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Long-term comparative risk of cardiovascular complications in patients receiving immune checkpoint inhibitors versus traditional chemotherapy: A real-world TriNetX analysis.
e24034 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer care and expand across combination regimens, but they can cause immune-related adverse events including cardiovascular toxicity in routine use. Prior studies and cardio-oncology series highlight an early hazard period after ICI initiation, with myocarditis often within weeks (and substantial morbidity and mortality, with associated arrhythmic and conduction complications including atrial fibrillation. In contrast, comparative real-world data have focused on acute presentations, and it remains unclear whether ICI exposure confers additional long-term risk for common chronic cardiovascular syndromes such as heart failure or sustained arrhythmias. Methods: This was a retrospective cohort study (January 1, 2018- January 1, 2026) in TriNetX comparing patients prescribed ICIs (PD-1: pembrolizumab, nivolumab, cemiplimab; PD-L1: atezolizumab, durvalumab, avelumab; CTLA-4: ipilimumab) versus only traditional chemotherapy (e.g., platinum agents, gemcitabine, etoposide, cyclophosphamide). We excluded patients with prior history of outcomes and those exposed to cardiotoxic agents (anthracyclines, HER2-targeted therapy, proteasome inhibitors, VEGF/VEGFR pathway agents). Propensity score matching adjusted for age, sex, race/ethnicity, metastatic burden (proxy C77–C79), and baseline comorbidities (HTN, diabetes, CKD, CAD/prior MI, stroke/TIA, hyperlipidemia, obesity, COPD, sleep apnea, anemia, valvular disease). Final matched cohorts included ~65,800 patients per arm. Results: ICIs were associated with higher risk of myocarditis (OR 3.84; 95% CI 2.92–5.05) and pericarditis (OR 1.08; 95% CI 1.01–1.15). Chemotherapy was associated with higher risks of arrhythmia (OR 0.83; 95% CI 0.79–0.86), atrial fibrillation/flutter (OR 0.90; 95% CI 0.86–0.95), and heart failure (OR 0.91; 95% CI 0.83–0.99). No significant differences were observed for MI, stroke/TIA, systolic HF, or cardiac arrest. Conclusions: In a large matched real-world cohort, ICIs showed a strong signal for immune-mediated inflammatory cardiotoxicity (myocarditis/pericarditis), aligning with prior reports that these events often present early and commonly involve arrhythmic/conduction complications. Conversely, traditional chemotherapy showed higher risk of broader arrhythmias and heart failure. These results support regimen-specific cardio-oncology surveillance with a focus on early ICI monitoring and provide real-world reassurance regarding the longer-term cardiovascular safety profile of ICIs as their applications continue to expand.
Changes and significance of immune-related indicators in patients with recurrent/metastatic nasopharyngeal carcinoma before and after PD-1 inhibitor combined with GP regimen chemotherapy.
e18036 Background: To investigate the dynamic changes of peripheral blood immune-related indicators and their association with therapeutic efficacy in patients with recurrent/metastatic nasopharyngeal carcinoma (NPC) treated with PD-1 inhibitors combined with the GP regimen. Methods: A retrospective analysis was conducted on 46 patients with recurrent/metastatic NPC. All patients received at least one PD-1 antibody inhibitor (camrelizumab/toripalimab/sintilimab/tislelizumab) combined with GP (gemcitabine + cisplatin) chemotherapy. Peripheral blood samples were collected at baseline and after three treatment cycles to measure immune-related indicators, including PD-1, CTLA-4, and Treg cells. The expression differences of these indicators at baseline between the objective response group (PR+CR) and the poor-response group (SD+PD), as well as their dynamic percentage changes during treatment, were compared. Univariate and multivariate logistic regression analyses were further performed to determine whether PD-1, CTLA-4, Treg, CD4+/CD8+ ratio, CD3+, CD4+, CD16+, PDC, and MDC were independent factors influencing treatment efficacy. Results: Baseline peripheral blood PD-1 expression was significantly lower in the objective response group (PR+CR) compared to the poor-response group (SD+PD) (p<0.05). Trends of decrease were observed in Treg, CD16+, CD4+, and CD4+/CD8+ ratio in the objective response group (p>0.05), while trends of increase were noted for CTLA-4, CD3+, MDC, and PDC (p>0.05). After treatment, levels of PD-1 and CD16+ decreased significantly compared to baseline (p<0.05). Although CTLA-4, Treg, CD3+, CD4+, CD4+/CD8+ ratio, MDC, and PDC showed decreasing trends post-treatment, the differences were not statistically significant (p>0.05). Multivariate logistic regression analysis indicated that PD-1 was an independent factor influencing treatment efficacy in patients with recurrent/metastatic NPC (p<0.05). Conclusions: PD-1 inhibitor combined with GP regimen chemotherapy demonstrates favorable efficacy in recurrent/metastatic NPC. Low baseline PD-1 expression may be associated with better therapeutic outcomes. The significant post-treatment decrease in PD-1 and CD16+ expression may suggest immune cell activation and migration to tumor sites following treatment.
Deep learning–based computer-aided detection and diagnosis system for malignant biliary stricture (with videos).
e16007 Background: Timely and precise diagnosis of malignant biliary stricture (MBS) remains challenging. Although digital single-operator cholangioscopy (DSOC) assists endoscopists, suboptimal diagnosis accuracy is observed. This study introduces a novel deep learning (DL)-based computer-aided detection (CADe) and computer-aided diagnosis (CADx) system to enhance MBS diagnosis. Methods: In this retrospective, multicenter study, the CADe and CADx system were developed using a two-stage convolutional neural network (CNN) architecture trained on 10,443 DSOC images from 174 patients across three hospitals in China. For CADe, the YOLOv11 object detection CNN was applied to detect typical cancer features in real-time. For CADx, the ResNet18 CNN provided diagnostic classification, with visualization explanations. Model performance was assessed through standard metrics and comparison with expert endoscopists. A practical platform demo was implemented to facilitate real world application. Results: The CADe system achieved a mean average precision at 50% intersection-over-union (mAP50) of 91.2% for identifying the targeted malignant features, with an overall precision of 92.0% and recall of 87.0%. The CADx model attained an area under the receiver operating characteristic curve (AUC) of 0.960 in internal validation and 0.843 in external validation. The system matched expert sensitivity while improving specificity and positive predictive value (PPV). The system demonstrated significant improvements compared to expert endoscopists (p < 0.05). Conclusions: This study presents the first CADe and CADx system for accurate, real-time MBS detection and diagnosis during DSOC with superior performance compared to conventional methods. The integration of CADe and CADx effectively enhances the potential clinical utility of AI-assisted DSOC for MBS diagnosis. Performance metrics of the DL-based MBS CADe and CADx system in diagnosis classification for MBS during DSOC. Metrics Internal validation External validation AUC (95% CI) 0.960 (0.945 – 0.975) 0.843 (0.826 – 0.860) Sensitivity (95% CI) 0.922 (0.892 – 0.946) 0.520 (0.485 – 0.556) Specificity (95% CI) 0.880 (0.822 – 0.922) 0.952 (0.946 – 0.958) Accuracy (95% CI) 0.908 (0.884 – 0.932) 0.887 (0.878 – 0.895) PPV (95% CI) 0.938 (0.907 – 0.961) 0.659 (0.621 – 0.696) NPV (95% CI) 0.851 (0.792 – 0.898) 0.918 (0.910 – 0.926) AUC, area under the curve; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value.
Understanding underuse of radiation therapy in older adults with high-risk prostate cancer.
e17017 Background: Radiation therapy (RT) is a cornerstone of curative treatment for high-risk prostate cancer. However, older adults are often undertreated, potentially due to concerns about comorbidities, life expectancy, or treatment-related toxicity. This study aimed to examine age-based trends in RT use in a large, population-based cohort to better understand potential disparities in care. Methods: We conducted a retrospective cohort study using SEER 22 data from 2012 to 2020. Men aged 60 years and older diagnosed with high-risk prostate cancer, poorly differentiated, Grade III and undifferentiated, anaplastic, Grade IV were included. Patients were categorized into age groups: 60–64, 65–69, 70–74, 75–79, 80–84, and ≥85 years. The primary outcome was receipt of RT, defined by the SEER "Radiation Recode" variable. Descriptive statistics were used to determine RT receipt by age group, and a Chi-square test was performed to assess statistical significance. Results: Among 507,964 eligible patients, the overall rate of RT receipt was 33.9%. However, RT use varied markedly by age. RT was administered to 31.3% of men aged 60–64, 37.1% of those 65–69, 45.9% of those 70–74, and 46.4% of men aged 75–79. Usage declined significantly in the oldest groups, with 32.4% of those aged 80–84 and only 13.0% of those aged ≥85 receiving RT. The association between age and RT receipt was statistically significant (Chi-square p < 0.001). Conclusions: In this large national cohort, radiation therapy use declined substantially with increasing age, particularly among men aged 85 and older. While some variation may be attributable to clinical factors such as frailty or competing health risks, the steep drop in RT receipt suggests that age may be an independent barrier to treatment. These findings raise important concerns about age-related disparities in prostate cancer care and highlight the need for patient-centered, individualized decision-making to ensure equitable access to evidence-based therapies.
Triple-negative breast cancer: Real-world evidence from a national oncologic reference center in Panama.
e13117 Background: Triple-negative breast cancer (TNBC) accounts for 10–15% of breast cancers and is associated with aggressive behavior and limited therapeutic options. Real-world data from Latin America remain limited. Methods: We performed a retrospective observational study of patients diagnosed with TNBC and treated at Panama’s National Cancer Institute between 2019 and 2021. The protocol underwent review and approval by an institutional ethics committee. The primary endpoint was overall survival (OS), defined from histologic diagnosis to death or last follow-up. Pathologic complete response (pCR) among patients receiving neoadjuvant therapy was a secondary endpoint. Eligible patients were women ≥18 years with pathologically confirmed TNBC and no prior participation in breast cancer trials during the study period. OS was estimated using the Kaplan–Meier method, with subgroup comparisons by log-rank test. pCR was obtained from surgical pathology reports. Missing data were coded as not available. Results: Among 2,730 breast cancer diagnoses, 351 (12.8%) were TNBC. Mean age was 55.1 years. Most patients presented with symptoms (88.9%) and 59.9% had stage III–IV disease, including 25.1% with metastases. Neoadjuvant chemotherapy was administered to 59.2% of patients, with pCR achieved in 51.4% of them. Three-year OS was 89.1%, 88.6%, 67.2%, and 8.7% for stages I–IV (P < 0.05). OS varied by systemic treatment: adjuvant (84.0%), neoadjuvant (83.7%), combined therapy (70.6%), no systemic treatment (54.7%), and palliative care (17.6%) (P < 0.05). Among patients receiving neoadjuvant or combined therapy, pCR was associated with improved 3-year OS (89.4% vs 68.6%; P < 0.05). Conclusions: This large real-world cohort from a national comprehensive center highlights a high burden of TNBC in Panama. Despite aggressive biological behavior, substantial pathologic complete response rates were observed, underscoring the impact of early detection strategies, molecular classification, multimodality systemic treatment and the value of population-based registries in generating context-specific evidence for Latin America.
Improving timely antibiotic administration in febrile neutropenia: A quality improvement initiative in a tertiary oncology hospital.
e24152 Background: Febrile neutropenia (FN) defined as (100.4 degree F sustained for 1 hour ) with an absolute neutrophil count (ANC) <500/µL or <1000 /µL with anticipated decline to below 500 /µL in next 48 hours is an oncologic emergency, and early administration of broad-spectrum empiric antibiotics—ideally within 60 minutes of fever recognition—is recommended to reduce sepsis-related mortality. This study evaluated the effect of an audit-and-feedback plus teaching intervention on timely antibiotic administration and documentation in neutropenic fever. Methods: This quality improvement project employed a single Plan-Do-Study-Act (PDSA) cycle to improve timely antibiotic administration in febrile neutropenia from June 21 ,2025 to January 10, 2026. Plan: A standardized fever protocol was developed based on IDSA/ASCO guidelines. Planned interventions included: (1) development and dissemination of a standardized protocol and data-collection checklist; (2) training 100% of clinical staff by senior faculty member; (3) implementation of a fever alert system using chart flags for real-time notification (4) ensuring adequate antibiotic stock in ward pharmacy. Do: Protocol finalization with administrative approval (week 1), staff training by senior oncologist in oncology ward and emergency department (week 2), and full ward rollout with streamlined workflows ensuring timely nurse notification within 5 minutes, physician ordering within 15 minutes, and administration within 60 minutes. Study: Data was collected daily via checklist. Act: Barriers identified. Results: A clinical audit was conducted in the medical oncology ward. In cycle 1, all adult inpatients with established neutropenia who developed fever and met criteria for FN were included (N=26). Time from fever recognition to first empiric IV antibiotic was classified as “on time” (within 1 hour of fever onset) or “not on time”, and case-sheet documentation was reviewed for completeness. After analysis, findings were presented, and a focused bedside teaching session was delivered by a senior oncologist . A second audit cycle then included a new cohort of FN episodes (N=35), using identical definitions and outcomes. In cycle 1, antibiotics were administered on time in 11/26 patients (42.3%), delayed in 10/26 (38.5%), and documentation was inadequate in 5/26 (19.2%). Following the intervention, cycle 2 showed marked improvement: antibiotics were on time in 28/35 patients (80.0%), delayed in 5/35 (14.3%), and documentation errors decreased to 2/35 (5.7%). Conclusions: A simple, low-cost audit-and-feedback strategy combined with targeted teaching substantially improved process-of-care indicators for neutropenic fever . Integrating regular audits and structured education into routine practice may help align FN management with international standards in resource-constrained settings.
Adjunctive and post-transplant doxycycline in systemic light-chain (AL) amyloidosis.
e19551 Background: Systemic immunoglobulin light-chain (AL) amyloidosis has high early mortality. Doxycycline has been adopted based on preclinical anti-amyloid fibril activity, but clinical data remain inconsistent. Importantly, doxycycline is used in two clinically and biologically distinct contexts: adjunctive frontline plasma cell-directed therapy and antimicrobial prophylaxis after autologous stem cell transplantation (ASCT), which warrant separate evaluation. Methods: Systematic review/meta-analysis of comparative studies (PubMed, Embase, Web of Science, Cochrane) through Dec 2025. Eligible adults received doxycycline as frontline adjunct or post-ASCT prophylaxis, non-pooled analyses by context. Studies required a doxycycline-free comparator and extractable endpoints. Primary endpoint: all-cause mortality; secondary: deep hematologic response (≥VGPR) and cardiac organ response. Random-effects models used small-sample robust variance estimation; observational findings interpreted for confounding/selection bias. Analyses were prespecified by clinical context to mitigate indication bias and immortal time bias. Risk of bias (RoB 2; ROBINS-I) was incorporated into sensitivity analyses and evidence certainty. Protocol registered on PROSPERO. Results: We identified 1,450 records; after deduplication, 906 were screened and 31 underwent full-text review. Six comparative studies were included (one randomized controlled trial, five observational cohorts). Four evaluated adjunctive frontline therapy in newly diagnosed patients on bortezomib-based regimens with frequent cardiac involvement; two compared doxycycline versus penicillin as post-ASCT prophylaxis. In frontline analyses (n=307), adjunctive doxycycline did not reduce 6-month all-cause mortality (RR 0.80, 95% CI 0.46–1.39; I²=17%) or 12-month mortality (RR 0.81, 95% CI 0.16–4.22; I²=84%). ≥VGPR was similar (RR 0.99, 95% CI 0.77–1.27; I²=7%), and cardiac response was not improved (heterogeneous; RR 1.36, 95% CI 0.58–3.17; I²=88%). Among post-transplant landmark survivors, pooled analyses from two retrospective cohorts showed lower 5-year all-cause mortality with doxycycline (RR 0.70, 95% CI 0.52–0.93; I²=0%). In Hartung–Knapp random-effects sensitivity analysis (k=2), the pooled 12-month mortality estimate remained non-significant (RR 0.81; p=0.814). Ten-year mortality favored doxycycline but was heterogeneous and not statistically significant (RR 0.67, 95% CI 0.42–1.07; I²=79%). Conclusions: Adjunctive doxycycline during frontline therapy did not reduce early mortality or improve hematologic or cardiac responses in AL amyloidosis. Doxycycline use as post-ASCT prophylaxis was associated with improved 5-year survival among landmark survivors; however, this signal derives from observational data and should be considered hypothesis-generating pending randomized evaluation.
Impact of regorafenib treatment on overall survival (OS) in advanced sarcoma patients.
11556 Background: Regorafenib has been evaluated in several sarcoma clinical trials and the common primary endpoint of these studies was Progression-Free Survival (PFS) according to RECIST, with OS as secondary endpoint. We aimed to assess the impact of regorafenib on OS using pooled analysis of REGOSARC (NCT01900743, five cohorts: liposarcoma, leiomyosarcoma, synovial sarcoma, other soft tissue sarcoma and non-adipocytic sarcoma post-pazopanib) and (NCT02389244, four cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma and chordoma). Both trials were placebo-controlled trials with potential switch to regorafenib in placebo-arm at progression. Methods: The primary endpoint was OS in months (mo.) from randomisation estimated by Kaplan-Meier method. The Hazard Ratio (HR) of death in a Cox model was stratified by histological . We used 2 methods for controlling regorafenib switch on OS: Rank-Preserving Structural Failure Time Model (RPSFTM; White et al. 1997) and Modified Iterative Parametric Estimation (MIPE: Zhang et al. 2016), with bootstrap-based 95%CI for both methods. Two populations were considered: in the primary analysis included all patients in both trials (n=355), and in secondary analysis excluded chordoma and liposarcoma patients (n=289), since regorafenib failed to demonstrate activity in these subtypes. Results: In primary analysis, the median age was 56.0 years (range, 16.0; 85.0); 325 patients (91.5%) had metastatic disease. 218 (61.4%) patients had soft tissue sarcoma and 137 (38.6%) patients had bone sarcoma. Median follow-up was 70.9 mo (IQR: 54.0-87.5). The median OS was 9.5 mo. (95%CI, 7.7-12.4) in Placebo arm versus 12.8 mo. (95%CI, 11.0-15.8) in regorafenib arm (HR: 0.85 (95%CI, 0.67-1.06); p=0.148). When correcting regorafenib switch effect, the estimated HR was 0.59 (0.31-1.25) and 0.62 (0.27-1.46) using RPSFTM and MIPE methods, respectively. Conclusions: In this pooled analysis, we observe a marked difference in OS, but which does not reach the , even after exclusion of chordomas and liposarcomas patients (20%-risk reduction, with p=0.083). After controlling for the switch effect, the corrected effect of regorafenib increased dramatically from 20% risk-reduction of death to a 45%-50% reduction in the population excluding chordomas and liposarcomas.
Nintedanib in advanced solid tumors: A meta-analysis of randomized controlled trials.
e15170 Background: Nintedanib (Vargatef/BIBF 1120) is an anti-angiogenic tyrosine kinase inhibitor evaluated across multiple advanced solid tumors, yet its overall efficacy and safety profile in randomized settings remain uncertain. Methods: We performed a PRISMA 2020 compliant systematic review and meta-analysis (PROSPERO-registered), searching PubMed, Scopus, Embase, Cochrane Library, and ClinicalTrials.gov from inception for phase II/III RCTs in adults with advanced/recurrent/metastatic solid tumors comparing nintedanib-based therapy vs placebo or other anticancer regimens. We pooled HRs for time-to-event outcomes and RRs for dichotomous outcomes using fixed/random-effects models based on I², conducted tumor-type subgroup analyses for PFS/OS, and assessed risk of bias using RoB 2. Results: Eighteen RCTs comprising 7,542 participants were included. Overall, nintedanib was associated with a borderline improvement in PFS versus control (HR 0.86, 95% CI 0.74–1.00; I² = 73.2%), with a clearer benefit in thoracic cancers (HR 0.79, 95% CI 0.73–0.87) and no significant PFS advantage in gynecologic, gastrointestinal, or urological subgroups. OS was not significantly improved (HR 0.92, 95% CI 0.84–1.01; I² = 42.3%), although thoracic cancers showed a subgroup signal (HR 0.84, 95% CI 0.73–0.96). ORR did not differ between groups (RR 1.00, 95% CI 0.79–1.27; I² = 22.5%). Grade ≥3 adverse events were not significantly increased overall (RR 1.14, 95% CI 0.90–1.43), but treatment discontinuation was higher with nintedanib (RR 1.53, 95% CI 1.18–1.98). Nintedanib increased risks of gastrointestinal (notably diarrhea) and hepatic toxicities (ALT/AST elevations), with additional signals for fatigue, leukopenia, and sepsis. Conclusions: Across randomized trials in advanced solid tumors, nintedanib demonstrates a modest and tumor type–dependent improvement in disease control, with the most consistent signal in thoracic malignancies, but without a reproducible benefit in overall survival or objective response. Its clinical utility may be limited by tolerability, particularly gastrointestinal and hepatotoxic adverse events, and higher discontinuation rates.
Nationwide trends, hospital volume, and drivers of survey-weighted 30-day unplanned readmission after pancreatic resection (NRD 2016–2022).
e16341 Background: National, survey-weighted benchmarking of 30-day unplanned readmission after pancreatic resection and its relationship with hospital volume remains limited across recent years. Methods: Using NRD 2016–2022, we identified each patient’s first pancreatic resection index admission per calendar year (ICD-10-PCS partial/total resection codes), restricted to 30-day readmission–eligible admissions. Hospital annual resection volume was categorized into year-specific quartiles. We estimated survey-weighted readmission rates and fit survey-weighted logistic regression (weights, hospital clustering, and stratification). Results: Among 28,265 eligible index resections, 2,859 had an observed 30-day unplanned readmission (crude 10.1%). Survey-weighted readmission declined from 10.1% in 2016 to 8.2% in 2022 and was lower in high-volume hospitals (Table 1). In adjusted models, Q4 vs Q1 volume was associated with lower odds of readmission, while extreme APR-DRG severity of illness was associated with higher odds (Table 1). The most common readmission diagnosis categories were Other (50.6%), Postoperative complication (29.4%), and Sepsis/Septicemia (10.5%). Conclusions: Survey-weighted national readmission after pancreatic resection remained near 8–11% and was consistently lower at higher-volume hospitals, supporting targeted transitional-care interventions and dissemination of high-volume program practices. Key survey-weighted estimates (NRD 2016–2022). Domain Comparison / Year Estimate (95% CI) 30-day unplanned readmission rate 2016 0.101 (0.090–0.113) 30-day unplanned readmission rate 2022 0.082 (0.072–0.093) Rate by hospital volume quartile Q1 (lowest) 0.143 (0.114–0.173) Rate by hospital volume quartile Q4 (highest) 0.094 (0.089–0.099) Adjusted odds (survey-weighted logistic) Q4 vs Q1 OR 0.69 (0.54–0.89) Adjusted odds (survey-weighted logistic) Elective vs non-elective OR 0.80 (0.70–0.93) Adjusted odds (survey-weighted logistic) APR-DRG severity extreme vs minor OR 1.72 (1.29–2.29)
Use of parsimonious Fitbit step metrics to improve frailty classification in adults ≥50 with cancer in NIH All of Us.
1657 Background: Frailty predicts treatment intolerance and adverse outcomes in older adults with cancer, yet scalable screening remains limited. Scalable frailty screening is particularly relevant for treatment selection and risk stratification in routine oncology care. We tested whether routine Fitbit step metrics improve frailty classification beyond basic variables and whether high-dimensional step-pattern features add benefit. Methods: Retrospective cross-sectional study in the NIH All of Us Research Program including adults ≥50 years with cancer history and Fitbit step data (N=378). Frailty was defined by a 33-item All of Us deficit frailty index (fit <0.15, vulnerable 0.15–0.25, frail >0.25); primary endpoint was frail vs not frail (fit+vulnerable). Valid wear day required ≥10 hours with activity or heart-rate evidence. Missing days were imputed for daily totals and minute-level profiles reconstructed using within-person donor days or weekday/weekend templates. Prespecified feature tiers were: basic (9), basic+average steps (10), and high-dimensional step-pattern features (108; minute-level intensity, variability, and frequency-domain summaries). Class-weighted elastic-net logistic regression, random forest, and gradient-boosted trees were tuned and evaluated with nested 5×5 cross-validation. Discrimination was pooled out-of-fold area under the receiver operating characteristic curve (AUC) with stratified bootstrap 95% confidence intervals (CI); incremental value used paired bootstrap ΔAUC. Results: Participants were 64.8±8.6 years; 67.7% were female. Frailty categories were fit 43.7%, vulnerable 40.7%, and frail 15.6% (59/378). Mean daily steps were lower in frail vs not frail participants (5505 vs 7648 steps/day). Elastic-net logistic regression with step features achieved the highest AUC (0.713, 95% CI 0.636–0.783) vs the basic model (0.644, 95% CI 0.567–0.720; ΔAUC 0.068, paired bootstrap 95% CI 0.002–0.133). At ≥90% specificity, sensitivity increased from 25.4% (15/59) to 39.0% (23/59). In secondary analyses predicting not-fit status (vulnerable/frail vs fit), adding step features improved AUC from 0.551 (95% CI 0.493–0.609) to 0.635 (95% CI 0.580–0.694). High-dimensional step features did not improve AUC. Conclusions: In adults ≥50 with cancer, a parsimonious step-based metric improved frailty classification and increased sensitivity at high specificity, while complex feature sets and models did not add benefit. These findings support low-burden step metrics as scalable adjuncts to frailty screening in oncology; external validation is needed.
Concordance of Ki-67 index and histologic grade between biopsy and surgical specimens in breast cancer: Implications of treatment decision-making.
e12593 Background: The Ki-67 index and histologic grade are key pathological features guiding systemic treatment decisions in Breast Cancer (BC). Variability between core biopsy and surgical specimens may impact management, including decisions regarding omission of sentinel lymph node biopsy. We evaluated the concordance of Ki-67 and histologic grade between biopsy and surgical specimens and quantified clinically meaningful Ki-67 differences. Methods: We conducted a retrospective analysis of BC patients with paired biopsy and surgical pathology specimens treated between 2023 and 2025 in a single oncology network in Brazil. Patients receiving neoadjuvant therapy were excluded. Ki-67 concordance was assessed using a 20% cutoff ( < 20% vs ≥20%) and by absolute differences > 10% between specimens. Concordance was evaluated using cross-tabulations and Fisher's exact tests. Surgical specimen grade was used as the reference for grade-specific Ki-67 analyses. Results: A total of 275 paired specimens were analyzed. Ki-67 ≥ 20% was observed in 49.1% of biopsy specimens and 54.2% of surgical specimens. In biopsy samples, 33.0% were grade 1, 53.3% grade 2, and 13.7% grade 3, compared with 23.6%, 58.2% and 18.2%, respectively, in surgical specimens. Median Ki-67 in biopsy samples was 12% (IQR 6-19%) for grade 1, 19% (IQR 10-30%) for grade 2, and 60% (IQR 30-70%) for grade 3. In surgical specimens, median Ki-67 was 12% (IQR 8-15%), 20% (IQR 13-29%), and 50% (IQR 25-60%), respectively. Overall, 25.1% of patients showed a Ki-67 difference > 10% bteween biopsy and surgery, including 10.9% with decrease and 14.2% with an increase in the surgical specimen. Ki-67 variation was most frequent in grade 3 tumors (20% decrease > 10%; 16% increase > 10%), but was also observed in grade 2 (8.8% decrease; 16.9% increase) and grade 1 tumors (9.2% decrease; 6.2% increase). Significant discordance was also observed for histologic grade (p < 0.001). Conclusions: Substantial variability in Ki-67 index and histologic grade exists between biopsy and surgical specimens, Approximately one third os cases crossed the 20% Ki-67 thershold, and histologic grade was upgraded to grade 3 in 13%. These findings highlight the limitations of relying solely on biopsy pathology for systemic treatment decisions, particularly in hormone receptor-positive disease, where Ki-67 and grade may influence adjuvant treatment considerations, including eligibility for CDK4/6 inhibitors and decisions regarding omission of sentinel lymph node biopsy. Routine reassessment of postoperative pathology may optimize treatment decision-making Surgery Ki-67 < 20% Surgery Ki-67 ≥ 20% p value Biopsy Ki-67 < 20% 98 (70.0%) 42 (30.0%) < 0.001 Biopsy Ki-67 ≥ 20% 28 (20.7%) 107 (79.3%) Surgery G1 Surgery G2 Surgery G3 Biopsy G1 53 (59.6%) 35 (39.3%) 1 (1.1%) < 0.001 Biopsy G2 10 (6.9%) 117 (81.3%) 17 (11.8%) Biopsy G3 1 (2.7%) 5 (13.5%) 31 (83.8%)
Evolving management of advanced-stage, resectable cutaneous squamous cell carcinoma.
e14582 Background: Patients (pts) with advanced-stage, resectable cutaneous squamous cell carcinoma (CSCC) have historically been treated with up-front surgery (US) +/- adjuvant radiotherapy (RT). More recently, the use of neoadjuvant immunotherapy (NEO) has shown promising outcomes. We aimed to describe our institutional experience with these approaches. Methods: We identified 300 pts with stage III (n = 139) or IV (n = 161) resectable CSCC treated 2010-2024 without prior RT. We compared patient characteristics with US (n = 194) vs. NEO (n = 106). Pathologic responses were classified as previously described. Treatment cohort features were compared by Chi-square or Fisher’s exact tests. Event-free survival (EFS) was calculated by the Kaplan-Meier method and defined as time from surgery to disease recurrence or death for US pts and progressive disease without subsequent surgery, recurrence or death for NEO pts. The effect of NEO vs. US was assessed by Log-Rank test. Results: Median age was 71 years (IQR 64-79). Recurrent disease at presentation was similar between cohorts (US-34%, n = 49 vs. NEO-28%, n = 30, p = 0.57). Pts receiving US had lower stage disease (stage III: US-54%, n = 104 vs. NEO-33%, n = 35, p < 0.001) and were more likely to be immunocompromised (US-19%, n = 37 vs. NEO-8%, n = 8, p = 0.008). In the NEO cohort, after a median 3 cycles anti-PD1, 82% (n = 87) of pts proceeded to surgery. Of these, 47 (54%) had a pathologic complete response (pCR), 10 (11%) near-pCR, 8 (9%) pathologic partial response (pPR) and the remaining were pathologic non-responders (pNR). Of the NEO patients who did not have surgery (n = 19, 18%): 11 declined surgery after clinical response, 2 declined surgery after progression, 2 died of other causes and 4 were lost to follow up. Post-op RT was more common after US (72%, n = 141 vs. NEO-26%, n = 28, p = < 0.001). Adjuvant chemotherapy (US-10% vs. NEO-5%) or immunotherapy (US-0% vs. NEO-9%) were infrequently applied. Median follow-up was 33 months for both US (IQR 16-76) and NEO (IQR 18-51). 2-year EFS was greater in the NEO cohort compared to US (90% vs 79%, p = 0.013). Any pathologic response at surgery after NEO (pCR, near-pCR, pPR) was associated with improved outcomes compared to pNR (2-yr EFS 98% vs. 61%, p = < 0.001). Conclusions: In a single-institution, retrospective series, NEO was associated with improved 2-year EFS compared to US. These data support the completion of an ongoing randomized phase 3 trial (NCT06568172) comparing NEO to US.
Comparison of longitudinal circulating tumor DNA (ctDNA) and carcinoembryonic antigen (CEA) for post-operative risk stratification in colorectal cancer (CRC).
3637 Background: ctDNA is a reliable biomarker that outperforms CEA for detecting molecular residual disease in CRC. However, the relative prognostic performance of these biomarkers across post-operative timepoints is not fully elucidated. Characterizing these temporal dynamics can provide essential insights for optimizing biomarker-guided surveillance. Methods: CEA and ctDNA (Signatera, Natera, Inc.) data at 12, 24, 36, 48, 72, and 96 weeks (wk) post-surgery from patients (pt) enrolled on the CIRCULATE-Japan GALAXY study were used to perform landmarked analyses. Disease-free survival (DFS) and overall survival (OS) were evaluated among pts who were event-free at each landmark. Hazard ratios (HRs) were estimated using Cox models adjusted for clinicopathological factors. Temporal trends in prognostic strength were assessed using weighted meta-regression across post-operative timepoints. Results: Of the 2,825 pts with CRC [84% stage I-III, 16% stage IV; median age 69 years (range 24-95)], 49% were female; 43% received adjuvant chemotherapy while 57% went directly to surveillance. At all evaluated landmarks, ctDNA- and CEA-positivity were associated with markedly higher risk of recurrence and death compared with ctDNA- and CEA-negativity, respectively. In DFS analyses, ctDNA outperformed CEA with substantially higher HRs at all landmarks (Table 1). The prognostic strength of ctDNA increased over time, with HRs increasing from 15.15 at 12 wks to 36.87 at 72 wks post-surgery and 32.31 through 96 wks. In contrast, CEA demonstrated modest and relatively stable DFS HRs across landmarks (range 2.04 to 3.43). Meta-regression analyses demonstrated a significant temporal strengthening of ctDNA’s prognostic performance for DFS (β:0.011 per wk, p=0.004), whereas no significant temporal trend was observed for CEA (p=0.33). In OS analyses, ctDNA positivity conferred high mortality risk at all landmarks, with HRs ranging from 8.40 to 14.15 (Table 1). Despite increasing prognostic association of CEA with OS at later landmarks, its HRs were lower than those of ctDNA. Conclusions: ctDNA-positivity consistently outperforms CEA in predicting disease recurrence and OS. ctDNA provides strong risk stratification at early postoperative time points, and its prognostic accuracy continually improves during longitudinal surveillance, confirming its superior performance for early risk assessment and personalized serial disease monitoring during surveillance. Clinical trial information: UMIN000039205. DFS and OS hazard ratios and ranges for ctDNA and CEA at all landmarks. Landmark ctDNA DFS CEA DFS ctDNA OS CEA OS 12 wk 15.15*** 2.68*** 8.4*** 3.65*** 24 wk 18.4*** 2.23*** 12.74*** 4.16*** 36 wk 19.36*** 2.04*** 9.81*** 5.41*** 48 wk 23.95*** 2.77*** 12.26*** 6.3*** 72 wk 36.87*** 3.43*** 14.15*** 8.72*** 96 wk 32.31*** 2.71* 8.45** 14.67*** *p<0.05, **p<0.001, ***p<0.0001.
Role of adjuvant pembrolizumab in resected stage III melanoma: Real-world evidence from a Peruvian reference center.
e21546 Background: Stage III melanoma carries a high risk of recurrence after surgery. Adjuvant pembrolizumab has demonstrated improved outcomes in randomized clinical trials; however, Latin American (LATAM) populations remain underrepresented, and access to immunotherapy in public healthcare systems is limited. We evaluated real-world outcomes of adjuvant pembrolizumab compared with observation in a public national reference center in Peru. Methods: We conducted a retrospective cohort study of patients with resected AJCC stage III melanoma treated between 2021 and 2024. Patients were classified according to receipt of adjuvant pembrolizumab or observation (no adjuvant anti-PD-1 therapy due to limited access). Efficacy outcomes included recurrence-free survival (RFS), defined as time from definitive surgery to first recurrence, and overall survival (OS), defined as time from surgery to death from any cause; patients alive were censored at last follow-up. Survival estimates were generated using the Kaplan–Meier method, and hazard ratios (HRs) were calculated using Cox proportional hazards models (two-sided p < 0.05). Multivariable models were adjusted a priori for age, sex, ulceration, AJCC substage, and adjuvant radiotherapy. Results: A total of 81 patients were included (pembrolizumab n = 47; observation n = 34), with a median age of 62 years. After a median follow-up of 36 months, 3-year RFS was 87.1% in the pembrolizumab group versus 42.8% in the observation group (HR 0.51; 95% CI 0.24–1.06; p = 0.073). Three-year OS was 87.1% versus 36.4%, respectively (HR 0.17; 95% CI 0.05–0.50; p = 0.002). Exploratory subgroup analyses suggested an OS benefit among females, patients aged ≥50 years, those with stage IIIC disease, BRAF wild-type tumors, and patients receiving adjuvant radiotherapy. Improved RFS was observed in patients with BRAF wild-type tumors (p = 0.049) and in tumors without ulceration (p = 0.045). Conclusions: In this real-world Peruvian cohort, adjuvant pembrolizumab was associated with significantly longer overall survival and numerically longer recurrence-free survival compared with observation in resected stage III melanoma. The RFS benefit appeared more pronounced in BRAF wild-type tumors and in the absence of ulceration. These findings support the effectiveness of adjuvant anti-PD-1 therapy in routine clinical practice within resource-limited settings such as LATAM.
Oncomovies: Cancer in cinema from early sound film to 2025.
9023 Background: Cinema has played a relevant role in shaping public representations of cancer, influencing social perceptions of illness, medical care, prognosis, and the patient–physician relationship. Over time, cancer narratives in film have evolved alongside medical knowledge, therapeutic advances, and cultural attitudes toward disease, suffering, and death. Building on previous analyses presented at ESMO (2012) and a systematic review published in 2014, this study provides an updated overview of how cancer has been portrayed in cinema up to 2025. Methods: We conducted a cross-sectional descriptive analysis of feature films in which cancer played a prompt, relevant, or plot-driving role. Films were identified through major movie databases (IMDb, AllMovie, MyMovies) and previous curated filmographies. Each film was independently reviewed and coded using a standardized data extraction framework including year of production, country, patient demographics, cancer type and anatomical classification, stage or phase of disease when specified, diagnostic and therapeutic representations, healthcare professionals’ roles, and narrative outcome. Data were aggregated and analyzed descriptively. Results: A total of 255 films produced between 1939 and 2025 were included. The majority originated from North America and Western Europe, with a progressive increase in geographic diversity after 2000. Solid tumors accounted for approximately 75% of depicted cancers, followed by hematologic malignancies (about 19%). The most frequently represented cancer types were breast cancer, brain tumors, leukemia, and lung cancer, while several high-incidence cancers in real-world epidemiology remained underrepresented. Central nervous system tumors and breast cancer were the most common anatomical classifications. When reported, cancer was often portrayed at an advanced or metastatic stage. Treatments were shown in most films, with chemotherapy being the most frequently depicted modality, followed by surgery and palliative care. Healthcare professionals appeared in the majority of narratives, though with varying degrees of realism. Death remained a common narrative endpoint. Conclusions: This updated analysis confirms persistent narrative patterns in cinematic representations of cancer, including a preference for younger patients, specific tumor types, and dramatic disease trajectories. While recent films show increased attention to diagnostic processes and treatment complexity, discrepancies between cinematic portrayals and epidemiological reality remain substantial. Oncomovies may represent both a valuable cultural resource for medical education and a potential source of misconceptions, underscoring the importance of critical engagement with cancer narratives in film.
cfDNA-based signatures of nucleosome organization to enable prostate cancer subtyping.
5130 Background: Neuroendocrine prostate cancer (NEPC) can arise from prostate adenocarcinoma (PRAD) via therapy-associated lineage plasticity and is characterized by reduced AR signaling and activation of neuroendocrine (NE) regulatory pathways. Nucleosome positioning, inferable from cell-free DNA (cfDNA) fragmentation patterns, reflects lineage-specific gene regulation. Recent studies have shown that active, open chromatin is associated with specific nucleosome spacing patterns, leading to an enrichment of longer cfDNA fragments, including di-nucleosome fragments. We hypothesized that fragmentomic signatures reflecting nucleosome positioning could distinguish PRAD from NEPC, providing a simple means to detect lineage plasticity from cfDNA. Methods: We analyzed cfDNA samples from 47 patients (8 with NEPC, 39 with PRAD) with hybrid-capture sequencing. Baits were designed to target adenocarcinoma (AC, 715 sites) and NE-associated regulatory elements (508 sites). For each sample, fragments overlapping each enhancer set were aggregated into 5-bp binned fragment-length distributions (18-500 bp). We quantified di-nucleosome (250-400 bp) and mono-nucleosome (120-180 bp) fragment counts at NE and AC regulatory elements. We calculated the log-ratio of NE versus AC di/mono values: log2 [(di/mono)_NE/(di/mono)_AC]. We also computed a position-free Transcriptional Activation Score (pfTAS) for each enhancer set using a published framework for estimating enhancer activity from cfDNA fragment size distributions, deriving an analogous log-ratio: log2 [pfTAS_NE/pfTAS_AC]. We tested if these ratios could distinguish NEPC versus PRAD, evaluating the area under the receiver operating characteristic curve (AUC) in the full cohort and by leave-one-out cross-validation (LOOCV). Results: The enhancer-specific di/mono log-ratio achieved complete separation between PRAD (median: -0.209; range: -0.449 to -0.090) and NEPC (median: 0.030; range: -0.056 to 0.218), yielding an AUC of 1.00 both in-sample and by LOOCV. The pfTAS log-ratio was also discriminative, with an AUC of 0.99 in-sample and an AUC of 0.89 by LOOCV. Overall, nucleosome fragmentation patterns provide a chromatin-based fragmentomic signal that enables accurate discrimination between PRAD and NEPC. Conclusions: Leveraging hybrid-capture cfDNA, we identified a biologically grounded chromatin-based signature that robustly discriminates NEPC from PRAD. By reflecting lineage-associated nucleosome positioning, this liquid biopsy-based approach provides a cost-effective and non-invasive molecular metric derived from routinely generated cfDNA sequencing data. It may be particularly useful in clinically challenging settings, including cases with mixed morphology or when a biopsy is difficult to obtain.
TACE/HAIC combined with bevacizumab and tislelizumab as third-line therapy for colorectal cancer with unresectable liver metastases: A prospective, observational real-world study (TABTiC).
e15617 Background: Microsatellite stable (MSS) colorectal cancer (CRC) with unresectable liver metastases has limited effective third-line options. This study evaluated the efficacy and safety of transarterial chemoembolization/ hepatic arterial infusion chemotherapy (TACE/HAIC) combined with bevacizumab and tislelizumab in this setting. Methods: This single-center, prospective, observational study enrolled 21 patients with MSS CRC and unresectable liver metastases who failed at least two prior systemic therapies. One patient was excluded per protocol, leaving 20 evaluable patients. All received at least one cycle of TACE/HAIC combined with bevacizumab and tislelizumab. Primary endpoints was overall response rate(ORR) after 1 month of receiving the first combination therapy. Secondary endpoints included progression-free survival (PFS) , overall survival (OS), disease control rate (DCR), safety, and exploration of predictive biomarkers. Results: After the first efficacy assessment, the DCR was 70% (14/20 patients with stable disease, SD). No complete or partial responses were observed. The 6-month and 12-month PFS rates were 68.0% and 42.0%, respectively. Median PFS was 7.0 months and OS were 12.0 months (OS data immature, follow-up ongoing). Patients with < 2 extrahepatic metastatic sites had significantly longer PFS (6.5 vs. 3.2 months, P = 0.03). Grade ≥3 adverse events occurred in 29.4% of patients, primarily neutropenia (11.8%), hypertension (8.8%), and liver dysfunction (5.9%), with no treatment-related deaths. Exploratory biomarker analysis suggested that lower baseline BMI (< 24 kg/m²) was associated with better outcomes (P < 0.05), and a greater decrease in absolute lymphocyte count (ALC) after treatment correlated with progressive disease (PD). Conclusions: The combination of TACE/HAIC, bevacizumab, and tislelizumab demonstrated promising disease control and survival benefit with a manageable safety profile as a third-line therapy for MSS CRC with unresectable liver metastases. Baseline BMI and extrahepatic metastatic burden may help identify patients more likely to benefit. Further studies are warranted to optimize the regimen and validate predictive biomarkers. Clinical trial information: ChiCTR2500101315.
Clinical activity of immune checkpoint inhibitors in patients with advanced sarcomas: A retrospective single-center experience.
e23569 Background: Sarcomas are rare mesenchymal malignancies with poor outcomes in metastatic disease. Efficacy of immune checkpoint inhibitors in sarcomas is inconsistent. We conducted a retrospective cohort study of sarcoma patients treated with ICIs at the University of New Mexico Comprehensive Cancer Center (UNMCCC) to evaluate survival, response, and outcomes. Methods: We retrospectively reviewed patients with histologically confirmed sarcoma treated with ICIs at UNMCCC from 12/2016 to 12/2024. Patient demographics, disease characteristics, molecular profiles, treatment details, and clinical outcomes were collected. Endpoints included real world progression-free survival (rwPFS), overall survival (OS), time on treatment (ToT) and response rate. Results: Fourteen patients with advanced sarcomas received ICIs. The median age at diagnosis was 66.5 years (range: 37-85), and 57% of patients were male. The most common histologic types of sarcomas were: Undifferentiated pleomorphic sarcoma (UPS) 28.5% (n = 4/14), leiomyosarcoma (21.4%, n = 3/14), dedifferentiated liposarcoma (14.2%, n = 2/14), and myxofibrosarcoma (14.2%, n = 2/14). Although 28.6% of patients (n = 4/14) were initially diagnosed with stage I disease, all patients (n = 14/14) were stage IV at time of ICI initiation. Primary tumor sites included soft tissue/extremities (n = 9/14). Most patients (78%, n = 11/14) had previously received chemotherapy and/or targeted treatment (anthracycline 54%, gemcitabine/docetaxel 36%, and TKI 45%) prior to the initiation of ICIs. ICIs included pembrolizumab (n = 9), pembrolizumab-pharmacologic ascorbate (n = 1), nivolumab (n = 2), ipilimumab-nivolumab (n = 1), ipilimumab-nivolumab-cabozantinib (n = 2), pembrolizumab-axitinib (n = 1). The median time from diagnosis-to-ICI initiation was 402 days. The median ToT was 19.5 weeks. Patients with UPS had a longer median ToT of 47 weeks compared with 16 weeks in patients with leiomyosarcoma. UPS also exhibited the longest mrw-PFS, 10 months (1.84-28.3), and 75% of patients (n = 3/4) remaining on treatment at 3 months. In contrast, patients with leiomyosarcoma had a median rw-PFS of 5.3 months (2.79-8.25). Partial responses were observed in 28.5% of patients, while 28.5% achieved stable disease. Progressive disease occurred in 28.5% of patients. Median overall survival from ICI initiation was 34.5 months (95% CI: 18.2-54.1). Conclusions: We observed heterogenous outcomes across histologic subtypes, with signals of durable clinical benefit particularly among patients with UPS. Despite most patients receiving ICIs in the post-chemotherapy setting, disease control was achieved in over half of the cohort, and nearly one-third experienced partial responses, supporting a potential role for ICIs. Immune-related adverse events were common but were not clearly associated with truncated treatment duration.
A phase 2 study of fruquintinib combined with sintilimab and chidamide in refractory MSS metastatic colorectal cancer: Preliminary efficacy and safety.
2631 Background: Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) has limited response to immune checkpoint inhibitors. Preliminary evidence from preclinical studies and the CAPability-01 trial suggest that combining anti-angiogenic therapy with epigenetic drugs such as histone deacetylase inhibitors can favorably remodel the tumor immune microenvironment and enhance the efficacy of PD-1 immune checkpoint blockade for advanced MSS-type mCRC. This study evaluates the efficacy and safety of the triple combination of fruquintinib, sintilimab, and chidamidein patients with refractory MSS mCRC. Methods: This is a single-arm, open-label phase 2 study. Eligible patients had histologically confirmed MSS-type mCRC, disease progression after ≥2 prior lines of therapy, ≥1 measurable lesion (RECIST v1.1), and ECOG 0–1. Patients received fruquintinib (5 mg orally on days 1–14, Q3w), sintilimab (200 mg IV on day 1, Q3w), and chidamide (30 mg orally twice weekly). The primary endpoint was mPFS. Secondary endpoints included ORR, DCR, mOS, DOR and safety. Tumor assessments were performed every 9 weeks. With a statistical hypothesis of improving the median PFS from 3.7 (historical control) to 6.0 m, a sample size of 46 patients was planned. Results: From January to December 2025, a total of 9 patients were enrolled. The median age was 60.0 years (39–72). All patients had MSS-type tumors, with a median of 2 prior lines of therapy (range: 2–4). Preliminary efficacy analysis showed that 4 patients achieved PR and 2 achieved SD, resulting in an ORR rate of 44.4% and a DCR rate of 66.7%. Given the limited sample size and relatively short follow-up of 9.1m at this preliminary analysis, mPFS and mOS were not yet reached. Treatment was generally tolerable. TRAEs of any grade occurred in all 9 patients. The most common TRAEs included hematological toxicities such as thrombocytopenia (66.7%), neutropenia (44.4%), and leukopenia (33.3%); hepatic laboratory abnormalities including elevated ALT 33.3%), and elevated AST (33.3%); as well as proteinuria (66.7%), hyperlipidemia (55.6%), increased blood creatine kinase (55.6%), and fatigue (1/9 with Grade 3). Grade ≥3 TRAEs were observed in 5 patients (55.6%), including Grade 3 neutropenia (2 patients), fatigue (1 patient), cutaneous adverse reactions (1 patient), and cholecystitis (1 patient). No treatment-related deaths occurred. Conclusions: Preliminary results indicate that the triple therapy of fruquintinib, sintilimab, and chidamide demonstrates promising response rate, disease control and a manageable safety profile in patients with refractory MSS-type mCRC. This combination strategy represents a potential therapeutic option for this population, who currently have limited treatments available. Further follow-up with a larger sample size and longer duration is needed to confirm its survival benefit. Clinical trial information: NCT06979908 .