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Effect of BMI and BMI and Charlson Comorbidity Index on mortality in pancreatic cancer: A single-institution study.

e16473 Background: Pancreatic cancer is an extremely aggressive disease known for its poor outcomes. There are limited prognostic factors identified to date. While elevated Body Mass Index (BMI) has been associated with increased risk of pancreatic cancer incidence in observational cohorts, its impact on mortality among diagnosed patients remains unclear. Our objective was to study impact of pre-treatment BMI and Charlson Comorbidity Index (CCI) on mortality in pancreatic cancer patients undergoing any cancer-directed treatment at our institute. Methods: Patients age 18+ diagnosed with pancreatic adenocarcinoma (ICD10- C25) from 3/1/2021 to 1/1/2024, and who received any pancreatic cancer treatment, were included. Demographic data, tumor characteristics, and treatment details were collected and managed in REDCap. BMI and CCI values at the time of diagnosis were captured. Patients who did not receive treatment were excluded. To determine the impact of BMI and CCI, we fitted a multivariable Bayesian cox proportional hazard regression model. BMI was fitted with splines with three knots to allow for non-linear effects on mortality. We specified a prior distribution that was normal, centered on 0, and where 95% of the distribution was between 0.2-5.0 hazard ratio (Normal (0, log(5)/1.96). Results: A total of 150 patients were included in the study. Sex was evenly split (M = 47% and F = 53%), most of the population was white (73%) and non-Hispanic (77%), and patients had a median age of 70 (62-77 IQR). The median BMI was 26.5 (23-31 IQR), tumor size was 35 mm (25-45 IQR), and most patients were stage 1 (35%). We did not find a relationship in the HR of mortality with BMI, when a BMI of 25 was used as a reference point. When exploring the non-linearity of BMI by clinical stage, there was no relationship either. CCI did not differ in HR when comparing values of 1, 2, 3+ to 0. Conclusions: We were unable to identify the relationship between pre-treatment BMI and CCI on mortality. Subgroup analysis of individual stages demonstrated similar results. Prospective studies with larger sample sizes are warranted to confirm and further elucidate these associations, including the role of metabolic factors. Analysis by type of treatment alone (surgery vs. chemo and radiation) may be useful in identifying a relationship.

Recent trends in utilization of outpatient medical oncology services.

11101 Background: Health systems face escalating demand from rising cancer incidence and treatment complexity. Effective health human resource planning is critical to accommodate these trends. Limited data are available on longitudinal utilization of medical oncology services, especially volumes and complexity of care. We sought to characterize real-world longitudinal utilization of outpatient medical oncology services across common solid tumors to inform workforce planning and policy. Methods: We conducted a retrospective, population-based retrospective cohort study using linked administrative health data from Ontario, Canada. Adults diagnosed between 2015 and 2022 with lung, colon, rectal, pancreatic, breast, melanoma, or prostate cancer were identified through the Ontario Cancer Registry. Medical oncology consultations, clinic visits, and systemic treatment encounters were captured from the provincial Activity Level Reporting database. Primary outcomes included consultation and systemic therapy initiation trend, and mean clinic and treatment visits during the first year following medical oncology consultation. Results: The cohort consisted of 332,604 patients (median age 68 years; 48.7% male), with new cases increasing from 39,688 in 2015 to 45,011 in 2022. Medical oncology consultation and systemic treatment initiation were encountered by 57.8% (range: 17.2% prostate to 92.8% breast) and 71.2% respectively (range: 45.1% melanoma to 82.8% breast). The proportion of patients with medical oncology consultation increased appreciably for pancreatic (59.8% to 79.0%), colon (55.8% to 60.2%), rectal (64.4% to 69.6%), and lung cancers (57.3% to 61.4%), with resultant growth in consultation volumes except for melanoma, colon and lung cancers. Total clinic visits increased from 131,950 in 2015 to 174,630 in 2022. Mean clinic visits per patient increased significantly for all cancers except prostate (p < 0.001), with the greatest increase observed in melanoma (+0.33 visits/year). Systemic therapy exposure increased across most cancers, most notably melanoma (25.7% to 47.2%) and prostate cancer (61.2% to 73.9%). Total systemic treatment visits increased from 129,380 in 2015 to 165,149 in 2022 with total and mean per patient trends exhibiting mixed, disease-specific patterns. Conclusions: Outpatient medical oncology service utilization per patient has expanded substantially over time, driven by rising volumes of consultations, systemic therapy and clinic visits. Taken with the rising complexity of care, these data suggest that consultation-based workload metrics likely underestimate service demand. Workforce planning models should incorporate follow-up care, treatment monitoring, and disease-specific trajectories to ensure sustainable, high-quality oncology care delivery.

SARC046: A phase II trial of nab-sirolimus in patients with progressing or symptomatic epithelioid hemangioendothelioma.

TPS11592 Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with about 120 cases diagnosed in the US per year. Although it is commonly considered an indolent disease, in its aggressive form clinical outcomes are poor. Molecularly, EHE is characterized by the presence of oncogenic fusions with HIPPO pathway effectors TAZ or YAP; TAZ-CAMTA1 or YAP-TFE3. YAP/TAZ are modulators of mTORC1 in preclinical models, suggesting that mTOR inhibition may be an effective treatment mechanism for EHE. Nab-sirolimus is albumin bound sirolimus, which achieves higher intratumoral accumulation compared to oral sirolimus and has demonstrated increased antitumor activity in preclinical cancer models compared to the oral mTOR inhibitors sirolimus and everolimus. This is an open label, multi-center, single arm, phase II clinical trial with a two-stage design, testing nab-sirolimus for progressing or symptomatic EHE. The primary objective is to determine ORR of nab-sirolimus in patients with EHE who require systemic treatment. We hypothesize that nab-sirolimus will have significant clinical efficacy for EHE as measured by the primary endpoint of objective response rate, as well as by secondary outcomes including progression free survival benefit over historical controls and by improvement in patient reported outcomes (PROs). If positive, this trial could lead to a new standard of care for treating EHE. Methods: This is a single arm, multi-center, phase 2 study with a two-stage design. Key inclusion criteria include histologically or cytologically confirmed EHE that is either progressing or clinically symptomatic, not a candidate for curative intent surgery, and requires systemic therapy in the opinion of the investigator, radiographically evaluable disease by RECIST v1.1, age ≥18 years, ECOG performance status ≤ 2, and adequate end organ function. With a Simon two-stage optimal design with one sided alpha 0.10, power 90%, assuming a historical control ORR 5% to detect an ORR of 20% (alternative hypothesis), 12 patients will be included in the first stage. If there is ≥ 1 response, an additional 25 patients will be enrolled to a total of 37 patients. ≥ 4 responses are needed for a significant result. The total planned accrual is 41 patients to account for unevaluable patients who may be enrolled, 10% above the required evaluable patients. Planned post hoc subgroup analyses will include outcomes by fusion type and presence of serosal effusions at the time of study enrollment. The trial is registered at clinicaltrials.gov NCT07104331. Clinical trial information: NCT07104331 .

Myoepithelial carcinoma: Defining natural history and therapeutic outcomes in a rare malignancy.

e18143 Background: Myoepithelial carcinoma (MEC) is a neoplasm derived from myoepithelial cells and characterized by an infiltrative growth pattern. These are very rare malignancies with limited published data describing outcomes. We sought to define the natural history of MEC and to identify best available treatments. Methods: In this retrospective series, we identified 70 patients with MEC seen at our institution from 1997-2025. Electronic medical records were reviewed to determine the patient and tumor characteristics, treatment regimens and response, and outcomes. The Kaplan Meier method was used to estimate survival, and log-rank tests were used to compare groups. Results: In our institutional cohort of 70 patients, MEC was most common in middle-aged individuals (median age = 52 years), with a predilection for head and neck sites (54/70, 77%). There was a slight predilection for male sex (40/70, 57%). The median overall survival (mOS) in our cohort was 87.2 months. Of 24 patients who developed metastatic disease, the predominant location was lung (n = 15, 62.5%) followed by bone (n = 11, 45%). For patients with localized disease (n = 66), the median recurrence-free survival (mRFS) was 55.4 months. The mRFS was not significantly different in patients who had resection alone (n = 39, mRFS = 60.0 months) compared with those treated with adjuvant radiation and/or chemotherapy (n = 27, mRFS = 51.1 months, p = 0.70). The primary systemic therapy utilized was platinum-based with few patients receiving doxorubicin or gemcitabine-based regimens. There were no significant clinical responses noted with systemic therapy. The median progression-free survival (mPFS) in patients with metastatic disease who received any systemic therapy was 3.1 months (n = 16). No significant difference in mOS was observed based on age, though there was a trend toward worse outcomes in younger patients (mOS for <30 years = 62.5 months, mOS for >30 years = 93.5 months, p = 0.88). The sample size of patients in the younger age group (n = 11) was small and only three patients in that subset were free of disease for >15 years. Conclusions: In our institutional experience with MEC, most patients were middle-aged with head and neck as the most common primary site. Outcomes were generally worse for younger patients. The lack of significant difference between the mOS between these age groups is attributed to a small sample size of patients in the younger age group with a wide confidence interval. Outcomes with currently available systemic therapy for metastatic disease were uniformly poor, emphasizing the need to develop novel treatment regimens moving forward. Future work is needed to discern the impact of specific genomic alterations (e.g. EWSR1-KLF15 fusion) on tumor biology and response to therapy.

Development and internal validation of a web-based risk assessment tool for chemotherapy-induced peripheral neuropathy: A retrospective cohort study.

e24154 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting toxicity that can impair quality of life and lead to dose reductions, treatment delays, or discontinuation, thereby undermining the effectiveness of anticancer therapy. This study aimed to identify key risk factors for CIPN and to develop a clinically translatable prediction model for early risk stratification to inform prevention and management. Methods: We developed a prediction model for chemotherapy-induced peripheral neuropathy (CIPN) in 371 cancer patients receiving chemotherapy at Zhongshan Hospital, Xiamen University (January 2023–September 2025). Missing data were handled using multiple imputation by chained equations. A multivariable logistic regression model was derived with predictors selected by stepwise AIC and/or LASSO, and coefficients were pooled using Rubin’s rules. A random-forest model was trained for benchmarking and interpreted using SHAP values. Internal validation used bootstrap resampling to assess discrimination (AUC) and calibration; clinical utility was evaluated by decision-curve analysis. The final model was implemented as an online risk calculator. Results: Among 371 patients receiving chemotherapy, CIPN occurred in 215 patients (57.95%). The final multivariable logistic model, derived using multiple imputation with pooled estimates, retained 5 predictors (Cancer Type, Triglycerides, Calcium, Globulin, Prothrombin Time). On bootstrap internal validation, the model showed good discrimination (AUC=0.805, 95%CI [0.771–0.860]) and satisfactory calibration (calibration slope =0.8856; intercept =0.0060; bootstrap-corrected calibration curve closely aligned with the ideal line). Decision-curve analysis demonstrated net clinical benefit across a clinically relevant threshold range (0-0.6). A web-based calculator was implemented to provide individualized risk estimates and facilitate bedside use. Conclusions: The proposed model demonstrated good discrimination and calibration on internal validation and may serve as a practical, user-friendly tool to support early identification and risk stratification of patients at high risk for CIPN.

Circulating tumor deoxyribonucleic acid (DNA) and treatment outcomes of gastroesophageal cancer: A systematic review and meta-analysis.

4185 Background: Gastroesophageal tumors are some of the most highly prevalent cancers worldwide. Despite the high prevalence and advancement in treatments, they represent a major cause of cancer-related deaths. Thus, advancement in gastroesophageal cancer treatment and post-treatment monitoring are imperative in improving disease prognosis. In this study, we aimed to investigate the association between pre- or post-treatment plasma circulating tumor deoxyribonucleic acid (ctDNA) and post-treatment outcomes. Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus on October 30, 2025 using ctDNA and gastroesophageal cancer as the keywords along with their related MeSH terms. Studies were included if they investigated the association between the detection of pre- or post-treatment plasma ctDNA and disease outcomes among patients with esophageal or gastric cancer. Our exposure of interest was the detection of pre- or post-treatment ctDNA in plasma while the outcomes of interest were tumor recurrence and tumor progression. The odds ratio (OR) and its 95% confidence interval (95%CI) were the effect measures of choice in the analysis. Results: We included a total of 1,897 patients with gastric or esophageal cancer from 21 prospective or retrospective cohorts. Our analysis revealed that pre-treatment detection of ctDNA in the plasma was associated with higher odds of tumor recurrence (OR=4.37; 95%CI: 1.20-15.92) and progression (OR=4.80; 95%CI: 2.51-9.18). These results were consistent in the subgroup analysis among patients with esophageal cancer while they lost their significance among patients with gastric cancer and among good quality studies (Newcastle Ottawa Scale>5). Moreover, the detection of post-treatment ctDNA was associated with higher odds of tumor recurrence (OR=6.14; 95%CI: 3.79-9.94) and progression (OR=8.28; 95%CI: 5.03-13.64). These results were consistent in the subgroup analysis of patients with esophageal cancer, gastric cancer and among good quality studies. Conclusions: Our results highlight that detection of pre-treatment but more so post-treatment ctDNA is associated with post-treatment cancer outcomes. Our results emphasize the potential use of ctDNA as a valuable tool for detection of early gastroesophageal cancer recurrence and post-treatment progression.

The impact of depth of response on long-term clinical outcomes: Exploratory analyses from multiple expansion cohorts of a phase 1/1b study of ficerafusp alfa plus pembrolizumab in first-line recurrent/metastatic (R/M) HPV-negative head and neck carcinoma (HNSCC).

6058 Background: Ficerafusp alfa is the first and only bifunctional EGFR-directed antibody designed to trap TGF-β, enabling tumor penetration of immune cells and driving deep and durable responses. Depth of response has been shown to correlate with prolonged progression free survival (PFS) and overall survival (OS) in several solid tumors. However, such data are limited in R/M HPV-negative HNSCC. Here we performed exploratory analyses to evaluate whether depth of response achieved with ficerafusp alfa and pembrolizumab is associated with prolonged duration of response (DOR), PFS and OS. Methods: Three cohorts of a phase 1/1b study (NCT04429542) in 1L, R/M HNSCC, with PD-L1 CPS ≥1 evaluated ficerafusp alfa (750mg QW,1500 mg QW, or 2000 mg Q2W) IV combined with pembrolizumab IV. Objective response rate (ORR) per RECIST v1.1, DOR, PFS, and OS were assessed. In the pooled efficacy evaluable set from the three cohorts, we explored if the magnitude of tumor regression, comparing tumor regression ≥80% regression (defined as a deep response) vs. tumor regression 0 to <80%, is predictive of longer-term clinical outcomes (DOR, PFS, OS). Results: As of December 16, 2025, 85 patients with HPV-negative disease were efficacy evaluable across three cohorts (n=30, n=28, and n=27 at 750mg, 1500mg, and 2000mg doses of ficerafusp alfa, respectively). Among these, the confirmed ORRs were 57%, 54%, and 48%, respectively, including 47%, 80%, and 77% of responders achieving a deep response. In the pooled efficacy evaluable set the percentage of patients with a deep response was 36%, with tumor regression 0 to <80% was 46%, and no tumor regression was 18%. mDOR was longer for patients with a deep response compared to patients with tumor regression 0 to <80% (21.9 mo vs 8.2 mo, HR 0.27). mPFS was also longer in patients with a deep response compared to patients with tumor regression 0 to <80% (26.4 mo vs 6.5 mo, HR 0.19). mOS was not reached (NR) in patients with deep response and 14.9 mo in patients with tumor regression 0 to <80% (NR vs 14.9 mo, HR 0.17). Conclusions: Ficerafusp alfa plus pembrolizumab demonstrated deep responses across multiple dose levels. Deep responses were associated with improved long-term efficacy outcomes, including DOR, PFS, and OS. This suggests that depth of response may represent a clinically meaningful surrogate for understanding long-term efficacy outcomes in HPV-negative HNSCC. Clinical trial information: NCT04429542 . Tumor Regression0 to <80%N=39 Tumor Regression ≥ 80% (Deep Response)N=31 mDoR (mo) 8.2 21.9 HR [vs < 80% tumor regression] (95% CI) N/A 0.27 [0.10, 0.71] mPFS (mo) 6.5 26.4 HR [vs No DR] (95% CI) N/A 0.19 [0.09, 0.40] mOS (mo) 14.9 NR HR [vs No DR] (95% CI) N/A 0.17 [0.07, 0.41]

Risk and patterns of recurrence for patients (pts) with advanced urothelial carcinoma (aUC) metastatic to liver after response to enfortumab vedotin + pembrolizumab (EVP).

4584 Background: EVP is the preferred frontline regimen in pts with aUC. Despite initial response to treatment, many pts treated with EVP ultimately have progression. We hypothesized that recurrence patterns would differ between pts with and without baseline liver metastases. Methods: UNITE is a multi-institutional retrospective database capturing clinical and treatment characteristics of pts with aUC receiving systemic therapies. We queried this database to identify pts who achieved an observed response (OR) to EVP. Pts were grouped by initial metastatic sites using a non-mutually exclusive approach. Descriptive statistics were used to summarize observed response rates (ORR) and recurrence patterns at time of progression. Progression-free survival (PFS) from start of EVP was estimated using the Kaplan-Meier method. The effect of liver metastases on PFS was assessed via multivariable Cox regression. Median-follow up time was estimated using the reverse Kaplan-Meier method. Statistical analyses were conducted in RStudio. Results: We identified 464 pts treated with EVP (median age 72; 74% male, 80% White). Best ORR in pts with baseline liver metastases (n=77) were complete response 9%, partial response 35%, stable disease 18%, and progressive disease 21%, compared with 18%, 37%, 27%, and 18%, respectively, in pts without baseline liver metastases (n=325). The estimated median follow-up time was 52 weeks (95% CI 48-62). Among pts with initial OR to EVP, those with baseline liver metastases showed a non-significant trend toward shorter PFS (HR 1.35; 95% CI 0.67–2.75; p=0.40) versus those without baseline liver metastases. Among pts with initial OR to EVP and subsequent progression the distribution of sites of recurrences at progression for those with (n = 10) and without (n = 40) baseline liver metastases were: liver (50% vs. 10%), lymph nodes (60% vs. 55%), lungs (50% vs. 38%), bone (20% vs 20%), and primary tumor (20% vs 25%). EVP responders with baseline liver metastases had a numerically higher rate of site-specific metastasis resolution at progression versus those with lymph node or lung metastases (Table). Conclusions: Our analysis suggests that liver metastases may be associated with shorter PFS among EVP responders, though these pts frequently do not retain liver metastases at time of progression. Study limitations include retrospective analysis, investigator-assessed response, small sample size, selection and confounding biases. Patterns of recurrence following EVP merits further evaluation. Metastatic Site Pts with Site-Specific Baseline Metastases (n) Pts with Resolution of Site-Specific Metastases at Progression, n (%) Pts without Baseline Metastases at Site (n) Pts who Remained Free of Site-Specific Metastases at Progression, n (%) Liver 10 5 (50%) 40 36 (90%) Lymph Nodes 37 12 (32%) 13 10 (77%) Lungs 26 8 (31%) 24 22 (92%)

Real-time detection of extravasation events of diagnostic and therapeutic radiopharmaceuticals in oncology

Background Radiopharmaceutical extravasation—when injected activity remains in soft tissue rather than entering the bloodstream—can compromise quantification in positron emission tomography/computed tomography (PET/CT) and, in therapeutic settings, deliver high local radiation doses. These effects may lead to inaccurate Standardized Uptake Value (SUV) measurements, potential misdiagnosis, repeat examinations, and to avoid patient risk. We assessed a simple, real-time approach for detecting extravasation during administration to enable immediate management and quantitative correction. Results Real-time monitoring with portable gamma detectors was applied to 885 diagnostic PET examinations ( 18 F-FDG, 68 Ga-DOTATOC/TATE, 68 Ga-PSMA-11) and 15 administrations of 177 Lu-DOTATATE therapy. In the diagnostic cohort, 53 extravasation events were identified and confirmed on PET images. Analysis of dose-rate–time curves yielded practical thresholds for extravasation detection: Δp in nor = 0.30 and ΔR t  = 388 µSv/h. A statistically significant association was observed between SUV correction factors and specific curve parameters, enabling prospective adjustment of SUV before image interpretation. In the therapeutic cohort, one extravasation was observed, with an estimated absorbed self-dose of 11.6 Gy to the affected region. The monitoring enabled timely intervention that limited unnecessary exposure and workflow disruption. Feasibility analyses indicated that, for diagnostic procedures, a single detector can be sufficient for reliable extravasation identification and for deriving SUV correction factors. Conclusions A real-time, detector-based strategy can identify radiopharmaceutical extravasation during injection, support immediate mitigation, and preserve diagnostic accuracy by allowing early SUV correction. In therapeutic applications, it can reduce risk by prompting management of rare but consequential events. The operational simplicity, low cost, and effectiveness demonstrated across both diagnostic and therapeutic scenarios support integration of this approach into routine clinical practice, with the added practicality that a single detector appears adequate for diagnostic workflows.

Tailoring Hybrid Copper Iodide Cluster Glasses via Ligand Design for Stable Multifunctional X‐Ray Imaging

ABSTRACT The development of glassy organic–inorganic hybrid material has attracted great interest, yet remains significantly challenging due to issues such as unstable melting, poor crystallization resistance, and limited environmental stability. In this study, we report a rational ligand engineering strategy for designing novel copper iodide cluster glasses. By using phosphine ligands with varying aromatic phenyl (Ph‐) and aliphatic cyclohexyl (Cy‐) groups, a series of zero‐dimensional Cu 4 I 4 (L) 4 (L = Ph 3 P, CyPh 2 P, and Cy 2 PhP) cubic clusters was synthesized. Variable‐temperature X‐ray absorption fine structure analysis, Raman spectroscopy, and molecular dynamics simulations reveal that melting proceeds through disruption of intermolecular electrostatic interactions rather than ligand dissociation. Density functional theory and rheological analyses further rationalize how ligand engineering regulates the thermodynamic behavior of the clusters. Systematic substitution of phenyl with cyclohexyl groups modulates intermolecular forces, effectively suppressing crystallization and enabling successful vitrification for the CyPh 2 P and Cy 2 PhP analogues. The resulting low‐melting Cu 4 I 4 (Cy 2 PhP) 4 glass exhibits a high glass transition temperature (352.3 K), excellent optical transparency (> 80%, 450–800 nm), and remarkable stability. These properties allow its application in high‐resolution, underwater, and high‐temperature X‐ray imaging. This work establishes a feasible design principle for organic–inorganic hybrid glasses and underscores their potential for advanced photonic applications.

Tunable electronic and optical properties of armchair SiSn nanoribbon under external electric field: A first-principles study

Ultrabroadband SnBi ₂ Te ₄ Photodetectors From Visible to Terahertz

ABSTRACT Ultrabroadband photodetectors (UB‐PDs) are seeing burgeoning deployment across a lot of technologies, including artificial intelligence, healthcare, optical communications, and biomedical imaging, which prompts urgent demands for high‐performance UB‐PDs. However, the existing photodetectors usually suffer from limitations of narrow operational bandwidth and low sensitivity at room temperature. SnBi 2 Te 4 , a novel topological insulator intercalation material, exhibits a narrow bandgap, unique surface‐state conductive transport properties, and a tunable band gap, making it an ideal candidate for room‐temperature ultrabroadband photodetection. In this study, we synthesize high‐quality layered SnBi 2 Te 4 crystals using the Chemical Vapor Transport (CVT) method. The fabricated detector achieves high‐performance broadband detection from visible to terahertz (THz) light through synergistic mechanisms of the conventional photoelectric effect and the electromagnetic‐induced well effect. In the visible‐infrared region, the photodetector shows a noise equivalent power of 8.5 pW·Hz −1/2 with the response time of 70 µs and responsivities of 19.4 A·W −1 at 980 nm and 13.9 A·W −1 at 635 nm, respectively. Additionally, the current responsivity (R i ) of the SnBi 2 Te 4 photodetector is 0.117 A·W −1 at the mid‐wave infrared (MWIR, 3 µm) band and 0.063 A·W −1 at the long‐wave infrared (LWIR, 10.6 µm) band. In the terahertz region, this detector achieves sensitive detection across the 0.02–0.519 THz spectral band, exhibiting an ultrafast response time of 1.83 µs. Finally, the excellent performance of the detectors is demonstrated by high‐resolution THz transmission imaging experiments at room temperature. Our study confirms the significant advantages of SnBi 2 Te 4 for ultrabroadband room‐temperature photodetection.

Spectroscopic response of carotenoids in chromoplasts in sunflower inflorescence

A tri-specific EGFR/cMet/VEGF antibody demonstrates potent multi-mechanistic activity in preclinical triple-negative breast cancer models

Spatial transcriptomic profiling of the tumor microenvironment associated with sunitinib response in metastatic renal cell carcinoma.

3119 Background: Metastatic clear cell renal cell carcinoma (ccRCC) exhibits heterogeneous clinical outcomes, and limited biomarkers are available to predict response to targeted therapies. This study evaluated cell compartment-specific transcriptional biomarkers predicting clinical response to the tyrosine kinase inhibitor (TKI) sunitinib. Methods: In this phase 2 single-arm clinical trial (NCT00715442), 46 patients with metastatic ccRCC received sunitinib pre- and post-cytoreductive nephrectomy. The primary endpoint was time-to-progression (TTP) and secondary endpoints included overall survival (OS) and sunitinib toxicity. To investigate spatial dynamics of therapeutic response to sunitinib, we applied whole-transcriptome digital spatial profiling (DSP) to tumor tissue to identify myeloid, endothelial, CD8+ T-cell and tumor compartment-specific transcriptional differences between responders (complete or partial response) and non-responders (stable or progressive disease). Results: For the 46 trial patients, the median duration of follow-up was 9.8 years (95% CI: 9.4 – NA). The median TTP was 8.2 months (95% CI: 6.1-19.3) and OS 36.3 months (95% CI: 19.7-70.5). Sunitinib-related adverse events occurred in 20% of patients, with grade 3 and 4 toxicities including hand-foot syndrome, fatigue, and hematologic abnormalities (thrombocytopenia, neutropenia). DSP analyses demonstrated that sunitinib responders display a tumor microenvironment enriched in pro-inflammatory and immunostimulatory programs. By contrast, non-responders displayed enrichment of immunosuppressive programs with elevated PD-L1 expression in myeloid cells and exhausted CD8+ T-cell signatures. Sunitinib resistance mechanisms involving pro-angiogenic VEGF-dependent and independent pathways were identified in non-responders, revealing potential therapeutic targets in combination with TKIs. Moreover, gene signatures developed based on DSP analysis of sunitinib response accurately predicted sunitinib response in an external patient cohort. Conclusions: Our findings underscore the relevance of spatial omics approaches to inform patient stratification and guide precision and combination treatment strategies aimed at mitigating TKI resistance in metastatic ccRCC. Clinical trial information: NCT00715442 .

Routine prognostic blood tests to compare survival outcomes with low-dose therapy in treatment-naïve and resistant advanced pancreatic cancer.

e16349 Background: Patients with advanced pancreatic cancer (APC) have limited effective treatment options and substantial unmet needs. Prognostic blood tests (PBTs) may identify patients most likely to benefit from specific therapeutic strategies, including low-dose chemotherapy. Methods: Patients with treatment-naïve (NAPC) or resistant (RAPC) stage IV APC and ECOG performance status 0–2 were enrolled. RAPC tumors had progressed after FOLFIRINOX, gemcitabine with nab-paclitaxel, or both. Treatment consisted of one-third standard doses of gemcitabine, irinotecan, 24-hour fluorouracil/leucovorin, and day-2 oxaliplatin. Upon progression, docetaxel and mitomycin C were added on day 2 without discontinuing prior therapy. Written informed consent was obtained, and the study was registered with IRBs, the FDA, and ClinicalTrials.gov in accordance with Helsinki standards. This was a prospective, intent-to-treat analysis. Uni- and multivariate analyses evaluated survival and interactions based on established cut points for PBTs, age, sex, and treatment resistance. Results: Median survival time (MST) was 13.5 months (95% CI, 12–15) for 53 patients with NAPC and 9.4 months (95% CI, 7.1–10.9) for 53 patients with RAPC (p = 0.39). The A.L.A.N. score (AS 0–2), defined by fewer than three unfavorable tests; serum albumin < 3.5 g/dL, neutrophil-to-lymphocyte ratio ≥3, absolute neutrophil count > 8,000/µL, and lymphocyte-to-monocyte ratio < 2.1, was the most powerful prognostic indicator (p < 10⁻⁹). Among favorable NAPC PBT subgroups (77% of patients), MSTs ranged from 13.6 to 17.2 months, with 24-month survival rates of 24–35% (p = 0.03 to 2.3×10⁻⁷). Unfavorable NAPC subgroups had MSTs of 8–12.5 months. Favorable RAPC PBT subgroups (81% of patients) demonstrated MSTs of 12.5–18.2 months, with 12-month survival rates of 50–75% (p = 0.02 to 4.5×10⁻⁴). Unfavorable RAPC subgroups had MSTs exceeding 6–8 months. Treatment was well tolerated, with no hospitalizations, infections, treatment discontinuations, or dose-limiting toxicities. Conclusions: Low-dose chemotherapy may safely prolong survival in a majority of patients with NAPC identified by favorable PBTs, as well as in select patients with RAPC and A.L.A.N. scores of 0–2. Future trials integrating independent PBTs (serum albumin, NLR, ANC, LMR) and interactive biomarkers (platelets, monocytes, hemoglobin) may refine patient selection, expand eligibility for those with unmet needs, support lower-dose strategies, enable timely recombination and rechallenge, and improve understanding of host-cell–associated resistance mechanisms. Clinical trial information: 119005 .

Practical prognostic tool for personalising first-line alectinib in ALK-positive NSCLC: A real-world model integrating neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and eosinophil count.

e20743 Background: Despite the efficacy of first-line alectinib in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), significant interpatient heterogeneity exists. Robust tools for individualized risk stratification using readily available parameters are lacking. Methods: This retrospective study developed and validated a prognostic nomogram for overall survival (OS). The training cohort comprised 127 patients from a Chinese academic center. The external validation cohort included 64 patients from the US Flatiron Health database. All patients received first-line alectinib. Feature selection was performed using the Boruta algorithm among baseline clinical and laboratory variables. A Cox model was used to build a nomogram, which was assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: The model identified three independent prognostic factors: neutrophil-to-lymphocyte ratio (NLR), absolute eosinophil count (AEC), and lactate dehydrogenase (LDH). The nomogram demonstrated good discrimination, with a C-index of 0.78 (95% CI: 0.69–0.87) in the training cohort, which was maintained at 0.77 (95% CI: 0.68–0.86) upon external validation. Calibration was excellent across all predicted timepoints (1-5 years). Using an optimal cut-off (57.97 points), patients were stratified into low- and high-risk groups. High-risk patients had significantly inferior median OS (14.7 vs. not reached, P < 0.001) and time to treatment failure (7.7 vs. 62.5 months, P < 0.001) in the training cohort, a finding robustly validated externally. DCA confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions: We developed and validated a practical prognostic nomogram based on three routine blood parameters (NLR, AEC, LDH) that effectively stratifies survival in ALK-positive NSCLC patients treated with first-line alectinib. This tool could facilitate personalized risk-adaptive management and enrich future clinical trials.

Real-world effectiveness of sacituzumab govitecan (SG) versus trastuzumab deruxtecan (T-DXd) in HER2-negative (HER2-) metastatic breast cancer (MBC) in China: A propensity-score–matched study.

3034 Background: SG and T-DXd are both antibody-drug conjugates (ADC) approved in China for HER2- MBC patients. However, direct real-world comparisons between these two therapies in HER2- MBC patients in China remain limited. This study aimed to evaluate and compare clinical outcomes of SG and T-DXd in Chinese patients with HER2- MBC in real-world practice. Methods: This retrospective study included 306 HER2- MBC patients, with 151 treated with SG and 155 treated with T-DXd. Separate propensity score matching (PSM) was performed for the triple-negative (TN) and hormone receptor-positive (HoR+) cohorts, respectively. Matching variables for both cohorts included age, HER2 expression, prior ADC use, number and site of metastases (liver, brain), and prior lines of therapy. For TN cohort only, DFI, prior taxane and PD-1/PD-L1 inhibitor use were additionally matched (caliper = 0.1). Clinical outcomes included real-world progression-free survival (rwPFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Median follow-up was 13.4 mo (SG-TN), 12.0 mo (SG-HoR+), 12.4 mo (T-DXd-TN), and 12.0 mo (T-DXd-HoR+). After PSM, 33 TN patients and 28 HoR+HER2- patients were matched in each treatment group. Baseline clinical characteristics were well-balanced. In TN patients, rwPFS was comparable between SG and T-DXd (5.0 vs 5.7 mo, HR=0.63, P =0.138). The comparable effectiveness of SG and T-DXd was also observed in both HER2-null ( P =0.498) and HER2-low ( P =0.250) subgroup. Meanwhile, SG showed a trend toward improved rwOS (NR vs 13.1 mo, HR=1.75, P =0.216). However, T-DXd demonstrated significantly higher ORR (18.2% vs 45.5%, P =0.017) and DCR (45.5% vs 75.8%, P =0.012) compared to SG. In HoR+HER2- patients, T-DXd showed significantly longer rwPFS compared to SG (9.8 vs 5.5 mo, HR=0.41, P =0.010), especially among those with HER2-low disease (8.4 vs 5.3 mo, HR=0.36, P =0.007); OS data were immature. ORR (14.3% vs 39.3%, P =0.035) and DCR (42.9% vs 85.7%, P <0.001) favored T-DXd, as well. Subgroup analyses indicated that T-DXd in those with DFI >12 months prolonged rwPFS than SG (10.2 vs 3.5 mo, HR=0.46, P =0.036). In HoR+ patients, the median rwPFS was significantly longer in T-DXd group than SG group in the majority of subgroups. Conclusions: In this real-world PSM analysis, T-DXd showed improved rwPFS compared with SG in HoR+HER2- MBC patients, while both regimens had generally comparable effectiveness in TN patients. These findings suggest that treatment selection may be influenced by hormone receptor status and the duration of DFI. Further prospective studies are warranted to validate these observations.

Effect of dose-escalated WBRT on survival in NSCLC leptomeningeal metastases: A multimodal analysis of local and systemic therapies.

e14021 Background: Leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) carry a dismal prognosis. Modern management combines systemic therapies (targeted therapy [TT], chemotherapy, and immunotherapy) with local therapies (whole-brain radiotherapy [WBRT] and intrathecal chemotherapy [IT]). While most centers use 30Gy/10 fractions WBRT, whether dose escalation provides additive benefit when combined with effective systemic therapies remains unclear. We evaluated survival outcomes across WBRT fractionation regimens in the context of contemporary multimodal local and systemic treatment strategies. Methods: We performed a retrospective analysis of 160 NSCLC patients with LM treated with WBRT at Sanjiu Brain Hospital between December 2019 and March 2024. Patients received one of three WBRT regimens: 30Gy/10 fractions, 36Gy/18 fractions, or 40Gy/20 fractions. Systemic therapies included TT, chemotherapy, immunotherapy, and VEGF inhibitors. Local therapies included WBRT and IT. Univariate and multivariate Cox proportional hazards models assessed the independent impact of WBRT dose, along with clinical factors including age, sex, mutation status, IT, and systemic therapy, on overall survival. The primary endpoint was overall survival from the time of WBRT completion. Results: Among 160 patients (82 males, 78 females), 91% received systemic TT (predominantly EGFR/ALK inhibitors) and 73% received IT, reflecting modern practice patterns. 13 (8%) received 30Gy/10f, 56 (35%) received 36Gy/18f, and 91 (57%) received 40Gy/20f. With a median follow-up of 259 days, 119 deaths occurred. Median OS was 325 days (95% CI: 258-387) for 40Gy/20f vs. 298 days (95% CI: 242-607) for 36Gy/18f vs. 120 days (95% CI: 80-NA) for 30Gy/10f (log-rank p=0.011). Both systemic and local therapies demonstrated survival benefit: TT (325 vs. 173 days without TT; HR 0.39, 95% CI: 0.21-0.70, p=0.002) and IT (346 vs. 199 days without IT; HR 0.62, 95% CI: 0.42-0.92, p=0.016). After adjusting for all treatment modalities, each component retained independent significance: 36Gy/18f WBRT (HR 0.29, 95% CI: 0.15-0.57, p<0.001), 40Gy/20f WBRT (HR 0.37, 95% CI: 0.20-0.70, p=0.002), TT (HR 0.35, 95% CI: 0.19-0.65, p<0.001), and IT (HR 0.57, 95% CI: 0.38-0.84, p=0.005). Conclusions: In NSCLC patients with LM, optimal outcomes require integration of both systemic and local therapies. Dose-escalated WBRT (36Gy/18f and 40Gy/20f) provides an independent survival benefit beyond standard 30Gy/10f, even in patients receiving effective systemic TT. Both local therapies (higher-dose WBRT and IT) and systemic therapy (TT) independently contribute to survival, suggesting comprehensive multimodal strategies incorporating all three modalities. These findings warrant prospective validation to optimize integrated treatment approaches in this poor-prognosis population.

Postoperative adjuvant hepatic arterial infusion chemotherapy combined with donafenib for hepatocellular carcinoma with solitary large tumor and microvascular invasion: A prospective, single-arm, phase II trial.

e16252 Background: Hepatocellular carcinoma (HCC) with a solitary large tumor (≥ 5 cm) and microvascular invasion (MVI) is associated with a high risk of recurrence and poor survival prognosis. Currently, no effective adjuvant therapy has been established for this patient population. This study aimed to evaluate the efficacy and safety of adjuvant hepatic arterial infusion chemotherapy (HAIC) combined with donafenib in this high-risk group. Methods: This prospective, multicenter, single-arm, phase II trial was conducted at three hospitals in China. Patients with histologically confirmed treatment-naïve HCC were enrolled if they had a solitary tumor (≥ 5 cm) and MVI prior to surgical resection and had received no postoperative adjuvant therapies within 4-8 weeks before enrollment. Eligible patients were scheduled to receive adjuvant HAIC (FOLFOX4 regimen) combined with donafenib. The primary endpoint was the 2-year recurrence-free survival (RFS) rate. Secondary endpoints included RFS, overall survival (OS), and safety. Results: A total of 30 patients were enrolled. The median age was 59 years, and 93.3% of patients were male. Most patients were HBsAg-positive (73.3%), and 93.3% had Child-Pugh A liver function. The median maximum tumor diameter was 6.7 cm (IQR: 5.6-8.2), and 40.0% of patients had an AFP level > 400 ng/ml. After a median follow-up time of 22.4 months, tumor recurrence occurred in 9 patients, including 6 with intrahepatic recurrence and 3 with extrahepatic metastasis. The 1-, 2-, and 3-year RFS rates were 78.6%, 55.5%, and 55.5%, respectively, and the median RFS was not reached. The corresponding OS rates were 100.0%, 89.3%, and 79.4%, respectively, with the median OS not reached. In subgroup analysis, patients with AFP ≤ 400 ng/ml had numerically better RFS and OS than those with AFP > 400 ng/ml (1-, 2-, and 3-year RFS rates: 100.0%, 59.1%, and 59.1% vs. 54.5%, 45.5%, and 45.5%, respectively, p = 0.112; 1-, 2-, and 3-year OS rates: 100.0%, 100.0%, and 100.0% vs. 100.0%, 78.8%, and 65.6%, respectively, p = 0.110). The most common treatment-related adverse events (TRAEs) were hand-foot skin reaction (70.0%), diarrhea (43.3%), decreased platelet count (20.0%), hair loss (20.0%), and hypertension (16.7%). Grade 3 TRAEs occurred in 8 patients (26.7%), and no grade 4 or above TRAEs occurred. Conclusions: Adjuvant HAIC combined with donafenib showed encouraging efficacy and a well-tolerated safety profile in HCC patients with a solitary large tumor and MVI, suggesting a potential new adjuvant treatment strategy for this high-risk population. Clinical trial information: NCT04962958 .