Search Results (11,724)

Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) 9th edition nodal subclassification. Methods: In this retrospective study, 90 consecutive patients with clinically node-positive (cN1-2) resectable locally advanced NSCLC who underwent neoadjuvant chemoimmunotherapy followed by curative-intent resection were included. Disease-free survival (DFS) was analyzed according to postoperative pathologic nodal status. Nodal status was assessed using the UICC/AJCC 8th edition (ypN0, ypN1, ypN2) and reclassified according to the 9th edition (ypN0, ypN1, ypN2a, ypN2b). Residual postoperative nodal disease was defined as residual pathologic nodal involvement (ypN+) in patients with clinically node-positive (cN+) disease at baseline. Results: The cohort comprised 90 patients (60% male, median age 63 years [interquartile range (IQR) 58–69]. Following neoadjuvant therapy, surgery revealed pathologic nodal clearance in 53 (58.9%) and residual nodal disease in 37 (41.1%) patients (ypN1, n = 16 [17.8%]; ypN2a, n = 15 [16.7%]; and ypN2b, n = 6 [6.7%]). DFS differed significantly by postoperative nodal status (global log-rank p < 0.001), with progressively poorer outcomes with increasing residual nodal burden. Conclusions: Residual nodal disease after neoadjuvant chemoimmunotherapy and surgery is associated with progressively inferior DFS according to its anatomic extent. The UICC/AJCC 9th-edition staging system provides clinically relevant prognostic granularity, supporting further investigation of mediastinal restaging and postoperative treatment strategies. Full article

Background/Objectives: Clinical outcomes with immune checkpoint inhibitors (ICIs), such as nivolumab, vary among patients with metastatic non-small cell lung cancer (NSCLC). The Lung Immune Prognostic Index (LIPI) may help stratify prognosis. This study evaluated the prognostic significance of LIPI in patients receiving second- or third-line nivolumab and developed a nomogram for individualized survival estimation. Methods: This single-center retrospective study included 142 patients with metastatic NSCLC who received second- or third-line nivolumab between February 2022 and December 2024, after progression on platinum-based chemotherapy. LIPI was calculated from baseline values obtained within 14 days before nivolumab initiation, based on a derived neutrophil-to-lymphocyte ratio (dNLR) > 3 and lactate dehydrogenase (LDH) > 225 U/L (institutional upper limit of normal), classifying patients as good-, intermediate-, or poor-risk (0, 1, or 2 factors, respectively). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method; independent prognostic factors were assessed by multivariable Cox regression, and a prognostic nomogram combining ECOG performance status, serum albumin, and LIPI was developed and internally validated. Results: By LIPI, 34.5%, 45.1%, and 20.4% of patients were at good, intermediate, and poor risk, respectively. Objective response and disease control rates were 29.6% and 55.6%. Median OS and PFS were 19.3/8.0/3.1 and 8.6/3.1/2.5 months across good, intermediate, and poor LIPI groups (log-rank p < 0.001). In multivariable analysis, ECOG 2 (hazard ratio [HR], 4.94), albumin per 1 g/dL (HR 0.27), and poor versus good LIPI (HR 3.74) were independently associated with OS. A nomogram combining these three factors showed acceptable discrimination (optimism-corrected Harrell C-statistic 0.742). Conclusions: LIPI was independently associated with prognosis in this cohort. Combining LIPI with ECOG and albumin may aid individualized risk assessment, pending external validation. Full article

Cancer nanomedicine has generated extensive preclinical evidence of improved drug delivery, pharmacokinetics, and tolerability, yet its clinical impact has often remained modest. This narrative review examines the interconnected biological, pharmacokinetic, manufacturing, regulatory, and clinical factors underlying this translational paradox. A structured literature search was conducted primarily in PubMed and Google Scholar, focusing on studies published between 2022 and 2026 while retaining seminal earlier reports. Major biological barriers include protein corona formation, mononuclear phagocyte system clearance, heterogeneous enhanced permeability and retention, complex tumor microenvironments, and intratumoral heterogeneity. These factors limit circulation, tumor accumulation, tissue penetration, drug release, and interpatient reproducibility. Translation is further constrained by off-target accumulation, uncertain long-term toxicity, non-standardized experimental methods, batch-to-batch variability, scale-up challenges, and fragmented regulatory pathways. Clinical experience shows that successful products are dominated by relatively established platforms and reformulations of known anticancer agents, whereas many actively targeted or structurally complex systems have failed to demonstrate sufficient efficacy or safety. Future progress will require mechanism-driven design, human-relevant preclinical models, harmonized characterization, quality-by-design manufacturing, early regulatory integration, biomarker-guided patient selection, and adaptive clinical trials. Aligning nanoparticle engineering with biological and clinical realities is essential for achieving meaningful patient benefit. Full article

Background/Objectives: Lung cancer in Romania is characterized by high mortality and a lack of organized screening programs, resulting in frequent late-stage diagnoses. This study evaluates diagnostic patterns, stage distribution, and screening eligibility in a Romanian tertiary cohort to highlight the limitations of standard screening criteria and provide evidence for scalable, regionally adapted early detection strategies. Methods: We conducted a retrospective observational study of consecutive lung cancer patients treated at the Oncological Institute of Bucharest. To balance external validity with analytical robustness, the population was divided into a full cohort (Set A, n = 3764) for population-level descriptive analyses and a complete-case subset (Set B, n = 1768). Set B was utilized to simulate theoretical screening eligibility using established guidelines (USPSTF, NCCN, ERS) and to calculate a Missed Opportunity Index (MOI) for early-stage case capture. Results: Advanced-stage disease (Stages III–IV) overwhelmingly dominated the cohort, accounting for approximately 82% of diagnoses among patients with available staging information. Essential screening variables like smoking history were missing in 71.4% of the full cohort. In the complete-case subset, established guideline-based screening models demonstrated high MOI values, failing to capture approximately 69–73% of early-stage (Stage I–II) cases. Conversely, age-only minimal models appeared highly performant, structurally capturing approximately 95% of the cohort due to broad inclusiveness. Conclusions: In retrospective eligibility simulations, smoking-based screening models were associated with high missed opportunity rates for Stage I–II cases, highlighting a mismatch between simplified Western risk models and the multidimensional reality of lung cancer epidemiology in this cohort. These findings strongly support the need to move toward multivariable risk prediction models and population-adapted screening strategies that integrate non-traditional risk factors to better align screening eligibility with the true distribution of disease in real-world settings. Full article

Background/Objectives: Lung-RADS was introduced to standardize the management of nodules detected during lung cancer screening. However, significant interobserver variability has been reported, and its consistency across different hospital settings remains insufficiently investigated. This study aimed to compare Lung-RADS categorization and diagnostic performance between tertiary and non-tertiary hospitals, and to evaluate interobserver variability and associated differences in recommended management. Methods: This single-tertiary-center, referral-based retrospective study included patients referred to a tertiary hospital after lung cancer screening at 29 non-tertiary hospitals between September 2019 and December 2023. CT images were reinterpreted at a tertiary hospital using Lung-RADS. A blinded review was performed by an independent thoracic radiologist, and interobserver variability was assessed using Cohen’s kappa. Discordance rate and major discordance (≥9-month follow-up difference) were determined. Sensitivity, specificity, and diagnostic accuracy were calculated and compared. Results: Sixty patients (median age, 63 years [interquartile range, 58–68]; 59 men and one woman) with 43 confirmed final diagnoses (18 of lung cancer and 25 of benign lesions) were included. Interobserver variability was fair between tertiary and non-tertiary hospitals (κ = 0.30), and between non-tertiary hospitals and thoracic radiologist (κ = 0.28), but almost perfect between tertiary hospital and thoracic radiologist (κ = 0.82). Lung-RADS discordance occurred in 50.0% of the cases (30/60), with 70.0% (21/30) classified as major discordance. Among the 43 patients with confirmed final diagnoses, specificity was significantly higher in tertiary hospital reports (68.0%, 95% CI 46.5–85.1) compared to non-tertiary hospital reports (20.0%, 95% CI 6.8–40.7; p = 0.001), while sensitivity was comparable (100.0%, 95% CI 81.5–100 vs. 88.9%, 95% CI 65.3–98.6; p = 0.480). Conclusions: Frequent discordances in Lung-RADS categorization were observed between tertiary and non-tertiary hospitals. Higher specificity was observed for tertiary hospital interpretations within this referral cohort. These discrepancies may affect patient management, highlighting the need for strategies to improve consistency. Full article

Objectives: To characterize the frequency and temporal patterns of anterior segment findings after radiotherapy for sinonasal and nasopharyngeal cancer, with particular focus on anterior segment neovascularization and its association with superselective intra-arterial cisplatin infusion with concurrent radiotherapy (RADPLAT). Methods: We retrospectively reviewed 113 patients treated with intensity-modulated radiotherapy between 2019 and 2022. Anterior segment findings were evaluated using the whole cohort as the denominator and among patients referred for ocular symptoms. Cumulative incidence was estimated with death as a competing risk using the Aalen–Johansen estimator and compared using Gray’s test. Results: Median follow-up was 1666 days. Forty-seven patients (41.6%) were referred to ophthalmology. Anterior segment findings occurred in 16/60 patients (26.7%) with nasal cavity cancer and 13/31 (41.9%) with maxillary sinus cancer (p = 0.16); 5-year cumulative incidences were 27.7% and 46.1%, respectively (p = 0.018). Anterior segment neovascularization occurred in 7/113 patients (6.2%), including 6/21 (28.6%) treated with RADPLAT and 1/92 (1.1%) without RADPLAT (p < 0.001); 5-year cumulative incidences were 31.4% and 1.4%, respectively (p < 0.001). Among patients with maxillary sinus cancer, neovascularization occurred in 5/19 RADPLAT-treated patients and 0/12 non-RADPLAT patients (p = 0.13); however, median follow-up was substantially shorter in the non-RADPLAT group (385 vs. 1784 days). Neovascularization developed late (median, 975 days), and four affected patients had final best-corrected visual acuity below 0.05. Conclusions: Anterior segment findings showed distinct temporal patterns after radiotherapy. Late, vision-threatening neovascularization was strongly associated with RADPLAT, although causality cannot be established because treatment selection was confounded by tumor site, disease extent, orbital invasion, and radiotherapy characteristics. These findings identify anterior segment neovascularization as an important safety signal warranting prospective evaluation. Standardized baseline ophthalmological assessment, long-term surveillance, and patient-level ocular dosimetry are needed to clarify mechanisms and define appropriate follow-up strategies. Full article

Background: Approximately 13% of NSCLC cases have KRAS G12C mutations. As therapeutic strategies targeting KRAS G12C-mutant NSCLC evolve, it is important to understand clinical presentation and current outcomes for these patients. Methods: This retrospective study used data from two US nationwide databases, an electronic health records (EHR) database and a clinico-genomic database (CGDB) of EHR data linked to data from comprehensive genomic profiling tests. Eligible patients had advanced NSCLC, initiated first-line therapy from August 2018 to December 2022, and had KRAS test results. Clinicopathologic characteristics, treatments, real-world progression-free survival (rwPFS), and overall survival (OS) were analyzed. Results: There were 1227 patients with KRAS G12C-mutant NSCLC in the EHR database and 447 in the CGDB. First-line regimen was platinum-based chemotherapy plus pembrolizumab for 46% and pembrolizumab monotherapy for 20%. Less than 40% of patients received second-line therapy. Median (95% CI) OS for KRAS G12C-mutant NSCLC patients in the EHR was 17.0 (15.2–18.9) months. Variables significantly associated with shorter OS included PD-L1 <1%, brain metastases, STK11 co-mutation, and poor performance status. Patients treated with platinum-based chemotherapy plus pembrolizumab had median rwPFS of 5.3 (4.5–7.3) months and OS of 12.8 (11.1–17.3) months in the CGDB; median OS was 15.6 (12.5–18.6) months in the EHR. Patients with PD-L1 ≥ 50% treated with pembrolizumab monotherapy had median rwPFS of 4.6 (3.0–15.6) months and OS of 20.4 (10.3–38.5) months in the CGDB; median OS was 22.1 (18.7–30.7) in the EHR. Conclusions: These data provide a real-world benchmark of outcomes for patients with KRAS G12C-mutant NSCLC receiving the current standard of care and indicate an unmet need for more effective first-line therapies. Full article

Background: Skeletal muscle depletion predicts poor outcomes in gastrointestinal cancers, but whether volumetric three-dimensional (3D) body composition adds anything over the standard two-dimensional (2D) single-slice approach in colorectal cancer (CRC) patients receiving chemoradiotherapy is unclear. We quantified CT-derived sarcopenia and directly compared 2D and 3D body composition metrics from a fully automated deep learning pipeline. Methods: We retrospectively analyzed 368 patients with CRC. Body composition was quantified automatically from CT using SMAT-BC, a pipeline combining TotalSegmentator-based vertebral localization with an nnU-Net Residual Encoder XL network incorporating a Transformer bottleneck for four-class tissue segmentation. Single-slice L3 (2D) and L1–L5 volumetric (3D) indices were derived. The primary endpoint was overall survival (OS); recurrence-free survival (RFS) was secondary. Cox proportional hazards models with bootstrap optimism correction were used. Measurement reproducibility was assessed in 25 external TCGA-COAD cases. Results: Sarcopenia was strongly associated with both overall and recurrence-free survival (unadjusted OS HR 2.16, 95% CI 1.55–3.00; unadjusted RFS HR 1.83, 95% CI 1.36–2.47; both raw p < 0.001; adjusted OS HR 1.89, 95% CI 1.57–2.28; adjusted RFS HR 1.44, 95% CI 1.22–1.70; FDR-adjusted p < 0.0001 for both). L3 single-slice indices were strongly correlated with volumetric indices (r = 0.91 for muscle index) and added discriminant value over the clinical model for overall survival (optimism-corrected C-index: clinical 0.602 (95% CI 0.578–0.626), clinical + 2D 0.631 (95% CI 0.609–0.654), clinical + 3D 0.599 (95% CI 0.574–0.624); DeLong p = 0.002 for clinical + 2D vs. clinical, FDR-adjusted p = 0.006). The 2D- and 3D-augmented models yielded overlapping bootstrap confidence intervals and were not clinically meaningfully different in this cohort (OS ΔC = +0.032, 95% CI +0.013 to +0.051; FDR-adjusted p = 0.006; RFS ΔC = +0.008, 95% CI −0.011 to +0.027; FDR-adjusted p = 0.612). Conclusions: Automated CT-derived sarcopenia is an independent predictor of survival in CRC patients receiving chemoradiotherapy. In our cohort, single-slice L3 measurement matched or exceeded volumetric discrimination, but the 2D- and 3D-augmented models yielded overlapping bootstrap confidence intervals for both endpoints: for overall survival, the DeLong FDR-adjusted p value for the 2D-versus-3D contrast was 0.006, and 0.612 for recurrence-free survival. Because no non-inferiority margin was pre-specified, the 2D–3D comparison is presented as exploratory, and we make no formal claim of non-inferiority or equivalence for either endpoint. The findings support single-slice L3 measurement as an efficient biomarker for risk stratification but warrant external validation in larger prospectively designed cohorts. Full article

Background: South Asian Americans (SAAs) represent the fastest-growing U.S. immigrant group but remain underrepresented in breast cancer research. This study utilizes the National Cancer Database (NCDB) to evaluate differences in tumor characteristics, treatment patterns, and survival outcomes between SAAs and non-Hispanic Whites (NHWs). Materials and Methods: A retrospective cohort analysis was conducted using NCDB data from 2004–2021. Women with breast cancer were stratified by race/ethnicity (SAA vs. NHW), and demographic, clinical, and treatment variables were compared. Outcomes assessed were overall survival (OS) and treatment delays, defined as initiation of surgery, chemotherapy, or radiation therapy > 60 days after diagnosis. Multivariable Cox proportional hazards models assessed OS. Results: Among 2,363,627 patients, 20,561 (0.9%) were SAAs and 2,343,066 (99.1%) NHWs. SAAs were younger at diagnosis, with 37.6% aged 20–49 vs. 20.6% of NHWs (p < 0.001). Insurance coverage differed, with SAAs more likely privately insured (63.0% vs. 54.2%, p < 0.001), less likely on Medicare (17.2% vs. 37.9%), and more often uninsured (4.5% vs. 1.2%). Time to first treatment was longer for SAAs (39.55 vs. 37.17 days, p < 0.001). Surgical delays >60 days increased mortality by 59%, while chemotherapy delays raised it by 44%. SAAs demonstrated higher survival at 5, 10, and 15 years (93%, 87%, 81%) vs. NHWs (87%, 76%, 64%). Median survival was 225.8 months but not estimable for SAAs. SAAs presented with aggressive subtypes: triple-negative and HER2-positive tumors. Conclusions: SAAs present younger with aggressive subtypes and treatment delays yet maintain survival advantages; reducing care barriers and clarifying tumor biology are vital to improving outcomes. Full article

Background and Objectives: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, and its global incidence rate constantly rises. However, there are no current epidemiological data for many regions, including Małopolska in southern Poland. This study aimed to characterize the clinical and histological profile of patients with BCC and to identify factors associated with local recurrence and the presence of multiple tumors. Materials and Methods: We performed a single-center, retrospective observational study consistent with STROBE guidelines at the Department of Dermatology and Allergology, University Hospital in Cracow. The included patients were adults with at least one histologically confirmed BCC treated between 2015 and 2025. Demographic, clinical, histopathological, and follow-up data were collected at patient and lesion levels. The results were evaluated using univariable tests, multivariable logistic regression, Kaplan–Meier survival analysis, and generalized estimating equations. Results: We included 108 patients (median age at first diagnosis, 73 years; 52% male) with 418 BCCs; the median follow-up duration was 84 months. Superficial BCC was the most common subtype among lesions with available histological subtype information (56%). The head and neck region was the most frequent anatomical site in this group (51%). Multiple BCCs were present in 62% of patients. Longer follow-up was independently associated with the presence of multiple BCCs. A history of actinic keratoses showed a positive but statistically nonsignificant association with multiple BCCs. Recurrence was observed in 15 lesions (3.6%). Female sex and H-zone involvement showed higher odds of recurrence. Conclusions: In this elderly cohort, multiple BCC tumors may reflect longer follow-up and cumulative actinic damage. Recurrence was relatively infrequent but associated with clinically relevant features, including H-zone involvement and female sex. These findings support an individualized, multifactorial approach to treatment and follow-up, taking into account age, sex, lesion burden, anatomical location, and histological subtype. Full article

Background: Disseminated invasive aspergillosis (IA) is an uncommon but devastating manifestation of disease, particularly when the central nervous system (CNS) is involved. The clinical features and outcomes of CNS dissemination, compared with isolated invasive pulmonary aspergillosis (IPA) and other disseminated forms, remain poorly characterized. Methods: Using an institutional database of 1157 cancer patients diagnosed with IA between 1993 and 2024, we identified 43 patients with disseminated IA, defined as infection involving ≥2 non-contiguous organ systems, including 8 with CNS involvement. Patients with disseminated IA were matched 1:3 to patients with IPA based on year of diagnosis. We compared clinical features, antifungal treatment, and outcomes between: (1) CNS-disseminated IA and IPA, and (2) CNS-disseminated IA and other forms of disseminated IA. Results: Baseline characteristics, including hematologic malignancy subtype, hematopoietic stem cell transplantation status, neutropenia, and antifungal prophylaxis, were similar across groups. Aspergillus fumigatus was the predominant species in all cohorts. No patients with CNS-disseminated IA achieved clinical response at end of therapy, versus 35% with IPA (p = 0.05) and 30% with other disseminated IA (p = 0.17). Twelve-week IA-associated mortality was significantly higher in CNS-disseminated IA than in IPA (88% vs. 45%, p = 0.028) and was higher than in other disseminated IA (88% vs. 46%, p = 0.05). Combination antifungal therapy was more frequently used in CNS-disseminated IA than in IPA (63% vs. 31%) and other disseminated IA (63% vs. 43%), while rates of ICU admission and mechanical ventilation were similar across groups. Conclusions: CNS involvement in disseminated IA defines a distinct, high-risk phenotype, with profoundly reduced treatment response and survival despite comparable baseline characteristics. Given the small number of CNS cases and the predominance of cases diagnosed during earlier study periods, these findings should be interpreted with caution. Although combination antifungal therapy was used more frequently in CNS-disseminated IA, no significant outcome benefit was observed, underscoring the need for improved therapeutic approaches for CNS aspergillosis in immunocompromised hosts. Full article

Background: Host-related factors such as skeletal muscle and adipose tissue characteristics are increasingly recognized as determinants of outcome in advanced non-small cell lung cancer (aNSCLC). However, the prognostic relevance of integrated body composition phenotypes in patients receiving first-line immunotherapy-based treatment remains unclear. Methods: We retrospectively analyzed patients with aNSCLC treated with first-line immune checkpoint inhibitors (ICI) alone or combined with chemotherapy (ICI–CT) between October 2018 and December 2023 at LMU University Hospital. AI-derived CT biomarkers included skeletal muscle volume index (SMVI), skeletal muscle density (SMD), visceral adipose volume index (VAVI), and subcutaneous adipose volume index (SAVI), normalized for height. Individual body composition parameters were analyzed as standardized continuous variables. For exploratory phenotype analyses, SMVI and VAVI were categorized using cohort-specific sex-stratified median values. An integrated body composition phenotype was defined as “high-muscle/low-visceral-adiposity” (high SMVI/low VAVI) or “low-muscle/high-visceral-adiposity” (low SMVI/high VAVI), with patients not meeting either definition classified as having an intermediate phenotype. Multivariable Cox regression adjusted for age, sex, treatment modality, and metastatic burden evaluated associations with progression-free survival (PFS) and overall survival (OS). Results: Of 116 screened patients, 103 with evaluable baseline CT imaging were included. The cohort predominantly comprised ever-smokers (81.6%) and patients with adenocarcinoma (62.1%). Higher SMD (per one standard deviation increase) was associated with improved overall survival (HR 0.72, 95% CI 0.52–1.00; p = 0.047), and higher VAVI was associated with a higher risk of death (HR 1.29, 95% CI 1.00–1.65; p = 0.048). Neither SMD nor VAVI was significantly associated with PFS, and SMVI and SAVI were not significantly associated with OS or PFS. In the exploratory integrated phenotype analysis, median OS was 29.5 months in the high-muscle/low-visceral-adiposity group, 16.2 months in the intermediate group, and 19.3 months in the low-muscle/high-visceral-adiposity group; however, the overall Kaplan–Meier comparison was not statistically significant (log-rank p = 0.385). Conclusions: AI-derived CT body composition assessment may provide complementary prognostic information in patients with aNSCLC receiving first-line immunotherapy-based treatment. Higher skeletal muscle density was associated with a lower risk of death, whereas higher visceral adiposity was associated with a higher risk of death. The exploratory integrated phenotype analysis did not demonstrate a consistent risk gradient across phenotype categories. These findings require validation in larger prospective cohorts before clinical implementation. Full article

Background: Locally advanced rectal cancer (LARC) treatment has shifted from the utilization of neoadjuvant chemoradiation (NACRT), followed by total mesorectal excision (TME) and adjuvant chemotherapy (AC) to the implementation of total neoadjuvant therapy (TNT). This transition was influenced by data from multiple studies reporting suboptimal compliance rates to adjuvant chemotherapy. As a result, a paradigm shift to TNT occurred, consisting of chemoradiation with chemotherapy, based on the RAPIDO and PRODIGE-23 studies. Methods: Following IRB approval, a single-institution retrospective chart review was conducted at a tertiary care academic institution for patients with LARC. Demographic, clinical, and treatment data were collected using REDCap. Patients were excluded if under 18 years of age, pregnant, or had stage 1 or metastatic rectal cancer. The primary objective was to evaluate TNT adherence; secondary objectives assessed adherence associations with demographic and clinical variables. Results: Two hundred twenty-nine patients with rectal cancer were initially included in the database, including 153 patients with LARC from 2019 to 2024. One hundred twenty-seven patients underwent TNT with an adherence rate of 87.5%. Statistically significant variables that contributed to adherence include male gender (p = 0.04) and non-use of recreational drugs (p = 0.04). Conclusions: This is the first real-world study assessing TNT adherence. The observed 87.5% adherence rate represents a significant improvement over historical data in which patients were treated with NACRT/TME/AC. Statistically significant variables that contributed to TNT adherence included male gender and non-use of recreational drugs. These factors may provide insight into gender differences and behavioral patterns that put patients in an at-risk category for non-adherence. Full article

Rnd3 is an atypical member of the Rho GTPase family whose activity is mainly regulated by expression, localization and protein stability rather than canonical GDP/GTP cycling. In cancer, Rnd3 has been described both as a tumor suppressor and as a tumor-promoting factor, creating an apparent functional paradox. We propose that this paradox is resolved by a mechanistic invariant: Rnd3 exerts a conserved inhibition of RhoA/ROCK1-dependent actomyosin contractility, whose phenotypic output is redirected by context-specific accessory effectors rather than reversed. In this review, we revisit this paradox by integrating evidence from mechanistic studies, tumor models and patient-associated datasets. We propose that Rnd3 should not be interpreted through a binary oncogene/tumor-suppressor framework, but rather as a context-dependent regulator of tumor cell state. In many tumor settings, Rnd3 repression or loss of Rnd3 function favors proliferation, apoptosis resistance and therapy resistance through pathways involving Notch, NF-κB, EGFR/ERK, EZH2-dependent chromatin regulation, m6A-mediated RNA control, microRNAs and chaperone-mediated autophagy. However, in selected contexts, including RTK-driven glioblastoma, hepatocellular carcinoma, non-small-cell lung cancer, melanoma and gastric cancer, Rnd3 may support tumor fitness, migration or invasive plasticity. We therefore propose a functional stratification model in which Rnd3 output depends on the biological process, tumor lineage, pathway activity and mechanical state of the cell. Full article

Recurrent non-melanoma skin cancer (NMSC) may be accompanied by cosmetic, functional, and emotional consequences. Aims: To examine associations among psychological symptoms, quality of life, resilience, and religiosity and to compare psychological outcomes between patients treated once and patients with recurrent facial NMSC. Methods: This cross-sectional study included 160 patients after surgery for facial NMSC (63 treated once and 97 with recurrent disease). Data were collected with a sociodemographic questionnaire, the Symptom Checklist-90-R (SCL-90-R), the Connor–Davidson Resilience Scale 25 (CD-RISC-25), the World Health Organization Quality of Life Scale (WHOQOL-BREF) and DUREL. Results: Greater psychological symptom severity was consistently associated with poorer scores across all WHOQOL-BREF domains. The overall multivariate group effect was significant (Pillai’s Trace = 0.235, F(6.149) = 7.641, p < 0.001, partial eta squared = 0.235). After Bonferroni correction for six follow-up tests, patients with recurrent NMSC had a higher adjusted GSI and lower adjusted psychological health scores than patients treated once (both p < 0.001). Adjusted differences in physical health, social relationships, environment, and CD-RISC were not statistically significant. Conclusions: Recurrent NMSC status was associated with greater psychological symptom burden and poorer psychological quality of life. Routine psychological screening may help identify patients who require further assessment or support. Full article