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The risk of osteoporosis in breast cancer patients is higher than that in healthy populations. The fracture and death rates increase after patients are diagnosed with osteoporosis. We aimed to develop machine learning-based models to predict the risk of osteoporosis as well as the relative fracture occurrence and prognosis. We selected 749 breast cancer patients from two independent Chinese centers and applied six different methods of machine learning to develop osteoporosis, fracture and survival risk assessment models. The performance of the models was compared with that of current models, such as FRAX, OSTA and TNM, by applying ROC, DCA curve analysis, and the calculation of accuracy and sensitivity in both internal and independent external cohorts. Three models were developed. The XGB model demonstrated the best discriminatory performance among the models. Internal and external validation revealed that the AUCs of the osteoporosis model were 0.86 and 0.87, compared with the FRAX model (0.84 and 0.72)/OSTA model (0.77 and 0.66), respectively. The fracture model had high AUCs in the internal and external cohorts of 0.93 and 0.92, which were higher than those of the FRAX model (0.89 and 0.86). The survival model was also assessed and showed high reliability via internal and external validation (AUC of 0.96 and 0.95), which was better than that of the TNM model (AUCs of 0.87 and 0.87). Our models offer a solid approach to help improve decision making.Prostate cancer (PCa) is the second most common male cancer worldwide, but effective biomarkers for the presence or progression risk of disease are currently elusive. In a series of nine matched histologically confirmed PCa and benign samples, we carried out an integrated transcriptome-wide gene expression analysis, including differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), which identified a set of potential gene markers highly associated with tumour status (malignant vs. benign). We then used these genes to establish a minimal progression-free survival (PFS)-associated gene signature (GS) (PCBP1, PABPN1, PTPRF, DANCR, and MYC) using least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses from The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) dataset. Our signature was able to predict PFS over 1, 3, and 5 years in TCGA-PRAD dataset, with area under the curve (AUC) of 0.64-0.78, and our signature remained as a prognostic factor independent of age, Gleason score, and pathological T and N stages. A nomogram combining the signature and Gleason score demonstrated improved predictive capability for PFS (AUC 0.71-0.85) and was superior to the Cambridge Prognostic Group (CPG) model alone and some conventionally used clinicopathological factors in predicting PFS. In conclusion, we have identified and validated a novel five-gene signature and established a nomogram that effectively predicted PFS in patients with PCa. Findings may improve current prognosis tools for PFS and contribute to clinical decision-making in PCa treatment.
Immunotherapy with nivolumab (a monoclonal antibody that targets the programmed cell death protein 1, PD1) has become the standard treatment for patients with metastatic renal cell carcinoma (mRCC) after progression to single-agent tyrosine kinase inhibitors. However, the optimal duration of immunotherapy in this setting has not yet been established.
We retrospectively reviewed all patients treated with nivolumab at our institution from January 2014 to December 2021 and identified those who discontinued treatment for reasons other than disease progression (PD). We then associated progression-free survival (PFS) and overall survival following treatment cessation with baseline clinical data.
Fourteen patients were found to have discontinued treatment. Four patients (28.6%) ceased treatment due to G3/G4 toxicities, whereas the remaining ten (71.4%) opted to discontinue treatment in agreement with their referring clinicians. The median duration of the initial treatment with nivolumab was 21.7 months (7.5-37r experience, the majority of patients who discontinued treatment in the absence of PD were still progression-free more than 18 months after discontinuation. Patients whose initial treatment duration was less than 12 months or who did not achieve a radiological objective response had a greater risk of progression. Immunotherapy rechallenge is safe and seems capable of achieving disease control.Necroptosis is closely related to the occurrence and development of tumors, including glioma. A growing number of studies indicate that targeting necroptosis could be an effective treatment strategy against cancer. Long non-coding RNA (lncRNA) is also believed to play a pivotal role in tumor epigenetics. Therefore, it is necessary to identify the functions of necroptosis-related lncRNAs in glioma. In this study, the transcriptome and clinical characteristic data of glioma patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were collected, and the differentially expressed necroptosis-related lncRNAs in TCGA that have an impact on overall survival (OS) were screened out to construct risk score (RS) formula, which was verified in CGGA. A nomogram was constructed to predict the prognosis of glioma patients based on clinical characteristics and RS. In addition, Gene Set Enrichment Analysis (GSEA) was used to analyze the main enrichment functions of these necroptosis-related lncRNAs and the immune microenvironment. A total of nine necroptosis-related lncRNAs have been identified to construct the RS formula, and the Kaplan-Meier (K-M) survival analysis showed significantly poorer outcomes in the high RS group in both TCGA and CGGA databases. Moreover, the receiver operating characteristic (ROC) curve shows that our prediction RS model has good predictability. Regarding the analysis of the immune microenvironment, significant differences were observed in immune function and immune checkpoint between the high RS group and the low RS group. In conclusion, we constructed a necroptosis-related lncRNA RS model that can effectively predict the prognosis of glioma patients and provided the theoretical basis and the potential therapeutic targets for immunotherapy against gliomas.
The prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children's Leukemia Group (SCCLG).
A total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction.
The frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count (
= 0.002) and poorer treatment response (
0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival (
= 0.030) and a higher risk of 3-year cumulative incidence ofrelapse
(
= 0.008), while no impact was observed on 3-year overall survival (
= 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence ofrelapse (hazard ratio = 2.809,
= 0.016).
CNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.
CNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.
Colorectal cancer (CRC), the third most common cancer in the USA, is a leading cause of cancer-related death worldwide. Up to 60% of patients develop liver metastasis (CRLM). Treatments like radiation and ablation therapies require disease segmentation for planning and therapy delivery. For ablation, ablation-zone segmentation is required to evaluate disease coverage. We hypothesize that fully convolutional (FC) neural networks, trained using novel methods, will provide rapid and accurate identification and segmentation of CRLM and ablation zones.
Four FC model styles were investigated Standard 3D-UNet, Residual 3D-UNet, Dense 3D-UNet, and Hybrid-WNet. Models were trained on 92 patients from the liver tumor segmentation (LiTS) challenge. For the evaluation, we acquired 15 patients from the 3D-IRCADb database, 18 patients from our institution (CRLM = 24, ablation-zone = 19), and those submitted to the LiTS challenge (
= 70). Qualitative evaluations of our institutional data were performed by two board-certified radiologists (interventional and diagnostic) and a radiology-trained physician fellow, using a Likert scale of 1-5.
The most accurate model was the Hybrid-WNet. On a patient-by-patient basis in the 3D-IRCADb dataset, the median (min-max) Dice similarity coefficient (DSC) was 0.73 (0.41-0.88), the median surface distance was 1.75mm (0.57-7.63 mm), and the number of false positives was 1 (0-4). In the LiTS challenge (
= 70), the global DSC was 0.810. The model sensitivity was 98% (47/48) for sites ≥15 mm in diameter. Qualitatively, 100% (24/24; minority vote) of the CRLM and 84% (16/19; majority vote) of the ablation zones had Likert scores ≥4.
The Hybrid-WNet model provided fast (<30 s) and accurate segmentations of CRLM and ablation zones on contrast-enhanced CT scans, with positive physician reviews.
The Hybrid-WNet model provided fast ( less then 30 s) and accurate segmentations of CRLM and ablation zones on contrast-enhanced CT scans, with positive physician reviews.Rhabdomyosarcoma (RMS) is a soft tissue sarcoma of skeletal muscle differentiation, with a predominant occurrence in children and adolescents. One of the major challenges facing treatment success is the presence of metastatic disease at the time of diagnosis, commonly associated with the more aggressive fusion-positive subtype. click here Non-coding RNA (ncRNA) can regulate gene transcription and translation, and their dysregulation has been associated with cancer development and progression. MicroRNA (miRNA) are short non-coding nucleic acid sequences involved in the regulation of gene expression that act by targeting messenger RNA (mRNA), and their aberrant expression has been associated with both RMS initiation and progression. Other ncRNA including long non-coding RNA (lncRNA), circular RNA (circRNA) and ribosomal RNA (rRNA) have also been associated with RMS revealing important mechanistic roles in RMS biology, but these studies are still limited and require further investigation. In this review, we discuss the established roles of ncRNA in RMS differentiation, growth and progression, highlighting their potential use in RMS prognosis, as therapeutic agents or as targets of treatment.
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