Zheng, Weili

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL. Conclusions Lp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

Abstract Objective . We proposed an experimental approach to build a precise machine-specific beam delivery time (BDT) prediction and delivery sequence model for standard, volumetric, and layer repainting delivery based on a cyclotron accelerator system. Approach . Test fields and clinical treatment plans’ log files were used to experimentally derive three main beam delivery parameters that impacted BDT: energy layer switching time (ELST), spot switching time, and spot drill time. This derived machine-specific model includes standard, volumetric, and layer repainting delivery sequences. A total of 103 clinical treatment fields were used to validate the model. Main results . The study found that ELST is not stochastic in this specific machine. Instead, it is actually the data transmission time or energy selection time, whichever takes longer. The validation showed that the accuracy of each component of the BDT matches well between machine log files and the model’s prediction. The average total BDT was about (−0.74 ± 3.33)% difference compared to the actual treatment log files, which is improved from the current commercial proton therapy system’s prediction (67.22%±26.19%). Significance . An accurate BDT prediction and delivery sequence model was established for an cyclotron-based proton therapy system IBA ProteusPLUS ® . Most institutions could adopt this method to build a machine-specific model for their own proton system.