Frontiers in Oncology最新文献

Introduction: Oral cavity cancer (OCC), primarily oral squamous cell carcinoma (OSCC), is a growing concern in Europe, particularly among younger populations. Preventable lifestyle factors and social determinants of health contribute significantly to the disease burden. Limited access to healthcare and delayed diagnoses further complicate treatment and reduce survival rates.

Methods: This systematic literature review adhered to PRISMA guidelines to explore trends in OSCC epidemiology, etiology, diagnosis, treatment, and survival across Europe. A comprehensive search strategy using PubMed, GLOBOCAN data, and the EUROCARE-5 study identified relevant articles focusing on human populations in Europe with a primary interest in OSCC epidemiology. Only peer-reviewed publications in English with full-text access were included.

Results: This study investigated the burden of OSCC across Europe, revealing variations in incidence, mortality, and prognosis. Eastern and Central Europe displayed the highest burden. Males exhibited a significantly higher risk compared to females. Age-related disparities existed in life expectancy and time to achieve favorable outcomes. HPV emerged as a growing risk factor for oropharyngeal cancer. Public health strategies should target modifiable risk factors and improve early detection.

Conclusion: This review reveals concerning disparities in European OSCC. Region, sex, and age all influence burden and prognosis. Future research should focus on controlling risk factors and personalized medicine to optimize treatment. This will lead to a Europe with reduced OSCC incidence and demonstrably better patient outcomes.

Penile squamous cell carcinoma (PSCC) is a largely neglected condition, predominantly affecting underdeveloped regions, and is associated with risk factors such as low socioeconomic status, phimosis, and human papillomavirus (HPV) infection. Unlike other urogenital cancers, its pathophysiology and therapeutic targets remain poorly understood, particularly regarding the immune response to the tumor microenvironment. This study aims to investigate immune cell infiltration profiles, dendritic cell maturation, and lymphocyte apoptosis in both HPV-positive and HPV-negative PSCC. Clinical and histopathological data, along with peripheral blood and tumor tissue samples, were collected from 30 patients (66.6% were HPV-positive and 33.3% HPV-negative), with an additional 19 healthy donors serving as controls. Tumor-infiltrating immune cells were analyzed following enzymatic digestion of tumor tissue, enabling detailed phenotypic characterization. A simulated tumor microenvironment was created using supernatants derived from primary cultures of HPV-positive PSCC tumors. Peripheral blood mononuclear cells were isolated and differentiated into dendritic cells (Mo-DCs) for further phenotyping and lymphoproliferation assays. Lymphocytes from healthy donors and patients were exposed to tumor culture supernatants to evaluate apoptosis induced by the tumor microenvironment. Results showed that HPV-positive tumors exhibited lower T lymphocyte frequencies compared to HPV-negative tumors. Additionally, patients infected with high-risk HPV demonstrated reduced maturation rates of Mo-DCs and decreased expression of co-stimulatory molecules on these cells compared to healthy donors. Furthermore, Mo-DCs from hrHPV-positive patients showed impaired lymphoproliferation capacity relative to controls, while HPV-negative patients exhibited a trend towards reduced lymphoproliferative ability. Regarding the simulated tumor microenvironment, lymphocytes from healthy donors underwent apoptosis, contrasting with patients' lymphocytes, which showed increased viability when cultured with tumor supernatants. These results underscore the impact of HPV infection on T lymphocyte infiltration, Mo-DC maturation, and lymphocyte survival in PSCC, offering critical insights for advancing our understanding of the tumor microenvironment and guiding the development of immunotherapy strategies.

Introduction: Local treatment can be distressful to breast cancer patients. We aimed to evaluate how different types of local treatment impact the quality of life of patients.

Methods: In this retrospective cohort study, one-year postoperative Breast-Q Satisfaction with Breasts scores were used as a surrogate for Quality of Life. Linear regression was used to estimate the impact of breast conservation, oncoplastic surgery, breast reconstruction, and radiation therapy on Breast-Q scores. All analyses were adjusted for multiple covariates.

Results: Of the 711 eligible patients, 349 female patients answered both the pre- and one-year postoperative questionnaires and were included in the final analysis. In total, 237 (68%) patients underwent breast-conserving surgeries and 112 (32%) underwent mastectomies. All mastectomy patients underwent breast reconstruction and 176 (74% of breast-conserving surgeries) underwent concomitant oncoplastic surgery. After multivariate analysis, mastectomy was associated with lower scores compared to breast-conserving surgery (-21.3; 95%CI: -36.2, -6.4, p=0.005), and oncoplastic surgery was associated with higher scores (9.2; 95%CI: 0.8, 17.6, p=0.032). There was a tendency for higher scores with the use of flaps in breast reconstruction and a tendency for lower scores with the use of radiation therapy, but the difference was not significant.

Conclusions: Breast-conserving surgery is associated with better quality of life than mastectomy. Additionally, oncoplastic surgery is associated with a better quality of life than standard breast-conserving surgery. Patients should be counseled whenever multiple options for surgery are possible, and efforts should be made to increase the availability of trained surgeons in oncoplastic techniques.

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease.

Methods: We evaluated whether bivalent single domain antibodies (VHHs) that link Vδ2-TCR specific VHHs with different affinities could support Vγ9Vδ2 T-cell expansion and could be incorporated in a bispecific engager format when additionally linked to a tumor antigen specific VHH.

Results: Bivalent VHHs that link a high and low affinity Vδ2-TCR specific VHH can support Vγ9Vδ2 T-cell expansion. The majority of Vγ9Vδ2 T-cells that expanded following exposure to these bivalent VHHs had an effector or central memory phenotype and expressed relatively low levels of PD-1. Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice.

Conclusion: By enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells.

Objectives: Differences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations.

Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach.

Results: A total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFS-HRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race.

Conclusion: Women or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics.

Systematic review registration: https://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.

Background: Pancreatic cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors.

Methods: PC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection.

Results: The number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73-1.52) and 1.00% (95% CI, 0.63-1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032.

Conclusions: It was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country's future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important.

[This corrects the article DOI: 10.3389/fonc.2023.1136376.].

Objective: This study aimed to explore the potential effects between various human plasma lipidomes and endometrioid endometrial cancer (EEC) by using Mendelian randomization (MR) methods.

Methods: This study designated a total of 179 human plasma lipidomes from the genome-wide association study (GWAS) database as the exposure variable. An EEC-related dataset from the GWAS (GCST006465) served as the outcome variable. MR analyses used the inverse variance-weighted method (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods for regression calculations, accounting for possible biases induced by linkage disequilibrium and weak instrument variables. Any lipidomes failing to pass heterogeneity and horizontal pleiotropy tests were deemed to lack significant causal impact on the outcome.

Results: The results of IVW analysis disclosed that a variety of human plasma lipidomes (n = 15) exhibited a significant causal effect on EEC (p < 0.05). A subset of these lipidomes (n = 13) passed heterogeneity and horizontal pleiotropy tests, which demonstrated consistent and viable causal effects (p < 0.05) including glycerophospholipids, glycerolipids, and sterols. Specifically, phosphatidylcholine (odds ratio [OR]: 1.065-1.129, p < 0.05) exhibited a significant positive causal effect on the occurrence of EEC. Conversely, sterol ester (OR = 0.936, p = 0.007), diacylglycerol (OR = 0.914, p = 0.036), phosphatidylcholine (OR: 0.903-0.927, p < 0.05), phosphatidylethanolamine (OR = 0.907, p = 0.046) and triacylglycerol (OR: 0.880-0.924, p < 0.05) showed a notable negative causal association with EEC, suggesting their inhibitory effects on the EEC occurrence.

Conclusions: The study revealed that human plasma lipidomes have complex impacts on EEC through Mendelian randomization. This indicated that the diversity of structural changes in lipidomes could show different effects on subtypes and then affect EEC occurrence. Although these lipids had the potential to be promising biomarkers, they needed to be further clinically validated nevertheless.

Introduction: Surgical site infections (SSI) are one of the most common complications after extensive sarcoma resections and represent a daily challenge. SSI occur in up to 50% of cases particularly in the peripelvic area. One possible approach to reduce infection rate is perioperative antibiotic prophylaxis. The aim of this study therefore was to investigate the influence of perioperative antibiotic prophylaxis on the infection rate and the possible influence of location-specific antibiotic prophylaxis with ampicillin/sulbactam.

Methods: This monocentric retrospective study included 366 patients who underwent sarcoma resections in the groin, proximal thigh, or gluteal region. All patients were operated on by 2 surgeons after neoadjuvant pretreatment if necessary. 3 groups of patients were defined. Group 1: In 60.4% of all cases, antibiotic prophylaxis was administered with cephalosporins (also clindamycin in case of penicillin allergy). Group2: In 9.8% of cases, ampicillin/sulbactam was used. Group 3: 29.8% of patients did not receive any antibiotic prophylaxis.

Results: In 31.1% of treated cases, antibiotic therapy was prolonged due to extended tumor resections. Postoperative infections occurred in 23.2% (85 cases), in 77 cases within the first 90 days (on average after 20 days). The median operating time, blood loss was higher, and tumor size were significantly larger in cases with infections, compared to patients without infection. In group 1 and 2 with perioperative single-shot prophylaxis, infection occurred in 24.1% of cases, compared to 13.5% of cases without prophylaxis (group 3) (p= 0.032). In the patients with prolonged antibiotic therapy, infection occurred in 31.6% of cases, compared to 16.3% of cases without prolongation (p< 0.001). In the group 2, infection occurred in 19.4% of cases compared to 24.9% of cases in the group 1 (p= 0.479). In the multivariate analysis, surgery time longer 80 min, blood substitution, neoadjuvant radio- and chemotherapy proved to be a risk factor for SSI.

Discussion: Region adapted perioperative antibiotic prophylaxis may reduce the risk of infection after extended sarcoma resection in the peripelvic area. However, the particular bacterial spectrum of this anatomic region should be taken into account when deciding which antibiotics to use.