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Anthocephalus cadamba leaf extract mediated synthesis of copper oxide nanoparticles and evaluation of their methylene blue dye degradation, antioxidant and anti-inflammatory properties

Reconciling High‐κ and Wide‐Bandgap Dielectrics (TbOCl) with Intrinsic Stability in 2D Electronics

ABSTRACT The practical implementation of two‐dimensional (2D) transistors is fundamentally limited by the lack of gate dielectrics that can simultaneously deliver a high dielectric constant, a wide bandgap, strong breakdown strength, and long‐term environmental stability‐an often‐overlooked yet critical requirement for reliable device integration. Here, we report 2D single‐crystalline TbOCl nanosheets as gate dielectrics that uniquely reconcile these competing demands. TbOCl exhibits a high dielectric constant (12.5), an ultrawide bandgap (∼6.6 eV), and a high breakdown field (11.9 MV cm −1 ). MoS 2 field‐effect transistors (FETs) gated by TbOCl exhibit excellent electrostatic control, yielding a near‐ideal subthreshold swing of 72 mV dec −1 , a small hysteresis of only 8 mV, and an ultra‐low gate leakage current of ∼10 −13 A. Notably, TbOCl‐based devices maintain ultrastable electrical performance after more than 9 months of ambient storage with negligible performance degradation. The superior stability originates from an intrinsic dual‐antioxidation mechanism that effectively suppresses oxidative degradation of the dielectric. Furthermore, logic inverters fabricated with TbOCl gate dielectrics exhibit fast switching behavior, with rise and fall times of 80 and 16 µs, respectively. Together, these results establish TbOCl as a stable, high‐performance 2D dielectric platform, offering a viable pathway toward reliable 2D electronic devices.

Forecasting the head and neck cancer burden in Vietnam: Projections from the Hanoi Cancer Registry.

e18075 Background: In Vietnam, head and neck cancers (HNC) represent a growing public health challenge. However, limited long-term, population-based evidence on HNC incidence complicates efficient health system planning, resource allocation, and prevention strategies. The objective of this study was to project HNC incidence in Northern Vietnam through 2045. Methods: HNC data (ICD-10 codes C00–C14 and C30–C32) from 1991 to 2020 were obtained from the Hanoi Cancer Registry, alongside population data from the Vietnam General Statistics Office. Age-standardized rates (ASR) were calculated based on the WHO World Standard Population (2000). Poisson regression models were used to identify joinpoints in historical trends and to estimate incidence over the next two decades. Future incidence was projected under the assumption that the estimated Annual Percentage Change (APC) from the most recently identified trend segment would remain constant through 2045. Results: The annual number of HNC cases in Hanoi increased fivefold between 1991 and 2020 (206 vs. 1,025 cases). ASR increased from 19.0 to 25.1 per 100,000 person-years. By 2045, the total annual number of new cases is projected to reach 2,501 (144% increase vs. 2020), with ASR projected to rise to 35.2 per 100,000 person-years (Table 1). The sharpest increases are projected among older age groups (60+ years), with incidence rates in men remaining consistently higher than in women. Conclusions: HNC incidence in Hanoi has risen historically and is projected to more than double by 2045 compared to 2020. This surge is driven by both the increasing risk of disease (rising ASR) and population aging. Our findings underscore the urgent need for targeted early screening, workforce expansion in oncology, and strengthened health system infrastructure to manage the escalating public health demand in Vietnam and other lower- and middle-income countries with similar demographics and cancer burden. Two-decade projection of age-standardized HNC incidence rates per 100,000 person-years in Hanoi, Vietnam. Year Cases (N) Crude Rate (95% CI) ASR (95% CI) 2020 1,025 12.5 (11.7-13.2) 25.1 (23.5-26.6) Projections 2025 1,262 14.1 (13.3-14.9) 26.9 (25.4-28.5) 2030 1,525 16.1 (15.3-16.9) 28.7 (27.3-30.2) 2035 1,848 18.7 (17.8-19.5) 30.7 (29.3-32.1) 2040 2,173 21.2 (20.3-22.1) 32.8 (31.4-34.2) 2045 2,501 23.6 (22.7-24.5) 35.2 (33.8-36.6)

Intismeran autogene to induce de novo neoantigen-specific T cells as adjuvant therapy in melanoma.

9564 Background: Intismeran autogene (intismeran) is an individualized mRNA-based neoantigen (neoAg) therapy designed to enhance endogenous antitumor T-cell responses by targeting patient-specific tumor mutations. In the phase 2 KEYNOTE-942 trial of resected high-risk melanoma, intismeran combined with pembrolizumab (pembro) significantly improved recurrence-free survival (RFS) vs pembro alone. Previously, it was shown that the combination induced greater expansion of de novo T-cell clonotypes, which correlated with RFS in the intismeran arm. Here, we show that de novo T-cell clonotypes are reactive to intismeran-encoded neoAgs. Methods: Peripheral leukapheresis samples longitudinally collected from a subset of intismeran plus pembro treated participants (pts) with melanoma from phase 1 and 2 studies (NCT3313778 and NCT03897881) were assessed at single-cell level to characterize neoAg-specific T cells. In 7 pts, functional assessment of neoAg-reactive CD8⁺ T cells was performed by intracellular cytokine staining and activation-induced marker assays. To define antigen specificity and phenotype of intismeran-induced T cells, we combined longitudinal bulk and single-cell T-cell receptor (TCR) sequencing with functional validation assays from 3 pts. De novo expanded TCRs were tested in Jurkat NFAT-luciferase reporter cells for reactivity against pt-specific intismeran mRNA cassettes and individual neoAgs. For reactive TCRs, minimal epitopes were mapped and mutant vs wild-type peptide reactivity was quantified. Results: Using the combination of bulk and single-cell TCR sequencing and Jurkat NFAT-luciferase reporter assays in 3 pts, we identified 20 TCRs expanded following intismeran therapy across all pts mapping to 11 neoAgs, providing direct evidence of intismeran-driven polyclonal T-cell expansion. These responses targeted multiple neoAgs with persistence >100 days after last intismeran dose. Reactive TCRs showed stronger recognition of mutant vs wild-type peptides, confirming antigen specificity. Functional assessment of T cells from 7 pts showed that neoAg-reactive CD8⁺ T cells secreted IFNγ and TNFα and coexpressed markers for degranulation/activation upon peptide restimulation, demonstrating functional activity. Flow cytometry–based characterization of neoAg-reactive T cells ex vivo revealed that these cells predominantly exhibited an effector-memory phenotype. Upon stimulation, they were polyfunctional (IFNγ⁺ TNFα⁺), mobilized CD107a, and were granzyme B⁺, consistent with cytotoxic effector function relevant to tumor control. Conclusions: Complementary sequencing and functional analyses demonstrated that adjuvant therapy with intismeran plus pembro induced durable, polyclonal, neoAg-specific T-cell responses with effector-memory characteristics, providing mechanistic data consistent with the clinical benefit observed in pts with melanoma. Clinical trial information: NCT3313778 & NCT03897881 .

Response rate of MSI-high/dMMR gastric, esophageal, and gastroesophageal junctional adenocarcinoma to neoadjuvant immunotherapy: A systematic review.

e16134 Background: The success of immunotherapy to treat metastatic microsatellite instability high (MSI-h)/deficient mismatch repair (dMMR) cancers has generated interest for potential use in the neoadjuvant setting. The National Comprehensive Cancer Network (NCCN) Guidelines for MSI-h gastric, gastroesophageal, and rectal cancer recommend considering neoadjuvant immunotherapy in the localized setting, but the recommendation is based on small phase II trials with only a few dozen patients. Despite promising initial results, evidence to support this practice remains limited. Methods: To strengthen the case for using neoadjuvant immunotherapy to treat localized gastrointestinal cancers, we conducted a systematic review to identify patients who received neoadjuvant immunotherapy for localized MSI-H/dMMR gastric, gastroesophageal, colon, and rectal cancers to determine the overall pathologic complete response (pCR) and major pathologic response (MPR, defined as at least 90% tumor shrinkage) rates. Gastric and gastroesophageal data was further analyzed for pCR and MPR rate with respect to immunotherapy only versus chemoimmunotherapy regimens. PubMed search parameters included microsatellite instability high (MSI-high) OR Mismatch repair deficient (dMMR) AND neoadjuvant immunotherapy. Case reports were excluded. Results: Review of the MSI-h/dMMR gastric and gastroesophageal populations included 264 patients from 18 studies, with a pCR (45.42%) and 28 with 90-99% tumor shrinkage for a MPR 55.28%. In the colon and rectal cancer populations, 701 patients across 18 studies showed pCR 70.19% and MPR 79.74% (68.91% and 83.58% for colon, respectively, and 89.36% and 94.68% for rectal). For gastric and gastroesophageal cancers, response rates for patients receiving immunotherapy only were comparable to those receiving chemoimmunotherapy with a PCR rate of 45.37% for IO therapy and 42.27% for chemoimmunotherapy. Conclusions: Our findings strengthen the NCCN guidelines recommending the use of neoadjuvant immunotherapy for MSI-h/dMMR localized gastrointestinal cancers. While the gastric and gastroesophageal data is insufficiently powered to draw a final conclusion, it appears to indicate that conjugate chemotherapy may not be required alongside immunotherapy. Further research should seek to determine the optimal immunotherapy regimen, including duration, and evaluate the potential for nonoperative management in patients who have a complete clinical response to treatment. Rate of pCR/MPR in MSI-high/dMMR esophageal, gastric, and gastroesophageal cancers - immunotherapy versus chemoimmunotherapy. Treatment for esophageal, gastric, gastroesophageal cancers Evaluable Patients pCR pCR (%) MPR MPR (%) pCR + MPR (%) Immunotherapy 108 49 45.37 17 15.74 61.11 Chemoimmunotherapy 97 41 42.27 2 2.06 44.33

Primary treatment approaches in advanced HRD-positive (BRCAm and BRCAwt) ovarian cancer in the Russian non-interventional OVARD study.

e17561 Background: Homologous recombination deficiency (HRD) positive status is a clinically meaningful biomarker in ovarian cancer (OC), associated with improved progression-free survival with the addition of olaparib (ola) to bevacizumab (bev) as maintenance after first-line therapy in PAOLA-1 study. The OVARD study evaluated real-world primary treatment patterns in HRD+BRCAm and HRD+BRCAwt high-grade OC (HGOC). Methods: This non-interventional study analyzed demographics, clinical characteristics, surgery and systemic treatment in HRD+BRCAm and HRD+BRCAwt HGOC using descriptive statistics; multivariable analysis explored factors associated with treatment choice. Results: A total of 400 patients (pts) with newly diagnosed HRD-positive HGOC (FIGO IC–IV) who completed surgery and first-line carboplatin/paclitaxel with or without bev at 29 Russian sites were analyzed: 234 BRCAm and 160 BRCAwt pts. HRD+BRCAm pts were younger (median 52 vs 61 years, p=0.000001) and more frequently had family (44.5% vs 7.5%) and personal (breast cancer 13.3% vs 1.3%) cancer history. HRD status results became available at median 83 days after diagnosis with primary cytoreduction and 105.5 days with interval cytoreduction from routine HRD-testing. Bev was added to first-line chemotherapy in 14.1% (33/234) of BRCAm vs 29.4% (47/160) of BRCAwt pts (p=0.00021), with subsequent ola+bev maintenance in 5.6% vs 17.5% (p=0.00014). Ola maintenance monotherapy was used more often in BRCAm (62.8% vs 35.6%, p=0.000001), while bev monotherapy was more frequent in BRCAwt (14.4% vs 5.1%, p=0.00153). Among pts with residual disease after cytoreduction, response rates to first-line therapy were comparable between BRCAm and BRCAwt (Table). Conclusions: HRD-positive status has become a routine biomarker at HGOC diagnosis and substantially influences first-line and maintenance treatment selection, with bev-containing regimens more often chosen in BRCAwt and ola-based maintenance widely used in both subgroups in real-world practice. Clinical trial information: NCT05918042 . Response on 1 st line therapy in pts with residual disease after cytoreduction. Type of objective response BRCAmn/N BRCAm% BRCAwtn/N BRCAwt% P value Complete response 19/43 44.19 13/36 36.11 0.46653 Partial response 7/43 16.28 10/36 27.78 0.21550

Long-term survival rates and cure modeling with dostarlimab plus chemotherapy in mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) primary advanced or recurrent endometrial cancer in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial.

5501 Background: Dostarlimab + carboplatin-paclitaxel (CP) demonstrated significant progression-free survival (PFS) and clinically meaningful overall survival benefits in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer (EC) in Part 1 of the phase 3 RUBY trial (NCT03981796). Median PFS was not reached for dostarlimab + CP vs 7.7 months for CP alone in this population. Moreover, plateauing of the PFS Kaplan-Meier (KM) curve suggested that a subset of patients with dMMR/MSI-H EC achieved durable disease control and potential for curative intent with dostarlimab + CP. Mixture cure models (MCMs) complement conventional outcome metrics by quantifying the proportion of patients considered "cured" and by modeling PFS among patients who remain uncured. Here we present an MCM applied to the PFS data from the dMMR/MSI-H population with up to 4.5 years of follow-up treated with dostarlimab + CP. Methods: At a median follow-up of 55.6 months (range 49.9–67.7 months), descriptive PFS analyses were conducted in the dMMR/MSI-H population from RUBY Part 1. MCMs were fitted to PFS data to estimate the proportion of patients treated with dostarlimab + CP who had a curative potential. In the MCM, patients with curative potential were assumed to be free of recurrence- and disease-related mortality risks, implying that any additional PFS events would come from death. Mortality risks were assumed to be similar to the background mortality expected in the general population (with matched demographic characteristics). Conversely, the uncured population was considered to be at risk for disease recurrence and death from all causes. Results: There was a low rate of progression since PFS was first analyzed, with only 4 new events reported with an additional 2.5 years of follow-up. The 4-year PFS rate was 57.9% (95% CI, 42.3%–70.6%) in the dostarlimab + CP arm vs 15.7% (95% CI, 7.2%–27.0%) in the control arm. The MCM analysis demonstrated that the majority of patients with dMMR/MSI-H EC (54%; 95% CI, 35%–72%) were considered “cured” with dostarlimab + CP. The PFS survival curves estimated from MCMs closely followed the KM curves reported from the RUBY trial data. The model appropriately captured the long-term survival plateau, instilling confidence in the robustness of the model predictions. Conclusions: With a minimum of 4 years of follow-up, updated PFS analyses demonstrated that the majority of patients remained alive and progression-free, illustrating durable disease control. Model-based predictions indicated the potential for cure in the dMMR/MSI-H primary advanced or recurrent EC population receiving dostarlimab + CP. These analyses may assist oncologists in understanding long-term survival outcomes and the proportion of patients with a curative potential. Clinical trial information: NCT03981796 .

Bridging guidelines and interoperability: mCODE STU4 coverage of NCCN breast cancer decision criteria.

e23188 Background: The minimal Common Oncology Data Elements (mCODE) initiative defines structured data elements using Fast Healthcare Interoperability Resources (FHIR) to improve interoperability of oncology electronic health record (EHR) data. However, mCODE does not explicitly encode disease-specific clinical decision logic contained in practice guidelines such as those from the National Comprehensive Cancer Network (NCCN). Understanding how mCODE represents guideline-driven decision criteria is essential to determine whether EHR data can reliably support guideline-based treatment recommendations, automated assessment of guideline adherence, and analysis of outcomes using routinely collected clinical data. We evaluated the extent to which NCCN breast cancer guideline decision criteria are representable using mCODE STU4 and identified gaps requiring extension. Methods: The NCCN Breast Cancer Guidelines (Version 1.2026) sections BINV-1 through BINV-16 and BINV-K were reviewed to identify decision criteria that drove branching within guideline pathways. Criteria were included if they required categorical or numerical values to determine downstream management. Each decision value was mapped to mCODE STU4 profiles when available, otherwise to US Core profiles or to standard terminologies (SNOMED CT, LOINC). Values lacking a structured representation were classified as unmappable. Results: Sections BINV-1 through BINV-16 and BINV-K yielded 28 decision criteria with 97 distinct values. Of these, 69 values (71%) were representable using mCODE profiles for staging, biomarker status, tumor characteristics, genetic status, performance status, and age. Fourteen values (14%) mapped to US Core profiles for pregnancy, menopausal or menstrual status, lymphovascular invasion, and symptomatic status. Fourteen values (14%) across seven criteria lacked representation and were unmappable. These included surgical margin status and distance, fertility preservation concerns, treatment candidacy assessments, and genomic assay thresholds, including 21-gene recurrence score cutpoints. Several mapped criteria lacked sufficient terminology granularity to represent NCCN-specific thresholds, such as ER-positive (> 10%) versus ER low-positive (1–10%). Conclusions: Most NCCN breast cancer decision values relevant to initial workup and treatment selection for non-metastatic invasive disease are representable using existing mCODE or US Core resources. However, clinically important gaps remain in surgical pathology detail, genomic assay thresholds, and treatment candidacy assessments. These findings define a focused roadmap for targeted mCODE profile and terminology extensions needed to more fully support portable guideline-based care, quality measurement, and secondary use of EHR data across health systems.

Incidence of uveal melanoma surveillance and related outcomes in the immunotherapy era in a rural healthcare system.

e21598 Background: Uveal melanoma has an incidence of 5 cases/million in the United States, with higher incidence among men and those of fairer complexions. Stage I patients have a 20% risk of recurrence to a distant site. Those who do recur tend to have poor outcomes, with median overall survival ranging from 3 to 30 months. This disease has no proven adjuvant therapy. After initial definitive treatment, surveillance alone is typically the most common recommendation, but guidance for surveillance imaging is lacking. We sought to determine the incidence of uveal melanoma surveillance along with associated health-related outcomes in these patients in our rural healthcare system. Methods: Following Institutional Review Board approval, we identified patients with uveal melanoma diagnoses treated with definitive therapy who had ≥3 months of follow-up between January 2010 and January 2023. Patients with metastatic disease at presentation were excluded. Via retrospective review of electronic health records, we captured demographics, disease, treatment, and recurrence specific variables. Appropriate analysis was completed in R version 4.4.3 with a significance level of 0.05. Results: Fifty-seven patients met inclusion criteria. Of these, 31 (54%) were men, 57 (100%) were White, and their median age at diagnosis was 62 years. Ten (18%) underwent enucleation for initial definitive treatment, 39 (68%) had plaque/radiation therapy, 2 (4%) had transpupillary thermal therapy, and 6 (11%) had unknown primary treatment. Following initial definitive treatment, 22 (39%) patients had routine surveillance visits, and 11 (19%) had routine imaging of the liver to screen for metastatic disease. Married patients were less likely than unmarried to participate in surveillance, while the remaining demographic variables were not significantly different. In total, 16 (28%) patients had recurrence. Of these, 9 (56%) had oligometastatic disease defined as 1 to 3 sites of metastasis, and 14 (88%) had at least 1 liver metastasis. Ten of the 16 (63%) received either checkpoint therapy or bispecific T-cell engager immunotherapy. Seven of the 16 (44%) participated in some form of surveillance. Overall survival of those who had surveillance imaging was not significantly different from those who did not. Conclusions: A minority of patients with definitively treated uveal melanoma participated in surveillance visits, and even fewer completed regular screening imaging. Recurrence rates reflected the national average and frequently involved the liver. No differences in survival rates were seen between patients who underwent surveillance (with or without imaging) and those who were not surveilled. This study was limited by small sample size at a single institution. More research is needed to assess the utility of uveal melanoma surveillance.

Implementing scalable psychosocial interventions to address patient-identified needs in hereditary cancer syndromes.

e22652 Background: Individuals with hereditary cancer syndromes (HCS), including hereditary breast and ovarian cancer and Lynch syndrome, face lifelong surveillance demands and complex psychosocial burdens affecting both cancer survivors and high-risk individuals. In our previous study, 81% of HCS patients expressed interest in support services including emotional and behavioral support, care coordination, family testing, and peer support. This study evaluates implementation and outcomes of targeted psychosocial interventions addressing patient-identified needs. Methods: As part of a quality improvement initiative, patients with HCS receiving care through a genetics and personalized cancer prevention program were offered support from an embedded genetic social worker. Services included: (1) peer support groups, (2) care coordination, (3) counseling addressing distress and family dynamics, (4) family cascade testing assistance, and (5) behavioral health referrals. Patients were contacted 2-4 weeks post-appointment to assess service utility. Follow-up included self-reported stress "before" and "after" using a validated 0-10 Numeric Rating Scale for stress (NRS) and likelihood of independently seeking services. Demographic and cancer history data were abstracted from medical records. Results: Eighty-six patients received social work support (median age 42 years, range 20-81; 92% female; 64% non-Hispanic White; 76% tested within past year; 29% cancer survivors; 46% Ashkenazi Jewish). Pathogenic variants included BRCA1/2 (45), CHEK2 (7), Lynch syndrome genes (13), RAD51D (3), BRIP1 (1), ATM (1). All completed stress assessments; 73% reported high stress (≥5) before intervention, decreasing to 47% after, with mean scores from 5.6 to 3.9 (95% CI, 1.4-2.4; p<0.001; Table 1). Patients utilized peer support groups (51%), care coordination (49%), family testing (39%), psychosocial counseling (29%). Many reported being unlikely to independently access support groups (70%) or psychosocial counseling (36%). Among support group attendees, 85% reported improved well-being. Conclusions: Psychosocial and educational interventions tailored to patients with HCS are feasible, well utilized, and reduce patient-reported stress. Integrated into routine gynecologic oncology care, these services address key challenges in coping, decision-making, and prevention, offering a scalable and replicable model for hereditary cancer care. Future studies are needed to evaluate strategies to optimize and expand scalability. HCS patient-reported stress levels before and after genetic social work intervention (n=86). Measure Before Intervention After Intervention Change p-value Mean stress score (0-10 NRS) 5.6 3.9 -1.7 <0.001 High stress prevalence (≥5), n (%) 63 (73%) 40 (47%) -26% <0.001

Colorectal cancer risk in cystic fibrosis: Systemic review and quantitative synthesis of epidemiologic, genetic, and clinical evidence.

e15639 Background: Increased survival rates in individuals with cystic fibrosis (CF) have revealed multiple long-term complications. Recent data suggests a substantially increased risk of these individuals developing colorectal cancer (CRC), potentially associated with CFTR dysfunction, altered intestinal mucus, chronic inflammation, or microbiome-mediated genotoxicity. We conducted a systematic review and quantitative synthesis to characterize CRC risk in CF and related CFTR-associated susceptibility. Methods: PubMed, Embase, and Google Scholar were searched for eligible studies evaluating CRC risk in CF patients. Population-based studies reporting standardized incidence ratios comparing CF patients to the generalized population were included for quantitative synthesis. Long-term follow up data was summarized narratively and categorized. Additionally, cohort, hospitalization, and single-center studies describing age of onset, clinical phenotype, and temporal trends were included in the narrative analysis. Genetic association studies evaluating CRC risk among heterozygous CFTR variant carriers were reviewed. Results: Two population based studies from England and France reported CRC-specific SIRs of 5.0 (95% CI 3.2-6.9) and 4.41 (95% CI 1.62-9.59) respectively, demonstrating markedly increased risk of CRC in CF patients. Long-term follow-up data from a study conducted in the US supports this association with reported SIRs of 7.4 (95% CI 3.7-13.2) at 10 years and 6.2 (95% CI 4.2-9.0) at 20 years among non-transplant CF patients. Additionally, across registry and cohort studies, CRC has occurred at younger age in CF patients, and there is increased prevalence of precancerous lesions identified via colonoscopy. Hospitalization based analyses show increased CRC over time in CF population with higher risk of CRC-related hospitalization compared to control group. Genetic association analyses demonstrated that heterozygous carriers of pathogenic CFTR variants exhibited modest, yet statistically significant increase in risk of CRC, with odds ratios ranging from 1.11 to 1.33, suggesting CFTR-related susceptibility. Mechanistic studies implicate that CF-associated mucus dysfunction and increased vulnerability to colibactin-mediated DNA damage may be an underlying cause of colorectal carcinogenesis. Conclusions: Overall, multiple lines of evidence demonstrate a substantially increased risk of CRC in CF patients. Complementary genetic, clinical, and mechanistic data support the possibility that CFTR plays a central role in susceptibility to CRC. These findings reinforce current recommendations for earlier CRC screenings and continued surveillance in CF patients and emphasize the need for prospective population-based studies as life expectancy among CF patients continue to improve.

Deep learning–based imaging models for predicting immune checkpoint inhibitor response in non–small cell lung cancer: A systematic review.

e20582 Background: Imaging-based machine learning models have been widely studied in medicine. Aside from diagnostic models, advanced models predicting prognosis or treatment response has been further studied. Predicting response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) is one of the important challenges in medicine since response is heterogenous, and multiple studies were done to predict ICI response. However, substantial heterogeneity exists across studies in terms of imaging modalities, feature extraction strategies, or modeling approaches, limiting the interpretability and robustness of the results. Methods: We conducted a systematic review of imaging-based machine learning studies evaluating immunotherapy response prediction. Eligible studies used imaging-derived inputs, including CT, PET-CT, whole-slide images (WSI), to predict treatment response or clinical outcomes. When multiple models with small methodological variation were reported within a single study, only the most representative or best-performing model was included. Given marked heterogeneity in model design and input data, pooled performance estimates and formal meta-analysis were not performed. Results: A total of 97 studies comprising 255 models were included. Most models (81%) relied on radiomics-based feature extraction combined with regression or classical machine learning models, whereas only 23 models from 15 studies used end-to-end deep learning. In subgroup analyses, non-radiomics models (0.77) demonstrated a higher pooled AUC than radiomics-based models (0.73). CT-based models (0.75) were the most frequently studied and showed superior pooled performance compared with other modalities such as PET-CT (0.66) and WSI (0.62). Outcome definitions varied widely, and external validation was inconsistently performed. Conclusions: : This systematic review shows that imaging-based immunotherapy response prediction research is mostly radiomics-driven models combined with classical machine learning, while end-to-end deep learning approaches remain uncommon. This pattern likely reflects practical constraints, as many studies analyzed 3D imaging data and integrated clinical features in relatively small cohorts, which may have limited the usage of end-to-end training or fine-tuning strategies, making radiomics-based classical machine learning approaches a more practical choice. The relatively lower performance observed for PET-CT and WSI models likely reflects smaller sample sizes and limited validation rather than modality limitations. Overall, heterogeneity in diagnostic modalities, modeling strategies, outcome definitions, and external validation is observed and more studies using larger cohorts with external validation will be important in AI-based immunotherapy response prediction studies.

Clinical outcomes in older adults with advanced thyroid cancer.

e18012 Background: Age is a prognostic factor in thyroid cancer, with older adults being at higher risk of aggressive histologic and genomic variants. Despite this, little is known about the benefits and risks of palliative-intent systemic therapy in older adults with advanced thyroid cancer. Methods: We performed a retrospective review of patients ≥ 65 years of age with advanced thyroid cancer referred to medical oncology at our institution for consideration of systemic therapy between 2015 and 2024 ( n = 114). Clinicopathologic, treatment, adverse event, and outcomes data were analyzed. Univariable and multivariable Cox proportional hazards models and Poisson regressions models were used to test for associations between clinicopathological variables and clinical outcomes. The study protocol was approved by the University Health Network Research Ethics Board. Results: 114 patients ≥ 65 years of age were referred to medical oncology for consideration of systemic therapy between 2015 and 2024. The median age was 73 (range 65 – 98) and median Charlson Comorbidity Index (CCI) score (not including points for age and thyroid cancer diagnosis) was 0. Most patients were functionally independent (93%) and had an ECOG performance status of 0 or 1 (88%). 65/114 patients received first-line systemic therapy. Median overall survival (OS) was 4.04 years (95% CI 3.09 – not estimable) in the whole cohort and 3.91 years (95% CI 2.84 – not estimable) in the treated cohort. First-line time-to-treatment discontinuation (TTD) in the treated cohort was 1.59 years (95% CI 0.75 – 4.45). Higher age, male sex, and anaplastic histology predicted shorter OS in the whole cohort. Higher age, male sex, higher CCI, and presence of a BRAF and/or TERT mutation predicted worse OS and/or TTD amongst treated patients. For patients receiving lenvatinib ( n = 37), adverse events led to significant proportions of patients requiring dose reductions (65%), treatment breaks (78%), emergency department (ED) visits (16%), and drug discontinuation (14%). Adverse events led to treatment breaks (56%), ED visits (67%), and drug discontinuation (22%) in patients receiving dabrafenib + trametinib ( n = 9). Geriatric oncology referral, polypharmacy, and presence of a BRAF mutation predicted higher number of ED visits in treated patients. Conclusions: Although survival outcomes were comparable to those described in younger adults, adverse events were common and impactful in older adults. Starting dose optimization and close monitoring based on an individual's risk factors for adverse events and ED visits should be considered. The benefits and risks of treatment must be reflected upon by oncologists with recommendations guided by patient values and preferences.

HRS-1167 (M9466), a PARP1 inhibitor, combined with abiraterone acetate and prednisone in metastatic castration-resistant prostate cancer: A phase 1b/2 study.

5036 Background: PARP inhibitors combined with novel hormonal agents (NHAs) have shown improved progression-free survival in metastatic prostate cancer compared to NHA alone. HRS-1167 (M9466) is a novel highly selective PARP1 inhibitor with established antitumor activity in advanced solid tumors. This multicenter, open-label, dose-finding and efficacy expansion phase 1b/2 study assessed the safety, tolerability and preliminary efficacy of HRS-1167 combined with AA-P in mCRPC (ClinicalTrials.gov, NCT06689163). Methods: Chinese adult mCRPC patients with homologous recombination repair mutations who were previously treated were enrolled. Eligible patients received oral HRS-1167 at 30 mg QD or 50 mg QD, combined with AA-P (abiraterone acetate 300 mg QD; prednisone 5 mg BID). Primary objectives were safety and tolerability. Results: As of Oct 31, 2025, 58 patients were enrolled and treated (HRS-1167 30 mg, n = 33; HRS-1167 50 mg, n = 25; prior NHA, 100%; BRCA mutation, 44.8%). Median follow-up was 3.0 months and 6.2 months in the 30 mg and 50 mg cohorts. Preliminary efficacy was summarized in the Table. Among patients with evaluable efficacy (n = 47), prostate-specific antigen response (PSA50) rate was 36.4% (8/22) in the 30 mg cohort and 52.0% (13/25) in the 50 mg cohort. Confirmed objective response rate (cORR) was 37.5% and 14.3%, and disease control rate (DCR) was 81.8% and 92.0%, respectively. HRS-1167 plus AA-P demonstrated particularly encouraging efficacy in patients with BRCA mutations: PSA50 rate was 100% (6/6) in the 30 mg cohort and 81.8% (9/11) in the 50 mg cohort, and cORR was 100% (2/2) and 33.3% (1/3), respectively. DCR was 100% in the BRCA -mutated subgroup. Treatment-emergent adverse events (TEAEs) were reported by 26 (78.8%) and 25 (100%) patients in the 30 mg and 50 mg cohorts (grade ≥3, 18.2% and 44.0%; serious, 9.1% and 32.0%). There were no TEAEs leading to death. The most common (≥5% of patients) grade ≥3 TEAEs were hematologic toxicities (anemia, 9.1% and 24.0%; decreased platelet count, 6.1% and 8.0%; decreased white blood cell count, 0% and 12.0%; decreased neutrophil count, 3.0% and 8.0%). Conclusions: HRS-1167 combined with AA-P showed promising efficacy in patients with mCRPC, especially those with BRCA mutations. The combination was well-tolerated with no new safety signals identified. Clinical trial information: NCT06689163 . Overall BRCA m 30 mg (N = 22) 50 mg (N = 25) 30 mg (N = 6) 50 mg (N = 11) PSA50, n (%) 8 (36.4) 13 (52.0) 6 (100) 9 (81.8) Time to PSA progression, months, median (95% CI) NR (3.7, NR) 6.5 (5.5, NR) NR (4.6, NR) 6.5 (3.8, NR) cORR, n/N* (%) 3/8 (37.5) 1/7 (14.3) 2/2 (100) 1/3 (33.3) DCR, n (%) 18 (81.8) 23 (92.0) 6 (100) 11 (100) N = efficacy evaluable patients; N* = patients with target lesions at baseline. PSA and tumor responses were confirmed. PSA, prostate-specific antigen; cORR, confirmed objective response rate; DCR, disease control rate; NR, not reached.

Evaluation of a novel blood-based lung cancer screening test in elevated-risk subjects.

10535 Background: Less than 20% of individuals recommended for lung cancer (LC) screening are screened each year by low dose computed tomography (LDCT), highlighting the need for a more acceptable screening modality. Tumor-associated extracellular vesicles and particles (EVPs) are highly abundant in blood and carry surface biomarkers from their tumor cell of origin, providing a readily measurable analyte class for blood-based screening tests. Test sensitivity may be improved by EVP abundance; specificity by simultaneous measurement of multiple co-localized cancer-related markers on a vesicle surface. We report performance of an EVP-based LC Screening Test in plasma samples from elevated risk participants in the National Lung Screening Trial (NLST). Methods: The LC Test (biomarkers and classifier) was locked following a training study, after which we validated consistent assay performance in an independent cohort. Here we evaluated the LC Screening Test in a blinded case-control study nested within the ACRIN Biomarker Arm of the NLST. The study included all available incident LC cases for which subject-matched blood samples were available from the year of diagnosis (T) and the year prior (T-1) (n = 48 cases; 96 samples). Controls were age-matched NLST subjects who had no LC detected before or within the trial follow up period (n = 60). LC Test results were determined blinded to case-control status, with unblinding by ECOG-ACRIN. LC Test sensitivity was calculated at a threshold pertaining to 90% specificity, superior to 87% reported specificity for LDCT in NLST (Lung RADS v1.1). LDCT positivity was based on Lung RADS v1.1 interpretation. Results: Across two screening encounters (T and T-1), 34.4% sensitivity, similar across stages, was observed for the blood-based LC Screening Test, compared to 39.5% sensitivity for LDCT, p = 0.53 McNemar test, indicating no significant difference in observed sensitivity between LDCT and the blood test. Complementarity in detection was observed between LDCT vs blood-test detected cases across all histologies. A mean 42% increase was observed in LC Screening Test scores from T-1 to T, indicating signal increase may provide additional sensitivity. Conclusions: The blood-based LC Screening Test exhibits similar performance to LDCT in detecting preclinical lung cancer in high-risk individuals and detects some LCs not found by LDCT. The data supports further evaluation of the LC Test for LC screening. Histology Dx Modality Total Detected Detected by One Test Detected by Both Detected by Neither Adenocarcinoma LDCT 37% (17/46) 24% (11/46) 13% (6/46) 44% (20/46) Adenocarcinoma Blood Test 33% (15/46) 20% (9/46) 13% (6/46) 44% (20/46) Squamous LDCT 42% (10/24) 29% (7/24) 13% (3/24) 50% (12/24) Squamous Blood Test 21% (5/24) 8% (2/24) 13% (3/24) 50% (12/24) Small Cell LDCT 43% (6/14) 14% (2/14) 29% (4/14) 36% (5/14) Small Cell Blood Test 50% (7/14) 21% (3/14) 29% (4/14) 36% (5/14) Other LDCT 42% (5/12) 50% (6/12) 17% (2/12) 25% (3/12) Other Blood Test 25% (3/12) 33% (4/12) 17% (2/12) 25% (3/12)

Camizestrant plus ribociclib in hormone receptor–positive/HER2-negative advanced breast cancer: The phase II CADILLAC trial.

TPS1150 Background: CDK4/6 inhibitors combined with endocrine therapy (ET) are the standard first-line treatment for hormone receptor–positive (HR+)/HER2–negative (HER2–) advanced breast cancer (ABC). Secondary endocrine resistance includes patients (pts) relapsing after ≥2 years of adjuvant ET during treatment or within 12 months of discontinuation but does not distinguish according to adjuvant ET duration; thus, whether HR+ tumors progressing after prolonged adjuvant ET (≥5 years) constitute a biologically and prognostically distinct entity remains unclear. Next-generation oral selective estrogen receptor degraders (SERDs) provide more potent estrogen receptor (ER) degradation and have demonstrated superiority over standard ET in pts with previously treated endocrine-resistant ABC. We hypothesized that camizestrant plus ribociclib as first-line therapy may improve outcomes versus historical ribociclib plus aromatase inhibitor (AI) or fulvestrant in HR+/HER2– ABC relapsing after long-term adjuvant ET. Methods: CADILLAC (NCT07195227) is an international, multicenter, open-label, single-arm, external historical-controlled phase II trial. A total of 150 pts with HR+/HER2– ABC who have not received systemic treatment for advanced disease will be enrolled from Spain, Germany, and China. Key eligibility criteria include: (a) ≥18 years; (b) histologically confirmed unresectable locally recurrent or metastatic breast cancer; (c) evaluable disease as per RECIST v.1.1; (d) prior adjuvant ET duration ≥5 years, including ≥2 of AI (with a cap of 30% pts with an ET-free interval ≥12 months); and (e) ECOG performance status 0-1. Pts will receive camizestrant 75 mg orally once daily continuously in 28-day cycles, combined with ribociclib 600 mg orally once daily on days 1-21 of each 28-day cycle, until unacceptable toxicity, disease progression, death, or discontinuation for other reasons, whichever occurs first. The primary endpoint is progression-free survival (PFS). Key secondary endpoints include overall response rate (ORR), clinical benefit rate (CBR), quality of life assessed by EORTC QLQ-C30 and QLQ-BR42 questionnaires, and safety according to NCI-CTCAE v5.0. PFS, ORR, and CBR will be locally assessed by investigators per RECIST v1.1. and compared with outcomes from a historical control cohort of at least 150 pts treated with ribociclib plus AI or fulvestrant. The null hypothesis is defined as a median PFS ≤20.3 months, whereas the alternative hypothesis corresponds to a median PFS ≥28.7 (target hazard ratio 0.707). The primary hypothesis will be tested using a stratified log-rank test at one-sided 5% significance level with 70% power. An effective total of 157 PFS events across arms is required. Interim efficacy and safety analyses are planned once the first 50 pts have completed ≥6 months of treatment. Enrollment will not be paused during this interim analysis. Clinical trial information: NCT07195227 .

Effectiveness outcomes by treatment-free interval among patients receiving palbociclib plus endocrine therapy in HR+/HER2− advanced breast cancer in the real-world setting: Results from the PERFORM study.

1061 Background: Combination of CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) is first-line (1L) standard of care for patients (pts) with HR+/HER2- advanced breast cancer (ABC). Treatment-free interval (TFI) is an established prognostic factor in ABC. Shorter TFI is associated with more aggressive disease biology, inferior treatment outcomes, and reduced overall survival (OS). Real-world (RW) evidence complements clinical trials by providing insights into pts underrepresented in clinical trials. We present interim analysis 5 (IA5) of the PERFORM study, evaluating outcomes by TFI in pts receiving 1L palbociclib + ET. Methods: The prospective, non-interventional study PERFORM (NCT04767594) enrolled pts across Germany and Austria receiving 1L palbociclib + ET. Primary endpoint is progression-free survival (PFS). Secondary endpoints include second line (2L) PFS, PFS2 (time from 1L start to progression on 2L or death) and OS. Tumor assessments followed local medical standards. Quality of life (QoL) was assessed using FACT-B questionnaires. Pts were stratified by TFI, defined as time from last (neo)adjuvant treatment to recurrence: >12 months, ≤12 months, and de novo advanced disease. Time-to-event endpoints were estimated using the Kaplan-Meier method. Results: At database cutoff (Sep 30th, 2025), 1268 pts were included in IA5 and 1010 pts had available TFI data for subgroup analysis (TFI >12 months: 373 pts; ≤12 months: 133 pts; de novo: 504 pts). Median age was 69.5, 64.4, and 68.8 years, respectively. Pts with TFI ≤12 months showed a more aggressive disease profile such as higher rates of G3 tumors, N2-3 nodal status and liver metastasis compared to other TFI subgroups. Overall median PFS was 25.5 months (95% CI: 23.0-28.6), while median PFS was 29.2 months (95% CI: 23.3-33.1) for TFI >12 months, 14.6 months (95% CI: 9.3-19.4) for TFI ≤12 months, and 31.5 months (95% CI: 26.5-36.7) for pts with de novo disease. Median PFS2 was 39.0 (95% CI:33.7-51.4), 21.2 (95% CI: 17.4-37.0), and 40.9 months (95% CI: 37.0-46.9) for TFI >12, ≤12, and de novo, respectively. Median OS was not reached for TFI>12 months and was 37.4 and 52.8 months for TFI ≤12 and de novo, respectively. QOL with 1L therapy was maintained in all subgroups. Conclusions: The PERFORM IA5 supports TFI as a relevant prognostic factor for pts treated with palbociclib + ET in the 1L RW setting. QOL was maintained in TFI subgroups. Longest clinical benefit was observed in pts with TFI > 12 months and those with de novo disease. Treatment was associated with shorter clinical outcome in pts with TFI≤12 months compared to those in other TFI subgroups. These results complement those in the RCT setting.

Optimal prostate-specific antigen cutoff for prostate cancer detection: A prospective cohort study.

5109 Background: Serum prostate-specific antigen (PSA) testing is crucial for detecting early stage and low-risk prostate cancer. However, standard and uniform PSA thresholds may underestimate risk in males with smaller prostate volumes and distinct epidemiologic characteristics. We aimed to evaluate data-driven, age-specific PSA thresholds for short-term prostate cancer detection in a large screening cohort. Methods: We analyzed 512,992 PSA measurements from 123,607 asymptomatic males undergoing annual or biennial health checkups in Kangbuk Samsung Cohort Study (KSCS) from 2011 to 2020. Incident prostate cancer within 1-year of each PSA measurement was identified through linkage to the Korea National Cancer Incidence Database. The dataset was randomly partitioned into training (70%) and test (30%) subsets. To estimate cancer risk, logistic regression models incorporating synthetic minority oversampling technique were used. Optimal PSA thresholds were determined using the Youden index in test datasets. Performance was evaluated by accuracy, precision, recall, and F1-score with bootstrap validation. Associations between risk factors and prostate-cancer risk were evaluated using Cox regression models. Results: During follow-up, 224 men developed prostate cancer. The optimal PSA cutoff in the overall population was 2.96 ng/mL. Age-specific thresholds increased with age, with males in their 40s, 50s, 60s, and age ≥70 years demonstrating cutoff values of 1.62, 2.54, 2.76, and 3.79 ng/mL, respectively. These thresholds demonstrated high discriminative performance (accuracy, 0.97; F1-score, 0.92) (Table). PSA values exceeding age-specific thresholds were associated with a 20.7-fold elevated risk of prostate cancer (HR 20.65; 95% CI, 16.33–26.12; P<0.001). Older age, family history of prostate cancer (HR 2.27; 95% CI, 1.58–3.27), and dyslipidemia medication use (HR 2.04; 95% CI, 1.49–2.80) were additional independent predictors. Conclusions: In this large prospective Asian cohort, age-specific PSA thresholds between 1.6 and 3.8 ng/mL provided robust short-term risk discrimination and identified male at substantially higher 1-year prostate cancer risk than those below the thresholds. Implementing age-adjusted PSA reference values may improve the precision and efficiency of early detection strategies in Asian male and better inform risk-adapted screening and diagnostic pathways. To determine their effect on long-term clinical outcomes, prospective validation is warranted. Age-specific PSA cutoffs and performance metrics. Cutoff value Accuracy Precision Recall F1-score Overall 2.96 0.97 0.89 0.96 0.92 40 ≤ Age < 50 1.62 0.93 0.70 0.99 0.82 50 ≤ Age < 60 2.54 0.95 0.80 0.95 0.87 60 ≤ Age < 70 2.76 0.91 0.66 0.99 0.80 Age ≥ 70 3.79 0.90 0.65 0.91 0.76

Oncology clinicians’ empathy association with mean number of visits and referrals to psychosocial oncology services.

e24125 Background: Referrals to psychosocial services is not standardized despite national mandates for distress screening and embedded psychological services. Nationally, approximately 3% of patients with cancer are ultimately referred to dedicated psychological/psychiatric services. This study evaluated oncologists’ knowledge, attitudes, and practice, racial biases, and empathy along with discreet numbers of patients seen, followed up in clinic, and referred to an academic medical center’s dedicated psychosocial service. Methods: Oncologists and Advance Practice Providers at a single institution were sent questionnaires containing Knowledge/Attitudes/Behavior (KAPb), Racial Colorblindness (COBRAS), and Interpersonal Reactivity Index (IRI) empathy scales. Demographic and practice data were collected such as age, licensure (physician versus APP), years in practice/career stage, race, sex, discreet number of patients seen (18 months duration of study), number of visits, and referrals to psychosocial oncology service. Descriptive and inferential statistical modeling using linear regression were conducted. Results: Twenty clinicians (10 oncologists: 10 APPs) responded (35% response rate). Clinicians referred 8.2 (13.2) patients on average (range 1-57) out of 380.6 (280.7) discreet patients over 987.2 (1063) visits or 2.1% (4.3) of their total patients to psychosocial services. Referrals were correlated with female sex (r = -.49, p = .03), seeing less patients (r = -.46, p = .03), and empathy (r = .51, p = .02). While controlling for age, sex, # discreet patients, empathy predicted 32% variance of referrals to psychosocial services. A higher average number of visits per patient was associated with empathy (t = .2.31, p-03) and more experience in oncology (t = 2.9, p = .01). Racial biases nor knowledge, attitudes or practice behavior influenced referrals. Conclusions: Referrals to psychosocial services are inadequate to meet the psychological distress with which patients present to oncology clinic. Referrals to psychosocial services should be standardized to meet patients’ psychological distress needs. These findings suggest enhanced empathy training could lead to increased referral patterns and considerations around how often patients are seen in clinic. Multivariate model predicting referrals to psychosocial oncology Services. Coefficient (unstandardized) SE t P 95% CI Age -.027 .113 -.24 .82 -.269, .215 Sex -1.632 1.563 -1.04 .31 -4.985, 1.721 # discreet patients -.005 .003 -1.78 .10 -.012, .001 Empathy (IRI total) .227 .109 2.11 .05* .008, .462 IRI =Interpersonal Reactivity Index.

Real-world feasibility and efficacy of a tailored exercise program in patients with cancer.

12040 Background: Exercise (EX) is associated with improved survival, symptom control, and management of treatment-related side effects in patients (pts) with cancer. However, evidence from large, real-world cohorts including unselected pts across different phases of the disease trajectory remains limited. This study aimed to evaluate the feasibility and effectiveness of a tailored EX program implemented in routine clinical practice. Methods: A three-month, bi-weekly supervised EX program was offered to consecutive cancer pts referred at the University Hospital of Verona, regardless of treatment status. The program included moderate-intensity aerobic exercise (10–30 minutes/session) and resistance training (2–3 sets of 8–12 repetitions; six exercises). The primary endpoint was feasibility, assessed by recruitment rate, adherence, and dropout. Secondary endpoints included cardiorespiratory fitness (six-minute walking test, 6MWT), muscular strength (handgrip strength test, HST), waist-hip ratio (WHR), and quality of life (QoL), measured using the EORTC QLQ-C30. Pre- and post-intervention outcomes were analyzed using descriptive statistics and paired Student’s t-tests. Results: A total of 2276pts were recruited (92% recruitment rate) with a median age of 57±12 years. The most frequent tumor types were upper gastrointestinal cancers (34%) and breast cancer (31,8%). 84% of patients were receiving systemic treatments, and 47% had metastatic disease. Overall, 156 pts completed the intervention (dropout rate 31%, mainly due to disease progression), with an adherence rate of 84%. Significant improvements were observed in WHR (−1.2%, p = 0.03), 6MWT (+25 m, p < 0.001), and HST (+1.9 kg, p < 0.01). QoL significantly improved in physical, role, emotional, and social functioning (all p < 0.01), along with reductions in fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and diarrhea. Global QoL and financial difficulties also significantly improved. Conclusions: In a real-world, unselected cohort of cancer pts across different treatment phases, a tailored EX program is feasible and associated with meaningful improvements in physical function and QoL. These findings support the integration of structured exercise programs into routine oncology care beyond controlled clinical trial settings. Clinical trial information: NCT04226508 .