Search Results (3,141)

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article

Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with the HERO RT de-escalation trial (NRG-BR008). Materials and methods: We queried the National Cancer Database for patients with early-stage HER2-positive invasive breast carcinoma treated with BCS and systemic therapy, stratified into HERO trial-aligned cohorts: Arm 1 (adjuvant systemic therapy) vs. Arm 2 (neoadjuvant systemic therapy, pathologic complete response). Within each cohort, patients receiving adjuvant RT were compared with those omitting RT. In the primary analysis, patients were propensity score matched (PSM) on demographics, diagnosis years, tumor characteristics, and trial stratification variables. Inverse probability of treatment weighting (IPTW) was additionally performed as a sensitivity analysis. Overall survival was evaluated using Kaplan–Meier, Cox regression, and restricted mean survival time (RMST). Results: In Arm 1 (818 patients, 94 deaths), 5-year OS was 96.9% with RT vs. 88.0% without RT, and 10-year OS was 94.3% vs. 68.5% (log-rank p < 0.001). RT omission was associated with higher mortality in the PSM Cox model (HR, 4.78; 95% CI, 2.84–8.02; p < 0.001), with an RMST advantage favoring RT of +2.86 months at 5 years and +12.55 months at 10 years (p < 0.001). In Arm 2 (176 patients, 10 deaths), 5-year OS was 97.6% with RT vs. 91.1% without RT, and OS at 107 months was 94.8% vs. 91.1% (log-rank p = 0.13). RT omission was not statistically significant in the PSM Cox model (HR, 3.40; 95% CI, 0.82–14.05; p = 0.09), though RMST favored RT (+1.83 months at 5 years, p = 0.004; +3.91 months at 107 months, p = 0.03). IPTW analyses were directionally consistent in Arm 1 (HR, 3.26; 95% CI, 2.52–4.21; p < 0.001) and inconclusive in Arm 2 (HR, 1.78; 95% CI, 0.80–3.95; p = 0.16). Conclusions: In this HERO-aligned national cohort, RT omission was associated with inferior OS in patients treated with adjuvant systemic therapy after BCS. Findings in the neoadjuvant pCR cohort were imprecise and hypothesis-generating. Given the retrospective registry design, lack of recurrence-specific endpoints, and potential residual confounding, results should not be interpreted as causal but support continued RT use outside prospective de-escalation trials. Full article

Despite the introduction of novel therapeutic options, the prognosis of advanced endometrial cancer remains poor. In recent years, increasing attention has been directed toward the molecular characterization of endometrial cancer. However, data specifically focusing on advanced-stage disease are still limited. In our single-center, retrospective, exploratory study with a limited sample size, we analyzed 32 patients with advanced or recurrent endometrial cancer treated at the Modena Cancer Center. Comprehensive molecular profiling was performed to assess DNA mutations, copy number variations, and RNA expression. We characterized the molecular landscape of this cohort, evaluated selected genomic alterations across predefined clinical subgroups, and explored their association with overall survival. Consistent with previous reports, a high prevalence of PTEN and PIK3CA mutations were observed. Patients experiencing relapse more than six months after diagnosis were more likely to harbor CTNNB1 mutations. KRAS mutations were more frequently detected in younger patients and in those with endometrioid histology, whereas PPP2R1A and TP53 mutations were enriched in tumors with non-endometrioid histology. Notably, CTNNB1 mutations were associated with a favorable prognostic impact, while KRAS mutations correlated with poorer overall survival. Our findings underscore the need for further investigation into the molecular landscape of advanced endometrial cancer, particularly in the context of therapeutic implications. Combinatorial treatment strategies targeting specific molecular alterations, such as KRAS, in combination with other targeted agents or therapeutic approaches, warrant further exploration. Full article

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. Full article

Background/Objectives: This study seeks to evaluate the clinical characteristics of newly diagnosed male breast cancers within the traditionally underserved Bronx population at risk for poorer health outcomes. Methods: We retrospectively searched our database for male patients who presented for mammographic evaluation between 1 January 2016 and 1 October 2024. The primary outcomes were the prevalence of biopsy-proven male breast cancer and its association with gynecomastia and TNM stage at diagnosis. Clinical data, including TNM staging, receptor status, risk factors, and patient demographics, were recorded for patients with biopsy-proven breast cancer based on biopsy results. Two dedicated breast imagers retrospectively evaluated mammograms of these patients to determine by consensus the presence of gynecomastia. Analyses were descriptive in nature. Results: During the study period, 423 screening mammograms and 1775 diagnostic mammograms were performed on male patients. Twenty-six male patients with biopsy-proven breast cancer were identified (two were bilateral and four were multifocal). In total, 69% of our male breast cancer patients (18 out of 26) demonstrated gynecomastia, which was similar across demographic groups, ranging from 63 to 75%. Out of the three patients with Stage 4 disease, two were Black and one was White. Stage 3 or higher disease was seen in 29% of our Black patients, 12% of our White patients, and 0% of our Hispanic patients. Conclusions: Male breast cancer in this Bronx population was frequently associated with gynecomastia and showed notable demographic disparities. Black patients presented with more advanced disease than other demographic groups. These descriptive findings highlight areas of further investigation and may help inform future outreach and early detection efforts in high-risk, underserved communities. This retrospective, single-institution analysis was limited by a small sample size and did not include formal statistical testing; therefore, the findings are descriptive and warrant validation with larger cohorts. Full article

A group of experts of different specialties involved in the care of prostate cancer (PCa) patients participated in the ENFOCA2 project, promoted by the Spanish Oncology Genitourinary Group (SOGUG), with the aim to review, discuss, and summarize current relevant aspects related to screening, diagnosis, imaging, risk-based approach, and molecular characterization of PCa. A multidisciplinary team (MDT) approach is essential to ensure that patients receive evidence-based care, promoting shared decision-making, and tailoring treatment to the patient’s unique values and preferences. Population-based screening based on risk-stratified algorithms is needed to overcome the limitations of opportunistic screening for detecting clinically significant PCa. Next-generation imaging (NGI) methods, such as prostate-specific membrane antigen (PSMA) PET/CT alone or combined with multiparametric MRI (mpMRI), have a promising role in different scenarios of the diagnostic process due to their high sensitivity. The diagnostic yield of mpMRI should be improved, especially for assessing extraprostatic extension. The use of specific molecular probes as imaging markers for MRI could improve the staging of metastatic disease. Protocols for germline testing developed by international societies, such as the European Association of Urology (EAU) and the National Comprehensive Cancer Network (NCCN), should be adapted at local levels, with BRCA1/2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2, EPCAM, and HOXB13 as the genes to be investigated. Genomic classifier tools help identifying aggressiveness of cancers and aid in personalized treatment decision-making. Joint efforts of multidisciplinary physicians are crucial to improve health outcomes for patients with PCa across the spectrum of this disease. Full article

Background/Objectives: In order to develop a comprehensive understanding of gastric-type endocervical adenocarcinoma (GEA), an increasingly prevalent HPV-independent cervical cancer, we summarized clinicopathological information and performed prognostic analysis. Methods: A total of 182 patients diagnosed with GEA at our center during the period 2014–2025 were included in this study. Nineteen GEA cases, 6 HPV-independent non-GEA cases, 59 HPV-associated usual endocervical adenocarcinoma cases, and 66 squamous cell carcinoma cases from online database were also included. Results: Vaginal bleeding (39.56%) and watery discharge (35.16%) were the most common symptoms. As many as 21.43% of patients had no specific complaints, and 80% of GEA showed no distinct mass through gynecological examination. A total of 64% of GEA were stage IIB–IV at diagnosis, with a 5-year survival of 41% versus 85% for stage I–IIA (p < 0.05). The rate of lymphovascular space invasion (LVSI), lymph node metastasis, and ovarian metastasis were 49.64%, 42.00%, and 29.29%, respectively. The 5-year survival and recurrence rates after primary therapy were 57% and 23%, respectively. For GEA treatment, surgery might be associated with improved overall survival for the population at stage III–IV. Survival analysis identified deep infiltration depth (≥2/3), a maximum diameter of the tumor (MDOT) of ≥3 cm, and ovary metastasis as potential indicators of worse OS and PFS for whole patients. Additionally, ovary metastasis indicated poor PFS and OS for stage I–II. Genomic information TP53 mutation, PTEN deletion and STK11 mutation might be the most prevalent genomic alterations. Conclusions: These findings indicated GEA as an aggressive cervical cancer, with high rate of lymph node metastasis, high recurrence rate and short 5-year survival. Ovary metastasis reflected advanced disease burden and surgery might be associated with improved survival in advanced stage. For genomic information, GEA showed genetic heterogeneity and a low level of genomic instability. Full article

Background: Female patients undergoing radical cystectomy (RC) for bladder cancer have historically presented with more advanced disease and poorer survival outcomes than males. These disparities have been attributed to biological differences, delayed diagnosis, and variations in treatment delivery. Recent data suggest, however, that outcomes may converge when patients are managed in standardized, multidisciplinary, high-volume centers. This study evaluated the influence of gender on perioperative features and oncological outcomes such as disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) at a tertiary uro-oncology center. Methods: We retrospectively reviewed a prospectively maintained database of patients who underwent open or robotic-assisted RC for histologically confirmed urothelial carcinoma between 2014 and 2023 at Guy’s and St. Thomas’ NHS Foundation Trust. Demographic, perioperative, and pathological variables were stratified by gender to assess their association with DFS, DSS, and OS. Results: A total of 887 patients were included: 640 men (72.2%) and 247 women (27.8%), with similar mean age (68.5 vs. 68.1 years) and tumour histology (pure urothelial carcinoma 85% vs. 83%). Men had a higher prevalence of diabetes and chronic kidney disease, but no significant differences were observed in time from referral to surgery (0.93 vs. 1.03 months, p = 0.93), use of neoadjuvant therapy (21.6% vs. 17.3%, p = 0.25), or surgical approach (p = 0.55). Pathological stage distribution was comparable between sexes (pT0–1: 44% vs. 50%; pT2–4: 56% vs. 50%; p = 0.13). Kaplan–Meier analysis revealed no significant gender-related differences in 12-month DFS (77.3% vs. 75.4%, p = 0.20), DSS (85.6% vs. 86.9%, p = 0.56), or OS (81.2% vs. 85.2%, p = 0.70). Conclusion: In this high-volume tertiary center, gender did not independently influence perioperative or survival outcomes following radical cystectomy. These findings suggest that standardized, multidisciplinary management within specialized bladder cancer pathways may mitigate the pathological and survival disparities historically associated with gender. Full article

Lung cancer (LC) remains the leading cause of cancer-related death worldwide, largely due to late-stage diagnosis and the limited performance of current screening strategies. In this preliminary study, headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME/GC-MS) was used to comprehensively characterize the urinary volatilome of LC patients and healthy controls (HCs), with the dual aim of defining an LC-associated volatilomic signature and identifying volatile organic metabolites (VOMs) with discriminatory potential. A total of 56 VOMs spanning multiple chemical classes were identified, revealing a distinct metabolic footprint between groups. LC patients exhibited markedly increased levels of terpenoids and aldehydes, consistent with heightened oxidative stress, including lipid peroxidation, and perturbed metabolic pathways, whereas HCs showed a predominance of sulphur-containing compounds and volatile phenols, likely reflecting active sulphur amino acid metabolism and/or microbial-derived processes. Multivariate modelling using partial least squares-discriminant analysis (PLS-DA, R² = 0.961; Q² = 0.941; p < 0.001), supported by hierarchical clustering, demonstrated robust and clearly separated group stratification. Among the detected VOMs, octanal, dehydro-p-cymene, 2,6-dimethyl-7-octen-2-ol and 3,7-dimethyl-3-octanol displayed the highest discriminative power, emerging as promising candidate urinary biomarkers of LC. These findings provide proof-of-concept that HS-SPME/GC-MS-based urinary volatilomic profiling can capture disease-specific molecular signatures and may serve as a non-invasive approach to support the early detection of LC, warranting validation in independent cohorts and integration within future multi-omics diagnostic frameworks. Full article

Background/Objectives: The COVID-19 pandemic profoundly disrupted gastric cancer care, reducing access to screening, delaying diagnosis, and altering therapeutic pathways worldwide. Beyond clinical challenges, it exposed structural weaknesses in healthcare systems but also accelerated innovation. Methods: We conducted a narrative review supported by a structured literature search (PubMed/MEDLINE, Scopus, Web of Science; 1 January 2014–30 November 2025), with a narrative synthesis of observational studies, registry analyses, and meta-analyses addressing COVID-19–related changes in gastric cancer epidemiology, diagnosis, treatment, vaccination, and telemedicine. A PRISMA-style flow diagram was used to illustrate study selection. Results: Elective endoscopy volumes fell by up to 80%, leading to diagnostic backlogs and increased proportions of advanced-stage gastric cancer. Surgical postponements, modified chemotherapy and radiotherapy schedules, and reduced molecular/genetic testing further compromised outcomes. Conversely, vaccination, telemedicine, capsule endoscopy, and adaptive triage frameworks enabled partial recovery of services. Geographical variations were observed in the recovery of gastric cancer care services, with regions that had established screening infrastructure generally resuming activity more rapidly, whereas others experienced ongoing delays and diagnostic backlogs. Conclusions: This review integrates epidemiological, diagnostic, and therapeutic evidence to demonstrate how COVID-19 redefined gastric cancer care. By highlighting regional disparities and outlining a conceptual model for oncologic resilience, it provides an innovative framework for future crisis preparedness. The lessons of the pandemic—digital health integration, flexible treatment protocols, and international collaboration—represent a foundation for more robust, equitable gastric cancer management in the post-pandemic era. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) remains the seventh most common cancer worldwide, characterized by late-stage diagnosis and poor 5-year survival rates. Oral squamous cell carcinoma (OSCC) is the most prevalent subtype. The identification of robust diagnostic, prognostic, and predictive markers is essential for personalized treatment monitoring. Methods: Following PRISMA and PICO standards, we conducted a comprehensive review of studies published over the past 10 years across PubMed/MEDLINE, Scopus, and Web of Science. The selection process was facilitated by AI-powered tools (Rayyan QCRI), and study quality was assessed using NOS or QUIPS. Results: 34 articles (including meta-analyses and original trials) were identified. Established clinical markers, such as p16-positivity (HR ≈ 0.55) and PD-L1 (CPS), remain significant. However, the molecular landscape is expanding to include high-risk lncRNA signatures (HR ≈ 2.50), immune checkpoints such as TIGIT (HR ≈ 1.85), and genomic alterations, including IL-10 promoter polymorphisms. We highlight that epigenetic silencing of p16 affects only about 25% of patients, while metabolic regulators (e.g., GLUT-1) and protein markers (e.g., MASPIN) offer critical predictive value for therapy response. Conclusions: The diagnostic and predictive paradigm is shifting toward a multi-omic approach that integrates DNA, RNA, proteins, and metabolic indicators. Future clinical use will rely on AI-driven multimarker panels and non-invasive liquid biopsies to enable real-time monitoring and de-escalation of treatment strategies. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. Full article

Effective and transparent medical diagnosis relies on accurate and interpretable classification of medical images across multiple modalities. This paper introduces an explainable multi-modal image analysis framework based on a dual-stream architecture that fuses handcrafted descriptors with deep features extracted from a custom MobileNet. Handcrafted descriptors include frequency-domain and texture features, while deep features are summarized using 26 statistical metrics to enhance interpretability. In the fusion stage, complementary features are combined at both the feature and decision levels. Decision-level integration combines calibrated soft voting, weighted voting, and stacking ensembles with optimized classifiers, including decision trees, random forests, gradient boosting, and logistic regression. To further refine performance, a hybrid class-specific feature selection strategy is proposed, combining mutual information, recursive elimination, and random forest importance to select the most discriminative features for each class. This hybrid selection approach eliminates redundancy, improves computational efficiency, and ensures robust classification. Explainability is provided through Local Interpretable Model-Agnostic Explanations, which offer transparent details about the ensemble model’s predictions and link influential handcrafted features to clinically meaningful image characteristics. The framework is validated on three benchmark datasets, i.e., BTTypes (brain MRI), Ultrasound Breast Images, and ACRIMA Retinal Fundus Images, demonstrating generalizability across modalities (MRI, ultrasound, retinal fundus) and disease categories (brain tumor, breast cancer, glaucoma). Full article