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Stage at diagnosis and survival outcomes in esophageal carcinoma: A multicenter real-world study.

e16087 Background: Esophageal carcinoma (EC) is a highly lethal malignancy, with prognosis largely dependent on stage at diagnosis. While early-stage disease may be curable, advanced-stage EC is associated with poor survival and high metastatic burden. Contemporary real-world data comparing outcomes by stage remain limited. We aimed to evaluate the impact of stage at diagnosis on survival and distant metastatic risk in a large global cohort. Methods: We conducted a multicenter retrospective cohort study using TriNetX, a federated global database, among adult patients (≥18 years) diagnosed with esophageal carcinoma (EC) between January 1, 2015, and January 9, 2026. Patients were stratified by stage at diagnosis into early- (0–II) and advanced- (III–IV) stage disease. The index date was defined as the first documented diagnosis of EC. Outcomes assessed included all-cause mortality at 6 months, 12 months, and 3 years, as well as the development of distant metastases to the liver, bone, and lung following diagnosis. 1:1 propensity score matching was performed using a nearest-neighbor approach. Outcomes were analyzed using Kaplan–Meier with the log-rank test and hazard ratios (HR) with 95% confidence intervals (CI); p < 0.05 was considered statistically significant. Results: A total of 14,261 patients with EC were identified, including 4,884 with stage 0–II and 9,377 with stage III–IV disease. After propensity score matching, adjusting for age, sex, race, and comorbidities, including hypertension, diabetes mellitus, obesity, prior myocardial infarction, and smoking history, 4,615 patients remained in each cohort. Early-stage disease was associated with significantly improved survival across all time points, with HR 0.38 (95% CI 0.34–0.43) at 6 months, HR 0.38 at 12 months (95% CI 0.35–0.42), and HR 0.40 (95% CI 0.37–0.43) at 3 years compared to those with advanced-stage disease. Moreover, advanced-stage disease was associated with a significantly higher incidence of liver metastases (HR 0.25, 95% CI 0.21–0.29) and bone metastases (HR 0.25, 95% CI 0.20–0.30). No statistically significant difference was observed in lung metastases between cohorts (HR 0.87; 95% CI 0.73–1.04). Conclusions: In this large real-world analysis, early-stage esophageal carcinoma was associated with substantially improved short- and long-term survival compared with advanced-stage disease. Advanced-stage EC demonstrated a significantly higher risk of liver and bone metastases, highlighting the systemic progression characteristic of later stages. These findings underscore the critical importance of early detection and timely intervention to improve outcomes in esophageal carcinoma.

Evolution of the pulmonary immune microenvironment from premalignant lesions to invasive lung adenocarcinoma: A spatial transcriptomic study.

e20029 Background: Pulmonary adenocarcinoma develops through a multistep process from premalignant epithelial lesions to invasive disease. While therapeutic advances have improved outcomes in advanced stages, the immune microenvironment during early lung carcinogenesis remains poorly understood. Atypical adenomatous hyperplasia (AAH) is a key precursor lesion whose study may provide insight into early mechanisms of tumor progression and identify biomarkers of aggressive behavior. Methods: We conducted a retrospective multicenter study including patients with pulmonary adenocarcinoma who underwent surgical resection between 2010 and 2025 at three Spanish hospitals (N=23). Regions of interest corresponding to invasive tumor, peritumoral stroma, and AAH were selected from FFPE samples. Spatial transcriptomic profiling was performed using the NanoString GeoMx Digital Spatial Profiler RNA platform with quality control, Q3 normalization, and paired statistical analyses accounting for intra-patient correlation. Penalized regression models were used to derive a gene signature, and associations with frequently mutated genes were explored using public databases. Molecular data were integrated with clinical outcomes. Results: Spatial transcriptomics revealed progressive gene expression changes across lung adenocarcinoma carcinogenesis. Genes upregulated in dysplasia compared with normal tissue (>2-fold change) included C4BPA, SERPINA1, MLPH, NKX2-1, CD24, GDF15, FOXJ1, THBS1, TPSAB1/B2, PECAM1, and MRC1. An eleven-gene expression signature accurately discriminated normal lung, AAH, and invasive adenocarcinoma (AUC 0.996). Signature genes were associated with epithelial differentiation, microenvironment remodeling, angiogenesis, and immune polarization. AAH lesions showed intermediate signature expression between normal tissue and invasive adenocarcinoma, consistent with gradual activation of tumor-associated transcriptional programs. While individual genes such as NKX2-1 correlated with improved overall survival in public datasets (p=0.011), the combined signature was not prognostic for overall survival (p=0.98). Conclusions: Premalignant pulmonary lesions, particularly AAH, already harbor transcriptomic alterations that distinguish them from invasive disease. This signature reflects progressive activation of biological programs during lung adenocarcinoma carcinogenesis and may help identify early biological vulnerabilities to prevent progression to invasive cancer.

Phase I dose-escalation results of ¹⁷⁷ Lu-NYM032 in patients with progressive metastatic castration-resistant prostate cancer (mCRPC).

5049 Background: 177 Lu-NYM032 is a novel prostate-specific membrane antigen (PSMA)-targeted radioconjugate with optimized properties. Phase I dose-escalation study evaluated its safety, tolerability, pharmacokinetics, radiation dosimetry and preliminary antitumor activity in patients with mCRPC. Methods: Eligible patients had PSMA-positive mCRPC confirmed by 68 Ga-NYM032 PET/CT, no discordant lesions on 18 F-FDG PET/CT, progression after ≥1 AR-targeted therapy and 1–2 prior taxane regimens (or unsuitability/refusal), ECOG 0–2, and no prior radioisotope therapy. A modified 3+3 dose-escalation design was used ( 177 Lu-NYM032: 1.9–7.4 GBq). Pharmacokinetics and dosimetry were evaluated using sequential blood samples and SPECT/CT imaging post-administration (Cycle 1: 2h, 24h, 48h, 7d, 14d; Cycles 2–4: 48h). Primary objectives were safety and maximum tolerated dose (MTD); secondary objectives included pharmacokinetics, dosimetry, and antitumor activity. Results: Eleven patients were enrolled across four dose levels: 1.9 GBq (n = 1), 3.7 GBq (n = 4), 5.55 GBq (n = 3), and 7.4 GBq (n = 3). Ten patients completed the study and one patient (3.7GBq) withdrew consent and discontinued the study prior to DLT evaluation. Ten Patients received 2–6 treatment cycles（at 6-week intervals）of 177 Lu-NYM032. Four patients were administered up to 6 cycles at 7.4 GBq per cycle, reaching a total cumulative activity of 44 GBq. Treatment was well tolerated; with most treatment-emergent adverse events being grade 1-2. Grade≥3 TEAEs related to 177 Lu-NYM032 were limited to anemia, decreased lymphocyte count, and hypokalemia. No dose-limiting toxicities were observed. Clearance of 177 Lu-NYM032 from the kidney occurs rapidly (half-life: 18.37-38.66 hours). Physiological distribution of the radiopharmaceutical was observed including in the salivary glands, lacrimal glands, liver, spleen, kidneys, and intestines–consistent with known PSMA expression patterns. While the mean tumor absorption dose (7.73 Gy/GBq in cycle 1) decreased over time, mean absorbed doses per cycle to kidneys and salivary glands remained relatively stable across the administered dose range (1.9-7.4 GBq): kidney doses were 0.47-0.64 Gy/GBq in cycle 1 and 0.42-0.63 Gy/GBq in cycles 2–4; salivary gland doses were 0.42-1.34 Gy/GBq in cycle 1 and 0.43-0.83 Gy/GBq in cycles 2-4. Among 10 evaluable patients, objective response rate was 20% and disease control rate was 80%. Of 3 RECIST v1.1 measurable, 2 (66.7%) partial responded, 1 (33.3%) stable. PSA50 and PSA90 responses were observed in 60.0% and 20.0% of patients, respectively. Median rPFS was 6.5 months; median overall survival was not reached. Conclusions: 177 Lu-NYM032 demonstrated a favorable safety profile and promising antitumor activity in patients with mCRPC, supporting further evaluation in Phase II studies. Clinical trial information: NCT06383052 .

Trend analysis of survival, socioeconomic, and racial disparities in esophageal squamous cell carcinoma.

e16133 Background: Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy in the US, with historically poor survival. Over the past decade, advances in staging and multimodality therapy have expanded the therapeutic landscape; however, whether these advances have translated into meaningful population-level survival gains has not been well characterized. Using population-based data, we evaluated temporal trends in survival among adults with ESCC, county-level income and race association with disparities in survival outcomes. Methods: We conducted a retrospective cohort study using the SEER database, including adults diagnosed with ESCC between 2010 and 2022. Patients were grouped into three diagnosis eras (2010–2013, 2014–2017, 2018–2022). Overall survival was measured from diagnosis to death from any cause. Because proportional hazards assumptions were violated, survival was summarized using restricted mean survival time (RMST), representing the mean number of months lived over 36 months. County level median household income was categorized into four strata ( < $60k, $60–79k, $80–94k, ≥$95k) as a proxy for socioeconomic access. Race analyses compared non-Hispanic Black and non-Hispanic Asian patients with non-Hispanic White patients. RMST differences and 95% confidence intervals (CI) were estimated for all comparisons. Results: Among 10,391 adults with ESCC, overall survival improved over time. Patients diagnosed in 2018–2022 lived 1.9 months longer during the first 36 months after diagnosis compared with those diagnosed in 2010–2013 (p < 0.001), indicating modest but measurable survival gains. Despite these improvements, substantial disparities were observed. Survival increased monotonically with county level income: compared with patients living in counties with median income < $60k, patients lived 1.3 months longer in $60–79k counties, 3.1 months longer in $80–94k counties, and 3.4 months longer in ≥$95k counties (all p < 0.001). Compared with non Hispanic White patients, non Hispanic Black patients lived an average of 2.7 months fewer, while non Hispanic Asian patients lived 1.2 months longer over the same 36 month period. Conclusions: Although survival among adults with ESCC in the US has improved over time, these gains remain modest and unevenly distributed. Patients living in higher income counties and non Hispanic White or Asian patients experienced longer survival, while non Hispanic Black patients and those in lower income counties had worse outcomes. Clinically, these findings underscore the need to improve equitable delivery of effective therapies. They highlight persistent place based and racial inequities in cancer outcomes. Overall survival by county-level income. County income group N Survival at 36 months (%) Median survival (months) RMST at 36 months <$60k 1758 15.9 6 11.9 $60k-$79k 3354 17.5 8 13.2 $80-$94k 2425 22.7 9 15.0 ≥$95k 2852 23.0 10 15.3

Analgesia profile and racial disparity in opioid use among cancer patients hospitalized in a public hospital in the countryside, Brazil.

e13753 Background: Cancer-related pain is highly prevalent across all stages of oncologic disease and is considered one of the main causes of avoidable suffering. Opioids are internationally recommended for the management of moderate to severe cancer pain; however, their use is unevenly distributed worldwide, with markedly lower consumption in low- and middle-income regions. In the United States, studies consistently demonstrate racial disparities in opioid access and dosing, disproportionately affecting Black patients. In Brazil, although opioid use is largely restricted to acute and cancer-related pain, national data evaluating racial disparities in opioid prescription are scarce. This study aimed to characterize the analgesic profile of hospitalized cancer patients and to investigate whether racial disparities in opioid use are present in a Brazilian public hospital. Methods: A retrospective, observational, descriptive, and comparative study was conducted at a public cancer hospital in São Bernardo do Campo, Brazil. Medical records of adult patients with histologically confirmed cancer admitted between January and June 2024 were reviewed. Sociodemographic data (race/colour categorized as White or Black [Black and Brown]), clinical characteristics, and analgesia-related variables were collected, including opioid type, fixed and rescue dosing, and dose adequacy. Statistical analyses included Student’s t-test, chi-square test, and Z test for proportions (p < 0.05). Results: A total of 402 hospitalizations were included. Most patients received opioids, predominantly morphine. Although Black patients presented higher mean opioid doses and longer hospital stays, no statistically significant racial differences were observed in opioid prescription patterns, dosing, or rescue administration. These findings contrast with international literature. The absence of disparities may be related to the structure of the Brazilian public health system, specialized oncology care, and standardized prescribing practices. Limitations include possible misclassification of race/colour due to heteroidentification in medical records. Inadequate pain score documentation and frequent rescue dose calculation errors were identified. Conclusions: In this public Brazilian hospital, opioid use for cancer pain management appeared not to be racially disparity, with no statistically significant disparities between White and Black patients. Despite limitations inherent to retrospective designs and incomplete documentation, the study contributes novel national data on opioid distribution stratified by race. The findings underscore the need to improve pain assessment records, optimize opioid prescribing practices, and implement standardized analgesia protocols to enhance cancer pain control within the public health system.

Transcriptomic analyses of molecular subsets and correlations with clinical outcomes from the phase 3 IMforte study of lurbinectedin (lurbi) + atezolizumab (atezo) maintenance treatment (Tx) in extensive-stage small-cell lung cancer (ES-SCLC).

8014 Background: Transcriptomic analyses of pre-Tx tumor samples from the Phase 3 IMpower133 study identified 4 molecular subtypes with distinct clinical outcomes to first-line (1L) Tx with atezo and chemotherapy (chemo). Neuroendocrine (NE) tumors with low tumor-associated macrophage (TAM)/high T-effector (T-eff) signal demonstrated longer overall survival (OS) vs non-NE tumors with high TAM/high T-eff, suggesting that TAM contributes to resistance to atezo. Lurbi, an alkylating agent that modifies the tumor microenvironment and synergizes with immune checkpoint inhibitors, could enhance atezo activity. Lurbi + atezo as 1L maintenance Tx significantly improved progression-free survival (PFS) and OS vs atezo in patients (pts) with ES-SCLC in the Phase 3 IMforte study (NCT05091567). We report exploratory biomarker analyses from IMforte. Methods: Adults with Tx-naïve ES-SCLC, without disease progression after induction with atezo + chemo, received maintenance Tx of either 3.2 mg/m² lurbi + 1200 mg atezo or 1200 mg atezo q3w until unacceptable toxicity or disease progression. Transcriptomic analyses were conducted on pre-induction Tx tumor samples to identify subgroups with concordance to previously reported SCLC subtypes (SCLC-A, -N, -I-NE and -I-non-NE), immune gene expression signatures (TAM, T-eff) and SLFN11 . Post-hoc exploratory analyses were conducted for correlation with IRF-assessed PFS and OS. Results: Of 483 randomized pts, 303 had samples for RNA sequencing. Of 303 tissue samples analyzed, 104 (34.3%) were classified as SCLC-A, 89 (29.4%) as SCLC-N, 46 (15.2%) as SCLC-I-NE and 64 (21.1%) as SCLC-I-non-NE. Clinical outcomes in the 303 pts (median [m] PFS: 5.5 vs 2.4 months [mo], hazard ratio [HR] 0.61; mOS: 13.5 vs 11.7 mo, HR 0.72, for lurbi + atezo [n = 150] vs atezo [n = 153], respectively) were consistent with the full analysis set. PFS and OS benefit from lurbi + atezo were comparable between NE (mPFS: 5.5 vs 2.1 mo, HR 0.58; mOS: 13.5 vs 11.7 mo, HR 0.74, for lurbi + atezo [n = 115] vs atezo [n = 124], respectively) and non-NE subtypes (mPFS: 4.6 vs 2.8 mo, HR 0.73; mOS: not reached vs 12.0 mo, HR 0.68, for lurbi + atezo [n = 35] vs atezo [n = 29], respectively). Pts with high TAM/high T-eff in the atezo arm had shorter OS vs those with low TAM/high T-eff. The addition of lurbi improved OS in the high TAM/high T-eff subgroup vs atezo alone (HR 0.56). SLFN11 expression was high at baseline across subtypes and had no predictive value for lurbi + atezo clinical benefit. Conclusions: The prevalence of the 4 SCLC subtypes and the TAM/T-eff pre-Tx data for IMforte are consistent with findings from IMpower133. PFS and OS were longer for lurbi + atezo vs atezo irrespective of molecular subset, though numerical trends suggest that lurbi may overcome TAM-mediated resistance to atezo. Clinical trial information: NCT05091567 .

Preliminary safety and efficacy of SYS6010 combined with enlonstobart in patients with recurrent or metastatic esophageal cancer: Results from a phase I/II study.

e16052 Background: SYS6010 is a novel antibody-drug conjugate (ADC), consisting of an anti-epidermal growth factor receptor (EGFR) humanized IgG1 monoclonal antibody linked to topoisomerase I inhibitor (JS-1). Enlonstobart is a fully humanized anti-PD-1 IgG4 monoclonal antibody. In most recurrent or metastatic (R/M) esophageal cancer (EC) and selected advanced solid tumors, PD-1 based chemo-immunotherapy is standard treatment yet limited by resistance. Mechanistically, certain EGFR-targeted ADCs can complement PD-1 immunotherapy and hold promise for enhancing anti-tumor activity. This phase I/II study (ChiCTR2400089402) is to evaluate the safety, tolerability, pharmacokinetic profile and preliminary efficacy of SYS6010 combined with Enlonstobart ± chemotherapy in patients with EGFR and ALK wild type locally advanced or metastatic non-small cell lung cancer and other advanced solid tumors. Here, we present the preliminary safety and efficacy results of SYS6010 combined with Enlonstobart in patients with R/M EC from the phase II portion. Methods: In the phase II EC cohort, eligible patients were those aged 18 to 75 years with R/M EC who had not received prior systemic therapy, or who had received adjuvant/neoadjuvant therapy with disease progression occurring at least 6 months after completion of treatment. Patients received SYS6010 at 3.6 mg/kg and Enlonstobart at 240 mg every 2 weeks (Q2W). Primary endpoints were safety, tolerability and objective response rate (ORR) assessed by investigators. Results: As of January 05, 2026 (data cut-off), 32 patients were enrolled. The median age was 63 years (range, 36-72) and 81.3% of patients were male. The median treatment exposure was 19.64 weeks (IQR, 12.43-25.86). 96.9% of patients experienced at least one treatment-emergent adverse event (TEAE). The incidence of grade ≥3 TEAEs was 31.3%. The most common grade ≥3 TEAEs were neutropenia (12.5%), leukopenia (6.3%) and anemia (6.3%). One patient experienced death, which was assessed as unrelated to treatment. No patients discontinued treatment due to TEAEs. 29 patients were evaluable for efficacy, with confirmed ORR and disease control rate of 65.5% (95% CI, 45.7-82.1) and 93.1% (95% CI, 77.2-99.2), respectively. The 6-month progression-free survival (PFS) rate was 68.2% (95% CI, 40.6-85.0). The confirmed 3-month duration of response (DOR) rate was 91.7% (95% CI, 53.9-98.8). Median PFS, median DOR and overall survival were not yet mature. Conclusions: This study demonstrates that the combination therapy of SYS6010 and Enlonstobart has the potential to represent a novel and effective treatment option for patients with R/M EC. The promising clinical activity, together with a manageable safety profile, supports further clinical development of this regimen. Clinical trial information: ChiCTR2400089402.

Assessment of ctDNA detection in prostate cancer using a 6-base epigenomics and fragmentomics approach.

e17132 Background: Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Early detection is crucial for improving outcomes and reducing mortality. Circulating tumor DNA (ctDNA) is a promising tool for the early detection of various solid tumors. However, ctDNA shedding rates in early-stage PCa are lower compared to other tumor types, complicating the distinction between cancerous and non-cancerous DNA fragments and reducing sensitivity. A multidimensional cfDNA analysis may enhance sensitivity and facilitate early PCa detection. Methods: We analyzed cfDNA from localized (lPCa, n = 57), metastatic (mPCa, n = 36), and healthy controls (n = 14) using duet evoC platform (biomodal), which enables simultaneous assessment of genetic and epigenetic features, including 5mC and 5hmC. Regions of interest were identified from differentially methylation analysis of TCGA tumor–normal pairs, comparison of prostate tissue to healthy cfDNA and genes known to be expressed in prostate tissue. 5mC and 5hmC levels were extracted for these regions along withgenome wide fragmentomics features, focusing on fragment size and end-motifs. Classifier models were developed, including using read level approaches, and evaluated under cross-validation, with performance assessed at high-specificity thresholds. Results: Early results that showed PCa cfDNA methylation profiling was concordant with TCGA-derived tumour methylation whereas lPCa had more modest differences and that integration of 5mC and 5hmC enhanced discrimination overall. Fragmentomics analysis also provided consistent and reproducible discrimination across disease stages. Therefore it was decided to use read level analysis and the combination of methylation and fragmentomic features to develop multiomic classifiers to detect early and late-stage disease. Integration of those multiomic features led to improved performance for detection of prostate cancer across disease stages at high specificity. Conclusions: cfDNA methylation reflects tumor biology in advanced disease, whereas fragmentomic features provide greater robustness for early detection. Integrating complete methylation with 5mC and 5hmC and fragmentomics enhances sensitivity in localized prostate cancer and may accelerate development of non-invasive diagnostic tools.

Racial and ethnic disparities in pancreatic cancer risk assessment using SEER–Medicare claims data.

e16010 Background: Racial and ethnic disparities in pancreatic cancer outcomes may be partially driven by differences in risk assessment using administrative healthcare data, highlighting the need for approaches that improve equity in claims-based risk stratification. Claims-based risk stratification models derived from Medicare data are increasingly used for population-level surveillance and early identification of high-risk patients; however, their performance across racial and ethnic groups has not been well characterized. Methods: Using the SEER–Medicare 2000–2019 linked dataset, we identified 26,849 patients aged 66 years or older with incident pancreatic cancer based on ICD-O-3 site codes, excluding cases diagnosed at autopsy or death certificate, those with inconsistent vital records, missing cause of death, or prior malignancy other than non-melanoma skin cancer. Longitudinal Medicare claims data including diagnoses (ICD-9/10), procedures, and healthcare utilization were used to construct claims-based risk stratification models to estimate 6-month pancreatic cancer risk. Model performance was evaluated overall and across racial and ethnic groups to assess disparities in predictive accuracy. Results: At the 6-month prediction horizon, overall model discrimination was moderate (AUROC 0.743). Substantial variation in predictive performance was observed across racial and ethnic groups, with lower accuracy among minority populations. After applying alternative modeling strategies designed to account for group imbalance during risk estimation, overall discrimination improved (AUROC 0.762), and inter-group performance disparities were substantially reduced (range decreased by 67%; standard deviation decreased by 70%). Group-specific AUROCs improved for White (0.847→0.886), Black (0.853→0.880), Asian (0.641→0.816), and Hispanic (0.845→0.860) beneficiaries. Conclusions: Claims-based pancreatic cancer risk stratification models exhibit meaningful racial and ethnic disparities in predictive performance among older adults. Modeling strategies that account for group imbalance can improve both overall discrimination and equity across racial and ethnic groups, supporting their use to address disparities in claims-based pancreatic cancer risk assessment. These findings underscore the importance of evaluating disparities in claims-based risk assessment tools used for cancer surveillance and population health management.

Impact of national health insurance "Ayushman Bharat" scheme of delivering high-quality cancer surgery in resource-constrained settings of low/middle-income countries: Correlation of out-of-pocket expenditure with quality metrics.

e13631 Background: Parameters for high quality cancer surgeries are stringent and have been defined for various organ systems. Resource constrained settings and financial impact of such procedures further limit the execution of such procedures in LMICs. This study has been done to analyse the impact of recently launched National State Health Insurance Scheme - "Ayushmann Bharat" (AB) in India over the feasability of performing such high quality cancer surgeries in financially backward regions of India. Methods: This is a retrospective observational study design which has evaluated the surgical oncology database of two centres - Upkar Cancer Institute, Varanasi (UCI) and Jharkhand Cancer Centre, Ranchi (JCC). Patients who underwent curative cancer surgeries between April 2024 till December 2025 were included; Standard definitions were used to define parameters for recording the grade of surgeries, the post-operative morbidity and the peri-operative parameters; Relevant published literature was used to extract comparison metrics for organ bases high quality cancer surgeries; Correlation tests were applied to study the Out-of-Pocket expenditure against the grade of surgeries at the two centres. Results: Database of 1500 patients was included for the analysis - JCC - 785 and UCI - 715; The organ system wise distribution was as follows - Breast Oncology 15%; Colorectal Oncology 20%; Hepato-biliary oncology 15%; Gyane and urological oncology 10%; Thoracic oncology 5%; Sarcomas and bone tumours 5%; Head Neck Oncology 30%. The distribution as per the grade of surgeries was as follows - grade 3 - 20%; grade 4 - 25%; grade 35%; grade 6 - 20%; The distribution of surgeries with respect to the AB scheme was as follows: 80% at JCC were operated under AB and 35% patients were operated under AB; The overall peri-operative morbidity profile as per the Clavein-Dindo classification was as follows - grade I - 77%; grade II - 8%; grade III - 8%; grade IV-5% and grade V - 2%; Multivariate regression analysis showed that the AB scheme did not have any impact on the peri-operative morbidity profile; Out of pocket expenditure analysis showed that there was no significant correlation seen between the out of pocket expenditure and the morbidity profile and failure-to-rescue for patients operated beyond the AB scheme. Conclusions: The implementation of the National State Health Insurance "Ayushmann Bharat" scheme has helped in the execution of high quality cancer surgeries in resource limited settings of LMIC, especially in financially backward portions of India with limited healthcare access. This has also resulted in reduced out of pocket expenditure for major cancer surgeries.

Sequencing strategy of immunotherapy with chemoradiotherapy in stage III non–small cell lung cancer: A pooled analysis of prospective trials.

e20041 Background: Consolidative immunotherapy(IO) after chemoradiotherapy (CRT) is the current standard of care for locally advanced stage III non–small cell lung cancer (NSCLC). Preclinical evidence supports synergistic antitumor effects of radiation and immunotherapy through tumor microenvironment modulation. Emerging clinical studies have demonstrated promising outcomes with combined CRT and IO in stage III NSCLC. However, the optimal sequencing strategy of IO and CRT to maximize survival benefit remains unclear. Methods: We conducted a systematic review of prospective clinical trials evaluating different sequencing strategies of IO combined with CRT in stage III NSCLC. Individual patient data were reconstructed from published Kaplan–Meier curves using a validated algorithm(IPDfromKM). Reconstructed patients were pooled across trials and categorized according to IO starting timing: before CRT(IO induction), concurrent with CRT(ICRT), after CRT(CRT-IO). Progression-free survival (PFS) and overall survival (OS) were analyzed using pooled Cox proportional hazards models. Results: Eleven phase II and III prospective clinical trials involving 2213 patients were included. The immunotherapy included PD-1 and PD-L1 inhibitors. PFS and OS time anchors differed across trials, with IO induction initiating earlier and CRT-IO initiating after completion of CRT. IO induction regimens showed significantly longer PFS than both CRT-IO (HR 0.66, 95% CI 0.56–0.78, p < 0.001) and ICRT (HR 0.65, 95% CI 0.55–0.78, p < 0.001); the median PFS was 31.71 months for IO induction, compared with 15.38 months for CRT-IO and 14.68 months for ICRT. This trend was consistent across IO subtypes. Both IO induction and CRT-IO regimens were associated with significantly better OS than ICRT (IO induction vs ICRT: HR 0.79, 95% CI 0.65–0.96, p = 0.017; CRT-IO vs ICRT: HR 0.82, 95% CI 0.71–0.95, p = 0.007). Median OS was 44.96 months for IO induction, 44.43 months for CRT-IO, and 37.88 months for ICRT. In sensitivity analyses excluding longer induction regimens, the PFS benefit with IO induction was preserved, while OS differences were directionally consistent but less stable. Conclusions: In data pooled across prospective trials, IO induction prior to CRT was associated with longer PFS and favorable OS compared with alternative sequencing strategies. Concurrent initiation of immunotherapy with CRT did not demonstrate survival benefit. Given the heterogeneity in trial design and endpoint anchoring difference, these findings are hypothesis-generating and support prospective evaluation of IO induction strategies. IO Sequencing Strategy Median PFS (mo) HR for PFS (95% CI) Median OS (mo) HR for OS (95% CI) IO induction 31.71 0.65 (0.55–0.78) 44.95 0.79 (0.65–0.96) CRT-IO 15.38 0.99 (0.88–1.12) 44.43 0.82 (0.71–0.95) ICRT 14.68 Ref 37.88 Ref

GDF-15 levels and clinical correlates in head and neck cancer patients: Developing a risk model for cachexia.

6099 Background: Cachexia is a challenging complication of cancer and its treatment, associated with an increased risk of death. Growth differentiation factor 15 (GDF15) is a known driver of cachexia in lung, pancreatic and colorectal cancer. However, we lack information about GDF15 role and temporal dynamics in patients with head and neck squamous cell carcinoma (HNSCC) receiving curative treatments. Here, we aimed to quantify circulating GDF15 in HNC patients and determine the relationship with indicators of cachexia and other prominent clinical correlates, namely oral mucositis (OM). Methods: Adults diagnosed with HNSCC, scheduled to receive definitive platinum based chemoradiotherapy (CRT), were recruited from four tertiary hospitals in Australia and Italy. Cachexia was determined using a variety of clinical parameters, including weight, grip strength, and upper arm circumference (UAC). OM was assessed using the World Health Organization (WHO) mucositis scale (grade 0-4). GDF15 was quantified in serially-collected serum using a commercial ELISA. All measures were assessed at baseline, week 3, end of treatment (EOT) and 3 months after treatment end. Results: Fifty-nine patients (pts) were enrolled, predominantly male (71%) with a mean age of 64+/-8 years. Main subsite of disease was oropharynx (44 cases, 75%), of whom 68% were HPV positive. Treatment was delivered with definitive intent in 90% of the cases. Median dose of RT was 70 Gy (66-70). At EOT, 77.3% of the pts met the diagnostic criteria for cachexia, with an average weight loss of 8.6% over the course of treatment. This was accompanied by a 7.7% and 5.6% average reduction in grip strength and UAC, respectively. Notably, these reductions continued beyond treatment cessation, with an average baseline weight loss of 9.8% after 3 months. Aligning with these outcomes, serum GDF15 levels were highly elevated following CRT compared to baseline (2.6 fold, P<0.0001), and correlated with reductions in weight (R 2 =0.168, P=0.0002), UAC (R 2 =0.1516, P<0.0001), grip strength (R 2 =0.1332, P<0.0001), as well as OM severity (R 2 =0.1013, P<0.0009). Conclusions: These data reveal that highly elevated GDF15 production correlates with OM and cachexia, providing strong clinical rationale to explore the biological basis of this new symptom cluster, as well as identifying a new clinical cohort that may benefit from GDF15 targeting agents.

Efficacy of primary cardioprotection with perindopril, bisoprolol, and trimetazidine in high-risk patients with breast and gastric cancer receiving anthracycline- and trastuzumab-containing therapy.

12028 Background: Anthracyclines and trastuzumab are the most common antitumor agents associated with a substantial risk of cardiotoxicity (CTX). Patients with high or very high cardiovascular risk represent a vulnerable population where even subclinical myocardial injury can translate into clinically significant cardiac dysfunction. The present study is aimed to evaluate the efficacy of primary cardioprotective therapy (CPT) in preventing both subclinical and overt CTX in high-risk patients undergoing anthracycline (A)- and/or trastuzumab (T)-containing treatment. Methods: This single-center prospective observational study included 92 cancer patients (pts) with high or very high risk of CTX according to the Mayo Clinic risk score. The study population consisted of 7 men (8%) and 85 women (92%), with a mean age of 60.6 ± 11.8 years. Breast cancer (BC) was the most common diagnosis (n = 84; 91%), while gastric cancer (GC) accounted for 8 cases (9%). 17 (33.3%) pts in the intervention group and 16 (39%) pts in the control group had a history of congestive heart failure. AC (doxorubicin/cyclophosphamide) regimen was administered in 54 BC patients, AC followed by T in 30 BC pts, T – in 8 GC pts. The intervention group (n = 51) received primary CPT with perindopril and bisoprolol; trimetazidine was added in patients at very high cardiovascular risk or with established coronary artery disease. The control group (n = 41) did not receive CPT due to intolerance or refusal. Echocardiography with left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), 24-hour blood pressure monitoring, and multibiomarker assessment (troponin I, NT-proBNP, MPO, sST2) were performed at baseline and at 1, 3, 6, 9, and 12 months. Results: The control group showed a significant increase in indexed left atrial volume and indexed left ventricular end-diastolic volume at 6 and 9 months, respectively, indicating cardiac remodeling, which represents one of the earliest manifestations of subclinical cardiotoxicity. GLS reduction ≥18% occurred in 21.2% of control pts vs. 7.1% in the intervention group (p < 0.05). Clinically significant cardiotoxicity with LVEF decline developed in 6 control pts vs. 1 in the intervention group. Cardiovascular complications were 2.5 times more frequent in the control group (70.1% vs. 24.8%). All-cause mortality at 12 months was significantly higher in the control group (11.7% vs. 5.1%, p = 0.04). Conclusions: In high-risk pts with BC and GC receiving anthracycline- and trastuzumab-containing therapy, primary CPT with perindopril, bisoprolol, and trimetazidine effectively prevents adverse cardiac remodeling, preserves myocardial systolic function, reduces the incidence of cardiovascular complications, and is associated with a significant reduction in one-year all-cause mortality.

Updated protocol: IMPROVEMF, a phase 1b trial of imetelstat (IME)+ ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1/2 or high-risk (HR) myelofibrosis (MF).

TPS6604 Background: In preclinical evaluations, sequential treatment (tx) with RUX, a Janus kinase inhibitor (JAKi), and IME, a telomerase inhibitor, selectively reduced MF hematopoietic stem cells (HSC) and progenitor cells. In the Phase 2 IMbark trial (NCT02426086), IME monotherapy showed clinical activity and disease-modifying potential in pts with INT-2 or HR MF relapsed/refractory to JAKi. These findings, and the nonoverlapping mechanisms of action, supported the evaluation of IME+RUX in frontline MF. IMproveMF (NCT05371964) is an open-label study of IME+RUX in pts with INT-1/INT-2/HR MF. In Phase 1 (dose finding), IME+RUX was generally well tolerated, with no dose-limiting toxicities at any dose, and a safety profile consistent with reports from other IME trials. Notably, a dose-dependent signal of clinical activity was observed. The pharmacokinetics for the combination were similar to those of previous monotherapy studies. Thus, the recommended Phase 1b dose of 8.9 mg/kg IME active dose (equivalent to 9.4 mg/kg IME sodium) was chosen. Methods: Phase 1b (dose confirmation and expansion) will enroll adult pts with INT-1/INT-2/HR MF with an Eastern Cooperative Oncology Group performance status ≤2 and peripheral blood and bone marrow blasts <10%, ≥2 active symptoms with a score of ≥3, or a total score of ≥10 on the MF Symptom Assessment Form v4.0, an absolute neutrophil count of ≥1.5×10 9 /L independent of growth factor support and platelets of ≥75×10 9 /L (updated criterion), no active systemic hepatitis infection, acute or chronic liver disease unrelated to underlying MF, and no prior history of HSC transplantation. The study was planned to evaluate 2 cohorts. In cohort A (JAKi-naive pts), upon enrollment, pts will start RUX for ≥12 weeks (24 weeks max); once the RUX dose is stable for 4 weeks, 8.9 mg/kg IME intravenously (IV) every 4 weeks will be added. Per the updated protocol (November 2025), the study will no longer recruit pts into cohort A. Existing enrollees will continue in the study per schedule. In cohort B, ~15 pts will be enrolled who are currently on first-line RUX per standard of care for ≥12 weeks, with ≥4 weeks at a stable dose, and will begin 8.9 mg/kg IME IV every 4 weeks after enrollment. Tx will continue until toxicity, disease progression, or withdrawal. The primary endpoint includes safety and symptom response rate at week 24 (proportion of pts with ≥50% reduction in total symptom score [TSS] at week 24 from start of IME+RUX tx). Secondary endpoints include absolute change in TSS at week 24, average absolute change in TSS over 24 weeks, spleen response (≥35% spleen volume reduction) at week 24, and progression-free survival. The primary analysis is planned ~6 months after the last pt’s first dose of IME+RUX; the final analysis will occur after the study ends. Cohort B is actively enrolling. Clinical trial information: NCT05371964 .

Carcinomas of unknown primary treated with molecularly guided therapies and immune checkpoint inhibitors: A subset from the I-PREDICT N-of-1 Precision Oncology study.

3135 Background: Carcinoma of unknown primary (CUP) is a heterogenous group of aggressive malignancies lacking a detectable primary site and collectively comprises 3–5% of cancer diagnoses. Current treatments rely upon empiric chemotherapeutic regimens with high toxicity, limited efficacy, and historic median overall survival times of 3-11 months. There is emerging evidence to support a precision medicine approach using molecularly guided therapies and tumor-agnostic biomarkers. Methods: We performed a subset analysis of patients previously enrolled in the I-PREDICT (NCT02534675) study who had a CUP that was treated with a combination of targeted therapies and biomarker-driven immune checkpoint inhibitors (ICI), based upon comprehensive genomic profiling and recommendations by a Molecular Tumor Board. Results: Among the 210 evaluable patients, 10 (4.8%) had a CUP from which 9 were molecularly matched to one or more targeted therapies and an ICI based on biomarkers for both types of agents. Baseline characteristics include median age of 67 years (range: 59 – 82), with the majority of patients being male (5/9, 56%), non-Hispanic white (7/9, 78%) and treatment naïve (8/9, 89%). Histological subtypes of CUP included poorly differentiated or unspecified (5/9), adenocarcinoma (3/9) and squamous cell carcinoma (1/9). Administered targeted therapies included bevacizumab (4/9), trametinib (4/9), palbociclib (1/9), crizotinib (1/9), everolimus (1/9), and lenvatinib (1/9), while ICI included nivolumab (6/9), pembrolizumab (2/9) and atezolizumab (1/9). ICI were matched based on positive PD-L1 immunohistochemistry (IHC) (6/9), TMB ≥10 mutations/megabase (4/9), SWI/SNF chromatin remodeling gene alterations (3/9), PD-L1 amplification (1/9), mismatch repair gene alterations (1/9) and microsatellite instability-high (1/9). Most patients were matched to >1 ICI biomarker (5/9). Most patients received treatment doublets (6/9, 67%) while the remaining received triplet regimens (3/9, 33%). The best overall response rate was 44% based on RECIST 1.1. This included partial response (4/9), stable disease (3/9), progressive disease (1/9) and not restaged (1/9). Median progression free survival (PFS) was 10.4 months (95% confidence interval [CI] 4.2 - not estimable [NE]) and median overall survival was 16.9 months (95% CI 6.9 - NE). One patient in particular achieved 36-months of PFS on trametinib + nivolumab as matched to NF1 R440* and PD-L1 IHC 5%. Grade ≥3 treatment related serious adverse events occurred in only one patient. Conclusions: As compared to historic chemotherapy treated cohorts, these results support the safety and efficacy of administering molecularly guided combination therapies including a targeted agent plus an ICI in CUP patients. Larger prospective trials of biomarker-matched N-of-1 combinations in CUP are warranted. Clinical trial information: NCT02534675 .

A phase 2, open-label, single-arm study of lirafugratinib in patients with previously treated, unresectable, locally advanced, or metastatic solid tumors (excluding cholangiocarcinoma) with <i>FGFR2</i> fusion or rearrangement.

TPS4251 Background: Tissue agnostic cancer therapies offer the potential to markedly change the treatment landscape by targeting oncogenic drivers rather than the tumor’s site of origin. Lirafugratinib is the first highly selective, irreversible inhibitor designed to target oncogenic fibroblast growth factor receptor ( FGFR)2 driver alterations and resistance mutations. In the phase 1/2 ReFocus Trial (RLY-4008-101; NCT04526106),46 subjects (Group 3) with non-cholangiocarcinoma solid tumors harboring FGFR2 fusion/rearrangements (f/r) received lirafugratinib 70 mg once daily. The ORR was 33.3% (95% CI 19.6 - 49.5). However, this sample size was insufficient to support regulatory approval of lirafugratinib for a tissue agnostic indication. Methods: The ELE-4008-202, phase 2, open-label, single-arm study (NCT07359820) is designed to further evaluate the efficacy and safety of lirafugratinib 70 mg in 20-30 subjects across 20 sites with FGFR2 f/r, previously treated, unresectable, locally advanced or metastatic, non-CCA solid tumors who have not received prior FGFR inhibitor therapy. The primary endpoint is objective response rate (ORR) by independent review committee (IRC) per RECIST v1.1; key secondary endpoints include duration of response (DOR) by IRC, investigator-assessed efficacy endpoints, safety, pharmacokinetic (PK) parameters, and quality of life (QoL) per EORTC QLQ-C30. Efficacy will also be evaluated for ORR, DOR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), time to response (TTR), time to progression (TTP) per investigator. Time to discontinuation (TTD) will also be assessed. Exploratory endpoints will include FGFR2 genotype per tissue assessment or liquid biopsy vs ORR and levels of other biomarkers in relationship to clinical activity. An interim analysis of the pooled efficacy dataset from ELE-4008-202 and Group 3 of RLY-4008-101 will be conducted once approximately 65 evaluable subjects with non-CCA tumors have been enrolled across ≥7 tumor types (≥5 subjects per tumor type). Enrollment of a tumor type may be capped once it has reached approximately 20% of the total subjects in the pooled data from the two studies. With 65 subjects, observing at least 21 subjects with a complete response (CR) or partial response (PR) (ORR ≥32%), will result in a 95% CI (lower bound &gt;20%) with the probability of observing ≥21 responders assuming a true ORR of 40% is approximately 92%. The results of this analysis will determine whether the pooled evaluable data from RLY-4008-101 and ELE-4008-202 meet regulatory requirements to support a tissue-agnostic indication for FGFR2 f/r non-CCA solid tumors. Clinical trial information: NCT07359820 .

Physical activity and sedentary behavior surveillance using accelerometers in Japanese urban adults: A descriptive study of participation and adherence

Background Representative data collection in accelerometer-based physical activity and sedentary behavior surveys is challenging. Although in-person protocols and monetary incentives are recommended to enhance recruitment, the participation outcomes of such methods have not been thoroughly examined. This study aimed to (1) quantify response and adherence rates for an in-person, incentivized accelerometer survey; (2) assess participant representativeness; and (3) characterize reasons and factors associated with participation. Methods This cross-sectional study randomly selected 650 Japanese adults aged 20–79 from resident registers in three major metropolitan areas. Trained investigators delivered and retrieved accelerometers and questionnaires. A 5000-yen incentive was provided upon completion. Primary outcomes were response and adherence rates (≥ 4 valid wear days). Participants’ representativeness was evaluated by comparing sociodemographic characteristics with national census data, and reasons for participation and non-participation were summarized. Results The response rate was 31.5%, and the adherence rate was 29.1%. Compared to census data, participants were older and more likely to be employed and living with others; however, gender distribution was comparable. Motivations for participation differed by age: older adults were mainly motivated by health-consciousness, whereas younger adults cited the monetary incentive. Non-contact at home was a major reason for non-participation among younger adults. Conclusions The in-person, incentivized protocol achieved a higher response rate than typical mail-based methods in Japan and produced a gender-balanced sample, although some selection bias remains. These findings suggest that while this resource-intensive protocol can enhance overall recruitment, future strategies tailored to participant sociodemographic characteristics are warranted to maximize accelerometer-based data collection.

Efficient photothermoelectric detection by layered Bi2 <b>+</b> 2 <i>n</i> O2 <b>+</b> 2 <i>n</i> Se <i>n</i> Cl2 superlattices with ultralow thermal conductivity

Photothermoelectric (PTE) detection, consisting of photothermal and thermoelectric conversion processes, is a promising self-powered strategy for room-temperature optoelectronic sensing. However, a fundamental trade-off between electrical and thermal transport remains a challenge in realizing an efficient PTE effect. Herein, the theoretical calculations, based on the modified two-temperature model and thermal diffusion equation, verify that extremely low thermal conductivity along both in-plane and out-of-plane, as well as a suitable carrier concentration, can achieve excellent PTE performance. In the experiment, furthermore, as a concept-proof, layered Bi–O–Se–Cl superlattice crystals (such as Bi4O4SeCl2 and Bi6O6Se2Cl2) provide an ideal platform to prove our theory because they have the same order thermal conductivity (0.1 W m−1K−1) as that of air (0.03 W m−1K−1). Spectacularly, the Bi6O6Se2Cl2 device demonstrates excellent optoelectronic detectivity at the infrared regime (a responsivity of 87.29 mV W−1 at 1550 nm, a noise-equivalent power of 10.63 nW Hz−1/2, a detectivity of 5.64 × 106 Jones, and a response time of 88 ms). This superior performance comes from optimized synergetic manipulations of extremely low thermal conductivity (in- and out-of-plane thermal conductivity are 0.62 and 0.2 W m−1K−1, respectively) and suitable carrier concentration (∼1020 cm−3), in line with theoretical prediction. This work not only proposes the criteria of material parameters to have an ideal PTE effect but also establishes Bi2 + 2nO2 + 2nSenCl2 superlattices as a promising self-powered broadband photodetector.

Synthesis and characterizations of ZnSe/PVA nanocomposites for optical and modulus study

Highly Stable Two‐Dimensional Conjugated Polymers Enabled by Scalable and Irreversible C─C Cross‐Coupling Reactions

ABSTRACT Two‐dimensional conjugated polymers (2DCPs) have garnered significant interest due to their high surface area, tunable topologies, and broad applicability across diverse fields. However, scalable synthetic methods for producing highly stable 2DCPs remain unknown. This study presents a fast and scalable method to synthesize highly stable 2DCPs via irreversible C─C cross‐coupling reactions. Mechanistic investigations reveal that precise cross‐coupling and π–π aggregate templates drive the rapid formation of regular 2D networks. Notably, the resulting 2DCPs exhibit exceptional chemical stability, serving as robust photocatalysts for C‒N cross‐coupling and oxidative hydroxylation reactions. Furthermore, a self‐standing 2DCP film demonstrates outstanding performance in optoelectronic synapses, with high resilience to harsh conditions. This work establishes a novel approach for synthesizing stable 2DCPs, enabling various applications under extreme conditions.