151751-Najiba-Chargi

262 CHAPTER 14 the creatinine-based Cockcroft-Gault formula, or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation and capped on a maximum value of 130 mL/ min), and albumin were examined as additional relevant covariates, as described in the Sup - plementary materials. In case that addition of the GFR and/or albumin resulted in a better fit of the baseline model (based on the objective function value (OFV), a drop in inter-individual variability (IIV) and a difference in effect size between the 25% and 75% quartile), body composition was also evaluated in combination with these covariates. Lastly, the final model was used to simulate the effects of different SMMs on the population predicted cisplatin concentrations. In this simulation the effects of different SMMs around the threshold of 25.8 kg for low SMM were predicted. For the chosen SMMs, the corresponding BSAs were extracted from the data to calculate the given dose for the virtual patients. STATISTICAL ANALYSIS Formal statistical testing for the PK model was performed using the likelihood ratio test (by means of the OFV which is minus twice the log likelihood) for the models without fixed coeffi - cients, a p -value of 0.005 was used to take into account multiple testing 23 and the degrees of freedomwere equal to the number of included relationships. For the models with fixed coef - ficients, the drop in OFV was used as a guidance. Other statistical analyses were performed using R (version 3.6.3). RESULTS PATIENTS’ CHARACTERISTICS In total, 50 patients were included between July 2018 and September 2020. Five patients even - tually did not participate in the study, 3 due to withdrawal of informed consent and 2 did not undergo CRT. Table 1 shows the characteristics of the included patients, 21 patients (46.7%) had low SMI. Median LSMI was 44.06 cm 2 /m 2 (interquartile range (IQR) 37.7-50.9). Patients with - out low SMMwere more likely to be overweight (58.3% versus 19%; p <0.01) and obese (25.0% versus 4.8%; p <0.01) compared to patients with low SMM. Majority of patients were treated in a primary setting (n=40, 88.9%) and had a tumor, node, metastasis (TNM) stage IV tumor according to the 8 th edition TNM cancer staging criteria (n=25, 55.5%). One patient received a weekly low-dose cisplatin schedule (40 mg/m 2 weekly) due to comorbidity.