Search Results (2,594)

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

Background/Objective: Early detection of metastatic progression remains a major challenge in precision oncology. Conventional radiological imaging cannot reliably identify micrometastatic disease. Although circulating tumor DNA is promising for minimal residual disease detection, organ-derived response biomarkers reflecting tissue adaptation to secreted factors remain unexplored. We hypothesized that integrating such biomarkers with global laboratory parameters would generate a synthetic variable with improved discrimination for de novo metastasis and mortality. Methods: This prospective observational pilot study enrolled 30 patients (median age 64.4 years; 56.7% female) with heterogeneous solid malignancies. Peripheral blood biomarkers responsive to tumor-secreted soluble factors (n = 11) were quantified using a multiplexed beads Luminex immunoassay. Global analytical parameters (n = 20) were derived from routine laboratory assessments. Hierarchical agglomerative clustering analysis generated two synthetic variables: Stigma (Ϛ) and Qoppa (Ϙ). Receiver operating characteristic curve analysis, Kaplan–Meier survival analysis, and Cox regression were used to evaluate the performance. Results: Qoppa demonstrated acceptable discriminatory performance for de novo metastasis (AUC = 0.78). For mortality prediction, performance varied by disease status (overall AUC = 0.78): superior in non-metastatic patients (AUC = 0.98) but negligible in those with baseline metastases. Kaplan–Meier analysis confirmed significant survival differences (p = 0.042 overall survival; p = 0.024 for metastasis-free survival in the non-metastatic subgroup). Differences in biomarker expression and clinical variables (stage, tumor burden, and metastatic burden) were observed between the high and low Qoppa strata. Conclusions: In this small heterogeneous pilot cohort, Qoppa provides a proof of concept that integrating organ-derived response biomarkers with routine laboratory parameters may capture clinically relevant signals for metastatic risk stratification in oncology patients. This composite parameter supports the generation of hypotheses for future biomarker-driven research and clinical test development. External validation in larger multicenter cohorts is required before clinical implementation. Full article

Background and Objectives: Sentinel lymph node (LN) biopsy (SLNB) remains to be the standard approach for surgical axillary staging of breast cancer (BC) patients. The aim of this study was to investigate the factors that affect axillary LN involvement in early BC patients. Materials and Methods: Clinically node negative early stage (cT1-2N0) BC patients having undergone breast conserving surgery (BCS) between February 2021 and January 2024 were included. During axillary exploration of all cases, sentinel LNs were excised and reserved for permanent section pathological examination (PS) only. Historical records of patients including clinicopathological features, surgical outcomes as well as pathological results were recorded and analyzed retrospectively. p < 0.05 indicated statistically significant results. Results: The study group consisted of 150 women with cT1-2N0 BC having undergone BCS with a median age of 59 (range: 25–81) years. According to the PS results of the sentinel LNs, the need for reoperation to complete axillary lymph node dissection was present in three (2%) patients. Tumors of the Luminal B subtype were significantly associated with increased sentinel LN positivity (p = 0.014). The risk of sentinel LN metastasis was found to be 5.2 times greater in patients with a Ki-67 ≥ %14 [OR: 5.224 (%95 CI:1.73–15.82, p = 0.003)] and the Ki-67 proliferation index was determined as an independent risk factor. Conclusions: In early-stage BC patients, PS of the excised sentinel LN offers sufficient axillary LN staging. On the other hand, a more careful clinical assessment is necessary for early BC patients harboring tumors with an elevated Ki-67 index and/or tumors of the Luminal B subtype. Full article

Background/Objectives: Despite significant advances in imaging technology, real-time intra-fraction monitoring of moving targets remains a challenge in markerless radiotherapy. This retrospective study investigates the use of ExacTrac Dynamic by Brainlab as an intra-fraction monitoring tool for stereotactic body radiotherapy (SBRT) in both early-stage NSCLC and oligometastatic disease. Methods: A total of 63 X-ray pairs from 21 patients were analyzed to evaluate tumor visualization with and without a surrogate approach. Statistical analysis was conducted to determine whether failures could be attributed to tumor size or localization using the Mann–Whitney U-test and Fisher’s exact test. The accuracy of the X-ray/digitally reconstructed radiograph (DRR) surrogate-based fusion was assessed by calculating and comparing the corresponding 3D vectors according to the linear mixed effects model, with a random slope effect for size of surrogate and a random intercept per patient. Results: Surrogates enhanced tumor visualization on X-ray/DRR fusions from 14.3% to 75.5%. Tumor size and lung affected (left or right) did not predict visualization success. Tumor location, however, tended to influence visibility, with lesions in the upper lobes being more readily visualized (88%) than those in the lower lobes (48.1%), although no statistical significance was reported (p > 0.05). Regarding geometric accuracy, 76% of the analyzed data points deviated less than 5 mm in the 3D vector measurements, the mean values were around 4 mm (±3 mm), and the medians were within 3 mm across all conditions. No statistically significant differences (p > 0.05) were found based on the surrogate size or the triggering time of the X-ray during the breathing cycle. Conclusions: Surrogate-based DRRs, referred to as Correlation Objects, demonstrate consistent geometric accuracy across multiple surrogate sizes and X-ray acquisitions, supporting the clinical translation of markerless lung targeting workflows for lung SBRT. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) constitutes a leading cause of mortality worldwide. Liver transplantation (LT) and liver resection (LR) represent the main curative-intent treatment modalities for early-stage HCC. LT can offer the advantage of both removing the HCC and alleviating the potential underlying liver disease, yet its application is limited by organ scarcity, waitlist dropout, and eligibility criteria. Hence, LR remains widely used due to greater accessibility but is associated with high recurrence rates. Salvage LT is a treatment option for patients with HCC recurrence post-LR, but up to 40% of patients develop non-transplantable recurrence (NTR), defined as recurrence beyond transplant criteria, which precludes LT and is associated in poor outcomes. Methods: The present review aims to summarize the current state of evidence on the comparison of LT and LR, the management of recurrent HCC, and the risk factors associated with NTR. Results: Clinical and histopathologic factors consistently associated with NTR across studies include larger tumor size, multiple tumors, elevated alpha-fetoprotein levels, underlying liver fibrosis or cirrhosis, microvascular invasion, and satellite nodules—features that reflect aggressive tumor biology and impaired hepatic reserve. Conclusions: Improved preoperative risk stratification and identification of patients at high risk for NTR is essential to inform optimal treatment selection. Full article

Background/Objectives: Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, with limited therapeutic options and poor prognosis despite maximal surgery, radiotherapy, and chemotherapy. The complex and immunosuppressive tumor microenvironment, pronounced intratumoral heterogeneity, and the presence of the blood–brain barrier (BBB) severely restrict the efficacy of conventional and emerging therapies. In this context, cell-based strategies leveraging macrophages, mesenchymal stromal cells (MSCs), and their derivatives have gained attention as “cellular allies” capable of modulating the GBM microenvironment and acting as targeted delivery platforms. Methods: This review systematically analyzes preclinical and early clinical literature on macrophage- and MSC-based therapeutic strategies in GBM, including engineered cells, extracellular vesicles (EVs), membrane-coated nanoparticles, and hybrid biomimetic systems. Studies were selected based on relevance to GBM biology, delivery across or bypass of the BBB, microenvironmental modulation, and translational potential. Evidence from in vitro models, orthotopic and syngeneic in vivo models, and available clinical trials was critically evaluated, with emphasis on efficacy endpoints, biodistribution, safety, and manufacturing considerations. Results: The reviewed evidence demonstrates that macrophages and MSCs can function as active therapeutic agents or delivery vehicles, enabling localized oncolysis, immune reprogramming, stromal and vascular remodeling, and enhanced delivery of viral, genetic, and nanotherapeutic payloads. EVs and membrane-based biomimetic platforms further extend these capabilities while reducing cellular risks. However, therapeutic efficacy is highly context-dependent, influenced by tumor heterogeneity, BBB integrity, delivery route, and microenvironmental dynamics. Clinical translation remains limited, with most approaches at preclinical or early-phase clinical stages. Conclusions: Cell-based and cell-derived platforms represent a promising but still evolving therapeutic paradigm for GBM. Their successful translation will require rigorous biomarker-driven patient selection, improved models that capture invasive GBM biology, scalable GMP-compliant manufacturing, and rational combination strategies to overcome adaptive resistance mechanisms. Full article

Malignant pleural mesothelioma (MPM) is a very aggressive tumor. The prognostic value of PD-L1 and BAP1 expression has been investigated in many studies. A retrospective study was conducted that analyzed PD-L1 and BAP1 expression as prognostic biomarkers in patients with MPM. The study included 53 patients with MPM. PD-L1 expression ≥ 1% was found in 39.6%, and BAP1 loss was found in 81.1% of patients. The median overall survival (mOS) was 11 months. Subtype of MPM (p = 0.045), early tumor stage (p = 0.049), therapy (p = 0.002), and good PS (0–1) (p = 0.012) were associated with better survival. Expression of PD-L1 and BAP1 did not show statistical significance regarding OS, but OS was numerically shorter in patients with PD-L1 ≥ 10% (5 vs. 12 months) and longer in patients with BAP1 loss (12 vs. 4 months). In patients with PD-L1 ≥ 1% and BAP1 loss, the median progression-free survival (mPFS) was numerically longer (10 vs. 7 months) but in patients with PD-L1 ≥ 1% and BAP1 positivity, PFS was statistically significantly shorter (1 vs. 7 months, p = 0.048). Our results did not show that PD-L1 and BAP1 are prognostic biomarkers for MPM, but positive PD-L1 expression and BAP1 loss were associated with worse survival in patients with MPM. Full article

Background/Objectives: Peritoneal surface metastases (PSMs) from colorectal cancer have high rates of peritoneal recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior studies dichotomize peritoneal recurrence into “early” and “late,” limiting insight into how clinicopathologic factors influence recurrence timing. This study aimed to identify predictors of peritoneal recurrence and quantify their continuous association with time to recurrence following CRS/HIPEC. Methods: Patients undergoing CC-0 CRS/HIPEC for colorectal PSM from 2018 to 2024 were identified from a prospectively maintained database. The primary outcome was peritoneal surface recurrence. Variables included peritoneal cancer index (PCI), tumor location, histology, HIPEC regimen, and KRAS/BRAF/SMAD4 status. Factors with p < 0.10 on univariable analysis were entered into multivariable logistic regression (recurrence: yes/no) and linear regression (time to recurrence). Results: Among 133 patients, 64 (48.1%) developed peritoneal recurrence. Median time to recurrence was 41.4 weeks (IQR 24.9–74.0), and PCI was higher among those who recurred (median 11.0 vs. 5.0, p < 0.01). Neither tumor stage, histology, intraperitoneal chemotherapy agent, nor molecular alterations were associated with increased risk of peritoneal recurrence. When controlling for PCI, right- and sigmoid-colon primaries independently predicted peritoneal recurrence compared to all other locations without influence on recurrence timing (right: OR 7.18; sigmoid: OR 6.54; p < 0.01). Among patients who recurred, each one-point increase in PCI corresponded to a 2.43-week earlier relapse (p < 0.01). Conclusions: Nearly half of patients with colorectal PSM recurred despite complete CRS/HIPEC. Tumor location predicted peritoneal recurrence, while PCI independently shortened time to relapse. Modeling PCI as a continuous predictor refines postoperative risk stratification and may inform individualized surveillance strategies. Full article

Background and Objectives: Aggressive cancer development is characterized by rapid tumor growth and progressive immune dysfunction. Tumor-derived microRNAs (miRNAs) emerge as master regulators of both malignant transformation and immune evasion, making them promising therapeutic targets. Using the highly aggressive CT-26 peritoneal adenomatosis model, this study explored the potential of selective miRNA inhibition to simultaneously suppress tumor growth and overcome immunosuppression. Methods and Results: Our results revealed that inhibition of miR-155, miR-21, and miR-17 by methylsulfonyl phosphoramidate (mesyl) oligonucleotides exhibited markedly different therapeutic profiles. miR-155 inhibition demonstrated minimal efficacy. miR-21 suppression provided early tumor regression and prevented cancer-associated thymic atrophy, translating into extended survival. miR-17 inhibition displayed delayed but superior tumor growth inhibition, significantly reducing pathologically elevated polymorphonuclear myeloid-derived suppressor cell (MDSC) populations, and nearly doubled animal lifespan. Combination therapy targeting all three miRNAs integrated these complementary mechanisms, maintaining consistent anti-tumor efficacy across early and late stages while providing thymic protection and MDSC reduction. Importantly, therapeutic responses in vivo substantially exceeded predictions based on in vitro tumor cell proliferation and motility measurements, revealing critical contributions of systemic immunomodulation. Conclusions: These findings demonstrate that miRNA inhibition reshapes tumor–immune interactions, positioning anti-miRNA therapeutics as immunomodulatory agents for effective colorectal cancer treatment. Full article

Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [¹⁸F]FDG PET/MRI’s diagnostic accuracy in EC staging and role in predicting tumor aggressiveness, molecular characterization, and recurrence. Methods: A prospective study (ClinicalTrials.gov, ID:NCT04212910) evaluating EC patients undergoing [¹⁸F]FDG PET/MRI before surgery (2018–2024). Histology, immunohistochemistry, and patients’ follow-up (mean FU time: 3.13y) were used as the reference standard. [¹⁸F]FDG PET/MRI, PET only, and MRI only were independently reviewed to assess the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive/negative predictive value (PPV, NPV). Imaging parameters were extracted from [¹⁸F]FDG PET and pcT1w, T2w, DWI, and DCE MRI. Spearman’s correlations, Fisher’s exact test, ROC-AUC analysis, Kaplan–Meier survival curves, log-rank tests and Cox proportional hazards models were applied. Results: Eighty participants with primary EC (median age 63 ± 12 years) were enrolled, with 17% showing LN involvement. [¹⁸F]FDG PET/MRI provided ACC = 98.75%, SN = 98.75%, and PPV = 100% for primary tumor detection, and ACC = 92.41%, SN = 84.62%, SP = 93.94%, PPV = 73.33%, and NPV = 96.88% for LN detection. PET/MRI parameters predicted LN involvement (AUC = 79.49%), deep myometrial invasion (79.78%), lymphovascular space invasion (82.00%), p53abn (71.47%), MMRd (74.51%), relapse (82.00%), and postoperative administration of adjuvant therapy (79.64%). Patients with a tumor cranio-caudal diameter ≥ 43 mm and MTV ≥ 13.5 cm³ showed increased probabilities of recurrence (p < 0.001). Conclusions: [¹⁸F]FDG PET/MR showed exceptional accuracy in EC primary tumor and LN detection. Derived parameters demonstrated potential ability in defining features of aggressiveness, molecular alterations, and tumor recurrence. 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

Background: Accurate preoperative staging is the cornerstone of therapeutic decision-making in gastric cancer (GC), yet standard modalities often fail to capture the full extent of disease, particularly in diffuse and poorly cohesive histotypes. This review aims to provide a comprehensive update on diagnostic imaging for GC, evaluating the established roles of CT, EUS, and PET/CT alongside the emerging capabilities of Magnetic Resonance Imaging (MRI) and Artificial Intelligence (AI). Methods: A structured narrative review was conducted by searching indexed biomedical databases for studies published between 2015 and 2024. A structured literature search screening process identified 410 relevant studies focusing on T, N, and M staging accuracy, quantitative imaging biomarkers, and radiomics. Results: While Multidetector CT remains the universal first-line modality, its sensitivity declines in infiltrative tumors and low-volume peritoneal carcinomatosis. EUS retains superiority for early (T1-T2) lesions but may offer limited value in advanced stages. Conversely, MRI (leveraging diffusion-weighted imaging (DWI) and multiparametric protocols) indicates superior soft-tissue contrast, potentially outperforming CT in the assessment of serosal invasion, nodal involvement, and occult peritoneal metastases. Furthermore, emerging fibroblast activation protein inhibitor (FAPI) PET tracers show promise in overcoming the limitations of FDG in mucinous and diffuse GC. Finally, radiomics and deep learning models are providing novel quantitative biomarkers for non-invasive risk stratification. Conclusions: Contemporary GC staging requires a tailored, multimodality approach. Evidence supports the increasing integration of MRI and quantitative imaging into clinical workflows to overcome the limitations of conventional techniques and support precision oncology. Full article

The incidence of peripheral lung squamous cell carcinoma (p-LUSC) has increased in recent years, but the clinical features of early-stage p-LUSC remain unclear. In the present study, we aim to elucidate the general clinical features of p-LUSC by comparing it with peripheral lung adenocarcinoma (p-LUAD). Patients with p-LUSC or p-LUAD who were at an early imaging stage and underwent complete lobectomy with systematic lymph node dissection were included. The clinical characteristics of p-LUSC were elucidated through comparative analysis with p-LUAD, and independent prognostic factors for recurrence-free survival were identified. A total of 103 patients with p-LUSC and 600 patients with p-LUAD were included. Compared with p-LUAD, all p-LUSC cases appeared as solid nodules (SDNs) on imaging, and p-LUSC was associated with the male sex, older age, smoking history, lobulation sign, interstitial pneumonia, and a shorter volume doubling time. In terms of malignant aggressiveness, p-LUSC demonstrated a significantly lower lymph node metastasis rate than SDNs of p-LUAD in the >2.0 to ≤3.0 cm group, while no statistically significant difference was observed between the two groups in the 0–2.0 cm group. As for prognosis, tumor size and lymph node metastasis were found as independent risk factors for tumor recurrence. Full article

Prostate cancer (PCa) is the leading cause of cancer-related deaths worldwide and the second most common cancer among men. Treatment options depend on factors like age, androgen sensitivity, PSA levels, Gleason score, TNM stage, and recurrence risk. Available treatments include hormonal therapy, radiation, surgery, and chemotherapy. Early immunological treatments were limited by poor lymphocyte infiltration and an immunosuppressive environment. Today, strategies such as dendritic cell vaccines, immune checkpoint inhibitors (ICIs), and adoptive cell therapy (ACT) are used. ACT, especially CAR T-cell strategies, aims to overcome traditional treatment limitations, particularly in advanced and metastatic castration-resistant prostate cancer (mCRPC), though it remains in early development. Personalized medicine uses molecular insights from the diseased tissue to tailor treatments. Variability in patient response, due to tumor heterogeneity and prior treatments, highlights the importance of personalized and combination therapies as future strategies for effective immunotherapy. This review explores the current landscape of PCa. We analyze treatment guidelines established by NCCN and EANM-ESTRO-ESUR-ISUP-SIOG. We comprehensively examine immunotherapeutic strategies currently available or under investigation for prostate cancer, with particular emphasis on ICIs, ACT with a focus on CAR T-cell therapy, combination approaches and therapeutic synergies, and predictive biomarkers of immunotherapy response. Additionally, we discuss the challenges and future directions in the implementation of immunotherapy for the management of prostate cancer. Full article

A key function of naturally occurring antibodies is to control pathologically altered cells, such as those with aberrant glycosylation. Age-related diminution in the pool of B cells producing these immunoglobulins is linked to impaired anti-tumor immunity. In this study, the levels of antibodies against tumor-associated carbohydrate antigens (TACAs)—common in gastric cancer (GC) and other malignancies—were analyzed in 235 treatment-naïve GC patients (stages I–IV) and 76 healthy donors using a printed glycan array (PGA). We found that anti-glycan IgM levels, but not IgG, reduced with age in both patients and donors. Crucially, IgM levels against most glycans were significantly lower in the GC cohort compared with healthy donors, a trend that remained after age adjustment. Furthermore, an immunohistochemical analysis revealed that human anti-GalNAcα (Tn) antibodies—a well-characterized TACA in gastrointestinal cancers—bound to tumor cells and exhibited perinuclear and membrane staining in non-tumor surface cells within the same organ. These data support the hypothesis that gastric cancer patients have reduced levels of anti-glycan IgMs, which are responsible for the early recognition of transformed cells. This specific immunodeficiency may contribute to a permissive environment for tumor development. Full article