen volume was 432 cm 3 (56.8–3528) in upfront and 270 cm 3 (3–2875) in post-chemotherapy operated patients. The overall margin positive rate was 5.5% (81/1483). Of 1483, 573 (38.6%) patients had type-1 oncoplastic parenchymal closure, 377 (25.4%) had local dermo-glandular flaps, 344 (23.2%) a latissimus dorsi myo-cutaneous flap, and 189 (12.7%) bilateral reduction mammoplasty. At median follow-up of 47 months, there were 245 (16.5%) recurrences--77(5%) local and 211(14%) distant--and 153 (10.3%) deaths, and the disease-free survival (DFS) and overall survival (OS) were 84.1% and 89.5% respectively. The local recurrence rate in EBC was 4% and LABC 7.4%. The 5-year DFS was 82.1%(95%CI-79.75%-84.84%) and OS was 88.5%(95%CI-86.54%-90.46%) across the whole cohort. On Cox regression, high clinical nodal stage (HR-1.47, 95%CI-1.04-2.08, p=0.03) and histological grade 3 (HR-1.87, 95%CI-1-07-3.29, p=0.03) were predictors of poor DFS whereas type of O-BCS did not have impact on survival. Conclusions: The local recurrence rate in O-BCS was 5.3% in our setting which is reassuring considering that 1/3 rd patients had locally advanced disease. A longer follow-up of this cohort of patients and future PROMs and QOL studies will be consolidatory.
Blinded comparison of natural killer cell detection with AI-driven nanophotonic imaging versus traditional spectral flow cytometry: Development of the CB-Scout assay.
e14539 Background: Chimeric antigen receptor natural killer (CAR-NK) cells and in vivo CAR-T therapies are emerging as promising alternatives to traditional CAR-T treatments. However, concerns regarding post-treatment persistence require ultra-sensitive analytical methods to reliably detect rare circulating cells. Spectral flow cytometry (SFC) typically detects events at ~1 in 10⁴ cells but is limited by background noise and reduced phenotypic clarity at low concentrations. Next-generation sequencing (NGS) achieves sensitivities approaching 1 in 10⁶ cells but lacks single-cell phenotypic resolution. Our objective was to develop an assay combining the workflow and phenotypic resolution of SFC with the sensitivity of NGS. CB-Scout employs AI-driven nanophotonic imaging to detect rare cells at frequencies of ≤1 in 10⁶ with high phenotypic resolution. We present initial analytical validation of CB-Scout for NK cell detection compared to SFC in PBMCs spiked with NK-92 cells. Methods: Activated NK-92 cells were spiked into a single-donor HLA-mismatched PBMC sample at concentrations of 0, 70, 200, 1,200, 6,000, or 9,000 cells per ~10 M PBMCs. Split aliquots were analyzed using CB-Scout (CellsBin; Vega 1.2 system) or SFC (Cytek Aurora) by blinded operators to assess sensitivity, linearity, specificity, and functional phenotyping. Cells were stained with a multicolor panel including surface (CD45, CD3, CD56, CD16, HLA) and intracellular markers (IFN-γ, TNF-α, Granzyme B, Perforin, CD107a). Ground-truth phenotyping was established using ~100K activated NK-92 cells. Performance metrics included limit of blank (LoB), detection (LoD), and quantification (LoQ) per CLSI EP17-A2. Results: CB-Scout achieved a LoD of ~0.61 cells/M vs. ~30 cells/M for SFC and a LoB < 0.05 cells/M vs. ~1 cell/M for SFC. At the 35-cell spike level (~6.4 M PBMCs), CB-Scout maintained a ~17% CV, meeting LoQ criteria, whereas SFC required ~350 cells to achieve comparable precision. CB-Scout demonstrated higher sensitivity and specificity, with no false positives in > 21 M blank PBMCs, while SFC produced ~1 false-positive per 1 M blank PBMCs. Linear quantification was observed across three orders of magnitude, with consistent single-cell functional marker resolution, whereas SFC showed false positives and distorted functional readouts at low concentrations (~1 in 10 5 ). Conclusions: Using an SFC-like workflow, CB-Scout provides superior sensitivity and phenotypic resolution for therapeutic NK cells, enabling ultra-sensitive detection below 1 cell per million. By matching or exceeding NGS sensitivity while preserving single-cell functional profiling, CB-Scout may offer an optimized approach for monitoring emerging cell therapies, including CAR-NK and in vivo CAR-T.
ZIP-code–level distress as a predictor for advanced stage and mortality in female breast cancer across a multiethnic cohort in Hawaiʻi.
1649 Background: Native Hawaiian and Pacific Islander (NHPI) patients experience worse breast cancer outcomes; however, the role of neighborhood-level structural disadvantage remains underexplored. We evaluated whether the Distressed Communities Index (DCI), a ZIP-code–level socioeconomic measure, is associated with stage at diagnosis and survival in a multiethnic breast cancer cohort. Methods: We conducted a retrospective cohort study of 10,421 female patients with breast cancer treated at a major tertiary cancer center in Honolulu, Hawaiʻi (2000-2024). DCI was assigned by residential ZIP code using the Economic Innovation Group DCI (American Community Survey 5-year estimates, 2019–2023) and dichotomized as low (DCI 1–3) versus high (DCI 4–5). Patients missing ZIP code or stage at diagnosis were excluded. Associations with advanced stage (III/IV) were assessed using logistic regression. Overall survival (OS), defined as time from diagnosis to death from any cause or last follow-up, was evaluated using multivariable Cox regression, adjusting for age, race/ethnicity, insurance, tumor characteristics, and stage. Results: The cohort included 1,982 White, 6,206 Asian, 2,067 NHPI, and 166 patients of other races/ethnicities. Baseline DCI distribution differed by race/ethnicity and insurance: NHPI patients were more likely to reside in high-distress communities than non-NHPI patients (38.9% vs 29.3% OR 1.54, p<0.001), as were Medicaid/uninsured patients compared with privately insured patients (51.4% vs 27.8%; OR 2.76, p<0.001). Advanced stage at diagnosis was more frequent in high-DCI neighborhoods than low-DCI neighborhoods (10.0% vs 6.7%; p<0.001) and remained independently associated with high DCI after adjustment (aOR 1.29; p=0.021). Higher DCI was also associated with worse survival (aHR 1.16, 95% CI 1.07–1.27; p<0.001), demonstrating a dose-response pattern across DCI categories (p for trend <0.001). No significant interaction was observed between DCI and NHPI status (p=0.493). Median OS was 247 (234-260) months for White patients, 247 (241-253) months for Asian patients, 227 (215-239) months for NHPI patients (log-rank p<0.001). In multivariable analysis, NHPI patients had higher mortality than White patients (HR 1.27, 95% CI 1.12–1.43; p<0.001), while Asian patients had improved survival (HR 0.78, 95% CI 0.71–0.87; p<0.001). Medicaid/uninsured remained independently associated with higher mortality (HR 2.18, 95% CI 1.85–2.57; p<0.001). Conclusions: ZIP-code–level socioeconomic distress is independently associated with advanced stage at diagnosis and mortality in breast cancer and disproportionately affects NHPI and Medicaid/uninsured patients. DCI identifies communities at higher risk and provides a scalable, policy-relevant tool to support geographically targeted navigation, screening access, and resource allocation strategies.
Recurrence patterns and survival in hormone receptor-positive/HER2-negative early breast cancer: A retrospective analysis from a public oncologic institution in Peru.
e23402 Background: Patients (pts) with hormone receptor (HR)-positive/HER2-negative early breast cancer (EBC) face a continued risk of recurrence, adversely impacting outcomes. This study aimed to describe clinicopathological features, recurrence patterns, and survival outcomes among pts who subsequently developed recurrence. Methods: Retrospective, descriptive cohort study including HR-positive/HER2-negative EBC Peruvian pts with first recurrence (early ≤5 years, late > 5 years) after curative-intent surgery, between 2020 and 2024. Clinicopathological and treatment data were retrieved from medical records. Time to recurrence (TTR) and overall survival (OS) were estimated using Kaplan–Meier methods. Cox proportional hazards regression models were used to identify factors associated with shorter TTR (earlier recurrence) and with OS. A p < 0.05 value was considered statistically significant. Results: A total of 139 pts were included. Median age was 55 years old (range 24-85), 97% had ECOG 0-1. Most were postmenopausal (68%) and had luminal B tumors (68%), with a mean Ki-67 value of 37% (5-80). The most frequent key anatomic features included T2 size (44%), node-positive disease (76%), and stage IIIB (36%). Relevant pathological characteristics were presence of lymphovascular invasion (59%), grade 3 (39%), non-ductal histology (51%), and progesterone receptor (PgR) expression < 10% in 25% of cases. Overall, 70% and 90% met “high-risk” criteria according to monarchE and NATALEE trials, respectively. Regarding treatment, 58% received neoadjuvant chemotherapy, 57% adjuvant chemotherapy, and 81% adjuvant radiotherapy. The most frequent first recurrence sites were locoregional (36%) and bone (34%). 58% had early recurrence. Within this recurrence cohort, TTR probabilities at 1, 3 and 5 years were 88%, 60% and 37%, respectively (median TTR, 48 months). Longer TTR (was observed in pts with T1-T2 tumors, stage I-II, ductal histology, and those who received adjuvant chemotherapy. After a median follow-up of 81 months from surgery, OS rates at 1, 3 and 5 years were 100%, 95% and 84%, respectively. T3-T4 tumors were associated with a higher risk of death vs. T1-T2 tumors (HR: 1.87, p = 0.026). Conclusions: In this Peruvian cohort of HR-positive/HER2-negative EBC pts, T1-T2 tumor size, stages I-II, ductal histology, and adjuvant chemotherapy were associated with later recurrence. Conversely, T3-T4 tumor size was linked with worse OS outcomes. Despite favorable OS rates, this cohort showed a substantial burden of early recurrence, probably influenced by a higher proportion of locally advanced disease at diagnosis. A considerable proportion met the criteria of “high-risk”, highlighting the recurrence landscape and the need for greater access to optimize adjuvant strategies in resource-limited settings.
Feasibility and preliminary efficacy of a 12-week remotely delivered exercise program in patients receiving immunotherapy: A phase II randomized controlled trial.
1638 Background: Patients with advanced cancer receiving immunotherapy experience reduced physical function, increased symptom burden, and poorer health-related quality of life (HRQOL). Limited access to structured exercise programs makes technology-supported interventions a potentially scalable alternative. We assessed the feasibility and preliminary efficacy of a 12-week remote exercise program on HRQOL, symptom burden, and fear of cancer recurrence (FCR), with an exploratory economic evaluation. Methods: In this Phase II trial, adult receiving immunotherapy alone or in combination were randomized 1:1 to a remote exercise intervention or usual care (UC). The study was powered to detect a 10-point difference in Functional Assessment of Cancer Therapy-General (FACT-G) scores (80% power, α=0.05). The intervention included weekly virtual sessions with an exercise physiologist, individualized Borg-guided exercise prescriptions, video support, and telehealth monitoring 12 weeks (30-45 minutes/day). Outcomes assessed at baseline and 12 weeks included HRQOL (FACT-G), symptom burden (Edmonton Symptom Assessment Scale; ESAS), and FCR (FCR-7). Between-group differences were analyzed using ANCOVA adjusted for baseline values, with effect sizes estimated using Cohen’s d. A preliminary provider-perspective cost-consequence analysis estimated cost per one-point FACT-G improvement. Results: Seventy patients were randomized (35 per arm); five died before 12 weeks (3 control, 2 intervention). Baseline characteristics were balanced. At 12 weeks, the intervention group had significantly higher FACT-G scores compared than UC (mean difference = 11.1; p<0.001; Cohen’s d=1.30). Symptom burden was lower in the intervention arm (p<0.001; Cohen’s d=1.68), and FCR was reduced (p=0.014; Cohen’s d=0.85). Group assignment remained a significant predictor in adjusted ANCOVA models (all p<0.01). Estimated intervention cost was R$7,023 per participant, or R$634 per FACT-G point gained. Conclusions: A 12-week remote exercise intervention produced a clinically meaningful 11-point improvement in HRQOL at an estimated cost of R$ 634 per FACT-G point, supporting its economic feasibility and scalability. The program reduced symptom burden and FCR. These findings justify larger trials to confirm effectiveness and further evaluate cost-effectiveness. Changes in patient-reported outcomes at 12 weeks. Outcome (scale) Group BaselineMean ± SD 12-weekMean ± SD Mean Change P-value Cohen’s d FACT-G Control (n=32) 87.3 ± 9.7 85.9 ± 10.2 -1.4 0.001 1.30 Intervention (n=33) 85.2 ± 9.1 96.9 ± 6.7 +11.8 ESAS Control (n=32) 17.3 ± 12.1 19.0 ± 12.8 +1.7 0.001 1.68 Intervention (n=33) 20.6 ± 9.6 5.5 ± 3.7 -15.1 FCR-7 Control (n=32) 15.0 ± 6.0 15.4 ± 6.5 +0.4 0 .014 0.85 Intervention (n=33) 16.2 ± 6.3 11.3 ± 3.8 -4.9
Effectiveness, safety, and patient-reported quality of life with first-line chemotherapy in advanced pancreatic cancer: A nationwide prospective multicenter observational study.
e16388 Background: In advanced pancreatic cancer, mFOLFIRINOX and gemcitabine plus nab-paclitaxel (GnP) are commonly used as first-line chemotherapy options, while it remains unclear which regimen provides superior clinical outcomes. We conducted a prospective real-world observational study to evaluate factors influencing first-line treatment selection and associated effectiveness and quality-of-life outcomes. Methods: This prospective, multicenter observational study enrolled patients with advanced pancreatic cancer initiating first-line palliative chemotherapy at 25 centers in Korea between January 2021 and June 2024, with follow-up of up to 12 months. First-line regimens were selected at investigators’ discretion, and factors related to treatment selection were prospectively collected. The primary endpoint was progression-free survival (PFS) assessed by investigator review per RECIST v1.1; secondary endpoints included overall survival (OS), safety, and quality of life assessed using FACT-Hep at baseline, 2 months, and 6 months. Results: A total of 799 patients were enrolled, of whom 787 were eligible for the final analysis. First-line regimens included mFOLFIRINOX (n = 423), GnP (n = 332), and gemcitabine monotherapy (n = 32). Selection of first-line therapy was primarily influenced by ECOG performance status (39.1%) and age (26.2%), with a higher proportion of patients aged ≤65 years receiving mFOLFIRINOX than GnP (52% vs 27%). With a median follow-up of 10.7 months (IQR, 5.4–12.3), mFOLFIRINOX was associated with longer median PFS than GnP (7.1 vs 5.3 months; HR, 0.70; 95% CI, 0.6–0.9) and longer median OS (15.9 vs 10.1 months; HR, 0.60; 95% CI, 0.5–0.8), with similar trends observed in patients aged ≥65 years. Second-line palliative chemotherapy was administered in 39.5% of patients overall (42.6% with mFOLFIRINOX vs 37.4% with GnP). Grade ≥3 adverse events were more frequent with mFOLFIRINOX than with GnP (32.6% vs 22.6%), including higher rates of grade ≥3 neutropenia (19.4% vs 12.3%). FACT-Hep scores were maintained over time, with small increases in the mFOLFIRINOX group at 2 and 6 months (+2.2, +1.9) and slight decreases in the GnP group (−2.6, −1.5), suggesting relatively better quality-of-life preservation with mFOLFIRINOX. Conclusions: In this nationwide prospective real-world study, selection of first-line chemotherapy for advanced pancreatic cancer was driven primarily by patient age and performance status. mFOLFIRINOX was associated with more favorable effectiveness outcomes than GnP, without clinically meaningful deterioration in quality of life, even in older patients. As fewer than 40% of patients received second-line palliative chemotherapy, these findings underscore the importance of optimal first-line treatment selection and may inform routine clinical decision-making.