Therapeutic Advances in Medical Oncology最新文献

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths in Germany. National data on the management of HCC remain scarce.

Objectives: This study aims to provide an up-to-date overview of clinical characteristics, treatment modalities, and survival outcomes among patients with HCC in Germany.

Design: This is a real-world retrospective study using health insurance data from BARMER.

Methods: Patients with an HCC diagnosis between 2016 and 2020 were identified in the BARMER database. Comorbidities, anticancer therapies, and treatment pathways of those patients were evaluated using descriptive statistics and survival analysis.

Results: A total of 2778 patients with HCC were identified. Of these, 1569 (56.5%) received any anticancer therapy. Transarterial chemoembolization (TACE; 22.3%), liver resection (LR; 20.9%), and systemic therapy (18.9%) were the most frequently used approaches. Survival varied significantly, with liver transplantation (LTx) offering the best outcomes, with a 5-year survival rate of 76%, followed by LR with 40%. Treatments with curative intent, including LTx, LR, and ablation, had a median survival of 40.4 months, compared to 9.7 months for non-curative modalities.

Conclusion: In Germany, a substantial proportion of HCC patients remain untreated. Therapies with curative intent, particularly transplantation, provide relevant survival benefits. Improving surveillance efforts could enhance the proportion of patients eligible for these modalities and may represent a critical step toward improved outcomes for patients with HCC.

Dedifferentiated ovarian carcinomas (DDOC) are rare and aggressive malignancies characterized by a mixture of differentiated and undifferentiated tumor components, often associated with poor prognosis. This case report describes a 55-year-old woman initially diagnosed with early-stage high-grade endometrioid ovarian carcinoma who experienced rapid disease progression during adjuvant platinum-based chemotherapy, culminating in death within 4 months. Retrospective molecular analyses revealed pathogenic variants in the SMARCA4 gene, leading to a revised diagnosis of DDOC. The tumor exhibited resistance to conventional chemotherapy, highlighting the challenges associated with managing this aggressive tumor subtype. In our case, molecular profiling identified two potentially targetable alterations: biallelic SMARCA4 loss and a pathogenic PIK3CA mutation, both of which may inform future therapeutic strategies. This case underscores the importance of integrating molecular diagnostics into routine practice for accurate classification and highlights the urgent need for personalized treatment strategies, including targeted and immunotherapy options, for this formidable tumor subtype.

Background: Hematoxylin and eosin (H&E) staining is routine in pathology but lacks cellular specificity. Multiplex immunofluorescence (mIF) captures spatial immune relationships in tumors, but cost and complexity limit clinical application. Novel approaches to yield similar information from readily available tumor histology are needed.

Objectives: Develop and validate a novel deep learning tool capable of translating standard H&E-stained histopathology images into high-fidelity synthetic mIF images that preserve immune cell information predictive of treatment response in breast cancer.

Design: Comparative model evaluation and predictive modeling in a retrospective breast cancer cohort.

Methods: Core-needle biopsies from 17 triple-negative breast cancer cases underwent mIF imaging. Hematoxylin and eosin and mIF images for DAPI (nuclei), pan-CK (tumor), CD3/CD4/CD8 (T-cells), and CD20 (B cells) were aligned. A pipeline outperforming standard Pix2Pix and CycleGAN image translation networks was developed, "multiplex Synthetic Immunofluoresence Generated through H&E Translation" (mSIGHT), which integrates a registration network to overcome misalignment between the input and target images. Generated images were evaluated with pixel-level metrics and biological metrics, including cell density and cell-to-cell adjacency. The pipeline was then applied to an external cohort to assess associations between predicted immune features and pathologic response to neoadjuvant chemotherapy.

Results: Generated images preserved immune cell distributions and proximity metrics correlated to the ground truth cell counts. In a cohort of 218 breast cancer cases treated with neoadjuvant chemotherapy, predicted density of CD8+ T cells was significantly associated with complete response (adjusted odds ratio 1.89, 95% confidence interval 1.23-2.80, p = 0.002), independent of receptor status, grade, and pathologist TIL annotations.

Conclusion: The mSIGHT pipeline enables translation of routine H&E slides into virtual mIF images with interpretable immune biomarkers, offering a scalable and affordable alternative to multiplex imaging. It also identifies immune features predictive of therapeutic response and has the potential to assist in the personalization of neoadjuvant therapy.

[This retracts the article DOI: 10.1177/1758835920982853.].

[This retracts the article DOI: 10.1177/1758835919875319.].

Background: Soft tissue sarcomas (STS) are rare, heterogeneous tumors with poor prognosis, often characterized by high recurrence rates and limited response to conventional chemotherapy in advanced stages. Vascular-targeting agents (VTA) have shown promising efficacy for STS in numerous clinical trials; however, the optimal agent and combination strategies remain undetermined.

Objectives: This work aims to compare the clinical efficacy and adverse events of different VTA-containing regimens for patients with STS.

Design: This study is a systematic review and network meta-analysis.

Data sources and methods: We searched PubMed, Embase, and the Cochrane Library for eligible randomized clinical trials. All trials with VTA as monotherapy or VTA-included regimens in the experimental or control groups were selected, except for some specific histological subtypes. Pooled hazard ratios (HRs) for survival data and odds ratios for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events with credible intervals were generated using R software. A Bayesian random-effects model was applied to rank different treatments based on the surface under the cumulative ranking curve (SUCRA) values.

Results: Seventeen articles covering 15 studies were included. Pairwise comparisons demonstrated prolonged progression-free survival (PFS) for tyrosine kinase inhibitor (TKI) versus placebo (HR 0.50, 95% confidence interval (CI) 0.32-0.83) and prolonged overall survival (OS) for monoclonal antibody plus chemotherapy versus placebo (HR 0.42, 95% CI 0.19-0.89). Vascular-disrupting agents (VDA) plus chemotherapy were ranked highest for OS (87.05%) and ORR (89.66%). TKI plus chemotherapy and TKI plus immunotherapy had higher SUCRA values for PFS (68.21%) and DCR (82.29%). TKI-based regimens were associated with higher incidences of hypertension, diarrhea, and elevated transaminase levels, whereas chemotherapy-based strategies resulted in higher incidences of hematological toxicity and constipation.

Conclusion: VTA-containing regimens showed promising activity and tolerability in patients with advanced STS. Combination regimens with TKI showed better efficacy for PFS and DCR. Novel VDA combined with chemotherapy showed potential to prolong OS and improve ORR.

Trial registration: PROSPERO website (registration number: CRD42024588134).

Background: Immunotherapy combinations like Pembrolizumab + Axitinib and Nivolumab + Ipilimumab have survival benefits over Sunitinib in advanced renal cell carcinoma (aRCC) first-line treatment. But their cost-effectiveness in the USA and China is unclear.

Objectives: To assess the cost-effectiveness of three first-line treatment regimens for untreated aRCC-Nivolumab plus Ipilimumab, Pembrolizumab plus Axitinib, and Sunitinib-from the perspective of national health service systems and indirect healthcare payers in China and the USA, with a focus on intent-to-treat (ITT) populations and International mRCC Database Consortium (IMDC) risk stratifications.

Design: Decision-tree and Markov models, based on KEYNOTE-426 and CheckMate 214 trials, simulated 5-year disease progression of eligible patients.

Methods: The model, constructed using TreeAge Pro 2022 (TreeAge Software, LLC, Williamstown, Massachusetts, USA), incorporated three health states: progression-free survival, progressive disease, and death. Economic parameters included direct medical costs (first-line and second-line treatments, adverse event management, monitoring), quality-adjusted life year (QALYs), and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analysis was performed to evaluate model uncertainty.

Results: Across favorable-risk, intermediate/poor-risk IMDC subgroups, and the ITT population, Nivolumab plus Ipilimumab sequential Cabozantinib demonstrated the optimal cost-effectiveness in both countries, with ICERs below the willingness-to-pay (WTP) thresholds. It was associated with lower costs and higher QALYs compared to the other two regimens. Pembrolizumab plus Axitinib sequential Cabozantinib was more cost-effective than sunitinib sequential Cabozantinib in both regions, with ICERs also below WTP thresholds.

Conclusion: In China and the USA, Nivolumab plus Ipilimumab is the most cost-effective first-line treatment for aRCC across different IMDC subgroups and the ITT population, followed by Pembrolizumab plus Axitinib, which outperforms sunitinib. These findings can guide clinical decision-making, though their generalizability is limited to China and the USA due to regional differences in drug pricing, payment systems, and market access.

Background: Despite advanced in systemic therapy for renal cell carcinoma (RCC), bone metastasis remains an adverse prognostic factor and major cause of mortality and morbidity. Orthopedic interventions may provide symptom relief, functional recovery, and survival benefit, yet the evidence is fragmented across heterogeneous studies.

Objectives: To systematically review the outcomes of orthopedic surgical interventions in patients with symptomatic bone metastases from RCC.

Design: Systematic literature review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources and methods: A comprehensive search of Embase, MEDLINE, and the Cochrane Library was conducted for studies published between January 1, 2014, and January 30, 2024. Eligible studies included randomized controlled trials, prospective observational studies, and retrospective studies reporting on orthopedic interventions for RCC bone metastases. Primary outcomes included overall survival, reoperation rates, complication rates, and quality of life.

Results: Of 2208 studies screened, 15 met the inclusion criteria. All were retrospective series or case series, limiting the strength of the evidence. Six studies focused on appendicular skeleton metastases, five on axial skeleton involvement, and four on both regions. Results were primarily reported narratively, with limited statistical analyses. Orthopedic surgical interventions-particularly when combined with targeted systemic therapy-were associated with longer overall survival. Among surgical approaches, complete metastasectomy was most consistently associated with improved survival compared with intralesional curettage and stabilization-only procedures.

Conclusion: Although available data suggest that orthopedic surgery, particularly complete metastasectomy, may improve overall survival and quality of life in RCC patients with bone metastases, the evidence is limited to retrospective and narrative reports. Some studies also suggest that outcomes may be further enhanced when surgery is integrated with systemic therapy. Given the poor prognosis associated with bone involvement in RCC, prospective randomized studies are urgently needed to define optimal patient selection, standardize management strategies, and integrate surgery with systemic therapy in a multidisciplinary framework.

Background: As metastasis drives the majority of breast cancer-related deaths, improving outcomes for metastatic breast cancer (MBC) remains a crucial challenge. Observational studies using target trial emulation are increasingly applied to estimate treatment effects, providing insights when randomized trials are not viable.

Objectives: To estimate the effect of progression-free survival (PFS) of metronomic chemotherapy of weekly paclitaxel plus cisplatin (DP) compared with treatment of the physician's choice (TPC) for MBC.

Design: This analysis was designed as a retrospective cohort study according to STROBE criteria.

Methods: This retrospective cohort study compared metronomic chemotherapy of weekly DP versus TPC in MBC. The DP regimen included paclitaxel (80 mg/m²) on days 1, 8, 15, 22 and cisplatin (25 mg/m²) on days 1, 8, 15 in a 28-day cycle. Women aged ⩾18 years with MBC treated with at least one prior therapy between April 2014 and January 2023 at Renji Hospital were included. Propensity score matching (1:3) adjusted for confounding. The matched cohort subsequently underwent emulation of a randomized target trial, including cloning, censoring and weighting. The primary endpoint was PFS.

Results: Among 313 matched patients (83 on DP, 230 on TPC), DP showed a median PFS of 13.5 months (95% CI 10.3-16.6) versus 7.9 months (95% CI: 6.7-9.1) for TPC (hazard ratio (HR) 0.77, 95% CI 0.60-0.99). Target trial emulation further improved PFS in the DP arm to 14.1 months (95% CI: 13.3-16.6) versus 8.3 months (95% CI: 8.0-8.6) for TPC (HR 0.59, 95% CI: 0.54-0.64). Subgroup analysis and sensitivity analyses confirmed result robustness.

Conclusion: This study demonstrates that weekly metronomic DP chemotherapy reduces disease progression in MBC patients, particularly in first-line settings. These findings support its potential as a treatment option and warrant further study for broader application.

Background: The management of hormone receptor-positive (HR+), HER2-negative early breast cancer in young women presents unique challenges due to the absence of standardized guidelines and variability in clinical decision-making. In Latin America, these challenges are compounded by disparities in healthcare systems and limited access to genomic testing and supportive services.

Objectives: To evaluate current attitudes, diagnostic strategies, and treatment practices among Latin American oncologists regarding the care of young women with HR+ early breast cancer.

Design: A cross-sectional survey study targeting practicing oncologists across Latin America.

Methods: A 30-item online questionnaire was distributed to 329 oncologists from 17 Latin American countries. The survey explored physician demographics, access to diagnostic tools, treatment preferences, and availability of support services, including genetic counseling and fertility preservation.

Results: The findings revealed significant heterogeneity in clinical practices. Among patients with a Recurrence Score (RS) of 20-25, 53.8% of oncologists recommended adjuvant chemotherapy, while 23.4% considered additional clinicopathologic features. Fertility preservation counseling was inconsistently offered: 29.5% provided it routinely, whereas 12.5% never did. Ovarian function suppression (OFS) was universally recommended by 46.2% of respondents, with breast cancer specialists showing more nuanced use than non-specialists (p = 0.019). Access to genetic counseling was limited, with 12.5% reporting no access. Temporary interruption of endocrine therapy to pursue pregnancy was supported by 41.0% of respondents, though approaches varied. Female oncologists were more likely to recommend extended endocrine therapy (73.2% vs 60.8%, p = 0.019) and to refer patients for sexual health support (19.3% vs 8.7%, p = 0.05).

Conclusion: This study highlights considerable variability in the management of young women with HR+ early breast cancer across Latin America. Physician gender, specialty, and resource availability significantly influence treatment decisions. These findings underscore the urgent need for regionally tailored clinical guidelines and improved access to diagnostic and supportive care resources to ensure equitable and evidence-based care.