SOURCE: A registry-based prediction model for overall survival in patients with metastatic oesophageal or gastric cancer

Prediction models are only sparsely available for metastatic oesophagogastric cancer. Because treatment in this setting is often preference-based, decision-making with the aid of a prediction model is wanted. The aim of this study is to construct a prediction model, called SOURCE, for the overall survival in patients with metastatic oesophagogastric cancer. Data from patients with metastatic oesophageal (n = 8010) or gastric (n = 4763) cancer diagnosed during 2005⁻2015 were retrieved from the nationwide Netherlands cancer registry. A multivariate Cox regression model was created to predict overall survival for various treatments. Predictor selection was performed via the Akaike Information Criterion and a Delphi consensus among experts in palliative oesophagogastric cancer. Validation was performed according to a temporal internal-external scheme. The predictive quality was assessed with the concordance-index (c-index) and calibration. The model c-indices showed consistent discriminative ability during validation: 0.71 for oesophageal cancer and 0.68 for gastric cancer. The calibration showed an average slope of 1.0 and intercept of 0.0 for both tumour locations, indicating a close agreement between predicted and observed survival. With a fair c-index and good calibration, SOURCE provides a solid foundation for further investigation in clinical practice to determine its added value in shared decision making

SOURCE: A registry-based prediction model for overall survival in patients with metastatic oesophageal or gastric cancer

Prediction models are only sparsely available for metastatic oesophagogastric cancer. Because treatment in this setting is often preference-based, decision-making with the aid of a prediction model is wanted. The aim of this study is to construct a prediction model, called SOURCE, for the overall survival in patients with metastatic oesophagogastric cancer. Data from patients with metastatic oesophageal (n = 8010) or gastric (n = 4763) cancer diagnosed during 2005⁻2015 were retrieved from the nationwide Netherlands cancer registry. A multivariate Cox regression model was created to predict overall survival for various treatments. Predictor selection was performed via the Akaike Information Criterion and a Delphi consensus among experts in palliative oesophagogastric cancer. Validation was performed according to a temporal internal-external scheme. The predictive quality was assessed with the concordance-index (c-index) and calibration. The model c-indices showed consistent discriminative ability during validation: 0.71 for oesophageal cancer and 0.68 for gastric cancer. The calibration showed an average slope of 1.0 and intercept of 0.0 for both tumour locations, indicating a close agreement between predicted and observed survival. With a fair c-index and good calibration, SOURCE provides a solid foundation for further investigation in clinical practice to determine its added value in shared decision making

Snake Venom Gland Organoids

Wnt dependency and Lgr5 expression define multiple mammalian epithelial stem cell types. Under defined growth factor conditions, such Adult Stem Cells (ASCs) grow as 3D organoids that recapitulate essential features of the pertinent epithelium. Here, we establish long-term expanding venom gland organoids from several snake species. The newly assembled transcriptome of the Cape coral snake reveals that organoids express high levels of toxin transcripts. Single cell RNA sequencing of both organoids and primary tissue identifies distinct venom-expressing cell types as well as proliferative cells expressing homologs of known mammalian stem cell markers. A hard-wired regional heterogeneity in the expression of individual venom components is maintained in organoid cultures. Harvested venom peptides reflect crude venom composition and display biological activity. This study extends organoid technology to reptilian tissues and describes an experimentally tractable model system representing the snake venom gland