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A Eutectic‐interface Engineered Al <sub>2</sub> TiO <sub>5</sub> Nanofibrous Aerogel for Superinsulation Under Extreme Conditions
ABSTRACT Ceramic aerogels that are both thermal super‐insulators and mechanically robust under extreme temperatures are urgently needed yet elusive, due to the inherent trade‐off between thermal resistance and thermomechanical stability. Here, we solve the problem by reporting a 3D, elastic aluminum titanate (Al 2 TiO 5 ) nanofibrous aerogel crafted via a eutectic‐interface engineering strategy. This approach employs a fully aqueous, scalable roll‐to‐roll electrospinning process, enabling the low‐temperature synthesis of a co‐continuous Al 2 O 3 –TiO 2 eutectic architecture—a structure previously attainable only in dense ceramics through ultra‐high‐temperature melt growth. The resulting aerogel (density: 25 mg·cm − 3 ) achieves an ultralow thermal conductivity of 0.033 and 0.103 W·m − 1 ·K − 1 at 25 and 1000°C, respectively. Moreover, the aerogel can resist direct flame at 1300°C without structural failure, and recovers elastically up to 90% after repeated compression at 50% strain. This superior performance arises from its eutectic interfaces, which act as efficient phonon scatterers for thermal insulation while also providing intrinsic thermal stability. This work not only demonstrates a viable, sustainable path for mass‐producing elastic ceramic aerogels but also establishes a new material design paradigm, transforming brittle eutectic oxides into lightweight, elastic thermal super‐insulators for aerospace and energy applications.
A multicenter pilot study of afatinib re-challenge in patients with <i>EGFR</i> -mutated non-squamous non–small cell lung cancer previously treated with osimertinib.
e20748 Background: Osimertinib (+ chemotherapy) is the standard first-line treatment for EGFR -mutated non-squamous non-small cell lung cancer (NSqNSCLC). However, evidence regarding the efficacy of EGFR-TKI re-challenge after progression on osimertinib remains insufficient. This study evaluated the efficacy and safety of afatinib as a subsequent therapy following progression on osimertinib and conventional chemotherapy. Methods: This multicenter, single-arm, phase II study enrolled patients (pts) with advanced/recurrent EGFR -mutated (del19 or L858R) NSqNSCLC and an ECOG PS 0–1. All pts underwent NGS-based comprehensive genomic profiling (CGP) after progressing on osimertinib. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: Between Oct 2022 and Dec 2024, 19 pts were enrolled. Due to slow accrual, the study was terminated before reaching the planned sample size. Of 17 evaluable pts, the ORR was 11.8% (95% CI: 1.5-36.4), mPFS was 4.5 mos. (95% CI: 2.9-9.2), and mOS was 20.8 mos. (95% CI: 9.0-NA). CGP identified several biomarkers potentially involved in osimertinib resistance, including EGFR C797S (n = 1), ERBB2 mutation (n = 1), PIK3CA mutation (n = 1), RET mutation (n = 1), and METex14 skipping (n = 1); however, no clear correlation between these markers and afatinib efficacy was observed. Any-grade adverse events (AEs) occurred in 88.2% of pts, with Grade 3 AEs in 29.4% (5/17), primarily diarrhea, which were manageable with dose interruptions or reductions. Conclusions: Afatinib re-challenge showed limited efficacy in pts with EGFR -mutated NSqNSCLC pretreated with osimertinib and chemotherapy. While the safety profile was consistent with previous reports, these findings suggest that alternative therapeutic strategies should be prioritized in this clinical setting. (UMIN000049225). Clinical trial information: UMIN000049225 .
Comprehensive genomic profiling to identify molecular determinants of efficacy of IDH1 inhibition in intrahepatic cholangiocarcinoma.
4147 Background: Ivosidenib (IVO) in IDH1 -mutant iCCA yields modest mPFS (2.7 m) with heterogenous responses. Molecular features driving this variability remain undefined. We sought to identify determinants of therapeutic efficacy via comprehensive analyses of co-occurring genomic alterations and oncogenic pathway activation. Methods: We analyzed 93 IDH1 -mutant iCCA cases (MD Anderson n=59, Moffitt n=23, Yonsei n=11) treated with IVO (n=78), IDH305 (n=15). We stratified patients (pts) into 3 groups based on co-occurring alterations: EC (Epigenetic/Chromatin remodeling: BAP1/ARID1A/PBRM1), PMF (Proliferative/Mitogenic signaling: PI3K/MAPK/FGFR), ACT (Amplified cyclins/CDKN2A-B/TP53), yielding 4 groups: G1 (EC-intact/low-oncogenic: EC+/PMF-/ACT-), G2 (signaling-driven: EC+/PMF+), G3 (cell-cycle-deregulated: EC+/ACT+), and G4 (EC-deficient: EC-). Cox models assessed group-specific treatment effects; TME characterization utilized 29 mRNA gene signatures (Bagaev, Cancer Cell 2021) (n=31) and paired pre/post-progression biopsies (n=4). Results: Survival analysis (n=93) revealed distinct stratification (p<0.0001): G1, the longest mPFS (11.4 m), significantly superior to G4 (3.5 m) and G3 (1.8 m). G1 had superior durability (12-m PFS 46.5%) over G2 and G4 (23.9%, 14.6%); G3 progressed rapidly (6-m 0%). G3 outcomes suggest that ACT co-mutations confer poor prognosis regardless of epigenetic context (HR 6.85, P=0.004). Transcriptomic analysis identified G1 as "inflamed-suppressed" (highest angiogenesis/Treg); G4 was "proliferative-inflammatory" (highest M1-macrophage/Ki67, p=0.04). Paired longitudinal analysis (n=4) identified genomic bypass via acquired kinase drivers (eg, NTRK1 amplification) and stromal adaptation with dense fibrotic remodeling. Radiographic hyperprogression on IVO (Kato criteria) was observed in 2 pts in G3 harboring CDKN2A loss. Conclusions: Co-occurring genomic alterations may serve as prognostic markers in IDH1 -mutant iCCA, suggesting distinct trajectories of response and resistance to IDH1 inhibition. This molecular classification could guide clinical decision-making by identifying pts likely to benefit from monotherapy vs pts requiring combination strategies to overcome intrinsic resistance. G1 G2 G3 G4 EC+ / PMF- / ACT- EC+ / PMF+ EC+ / ACT+ EC- N (%) 28 (30%) 19 (20%) 5 (5%) 41 (44%) mPFS (95% CI) 11.4 mo (6.2-NR) 5.6 mo (3.7-9.2) 1.8 mo (0.9-3.5) 3.5 mo (2.1-5.8) 3-M Rate 80.9% (66.3-95.5) 88.9% (74.8-100) 20.0% (0.0-55.1) 59.5% (44.5-74.5) 6-M Rate 72.4% (55.8-89.0) 47.9% (25.4-70.4) 0.0% (0.0-0.0) 23.4% (10.4-36.4) 12-M Rate 46.5% (28.0-65.0) 23.9% (4.7-43.1) 0.0% (0.0-0.0) 14.6% (3.8-25.4) Hazard Ratio Reference (1.0) 2.15 (p=0.03) 6.85 (p=0.004) 2.94 (p=0.002) TME Phenotype Angiogenesis / Treg-High Fibrotic (CAF-High) Senescent / Dormant Proliferative / M1-High
Construction of an in-vitro peritoneal metastasis model and evaluating its feasibility for experimental peritoneal metastasis research.
e15527 Background: Currently, a wide range of therapeutic strategies are studied and developed for the treatment of peritoneal metastasis (PM). However, there is a lack in standardized in-vitro models that accurately mimic PM. This study introduces a novel in-vitro peritoneal metastatic model (PMM) designed to enable consistent, reproducible, and physiologically relevant evaluation of potential PM therapies. Methods: Peritoneal lavage fluid was collected laparoscopically from swine and centrifuged to isolate peritoneal progenitor cells (PPC). The PPC were cultured for 7 days before introducing commercially available HT-29 colorectal cancer cells. Co-cultures were maintained until distinct metastatic nodule formation developed. The PMM was subsequently exposed to Oxaliplatin (OX) to assess treatment responses. Formed nodules were detached using Ethylenediaminetetraacetic Acid (EDTA), then isolated and quantified. Results: The approach successfully generated a dense PMM that reproduced features of early micrometastatic disease. HT-29 cells formed diverse three-dimensional nodule structures atop the two-dimensional PPC layer. Following OX exposure, variable regrowth patterns and distinct interactions with the reconstructed peritoneal surface were observed, reflecting clinically relevant heterogeneity and chemoresistance. EDTA treatment enabled efficient removal and standardized harvesting of metastatic nodules for further analyses. Conclusions: Peritoneal lavage fluid provides a reliable source of PPC for constructing a physiologically relevant PMM. This model supports standardized, quantitative assessment of therapeutic interventions and more accurately reflects the complexity and chemoresistant nature of PM compared with conventional 2D cultures. This study offers a valuable platform for advancing metastatic cancer research while reducing reliance on animal models.
Immune effector cell–associated enterocolitis (IEC-EC) incidence and characterization in cilta-cel–treated patients with RRMM in CARTITUDE clinical studies.
7533 Background: Ciltacabtagene autoleucel (cilta-cel) shows benefit for patients (pts) with relapsed/refractory multiple myeloma (RRMM). A recently recognized uncommon adverse reaction, IEC-EC is characterized by severe/persistent diarrhea typically 1–3 months post CAR-T cell infusion. Here we summarize incidence and features of IEC-EC in clinical trials of cilta-cel for RRMM. Methods: 483 pts across RRMM studies (CARTITUDE-1, -2, -4, and CARTIFAN-1) were evaluated for evidence of IEC-EC. The clinical picture and nomenclature for IEC-EC were described in the real-world setting after infusion of most pts. As such, retrospective analysis was performed to identify cases consistent with IEC-EC, defined as prolonged (≥3 weeks) and severe (≥grade 3) diarrhea after cilta-cel infusion, without clear infectious etiology. Correlative biomarker analyses included peripheral CAR-T cell expansion/persistence, immune cell composition, and cytokines/inflammatory markers. Centralized pathomorphological review and immunohistochemical analysis of available biopsies was conducted. Results: Across RRMM studies, 6/483 (1.2%) pts demonstrated the clinical picture of IEC-EC, presenting 12–214 days after receiving cilta-cel (median onset 67 days post infusion). Best response was CR/sCR for all subjects. Pts received therapies including steroids (4/6). Four pts experienced symptom resolution within 123–227 days; 2 had persistent symptoms until death (causes: multiorgan failure and COVID19). Pts with IEC-EC had lower levels of B cells and higher levels of CAR+ T cells and inflammatory cytokines (eg, IL-6) at onset compared to a GI symptom-free control group at comparable time; while all cilta-cel–treated pts experienced B cell depletion, pts with IEC-EC had more prolonged deficiency. Histological analyses of GI biopsies from 5 pts with IEC-EC revealed plasma cells, normally present in the GI tract, were absent. CAR-T cells were detected and localized to the lamina propria and were not observed juxtaposed with epithelia, making it unlikely direct damage to epithelia was caused by CAR-T cells. Histologic damage was greater in the small intestine (predominantly duodenum) than the colon. Conclusions: Retrospective analysis of cilta-cel trials identified a low IEC-EC incidence (1.2%). Findings support a reactive mechanism involving plasma cell depletion and immune dysregulation rather than direct CAR-T cell cytotoxicity and highlight the importance of upper endoscopy to identify injury patterns in the small intestine that may be less pronounced in the colon. Although the pathophysiology is not fully defined, increased awareness and earlier diagnosis may improve understanding of management and enhance likelihood of IEC-EC reversibility.
Stage-specific associations between clinical, demographic, and treatment factors and long-term survival in ovarian cancer.
e17610 Background: Ovarian cancer remains the deadliest gynecologic malignancy, largely due to advanced-stage presentation and variation in access to care. While surgery and chemotherapy are central to management, the relative importance of clinical and system-level factors may differ by disease stage. We examined stage-specific associations between demographic, clinical, and treatment factors and long-term survival among surgically treated patients. Methods: Adults with surgically treated ovarian cancer were identified from the National Cancer Database (2004–2020). Pathologic stage was defined using AJCC criteria and grouped to correspond with FIGO 2014 I–IV categories. Survival was categorized as 0–2, 2–5, or >5 years from diagnosis. Ordinal logistic regression assessed associations between demographic, socioeconomic, tumor, and treatment factors and the odds of belonging to a higher survival category, reported as adjusted odds ratios (aORs). Results: Among 23,560 patients, 39.5%, 11.8%, 35.6%, 13.1% had stage I, II, III, and IV disease, respectively. In stage I, Medicaid insurance (aOR 0.72, p < 0.05), higher comorbidity (aOR 0.86, p < 0.001), low income (aOR 0.75, p < 0.05), and 30-day readmission after surgery (aOR 0.69, p < 0.05) were associated with lower survival. In stage II, Non-Mexican Hispanic ethnicity (aOR 0.57, p < 0.05), uninsured status (aOR 0.46, p < 0.05), and mesenchymal histology (aOR 0.49, p < 0.001) were associated with lower survival, while chemotherapy was associated with higher survival (aOR 1.51, p < 0.001). In stage III, older age (aOR 0.98, p < 0.001) and higher comorbidity (aOR 0.89, p < 0.05) were associated with lower survival. Asian/Pacific Islander (aOR 0.63, p < 0.05) and American Indian/Other patients (aOR 0.55, p < 0.05) had reduced survival odds. Care in Medicaid expansion states (aOR 1.22, p < 0.05) and absence of postoperative readmission (aOR 1.50, p < 0.001) were associated with higher survival. In stage IV, Black race (aOR 0.68, p < 0.05) and non-private insurance (aOR 0.23–0.65, p < 0.05) were associated with lower survival. Mesenchymal or non-epithelial histology remained adverse (aOR 0.50, p < 0.001). Chemotherapy showed the strongest association with higher survival across all stages (aOR 1.51–2.86, p < 0.001). Conclusions: Associations between survival and clinical or system-level factors vary substantially by ovarian cancer stage. Early-stage outcomes were most strongly associated with patient health status and perioperative recovery, whereas in advanced disease, chemotherapy access and insurance status showed the strongest associations with long-term survival. These findings highlight stage-specific vulnerabilities in care delivery that may contribute to observed survival differences.
Immunotherapy for advanced gastric cancer: Experience from Uzbekistan.
e23352 Background: Gastric cancer is a major cause of cancer-related mortality worldwide and remains highly prevalent in Central Asia, including Uzbekistan. Perioperative FLOT chemotherapy is the current standard of care; however, its efficacy is limited in molecular subgroups such as microsatellite instability–high (MSI-H) tumors. Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have shown promising results in biomarker-selected patients. Methods: A real-world study was conducted at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology between 2021 and 2025. Patients with locally advanced gastric cancer underwent routine MSI testing. MSI-H patients received either standard perioperative FLOT chemotherapy or FLOT combined with pembrolizumab. The primary endpoints were major pathological response (MPR), conversion from initially inoperable to operable disease, 6-month disease-free survival (DFS), and overall survival (OS). Results: Chemoimmunotherapy demonstrated superior outcomes compared with chemotherapy alone. Major pathological response was achieved in 60% of patients versus 12.5%. Conversion to operable status occurred in 75% versus 25% of cases. Six-month DFS was 95% in the chemoimmunotherapy group compared with 58% in the chemotherapy group. Median overall survival was not reached in the chemoimmunotherapy group, whereas it was 14.2 months with chemotherapy alone. Conclusions: Chemoimmunotherapy demonstrated superior outcomes compared with chemotherapy alone. Major pathological response was achieved in 60% of patients versus 12.5%. Conversion to operable status occurred in 75% versus 25% of cases. Six-month DFS was 95% in the chemoimmunotherapy group compared with 58% in the chemotherapy group. Median overall survival was not reached in the chemoimmunotherapy group, whereas it was 14.2 months with chemotherapy alone.
Efficacy and safety of adjuvant immune checkpoint inhibitors in resected renal cell carcinoma: Systematic review and meta-analysis of phase III trials.
e16514 Background: Phase III trials of adjuvant immune checkpoint inhibitors (ICIs) in resected renal cell carcinoma (RCC) have yielded conflicting results. Pembrolizumab improved disease-free survival (DFS) in KEYNOTE-564, whereas atezolizumab, nivolumab-based, and perioperative regimens were negative. Whether benefit represents a class effect is unclear. Methods: A systematic review identified phase III randomized controlled trials of adjuvant or perioperative ICIs versus placebo/observation in resected RCC at increased risk of recurrence. The primary endpoint was DFS/recurrence-free survival (RFS); secondary endpoints included overall survival (OS) and safety. Random-effects meta-analyses with Hartung–Knapp adjustment were performed, with heterogeneity quantified by I². Results: Five trials met inclusion criteria (KEYNOTE-564, IMmotion010, CheckMate 914 Parts A and B, PROSPER; N = 3,947). Pooled DFS/RFS favored ICIs but did not reach statistical significance: hazard ratio (HR) 0.86 (95% CI 0.73–1.01, p = 0.058; I² = 13%). Only KEYNOTE-564 (pembrolizumab) met its primary endpoint (HR 0.72, 95% CI 0.59–0.87), whereas atezolizumab, adjuvant nivolumab (with or without ipilimumab), and perioperative nivolumab each showed nonsignificant effects (HRs 0.87–0.95). OS data were available from three trials (KEYNOTE-564, PROSPER, IMmotion010); the pooled OS HR was 0.90 (95% CI 0.36–2.25, p = 0.68) with substantial heterogeneity (I² = 73%), reflecting a significant OS benefit only in KEYNOTE-564 (HR 0.62, 95% CI 0.44–0.87) and a numerical increase in risk of death with perioperative nivolumab in PROSPER (HR 1.28, 95% CI 0.84–1.95). Grade ≥3 treatment-related adverse events occurred in 14–28% of ICI-treated patients versus 1.2–5% with placebo/observation, and discontinuations due to toxicity in 10–29% versus approximately 2%, respectively; 13 treatment-related deaths were reported across ICI arms. Conclusions: Across contemporary phase III trials, adjuvant ICIs for resected RCC do not demonstrate a consistent class-wide benefit. The DFS/RFS and emerging OS advantages appear specific to pembrolizumab, whereas atezolizumab, nivolumab-based regimens, 6-month treatment courses, and perioperative strategies have not improved outcomes. Current evidence supports pembrolizumab as the only evidence-based adjuvant ICI for high-risk RCC, and highlights the need for further biomarker-driven and regimen-optimized studies.
Spectrum of autosomal recessive pediatric cancer predisposition syndromes in a population with high consanguinity.
e22637 Background: Most studies of pediatric cancer predisposition syndromes (CPS) are derived from Western populations, resulting in limited understanding of CPS spectra in low- and middle-income countries. We aimed to characterize the genetic landscape of CPS among children of Arab ancestry treated at King Hussein Cancer Center (KHCC), with a particular focus on the impact of consanguinity. Methods: We conducted a retrospective review of children (<18 years) referred to the KHCC Pediatric Cancer Predisposition Clinic between January 2020 and October 2025. Germline testing was performed using targeted next-generation sequencing panels (Invitae) covering cancer predisposition, immunodeficiency, and bone marrow failure syndromes. Patients were stratified based on reported parental consanguinity. Results: A total of 230 pediatric cancer patients underwent germline testing. Median age at cancer diagnosis was 5 years (range, 0.2–18), and 55% were male. The most common indications for CPS evaluation were a family history of cancer (59%), followed by tumor types suggestive of an underlying predisposition syndrome (46%). The overall consanguinity rate was 26%, increasing to 35% among patients with a positive family history. Overall, 76 patients were diagnosed with 24 distinct CPSs. Among children from consanguineous families, 27 of 30 (90%) had autosomal recessive (AR) CPSs, while 3 of 30 (10%) had autosomal dominant (AD) conditions. In the non-consanguineous group, 45 of 46 (98%) had AD CPSs, and one child (2%) had a mitochondrial disorder due to a heteroplasmic variant. The most frequent CPSs were constitutional mismatch repair deficiency (CMMRD, n=11), RB1-related predisposition (n=10), neurofibromatosis (n=8), and Li-Fraumeni syndrome (n=6). Variants of uncertain significance (VUS) considered likely contributory were identified in 17 patients. Genetic testing was negative in 54 of 230 patients (23%). Conclusions: Consanguinity profoundly shapes the spectrum of pediatric CPS in Arab populations, with a marked predominance of autosomal recessive syndromes. These findings underscore the need for population-specific genetic evaluation strategies. Future efforts should prioritize systematic reclassification of VUS through integrated tumor–germline analyses, trio-based testing, and functional studies. Broader implementation of whole-exome and whole-genome sequencing is essential for clinically high-risk patients with negative panel testing, particularly in highly consanguineous populations.
Association of estrogen receptor status with survival outcomes in neuroendocrine carcinoma of the breast: A SEER Research Plus analysis (2010–2021).
e12759 Background: Neuroendocrine carcinoma of the breast (NECB) is a rare histologic sub-type with heterogeneous clinical behavior. Although NECB is frequently hormone receptor–positive, the prognostic relevance of estrogen receptor (ER) status remains incompletely defined due to evolving histologic classifications and reliance on small, heterogeneous series. We evaluated survival outcomes by ER status using a contemporary population-based cohort. Methods: We identified malignant NECB cases diagnosed between 2010 and 2021 in the SEER Research Plus database and restricted analyses to first primary tumors with known ER status. ER status was defined using SEER breast ER re-code variables (ER-positive coded as 0; ER-negative coded as 1). Observed overall survival (OS) was summarized at 1–5 years, and median observed survival was estimated using SEER*Stat survival analyses. Survival patterns were further examined in analyses stratified by stage at diagnosis, age, and receipt of surgery. Results: Among 221 patients with NECB and known ER status, 159 (72.0%) were ER-positive and 62 (28.0%) were ER-negative. Median observed survival was not reached in the ER-positive group compared with 55.8 months in ER-negative disease. ER-positive NECB demonstrated superior observed survival across all evaluated time-points, including 1-year OS (87.5% vs 75.6%), 3-year OS (76.2% vs 55.8%), and 5-year OS (65.4% vs 47.4%) for ER-positive versus ER-negative tumors, respectively. The survival advantage associated with ER-positive NECB persisted in analyses stratified by stage at diagnosis, age, and receipt of surgery. Conclusions: In this contemporary population-based analysis, ER-positive NECB was associated with substantially improved survival compared with ER-negative disease. These findings support ER status as a clinically relevant prognostic factor in NECB and provide contemporary survival benchmarks that may inform risk stratification and future outcomes research in this rare breast cancer sub-type.
Early inpatient chemotherapy in central nervous system (CNS) tumors: Predictors, treatment patterns, and in-hospital outcomes.
e14035 Background: Timely inpatient chemotherapy may alter the trajectory of acute CNS tumor hospitalizations by controlling disease burden before critical complications develop. We evaluated demographic, clinical, and hospital factors associated with receipt of chemotherapy within the first hospital day (Day 0–1) and examined whether early administration improves in-hospital outcomes. Methods: Using the Nationwide Inpatient Sample, we identified 332,100 CNS tumor hospitalizations from 2016–2020. Patients were stratified by chemotherapy given within Day 0–1 versus after Day 1. Categorical outcomes were compared with Pearson chi square tests and continuous variables with Welch’s t-tests. Multivariable logistic regression identified independent predictors of early chemotherapy, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Only 4.5% received early chemotherapy. They were markedly younger (11.6 ± 13.6 vs 52.5 ± 22.4 years, p<0.001) and had lower comorbidity burden (CCI 3.14 ± 2.26 vs 4.87 ± 2.57, p<0.001), early treated patients experienced dramatically better outcomes across nearly every major complication. Mortality was lower (0.2% vs 3.6%, p<0.001), as were rates of mechanical ventilation (0.4% vs 5.5%), vasopressor use (0.1% vs 0.8%), acute kidney injury (1.5% vs 6.5%), sepsis (0.9% vs 5.6%), hemorrhage (0.8% vs 9.6%), organ failure (2.9% vs 24.7%), venous thromboembolism (0.5% vs 6.7%), major adverse cardiac events (0.3% vs 7.6%), cerebral edema (2.2% vs 39.9%), seizures (4.8% vs 25.3%), brain herniation (3.1% vs 13.1%), and Do-Not-Resuscitate orders (0.7% vs 14.1%) (all p<0.001). Early chemotherapy was also linked to shorter stays (4.77 ± 6.85 vs 6.94 ± 9.54 days) and lower total charges ($65,599 ± 137,225 vs $102,763 ± 146,139, p<0.001). Logistic regression confirmed that early chemotherapy independently predicted lower odds of death (aOR 0.55, 95% CI 0.37–0.81), organ failure (0.33, 0.28–0.39), sepsis (0.27, 0.22–0.33) and MACE (0.63, 0.46–0.85) even after adjusting for age, comorbidity, and hospital factors. Notably, transfusion (10.6% vs 3.0%, p<0.001) and frailty/malnutrition (13.7% vs 6.3%, p<0.001) were more frequent in early chemotherapy, indicating higher tumor burden and treatment intensity. Conclusions: Early inpatient chemotherapy for CNS tumors is strongly associated with markedly lower in-hospital mortality and critical complications despite higher indicators of disease acuity. These findings underscore the potential protective effect of initiating chemotherapy on the day of admission and support efforts to streamline early treatment pathways for hospitalized CNS tumor patients.
RADIANCE predictive score: A new model of radiological markers for prediction of antiangiogenics efficacy in pretreated metastatic colorectal carcinoma (mCRC)—RADIANCE trial.
e15553 Background: Antiangiogenic agents are widely used in mCRC. The ABACO trial recently showed that high angiogenesis genes expression in tumor samples, correlates with response to Cabozantinib. However, genomic predictors are poorly reproducible in clinical practice. The RADIANCE trial evaluates whether radiological biomarkers could predict antiangiogenics efficacy. Methods: We conducted a retrospective, observational study of mCRC patients (pts), progressed after ≥2 systemic regimens, treated with Cabozantinib (Cabo), Trifluridine–Tipiracil plus Bevacizumab (TT+B), Regorafenib (Rego), or Trifluridine–Tipiracil (TT) alone. Pts required ≥ 1 measurable lesion per RECIST 1.1 on baseline CT-scan. Radiological features assessed included intratumoral vascularization (ITV) (ΔHU portal–unenhanced > or ≤ 20), calcification (Calc) (Humax > or ≤ 150), and density (Dens) (HUbasal > or ≤ 50). Results: 63 pts with heavily pretreated mCRC were included. 19 pts received respectively Cabo and TT+B, 15 TT and 10 Rego. Liver and peritoneal metastases were the main target lesions studied across cohorts. ITV was significantly associated with improved outcomes in pts treated with antiangiogenics. In the Cabo cohort, pts with metastases showing higher ITV experienced a significantly longer median PFS (4.14 vs 2.03 months (mo); HR 0.30, p = 0.037) and a higher DCR (77.8% vs 25%). In the TT+B and Rego cohorts, a favorable trend in PFS (8.05 vs 3.63 mo and 5.11 vs ~1 mo respectively) was observed in the same subgroups. In TT+B treated pts, greater ITV was also associated with a significantly higher DCR (90.9% vs 25%, p = 0.006). Among all pts treated with antiangiogenics (n = 45), higher ITV correlated with statistically significant longer PFS (5.22 vs 2.33 mo; HR 0.45, p = 0.012) and higher DCR (75% vs 19%, p = 0.00028). No association was observed in pts treated with chemotherapy (Cht) alone. Absence of baseline Calc (HUmax ≤150) showed a consistent, though non-significant, trend toward improved PFS and DCR in antiangiogenic-treated pts, in particular in TT+B and Cabo cohorts, while no benefit was observed with Cht alone. No association, instead, between baseline metastases Dens and clinical outcomes was observed. An integrated model combining ITV and Calc stratified pts into 4 prognostic groups, with progressively decreasing PFS and DCR. Pts with high ITV and non-calcified metastases achieved the best outcomes (mPFS 7.52 mo; DCR 80%). A radiological predictive score based on ITV and Calc was, therefore, developed (high/low ITV: 2/0, Calc yes/no: 0/1). A composite score ≥2 identified patients with a higher likelihood of benefit from antiangiogenics. Conclusions: Our work points out that ITV and absence of Calc, at baseline CT-scan, may be associated with benefit from antiangiogenics. Findings are preliminary and need validation in larger prospective cohorts.
Surrogate end points for overall survival: A meta-analysis exploring adequacy of progression-free survival and objective response in randomized NSCLC trials.
e20702 Background: Surrogate endpoints such as progression-free survival (PFS) and objective response rate (ORR) are widely used in advanced non–small cell lung cancer (NSCLC) trials, yet their ability to reliably predict overall survival (OS) remains uncertain, particularly in the post-2015 era of immune checkpoint inhibitors and targeted therapies. We evaluated trial-level surrogacy of PFS and ORR for OS across randomized clinical trials using random-effects weighted meta-regression, with prespecified analyses by trial era. Methods: We conducted a systematic, trial-level meta-analysis of randomized studies in advanced or metastatic NSCLC reporting OS hazard ratios (HRs) and at least one surrogate endpoint (PFS HRs and/or ORR). The protocol was prospectively registered in PROSPERO (CRD420251266621). PubMed/MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from inception through the final search date. Two reviewers independently screened records and full texts, resolving discrepancies by consensus or third-party adjudication. Treatment effects were analyzed on the log scale (log[HR] for OS and PFS; log[RR] for ORR), with standard errors derived from 95% confidence intervals when required. Trial-level surrogacy was assessed using random-effects weighted least-squares meta-regression, modeling log(HR_OS) as a function of log(HR_PFS) and separately log(RR_ORR). Era-stratified analyses (pre-2015, 2015, post-2015) and interaction testing were prespecified. Surrogacy strength was quantified using a weighted R² analogue. Small-study effects were evaluated using Egger’s regression. Analyses were performed using Python (version 3.14.2). Results: A total of 190 trials were included; 150 contributed to the PFS–OS analysis and 98 to the ORR–OS analysis. Overall, PFS showed a statistically significant but modest association with OS (β = 0.331; 95% CI, 0.230–0.433; p < 0.001), explaining limited between-trial variability (R² = 0.216). In post-2015 trials (k = 124), the association remained significant (β = 0.332; p < 0.001) but explained little OS variability (R² = 0.193), with no significant interaction by era. ORR demonstrated a weak and inconsistent association with OS (overall β = −0.256; p = 0.029), with non-significant associations in pre-2015 trials. Egger regression showed no evidence of small-study effects. Conclusions: Across randomized trials in advanced NSCLC, PFS and objective response demonstrate limited trial-level surrogacy for overall survival. Surrogacy strength did not meaningfully improve in the post-2015 era despite widespread adoption of immune checkpoint inhibitors and targeted therapies. These findings support cautious reliance on PFS or ORR as substitutes for OS in contemporary NSCLC trials and underscore the need for OS validation or context-specific endpoint selection.
Incorporating CA19-9 testing in a prospective study of pancreatic cancer surveillance (PCS) among high-risk individuals (HRIs).
10527 Background: For individuals at an increased risk of pancreatic cancer (PC), imaging-based PCS is recommended. However, despite PCS among such individuals, when PC is diagnosed, it is found at an advanced stage in over 25% of individuals. Blood-based biomarkers of PC, such as carbohydrate antigen 19-9 (CA19-9) and HbA1C, can be abnormal prior to radiographic findings among individuals with PC. However, it is unknown whether prospective assessment of these biomarkers would allow for earlier detection or interval PC of PC among HRIs undergoing PCS. Methods: We conducted a single-institution (Dana-Farber Cancer Institute) prospective study of HRIs undergoing imaging-based PCS with annual MRCP and/or EUS (NCT06122896). All participants signed informed consent; the institutional IRB approved the study. CA19-9 was measured at baseline and every 6 months. Individuals with normal imaging but abnormal CA19-9 value underwent additional imaging, and short-interval repeat CA19-9 measurement. Personalized, genotype-adjusted, CA19-9 reference ranges were calculated based on fucosyltransferase (FUT) enzymes FUT3 and FUT2 variant analysis. Herein, we report outcomes from baseline PCS assessment. We measured the specificity of unadjusted and adjusted CA19-9. Results: 231 HRIs (mean age 62, 71% female, 47% with a previous history of cancer) underwent baseline PCS. 105 HRI (46%) had a pathogenic germline variant (PGV) predisposing to PC and met 2023 NCCN eligibility criteria for PCS surveillance, 77 (33%) HRI had a family history of PC without a predisposing PGV; 49 HRI (21%) had other indications for PCS. 153 (66%) HRIs underwent baseline PCS with MRCP [Table]; the remainder underwent an EUS. No HRIs were diagnosed with PC on baseline imaging. 98 (42%) HRI had pancreatic cyst(s) detected on baseline imaging. All abnormal CA19-9 tests (unadjusted = 5, genotype-adjusted = 1) were considered false positives as additional imaging did not reveal additional pancreatic pathology. The specificity of unadjusted and genotype-adjusted CA19-9 was 97.8% (95% CI: 95.0-99.3) and 99.5% (95% CI 97.3-100). Two individuals with concern for a focal lesion on EUS underwent immediate workup with imaging (n=1) and biopsy (n=1), both with reassuring findings. One individual was found to have a paraganglioma. Conclusions: Baseline unadjusted CA19-9 testing led to unnecessary follow-up studies in 2% of HRI undergoing imaging-based PCS. Genotype-adjusted CA19-9 may have superior specificity compared to unadjusted CA19-9. Longitudinal biomarker assessment, including serial CA19-9 and HbA1c, is ongoing. Clinical trial information: NCT06122896 . Characteristic n (%) Baseline imaging MRCPEUS 231 (100)153 (66)78 (34) Individuals with cystic lesion(s) detected 98 (42) Individuals with cyst(s) > 1cm 21 (9) MPD > 4mm 2 (0.9) Elevated unadjusted CA19-9 (> 35 U/mL) 5/229 (2.2) Elevated genotype-adjusted CA19-9 1/205 (0.5) MPD: main pancreatic duct.
Epidemiological trends and burden of liver cancer mortality due to hepatitis B in Sub-Saharan Africa: A retrospective analysis from 1990 to 2023 with advanced machine learning forecasting to 2050.
e16233 Background: Liver cancer due to hepatitis B virus (HBV) remains a major cause of cancer mortality in sub-Saharan Africa, where high chronic HBV prevalence, limited vaccination coverage, and late diagnosis drive substantial burden. Methods: This study utilized age-standardized mortality rates (ASMR per 100,000) for HBV-related liver cancer from the IHME Global Burden of Disease 2023 database for sub-Saharan Africa, stratified by sex (Both, Female, Male), covering 1990–2023. Historical trends were quantified using estimated annual percentage change (EAPC) derived from log-linear regression of ASMR. Future mortality projections to 2050 were generated using autoregressive integrated moving average (ARIMA) time-series models. ARIMA parameters (p, d, q) were selected via auto.arima algorithm based on minimizing AIC, with non-seasonal differencing applied as needed to achieve stationarity. Models were fitted to the full historical series, producing point forecasts and 95% prediction intervals (PI) assuming Gaussian errors. Results: In sub-Saharan Africa, age-standardized mortality rates (ASMR per 100,000) for HBV-related liver cancer declined substantially from 1990 to 2023. For Both sexes, ASMR fell from 5.88 in 1990 to 3.93 in 2023, with an estimated annual percentage change (EAPC) of -1.75% (95% CI -1.89 to -1.61). Males showed a steeper absolute and relative decline, dropping from 10.00 (1990) to 6.71 (2023) (EAPC -1.75%, 95% CI -1.90 to -1.60), while females declined more modestly from 1.90 to 1.47 (EAPC -1.25%, 95% CI -1.40 to -1.11). The male decline was consistent through the early decades but showed a clear plateau and recent upturn after 2019 (ASMR 5.87 in 2019 → 6.71 in 2023). ARIMA projections indicate reversal of the long-term trend, with male ASMR forecasted to rise from 7.15 (95% PI 6.95–7.35) in 2024 to 10.57 (95% PI 3.36–17.78) by 2050. Females followed a similar but less pronounced trajectory, with ASMR remaining relatively low and stable until a modest recent increase (1.25 in 2019 → 1.47 in 2023). Projections forecast female ASMR increasing from 1.59 (95% PI 1.54–1.65) in 2024 to 4.91 (95% PI 0.43–9.38) by 2050. Overall (Both sexes), the historical decline reversed in forecasts, with ASMR projected to rise from 4.24 (95% PI 4.14–4.35) in 2024 to 5.66 (95% PI 1.50–9.82) by 2050, largely driven by the male resurgence. Conclusions: HBV-related liver cancer mortality in sub-Saharan Africa declined substantially from 1990–2023 (EAPC -1.75%), with greater reductions in males (from 10.00 to 6.71) than females (1.90 to 1.47). However, ARIMA projections forecast a reversal, with ASMR rising to 5.66 (Both) by 2050, males reaching 10.57 and females 4.91. Intensified HBV vaccination, antiviral therapy scale-up, screening, and linkage to care are urgently needed to prevent projected resurgence.
Comprehensive genomic profiling of matched ctDNA and tissue from patients with four common cancers enrolled to the NCI-MATCH trial.
3045 Background: In the NCI-MATCH trial (NCT02465060), tumor tissue from 5,954 patients with advanced cancers underwent next-generation sequencing using the Oncomine Comprehensive Assay v2 (OCAv2) to determine eligibility. Most tumors lacked a qualifying mutation of interest (MOI) for assignment. Plasma from 1,301 patients with common cancers – [colorectal (COADREAD), breast (BREAST), non–small cell lung (NSCLC), and prostate (PRAD) (OncoTree codes are shown in parentheses)] was analyzed to characterize circulating tumor DNA (ctDNA) and assess its utility for detecting clinically relevant MOIs. Methods: Cell-free DNA was extracted from plasma collected in Streck tubes at enrollment. ctDNA profiling was performed using the NCI ctDNA Research v2 assay (523 genes) on the Illumina NovaSeq 6000. Matched tumor tissue was analyzed using OCAv2 (143 genes). Positive percent agreement (PPA) was calculated using tissue as the reference. Blood-based microsatellite instability (bMSI) was assessed across ~2,400 loci, with bMSI-high (bMSI-H) defined as sum Jensen-Shannon Distance (sumJSD) ≥0.2. Blood-based tumor mutation burden (bTMB) was defined as total SNVs and indels per Mb. Results: Of 1,301 patients, 1,148 (88%) yielded evaluable ctDNA results (COADREAD, n=487; BREAST, n=367; NSCLC, n=220; PRAD, n=74). Overall PPA with matched tissue was 90.3%. Discordant samples had significantly lower median tumor fraction by maximum somatic allele frequency (MSAF; 0.39%) than concordant samples (12.04%). Median MSAF by histology was 14% (COADREAD), 7% (BREAST), 8% (NSCLC), and 5% (PRAD). Clinically relevant fusions detected exclusively in ctDNA included RET (1% NSCLC), EML4::ALK (2% NSCLC), FGFR2 (1% COADREAD; 2% BREAST), and NTRK1 (<1% COADREAD and BREAST), corresponding to actionable NCI-MATCH arms [ FGFR2/3 - arm K (erdafitinib), ALK - arm F (crizotinib), NTRK - arm Z1E (larotrectinib)]. Actionable ctDNA-only mutations in PRAD included ATM and MLH1. Twenty-eight cases were bMSI-H (MSAF ≥0.02; sumJSD ≥0.2), of which 13 were mismatch repair-deficient by tissue testing (MLH1/MSH2 nuclear stain-negative). bMSI-H was most frequent in COADREAD (7%). Ten cases (seven COADREAD, two NSCLC, one PRAD) were MMR-proficient by tissue but bMSI-H by ctDNA. Twenty-four cases had high bTMB (≥20 mut/Mb; MSAF ≥0.02), all of which were also bMSI-H. Conclusions: ctDNA - tissue concordance NCI-MATCH in these four cancer histologies was high (90.3%), supporting liquid biopsy as a practical alternative when tissue is unavailable. Detection of ctDNA-only alterations highlights tumor heterogeneity in advanced cancers and identifies additional therapeutic opportunities.
First-line fovinaciclib versus placebo combined with aromatase inhibitor for advanced breast cancer: A randomized, double-blind phase 3 study.
1090 Background: Endocrine therapy combined with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is the standard first-line therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Fovinaciclib is a novel CDK4/6 inhibitor that showed survival benefit when added to fulvestrant in the later-line setting. This randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy and safety of fovinaciclib plus an aromatase inhibitor (AI) as initial therapy. Methods: Adult women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting were enrolled across 63 centers. Eligible patients were randomized in a 1:1 ratio to receive oral fovinaciclib (200 mg, once daily, days 1–21) or placebo plus an AI (letrozole 2.5 mg or anastrozole 1 mg, orally, once daily, days 1–28) in 28-day cycles. Pre- or perimenopausal patients also received goserelin (3.6 mg, subcutaneous, day 1). The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR). Secondary endpoints included other efficacy endpoints and safety. Results: A total of 417 patients were assigned to the fovinaciclib ( n = 208) or placebo arm ( n = 209) with balanced baseline characteristics. At the protocol-specified interim analysis (median follow-up 16.6 months, data cutoff date June 25, 2024), adding fovinaciclib significantly improved PFS (hazard ratio 0.55, 95% CI 0.38–0.77; p = 0.0003): median PFS was not reached in the fovinaciclib arm and 20.2 months (95% CI 16.4 months–not evaluable) in the placebo arm. The 2-year PFS rates were 65.5% (95% CI 55.3%–73.9%) and 38.9% (95% CI 27.5%–50.2%), respectively. Consistent PFS benefit was observed in investigator assessments (hazard ratio 0.49 [95% CI 0.36–0.68], p < 0.0001) and across most subgroups. Fovinaciclib also showed favorable results across secondary efficacy endpoints. OS data remain immature. Treatment-emergent adverse events (TEAEs) occurred in 207 (99.5%) and 199 (95.2%) patients in the fovinaciclib and placebo arms, respectively, with serious adverse events (SAEs) reported in 30 (14.4%) and 24 (11.5%). Discontinuation due to TEAEs was only 1.4% in both arms. The most common TEAEs were hematologic toxicities, which did not lead to SAEs or study drug discontinuation. Grade ≥3 gastrointestinal toxicities (2.4% versus 0) or renal toxicities (0 versus 0.5%) were rare. Conclusions: Adding fovinaciclib to first-line AI therapy provided a significant and clinically meaningful PFS benefit, along with consistent improvements in other survival outcomes and a manageable safety profile. These findings support fovinaciclib as a first-line treatment option for patients with HR-positive, HER2-negative advanced breast cancer. Clinical trial information: NCT05439499 .
Antitumor activity of amivantamab by consensus molecular subtypes in <i>RAS</i> / <i>BRAF</i> wild-type metastatic colorectal cancer: Secondary analyses from the phase 1b/2 OrigAMI-1 study.
3548 Background: Colorectal tumors are classified by mutational subtypes and sidedness, which inform treatment and outcomes. They can also be classified into four Consensus Molecular Subtypes (CMS1–4), with CMS2 ( EGFR -dependent, canonical) typically showing better prognosis and CMS4 ( EGFR -independent, MET pathway associated, mesenchymal) associated with poor prognosis and limited response to traditional EGFR inhibition (Thanki Int Biol Biomed J 2017, Woolston Cancer Cell 2019). In prior analyses, cetuximab monotherapy demonstrated greater antitumor activity against CMS2 RAS wild-type (WT) vs CMS4 RAS WT tumors (disease control rate [DCR]: 68% vs 29%; Chowdhury JCO Precis Oncol 2023), suggesting CMS4 may limit cetuximab efficacy de novo. Additionally, CMS2 to CMS4 subtype switching has been described as a cetuximab monotherapy resistance mechanism (Woolston Cancer Cell 2019). Amivantamab, an EGFR–MET bispecific antibody approved for EGFR -mutated NSCLC, has demonstrated antitumor activity in refractory metastatic colorectal cancer (mCRC), independent of sidedness. Given the role of MET in mesenchymal subtypes (CMS4), targeting with amivantamab could demonstrate antitumor activity in both CMS2 and CMS4. Methods: OrigAMI-1 (NCT05379595) enrolled participants with mCRC harboring WT KRAS , NRAS , BRAF , and EGFR ectodomain and without ERBB2 / HER2 amplification. Participants with left-sided mCRC without (Cohort A) or with prior anti-EGFR therapy (Cohort B), and those with right-sided disease (Cohort C), received intravenous amivantamab monotherapy. All enrolled participants had 2–3 prior lines of therapy in the metastatic setting. CMS assignment and expression changes in key EGFR/MET ligands at baseline (n = 76) and Cycle 3 Day 1 (C3D1; n = 17) were analyzed by whole-transcriptome RNA-sequencing of biopsies. Results: CMS2 (canonical) and CMS4 (mesenchymal) comprised ~95% of tumors. Clinical outcomes for CMS2 (n = 42) and CMS4 (n = 31) were comparable: median PFS was 4.2 vs 5.3 months ( P = 0.5), respectively, and median OS was 11.3 vs 13.5 months ( P = 0.6). PFS and OS within CMS2 and CMS4 subgroups remained consistent across sidedness. Overall response rate and DCR were comparable between CMS2 and CMS4 (26% vs 16% and 83% vs 74%, respectively). Genomic profiles derived from ctDNA were similar for CMS2 and CMS4; however, baseline AREG / EREG mRNA expression was higher in CMS2. Paired biopsies demonstrated antitumor activity with or without subtype switching at C3D1. Amivantamab treatment generally decreased AREG / EREG and increased HGF expression, independent of subtype or response. Conclusions: Amivantamab monotherapy demonstrated consistent antitumor activity in both canonical, EGFR -dependent (CMS2) and mesenchymal, EGFR -independent (CMS4) tumors unlike traditional EGFR inhibitors in refractory RAS / BRAF WT mCRC. Clinical trial information: NCT05379595 .
Temporal patterns of irAE onset by treatment regimen and organ system in a pan-cancer ICI-treated cohort.
e23398 Background: Immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) can manifest at heterogeneous timepoints, reflecting distinct patterns of immune activation. Early-onset irAEs may require heightened surveillance, yet clinical determinants of early onset remain poorly characterized. Methods: We identified a real-world cohort of metastatic cancer patients treated with ≥1 ICI within the Brown University Health system from 2015-2025. Patients who developed ≥1 irAE were included. Time from ICI initiation to first irAE was calculated and dichotomized as early ( < 6 weeks) vs ≥6 weeks. Clinical and treatment characteristics were compared across timing groups, and multivariable logistic regression was used to identify predictors of early onset. Treatment regimen, cancer type, race, biological sex, smoking history, and baseline creatinine were included as prespecified covariates. Odds ratios (OR) and p-values were reported. Results: Among 2,134 ICI-treated patients, 510 (23.9%) developed an irAE (median age 70, IQR 63-80; 56% male; 89% White; 79% ever smokers). The most common cancers were thoracic (45%), genitourinary (25%), and melanoma/skin (10%). Treatment regimens included ICI monotherapy (63%), ICI + targeted/chemotherapy (26%), and dual-ICI (10%). Among irAEs, 137 (26.9%) were early-onset and 373 (73.1%) occurred ≥6 weeks. Treatment regimen was significantly associated with early-onset irAEs, with lower odds of occurring < 6 weeks for ICI + targeted/chemotherapy (OR 0.46, p = 0.02) and ICI monotherapy (OR 0.48, p = 0.02) compared to dual-ICI. Endocrine irAEs exhibited a delayed temporal pattern, with significantly lower odds of occurring < 6 weeks (OR 0.32, p = 0.001). In a multivariable model including treatment regimen and endocrine irAEs, both covariates retained statistical significance, indicating independent effects. Race, biological sex, smoking history, thoracic cancer, genitourinary cancer, and baseline creatinine were not associated with timing of onset. Conclusions: Approximately one-quarter of irAEs occurred within 6 weeks of ICI initiation, with early-onset events more frequent among patients receiving dual-ICI therapy, whereas endocrine irAEs occurred later in the treatment course. Dual-ICI regimens generate stronger early immune activation, consistent with early-onset irAEs, while endocrine irAEs reflect evolving autoimmune glandular injury. These temporal patterns may inform regimen-specific surveillance strategies and support timing-informed approaches to irAE risk assessment.
The association between social capital and cancer screening rates in the United States.
e22550 Background: Cancer screening remains a cornerstone of cancer prevention, yet substantial geographic variation persists in screening uptake across the United States (U.S.). While prior studies have examined social capital and cancer screening primarily at the individual and neighborhood levels, data examining these associations at the county level remain limited. We assessed the association between county-level social capital and breast, cervical, and colorectal cancer screening rates across all 50 U.S states and Washington, DC. Methods: This was an ecological study using retrospective data obtained from the CDC’s PLACES 2023 dataset which includes county-level breast, cervical, and colorectal screening rates consistent with USPTF recommendations. County-level social capital was measured using the standardized Social Capital Index (SCI) developed by the U.S. Congress’ Social Capital Project, a composite measure encompassing family stability, trust and confidence in institutions, community cohesion, social network characteristics, and civic engagement. Counties were categorized as having low (less than −1 SD), average (−1 to +1 SD), or high (greater than +1 SD) social capital relative to the mean across all counties. Associations between county-level social capital and cancer screening rates were assessed using multilevel negative binomial regression models with robust standard errors. Results: Among 2,991 counties analyzed, 65% had average, 15% had low, and 20% had high social capital. Cervical cancer screening rates were significantly higher in counties with average (RR 1.010; 95% CI, 1.008–1.013) and high (RR 1.019; 95% CI, 1.015–1.022) social capital compared with counties with low social capital. Similarly, colorectal cancer screening rates were higher in counties with average (RR 1.021; 95% CI, 1.016–1.025) and high (RR 1.035; 95% CI, 1.029–1.041) social capital compared with low social capital counties. In contrast, breast cancer screening rates were modestly lower in counties with average social capital (RR 0.993; 95% CI, 0.989–0.997), compared with counties with low social capital, while the association with high social capital was inconclusive (RR 1.000; 95% CI, 0.994–1.005). Conclusions: Higher county-level social capital was associated with increased cervical and colorectal cancer screening rates, whereas associations with breast cancer screening were weaker and inconsistent. These findings suggest that structural and social determinants reflected in social capital such as family stability, community cohesion, civic engagement, and trust in institutions, may influence population-level uptake of preventive health services. Public health strategies that strengthen social capital may complement health system-based efforts to improve cancer screening coverage.