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.
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.
Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent malignancy. While Cemiplimab has transformed the treatment landscape across various disease stages, reliable pretreatment biomarkers for risk stratification remain lacking.. The Global Immune–Nutrition–Inflammation Index (GINI) is a composite biomarker integrating systemic inflammation and nutritional status into a single score. This study aimed to evaluate the prognostic value of the pretreatment GINI in patients with cSCC receiving Cemiplimab across all treatment settings. Methods: This retrospective cohort study evaluated 73 patients with unresectable, locally advanced, or metastatic cSCC treated with Cemiplimab between 2020 and 2023. Pretreatment laboratory parameters were extracted to calculate the GINI score. Receiver operating characteristic (ROC) curve analysis determined the optimal GINI cutoff to stratify patients into low- and high-GINI groups. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed using Kaplan–Meier curves and multivariable Cox proportional hazards models. Results: An optimal GINI cutoff of 74.4 divided the cohort into low-GINI (38%) and high-GINI (62%) groups. In the multivariable Cox regression models, a high pretreatment GINI remained independently associated with both inferior OS (adjusted HR 2.51, 95% CI 1.05–6.01, p = 0.039) and inferior PFS (adjusted HR 3.22, 95% CI 1.45–7.14, p = 0.004). When compared against five established inflammatory biomarkers (NLR, PLR, LMR, PNI, and CAR), the GINI consistently demonstrated comparable prognostic performance across multiple statistical approaches. Conclusions: The pretreatment GINI is a candidate prognostic marker for patients with cSCC undergoing Cemiplimab therapy. Given its cost-effectiveness and ready availability from routine clinical laboratory workups, the GINI score may improve prognostic risk stratification and could potentially inform risk assessment and clinical monitoring in real-world oncological practice.
Complete resection remains the only potentially curative treatment for localized intrahepatic cholangiocarcinoma (iCCA), yet postoperative recurrence is common, particularly in patients with high-risk disease. Neoadjuvant systemic therapy may permit earlier control of occult micrometastatic disease, optimize the delivery of systemic treatment, and provide an in vivo assessment of tumor biology prior to major hepatectomy. These potential benefits must be balanced against treatment-related toxicity, surgical delay, and the risk of disease progression precluding resection. Early evidence was primarily derived from retrospective studies, which yielded inconsistent survival outcomes and exhibited substantial vulnerability to confounding and treatment-selection bias. The single-arm NEO-GAP trial subsequently demonstrated the feasibility of administering neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel followed by surgical resection. More recently, the randomized phase II–III ZSAB-neoGOLP trial showed that neoadjuvant gemcitabine–oxaliplatin, lenvatinib, and toripalimab followed by surgery prolonged median event-free survival compared with upfront surgery (median: 18.0 vs. 8.7 months) without substantially compromising surgical feasibility. However, the interim overall survival analysis was inconclusive, and the generalizability of these findings beyond selected, medically fit patients treated at Chinese centers remains uncertain. This narrative review critically appraises the evolving evidence, discusses patient selection and perioperative treatment, and identifies priorities for future research. Current evidence supports the selective consideration of neoadjuvant therapy in medically fit patients with technically resectable but oncologically high-risk iCCA, rather than its routine use in all resectable cases.
Background: Comorbidity is an important determinant of treatment selection and in-hospital complications in patients with head and neck cancer (HNC) and thyroid cancer (TC), yet population-based evidence on this relationship remains limited. Methods: We analyzed nationwide Diagnosis-Related Groups (DRG) data from 1,552,028 inpatient HNC and TC treatments of patients aged ≥30 years in Germany between 2005 and 2021. The aim was to characterize the association of comorbidity and severe treatment-related procedure-coded inpatient events (IEs) with gender, age, tumor subsite, and treatment type. Results: The largest proportion of treatments occurred in patients aged 60–69 years (33.5%). The most frequent tumor subsites were the oropharynx, thyroid gland, oral cavity, larynx, and hypopharynx, with 35.52, 33.84, 33.60, 26.12, and 15.76 treatments per 100,000 population per year, respectively. Overall, 38% of cases had a Charlson Comorbidity Index (CCI) ≥ 1, with the highest mean CCI observed for C14 (other sites of the lip, oral cavity and pharynx) and C12 (piriform sinus). IEs requiring additional in-hospital treatment occurred in 19.3% of cases. After adjustment for age, tumor location, and treatment type, men had a lower risk of IEs than women (OR 0.929; CI 0.919–0.939; p < 0.001). Increasing comorbidity was associated with a higher IE risk, reaching a plateau at CCI ≥ 4 (OR 2.135; CI 2.029–2.246; p < 0.001). IE risk was high during chemotherapy/immunotherapy (OR 29.527; CI 28.897–30.170; p < 0.001), followed by surgery (OR 3.465; CI 3.433–3.498; p < 0.001), whereas radiotherapy showed the lowest risk (OR 1.339; CI 1.313–1.366; p < 0.001). Conclusions: These findings highlight substantial heterogeneity in comorbidity and IE risk among patients with HNC or TC.
Background: Stage II/IIIA colorectal cancer (CRC) patients have a relatively high 5-year overall survival rate after surgical resection alone, but more than 50% of patients receive adjuvant chemotherapy. This study investigates a technology that applies artificial intelligence (AI) to conventional histopathology images to identify patients at risk of recurrence. Methods: HistoNav, a novel AI deep-learning algorithm based on Vision Transformer, Graph Neural Networks and Convolutional Neural Networks was designed to analyse H&E-stained formalin-fixed paraffin-embedded (FFPE) samples (n = 2095) to stratify Stage II/IIIA CRC patients into low-, intermediate-, and high-risk groups. Results: Data analysis revealed a 5-year disease-specific survival (DSS) of 93.2%, 84.3%, and 69.3% for low-, intermediate-, and high-risk groups, respectively. The hazard ratio for the high versus low-risk group (HR = 4.611, 95% CI: 2.776–7.662; p < 0.000001) was statistically significant, demonstrating HistoNav’s potential to stratify patients based on recurrence risk. Conclusions: HistoNav can effectively identify CRC patients with good prognosis using the digital images of H&E-stained resection samples and will support clinical decisions around the use of adjuvant chemotherapy.
This review aims to provide a comprehensive overview of the currently available therapies for primary vitreoretinal lymphoma (PVRL) and to evaluate emerging therapeutic strategies that may improve patient outcomes. A comprehensive literature search was conducted in databases including PubMed/MEDLINE, Embase, and Scopus for studies published up to 2026. Search terms included “primary vitreoretinal lymphoma”, “intravitreal methotrexate”, “rituximab”, “radiotherapy”, “targeted therapy”, and “immunotherapy”. Eligible publications included randomized controlled trials, prospective and retrospective studies, observational studies, systematic reviews, relevant clinical guidelines, case series, and case reports. Studies were independently screened and assessed by two reviewers. Current therapeutic strategies include intravitreal chemotherapy, systemic high-dose methotrexate-based regimens, and radiotherapy, either as monotherapy or in combination. While intravitreal approaches provide effective local disease control, they fail to address occult or subsequent central nervous system (CNS) dissemination, necessitating the use of systemic treatments in selected patients. In recent years, significant progress in the understanding of PVRL pathophysiology, including the role of MYD88 mutations and interleukin-10 signaling, has paved the way for the development of targeted and immunomodulatory therapies. Agents such as Bruton’s tyrosine kinase inhibitors, immunomodulatory drugs, and immune checkpoint inhibitors have demonstrated promising results in early clinical studies, particularly in relapsed or refractory disease. Despite advances in diagnostic techniques, the management of PVRL remains challenging due to its heterogeneous presentation, high relapse rates, and frequent progression to CNS involvement.
Background: Multiple myeloma (MM) remains an incurable plasma cell malignancy characterized by marked clinical heterogeneity. Existing prognostic frameworks, including the International Staging System (ISS) and FISH-defined cytogenetic risk, are anchored at diagnosis and do not capture the evolutionary dynamics of disease or treatment response, leaving an unmet need for risk models that retain prognostic validity longitudinally. Methods: Using transcriptomic data from 762 CD138-selected MM plasma cells from newly diagnosed patient samples in the MMRF CoMMpass study (NCT01454297), we computed single-sample pathway activity scores for 469 curated cancer-relevant pathways (MSigDB Hallmark; Reactome) and learned a Bayesian causal network linking pathway activity to survival. The model was validated in five independent diagnostic cohorts (n = 1255) and in two independent treatment and relapsed/refractory cohorts (n = 319). Longitudinal risk tracking was additionally assessed in a 46-patient subset of the discovery cohort with serial pre- and post-treatment sampling. Results: The network identified five pathways associated with survival: unfolded protein response (UPR), FLT3 signaling through SRC family kinases, G2M DNA replication checkpoint, metabolism of selenium compound (SeMet), and nicotinate metabolism. The composite survival score stratified patients into high-risk (n = 76; 10%) and standard-risk groups with markedly divergent survival (median 1170 days vs. not reached; p < 0.0001). The score remained an independent prognostic factor after adjustment for age, sex, ISS stage, and KRAS, TP53, and UBR5 mutational status (HR 4.93; 95% CI 2.96–8.19; p < 0.001), and replicated across all five external diagnostic cohorts. Critically, the model retained prognostic discrimination in previously treated (GSE57317; p < 0.0001) and relapsed/refractory (GSE9782; p < 0.0001) settings, and patients transitioning from standard- to high-risk between serial samples exhibited significantly inferior survival compared to standard-risk patients. Conclusions: This pathway-based Bayesian network provides a reproducible, dynamically applicable risk model for MM that captures information complementary to ISS and FISH-defined cytogenetics. The framework supports longitudinal patient monitoring and may inform trial enrichment strategies and closer surveillance for high-risk subpopulations.
Background/Objectives: Renal mass biopsy (biopsy) is increasingly incorporated into the evaluation of localized renal masses, yet its role in guiding management remains variable among clinical practices. We evaluated the clinical association of biopsy using a simplified classification system categorizing biopsy results as Biopsy Actionable for Immediate Treatment (BAIT) or Biopsy Actionable for Active Surveillance (BAAS)—assessing how biopsy-derived histology influences real-world management. Methods: We identified all patients undergoing biopsy for a renal mass measuring 2–7 cm at a single academic center between 2010 and 2025. After excluding nondiagnostic biopsies, repeat biopsies, and biopsies performed for metastatic diagnosis, 1395 patients formed the analytic cohort. Histologic subtypes and initial treatment were evaluated. Multivariable logistic regression assessed predictors of (1) radical versus partial nephrectomy, (2) surgery versus thermal ablation, and (3) active surveillance versus intervention, adjusting for tumor diameter, age, and BAIT/BAAS status. Results: Of 1395 patients, 1119 (80.2%) had BAIT pathology and 276 (19.8%) had BAAS pathology. Initial management included surgery (36.3%), thermal ablation (36.3%), active surveillance (24.2%), no treatment (1.7%), and radiation (1.5%). BAAS pathology was strongly associated with the selection of active surveillance (OR 21.80, p < 0.001). Larger tumor diameter was the principal driver of radical nephrectomy (OR 2.04/cm, p < 0.001) and of choosing surgery over ablation (OR 2.05/cm, p < 0.001). Younger age was associated with selection of surgery over ablation (OR 0.93/year, p < 0.001). Biopsy histology showed a stronger association with surveillance selection than either tumor diameter or age. Conclusions: Biopsy provides actionable diagnostic information for patients with 2–7 cm renal masses, identifying benign or indolent pathology in nearly one in five patients. BAIT/BAAS categorization was strongly associated with the selection of active surveillance for renal masses.
Background/Objectives: Acute lymphoblastic leukemia (ALL) treatment is effective but involves the use of cardiotoxic anthracyclines. Data on three-dimensional (3D) strain echocardiography utility in the monitoring of acute and early-onset cardiotoxicity in children with ALL are scarce. The aim was to assess the left ventricular function in 3D strain echocardiography in children with ALL treated with anthracyclines in reference to a healthy cohort and to assess risk factors of possible subclinical cardiotoxicity. Methods: For this study, medical records from between May 2023 and December 2024 were retrospectively analyzed, and the echocardiographic data were reassessed. The study group consisted of children diagnosed and treated for ALL for at least 6 months with the use of daunorubicin and doxorubicin (or only with daunorubicin) who underwent routine cardiological evaluation with 3D echocardiography in >6 months and <2 years from the beginning of treatment. The echocardiographic records were reassessed offline to analyze the left ventricle 3D global longitudinal (GLS 3D), circumferential (GCS 3D) and radial (GRS 3D) strain. The results were compared with the results of 24 apparently healthy peers matched by sex and age. A set of models was developed to test literature-based subclinical cardiotoxicity determinants in relation to the obtained 3D strain values. Results: The study group consisted of 42 children (22 males and 20 females) aged 2–17 years (mean 7.7 ± 4.1 years) treated for ALL. The median time from the first anthracycline dose was 0.59 (IQR1 = 0.5; IQR3 = 0.96) years with a cumulative equivalent anthracycline dose of 158.2 ± 78.0 (min. 48.0–max. 451.8) mg/m2. Statistically significant differences between study and control groups were observed in terms of LVEF 3D (53.9 ± 4.4% vs. 59.1 ± 5.8%, p < 0.001), GLS 3D (−21.8 ± 4.2% vs. −25.2 ± 3.6%, p < 0.001), GCS 3D (−22.3 ± 3.8% vs. −27.3 ± 4.7%, p < 0.001) and GRS 3D (37.1 ± 5.0% vs. 44.6 ± 5.7%, p < 0.001). None of the previously described cardiotoxicity risk factors—age at the diagnosis, sex, age at treatment initiation, body surface area (BSA) at treatment initiation, time since treatment initiation, ALL subtype, total anthracycline dose and doxorubicin treatment—were statistically significant in the GLS or GCS models. Conclusions: GLS 3D, GCS 3D and GRS 3D of the left ventricle may be sensitive indicators of myocardial dysfunction in children with ALL treated with anthracyclines. The relation of the previously described cardiotoxicity risk factors to the 3D strain values and myocardial dysfunction is inconclusive; further studies are warranted.
Background/Objectives: Tanzania is a low-to-middle-income-country (LMIC) which endures significant adverse impact from HIV-1- and HPV-associated malignancies. We investigated the performance of visual inspection with acetic acid (VIA) compared to the Pap smear. Methods: Screening performance was assessed in a cross-sectional study design across rural catchment clinics in Bagamoyo and Chalinze, and an urban site, Ocean Road Cancer Institute (ORCI), in Dar es Salaam. Pap smears were performed and were read in triplicate by readers blinded to HIV status and patient demographic data. Blood samples were collected for HIV status confirmation. All cytopathology, VIA, and HIV status data were compared with patient demographic factors. Results: Here we present results from 672 patients. Analysis of participants across the cohort revealed a high rate of HIV (25%) and exchange of “sex for money” in the rural site of Chalinze. Bagamoyo and ORCI had slightly lower HIV rates of about 16% and 12%, respectively. Despite the high HIV rates in Chalinze (25%), there was a contrastingly low-level of detectable lesions by VIA (9%) in this region. Conclusions: Overall, VIA-positive cases were 26% HSIL-positive, whereas VIA-negative cases were 14% HSIL-positive, suggesting that performance of VIA is limited.
Background/Objectives: Magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (IGABT) is the preferred standard for cervical cancer, but access remains limited in many settings. Computed tomography (CT)-based IGABT provides a practical alternative. We evaluated clinical outcomes and prognostic factors following its routine implementation. Methods: This retrospective cohort study included patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage I–IVA cervical carcinoma treated with definitive radiotherapy incorporating CT-based IGABT from January 2019 to December 2021. Patients received pelvic external beam radiotherapy (45–50.4 Gy in 23–28 fractions), with or without concurrent platinum-based chemotherapy, followed by four high-dose-rate brachytherapy fractions. Local control and overall survival were estimated using Kaplan–Meier analysis, and prognostic factors were evaluated using Cox regression. Results: Among 237 patients, 56.9% had FIGO stage III–IV disease, and hybrid intracavitary/interstitial brachytherapy was used in 30.2% of fractions. The mean high-risk clinical target volume D90 (HR-CTV D90) was 85.4 ± 2.7 Gy EQD2. Median follow-up was 59.9 months for local control and 71.1 months for overall survival. The 5-year local control and overall survival rates were 84.4% (95% CI, 79.1–88.5%) and 62.9% (95% CI, 56.3–68.8%), respectively. Squamous histology was independently associated with improved local control and overall survival. HR-CTV D90 ≥ 85 Gy EQD2 was associated with improved local control, whereas ≥4 chemotherapy cycles and overall treatment time ≤ 56 days were associated with improved overall survival. Conclusions: Routine CT-based IGABT achieved clinically meaningful outcomes despite the high proportion of advanced-stage disease. Achieving HR-CTV D90 ≥ 85 Gy EQD2, delivering ≥4 chemotherapy cycles, and completing treatment within 56 days were associated with improved outcomes.
Background: Persistent human papillomavirus (HPV) can cause low- or high-grade cervical lesions, which may progress to cervical cancer. This prospective, multicenter, real-world study assessed the effectiveness, tolerability and safety of a Coriolus versicolor-based vaginal gel for the regression of HPV-related low-grade cervical lesions in routine Greek practice. Methods: PAPILOBS-GR is a multicenter, open-label, non-interventional, prospective observational, non-comparative study conducted across 45 sites in Greece. Women aged ≥18 years with ASCUS/LSIL cytology and concordant colposcopy were enrolled. Participants received Coriolus versicolor-based vaginal gel for six months. A second 6-month cycle was offered if needed. The primary endpoint was lesion regression. Secondary endpoints included HPV clearance, patient satisfaction, biopsy evolution, tolerability, and safety. Results: Of 524 enrolled patients (mean age: 34.4 ± 10.0 years; 40.5% HR-HPV), 494 (94.3%) completed the study. Overall, 75.9% achieved lesion regression (72.1% at 6 months and 34.0% at 12 months). HPV clearance occurred in 72.0% overall (68.1% at 6 months and 50.0% at 12 months). Exploratory comparisons showed generally consistent effectiveness across subgroups, including women with HR-HPV, those aged >40 years, and vaccinated participants. No significant differences in clinical endpoints were observed in association with age or vaccination status. Among 22 patients with baseline and 12-month biopsies, 59.1% showed histological improvement. Satisfaction scores exceeded 8/10 at 6- and 12-month follow-ups. Only two non-serious possibly product-related adverse events were reported. Conclusions: Coriolus versicolor-based vaginal gel was associated with high rates of lesion regression and excellent tolerability, reinforcing previous clinical findings and supporting its potential role as an adjunctive approach during watchful waiting for HPV-positive low-grade cervical lesions.
Cellular responses depend on the coordinated regulation of receptor activation, trafficking, and signaling across distinct membrane and intracellular compartments. Proteoglycans (PGs), traditionally regarded as structural components of the extracellular matrix and co-receptors, are now emerging as active organizers of receptor dynamics. This review examines the mechanisms through which PGs regulate receptor trafficking and spatial signaling in cancer. Recent studies addressing the roles of proteoglycans in receptor clustering, endocytic pathway selection, intracellular trafficking, recycling, lysosomal degradation, endosomal signaling, exosome biogenesis, and nuclear receptor transport were evaluated, with particular attention to the strength of direct evidence for trafficking. Particular attention was given to the complementary functions of proteoglycan core proteins, glycosaminoglycan chains, and extracellular matrix remodeling in shaping receptor behavior. Current evidence demonstrates that proteoglycans govern multiple stages of receptor biology by controlling ligand presentation, receptor accessibility, membrane organization, intracellular trafficking, and signaling persistence. Individual proteoglycans exert distinct effects on receptor fate, ranging from receptor downregulation and degradation to sustained endosomal signaling and nuclear receptor translocation. Cancer-associated alterations in proteoglycan expression, glycosaminoglycan sulfation, heparanase activity, ectodomain shedding, and glycocalyx organization remodel signaling networks, strengthen communication between tumor and stromal cells, and promote tumor progression, immune modulation, metastasis, and therapeutic resistance. Proteoglycans have emerged as fundamental regulators of receptor trafficking and signaling architecture. Through the integration of extracellular matrix organization with receptor dynamics, they shape the spatial and temporal properties of oncogenic signaling. This conceptual framework broadens our understanding of tumor biology and identifies proteoglycan-dependent regulation of receptor trafficking as a promising avenue for future therapeutic intervention.
Background/Objectives: Cardiovascular morbidity following definitive chemoradiotherapy (CRT) for lung cancer is a major concern in Appalachia due to high rates of smoking and pre-existing cardiovascular disease. This study characterized the cardiovascular burden following CRT in a real-world Appalachian population. Methods: A retrospective study was conducted among Appalachian patients with lung cancer treated with definitive CRT from 2013 to 2025. Cardiovascular adverse event (CVAE) incidence, spectrum, and temporal distribution were characterized. Kaplan–Meier and Cox regression analyses evaluated time to CVAE and overall survival (OS). Exploratory machine-learning (ML) models assessed CVAE and mortality prediction. Results: Fifty-one patients (59%) experienced a CVAE. NSTEMI (15/51, 29%) and pericardial disease (15/51, 29%) were most frequent, followed by arrhythmia (8/51, 16%). Ischemic events occurred predominantly within the first year, whereas pericardial events were concentrated within 2 years. Median CVAE-free survival was 22.6 months, with estimated cumulative CVAE occurrence of 28.3% at 1 year and 50.0% at 2 years. After adjustment for age, cardiovascular comorbidity, and M stage, heart V20 (HR, 1.024 per 1% increase; 95% CI, 1.005–1.044; p = 0.015) and V30 (HR, 1.031; 95% CI, 1.004–1.058; p = 0.025) were associated with increased CVAE hazard. Median OS was 29 months; pre-existing cardiovascular comorbidity was associated with mortality (HR range, 2.16–2.45). Exploratory ML showed limited CVAE prediction but moderate mortality discrimination after feature selection (maximum AUC, 0.71). Conclusions: Cardiovascular morbidity was common and accumulated over time following definitive CRT in this Appalachian cohort. These findings support attention to baseline cardiovascular risk, cardiac radiation exposure, and longitudinal cardiovascular surveillance.
Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma that is histologically and clinically heterogeneous. Skeletonization is a computer vision technique used in image description, segmentation, and pattern recognition. Objectives: This retrospective observational study analyzed the 2D-topological heterogeneity of DLBCL. Methods: A series of 153 patients, including 110 patients with DLBCL and 43 patients with reactive lymphoid tissue, were analyzed by skeleton analysis using hematoxylin and eosin (H&E) digitized images. The skeletonization variable was correlated with several clinicopathological characteristics of the patients, including cell of origin Hans’ classifier and Lymph2Cx assay, MYC and BCL2 rearrangement by FISH, immunohistochemistry of BCL2, CASP8, cCASP3, CD163, CDK6, cPARP, CSF1R, E2F1, ISY1, Ki69, LMO2, MDM2, MYC, MYO, TNFAIP8, PD-L1, and p53, and gene expression using a pancancer immune profiling panel. Results: In comparison with reactive tissue, DLBCL was characterized by lower skeletonization: 5665.20 ± 1012.82 vs. 6341.16 ± 548.23, respectively (p < 0.001). Within the DLBCL diagnostic category, high skeletonization correlated with poor overall survival (hazard risk = 2.5, p = 0.003). High skeletonization was also correlated with higher Epstein–Barr virus (EBV) EBER positivity, death within the first two years, high histological entropy, and lower CD5, E2F1, BCL2, ISY1, and TNFAIP8 protein levels (all p values < 0.05). Gene expression was available in a representative subset of 30 cases, including 18 cases with high skeletonization and 12 cases with low skeletonization. High skeletonization was characterized by upregulation of 166 immuno-oncology genes, such as CD274 (PD-L1), NFKB1A, CD68, CSF1R, CCR5, ITGAM, and TGFB1, and enrichment of IL6 JAK STAT3 signaling, inflammatory response, TNF, NFKB, KRAS, apoptosis, and macrophage function pathways by gene set enrichment analysis (GSEA). In multivariate COX regression analysis for overall survival, the prediction value of skeletonization was independent of Hans’ classifier, the International Prognostic Index (IPI), and EBER (p = 0.030, hazard risk = 2.2). Conclusions: DLBCL is characterized by lower skeletonization than reactive lymphoid tissue. In DLBCL, high skeletonization is associated with poor prognosis and enrichment of immuno-oncology markers.
Background/Objectives: Patients with suspicious prostate mpMRI but negative baseline biopsy remain challenging to manage, as some are later diagnosed with clinically significant prostate cancer (csPCa). This study evaluated whether baseline whole-gland radiomic features from T2-weighted imaging and apparent diffusion coefficient (ADC) maps could predict subsequent csPCa detection. Methods: This retrospective radiomics sub-analysis of the MULTIPROS trial included men with suspicious baseline mpMRI findings (PI-RADS v2.0 categories 3–5) and no csPCa detected at baseline biopsy. The primary outcome was subsequent csPCa detection during follow-up, defined as ISUP Grade Group ≥2. Whole-gland prostate segmentation was performed on baseline T2-weighted images using a semi-automated approach with manual refinement, and the resulting T2-derived masks were applied to the spatially corresponding ADC maps. Radiomic features were extracted using PyRadiomics version 3.1.0a2 after standardised preprocessing. Feature robustness was assessed in a 20-patient reproducibility subset using intra- and inter-reader intraclass correlation coefficients, followed by correlation filtering and LASSO-based feature prioritisation. Radiomics-only, clinicoradiological-only, and clinicoradiological–radiomic logistic regression models were evaluated using stratified five-fold cross-validation. Results: T2-based modelling included 151 patients, of whom 36/151 (23.8%) had subsequent csPCa detected; the median time to csPCa detection or last follow-up was 64 months. ADC analyses included 144 patients, of whom 34/144 (23.6%) had subsequent csPCa detected. The T2 clinicoradiological–radiomic model achieved a mean AUC of 0.696 ± 0.060, compared with 0.713 ± 0.072 for the T2 clinicoradiological-only model and 0.456 ± 0.091 for the T2 radiomics-only model. In the ADC-available cohort, ADC radiomics-only, ADC clinicoradiological–radiomic, and combined T2 + ADC clinicoradiological–radiomic models achieved mean AUCs of 0.684 ± 0.052, 0.635 ± 0.157, and 0.663 ± 0.106, respectively. Calibration was imperfect, with deviations at higher predicted probabilities and overprediction in the highest predicted-risk bin. Conclusions: Baseline whole-gland MRI radiomics showed limited and inconsistent predictive value for subsequent csPCa detection after negative biopsy and did not demonstrate consistent incremental improvement over clinicoradiological predictors. These findings are exploratory and hypothesis-generating, and external validation is required before clinical use.
Background/Objectives: The transperineal approach is the recommended standard for prostate biopsy. We aimed to determine whether anesthesia type—local anesthesia (LA) versus general anesthesia (GA)—independently influences clinically significant prostate cancer (csPCa) detection in transperineal magnetic resonance imaging (MRI)-targeted biopsy and to evaluate its impact on biopsy–prostatectomy pathological concordance. Methods: This single-center retrospective study included biopsy-naive men undergoing cognitive-fusion transperineal prostate biopsy under LA or GA. Propensity score matching (1:1) was performed on age, prostate-specific antigen, PI-RADS score, and prostate volume. The primary outcome was csPCa detection (ISUP Grade Group ≥ 2) on combined systematic and targeted biopsy. Secondary outcomes included overall and high-grade cancer detection and biopsy–prostatectomy pathological concordance. Results: After matching, 220 pairs (440 patients) were analyzed. csPCa detection on combined biopsy did not differ between LA and GA (40.5% vs. 37.7%, p = 0.625; absolute risk difference −2.7 percentage points, 95% CI −11.8 to 6.4; relative risk 0.93, 95% CI 0.74–1.18), nor did overall (54.5% vs. 55.0%, p = 1.000) or high-grade cancer detection (21.4% vs. 24.1%, p = 0.569). Similarly, no significant differences were observed for systematic biopsy alone (csPCa: 36.4% vs. 34.5%, p = 0.765) or targeted biopsy alone (csPCa: 35.9% vs. 35.0%, p = 0.921). Subgroup and multivariable analyses showed that anesthesia type was not an independent predictor of csPCa (adjusted odds ratio 0.887, 95% CI 0.553–1.423, p = 0.620). Biopsy–prostatectomy pathological concordance did not differ significantly between groups in the 121 prostatectomy patients. Conclusions: Anesthesia type was not significantly associated with csPCa detection in transperineal cognitive-fusion biopsy, and pathological concordance was similar between LA and GA. These findings support the feasibility of LA transperineal biopsy, although the confidence intervals do not establish formal equivalence between the two approaches.
Background/Objectives: Obesity is a well-established risk factor for several cancers, yet few studies have explored survivorship outcomes among obesity-related cancer (ORC) survivors—a growing public health concern. Beyond cancer risk, obesity is associated with poorer health-related quality of life (HRQoL), greater comorbidity burden, and adverse lifestyle behaviors during survivorship. This study examined differences in these outcomes between ORC and non-ORC survivors living in Puerto Rico. Methods: We analyzed 569 cancer survivors aged ≥21 years actively undergoing treatment from the Impact of Social Determinants of Health on the Cancer Care Continuum in Cancer Survivors in Puerto Rico Study, with survey data collected between 2023 and 2025. ORC status was classified based on the presence of a primary ORC (n = 262); all others were classified as non-ORC (n = 307). Outcomes included: (1) HRQoL, assessed using the Functional Assessment of Cancer Therapy-General overall score and domains; (2) comorbidities; and (3) lifestyle behaviors (i.e., physical activity, alcohol use, and smoking status). Poisson regression models with robust standard errors estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for all outcomes except smoking status and comorbidity burden, which were analyzed using multinomial logistic regression models to estimate adjusted relative risk ratios (aRRRs). Results: ORC survivors had a higher relative risk of former smoking (vs. never smoking) than non-ORC survivors (aRRR: 1.74, 95% CI: 1.02–2.96). No other differences were observed between groups. Older ORC survivors reported better emotional (aPR = 0.59, 95% CI: 0.41–0.85) and physical (aPR = 0.74, 95% CI: 0.58–0.95) well-being than older non-ORC survivors. Among male participants, ORC survivors reported a lower prevalence of moderate/exceeded drinking than non-ORC survivors. Conclusions: Findings highlight a higher relative risk of former smoking (vs. never smoking) among ORC survivors compared with non-ORC survivors, with additional sex- and age-specific patterns in alcohol use and emotional/physical well-being.
Immune checkpoint blockade (ICB) has transformed cancer therapy, but clinical responses remain heterogeneous across tumor types and patient populations. Cancer-associated fibroblasts (CAFs) are key stromal components of the tumor microenvironment and can contribute to immunotherapy resistance through immune exclusion, extracellular matrix remodeling, chemokine signaling, and interactions with suppressive immune cells. Although CAF-directed strategies are under active investigation, their clinical translation is limited by marked CAF heterogeneity and the lack of scalable biomarkers for patient stratification. Computational pathology based on hematoxylin and eosin (H&E) whole-slide images (WSIs) provides a potential approach for extracting stromal and spatial features from routine histology, although digitized WSIs and the infrastructure required for large-scale AI analysis are not universally available. In this review, we synthesize current evidence on CAF classification, CAF-mediated immunotherapy resistance, H&E-based computational pathology, and emerging histology-based biomarker models. We further propose a conceptual roadmap for developing CAF-aware H&E spatial signatures with potential relevance to future immunotherapy stratification. Current evidence supports the biological rationale and computational feasibility of this approach, whereas its clinical utility remains to be established through rigorous external validation and prospective clinical evaluation.
