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New prostate cancer risk groups by PSMA-PET (PPP3): an international, retrospective, registry-based cohort study
No full textBackground
Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use, and trial study design. We report improved risk classification based on PSMA-PET Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP) nomograms (PPP3) to prognosticate 3-year, 5-year, and 7-year overall survival.
Methods
In this international, retrospective, registry-based cohort study, we collected data from the PROMISE PET registry with ongoing overall survival follow-up. Male patients (aged ≥18 years) with histological proven prostate cancer at any disease stage and any performance status, who underwent any PSMA-PET between Dec 6, 2012, and June 26, 2024, were included in the registry. Patients with neuroendocrine pattern or metastasised or disseminated malignancy other than prostate cancer were excluded. 35 investigator sites in Europe, Asia, Australia, North America, and South America were split pairwise (2:1) into development and validation cohorts. Entire investigator sites were split pairwise according to their site characteristics (ie, number of patients per disease group, country, follow-up). The primary study objective was overall survival. PPP3 nomograms were created based on Cox regression models with least absolute shrinkage and selection operator penalty to prognosticate 3-year, 5-year, and 7-year overall survival. Calibration curves and Harrell's c indices were applied and head-to-head comparison with clinical risk scores separated for each disease subgroup was conducted. Based on the visual PPP3 nomogram, a simplified risk-stratification table was created.
Findings
We analysed 11 154 patients and 7253 were included in the development cohort and 3901 in the validation cohort. Median follow-up to censoring or death was 4·9 years (IQR 3·5–6·6). Clinical disease group and PROMISE metrics were combined into visual and quantitative PPP3 nomograms, respectively. C indices were 0·83 (95% CI 0·82–0·84) for the visual nomogram and 0·84 (0·82–0·85) for the quantitative nomogram. Both nomograms and the simplified risk stratification table were accurate and equal or superior compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate, European Association of Urology, a nomogram defined by Gafita and colleagues, and National Comprehensive Cancer Network).
Interpretation
We present new risk nomograms by PROMISE along with a simple table to prognosticate 3-year, 5-year, and 7-year overall survival in prostate cancer. PROMISE and PPP3 assessments are freely available online for global implementation
P01.007.C Multi-locus inherited neoplasia allele syndrome (MINAS): prevalence and phenotype in the German Consortium of Hereditary Breast and Ovarian Cancer [Abstract]
No full textIntegrated reporting: the relevance of connectivity in intellectual capital disclosures for market valuation
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Increased expression of CD36 and CD163 in clear cell renal cell carcinoma suggests an association between lipid transport and an "M2-like" macrophage phenotype
No full textBackground
Clear cell renal cell carcinoma (ccRCC) is marked by intracellular lipid accumulation and dysregulated lipid metabolism, features that contribute to tumor progression and possibly immune suppression. Tumor-associated macrophages (TAMs) in ccRCC are abundant and phenotypically diverse, with CD68 marking general macrophage presence and CD163 indicating alternatively activated, immunosuppressive (M2-like) subsets. The fatty acid transporter CD36 and the metabolic regulator CD147 can be found in tumors and may influence macrophage polarization, but their associations with TAM phenotypes and tumor lipid content in ccRCC remain unclear.
Methods
Samples from 23 ccRCC patients were analyzed. Oil Red O staining quantified lipid accumulation. Immunohistochemistry for CD36, CD147, CD68, CD163, and CD3 was evaluated using both automated area-based quantification and semi-quantitative observer scoring. Flow cytometry of freshly resected tumors was used to assess the expression of CD36, CD147 and the infiltration with macrophages and CD8 T cells. Lipidomic analyses were performed from ccRCC tissues (n=5). RNA expression data from TCGA (n=533) were used for validation. Single-cell RNA sequencing data from two published datasets were analyzed to characterize cell-type-specific expression of lipid metabolism and macrophage markers.
Results
ccRCC tumors showed an increased lipid accumulation and the expression of CD36 was detected on both CD45-negative cells and macrophages. Macrophages expressed CD163, suggesting a M2-like phenotype and CD163 expression was higher in larger ccRCC tumors. CD163 on macrophages positively correlated with CD36 on CD45-negative cells from ccRCC tumors, while CD8 T cells showed a trend to lower numbers in tumors with high CD36 expression on CD45-negative cells. CD147 was broadly expressed on CD45-negative and CD45-positive cells and positively correlated with CD36 on CD45-negative cells as well as with CD163 on macrophages. Tumors accumulated triacylglycerols, which correlated with CD163. Single-cell RNA-seq revealed CD163 expression across all TAM subsets and a compartmentalized distribution of lipid metabolism genes.
Conclusions
Lipid metabolic markers CD36 and CD147 are expressed in ccRCC tumors and correlations with immune cell subsets suggest their role in suppressing anti-tumor immunity. These findings suggest the existence of a metabolic-immune axis in ccRCC and provide a rationale for targeting TAM metabolism to enhance immunotherapeutic efficacy
Effects of cancer treatment on somatosensory and nociceptive processing in children and adolescents: a systematic review
No full textChemotherapy-induced peripheral neuropathy remains a major complication in pediatric cancer, with disrupted somatosensory and nociceptive processing being a key aspect. This review synthesizes empirical studies on alterations in somatosensory and nociceptive processing in children and adolescents with cancer. We conducted this review in accordance with PRISMA 2020 guidelines and preregistered it in PROSPERO. A systematic search was performed in MEDLINE, CINAHL, and Web of Science in April 2025. Eligible studies were screened by two independent reviewers and synthesized narratively. Risk of bias was assessed using the Newcastle Ottawa Quality Assessment Scale for Case–Control Studies. Nine studies met the inclusion criteria, all using cross-sectional designs and quantitative sensory testing (QST) or other pain protocols. Overall, findings suggest altered somatosensory processing in this population, with higher mechanical and thermal detection thresholds in patients compared to controls. Findings on nociceptive processing were more heterogeneous, with most studies suggesting unaltered pain sensitivity in the lower pain range and increased sensitivity in the higher pain range, highlighting increased pain vulnerability to more intense pain stimuli following cancer and its treatment. This review reveals a pattern of decreased somatosensory processing and increased nociceptive processing in pediatric patients/survivors with cancer, likely attributable to damage of peripheral nervous tissues as well as central sensitization
Wer hütet die Verwaltung? Mögliche Missbrauchsgefahr der beamtenrechtlichen Remonstration
No full textRNA at lipid/water interfaces: molecular insights from coarse-grained simulations and reflectivity data predictions
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Predictive factors in spinal meningiomas – a comparative analysis with intracranial meningiomas of a high-volume skull and base center
No full textMicrosurgical resection remains the gold standard in the treatment of spinal meningiomas. Available data suggest more favorable clinical outcomes compared to intracranial meningiomas. This study aims to enhance risk stratification and optimize treatment strategies by analyzing clinical and histopathological predictive factors for spinal meningiomas in a large single-center cohort. We present the analysis of 217 spinal meningiomas of our institutional meningioma cohort treated between October 2003 and March 2017. Clinical parameters of the patients such as sex, age, location of the meningioma and extent of resection were recorded besides histological features. Other parameters included follow-up and recurrence. The outcome parameters for spinal meningiomas were evaluated and compared with 1767 intracranial meningiomas. Among 217 spinal meningiomas, 80.37% (n = 172) were completely resected. The majority (96.31%, n = 209) were classified as CNS WHO grade 1. In contrast, the proportion of WHO grade 1 among intracranial meningiomas was 78.21% (n = 1382, p < 0.0001). Patients with spinal meningiomas had a lower recurrence rate with 6.91% (n = 15), versus 23.94% (n = 423) of patients with intracranial meningiomas (p < 0.0001). Multivariate analysis identified Simpson resection grade (p < 0.0001) and higher WHO grade (p = 0.0156) as independent prognostic factors for risk factors for progression in spinal meningiomas. For intracranial meningiomas, male gender (p = 0.0106) and resection of a recurrent tumor (p < 0.0001) were additionally identified as independent negative prognostic parameters. Spinal meningiomas are associated with a more favorable prognosis compared to their intracranial counterparts. The most significant and modifiable prognostic factor is the achievement of gross total resection. Given the technical complexity of surgery, spinal meningiomas should preferably be treated in high-volume centers with experienced surgeons to achieve this goal while minimizing morbidity and ensuring durable tumor control