The authors' accepted manuscript "TACE Combined with Hepatic Arterial Infusion of Nivolumab for Inhibiting Tumor Angiogenesis in Hepatocellular Carcinoma" [Oncol Res Treat. 2025; https://doi.org/10.1159/000549516] by Sujing Zhang, Zheng Zheng, Changwang Zhang, Xueqian Liu, Xinlei Shi, and Wenhua Ma has been retracted by the Publisher and the Editor on behalf of the authors.After peer review, the accepted, unedited manuscript was published online as Early View. Subsequently, the authors requested to withdraw the manuscript from the journal. As the article is not approved by the authors for publication, we are retracting the Early View accepted, unedited manuscript.

Leucine-rich α-2 glycoprotein 1 (LRG1) is a multifunctional pro-inflammatory signaling molecule that has been proposed as a promising biomarker and potential therapeutic target across various types of cancer. Prospective studies investigating LRG1 in breast cancer patients are scarce. The purpose of this study was to investigate whether circulating LRG1 levels are associated with overall survival in patients with metastatic breast cancer. The present study encompassed 47 individuals with ER-positive/HER2-negative metastatic breast cancer who were scheduled to receive treatment with CDK4/6 inhibitors in combination with endocrine therapy as a first or second line of treatment. The primary endpoint was three-year overall survival. Plasma LRG1 levels were measured using an enzyme-linked immunosorbent assay. LRG1 levels were significantly associated with advanced age, C-reactive protein, invasive lobular carcinoma, and the presence of lung metastases. During the three-year follow-up period, 30% of participants died. Kaplan-Meier analysis based on the optimal cutoff indicated that patients with elevated LRG1 levels had a significantly higher risk of mortality compared to those with lower concentrations (log-rank p = 0.008), with a hazard ratio (HR) of 3.22 [95% CI: 1.32-11.05]; P = 0.013. This association remained significant after adjustment for potential confounders. Similarly, when modeled as a log₂-transformed continuous variable, LRG1 levels were also significantly associated with overall survival (HR per doubling = 5.82 [95% CI: 1.35-25.13]; P = 0.018). LRG1 significantly predicted three-year overall survival in patients with metastatic breast cancer, supporting its potential as a prognostic biomarker.

HER2-low breast cancer is a newly characterized subgroup with unclear prognostic implications. This study investigates the prognostic role of Ki67 in hormone receptor-positive (HR+) HER2-low and HER2-positive breast cancer. We retrospectively analyzed 224 HR+ breast cancer patients from four tertiary centers (96 HER2-low, 128 HER2-positive). Patients were stratified into Stage I-III (n=156) and Stage IV (n=68). Survival outcomes were assessed according to HER2 and Ki67 status using Kaplan-Meier analysis and Cox regression. HER2-low patients were older (≥65 years: 65% vs. 28%, p<0.001). In Stage I-III patients, disease-free survival (DFS) was significantly longer in the HER2-low subgroup (median: 86 vs. 59 months; p<0.001) and in those with Ki67 <20% (median: 74 vs. 34 months; p<0.001). Multivariable analysis confirmed high Ki67 (HR: 1.664; 95% CI: 1.564-2.048; p<0.001), hormone receptor negativity (HR: 1.967; 95% CI: 1.614-2.433; p=0.020), larger tumor size, and axillary nodal involvement as independent predictors of poor DFS. Among Stage IV patients, overall survival (OS) did not differ significantly by HER2 status (34 vs. 28 months; p=0.427) but was significantly shorter in those with Ki67 ≥20% (18 vs. 29 months; p<0.001). In multivariable analysis, high Ki67 (HR: 2.174; 95% CI: 1.994-2.256; p<0.001), hormone receptor negativity (HR: 1.649; 95% CI: 1.184-2.143; p<0.001), and presence of brain metastasis (HR: 1.564; 95% CI: 1.379-1.994; p<0.001) were independent predictors of poor OS. Ki67 appears to be an important prognostic biomarker in HR+ breast cancer across both HER2-low and HER2-positive subgroups. Dual stratification by HER2 and Ki67 status may improve risk assessment and help identify high-risk subgroups who could benefit from treatment approaches beyond endocrine therapy alone. These findings warrant confirmation in prospective studies.

Introduction: Elderly, frail, or cisplatin-ineligible patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) have a poor prognosis. To date, no standard of care has been defined for this population. Methods: The randomized, open-label phase 2 study was conducted to determine whether first-line treatment with pembrolizumab (PEM) is superior to methotrexate (MTX) in elderly, frail, or cisplatin-ineligible patients with R/M HNSCC not amenable to local therapies. Patients were randomized 1:1 to receive PEM 200 mg q3w or MTX 40 mg/m2 IV weekly until disease progression or unacceptable toxicity. The primary end point was overall survival after 1 year (1YOS); secondary endpoints were time to failure of strategy (TTFS) at 1 year, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 100 planned participants, 47 (23 in the PEM and 24 in the MTX group) were enrolled. The trial was terminated prematurely. Efficacy did not differ between the treatment arms (1YOS 17.4% for PEM vs. 37.5% for MTX [p = 0.12]). ORR was 17.4% with PEM vs. 12.5% with MTX (p = 0.70), TTFS at 1 year was 91% vs. 100% (p = 0.47), median PFS was 1.8 vs. 2.7 months (p = 0.83), and median OS was 6.1 vs. 9.7 months (p = 0.50), respectively. PD-L1 expression did not impact primary and secondary endpoints. Safety parameters favored PEM. Conclusion: ELDORANDO failed to demonstrate benefit of PEM over MTX regarding 1YOS, ORR, PFS, or OS. The optimal treatment strategy for fragile patients remains to be determined.