Clinical & Translational Oncology最新文献

Background: TMPRSS2:ERG gene fusion is a common alteration in prostate cancer and is regulated by androgen receptor signaling. We investigated whether ERG expression, assessed by immunohistochemistry (IHC), predicts clinical outcomes in patients with intermediate- or high-risk localized prostate cancer treated with combined androgen blockade (CAB) and radiotherapy (RT).

Material and methods: We retrospectively analyzed patients treated with CAB (GnRH agonists + antiandrogens) and normofractionated RT. ERG expression was evaluated using IHC. Overall survival (OS) was estimated with Kaplan-Meier curves. Prostate cancer-specific survival (PCSS), biochemical recurrence-free survival (bRFS), and progression-free survival (PFS) were assessed using competing risk models.

Results: A total of 86 patients were included (median follow-up 173 months). ERG expression was positive in 69%. No significant differences were observed in OS (HR 1.03; p = 0.92), PCSS (HR 0.44; p = 0.22), bRFS (HR 0.51; p = 0.19), or PFS (HR 0.56; p = 0.30) between ERG-positive and ERG-negative groups.

Conclusions: ERG expression assessed by IHC was not associated with clinical outcomes in this population. These results do not support its role as a predictive biomarker in patients treated with CAB and RT. Further prospective studies are warranted to confirm these findings.

Background: This study investigates the differential expression of ENO2 in serum extracellular vesicles (EVs) of patients with diffuse large B cell lymphoma (DLBCL) and its correlation with clinicopathological characteristics and prognosis.

Methods: Serum samples before receiving treatment, clinicopathological characteristics, and follow-up information were collected from 78 patients with DLBCL, and 40 patients with reactive hyperplasia of lymph nodes (RH) were selected as the control group. ENO2 expression in serum EVs was detected by RT-qPCR and Western blot. The diagnostic value of ENO2 in serum EVs for DLBCL was analyzed by ROC curve. The correlation between ENO2 expression and clinicopathological data was analyzed by chi square test. The 5-year overall survival (OS) was analyzed by Kaplan-Meier method. The COX proportional hazards model was employed for analyzing prognostic risk factors of DLBCL.

Results: ENO2 is highly expressed in serum EVs of DLBCL patients. ENO2 in serum EVs has moderate diagnostic efficacy for DLBCL, with a sensitivity, specificity, and AUC of 0.808, 0.725, and 0.789, respectively. ENO2 expression is closely related to ECOG score, LDH level, Ann Arbor stage, IPI, and Bcl-2. DLBCL patients with age (> 60 years), ECOG (2-4), LDH level (High), Ann Arbor stage (III + IV), IPI score (3-5), Ki-67 (≥ 70%), Bcl-2 (positive), and ENO2 protein (high expression) have lower 5-year OS. ENO2 protein (high expression), ECOG (2-4), Ann Arbor stage (III + IV), and Ki-67 (≥ 70%) are independent prognostic risk factor for DLBCL.

Conclusions: ENO2 is correlated with the clinicopathological characteristics of DLBCL and is an independent prognostic risk factor.

Background: Despite the therapeutic advances of immune checkpoint inhibitors in advanced melanoma, early identification of treatment non-responders remains a major clinical need. Dynamic changes in peripheral blood biomarkers may provide a cost-effective and non-invasive strategy to monitor treatment response during the early phase of immunotherapy.

Methods: We retrospectively analyzed 70 patients with advanced melanoma treated with combination ipilimumab and nivolumab between 2017 and 2025. Dynamic changes in neutrophil-to-lymphocyte ratio (ΔNLR), lymphocyte-to-monocyte ratio (ΔLMR), platelet-to-lymphocyte ratio (ΔPLR), systemic immune-inflammation index (ΔSII), eosinophil count (ΔEosinophils), and lactate dehydrogenase (ΔLDH) were calculated as the ratio of post-treatment (prior to the third cycle) to pre-treatment (baseline) values. ROC analysis and logistic regression models assessed each biomarker's predictive value for objective response. Each delta marker was tested in a separate multivariate model adjusted for clinical covariates identified through univariate analysis.

Results: Among 70 patients, 28 (40.0%) achieved an objective response. ΔNLR and ΔLMR showed the strongest discriminative performance (AUCs: 0.836 and 0.793, respectively). In multivariate models incorporating univariate-selected clinical covariates, high ΔNLR (OR = 20.3, 95% CI 4.65-88.45) and low ΔLMR (OR = 22.66, 95% CI 5.07-101.34) remained independently associated with non-response (both p < 0.001). These biomarkers also improved the predictive performance of the clinical model (ΔAUC: + 7.7%).

Conclusions: Routine assessment of early dynamic changes in ΔNLR and ΔLMR after two cycles of ipilimumab-nivolumab therapy can enable timely identification of non-responders in advanced melanoma, allowing early discontinuation or switching of treatment to avoid unnecessary toxicity and cost. These biomarkers rely on standard blood counts and are readily applicable in clinical practice. Nevertheless, the retrospective single-center design and moderate sample size limit the generalizability of our findings, and prospective validation in larger, independent cohorts is warranted.

Background: Male breast cancer (MBC), a rare disease accounting for less than 1% of all cancers in men and approximately 1% of all breast cancers globally, exhibits unique biological and clinical characteristics that distinguish it from female breast cancer (FBC). To identify the latest developments and trends in MBC research, we performed a comprehensive analysis of relevant literature and generated visual representations of the data. Building on these outcomes, we delve into the insights gained, aiming to enhance the ongoing comprehension of MBC.

Methods: We conducted a search of the Web of Science Core Collection (WoSCC) for English-language articles and reviews on MBC published from 1982 to 2024. Following a rigorous dual-researcher screening process, we refined the dataset to 6802 relevant records. Subsequently, we employed Microsoft Excel for initial data organization and processing. For in-depth analysis and visualization of journal, country/region, author/institution trends, as well as keyword patterns, we utilized a combination of R Package, VOSviewer, and CiteSpace. This multi-tool approach enabled us to extract and present meaningful insights from the data.

Results: MBC research has risen since 1996, with a 2024 peak at 503 publications, reflecting advances like BRCA1/2 gene discoveries. The USA leads in publications and citations, with North America and Europe being the most collaborative regions. Key journals include Breast Cancer Research and Treatment, and leading contributors are Ottini, Laura and Van Diest, Paul J. Research focuses on MBC's genetic links (e.g. BRCA mutations) and clinical features, with emerging topics like precision medicine and immunotherapy.

Conclusion: MBC research has grown but remains concentrated in high-income countries. Future efforts should explore MBC's unique biology, improve diagnostic/therapeutic strategies, and involve global, interdisciplinary collaboration to enhance patient outcomes.

Background: Radiation oncology (RO) is essential in cancer treatment. Unplanned interruptions reduce tumor control, yet no validated management guidelines exist. The Italian Association of Radiation and Clinical Oncology (AIRO) conducted a national survey to assess the prevalence, causes, and management strategies for RT interruptions across Italy.

Methods: This cross-sectional survey was conducted between April and June 2022. A 34-question survey was emailed to directors of all Italian ROT centers, covering: (1) demographic and institutional characteristics; (2) radiobiological knowledge of ROT interruptions; (3) clinical management and compensation strategies.

Results: A total of 104 centers responded. Respondents had a median age of 57 years (range 34-74), and most worked in General Hospitals (64%). Centers had a median of 2 LINACs (range 1-6), with 16% operating only one LINAC. 96% of radiation oncologists (Ros) considered ROT interruptions a critical issue, particularly in curative (51%) and adjuvant (29%) settings. 42% defined an interruption of > 5 days as critical, and 63% believed treatment phase did not influence impact. 29% of ROs followed formal guidelines [e.g., Royal College of Radiographers (RCR)]. The main causes of interruptions were LINAC breakdowns (22%), toxicity (22%), and patient compliance issues (22%). 24% of ROs followed codified procedures for managing interruptions; 84% regularly monitored treatment breaks. Dose recovery strategies: 28% always compensated, 59% occasionally compensated, primarily by increasing total dose (48%) or working on Saturdays (20%).

Conclusion: This study reveals variability in ROT interruption management, stressing the need for AIRO guidelines, collaboration, and modern radiobiological integration.

Background: NK/T-cell lymphoma (NKTCL) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Histone acetylation, which can regulate gene expression, plays a crucial role in epigenetic control. Sodium butyrate (NaB), a nonspecific inhibitor of histone deacetylase (HDAC), has antitumor effects on various malignancies. However, the mechanism of NaB in NKTCL remains poorly understood.

Methods: NKTCL cells were treated with specified concentrations of NaB for designated durations. Cell viability was assessed using the CCK-8 method, whereas flow cytometry was used to evaluate apoptosis and the cell cycle. RT-qPCR and western blot analyses were conducted to measure the expression levels of genes associated with the cell cycle, apoptosis, autophagy, HDAC, EBV, and molecules in the PI3K/Akt/mTOR and JAK/STAT signaling pathways.

Results: NaB downregulated the expression of HDAC 3, 4, 5, 8, 9, and 10 in NKTCL cell lines, leading to a significant reduction in cell viability and G₂ phase cell cycle arrest. NaB induced apoptosis in NKTCL cell lines and inhibited the JAK/STAT signaling pathway, which was further promoted by the JAK2 inhibitor fedratinib. Moreover, NaB induced autophagy and suppressed the PI3K/Akt/mTOR signaling pathway in NKTCL cell lines. Additionally, NaB upregulated the transcription of lytic genes (TK, BMRF1, BMRF2, BRLF1, BMLF1, BNRF1, and BZLF1) in NKTCL, indicating its potential to induce EBV lytic infection.

Conclusions: NaB effectively promotes apoptosis and inhibits the JAK/STAT signaling pathway in NKTCL, which is further promoted by the JAK2 inhibitors fedratinib. Furthermore, NaB induces EBV reactivation and lytic infection in NKTCL, suggesting its ability to transition EBV from a latent to a lytic form.

Purpose: We aimed to evaluate the effectiveness and safety of osimertinib as a first-line therapy in patients with advanced EGFR-mutated non-small cell lung cancer (aNSCLC) in a Spanish real-world setting.

Methods: This retrospective observational study was conducted at eight centers. The primary objective was to assess the effect of osimertinib on progression-free survival (PFS). The secondary objective was to evaluate the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and drug toxicity.

Results: A total of 181 patients with aNSCLC were included in this study. The median PFS and OS were 15.8 (95% CI 12.5-19.0) and 29.3 (95% CI 21.1-37.5) months, respectively. An Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ≥ 2 was associated with shorter PFS, whereas the presence of common EGFR mutations (exon 19 deletion and exon 21 L858R) was associated with longer PFS. Similarly, the age ≥ 70 years and an ECOG PS ≥ 2 were associated with a shorter OS, whereas the exon 19 deletion was associated with a longer OS. In addition, the overall ORR was 71.3% (CI 95% 64.7-77.9%), and the DCR was 87.8% (CI 95% 83.1-92.6%), with exon 19 deletion associated with a greater treatment response. Finally, 77% of the patients reported mild adverse reactions. Severe toxicity was not observed.

Conclusions: This study supports the effectiveness and tolerable safety profile of osimertinib as first-line treatment for patients with aNSCLC in a real-world setting. Exon 19 deletion appears to be a strong predictor of greater effectiveness in patients with aNSCLC.

Background: Thyroid nodules categorized as TIRADS 3 are typically considered low risk for malignancy (estimated < 5%) under the 2017 ACR TI-RADS guidelines. However, the real-world application of these criteria may vary, with many TIRADS 3 nodules undergoing fine-needle aspiration (FNA) despite recommendations for surveillance. This study aimed to identify clinical and ultrasonographic predictors of malignancy in TIRADS 3 nodules to enhance risk stratification.

Methods: This retrospective, single-center study included 200 patients aged 18-65 years with ultrasound-confirmed TIRADS 3 thyroid nodules who underwent FNA between January 2021 and December 2022. Although ACR guidelines recommend biopsy for nodules ≥ 2.5 cm, FNA was also performed in smaller nodules presenting with high-risk features such as capsule bulging or central-peripheral vascularity. Data were collected from anonymized hospital records. Multivariate logistic regression was used to identify independent predictors of malignancy.

Results: The malignancy rate was 20%, exceeding the expected threshold for TIRADS 3 nodules. Capsule expansion (OR 18.50, p < 0.001), central-peripheral vascularity (OR 4.99, p = 0.004), and a family history of thyroid cancer (OR 13.08, p = 0.001) were identified as significant predictors. All malignancy diagnoses were based on cytological findings (Bethesda V/VI), with no histopathologic confirmation available.

Conclusion: Certain TIRADS 3 nodules may possess a higher malignancy risk than traditionally assumed. Incorporating additional ultrasound features and clinical context may improve diagnostic accuracy. Future prospective studies with histopathological confirmation are warranted to validate these predictors.

Background: Antibody-drug conjugates (ADC) improved survival in patients with HER2-positive MBC. To date, there is  no prognostic biomarker in routine practice for these patients. HER2-ECD is associated with poor prognosis but has not yet been studied in patients receiving ADC.

Methods: This monocentric retrospective study assessed in HER2-positive MBC patients shows the prognostic value on OS and PFS of (1) baseline HER2-ECD and CA15-3 and (2) HER2-ECD and CA15-3 after 3 months of treatment with TDM-1. At baseline, patients were divided according to the median value of HER2-ECD and CA15-3 from study population. For kinetic assessments, we compared survival outcomes according to the evolution of HER2-ECD and CA15-3 (stable/decrease vs increase).

Results: 40 patients were included. For both biomarkers, baseline values were not prognostic for OS neither PFS. Patients with stable or decrease HER2-ECD at 3 months had a significantly longer OS (median 43 versus 15.3 months, p < 0.0001) and PFS (median 9.4 versus 2.9 months, p = 0.0018) than patients with decrease, confirmed in multivariate analysis (p = 0.004 for OS and < 0.0001 for PFS). In contrast, CA15-3 kinetic was only prognostic for PFS (median 9.6 versus 4.9 months, p = 0.019), confirmed in multivariate analysis (p = 0.008).

Conclusion: In this retrospective cohort, HER2-ECD kinetic was a prognostic biomarker for OS and PFS in patients with an HER2-positive MBC treated with TDM-1.

Background: This study aimed to develop and validate a hybrid deep learning (DL) model that integrates convolutional neural network (CNN) and vision transformer (ViT) architectures to predict distant metastasis (DM) in patients with non-small cell lung cancer (NSCLC) using ¹⁸F-FDG PET/CT images.

Methods: A retrospective analysis was conducted on a cohort of consecutively registered patients who were newly diagnosed and untreated for NSCLC. A total of 167 patients with available PET/CT images were included in the analysis. DL features were extracted using a combination of CNN and ViT architectures, followed by feature selection, model construction, and evaluation of model performance using the receiver operating characteristic (ROC) and the area under the curve (AUC).

Results: The ViT-based DL model exhibited strong predictive capabilities in both the training and validation cohorts, achieving AUCs of 0.824 and 0.830 for CT features, and 0.602 and 0.694 for PET features, respectively. Notably, the model that integrated both PET and CT features demonstrated a notable AUC of 0.882 in the validation cohort, outperforming models that utilized either PET or CT features alone. Furthermore, this model outperformed the CNN model (ResNet 50), which achieved an AUC of 0.752 [95% CI 0.613, 0.890], p < 0.05. Decision curve analysis further supported the efficacy of the ViT-based DL model.

Conclusion: The ViT-based DL developed in this study demonstrates considerable potential in predicting DM in patients with NSCLC, potentially informing the creation of personalized treatment strategies. Future validation through prospective studies with larger cohorts is necessary.