An enhanced prognostic score for overall survival of patients with cancer derived from a large real-world cohort.

BACKGROUND: By understanding prognostic biomarkers, we gain insights into disease biology and may improve design, conduct, and data analysis of clinical trials and real-world data. In this context, we used the Flatiron Health Electronic Health Record-derived deidentified database that provides treatment outcome and biomarker data from >280 oncology centers in the USA, organized into 17 cohorts defined by cancer type. PATIENTS AND METHODS: In 122 694 patients, we analyzed demographic, clinical, routine hematology, and blood chemistry parameters within a Cox proportional hazard framework to derive a multivariable prognostic risk model for overall survival (OS), the 'Real wOrld PROgnostic score (ROPRO)'. We validated ROPRO in two independent phase I and III clinical studies. RESULTS: A total of 27 variables contributed independently and homogeneously across cancer indications to OS. In the largest cohort (advanced non-small-cell lung cancer), for example, patients with elevated ROPRO scores (upper 10%) had a 7.91-fold (95% confidence interval 7.45-8.39) increased death hazard compared with patients with low scores (lower 10%). Median survival was 23.9 months (23.3-24.5) in the lowest ROPRO quartile Q1, 14.8 months (14.4-15.2) in Q2, 9.4 months (9.1-9.7) in Q3, and 4.7 months (4.6-4.8) in Q4. The ROPRO model performance indicators [C-index = 0.747 (standard error 0.001), 3-month area under the curve (AUC) = 0.822 (0.819-0.825)] strongly outperformed those of the Royal Marsden Hospital Score [C-index = 0.54 (standard error 0.0005), 3-month AUC = 0.579 (0.577-0.581)]. We confirmed the high prognostic relevance of ROPRO in clinical Phase 1 and III trials. CONCLUSIONS: The ROPRO provides improved prognostic power for OS. In oncology clinical development, it has great potential for applications in patient stratification, patient enrichment strategies, data interpretation, and early decision-making in clinical studies.

A review of selected pumping systems in nature and engineering--potential biomimetic concepts for improving displacement pumps and pulsation damping.

The active transport of fluids by pumps plays an essential role in engineering and biology. Due to increasing energy costs and environmental issues, topics like noise reduction, increase of efficiency and enhanced robustness are of high importance in the development of pumps in engineering. The study compares pumps in biology and engineering and assesses biomimetic potentials for improving man-made pumping systems. To this aim, examples of common challenges, applications and current biomimetic research for state-of-the art pumps are presented. The biomimetic research is helped by the similar configuration of many positive displacement pumping systems in biology and engineering. In contrast, the configuration and underlying pumping principles for fluid dynamic pumps (FDPs) differ to a greater extent in biology and engineering. However, progress has been made for positive displacement as well as for FDPs by developing biomimetic devices with artificial muscles and cilia that improve energetic efficiency and fail-safe operation or reduce noise. The circulatory system of vertebrates holds a high biomimetic potential for the damping of pressure pulsations, a common challenge in engineering. Damping of blood pressure pulsation results from a nonlinear viscoelastic behavior of the artery walls which represent a complex composite material. The transfer of the underlying functional principle could lead to an improvement of existing technical solutions and be used to develop novel biomimetic damping solutions. To enhance efficiency or thrust of man-made fluid transportation systems, research on jet propulsion in biology has shown that a pulsed jet can be tuned to either maximize thrust or efficiency. The underlying principle has already been transferred into biomimetic applications in open channel water systems. Overall there is a high potential to learn from nature in order to improve pumping systems for challenges like the reduction of pressure pulsations, increase of jet propulsion efficiency or the reduction of wear.