Oncology Research and Treatment最新文献

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by Sujing Zhang, Zheng Zheng, Changwang Zhang, Xueqian Liu, Xinlei Shi, and Wenhua Ma has been retracted by the Publisher and the Editor on behalf of the authors.After peer review, the accepted, unedited manuscript was published online as Early View.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.

Background & objective: 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.

Methods: 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.

Results: 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).

Conclusions: LRG1 significantly predicted three-year overall survival in patients with metastatic breast cancer, supporting its potential as a prognostic biomarker.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: Management of advanced renal cell carcinoma (RCC) has evolved significantly in the last years. Systemic treatment of clear cell RCC, the predominant subtype, is performed with immune checkpoint inhibitors (ICIs), anti-VEGF tyrosine kinase inhibitor (TKI), HIF2α inhibitors and mTOR inhibitors.

Summary: The application of ICI in early disease has raised new challenges regarding subsequent therapy strategies and management of new toxicities of immunotherapy-based combination therapies. Systemic treatment for non-clear cell RCC is challenging due to the lack of robust clinical evidence for effective treatment regimens. Recent phase-2 data also indicate a benefit of ICI-combination therapies for non-clear cell RCC. For oligometastatic or oligoprogressive diseases, local therapy with cytoreductive nephrectomy, metastasectomy or stereotactic radiation can be considered. This review provides a comprehensive overview of current treatment strategies for advanced RCC, including systemic therapies for both clear cell and non-clear cell subtypes, management of treatment-associated toxicities, and the role of local therapies.

Key messages: Combination therapy for clear cell RCC is standard in first-line therapy and published data also support its use in non-clear cell carcinoma. Local therapies can be considered in selected patients. In subsequent treatment lines TKIs, mTOR inhibitors and the HIF2α inhibitor belzutifan are used.

Background: Urothelial carcinoma (UC) is a significant global health burden and shows consistent increase in incidence. The treatment landscape for advanced or metastatic urothelial carcinoma (mUC) has evolved, but significant challenges remain to prolong survival. The article is based on the content of the recent guidelines and a selective literature search.

Summary: For many years in the past, cisplatin-based chemotherapy was the standard first-line therapy for eligible patients. But chemotherapy alone provides limited long-term benefit, and a large proportion of patients either progress rapidly or are ineligible for cisplatin due to comorbidities. This demonstrates the medical need and led to the development of immune checkpoint inhibitors and antibody-drug conjugates (ADCs) in the field of mUC treatment. More recently, the introduction of ADCs further enlarged the medical armamentarium in mUC patients and was further explored as combined regimens. The combination of enfortumab vedotin (EV) and pembrolizumab was superior to standard platin-based chemotherapy as did nivolumab plus gemcitabine with cisplatin, which permanently transformed the medical treatment landscape in mUC. Today, EV plus pembrolizumab is the first-line standard in treatment of therapeutic advanced or mUC. New options are also emerging, such as molecular therapies that target the fibroblast growth factor receptor. In the future, targeted therapy could also be used in the perioperative area.

Key message: Today, EV combined with pembrolizumab sets a new standard of care in medical treatment of a/mUC patients. Compared to platinum-based therapy, EV plus pembrolizumab doubled the overall survival probability and reported a median OS of 31.5 months, which is a new hallmark of palliative medical treatment in this disease. This novel therapy in combination with molecular therapies, novel devices, and molecular markers offers a great opportunity for the next step in medical development in localized UC, and its clinical applicability is being investigated in ongoing studies.

Background: Penile cancer is a rare, aggressive malignancy, with incidence varying geographically. The primary risk factor is human papillomavirus (HPV) infection. Squamous cell carcinoma represents the most common histological subtype, accounting for around 95% of cases. For advanced penile carcinoma, prognosis remains poor with a 5-year survival rate of 16% in stage IV disease. Treatment is largely centred on palliative systemic therapy. This review provides an overview of the evidence on palliative systemic treatment for advanced penile cancer, including chemotherapy, immunotherapy, and targeted therapy, as well as emerging treatment strategies.

Summary: Cisplatin-based chemotherapy is the established first-line treatment for advanced penile cancer, but its efficacy is often limited and short-lived. Immune checkpoint inhibitors showed limited but promising efficacy in penile carcinoma, with some patients experiencing durable responses, particularly those with high tumour mutational burden, HPV positivity, or high PD-L1 expression, though further research is needed to identify predictive biomarkers for optimal patient selection. HPV vaccine-based therapies targeting HPV oncoproteins, adoptive T-cell therapies and agents like binatrafusp alfa are showing potential in HPV-associated cancers, though their role in penile cancer remains uncertain. Ongoing clinical trials are investigating potentially synergistic combination therapies, such as HPV vaccines with checkpoint inhibitors or immune therapies combined with chemotherapy or tyrosine kinase inhibitors.

Key messages: Cisplatin-based chemotherapy remains the first-line treatment for advanced penile cancer, while immunotherapy and targeted therapies show promise but require further investigation. Enrolling patients in clinical trials and conducting early tumour molecular sequencing, if possible, are crucial for improving outcomes and identifying effective treatment targets.

Introduction: The goal of our study was to generate a standardized assessment of postoperative complications and functional results in patients undergoing salvage lymph node dissection (sLND) in a multimodal setting with prior primary therapy and possibly multiple courses of radiation due to nodal-recurrent prostate cancer.

Patients and methods: This study included 173 patients that underwent sLND between 2005 and 2019. Postoperative complications were reported according to Clavien-Dindo-Classification (CDC). Health-related quality of life (QoL) was assessed prospectively using a validated questionnaire (EORTC QLQ-C30). Postoperative urinary incontinence was quantified with the assessment of pad usage and the ICIQ-SF questionnaire.

Results: The any-grade complication rate after sLND was 67% (n = 115 patients). A total of patients (n = 42) had severe postoperative complications (CDC grade ≥IIIa). No grade V complications were reported. The number of lymph nodes removed was higher in patients with any-grade complications (median 32 versus 25, p = 0.03), while the number of lymph node metastases was higher in patients with severe complications (median 7 versus 3, p = 0.03). However, no clinical parameter was independently associated with complications. A total of 56% patients did not require any pads postoperatively. Median postoperative ICIQ-SF score was 5 and was higher in patients with any prior radiation (median 6 versus 0, p = 0.03). Radical prostatectomy as primary therapy (p = 0.01) and any prior radiation (p = 0.01) were independent predictors of any incontinence. Patients' QoL was rated as moderate, with an impairment in QoL in 39% of the follow-up cohort.

Conclusion: SLND is a treatment option in selected patients with nodal-recurrent prostate cancer with considerable complication rates and possible functional impairments that need to be discussed with the patient when balancing the indication for this metastasis-directed treatment option.

Background: Advanced stages of prostate cancer (PCa), in particular metastatic castration-resistant prostate cancer, are associated with significant morbidity and mortality. The androgen receptor (AR) signaling pathway is a cornerstone of therapeutic intervention, but resistance mechanisms and disease progression demand increasingly complex treatment strategies.

Summary: We provide a comprehensive overview on the management of metastatic PCa, highlighting the evolution of treatment approaches and their clinical implications. Androgen deprivation therapy remains the backbone of therapy, enhanced by androgen synthesis inhibitors, AR inhibitors, and emerging AR degraders. Taxane-based chemotherapy, radiopharmaceuticals like radium-223 and lutetium-177 PSMA-617, and PARP inhibitors have expanded the therapeutic arsenal. Novel treatment approaches are in preclinical and clinical development. Various factors must be taken into account when deciding on the optimal treatment strategy including disease and patient-specific aspects. In addition, previous treatment lines may impact the efficacy of subsequent therapeutic approaches.

Key messages: The growing number of treatment options and a better understanding of the biological processes involved in tumor progression and the development of resistance are enabling increasingly individualized treatment of patients with advanced PCa.