Browse Articles

Racial and ethnic differences in colorectal cancer screening effectiveness in the PLCO trial.

e15687 Background: Colorectal cancer (CRC) screening has been shown to reduce CRC-related mortality, yet substantial racial and ethnic disparities persist. Whether CRC screening confers equivalent mortality benefit across racial and ethnic groups, and the mechanisms underlying potential heterogeneity if any, remains unelucidated. Methods: We conducted a secondary analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, including 154,852 participants aged 55–74 years randomized to CRC screening or usual care. After excluding those with incomplete diagnostic data, 2,123 were eligible for analyses (929 in the screening arm, 1,195 in the control arm). Primary outcomes included cumulative incidence and CRC-specific mortality. Age-adjusted CRC mortality rates (AR, per 100,000) and crude rates (CR) were estimated by race/ethnicity and trial arm. Effect heterogeneity was assessed descriptively with trial-center analyses given correlations between center and racial/ethnic composition. Results: Overall, CRC screening was associated with lower cumulative CRC incidence and CRC-specific mortality compared with usual care. However, the magnitude of mortality reduction varied substantially by race/ethnicity (Table). Trial-center analyses demonstrated wide heterogeneity and screening–control separation across. For instance, data from Pennsylvania and Hawaii centers which has a high proportion of either non-Hispanic Black participants or Native Hawaiian/Pacific Islanders, had no mortality separation after 20 years of follow-up. Conclusions: Within a large randomized trial data, CRC screening effectiveness on mortality was not uniform across racial and ethnic groups. To enhance CRC screening benefits and to address the racial differences, downstream care processes have to be optimized rather than focusing on screening exposure alone. Future prospective data is warranted to address inequities in the full screening-to-diagnosis-to-treatment continuum and find out in which stage of care a care delivery disruption occurs. Colorectal cancer mortality by race/ethnicity and screening arm in the PLCO trial. Race/Ethnicity Age-standardized Mortality Rate per 100,000 (95% CI)　 Risk Reduction (95% CI) Screening Control Absolute Relative (%) White 362.1(313.8–410.3) 538.5(479.4–597.6) 176.4(100.1–252.7) 32.8(20.1–43.4) Black 680.8(405.8–955.7) 808.6(499.1–1118.2) 127.9(-286.2–541.9) 15.8(-46.9–51.7) Hispanic 455.8(86.7–824.8) 654.3(198.2–1110.4) 198.5(-388.2–785.3) 30.3(-102.8–76.1) Asian 333.0(84.7–581.2) 588.2(252.3–924.0) 255.2(-162.4–672.9) 43.4(-44.8–77.9)

Predictors of pathologic complete response following neoadjuvant TCHP in HER2-positive breast cancer.

e12519 Background: In HER2+ breast cancer (BC), pathologic complete response (pCR) following HER2-directed neoadjuvant therapy is an established surrogate marker for long-term survival. In a HERMET trial, the addition of metformin to standard docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) did not result in a significant improvement in pCR rates. We performed a post hoc analysis of all participants enrolled in the HERMET trial to identify pathologic predictors of pCR. Methods: This single-center study enrolled 61 patients with operable HER2+ BC (tumor ≥2 cm and/or node-positive) who were randomized 1:1 to neoadjuvant TCHP for 6 cycles + placebo (n = 30) or metformin (n = 31). The primary endpoint was pCR, defined as the absence of residual invasive disease in the breast and axillary lymph nodes at the time of surgery. Logistic regression was performed using a prespecified multivariable model that included estrogen receptor (ER) status (0–9% vs ≥10%), HER2 category (IHC 3+ vs 2+), and Ki-67. Results: 61 patients were enrolled between August 17, 2017, and March 21, 2023; median age was 51 years. Overall, pCR was achieved in 30 of 61 (49.2%). HER2 IHC 3+ disease was present in 53 (86.9%), while 8 (13.1%) had HER2 IHC 2+ FISH positive disease. pCR occurred in 29 of 53 (54.7%) with HER2 IHC 3+ tumors compared with 1 of 8 (12.5%) with HER2 IHC 2+ tumors (Fisher’s exact p = 0.053). Ki-67 was available for 51 patients. Median Ki-67 was higher among patients who achieved pCR compared with those who did not (40% vs 32%). On univariate analysis, higher Ki-67 was associated with increased odds of pCR (odds ratio [OR] 1.03 per 1% increase; p = 0.028). In the prespecified multivariable model including ER status and HER2 category (N = 61), ER 0–9% was independently associated with higher odds of pCR compared with ER ≥10% (adjusted OR 2.7; 95% CI, 1.0–7.6; p = 0.049). HER2 IHC 3+ disease demonstrated a large but statistically borderline association with pCR compared with HER2 IHC 2+ disease (adjusted OR 7.8; 95% CI, 0.9–70; p = 0.061). Conclusions: Although patients with HER2+ BC defined as IHC 2+ with FISH amplification are treated similarly to those with IHC 3+ disease, their pCR rates were comparable to those observed in hormone receptor–positive, HER2-negative BC. Clinical trial information: NCT03238495 . pCR by ER status and HER2 category. Variable Group N pCR N (%) ER 0-9% 23 15 (65.2) ≥10% 38 15 (39.5) HER2 2+ 8 1 (12.5) 3+ 53 29 (54.7)

The procedural position of multi-cancer early detection (MCED) in cancer screening paradigm: A simulation modelling study.

e23138 Background: While multi-cancer early detection (MCED)—a promising approach using one blood sample to detect multiple cancers—could supplement or replace standard-of-care (SOC) screening, its optimal position in population-based screening paradigm remains uncertain. This study aimed to evaluate the effectiveness and cost-effectiveness of integrating MCED at various phases of the screening process. Methods: We recalibrated the National Cancer Center (NCC) modeling framework to align with the latest population-based empirical data. The calibrated model was then used to simulate the natural history of the five highest-mortality cancers in China (lung, liver, colorectal, esophageal, and stomach) over a lifetime horizon for the entire Chinese population, with screening targeted at ages 50–74.The evaluated screening scenarios included no screening, risk-based SOC screening, and four screening strategies incorporating MCED: MCED used as a risk-assessment method (S1), MCED used as a clinical screening method (S2), MCED interception followed by SOC triage for MCED-negative individuals (S3), and MCED used as a supplemental screening for questionnaire non-high-risk individuals and SOC non-compliers (S4). The primary outcome was the 5% discounted incremental cost-effectiveness ratio (ICER), with a willingness-to-pay (WTP) threshold of three times per-capita GDP ($42,857 per quality-adjusted life-year [QALY] gained). Secondary outcomes included stage III-IV cancer diagnoses, cancer deaths, number needed to screen (NNS) to prevent one death. Sensitivity analyses were performed to assess the probability of cost-effective. Results: Compared with no screening, discounted ICERs for risk-based SOC and MCED strategies S1 to S4 were $1,808, $52,195, $26,726, $26,876, and $16,595 per QALY, respectively. Versus risk-based SOC, the ICERs for S4 and S3 were $33,809/QALY and $39,761/QALY. When using risk-based SOC as reference, S3 reduced stage III–IV cancer diagnoses by 6.9% and cancer mortality by 4.3%, while also improving screening efficiency by reducing the NNS from 240 to 81. S4 provided intermediate benefits with a 1.8% reduction in mortality, whereas S1 and S2 yielded smaller mortality reductions (<1.2%). Probabilistic sensitivity analysis indicated that S3 had the highest probability of being cost-effective at the WTP threshold (43.9%). Conclusions: Using MCED interception followed by SOC triage for MCED-negative individuals (S3) likely represents the most appropriate position for MCED in the cancer screening paradigm. In contrast, using MCED as a supplemental screening for questionnaire non-high-risk individuals and SOC non-compliers (S4) offers a lower-cost but suboptimal alternative.

Trended real-world analysis of drug-treated mCRPC: Assessment of a diagnostic and co-management gap despite community practices managing a higher-risk population.

e17038 Background: the management of metastatic castration-resistant prostate cancer (mCRPC) is increasingly complex, demanding greater multidisciplinary collaboration and reliance on advanced diagnostics. This study quantifies the real-world evolution of co-management, patient risk profiles, and diagnostic testing patterns between US academic and community settings. Methods: data were extracted from the Ipsos Global Oncology Monitor. We analyzed two consecutive 12-month cohorts of US mCRPC patients on active systemic therapy: 791 patients from Aug '23-Sep '24 and 645 from Aug '24-Sep '25. A year-over-year comparative analysis of patient characteristics, co-management rates, and diagnostic utilization was performed, stratifying by specialty (Oncology vs. Urology) and practice type (Academic vs. Community). Results: a significant trend towards multidisciplinary care was observed, with overall co-management increasing from 32% to 43% (p < 0.01). This growth was driven exclusively by the academic setting, which saw a threefold increase (18% to 64%; p < 0.01), while the community setting remained stable at 36%. This occurred even as community practices managed a higher-risk patient population, characterized by a dual burden of both more aggressive disease biology (67% vs. 48% with Gleason score 8-10; p < 0.01) and a greater prevalence of significant comorbidities (e.g., hypertension 70% vs. 41% p < 0.01; cardiovascular disease 25% vs. 15%; p < 0.01). Concurrently, the gap in PSMA-PET utilization between Oncologists/Heam Oncs (increasing from 60% to 80%) and Urologists (stationary at ~55-58%) widened significantly. This diagnostic disparity is also correlated with regimen choice, with Urologists favoring more often hormonal-only regimens linked to less frequent (quarterly) PSA testing. Conclusions: The mCRPC treatment landscape is rapidly consolidating around a co-management model, but this evolution is primarily confined to the academic setting, likely due to the infrastructure required for complex novel therapies. A concerning and widening gap in the adoption of PSMA-PET imaging persists, with urologists lagging significantly behind oncologists. This diagnostic disparity creates a critical barrier to care, as it may limit access to PSMA-targeted therapies for the higher-risk population predominantly managed in the community. These findings highlight an urgent need for educational and system-level changes to harmonize the application of advanced diagnostics and ensure equitable access to modern, evidence-based mCRPC care across all practice settings.

Early lessons from the implementation of a pan-African clinico-genomic cancer platform: The African Cancer Atlas.

10602 Background: Limited representation of African populations in cancer genomics constrains the clinical applicability of precision oncology. We describe the establishment and early outcomes of The African Cancer Atlas (TACA), a multi-site platform integrating genomics, harmonized clinical data, and community engagement for adult breast cancer research across Africa. Methods: TACA, led by Yemaachi Biotech, has so far been implemented across five countries (Ghana, Nigeria, Côte d’Ivoire, Kenya, and Seychelles). In early 2025, foundational activities included institutional review board (IRB) approvals, execution of memoranda of understanding and material transfer agreements, site activation, and structured engagement with clinicians, patient advocates, and community stakeholders through Yemaachi’s African Cancer Network to support trust-building and study uptake. Participant recruitment began in July 2025. Breast cancer patients were enrolled following IRB approval, with informed consent supported by site-based education on genomics research. Clinical data were captured in UVOSYO-Yemaachi’s clinical database. Peripheral blood was collected at recruitment, and formalin-fixed paraffin-embedded (FFPE) tumor tissue was obtained subsequently and shipped to our central laboratory in Accra. Blood and tissue underwent DNA extraction and quantitative and qualitative quality control (QC) prior to sequencing. Results: To date, 236 participants have been recruited across the five TACA sites. Blood-derived DNA demonstrated acceptable quality for downstream sequencing, whereas FFPE tumor tissue quality varied substantially, leading to exclusion of cases that failed QC. Among enrolled participants, 97.9% were female, with a mean age of 50.8 years (SD 13.1). A total of 26.7% reported a family history of cancer, with participants in Seychelles having the most significant family history of 87% (p < 0.001) Triple-negative breast cancer accounted for 38.1% of tumors overall, ranging from 21.1% in Kenya to 68.1% in Nigeria. Significant between-country variation was observed for triple-negative breast cancer (p < 0.001) and hormone receptor status (all p < 0.001). Key implementation challenges included prolonged IRB approval timelines related to limited familiarity with cancer genomics, cross-border biospecimen transport constraints necessitating in-country DNA extraction in some settings, and variability in FFPE tissue quality impacting sequencing yield. Conclusions: TACA demonstrates the feasibility of coordinated multi-country recruitment and clinical data harmonization for adult cancer genomics in Africa, while highlighting critical regulatory, logistical, and biospecimen quality barriers.

Real-world comparative effectiveness of decitabine/cedazuridine plus venetoclax versus azacitidine plus venetoclax in older or unfit patients with newly diagnosed acute myeloid leukemia.

e18533 Background: Older and medically unfit patients with Acute Myeloid Leukemia (AML) are unable to tolerate intensive induction chemotherapy and historically experience poor survival. The addition of venetoclax to hypomethylating agents (HMAs) has significantly improved outcomes in this population. However, real-world outcomes frequently differ from clinical trial results due to comorbidity burden, treatment interruptions, and toxicity. Oral decitabine/cedazuridine offers pharmacokinetic equivalence to intravenous decitabine and greater treatment convenience, yet comparative real-world effectiveness and safety data versus venetoclax/azacitidine remain limited. We evaluated survival and adverse event outcomes between these regimens in a multi-center real-world cohort. Methods: CWe performed a retrospective cohort study using the TriNetX federated electronic health record network. Adults >50 years with newly diagnosed AML receiving first-line decitabine/cedazuridine plus venetoclax (CDV) or azacitidine plus venetoclax (AV) were included. Patients with acute promyelocytic leukemia or prior stem cell transplantation were excluded. Propensity score matching was conducted for age, sex, race, prior myelodysplastic syndrome, TP53 status, and Charlson Comorbidity Index–associated conditions. All analysis were carried out post matching. The primary outcome was all-cause mortality (ACM). Secondary outcomes included anemia, neutropenic fever, neutropenia, major adverse cardiovascular and cerebrovascular events (MACCE), tumor lysis syndrome, and sepsis. Outcomes were assessed at 6 months, 1 year, and 2 years using Kaplan–Meier analysis and Cox proportional hazards models. Results: After matching, 233 patients were included per cohort. ACM for CDV versus AV at 6 months, 1 year, and 2 years was 21.0% vs 27.9%, 32.6% vs 42.5%, and 37.8% vs 49.8%, respectively. Compared to AV, CDV significantly reduced the risk of mortality at 1 year (HR 0.739; 95% CI 0.548-0.997, p=0.047) and 2 years (HR 0.704; 95% CI 0.533-0.929, p=0.013). At 1 year, CDV was associated with reduced hazard of anemia (HR 0.510, 95%CI 0.433-0.765, p=0.0001), neutropenic fever (HR 0.554, 95%CI 0.427-0.719, p<0.0001), and MACCE (HR 0.606, 95%CI 0.360-0.961, p=0.045), with no significant differences in neutropenia, tumor lysis syndrome, or sepsis. Conclusions: In this real-world analysis of older or unfit patients with newly diagnosed AML, CDV was associated with significantly improved survival and a favorable toxicity profile compared with AV. These findings extend pivotal trial data into routine clinical practice and suggests CDV may have a clinically meaningful advantage over AV in this high-risk population. Prospective studies are warranted to confirm these observations and refine frontline treatment selection.

A phase I/II study of CDX-1140, a CD40 agonist, in combination with capecitabine and oxaliplatin (CAPOX) and pembrolizumab in subjects with biliary tract carcinoma: Phase 1 results.

4129 Background: Second line therapy shows limited efficacy in biliary tract carcinoma (BTC). We have demonstrated potent anti-tumor effects of anti-CD40/anti-PD1 plus chemotherapy in murine cholangiocarcinoma (Diggs et al. J Hepatol 2021 74:1145). CDX1140 is a human IgG2 activating anti-CD40 antibody. Based on these preclinical studies we conduct a phase I/II study testing the combination of CDX-1140 plus pembrolizumab (pem), capecitabine (cap) and oxaliplatin (ox) in BTC patients previously treated with at least one line of systemic therapy. Safety and tolerability were assessed in the phase I portion. Methods: Between Aug 2024 and Jun 2025 a total of 9 participants were enrolled into the Phase I portion of the trial. 1000 mg cap was given p.o. bid on days 1-14 plus 130 mg/m2 ox i.v. on day 1 of a 21-day treatment cycle. CDX1140 was dosed at 0.72 mg/kg dose level 1 (DL1) and 0.36 mg/kg (DL-1) i.v. on day 8 plus 200 mg pembrolizumab i.v on day 8. The DLT period was 35 days, starting on day 8 of cycle 1 after CDX-1140 administration. Enrolment into the phase II portion was started after the recommended dose of CDX-1140 had been determined. Results: We enrolled a total of 9 patients (pts) into the phase I portion. All patients had received at least one line of prior systemic chemotherapy including antiPD1/PD-L1. 2 out of the first 3 pts treated at DL1 developed a grade 3 thrombocytopenia and we reduced dosing to DL-1. 1 out of 6 pts treated at DL-1 developed a grade 3 thrombocytopenia and DL-1 was considered safe. Other treatment related grade 3/4 AEs were: lymphopenia, leukocytopenia, anemia, skin rash and hypotension. Most patients developed grade 1/2 arthralgia. At data cut-off (Dec/15/25) PFS for the nine patients was 7.3 months (range: 2.3 - 19.1 months). DCR was 56 % with 2 patients demonstrating a PR and 3 pts with SD. Conclusions: We have completed the phase I portion of our trial and demonstrate that CDX1140 plus pem, cap and ox is safe and tolerable in pts with BTC. No new and or unexpected toxicities were observed. We observed encouraging clinical responses. Patients will be enrolled to the phase II portion and updated results will be presented. Clinical trial information: NCT05849480 .

An Artificial Molecular Pump Powered by Light

ABSTRACT Replicating the ability of biological systems to convert energy into directional molecular motion to perform functions is a central challenge in nanoscience. Artificial molecular pumps that can move substrates energetically uphill remain elusive, particularly when powered by light in an autonomous fashion. We report a molecular pump that uses light to actively transfer macrocycles from solution into a high‐energy intramolecular compartment. The system operates via a photon‐driven energy ratchet mechanism, sustaining a non‐equilibrium distribution of species under continuous irradiation. All relevant kinetic and thermodynamic parameters were determined, and a comprehensive mechanistic model was developed. This minimalistic and robust design establishes a foundation for fully synthetic light‐controlled non‐equilibrium systems with potential applications in adaptive materials and solar energy conversion.

Biogenic, facile, and sustainable pathway of obtaining ZnO-PS nanoparticles through Pisum sativum waste peels, their characterization and cytotoxic assessment against HeLa cell line via experimental and computational methods

Oxygen‐Synergized All‐Fiber Hydrovoltaics With Milliamp Output Toward Self‐Powered Breathable Electronics

ABSTRACT Eruptive development of wearable technology has evoked great demand for decentralized energy supplies harvesting ubiquitous environmental stimuli, such as water evaporation. Conventional hydrovoltaic power generators (HPG) collect energy through directional ion migration originating from water gradient in functional materials, while the unsatisfactory electrical output severely hinders the practical applications. Herein, we develop a liquid‐induced high‐performance all‐fiber HPG for sustainable self‐powered electronics by constructing an ion‐enriched storage electrode and coincidently inducing an oxygen‐involved reaction in the solid‐liquid‐gas interface of the functional layer. Taking advantage of the hierarchical structural configuration of HPG, we verify the dual pathway synergistic electricity generation mechanism of hydrovoltaic effect and oxygen‐involved redox through in situ characterization and theoretical calculations. Significantly, the HPG exhibits an impressive power density of 164.5 µW cm −2 , an extraordinary current density of 1.25 mA cm −2 , a high air‐permeability of 428.4 mm s −1 , and an excellent sustainability with high output retention of 88% after 150 cycles of washing, outperforming most of the counterparts. As demonstration of applications, the as‐assembled HPG power supply packs can directly drive various wearable electronics without extra energy storage devices or rectification circuits, demonstrating the great expectation for the development of evaporation energy harvesters and self‐powered wearable electronics.

A Bipolar Integrated Electro‐Chemocatalysis System for Continuous‐Flow Paired Synthesis of Cyclohexanone Oxime at Industrial‐Relevant Current Density

ABSTRACT ε‐Caprolactam production critically depends on cyclohexanone oxime (CHO), yet its sustainable synthesis remains constrained by the handling and utilization of hydrogen peroxide (H 2 O 2 ). Here, we developed a bipolar integrated electro‐chemocatalysis system (BIECS) that enables continuous‐flow paired CHO synthesis under ambient conditions with unprecedented efficiency. Using oxygen‐vacancy‐enriched bismuth oxide nanofibers as a bifunctional electrocatalyst, the system simultaneously drives the two‐electron oxygen reduction and water oxidation reactions at the cathode and anode, respectively, achieving remarkable cell Faradaic efficiencies up to 165% for H 2 O 2 production, which then on‐site reacts with cyclohexanone and NH 3 over titanium silicon‐1 with near‐unity selectivity. Consequently, the BIECS delivers remarkable apparent electron efficiency of 120%–160% for cascade CHO production and achieves an exceptional productivity of up to 5.04 mmol h −1 cm −2 at industrial‐relevant current density with excellent stability over 150 h for continuous‐flow electrolysis. Combined experimental and theoretical studies reveal that the oxygen vacancies of the catalyst modulate the adsorption energetics and configuration of the key OOH * intermediate, thereby promoting highly selective two‐electron pathways at both electrodes and enhancing the cascade ammoximation kinetics. This work establishes a scalable strategy that integrates paired electrocatalytic H 2 O 2 synthesis with chemocatalytic ammoximation, providing a highly efficient platform for sustainable CHO production.

Nutritional care practices in oncology services in Senegal: A multicenter health services research audit.

e23115 Background: Malnutrition is a major yet under-addressed determinant of outcomes in cancer care. Its impact on morbidity, treatment tolerance, and survival is well established; however, integration of nutritional assessment into routine oncology services remains inconsistent, particularly in low- and middle-income countries. This study evaluated nutritional care practices as a component of health service delivery in oncology and onco-hematology units in Senegal. Methods: We conducted a multicenter professional practice audit using a structured questionnaire assessing four domains: organization of nutritional services, healthcare providers’ knowledge, clinical practices, and perceived barriers to nutritional care. Physicians and nurses involved in the management of solid and hematologic malignancies were surveyed across major oncology referral centers in Dakar. Descriptive analyses were performed using Sphinx Plus and SPSS software. Results: Forty-eight healthcare professionals participated, including residents (52.1%) and nurses (20.8%). One-third worked in oncology-related departments. Most respondents (64.6%) reported the absence or unawareness of a formal nutrition support structure within their institution. Nutritional screening was primarily considered the responsibility of the treating physician (54.2%), with limited multidisciplinary involvement. Screening relied mainly on body mass index and weight loss (66.7%), while validated tools were rarely used. Nutritional evaluation was more frequently performed at admission (56.3%) than during hospitalization (27.1%). Assessment remained subjective in 37% of cases, and dietitian involvement was inconsistent (40.7%). Structural barriers were prominent, with reported difficulties in implementing enteral (96.9%) and parenteral nutrition (100%). Only 12.5% of participants had received formal training in malnutrition management. Conclusions: Nutritional care delivery in oncology services in Senegal is limited by organizational gaps, insufficient training, and lack of multidisciplinary coordination. Strengthening nutrition services represents a key opportunity for improving quality of cancer care.

A complement atlas of head and neck squamous cell carcinomas to reveal intratumoral complement control and identify factor H as a therapeutic target in oral cavity and HPV-negative oropharyngeal tumors.

e18049 Background: Oral Cavity Squamous Cell Carcinoma (OCSCC) and HPV-negative oropharyngeal SCC (HPV-negative OPSCC) together account for nearly 40% of Head and Neck SCC (HNSCC) and remain an unmet clinical need, with poor prognosis and limited benefit from multimodal therapies, including immune checkpoint inhibitors. The innate immune complement system has emerged as a druggable pathway in cancer, with strategies targeting C3a/C5a signaling or tumor-bound complement regulators to restore membrane attack complex (MAC)–mediated cytotoxicity. GT103, an antibody targeting tumor cell–associated complement regulator Factor H (FH), exemplifies this approach and is currently being evaluated in lung cancer in combination with anti-PD1. However, the role and regulation of complement activation across HNSCC subtypes remain poorly defined. Methods: We established a comprehensive complement atlas of HNSCC using an integrated Complementomics approach combining hyperplex imaging, plasma profiling, and clinical annotation from an institutional longitudinal biobanking cohort: SCANDARE (NCT03017573). Results: We enrolled 159 patients with early-stage HNSCC in the SCANDARE study. Plasma profiling of 17 complement proteins and activation fragments revealed selective alternative pathway activation in OCSCC and OPSCC, with coordinated elevation of Ba and the anaphylatoxins C3a, and C5a. Tumor profiling revealed a dense infiltration of C5aR1-positive macrophage and neutrophil subsets, driven in part by local C5a generation in OCSCC and OPSCC. In situ complement cascade did not reach the terminal step with formation of cytotoxic Membrane Attack Complex (MAC). This could be explained by the binding of FH to tumor cells surface of OCSCC and OPSCC HPV-negative, but not OPSCC HPV-positive. This FH was likely derived from the circulation, as local expression was minimal and it was elutable from our ex vivo preclinical model (Patient Tumor-Derived Fragment), indicating active local inhibition of alternative pathway–mediated cytotoxicity. As autoantibodies against this form of tumor-bound FH tumor neoantigen were protective in lung and renal cancer, we searched them in HNSCC. Positivity was observed in only a small number of patients, primarily in FH-rich OCSCC and HPV-negative OPSCC, suggesting that this potentially protective autoimmunity is rare. Conclusions: OCSCC and OPSCC HPV-negative exhibit a distinctive complement phenotype characterized by systemic anaphylatoxin generation without intratumoral complement-mediated cytotoxicity, mediated by tumor cell-associated FH. Targeting this FH with GT103 may overcome the regulatory barrier, restore immunogenic cell death mediated by the MAC, and enhance responses to immunotherapy, supporting clinical evaluation in these HNSCC subtypes.

Minimal residual disease dynamics in newly diagnosed multiple myeloma and impact on progression-free survival: A cohort study.

7570 Background: Minimal residual disease (MRD) is a sensitive tool for evaluating treatment response in multiple myeloma (MM) and is a surrogate marker of progression-free survival (PFS) and overall survival (OS). Consecutive MRD evaluations offer important information regarding the depth and the duration of response to treatment and can be used to guide the patients’ management. Methods: This single center, retrospective study included patients with newly diagnosed MM (NDMM), who were evaluated with at least 3 consecutive MRD tests. Four subgroups of patients were identified: sustained MRD positive (sMRDpos), sustained MRD negative (sMRDneg), converted to MRD negative (conMRDneg) and converted to MRD positive (conMRDpos). The aim of the study was to compare PFS between groups. Results: Overall, 335 NDMM patients were included in the analysis. The median age at diagnosis was 59 years (range 35-89), and the median number of assessments was 5 (range 3-14). Regarding risk stratification, 56 (16.7%) were ISS-3, and 52 (15.5%) were labeled as high-risk per the novel IMS/IMWG HRMM criteria. The median number of MRD evaluations in each patient was 5 (range 3-13). One third received quadruplet regimen. The median follow-up of the cohort was 6.1 years. Patient distribution according to MRD status was as follows: 191 (57%) sustained negativity, 40 (12%) sustained positivity, 53 (15.8%) converted to negative, whereas 51 (15.2%) converted to positive. Median PFS and OS were not achieved in any of the MRD subgroups. Sustained MRD negativity was associated with superior PFS compared to all the other subgroups (HR=0.21, 95% CI: 0.10 – 0.42, p<0.001). Sustained MRD positivity was associated with significantly inferior PFS compared to sMRDneg (HR=4.84; 95% CI: 1.91 – 12.30, p<0.001) and conMRDpos had also inferior PFS compared to the sMRDneg (HR= 6.04, 95% CI: 2.74 – 13.31, p<0.001). Furthermore, the presence of at least one MRD positive, at any time-point, was associated with inferior PFS compared to the sMRDneg (HR= 4.29, 95% CI: 2.05 – 8.99, p<0.001). Among the sustained MRD negative patients, high risk cytogenetics yielded a trend towards worse PFS (HR= 1.42. 95% CI: 0.30 - 6.69, p=0.659), possibly suggesting that sMRDneg overrides high risk cytogenetics. Finally, among the 165 patients who sustained MRD negativity, the median number of MRD tests were 5 (range 3-14). Among these patients with more than 5 tests had superior PFS, compared to less than 5, with a HR= 0.04, 95% CI: 0.01 – 0.33, p=0.003 signaling no further need of additional consecutive MRD testing in such patients. Conclusions: In patients with NDMM in the real-world setting, sustained MRD negativity is associated with prolonged PFS, even in HR patients, whereas the presence of even one MRD positive result impacted PFS.

From infancy to young adulthood: Exploring the divergent genomic mechanisms that drive AML.

6544 Background: Pediatric & young adult Acute Myeloid Leukemias (pAML & YA AML) are an uncommon, heterogenous, & clinically challenging group of malignancies, as age ranges widely & proper therapy selection (i.e. pediatric vs. adult regimens, etc.) can be unclear. The genomics of these disorders can help understand distinct disease biology, better risk stratification, & improve outcomes. Methods: Bone marrow, peripheral blood, or FFPE samples from 870 suspected AML patients were sequenced using a 302 gene panel to detect SNVs/indels. 466 underwent RNA fusion detection of 184 genes & DNA analysis for CNV detection of 24 genes. Only pathogenic/likely pathogenic variants were included in the analysis. AML patients were split into 4 groups based on age: Infant (≤3, n=30), Childhood (4-14, n=51), Adolescent (15-19, n=51), YA (20-35, n=738). 4750 DNA/RNA sequenced adult AML patients (>35) were also included in the analysis. Statistics were performed using Fisher’s exact test. Results: pAML patients (infant, childhood, & adolescent) had a high prevalence of FLT3 & NRAS variants (17.4% & 15.2%) & fusions (26.2%) while YA AML had a high prevalence of fusions (29.2%), FLT3 (20%), NRAS (12.5%), & WT1 (12.6%) variants. Adult AML had a high prevalence of TET2 (18.4%), DNTM3A (18.3%), ASXL1 (16.8%), SRSF2 (14.8%), & TP53 (14.2%) variants, highlighting an increased prevalence of mutations associated with clonal hematopoiesis or prior chronic myeloid neoplasms. Infant AML had a higher number of GATA1 variants (33.3% vs. 0% - 2%, p<0.00001) vs. childhood, adolescent, & YA AML; trisomy 21 was present in 90% of patients by CNV detection. Fusions were only found in 5% of infant AML (p=0.02) vs. 29.2% - 34.5% in other groups. FLT3 variants were lower in infant (10%) and childhood AML (13.7%) vs. adolescent (25.5%) & YA (20%) while NRAS variants were higher in adolescent AML (21.6% vs. 6.7% - 13.7%). Childhood AML had a higher prevalence of RUNX1 fusions (16.1% vs. 0 – 5.4%, p=0.03) & Adolescent AML had a higher prevalence of PML::RARA fusions (13.8% vs. 0% – 6.5%) vs. other groups. YA AML had a higher prevalence of WT1 variants (12.6% vs. 0% - 7.8%, p=0.02). CNV loss in IKZF1 (7p12) were more prevalent in adolescent AML (10.3% vs. 0-0.5%, p=0.002); EZH2 CNV loss (7q36) were more prevalent in YA & childhood AML (4.7% & 3.4% vs. 0%). Upon aggregating genes by their molecular function, infant AML had a lower prevalence of variants in epigenetic genes (6.7% vs. 15.57-24.8%, p=0.02), RAS (10% vs. 23.2%-25.5%), & signaling genes (16.7% vs. 27.5% – 41.2%). Variants in DNA repair genes were more frequent in adolescent AML (13.7% vs. 3.9% - 6.7%, p=0.01). Conclusions: Infant, childhood, adolescent, & YA AML harbor unique genetic profiles that distinguish themselves from each other and reflect divergent and evolutionarily favored mechanisms behind leukemogenesis. Understanding these genetic profiles can help predict prognosis & help tailor more effective treatments.

JAK inhibitors vs traditional therapy for myelofibrosis; A meta-analysis of randomized clinical trials.

e18603 Background: Myelofibrosis (MF) is a type of myeloproliferative neoplasm. The pharmacological standard of care is the Janus kinase (JAK) inhibitor class (e.g., Ruxolitinib, Pacritinib, Momelotinib, Fedratinib), which targets key disease drivers. However, traditional therapies, often grouped as Best Available Therapy (BAT), including hydroxyurea and hematopoietic stem cell transplant, remain a significant comparator. A precise synthesis of data is needed to define the overall risk-benefit profile of JAK inhibitors versus these traditional treatments. This meta-analysis compares the efficacy (e.g., spleen volume reduction) and safety(e.g., hematological adverse events) of JAK inhibitors against traditional therapies for MF. Objective: To compare efficacy and safety of JAK inhibitors against traditional therapies in adult patients( age > 18 years ) with myelofibrosis. Methods: Following PRISMA guidelines, a systematic literature search of Randomized controlled trials(RCTs) was conducted in PubMed, Embase, and Clinical Trials Databases upto January 2026. We compared the efficacy and safety of JAK inhibitors to the traditional therapies often grouped as best available therapies including hydroxyurea, hematopoietic stem cell transplant and other measures in adult patients( age >18 years) diagnosed with Myleofibribrosis. Outcomes were splenic volume reduction and adverse hematological events such as Anemia and thrombocytopenia. Results: Eight RCTs involving 1917 patients with Myleofibrosis: 62% (1233) of patients were randomized to receive JAK inhibitors and 36% ( 682) participants were randomized to receive traditional therapies. This meta-analysis showed that the number of patients achieving spleen volume reduction ≥ 35 % at 24 weeks was significantly higher in JAKi compared to traditional therapies including placebo (RR: 6.11, 95% CI 3.56 to 10.49, I2= 0 %, with sensitive analysis by excluding two studies, while without sensitive analysis including two studies(RR:9.34, 95%CI 3.73 to 23.34, I2=77%) and the difference was statistically significant. Compared to traditional therapies, patients treated with JAKi showed higher adverse hematological adverse effects such as Anemia (OR: 1.55, 95%CI; 1.02 to 2.35, I2=56%) and thrombocytopenia (OR: 1.54 95% CI; 0.85 to 2.2.79, I2=84%). However, even though thrombocytopenia was observed, it was not found to be statistically significant. Conclusions: Overall, this meta analysis shows that JAK inhibitors have higher efficacy in reducing the splenic volume as compared to traditional therapies. However, JAK inhibitors are associated with more hematological side effects, specifically Anemia and thrombocytopenia. The limitations in the new trials should also be kept in mind while interpreting the results.

Second primary lung cancer in lung cancer survivors: Clinical characterization and screening.

e22532 Background: Lung cancer survivors remain at risk for second primary lung cancers (SPLC). However, optimal surveillance strategies are poorly defined, and the incidence, timing, and clinical characteristics of SPLC remain insufficiently characterized. Methods: We conducted a retrospective institutional cohort study including patients with histologically confirmed lung cancer. SPLC was defined as a new primary lung tumor arising after an initial non-metastatic diagnosis. Demographic, clinical, pathological, and outcome data were collected. Eligibility for lung cancer screening was assessed at the time of initial lung cancer diagnosis according to U.S. Preventive Services Task Force (USPSTF) criteria. Group comparisons were performed using chi-square or Fisher’s exact test and t-test or Mann–Whitney test, as appropriate. Results: Among 562 patients with lung cancer, 41 (7.3%) developed a second primary lung cancer (SPLC). The SPLC cohort was predominantly female (70.7%), with a mean age of 63.4 years at SPLC diagnosis. Most patients had a history of smoking exposure (82.1%), while 17.9% were never-smokers. In addition, 30.8% had a prior non-pulmonary primary malignancy. The mean interval between the first and second primary tumors was 53.1 months, frequently exceeding commonly adopted post-treatment surveillance periods. Eleven patients (26.8%) were diagnosed with SPLC outside established screening criteria. Compared with those meeting screening eligibility, patients outside screening criteria were more likely to have adenocarcinoma histology (p = 0.01), to be never-smokers (p < 0.001), to have no history of COPD (p = 0.02), and to present with metastatic disease more frequently (p = 0.03). Conclusions: SPLC frequently develops after prolonged intervals beyond standard surveillance. Nearly one in four cases arise outside current screening criteria and are associated with a higher burden of metastatic disease, underscoring limitations of existing screening frameworks and supporting risk-adapted surveillance strategies for lung cancer survivors.

Regional disparities in prostate cancer mortality in the African Union: A retrospective analysis (1980-2023).

5053 Background: Prostate cancer represents a substantial health burden among men in Africa and is an important contributor to cancer-related mortality, with considerable variation observed across African regions. This study uses data from the Global Burden of Disease (GBD) project to evaluate regional variations in prostate cancer age-standardized death rates (ASDR) from 1980 to 2023. Methods: Prostate cancer mortality data were extracted from the GBD 2023 database for the period 1980–2023. Age-standardized death rates (ASDRs) per 100,000 population were obtained for African regions as defined by the GBD classification, including Northern Africa, Central Africa, Eastern Africa, Western Africa, Southern Africa and the African Union aggregate. Temporal patterns from 1980 to 2023 were evaluated using joinpoint regression analysis, and average annual percentage change (AAPC) estimates were calculated to quantify long-term trends. Statistical significance was determined using corresponding p-values (less than 0.05) and 95% confidence intervals. Results: From 1980 to 2023, a gradual rise in the ASDR per 100,000 was observed in the African Union with substantial regional variations. It gradually increased from 8.78 per 100,000 in 1980 to 11.44 per 100,000 in 2023 (AAPC: 0.68; 95% CI: 0.51 to 0.84; p< 0.000001). The highest ASDR were observed in Central Africa. It increased from 13.72 per 100,000 in 1980 to 18.63 per 100,000 in 2023 (AAPC: 0.77; 95% CI: 0.62 to 0.91; p< 0.000001). This was followed by Western Africa increasing from 10.64 per 100,000 in 1980 to 16.06 per 100,000 in 2023 (AAPC: 0.96; 95% CI: 0.82 to 1.09; p< 0.000001). A slight increase was also observed in Southern Africa rising from 10.70 in 1980 to 12.07 (AAPC: 0.26; 95% CI: -0.0045 to 0.543; p< 0.053). Eastern Africa showed a slight increase in ASDR from 8.95 per 100,000 in 1980 to 10.36 per 100,000 in 2023 (AAPC: 0.43; 95% CI: 0.24 to 0.62; p< 0.000009). Northern Africa had consistently the lowest ASDR. It rose from 2.35 per 100,000 in 1980 to 4.32 per 100,000 in 2023 (AAPC: 1.41; 95% CI: 1.27 to 1.56; p< 0.000001). Conclusions: Prostate cancer remains the leading cause of cancer-related death among men in the African Union, particularly in Central Africa. High mortality is driven by limited healthcare access and late-stage diagnosis. Strengthening screening programs and improving specialized care can reduce this rising burden. Trends in age standardized death rate (ASDR) per 100,000 due to prostate cancer in the African Union. Region ASDR 1980 (per 100,000) ASDR 2023 (per 100,000) AAPC (95% CI) African Union 8.79 11.45 0.68* (0.51 - 0.84) Central Africa 13.72 18.63 0.77* (0.62 - 0.92) Eastern Africa 8.95 10.36 0.44* (0.24 - 0.63) Northern Africa 2.35 4.33 1.42* (1.27 - 1.57) Southern Africa 10.70 12.08 0.26* (-0.01 -0.54) Western Africa 10.64 16.06 0.96* (0.82 - 1.10) AAPC = Average Annual Percentage Change; *p< 0.05.

Utilization of computed tomography scans and lung cancer development in patients with pulmonary symptoms: A national database study.

e13594 Background: Lung cancer screening with chest computed tomography (CT) is recommended for asymptomatic 50–80-year-olds who have a significant smoking history. Pulmonary symptoms in such patients may further increase the risk of a lung cancer diagnosis. We sought to determine rates of CT utilization and lung cancer diagnosis in otherwise screen-eligible patients who present for an ambulatory medical encounter with pulmonary symptoms. Methods: We identified patients in the Epic COSMOS national database, age 50-80, who had an ambulatory office visit in 2023 for > 1 of 9 defined ICD-10 codes of pulmonary symptoms associated with lung cancer (cough, shortness of breath, chest pain on breathing). We excluded patients with prior cancer, those with hemoptysis, and those who had a chest CT within the preceding year. To evaluate the relationship of symptoms with lung cancer, we also analyzed screen-eligible patients (based on age and a > 20 pack year smoking history) with an anchor encounter in 2023 who did not have pulmonary symptoms. Results: We identified 1,047,894 analyzable patients with pulmonary symptoms, 37,339 who were otherwise screen eligible. In addition, we identified 360,531 screen-eligible patients without symptoms. In those with pulmonary symptoms, a chest CT was performed in 5.1% of patients within 2 months of the ambulatory visit. On multivariable analysis, factors associated with chest CT utilization included smoking, age, race, gender, ethnicity, and the presence of multiple pulmonary symptoms ( p <0.0001 for all comparisons). The highest rate of CT utilization, 12.2%, was in otherwise screen-eligible patients with pulmonary symptoms. The 2-year cumulative incident rate of lung cancer for those with pulmonary symptoms was 0.8%, with higher rates noted in people who smoke (current/former smoker: 2.0% (n=163,439) vs. never-smoker: 0.3% (n=231,296), p <0.0001). Comparison of 2-year lung cancer rates within patients with > 20 pack year histories with or without symptoms revealed a much higher rate in those who had pulmonary symptoms (4.6% (n=37,339) vs. 3.1% (n=360,531), p <0.0001, on Cox proportional Hazards Ratio (HR) 1.79, 95% CI: 1.69 – 1.90). Patients with > 20 pack year histories with symptoms had lower rates of surgery and stereotactic body radiation and higher rates of systemic therapy for their cancer compared to patients with > 20 pack year histories without symptoms, suggesting they had more advanced stage disease. Conclusions: Chest CT imaging is uncommon in patients 50–80 years old presenting with pulmonary symptoms, even in those who would otherwise meet eligibility criteria for lung cancer screening. Patients aged 50-80 with > 20 pack year smoking history who have pulmonary symptoms have a relatively high 2-year incidence of lung cancer.

Spatial characterization and predictive implications of the tumor immune microenvironment in stage III melanoma under neoadjuvant immunotherapy.

e21534 Background: Despite recent trials establishing neoadjuvant immune checkpoint blockade (ICB) as the standard of care for clinical stage III melanoma, nearly half of patients fail to achieve adequate pathologic response and clinical trajectory remains highly variable. These limitations emphasize the need for robust biomarkers to guide patient selection. Here, we used spatial proteomics to characterize the tumor immune microenvironment before and after neoadjuvant ICB, and to identify features of favorable response. Methods: Samples were collected from 10 stage III melanoma patients who underwent neoadjuvant nivolumab/relatlimab (n = 7) or ipilimumab/nivolumab (n = 3). Pre-ICB samples were obtained via core biopsy or fine-needle aspiration at diagnosis, while post-ICB samples were from lymph node dissection. Clinical outcomes were documented by pathologist assessment and systematic chart review. Multiplex immunofluorescence was performed using the Lunaphore COMET. A custom Python-based pipeline was created for data analysis after image acquisition. Results: Spatial mapping of annotated cell types revealed marked differences in immune cell distribution and composition correlating with treatment response. Pre-ICB samples from patients with major pathologic response (MPR, ≤10% residual viable tumor) showed decreased segregation between immune-rich and tumor regions, whereas post-ICB samples revealed response-dependent patterns of immune infiltration: non-MPR patients with rapid clinical progression (n = 3) exhibited sparse immune cells within the tumor bed, non-MPR patients with clinically stable disease (n = 3) showed immune aggregates, and MPR patients (n = 4) demonstrated dense immune infiltration. From a compositional standpoint, MPR patients exhibited a higher relative abundance of immune cells with lymphoid predominance, including increased CD8 + :CD4 + T cell and CD8 + T cell:M2 macrophage (CD68 + CD163 + ) ratios in both pre- and post-ICB samples. Within this group, CD8 + T cells displayed lower post-ICB expression of PD-1 and LAG-3. Notably, CD8 + HLA-DR + NK cells (CD3 - CD56 + ) were also uniquely identified in B cell clusters post-ICB in MPR patients, suggesting an immunoregulatory phenotype with cytotoxic potential. In contrast, non-MPR patients were characterized by a CD4 + T cell predominant lymphoid population and a higher relative abundance of myeloid cells after treatment. Conclusions: Collectively, these findings highlight CD8 + T cell-centric spatial immune features as potential predictive biomarkers of response to neoadjuvant ICB in stage III melanoma. The emergence of CD8 + HLA-DR + NK cells further suggests coordinated innate-adaptive immune crosstalk beyond adaptive enhancement alone. Moreover, in non-MPR patients, persistence of immune aggregates post-ICB may help distinguish a favorable clinical trajectory.