Search Results (50,291)

Background: Second-line treatment selection in relapsed extensive-stage small-cell lung cancer (ES-SCLC) is commonly guided by the platinum-free interval, but the optimal approach for patients progressing 3–6 months after first-line platinum-based therapy remains uncertain. We compared platinum-containing doublet chemotherapy with single-agent chemotherapy in this clinically ambiguous subgroup. Methods: This multicenter retrospective real-world cohort study included patients with ES-SCLC or recurrent metastatic SCLC after prior limited-stage disease who received first-line platinum-based chemotherapy, achieved disease control, and progressed within a platinum-free interval of 90–180 days. Treatment allocation was at the discretion of the treating physician and was not randomized. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Because of the non-randomized design, the treatment effect was examined across multiple analytic approaches, including multivariable Cox regression, propensity score adjustment, and stabilized inverse probability of treatment weighting (IPTW). Results: Of 105 patients, 54 received single-agent chemotherapy and 51 received platinum-containing doublet therapy; 39 (37.1%) had received first-line atezolizumab. Baseline characteristics were imbalanced in favor of the doublet group, which had a longer platinum-free interval, fewer pleural metastases, and a higher rate of objective response to first-line therapy. ORR was higher with doublet therapy (31.4% vs. 11.1%, p = 0.016), as was DCR (62.7% vs. 33.3%, p = 0.003). Median PFS was 4.4 months (95% CI 3.4–5.8) with doublet therapy versus 3.1 months (95% CI 2.7–3.7) with single-agent chemotherapy (unadjusted HR 0.53, 95% CI 0.36–0.80; p = 0.002). Median OS was 6.5 months (95% CI 5.4–8.0) versus 5.4 months (95% CI 4.1–6.0), a difference that was not statistically significant (HR 0.68, 95% CI 0.46–1.01; p = 0.054). The PFS estimate favored doublet therapy in all sensitivity analyses but was attenuated with increasingly complete adjustment for treatment selection (multivariable HR 0.46, 95% CI 0.29–0.72; propensity-adjusted HR 0.58, 95% CI 0.38–0.88; IPTW HR 0.68, 95% CI 0.38–1.20, p = 0.184). No OS estimate reached statistical significance in any model. Grade ≥ 3 adverse events were similar between groups (66.7% vs. 64.8%, p = 0.842). Conclusions: In this non-randomized cohort of patients relapsing within a 90–180-day platinum-free interval, platinum-containing doublet chemotherapy was associated with higher response rates and longer PFS, without an increase in severe toxicity, but no overall survival benefit was demonstrated. Because baseline prognostic factors consistently favored the doublet group and the PFS advantage was attenuated after propensity-based adjustment, these findings should be regarded as hypothesis-generating. They are nonetheless consistent with randomized data showing improved PFS but not OS with platinum rechallenge, and support platinum-containing rechallenge as a reasonable option in carefully selected patients rather than as a demonstrated survival-prolonging strategy. Full article

Objective: This study aims to investigate the expression of CAVIN3 in cervical cancer, its effect on radiotherapy outcomes, and its potential molecular mechanisms. Materials and Methods: The GEPIA2 database was used to screen genes that may affect cervical cancer prognosis. Then, we analyzed 133 cervical cancer patients from the TCGA database who received radiotherapy to evaluate CAVIN3 gene expression and function. Receiver operating characteristic (ROC) curves and Cox regression models were employed to assess the diagnostic value of CAVIN3 and its association with radiotherapy outcomes. GSEA, GO, and KEGG databases were used to perform pathway enrichment analysis of CAVIN3-related signaling pathways. We also collected pretreatment biopsy specimens from 66 patients who were subsequently treated with radiotherapy from our center to validate the findings from the database analysis. Results: In the TCGA database, CAVIN3 expression was significantly lower in cervical cancer tissues than in normal cervical tissues (p = 0.019), a finding that was independently corroborated in our own cohort (p = 0.002). Receiver operating characteristic analysis yielded area-under-the-curve values of 0.894 for the TCGA RNA-seq data and 0.947 for our center, underscoring the gene’s potential diagnostic utility. Next, we stratified cervical cancer patients who received radiotherapy by intratumoral CAVIN3 levels. Notably, the low-expression group consistently showed better treatment outcomes. In the TCGA cohort, high CAVIN3 expression was associated with significantly shorter median overall survival (mOS, 31.8 months versus not reached within follow-up; p = 0.043). This pattern was confirmed in our validation cohort, where high CAVIN3 expression predicted markedly inferior median progression-free survival (mPFS, 9.8 vs. 59.9 months; p < 0.05) and mOS (17.45 months vs. not reached; p < 0.05). Consistent with these survival differences, the objective response rate to radiotherapy was lower in the high-expression group than in the low-expression group (56.5% vs. 88.2%, p = 0.006), revealing better radiotherapy response among tumors with low CAVIN3 expression. Enrichment analysis revealed that the high CAVIN3 expression group was primarily enriched in pathways related to extracellular matrix formation and remodeling, extracellular matrix–cell membrane interactions, cell adhesion and migration, integrin β1 signaling, and the regulation of cell growth, differentiation, and apoptosis. Together, these functions indicate a more differentiated, matrix-attached phenotype that can promote radioresistance. Conversely, low CAVIN3 expression likely reflects a poorly differentiated state with diminished matrix interaction, which renders the tumor more vulnerable to radiation. Conclusions: CAVIN3 downregulation is a frequent event in cervical cancer and may contribute to tumor susceptibility. Paradoxically, within tumors, low expression of CAVIN3 is associated with an enhanced response to radiotherapy, likely stemming from the underlying phenotype characterized by poor differentiation and heightened radiosensitivity. Therefore, CAVIN3 expression levels are correlated with cervical cancer development and the radiotherapy response of cervical cancer patients. Full article

Background and Objectives: The relative prognostic information provided by different nodal metrics and the independent role of primary tumor size remain unclear in gastric cancer. This study evaluated the association of metastatic lymph node count and primary tumor size with disease-free survival (DFS) in stage II–III gastric cancer (GC) treated with a surgery-first approach. Materials and Methods: This retrospective single-center study included 128 patients who underwent curative-intent gastrectomy between 2003 and 2019 without neoadjuvant treatment. A multivariable Cox model with clinically prespecified covariates was fitted. Metastatic lymph node count, pathological N (pN) category, lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were each added separately to the same base clinical model and compared using the Akaike information criterion (AIC). Results: During a median follow-up of 114.3 months, 86 DFS events occurred. Each additional metastatic lymph node was independently associated with a higher hazard of a DFS event (HR, 1.049; 95% CI, 1.022–1.076; p < 0.001), and this association persisted across four sensitivity analyses. Primary tumor size was not independently associated with DFS. All four nodal metrics improved model fit, with LNR yielding the lowest AIC. Conclusions: Metastatic lymph node count was independently and robustly associated with DFS, whereas primary tumor size was not. Although LNR provided the best relative model fit, these within-cohort comparisons do not establish clinical superiority, and external validation is required. Full article

Background: Radiotracer- and magnetic seed-based targeted axillary staging techniques are increasingly used after neoadjuvant chemotherapy (NAC) in patients with initially node-positive breast cancer who convert to clinical node-negative (ycN0) status. However, these technologies remain unavailable in many centres worldwide. We evaluated the effectiveness of radiotracer-free axillary staging using dual-tracer sentinel lymph node biopsy (SLNB) with indocyanine green (ICG) and methylene blue, with particular focus on the clinical implications of clipped node non-retrieval. Methods: This retrospective single-centre cohort study included 49 patients with biopsy-proven cN1 breast cancer who achieved ycN0 status following NAC and underwent dual-tracer SLNB using ICG and methylene blue between 2021 and 2024. Clipped node retrieval rates, tracer-specific detection patterns, recurrence outcomes, and disease-free survival (DFS) were analysed. Clinical outcomes, including recurrence and disease-free survival, were compared between patients with successful and unsuccessful clipped node retrieval. Results: Clipped node retrieval was achieved in 41 of 49 patients (83.7%). ICG outperformed methylene blue for clipped node identification (80.5% vs. 61.0%) and was the sole detecting tracer in 39.0% of cases. Using methylene blue alone would have reduced the retrieval rate to 51.0% (p = 0.001). ICG identified the clipped node in all six patients with axillary micrometastases (ypN1mi). Clipped node non-retrieval occurred in eight patients, all of whom had negative SLNB findings and did not undergo completion axillary lymph node dissection. Recurrence rates were similar between the retrieval and non-retrieval groups (17.1% vs. 12.5%, p = 1.000), and no isolated axillary recurrences were observed. Baseline tumour size was the only independent predictor of disease-free survival in multivariable analysis (HR 2.05, 95% CI 1.20–3.51; p = 0.008). Conclusions: Radiotracer-free axillary staging using ICG and methylene blue achieved a high clipped node retrieval rate in patients with ycN0 breast cancer after neoadjuvant chemotherapy. ICG significantly improved clipped node identification compared with methylene blue alone and identified the clipped node in all patients with residual nodal micrometastatic disease. Among patients with negative SLNB findings, clipped node non-retrieval was not associated with higher recurrence rates or worse disease-free survival during follow-up. However, given the small number of clipped node non-retrieval cases (n = 8) and recurrence events (n = 8), these findings should be interpreted with caution and require confirmation in larger prospective studies. These findings support the feasibility of a radiotracer-free dual-tracer approach in settings where radiotracer-based techniques are not available. Prospective multicentre studies are warranted to validate both the oncological performance of radiotracer-free axillary staging and the clinical implications of clipped node non-retrieval. Full article

Accurate segmentation of non-small cell lung cancer (NSCLC) on positron emission tomography/computed tomography (PET/CT) is an essential prerequisite for automated metabolic tumor volume (MTV) quantification and staging. Although deep learning models achieve high performance on large-scale datasets, their generalization across different clinical domains is limited by variations in imaging protocols and patient demographics. This study aims to evaluate several deep learning architectures and investigate a transfer learning strategy to mitigate domain shift. Three architectures, including ResNet-backbone 3D U-Net, nnU-Net v2, and Swin UNETR, were benchmarked from scratch and compared with a fine-tuned nnU-Net initialized with AutoPET II weights. Results on the internal dataset showed that the fine-tuned nnU-Net achieved a Dice similarity coefficient (DSC) of 83.4 ± 6.5%, a 95% Hausdorff distance (HD95) of 5.1 ± 3.6 mm, and a precision of 89.6 ± 8.2%. Compared to the nnU-Net v2, the fine-tuned nnU-Net improved the absolute DSC by 6.8% while reducing local training time by 37.5% by bypassing the initial feature-learning phase. The fine-tuned nnU-Net model also demonstrated a high correlation between the MTV and the ground truth (Pearson r = 0.96, p < 0.001), indicating its potential as a reliable automated approach for quantitative MTV extraction and NSCLC prognostic-related analysis. Full article

Colorectal cancer (CRC) exhibits substantial heterogeneity across ancestry, age at onset, and treatment exposure. Although dysregulation of the WNT signaling pathway is a hallmark of CRC, its associations with genomic burden and survival across diverse clinical contexts remain incompletely understood. We analyzed 2562 CRC cases from AACR Project GENIE and cBioPortal, stratified by ancestry (African American [AA] and non-Hispanic White [NHW]), age at onset (early vs. late), and FOLFOX treatment status. Associations between WNT pathway alterations, genomic burden (mutation count, tumor mutational burden, and fraction of genome altered), and survival were assessed using conventional statistical methods. AI-HOPE and AI-HOPE-WNT conversational artificial intelligence platforms were used to facilitate data integration and exploratory analyses. WNT pathway alterations were highly prevalent across all subgroups and were predominantly driven by APC alterations. Late-onset CRC, particularly among NHW patients not treated with FOLFOX, exhibited higher mutation burden and enrichment of AXIN1 and AXIN2 alterations. Survival analyses demonstrated context-dependent associations between WNT alterations and outcomes. Among early-onset FOLFOX-treated patients, WNT alterations were associated with differential survival. In NHW patients, WNT alterations were linked to improved survival across multiple clinical settings, whereas associations in AA patients were more limited and context-specific. WNT pathway alterations are pervasive in CRC but exhibit ancestry-, age-, and treatment-dependent associations with genomic complexity and survival. AI-guided analyses may accelerate identification of clinically relevant subgroup-specific molecular patterns. Full article

Background/Objectives: Early identification of breast cancer patients unlikely to benefit from neoadjuvant chemotherapy (NAC) remains a pressing clinical problem because ineffective therapy delays definitive surgery and exposes patients to unnecessary toxicity. Quantitative ultrasound (QUS) and shear wave elastography (SWE) probe complementary tissue properties—scatterer microstructure and mechanical stiffness—that may change before macroscopic tumor shrinkage. This study aimed to evaluate whether multi-parametric ultrasound (mpUS) radiomic kinetics, analyzed with a machine learning ensemble and interpreted with SHAP, could predict pathologic response to NAC. Methods: A prospective observational cohort enrolled 135 women with biopsy-proven stage II–III breast cancer treated with NAC within the multidisciplinary breast pathway shared between Vasile Goldis Western University of Arad and Victor Babes University of Medicine and Pharmacy Timisoara (Pius Brinzeu County Emergency Hospital). All patients underwent standardized QUS and SWE acquisitions at baseline, week 1, and week 3. Response was defined pathologically at surgery as residual cancer burden (RCB) class 0/I versus II/III. Group comparisons used Welch’s t-test, Mann–Whitney U, chi-square, and Fisher’s exact tests; correlations used Spearman’s rho. A stacked machine learning ensemble (four base learners—XGBoost, random forest, support vector machine, and L2-penalized logistic regression—combined by a separate second-stage logistic meta-learner) was trained with nested 10-fold cross-validation, bootstrap stability assessment, SHAP-based interpretability, and decision curve analysis. Results: Sixty patients (44.4%) were responders and 75 (55.6%) were non-responders. Responders showed greater week 3 increases in mid-band fit (3.4 ± 0.9 vs. 1.2 ± 0.8 dB, p < 0.001), entropy (0.7 ± 0.2 vs. 0.2 ± 0.2, p < 0.001), and more pronounced SWE mean stiffness reduction (−44.1 ± 9.7 vs. −12.1 ± 8.6 kPa, p < 0.001). The stacked ensemble integrating clinical, QUS, and SWE kinetic features reached an AUC of 0.93 (95% CI 0.88–0.97) versus 0.71 for the clinical-only model (all reported performance figures represent internal cross-validation only). SHAP analysis identified Δ MBF and Δ entropy at week 3 as the dominant features, with high bootstrap stability. Conclusions: Multi-parametric ultrasound radiomic kinetics integrated through a machine learning ensemble may provide an interpretable early-response biomarker for NAC in breast cancer, pending external validation. Full article

Background: Mismatch repair deficiency (MMRd) is a central molecular determinant of colorectal cancer (CRC) biology, prognosis, and treatment response, and Universal Tumour Screening (UTS) is advocated for Lynch syndrome (LS) detection; yet real-world performance across clinical subgroups remains limited. We evaluated MMRd distribution and UTS-based LS detection in a large consecutive surgical cohort. Methods: We retrospectively analyzed 1022 consecutive CRC patients undergoing surgical resection at the University Hospital of Padua (2015–2023). MMR status was assessed by immunohistochemistry; MMRd cases underwent reflex BRAF mutation testing and, when available, MLH1 promoter methylation analysis, followed by germline multigene panel testing for suspected LS. Clinicopathological features were compared by MMR status, age at onset, and tumour location. Results: MMR testing was performed in 875 patients (85.6%), rising from 67.0% (2015–2017) to 97.4% (2021–2023). MMRd was identified in 139 tumors (15.9%) and was independently associated with age ≥ 70 years, colonic location, and stage 0–II. Of 22 patients with confirmed LS, 13 (59.1%) were newly identified through UTS; family history showed no significant univariate association with LS status and was not independently associated with MMRd after multivariable adjustment. MMRd prevalence was numerically higher in early- than late-onset CRC (20.0% vs. 15.4%), approaching significance after multivariable adjustment (OR 1.90, 95% CI 0.99–3.64; p = 0.054); hereditary syndromes were also more frequent in early-onset disease. MMRd was markedly rarer in rectal than colonic cancer (4.1% vs. 22.5%; p < 0.0001), though MMRd rectal cancers arose in younger patients. Conclusions: UTS identified a substantial proportion of LS carriers missed by age- or family-history criteria. The relationship between age and MMRd prevalence proved more nuanced than a simple comparison would suggest, reinforcing the value of universal over selective testing across the age spectrum, while MMRd rectal cancer shows a distinct younger profile relevant to immunotherapy-based organ preservation. Full article

Breast cancer (BC) is the most frequently diagnosed malignancy and generally the leading cause of cancer-related mortality among women worldwide. Molecular targeted therapies, including endocrine treatment for hormone-responsive tumors, anti-HER2 agents for HER2-positive tumors and PARP inhibitors (PARPis) for homologous recombination-deficient (HRD) tumors, have significantly improved patient outcomes, but several clinical challenges are still open. The development of acquired resistance strongly limits the long-term efficacy of current treatment strategies, underscoring the necessity to identify novel therapeutic approaches for breast cancer therapy. In this review, we summarize and discuss recently investigated natural compounds with anti-breast cancer activity, ranging from polyphenols, terpenoids, alkaloids, sulfur-containing compounds and the emerging plant-derived extracellular vesicles. We focus on their ability to induce DNA damage or oxidative stress, modulating the DNA damage response (DDR) and interfering with key oncogenic signaling pathways. We also discuss the potential of these compounds to enhance the efficacy of conventional therapies, thereby offering a promising role in overcoming clinical resistance. Despite clinical relevance remains under development and further studies are required; many of the natural compounds examined here appear to effectively target DDR signaling and oncogenic pathways, supporting their potential use in breast cancer therapy. Full article

Background/Objectives: Human papillomavirus (HPV) is the leading cause of cervical cancer and anogenital malignancies, yet its clinical presentation, genotype distribution, co-infection patterns, and viral load are poorly characterised in tertiary-care referrals. This study aimed to identify predictors of HPV positivity and describe genotype, co-infection, and relative viral copy number (Cq values) in this setting. Methods: A retrospective case–control study of 234 patients (97 HPV-positive, 137 HPV-negative) used a 37-genotype qPCR platform at a tertiary-care hospital between January-December 2025. Demographic data, clinical diagnosis categories, genotype profiles, co-infection patterns, and cycle quantification (Cq) values were recorded, and multivariable logistic regression identified independent predictors of HPV positivity. Results: HPV positivity was 41.5% (97/234). Only the clinical diagnosis category independently predicted HPV status. Compared with non-specific presentations, patients with anogenital or viral warts (aOR: 4.25; 95% CI: 1.49–12.14; p = 0.007) and vaginal or vulvar inflammation (aOR: 2.08; 95% CI: 1.19–3.63; p = 0.010) had higher odds of positivity. High-risk genotypes were the second most frequently detected category (40.00% of detections), after low-risk genotypes (48.21%), with HPV-16 leading among high-risk types. Co-infection occurred in 44.3% of HPV-positive patients, mostly involving mixed-risk genotypes. Patients with anogenital warts had lower Cq values than those with urinary tract complaints (p = 0.011), reflecting higher relative viral copy numbers per swab. Conclusions: HPV positivity and relative viral copy number (as approximated by Cq values) tracked more closely with clinical presentation than with demographic background. The dominance of low-risk and high-risk genotypes and the prevalence of mixed-risk co-infections were consistent with the symptomatic profile of the cohort. These findings support interpreting HPV results in light of clinical presentation and extended genotyping with relative viral copy number quantification in tertiary settings. Full article

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy associated with rapid proliferation, early metastatic spread, and poor long-term survival. Despite high initial responsiveness to chemotherapy and radiotherapy, most patients experience relapse, and therapeutic progress historically remained limited. Recent years, however, have seen meaningful advances that are beginning to reshape the management of SCLC. In extensive-stage disease, the incorporation of PD-L1 inhibitors into platinum-etoposide chemotherapy has established chemoimmunotherapy as the first-line standard, while underscoring the continued need for more durable disease control. In limited-stage SCLC, consolidation durvalumab following concurrent chemoradiotherapy has emerged as a practice-changing strategy with significant survival benefit. In relapsed disease, DLL3-targeted therapy has opened a new therapeutic avenue, with tarlatamab demonstrating clinically relevant efficacy in previously treated extensive-stage SCLC and becoming the first approved bispecific T-cell engager in this setting. Alongside these milestones, ongoing investigation is focused on maintenance strategies, novel targeted agents, biomarker development, molecular subtyping, and more effective integration of systemic therapy with radiation-based approaches. Nevertheless, resistance, toxicity management, central nervous system involvement, and the absence of validated predictive biomarkers remain major barriers to sustained progress. This narrative review examines recent advances in the biology and clinical management of SCLC, with emphasis on practice-changing developments, emerging therapeutic platforms, and future strategies aimed at improving outcomes in this historically difficult-to-treat disease. Full article

Background/Objectives: This study aimed to examine personality profiles at the intrapsychic level (“Oneself”) in adult and older patients with cancer and to compare potential differences between these age groups. Methods: In this observational, cross-sectional comparative study, 273 patients with cancer (all disease stages) were categorized into two age groups: adults (40–64 years, n = 141) and older adults (≥65 years, n = 132). Personality was assessed using the Structural Analysis of Social Behavior (SASB) Form-A. Descriptive and inferential bivariate statistical analyses, including Chi-square tests and independent-samples t-tests, were performed to evaluate differences between the two age groups. To further examine the association between age group and SASB Cluster 1, a multivariable exploratory post hoc factorial General Linear Model (factorial GLM) was conducted. Results: Comparisons between adults and older adults revealed significant differences in socio-demographic backgrounds, with older patients being more frequently widowed and having lower educational attainment (both p < 0.001). Regarding personality dimensions, a significant difference was observed exclusively in SASB Cluster 1 (Autonomy-Assertive and Separating), with higher scores among older participants (4.4 vs. 3.9; p = 0.002). However, in the adjusted factorial GLM, the main effect of age group was no longer statistically significant (p = 0.054), and no significant two-way interactions emerged, including the age-group-by-education interaction (p = 0.222). This indicates that the initial unadjusted age-group association was attenuated after accounting for selected socio-demographic variables. No significant differences were found between the two groups in the remaining SASB Clusters. Conclusions: These findings caution against overestimating the role of chronological age as an isolated variable in psycho-oncological research. Personality differences in Cluster 1 co-occur with distinct cohort-specific and socio-demographic life-course profiles. Understanding how personality relates to shifting socio-demographic circumstances across the lifespan may support the development of more tailored, context-sensitive psycho-oncological interventions. Full article

Lymphoid malignancies comprise a diverse group of hematologic cancers characterized by extensive genetic, epigenetic, and microenvironmental heterogeneity. Despite substantial advances in targeted therapies and immunotherapeutic approaches, disease relapse and therapeutic resistance remain major clinical challenges. Increasing evidence suggests that malignant lymphoid cells are highly dependent on protein homeostasis (proteostasis) networks to cope with the elevated proteotoxic stress imposed by oncogenic signaling, rapid proliferation, immunoglobulin synthesis, and microenvironmental stressors. This dependence, often referred to as proteostasis addiction, represents a critical vulnerability that can be therapeutically exploited. Proteostasis is maintained through an integrated network that regulates protein synthesis, folding, quality control, and degradation. In lymphoid malignancies, dysregulation of these pathways drives adaptive responses involving molecular chaperones, the unfolded protein response (UPR), the ubiquitin–proteasome system (UPS), and autophagy–lysosome pathways. These mechanisms collectively enable tumor cells to survive conditions that would otherwise induce proteotoxic collapse and cell death. Notably, the clinical success of proteasome inhibitors in plasma cell neoplasms has provided proof of concept that targeting proteostasis can yield meaningful therapeutic benefit. In this review, we discuss the major sources of proteotoxic stress in lymphoid malignancies and summarize the molecular mechanisms that sustain proteostasis addiction. We further examine current and emerging therapeutic strategies aimed at disrupting proteostasis networks, including proteasome inhibitors, UPR-targeted agents, chaperone-directed therapies, and novel targeted protein degradation technologies. Finally, we highlight the contribution of proteostasis remodeling to therapeutic resistance and discuss future opportunities for biomarker development and precision medicine. A deeper understanding of proteostasis dependencies may facilitate the identification of novel therapeutic vulnerabilities and improve outcomes for patients with lymphoid malignancies. Full article

Background: Prostate cancer patients with intermediate disease risk [Gleason score (GS)7] can be divided into two groups: GS = 7(3 + 4) (ISUP 2) (favorable disease risk) and GS = 7(4 + 3) (ISUP 3) (unfavorable disease risk). Low-dose-rate brachytherapy (LDR-BT) is an effective treatment for low- and intermediate-disease-risk patients. Objectives: The main goal of this study was to evaluate the effectiveness of LDR-BT monotherapy in prostate cancer patients classified as ISUP 3 when compared with ISUP 2 patients. Methods: This was a retrospective study that evaluated prostate cancer patients classified as ISUP 2 and ISUP 3 followed up at the Center for the Treatment of Urological Diseases, Portugal, who underwent LDR-BT. Overall survival (OS), biochemical recurrence-free survival (BRFS), bone metastasis and complications post-LDR-BT treatment were evaluated. Results: A total of 602 patients classified with GS = 7 (481/602 ISUP 2 and 121/602 ISUP 3) treated with LDR-BT were recruited. High OS rates and a reduced frequency of complications were described in both groups of patients. ISUP 3 patients had a lower BRFS rate, a higher risk of biochemical recurrence, and developed more bone metastasis in a shorter period when compared with ISUP 2 patients. No significant differences were detected in prostate-cancer-specific mortality between groups. Conclusions: LDR-BT monotherapy is a safe and effective treatment for prostate cancer patients with favorable and unfavorable intermediate disease risk, with similar OS rates and reduced complications. Full article

Alterations in body composition are clinically relevant features occurring in patients with breast cancer (BC), but the mechanism remains poorly defined. We investigated whether circulating microRNAs (miRNAs) involved in skeletal muscle (SM) and adipose tissue (AT) metabolism are associated with body composition alterations in BC. We analyzed by RT-qPCR circulating levels of SM- and AT-related miRNAs in a cohort of breast cancer patients (BCPs) (n = 46) and controls (n = 16). Associations between miRNA profiles and body composition parameters were evaluated. miR-21, miR-29a, and miR-29b were upregulated in BCPs compared with controls (all p < 0.05). miR-133a was downregulated in patients with low muscle mass (p = 0.040), independently of adiposity. miR-133a was found to be lower in BCP subgroups with LUM-B and low levels of muscularity compared to those with LUM-A or LUM-B with high muscularity levels (all p < 0.05). Correlation analyses supported a closer association of miR-133a with SM-related parameters than with fat mass. miR-21, miR-29a and miR-29b appeared to reflect tumor-related systemic signaling. miR-133a was associated with reduced SM mass and influenced by tumor molecular subtype. These results suggest that miR-133a might represent a potential mediator of cancer-associated SM alterations and warrant validation in larger longitudinal studies. Full article