Cancers最新文献

Background/objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. The classic variant (cPTC) is characterized by indolent behavior and excellent prognosis. However, rare subtypes of PTC most often exhibit adverse clinical behavior. The aim of the study was to assess the aggressiveness of rare variants of PTC by analyzing clinicopathological characteristics (CPCs) and survival outcomes.

Methods: We analyzed 80 patients with rare PTC variants treated between 2009 and 2019 who were compared with cPTC and matched with a control group for age and tumor size. The variants were categorized into high-risk (HRV: tall cell, diffuse sclerosing, columnar cell, and hobnail variants), intermediate-risk (IRV: solid variant (SV)), and low-risk (LRV: oncocytic (OV) and Warthin-like (WLV)) variants. Different CPCs (capsule and blood vessel invasion, lymphonodal metastases, microscopic and macroscopic extrathyroid extension, multifocal and bilateral presentation) and survival outcomes-overall (OS), disease-specific (DSS), and disease-free survival (DFS) were compared.

Results: HRVs exhibited significantly more aggressive CPCs and worse OS, DSS, and DFS compared to cPTC (p < 0.001). IRVs showed no significant difference in CPCs or survival outcomes compared to cPTC. LRVs showed excellent survival but were associated with several unfavorable CPCs. Multivariate analysis identified classification in HRVs as the only independent predictor of recurrence (p = 0.014).

Conclusions: Tumors in the HRV group should retain their status as aggressive PTC variants due to unfavorable behavior and poorer prognosis. SVs, despite earlier assumptions, do not exhibit aggressive characteristics. Although the OV and WLV have similar survival to cPTC, their potential for adverse CPCs requires caution.

(1) Background: Advance-stage endometrial cancer is a rare disease that encompasses a heterogeneous group of patients. Primary surgery is the treatment of choice, while neoadjuvant chemotherapy (NACT) seems to be an alternative option for inoperable frail patients. The aim of this study was to identify possible prognostic factors for advance-stage endometrial cancer patients. (2) Methods: We retrospectively analyzed the records of patients with endometrial cancer that underwent surgery in the 1st Department of Obstetrics-Gynecology from 2012 to 2023. Patients with advance-stage disease (FIGO stage III-IV) were included, while those with incidental microscopic lymph node metastases after staging lymphadenectomy were excluded. (3) Results: The population of this study consisted of 89 women. Patients were obese, with moderate comorbidities and a median age of 64 years old. The majority of them (75.3%) had FIGO stage IIIC disease, while one-fourth (24.7%) presented with peritoneal metastases (FIGO stage IV). Most patients had endometrioid, high-grade tumors, with substantial lymphovascular space invasion (LVSI) and deep myometrial invasion. Complete gross resection was achieved in 92.1% of the patients. NACT was administrated in 14.6% of the population. Deep myometrial invasion and non-endometrioid histology were recognized as independent prognostic factors for worse PFS, but no association was found for OS. Concerning survival rates, the median progression-free (PFS) and overall (OS) survival were 44 and 70 months, respectively. (4) Conclusions: Myometrial invasion and histological subtypes seem to affect the recurrence rate of advanced endometrial cancer patients. NACT could likely be an alternative for primarily inoperable and frail patients, but does not appear to alter survival rates.

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence on pregnancy after early HR+ breast cancer, with particular emphasis on prospective data from the POSITIVE trial. We examine the safety of temporary endocrine therapy interruption, the impact of assisted reproductive technologies (ART) in achieving pregnancy, breastfeeding feasibility and impact, hormonal predictors of fertility, pregnancy outcomes and considerations for special populations, including BRCA mutation carriers. Retrospective studies have suggested no adverse survival impact associated with pregnancy after breast cancer. The POSITIVE trial provides prospective evidence that temporary interruption of endocrine therapy to attempt pregnancy does not increase short-term recurrence risk in selected patients. Approximately three-quarters of participants achieved pregnancy. Fertility preservation and ART were commonly used and were not associated with worse short-term oncologic outcomes. Biomarkers such as anti-Müllerian hormone offer supportive but imperfect prediction of fertility potential. Breastfeeding was feasible for many women and did not adversely affect breast cancer outcomes. Available data among BRCA mutation carriers are reassuring but largely observational. Current evidence supports the safety and feasibility of pregnancy after early HR+ breast cancer in carefully selected patients. However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making.

Background: MYC dysregulation is frequent in ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy without precision therapy. Fatty acid synthase (FASN) expression and lipid metabolism are commonly perturbed in high-MYC-expressing tumors; however, the role of MYC and FASN in the coregulation of lipid biosynthesis and tumorigenesis in SebCA is unknown. Methods: The aim of this study was to characterize the effects of FASN inhibition on MYC expression, oncogenic processes, and lipid profiles in vitro, using non-neoplastic human Meibomian gland epithelial cells (HMGECs) and three primary SebCA cell lines, and in vivo, utilizing a conditionally MYC-overexpressing mouse model. Results: FASN inhibition reduced cell viability, proliferation, and clonogenicity and altered the saturation profile of fatty acids across multiple lipid classes. The relative saturation of ceramides was the most variable between treatment conditions. MYC overexpression in the murine Meibomian gland promoted proliferation while suppressing sebaceous differentiation. Subsequent topical FASN inhibition further reduced sebaceous differentiation, attenuated PLIN2 expression, and induced apoptotic cell death. Conclusions: Collectively, these findings suggest that MYC expression in SebCA is responsive to FASN inhibition. Pharmacologic targeting of FASN reveals a metabolic vulnerability that may serve as a target for future therapeutic development.

Background/objectives: Relapsed or refractory follicular lymphoma (rrFL) remains difficult to treat in elderly or frail patients who cannot tolerate standard-dose immuno-chemotherapy as well as novel therapies. Metronomic chemotherapy (mCHEMO) may offer sustained antitumor activity with reduced toxicity. This study assessed the clinical activity and safety of R-DEVEC or R-DEVEC-light in rrFL patients following lenalidomide discontinuation or ineligibility.

Methods: Data from the ReLLi Lymphoma Registry (2013-2025) were retrospectively analyzed. Eligible patients had rrFL after ≥1 prior therapy and initiated mCHEMO at least six months before data cutoff. Thirteen patients received DEVEC or the etoposide-free DEVEC-light regimen; all but one also received rituximab. Responders received maintenance vinorelbine, low-dose prednisone, and rituximab, followed by vinorelbine-only maintenance until progression or intolerance. Responses were assessed by CT after cycle two and PET/CT at completion of six induction cycles.

Results: median age was 77 years (range 58-92); most patients were frail and had advanced disease. At the end of induction, 84% achieved remission (46% CR, 38% PR), with three PR converting to CR during maintenance. After a median follow-up of 27 months, the PFS was 42% (95CI 15-69%) and the OS 73% (95CI 47-100%). A transformation occurred in one patient; the main toxicity was grade 3 neutropenia (31%). DEVEC-light showed improved tolerability versus full DEVEC, with manageable infections and rare discontinuations.

Conclusions: Metronomic R-DEVEC-light is a feasible and effective disease-controlling strategy for frail, heavily pretreated rrFL patients who do not tolerate lenalidomide and are excluded from modern therapies. This schedule warrants further prospective evaluation and exploration in combination with targeted agents.

Background: The aim of this study was to evaluate the effectiveness of bevacizumab in advanced cervical cancer (CC) patients using nationwide data after its inclusion in South Korea's National Health Insurance (NHI), considering various clinicopathologic factors. Methods: This retrospective study analyzed 3869 advanced CC patients from South Korea's cancer registry (2012-2019), alongside claims and death records (2012-2021). Among these 2792 patients diagnosed after bevacizumab's NHI inclusion (August 2015), survival outcomes were compared between those receiving bevacizumab with platinum-based chemotherapy (n = 1787, 64.0%) versus chemotherapy alone (n = 1005, 36.0%). Overall survival (OS) was assessed using Cox proportional hazard regression with inverse probability of treatment weighting. Results: Following NHI coverage of bevacizumab, median OS increased from 1.5 to 2.5 years, and the 5-year OS rate increased from 25.6% to 41.4% (weighted hazard ratio [wHR], 0.63; 95% confidence interval [CI], 0.60-0.67). Among patients receiving bevacizumab, median OS was 2.6 years compared to 2.2 years for those not receiving bevacizumab, with 5-year OS rates of 42.0% and 40.2%, respectively (wHR, 0.84; 95% CI, 0.78-0.90). Subgroup analyses revealed that bevacizumab was associated with significantly better OS in patients with prior concurrent chemoradiation therapy (CCRT) history (wHR, 0.67; 95% CI, 0.61-0.75), regardless of histologic subtype (squamous cell carcinoma [SCC]: wHR, 0.69 [95% CI, 0.61-0.78] vs. non-SCC: wHR, 0.66 [95% CI, 0.55-0.79]). Conclusions: The national investment in the implementation of bevacizumab was associated with favorable survival outcomes in advanced CC patients. Particularly, bevacizumab showed pronounced survival benefit for patients with prior CCRT history, regardless of histologic subtype.

Quiescin sulfhydryl oxidase 1 (QSOX1) is a disulfide bond-forming enzyme with both disulfide isomerase and oxidoreductase activities. It plays an important role in protein folding, stability, and secretion. Growing evidence demonstrates that QSOX1 is upregulated in multiple cancer types and influences key behaviors of cancer cells, including proliferation, migration, invasion, and metastasis. Elevated QSOX1 expression is also associated with tumor malignancy and disease relapse. However, the molecular mechanisms by which QSOX1 drives cancer progression remain incompletely understood. In this review, we summarize current knowledge of QSOX1 expression and regulation in cancer, discuss its functional roles, and highlight key unanswered questions to warrant further investigation.

Cachexia is a muscle-wasting syndrome that has a 50% overall prevalence across all cancers and is known to affect both survival and quality of life. However, its measurement, classification, and impact in individuals with primary brain tumors is unclear. Now, evidence is emerging that cachexia has a direct effect on both clinical and physical function outcomes for individuals with glioblastoma multiforme (GBM). Herein, we outline a standardized approach to the diagnosis of cachexia in the GBM population, incorporating several available clinical tools to ensure the link between clinical prognosis and quality of life.

Ovarian cancer remains the most lethal gynaecological malignancy primarily due to late-stage diagnosis, high recurrence rate, and limited treatment efficacy. Current diagnostic tools, including imaging and serum markers, lack sufficient sensitivity and specificity for early detection. Increasing evidence highlights the critical role of myeloid-derived immune cells within the tumour microenvironment in shaping ovarian cancer progression and therapy response. Monocytes and their derivatives are central regulators of immune suppression, chemoresistance, and metastatic dissemination in ovarian tumours. Their recruitment and polarisation are governed by several signalling pathways offering promising therapeutic targets. Strategies including monocyte depletion, TAM reprogramming, MDSC maturation, DC vaccines, and their synergistic use with chemotherapy or immune checkpoint inhibitors are being explored to restore anti-tumour immunity in ovarian cancer. Parallel to therapeutic potential, the lymphocyte-to-monocyte ratio and its reciprocal monocyte-to-lymphocyte ratio have also emerged as potential accessible and cost-effective prognostic tools that predict disease aggressiveness and survival in ovarian cancer. This review features the diagnostic, prognostic, and therapeutic significance of monocytes and their derivatives in ovarian cancer management and highlighting new opportunities for next-generation immunomodulatory therapies.

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental studies across various tumor types. The method consists of a first irradiation, performed before nano-assemblies administration. This is intended to sensitize the tumor by inducing a hyperthermic effect, leading to increasing blood supply, enhancing endothelial damage/permeation and inflammatory activation, with the final goal of improving the diffusion/retention of nano-assemblies in the tumor. Subsequently, the second microwave irradiation follows the injection in the hepatic artery and diffusion in the tumor of the activated nano-assemblies, to further determine a strong, but localized and focalized hyperthermic action. Nano-magnetic assemblies for hyperthermia accomplish the proposed chemo-thermal delivery, i.e., act per se on the tumor and also destabilize co-administered assemblies of nanoparticles loaded with chemotherapeutics, which would be consequently released locally in the most efficient way. This article aims to demonstrate the efficacy of this therapeutic approach in a rat liver model and its potential applicability in patients with liver tumors. Methods: Adult male Wistar rats were used to obtain liver samples, which were divided into three groups, each receiving a different hyperthermia protocol in terms of temperature (41-45 °C), duration, and co-administration of nanoparticles. Results: The most suitable exposure temperature for rat liver appears to be 42 °C, resulting in vacuolar degeneration lesions at the focal level. The effects of thermal conditioning do not appear to be homogeneous in the tested liver, and the controlling environment and methodology should be improved in the near future. The level of hepatic inflammation, as indicated by elevated interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, appears negligible under the current hyperthermia protocol. Conclusions: Two-stage microwave hyperthermia using magnetic nanoparticles is a promising therapeutic modality for liver cancer, with promising results from animal studies opening the way for further research in humans.