Development of prediction models for lymph node metastasis in endometrioid endometrial carcinoma

Background In endometrioid endometrial cancer (EEC), current clinical algorithms do not accurately predict patients with lymph node metastasis (LNM), leading to both under- and over-treatment. We aimed to develop models that integrate protein data with clinical information to identify patients requiring more aggressive surgery, including lymphadenectomy. Methods Protein expression profiles were generated for 399 patients using reverse-phase protein array. Three generalised linear models were built on proteins and clinical information (model 1), also with magnetic resonance imaging included (model 2), and on proteins only (model 3), using a training set, and tested in independent sets. Gene expression data from the tumours were used for confirmatory testing. Results LNM was predicted with area under the curve 0.72–0.89 and cyclin D1; fibronectin and grade were identified as important markers. High levels of fibronectin and cyclin D1 were associated with poor survival (p = 0.018), and with markers of tumour aggressiveness. Upregulation of both FN1 and CCND1 messenger RNA was related to cancer invasion and mesenchymal phenotype. Conclusions We demonstrate that data-driven prediction models, adding protein markers to clinical information, have potential to significantly improve preoperative identification of patients with LNM in EEC.publishedVersio

Evaluation of an Artificial Intelligence Model for Identification of Intracranial Hemorrhage Subtypes on Computed Tomography of the Head

Background Intracranial hemorrhage is a critical finding on computed tomography (CT) of the head. This study compared the accuracy of an artificial intelligence (AI) model (Annalise Enterprise CTB Triage Trauma) to consensus neuroradiologist interpretations in detecting 4 hemorrhage subtypes: acute subdural/epidural hematoma, acute subarachnoid hemorrhage, intra‐axial hemorrhage, and intraventricular hemorrhage. Methods A retrospective stand‐alone performance assessment was conducted on data sets of cases of noncontrast CT of the head acquired between 2016 and 2022 at 5 hospitals in the United States for each hemorrhage subtype. The cases were obtained from patients aged ≥18 years. The positive cases were selected on the basis of the original clinical reports using natural language processing and manual confirmation. The negative cases were selected by taking the next negative case acquired from the same CT scanner after positive cases. Each case was interpreted independently by up to 3 neuroradiologists to establish consensus interpretations. Each case was then interpreted by the AI model for the presence of the relevant hemorrhage subtype. The neuroradiologists were provided with the entire CT study. The AI model separately received thin (≤1.5 mm) and thick (>1.5 and ≤5 mm) axial series as available. Results The 4 cohorts included 571 cases of acute subdural/epidural hematoma, 310 cases of acute subarachnoid hemorrhage, 926 cases of intra‐axial hemorrhage, and 199 cases of intraventricular hemorrhage. The AI model identified acute subdural/epidural hematoma with area under the curve of 0.973 (95% CI, 0.958–0.984) on thin series and 0.942 (95% CI, 0.921–0.959) on thick series; acute subarachnoid hemorrhage with area under the curve 0.993 (95% CI, 0.984–0.998) on thin series and 0.966 (95% CI, 0.945–0.983) on thick series; intraaxial hemorrhage with area under the curve of 0.969 (95% CI, 0.956–0.980) on thin series and 0.966 (95% CI, 0.953–0.976) on thick series; and intraventricular hemorrhage with area under the curve of 0.987 (95% CI, 0.969–0.997) on thin series and 0.983 (95% CI, 0.968–0.994) on thick series. Each finding had at least 1 operating point with sensitivity and specificity >80%. Conclusion The assessed AI model accurately identified intracranial hemorrhage subtypes in this CT data set. Its use could assist the clinical workflow, especially through enabling triage of abnormal CTs

Polymorphisms in inflammation pathway genes and endometrial cancer risk

Background: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis