Clinical & Translational Oncology最新文献

Background: In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction.

Methods: We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system.

Results: The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups.

Conclusion: The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.

Purpose: The healthcare system contributes approximately 5% of global greenhouse gas emissions, yet the environmental impact of radiotherapy treatments remains inadequately assessed.

Material and methods: We selected all breast cancer patients (1959 patients) treated with adjuvant radiotherapy between 2015 and 2023 in one institution. We analyzed the CO₂ emissions associated with travel. We also selected 60 patients randomly to analyze treatment-associated carbon emissions. We compared three different fractionation schemes: normofractionation (25-30 fractions, fx), hypofractionation (15-18fx), and ultra-hypofractionation (5-6fx).

Results: Our study revealed a significant reduction in carbon emissions within the 5-fractions group compared to the 15-fractions group (26.69kg vs 57.13kg, p < 0.001), saving approximately the CO₂ emissions associated with the electricity consumption of an average Spanish household for 12 days, or the emissions of a passenger flying from Madrid to Barcelona.

Conclusion: Most of the carbon footprint of radiotherapy is due to travel. Hypofractionation could be an appropriate solution to protect the environment.

Introduction: Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs.

Materials and methods: From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples.

Results: In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection.

Conclusion: SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

Objectives: The role of tumor-associated macrophages (TAMs) in cervical cancer (CC) remains controversial. Here, we report a meta-analysis of the association between TAMs infiltration and clinical outcomes.

Methods: PubMed, Embase, Web of Science, and CNKI were searched systematically from inception until December 20, 2023. Studies involving TAMs and prognosis, clinical, or pathological features were included. Quality assessments of the selected studies were assessed. The fixed-effect or random-effects model, standard mean difference (SMD), odds ratios (OR), or hazard ratios (HR) with 95% confidence intervals (CIs) were used as the effect size estimate.

Results: 26 eligible studies with 2,295 patients were identified. Our meta-analysis revealed that TAMs were overexpressed in CC (OR = 12.93, 95% CI = 7.73-21.61 and SMD = 1.58, 95% CI = 0.95-2.21) and that elevated TAM levels were strongly associated with lymph node metastasis (LNM) (SMD = 0.51, 95% CI = 0.90-2.01) and FIGO stages (SMD = 0.46, 95% CI = 0.08-0.85). Subgroup analysis indicated a significant positive correlation between LNM and TAMs density in tumor stroma, but not in cancer nests (SMD = 0.58, 95% CI = 0.31-0.58). Furthermore, in early stage, a stronger correlation exists between LNM and TAM density (SMD = 1.21, 95% CI = 0.75-1.66). In addition, it revealed that patients with high TAMs expression had poorer overall survival (OS) (HR = 2.55 95% CI = 1.59-4.07) and recurrence-free survival (RFS) (HR = 2.17, 95% CI = 1.40-3.35).

Conclusions: Our analyses suggest that a high density of TAMs predicts adverse outcomes in CC.

Background: Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC).

Methods: We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines.

Results: PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells.

Conclusion: Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC.

Objective: The survival benefit of first-line treatment with bevacizumab in advanced ovarian cancer patients are multifaceted. In our study, we aimed to identify potential markers of bevacizumab efficacy to help predict which patients would experience survival benefits.

Methods: This was a retrospective analysis of 114 patients examined from January 1, 2015, to March 1, 2023, and data on clinical, biological, and imaging variables, such as ascites, serum LDH, and CA125, were extracted from electronic medical records. We performed a correlation analysis and principal component analysis to investigate correlations among variables and reduce their dimensionality. Then, univariate and multivariate Cox proportional hazards regression analyses were used to identify the predictors of progression-free survival.

Results: Favorable KELIM score (≥ 1, HR 0.376, 95% CI [0.202-0.700], p = 0.002), which indicated better chemosensitivity, and lower LDH levels (≤ 210 U/L, HR 38.73, 95% CI [6.108-245.6], p < 0.001) were found to be independent predictors of a treatment benefit with bevacizumab in patients with advanced ovarian cancer. Regardless of LDH level, patients with favorable KELIM scores had a higher progression-free survival (PFS) benefit (p = 0.18). Among patients with unfavorable KELIM scores, those with higher LDH levels had the lowest PFS benefit (median: 11.5 months, p = 0.0059).

Conclusion: Patients with poor chemosensitivity and low LDH levels are more likely to benefit from first-line bevacizumab treatment. The combination of the two markers can be a helpful predictor of patients who are most likely to benefit from treatment and a guide for treatment decisions-making. Retrospectively registered: 2020-MD-371, 2020.10.12.

Pancreatic cancer has doubled over the previous two decades. Routine therapies are becoming incredibly resistant and failing to compensate for the burden caused by this aggressive neoplasm. As genetic susceptibility has always been a highlighted concern for this disease, identifying the molecular pathways involved in the survival and function of pancreatic cancer cells provides insight into its variant etiologies, one of which is the role of AMPK. This regulating factor of cell metabolism is crucial in the homeostasis and growth of the cell. Herein, we review the possible role of AMPK in pancreatic cancer while considering its leading effects on glycolysis and autophagy. Then, we assess the probable therapeutic agents that have resulted from the suggested pathways. Studying the underlying genetic changes in pancreatic cancer provides a chance to detect and treat patients suffering from advanced stages of the disease, and those who have given up their hope on conventional therapies can gain an opportunity to combat this cancer.

Background: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations.

Methods: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups.

Results: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups.

Conclusions: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

Background: This study examines lung cancer incidence in Spain (1990-2019) through age-period-cohort (A-P-C) analysis and Global Burden of Diseases (GBD) data, unravelling the complex interplay of age, period, and birth cohort in shaping these trends.

Methods: Utilizing GBD and Spanish population data, the study calculates age-standardized incidence rates (ASIRs) and employs Joinpoint analysis to identify significant trends. A-P-C analysis dissects the individual effects of age, calendar period, and birth cohort on incidence patterns.

Results: Between 1990 and 2019, almost 738,000 cases of lung cancer were diagnosed in Spain, with an average annual increase of 1.7%. The ASIR of lung cancer in Spain from 1990 to 2019 showed a sustained upward trend in women (Average Annual Per cent Change: 2.5%, P < 0.05), reaching 23.3 cases per 100,000 in 2019, whilst men experienced a significant decrease in incidence rates (AAPC: -0.6%, P < 0.05), falling to 108.9 in 2019. The male-to-female incidence ratio decreased from 12.2 in 1992 to 4.9 in 2019. Joinpoint analysis identified distinct periods for both sexes, with men showing stability, decline and then a significant decrease, whereas women showed an initial increase followed by a decrease. The longitudinal age curves showed a consistently higher incidence risk in men, peaking in the 80-84 age group. Male cohorts since the 1920s showed a decreasing relative risk, whereas women showed fluctuations in risk over time.

Conclusion: Lung cancer rates are falling in Spain, especially amongst men, due to lower smoking rates. The gender gap is closing, but prevention targeted at women is needed. Tighter tobacco control and research into other risk factors are essential. Understanding the long-term effects of smoking and early exposure is key to better prevention and treatment in Spain.