Clinical & Translational Oncology最新文献

Purpose: This study aimed to investigate the prevalence and characteristics of burnout among Radiation Oncology residents in Spain, focusing on its associated risk factors and implications for residency training.

Materials and methods: A cross-sectional online survey was conducted from June to September 2024, using the Maslach Burnout Inventory (MBI) to evaluate emotional exhaustion, depersonalization, and self-fulfillment. Residents from various Spanish regions completed an anonymous questionnaire covering workload and burnout.

Results: Fifty residents, predominantly in their third (38%) and fourth (42%) years of training, participated. High emotional exhaustion was reported by 58%, while 54% exhibited elevated depersonalization. Self-fulfillment scores were low in 32%. Overall, 70% experienced at least one burnout symptom, with 12% meeting criteria for full-burnout syndrome. An inverse correlation between self-fulfillment and emotional exhaustion was observed (p = 0.007). Trends suggested higher burnout risk in senior residents (R3-R4) compared to juniors (R1-R2), though these differences were not statistically significant (OR = 1.682; p = 0.086).

Conclusion: The findings reveal a high prevalence of at least one burnout symptom among Radiation Oncology residents in Spain, with emotional exhaustion and depersonalization notably elevated. However, full-burnout syndrome is not prevalent. These findings underscore the need for reforms in residency training programs, emphasizing workload management, well-being initiatives, and support for scientific and professional development.

Background: Head and neck squamous cell carcinoma (HNSCC) ranks among the most lethal solid tumors in humans, with a five-year survival rate hovering around 50%. The limited understanding of its biological foundation has hindered the development of efficacious targeted therapeutics.

Methods: TCGA database and immunohistochemistry were deployed to confirm the expression levels of ubiquitin specific protease 14 (USP14). CCK8 method was used to evaluate the influence of USP14 on cisplatin resistance. Further investigations into the role of USP14 were conducted through assessments of cell proliferation, colony formation, and Transwell assays. The impact of USP14 expression on ferroptosis was evaluated by measuring GSH/GSSG ratios, Fe²⁺ concentrations, and lipid peroxide levels. Co-IP was employed to verify the interaction between USP14 and FABP5.

Results: Our analysis revealed that USP14 ranked among the most prominently upregulated deubiquitinases (DUBs) in tissue samples of HNSCC. Notably, aberrant USP14 expression was linked to tumorigenesis and the malignant evolution of HNSCC and further suggested a poor prognosis. In vitro experiment revealed that USP14 depletion markedly inhibited cell growth, cisplatin resistance, invasion and migration capabilities of HNSCC cells. Mechanically, USP14 inhibits FABP5 ubiquitination and degradation, thus positively modulating FABP5 expression. Subsequent analyses demonstrated that the loss of USP14 promoted ferroptosis in HNSCC cells. Finally, in vivo xenograft experiments confirmed that the USP14 small molecular antagonist IU1 could effectively attenuate cisplatin resistance in HNSCC.

Conclusion: The results indicate that the USP14-FABP5 axis exerts oncogenic effects on HNSCC, providing a potential target for diagnosing and treating this type of malignancy.

Background: Cervical cancer is the fourth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in women globally. Recent advances in immunotherapy have demonstrated promising results. This study analyses the real-world impact of adding immunotherapy for patients with stage IV cervical carcinoma.

Material and methods: This longitudinal retrospective observational study included patients with stage IV cervical carcinoma in the first metastatic setting treated between 2010 and 2023 at the University Hospital Nuestra Señora de Candelaria in Tenerife, Spain. To evaluate the primary objective, patients were divided into two groups depending on whether they had received immunotherapy with pembrolizumab or not. The primary endpoint was 12-month progression-free survival in patients receiving immunotherapy compared to those not receiving it.

Results: A total of 56 patients were analyzed, of whom 31 were tested for PD-L1. Among those tested, 25 patients (84%) were PD-L1 positive, and 18 of them (72%) received immunotherapy. The objective response rate was significantly higher, being 94% in the group that received immunotherapy, compared to 32% in the group that did not (p < 0.001). At 12 months, the cumulative probability of progression-free survival was estimated at 94.4% for the immunotherapy group versus 59.7% in the non-immunotherapy group (p = 0.009), with a hazard ratio of 0.116 (CI_95%: 0015 - 0.883; p = 0.038). Immunotherapy alone or combined with bevacizumab showed similar progression-free survival probabilities. However, these outcomes were significantly different when compared to patients who received neither therapy (p < 0.001).

Conclusions: Our findings confirm that immunotherapy significantly improves progression-free survival and objective response rates in metastatic cervical carcinoma, aligning with the results from the KEYNOTE-826 trial. The implementation of PD-L1 testing and the addition of immunotherapy whenever possible are challenges to be achieved in clinical practice.

Soft-tissue sarcomas are rare, diverse malignant tumors of mesenchymal origin, requiring diagnosis and treatment by a specialized multidisciplinary team. Initial assessment includes radiology and biopsy, followed by wide surgical resection with clear margins for localized cases. Radiotherapy is recommended for large, deep, high-grade tumors or after incomplete resection, while perioperative chemotherapy may be considered for high-risk cases. In oligometastatic disease, combining local and systemic therapies is an option. Anthracycline-based chemotherapy is the first-line treatment in advanced disease, though other drugs show efficacy in certain subtypes. Given the limited options, enrolling in clinical trials is advised for patients needing further treatment.

Introduction: Neoadjuvant chemotherapy (NACT) is a treatment option for early-stage hormone receptor-positive human epidermal growth factor receptor 2-negative (HR + /HER2-) breast cancer. Despite its use, pathological response rates in this subtype are often lower, and the impact of individual risk factors remains unclear. This study aimed to identify biomarkers and create a predictive score for NACT response.

Methods: This retrospective, single-center study included patients with stage IIA-IIIC HR + /HER2- breast cancer treated with NACT and surgery (2019-2023). Multiple logistic regression analyzed associations between clinicopathological variables and pathologic response (partial/complete vs. absent) (p < 0.05). The best-performing model was used to develop a risk score.

Results: The study included 101 patients. Significant predictors of pathological response included tumor grade (G2/3 vs. G1), menopausal status (pre- vs. post-menopausal), and intrinsic subtype (luminal B vs. A).

Conclusions: A dynamic calculator was created incorporating grade, hormonal status, intrinsic subtype, and Ki-67. This tool provides real-time input, facilitating personalized therapeutic decision-making.

Purpose: Prognosis of HNSCC has not changed over the last decades. MicroRNAs mediate gene expression and participate in regulating cellular biological processes. Its aberrant expression is an important event in the development of several cancers, including head and neck squamous cell cancer. The aim of the study is to determine if circulating miRNAs are reliable diagnostic indicators and can be used to monitor head and neck cancer.

Methods/patients: An observational, longitudinal, prospective, analytical study was conducted, with a case-control design, in which 37 head and neck squamous cell cancer patients at diagnosis were compared with 30 healthy patients. Blood samples were obtained and free miRNA expression levels of 17 miRNAs were determined by PCR-RT. Follow-up of HNSCC was carried out for one year with blood extractions at 7 days for surgical patients, and 1, 2, 6 and 12 months after finishing treatment for all patients.

Results: Seventy-eight percent of the participants in HNSCC group and 57% among control group were men. Smokers and alcohol consumers exhibit increased susceptibility to HNSCC, and risk rises to 63.4% (R² = 0.634) when both factors are combined. HNSCC patients overexpressed miR-21-5p and miR-122, while miR-195-5p is downregulated. Elevated miR-21-5p levels correlates with tumour size and miR-374b-5p, with advanced stage (p = 0.005).

Conclusion: Our findings suggest that the evaluation of certain miRNAs' expression levels in plasma can be used as potential markers for HNSCC diagnosis. Further assays with larger samples could be performed to validate data and establish a cut-off expression level for our proposed miRNAs.

Background: Breast cancer remains a leading cause of morbidity and mortality among women worldwide. According to the recent statistics by World Health Organization (WHO), it is the leading cause of death from cancer in women worldwide and it is the most frequently diagnosed cancer. This meta-analysis aims to systematically evaluate the efficacy and safety of S-ketamine in patients undergoing modified radical mastectomy.

Method: We searched five databases; PubMed, Scopus, Science Direct, Web of Science, and Medline Plus. We included six studies. The applicable outcomes for meta-analysis about efficacy and safety of S-ketamine in patients undergoing modified radical mastectomy.

Results: Six RCTs included in our meta-analysis found that Esketamine group had a statistically significant lower VAS score after 4 h, after 6 h, after 24 h, after 48 h; (MD = -1.54; 95% CI [-1.65, -1.42], P < 0.00001), (MD = -0.55; 95% CI [-0.66, -0.45], P < 0.00001), (MD = -0.75; 95% CI [-0.84, -0.66], P < 0.00001,), (MD = -0.26; 95% CI [-0.48, -0.03], P = 0.03) P < 0.00001), respectively.

Conclusion: We conclude that S-ketamine is valuable for reducing pain and safe in patients undergoing modified radical mastectomy.

Objective: The main goal of the present research is to explore the potential link of body mass index (BMI) with different survival metrics in breast cancer patients. Our aim is to offer the latest and most thorough meta-analysis, assessing the strength and reliability of the connection that BMI has with prognostic indicators in this disease.

Patients and methods: As of January 2024, we conducted a systematic literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases. Our search aimed to identify studies examining BMI as an exposure factor, with breast cancer patients constituting the study population, and utilizing adjusted hazard ratio (HR) as the data type of interest.

Results: The evidence synthesis incorporated a total of 61 eligible articles involving 201,006 patients. Being underweight posed a risk factor for overall survival (OS) in breast cancer patients compared to normal weight (HR 1.15, 95% CI 0.98-1.35; P = 0.08). Overweight or obesity, in comparison to normal weight, was a risk factor for OS (HR 1.18, 95% CI 1.14-1.23; P < 0.00001), disease-free survival (DFS) (HR 1.11, 95% CI 1.08-1.13; P < 0.00001), relapse-free survival (RFS) (HR 1.14, 95% CI 1.06-1.22; P = 0.03), and breast cancer-specific survival (BCSS) (HR 1.18, 95% CI 1.11-1.26; P < 0.00001), but not for progression-free survival (PFS) (HR 0.91, 95% CI 0.76-1.10; P = 0.33). Notably, in subgroup analyses, overweight patients achieved prolonged PFS (HR 0.80, 95% CI 0.64-0.99; P = 0.04), and compared to the obese population, the overweight cohort exhibited a significant difference in OS (HR 1.11, 95% CI 1.05-1.16; P < 0.00001) and DFS (HR 1.06, 95% CI 1.03-1.10; P = 0.0004), with a considerably stronger association. Furthermore, compared to HER- patients, HER + patients exhibited a greater predictive value for OS (HR 1.23, 95% CI 1.10-1.37; P = 0.0004), RFS (HR 1.30, 95% CI 1.03-1.64; P < 0.00001), and DFS (HR 1.10, 95% CI 1.03-1.17; P = 0.003).

Conclusions: The results of our meta-analysis reveal a notable association between BMI and various survival measures in breast cancer prognosis. These findings provide a solid basis for predicting breast cancer outcomes and implementing more effective therapeutic approaches.

Purpose: This study aims to develop radiomics models and a nomogram based on machine learning techniques, preoperative dual-energy computed tomography (DECT) images, clinical and pathological characteristics, to explore the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC).

Methods: We retrospectively recruited of 87 patients diagnosed with ccRCC through pathological confirmation from Center I (training set, n = 69; validation set, n = 18), and collected their DECT images and clinical information. Feature selection was conducted using variance threshold, SelectKBest, and the least absolute shrinkage and selection operator (LASSO). Radiomics models were then established using 14 classifiers to predict TME cells. Subsequently, we selected the most predictive radiomics features to calculate the radiomics score (Radscore). A combined model was constructed through multivariate logistic regression analysis combining the Radscore and relevant clinical characteristics, and presented in the form of a nomogram. Additionally, 17 patients were recruited from Center II as an external validation cohort for the nomogram. The performance of the models was assessed using methods such as the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).

Results: The validation set AUC values for the radiomics models assessing CD8⁺, CD163⁺, and αSMA⁺ cells were 0.875, 0.889, and 0.864, respectively. Additionally, the external validation cohort AUC value for the nomogram reaches 0.849 and shows good calibration.

Conclusion: Radiomics models could allow for non-invasive assessment of TME cells from DECT images in ccRCC patients, promising to enhance our understanding and management of the tumor.

Background: Perioperative blood transfusion (BT) is frequent in the treatment of gastric cancer (GC), but its effects on the prognosis of GC remains controversial. In this study, we aimed to further confirm the relationship of perioperative BT with GC overall survival and to evaluate the predictive value of microRNA-338-3p (miR-338-3p) for the prognosis of GC patients who received perioperative BT.

Methods: Clinical data and serum samples were collected and analyzed from 246 patients with GC. Five-year follow-up survival information was assessed by Kaplan-Meier survival analysis. miR-338-3p relative expression was assessed by RT-qPCR, and its relationship with the prognosis of GC patients, who received perioperative BT, was evaluated using Kaplan-Meier curves and Cox regression analysis.

Results: GC patients received perioperative BT had poor 5 year survival than those without BT. In patients received BT, miR-338-3p expression was higher in survival cases than died population and high miR-338-3p was independently associated with better overall survival prognosis.

Conclusion: Perioperative BT is related with poor prognosis in GC patients and miR-338-3p may be a prognostic biomarker for GC patients received perioperative BT. BT in perioperative GC patients should be cautious, especially for those with low levels of miR-338-3p.