Clinical & Translational Oncology最新文献

Aim: To assess for the first time the safety and feasibility of combining photon-IntraOperative RadioTherapy (ph-IORT) with hypofractionated whole-breast irradiation (hWBI) in patients referred to adjuvant radiotherapy after Breast-Conserving Surgery (BCS).

Methods: From February 2019 to August 2020, patients referred for breast-conserving surgery (BCS) in our institution were prospectively included in the present trial. BCS was discussed in the multidisciplinary tumor board (MTB). 20 Gy were prescribed to the surface of the applicator of an Intrabeam^®ph-IORT during BCS. hWBI (40.5 Gy/2.67 Gy/15frx) was planned to be administered 3-5w after BCS. All patients were treated by hWBI VMAT-Rapid-Arc&Daily Exac-Trac-IGRT. Systemic adjuvant treatment was indicated following international guidelines. The aim of this study was to assess for the first time the local control, cancer-specific survival, and overall survival rates of BC patients treated by combined photon-IORT-boost and hWBI after BCS. Secondary endpoints include the long-term toxicity and cosmetic outcomes observed in these patients.

Results: Fifty-seven patients were included in the trial. No ≥ G3 late toxicity was observed at 12 months of follow-up and thereafter. After a median follow-up of 61 months (range 54-66 months), all patients were free of local or regional relapse. Two patients had a second tumor in the contralateral breast. One triple-negative patient developed lung metastases 3 years after her initial diagnosis. Cause specific and overall survival were 100% at 5 years.

Conclusion: We demonstrated for the first time that ph-IORT + hWBI is effective and safe in the long-term for patients referred to adjuvant RT after BCS.

Glioblastoma (GBM) is one of the most common primary malignant brain tumors. Annually, there are about six instances recorded per 100,000 inhabitants. Treatment for GB has not advanced all that much. Novel medications have been investigated recently for the management of newly diagnosed and recurring instances of GBM. For GBM, surgery, radiation therapy, and alkylating chemotherapy are often used therapies. Immunotherapies, which use the patient's immune reaction against tumors, have long been seen as a potential cancer treatment. One such treatment is the dendritic cell (DC) vaccine. This cell-based vaccination works by stimulating the patient's own dendritic cells' antigenic repertoire, therefore inducing a polyclonal T-cell response. Systematic retrieval of information was performed on PubMed, Embase, and Google Scholar. Specified keywords were used to search, and the articles published in peer-reviewed scientific journals were associated with brain GBM, cancer, and Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination. Selected 90 articles were used in this manuscript, of which 30 articles were clinical trials. Compared to shared tumor antigen peptide vaccines, autologous cancer DCs have a greater ability to stimulate the immune system, which is why dendritic cell fusion vaccines have shown early promise in several clinical studies. Survival rates for vaccinated patients were notably better compared to matched or historical controls. For newly diagnosed patients, the median overall survival (mOS) ranged from 15 to 41.4 months, while the progression-free survival (PFS) ranged from 6 to 25.3 months. We discovered through this analysis that autologous multiomics analysis of DC vaccines showed enhanced antitumor immunity with a focus on using activated, antigen-loaded donor DCs to trigger T-cell responses against cancer, particularly in glioblastoma. It also showed improved patient survival, especially when combined with standard chemoradiotherapy. DC vaccines show promise in treating GBM by enhancing survival and reducing tumor recurrence. However, challenges in vaccine production, antigen selection, and tumor heterogeneity highlight the need for continued research and optimization to improve efficacy and patient outcomes.

Background: In triple-negative breast cancer (TNBC) patients receiving adjuvant capecitabine, the impact of HER2 expression on survival outcomes is unclear.

Methods:  Between June 2017 and December 2023, 112 patients with TNBC who received adjuvant capecitabine due to residual masses after neoadjuvant chemotherapy (NACT) in three hospitals were identified. HER2 is analyzed through immunohistochemistry (IHC) and/or in situ hybridization in the core biopsy and/or post-surgical histopathologies. Relapse-free survival (RFS) and overall survival (OS), according to HER2 expression (0, 1 + , 2 +) status, were calculated (Kaplan-Meier method).

Results:  Seventy-eight (69.6%) patients had HER2 zero, 20 (17.9%) patients had HER2 + 1, and 14 (12.5%) patients had HER2 + 2/ISH- BC. The 5-year OS was 62.6%, and the 5-year RFS was 55.8%. HER2 2 + expression was associated with worse OS (27.5 vs. 84.5 months; HR 4.82, 95% CI 2.15-10.80, p < 0.001) and worse RFS (11.90 months vs. not reached; HR 4.30, 95% CI 2.06-8.99, p < 0.001) compared with HER2 0/1 + expression. The 5-year OS rates were 32.7% and 72.1%, and the 5-year RFS rates were 30.6% and 64.7% in the HER2 2 + and HER2 0/1 + groups, respectively. No statistically significant differences were detected in clinicopathologic features or pathologic responses to NACT according to the HER2 expression level.

Conclusions:  Despite the use of the adjuvant capecitabine in HER2 2 + TNBC patients, these poor results will pave the way for further investigations of anti-HER2 therapeutic agents in adjuvant treatment.

Introduction: Peripheral blood mononuclear cells (PBMCs) trafficking is regulated by chemokines, which modulate leukocyte migration toward tumors and may collaborate in the efficacy of immunotherapy. In our study, we investigated whether the CXCL12/CXCR4 axis plays a role in the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) by analyzing CXCR4 expression for CXCR4 in peripheral blood (PB), and the expression of its ligand CXCL12 in tumor.

Methods: We identified PBMCs expressing CXCR4 using flow cytometry in a prospective cohort of NSCLC patients before starting anti-PD-1 immunotherapy. As a control, we studied patients with advanced cancer before starting any non-immunotherapy treatment. The relative frequency of PBMCs was correlated with treatment outcomes. Uni- and multivariate survival analyses were performed. The expression of CXCL12 in tumor tissue was studied and correlated with the expression of its receptor (CXCR4) in PBMCs.

Results: The experimental group included 39 patients and the control group included 40. Low expression of CXCR4-expressing CD8 + T lymphocytes was correlated with a greater benefit from immunotherapy: median OS NR vs. 22.0 months, HR 0.6, p < 0.01; and median PFS 14.2 vs. 5.0 months, HR 0.38, p = 0.05. These differences were not observed in controls. Low expression in PB of these lymphocytes was correlated with a higher expression of CXCL12 in tumor (trend toward significance: p = 0.14).

Conclusion: Patients diagnosed with advanced NSCLC with low percentage of cytotoxic T lymphocytes expressing CXCR4 in PB, show greater benefit from immunotherapy, probably due to increased tumor infiltration by lymphocytes in response to CXCL12 produced by the tumor.

Purpose: Prostate-specific antigen (PSA) bounce is a transient elevation in PSA levels commonly observed after radiotherapy. This study aims to investigate the characteristics, timing, and clinical implications of PSA bounce (PSA-B) in prostate cancer patients treated with external beam radiotherapy (EBRT), exploring potential causes and its relevance in patient management.

Materials and methods: Between 2013 and 2019, 629 patients with localized prostate cancer were treated with EBRT. After excluding patients with fewer than four PSA measurements or follow-up under 3 years (n = 184), 445 patients were analyzed. The median follow-up duration was 5.9 years (36-105 months). PSA-B was defined as a rise of ≥ 0.2 ng/mL above the nadir, followed by a subsequent decline to or below the nadir. PSA relapse was defined according to Phoenix definition.

Results: A total of 64 patients (14.4%) experienced PSA-B at a median of 31 months (6-68 months). Univariable analysis identified age (p < 0.001), risk group (p < 0.001), perineural invasion (p < 0.007), radiotherapy duration (p < 0.001), and the absence of concurrent hormonal therapy (p < 0.001) as independent predictors of PSA-B. Multivariable analysis confirmed age and high-risk group as significant factors. PSA relapse occurred in 10.3% of cases, with only one patient who experienced both PSA-B and relapse.

Conclusions: PSA-B is a common phenomenon in localized prostate cancer patients post-EBRT. Factors such as age, risk group, perineural invasion, radiotherapy duration, and hormonal treatment use are associated with PSA-B occurrence. Understanding its mechanisms is crucial for optimizing prostate cancer management.

Extracellular vesicles (EVs) play a crucial role in the complex process of cancer metastasis by facilitating cellular communication and influencing the microenvironment to promote the spread and establishment of cancer cells in distant locations. This paper explores the process of EV biogenesis, explaining their various sources that range from endosomal compartments to plasma membrane shedding. It also discusses the complex mechanisms that control the sorting of cargo within EVs, determining their chemical makeup. We investigate the several functions of EVs in promoting the spread of cancer to other parts of the body. These functions include influencing the immune system, creating environments that support the formation of metastases before they occur, and aiding in the transformation of cells from an epithelial to a mesenchymal state. Moreover, we explore the practical consequences of EV cargo, such as nucleic acids, proteins, and lipids, in influencing the spread of cancer cells, from the beginning of invasion to the creation of secondary tumor sites. Examining recent progress in the field of EV-based diagnostics and treatments, we explore the potential of EVs as highly promising biomarkers for predicting the course of cancer and as targets for therapeutic intervention. This review aims to provide a complete understanding of the biology of EVs in the context of cancer metastasis. By unravelling the nuances of EV biology, it seeks to pave the way for new tactics in cancer detection, treatment, and management.

Purpose: The purpose of this study was to investigate the therapeutic efficacy of the combination of microwave ablation (MWA) with immune checkpoints blockade and TLR9 stimulation in the treatment of non-small cell lung cancer (NSCLC) using the C57BL/6 tumor-bearing mice model.

Materials and methods: Tumor-bearing mice were treated with MWA, programmed cell death protein1 blockade (PD-1) plus MWA (MWA + P), TLR9 agonist CpG ODNs and MWA (MWA + C), PD-1 blockade and CpG ODNs (P + C), MWA plus PD-1 blockade and CpG ODNs (MWA + P + C), or untreated. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 15 after MWA, ten mice from the combination therapy group received tumor rechallenge with LLC cells and the volumes of rechallenge tumor were calculated every 5 days. Immune cells were identified by immunohistochemistry and flow cytometry, and the concentrations of IFN-γ、TNF-α and TGF-β were identified by enzyme-linked immunosorbent assay (ELISA).

Results: The MWA + P + C combination therapy significantly prolonged tumor-bearing mice survival and reduced tumor size compared to untreated group, MWA group, MWA + P group, M + C group, P + C group. The combination therapy also protected most surviving mice from LLC tumor rechallenge. CD8 + T-cell in tumor and spleen were remarkably induced by MWA + P + C and Treg cell further diminished by combination therapy. Both tumor necrosis factor-alpha (TNF-α) and interferon-gama (IFN-γ) concentrations in plasma were significantly elevated in the combination therapy group compared to other groups, while transforming growth factor Beta (TGF-β) was reduced.

Conclusion: MWA combined with immune checkpoints blockade and TLR stimulation could significantly enhance antitumor efficacy with augmented specific immune responses, and the combination therapy is a promising approach to treat non-small cell lung cancer (NSCLC).

Background: There are gaps and unanswered questions in clinical guidelines regarding several aspects of the management of patients with cutaneous squamous cell carcinoma (cSCC).

Methods: A scientific committee of ten cSCC specialists in Spain (dermatology, medical oncology, oral and maxillofacial surgery, plastic surgery, and radiotherapy) used ADAPTE methodology to develop recommendations by: (i) identifying clinical questions not fully answered by clinical practice guidelines; (ii) systematically reviewing the literature (published between November 2017 and July 2023 in PubMed and the Cochrane database) and grading the evidence (using Oxford levels); (iii) developing recommendations and assessing those with no consensus among the scientific committee or with evidence level 3-5 or strength of recommendation under C or D in a two-round Delphi method; and (iv) developing the final recommendations in the form of answers to key clinical questions, grading the strength of recommendation. An external group of 32 experts plus the members of the committee participated in both Delphi rounds, evaluating the appropriateness and need of the recommendations.

Results: Initially, 33 recommendations were made for 26 questions; 19 recommendations were evaluated with the Delphi method. All 19 recommendations were deemed appropriate and necessary. A total of 27 final recommendations were made, concerning initial patient management, treatment of the primary tumour, management of advanced disease, specific populations, supportive and palliative care, and follow-up.

Conclusion: We developed 27 recommendations that answer clinical questions on the management of patients with cSCC, providing guidance on aspects that are unclear in clinical guidelines or on which guidelines differ.

Background: ANGPT2 plays important roles in cancer development. However, there is still no systematic analysis of ANGPT2 in pan-cancer.

Methods: In this paper, we conducted a pan-cancer analysis to investigate the characteristics of ANGPT2. Furthermore, we investigated the impact of genetic and epigenetic factors on ANGPT2 expression by bioinformatics and assays.

Results: By several TCGA and GEO databases, we identified elevated expression of ANGPT2 in various tumor types. Besides, high expression of ANGPT2 induced poor prognosis of patients in multiple tumors. Through enrichment analysis, we found that ANGPT2 participated in various biological processes, including angiogenesis and immunity. Various immune analyses indicated that high expression of ANGPT2 might suggest a propensity towards a hot tumor microenvironment, but its impact on immunotherapy was negative. Bioinformatics analysis and experiments confirmed that genetic and epigenetic factors explained part of the mechanism behind ANGPT2 abnormal expression. Finally, we screened candidate drugs targeting the ANGPT2 protein by molecular docking and molecular dynamics simulation.

Conclusion: ANGPT2 has diagnostic and prognostic values in multiple tumor types. Though with a hot tumor microenvironment, ANGPT2 high expression patients are not suitable for immunotherapy because of its proangiogenic function, contributing to selecting the exact patients for immunotherapy. Both genetic and epigenetic factors influenced ANGPT2 expression, with the influence of super-enhancer being more pronounced. This paper for the first time did the systematic analysis of ANGPT2 and showed its characteristic in pan-cancer. We summarized the biomarker role of ANGPT2 on tumor diagnosis and prognosis, as well as its target role on tumor immunotherapy.

Breast cancer is a complicated malignancy and is known as the most common cancer in women. Considerable experiments have been devoted to explore the basic impacts of the tumor stroma, particularly the extracellular matrix (ECM) and stromal components, on tumor growth and resistance to treatment. ECM is made up of an intricate system of proteins, glycosaminoglycans, and proteoglycans, and maintains structural support and controls key signaling pathways involved in breast tumors. ECM can block different drugs such as chemotherapy and immunotherapy drugs from entering the tumor stroma. Furthermore, the stromal elements, such as cancer-associated fibroblasts (CAFs), immune cells, and blood vessels, have crucial impacts on tumor development and therapeutic resistance. Recently, promising outcomes have been achieved in using nanotechnology for delivering drugs to tumor stroma and crossing ECM in breast malignancies. Nanoparticles have various benefits for targeting the breast tumor stroma, such as improved permeability and retention, extended circulation time, and the ability to actively target the area. This review covers the latest developments in nanoparticle therapies that focus on breast tumor ECM and stroma. We will explore different approaches using nanoparticles to target the delivery of anticancer drugs like chemotherapy, small molecule drugs, various antitumor products, and other specific synthetic therapeutic agents to the breast tumor stroma. Furthermore, we will investigate the utilization of nanoparticles in altering the stromal elements, such as reprogramming CAFs and immune cells, and also remodeling ECM.