151751-Najiba-Chargi

247 Systemic therapy: skeletal muscle mass and anti-cancer drug toxicity Figure 4. Forest plots for the association between low skeletal muscle mass (SMM) and the odds to develop anti-cancer drug toxicity, specifically. (A) toxicity ≥ grade 3 which was used as the toxicity endpoint in 6 studies. (B) shows a selection of studies that besides the same toxicity endpoint also used the same cut-off values established by Martin et al., 2013 47 , as well as the same measurement techniques using CT at the L3 vertebrae. For each forest plot, the combined effect of the studies is plotted with a black diamond. SUBGROUP ANALYSIS The studies that investigated the influence of a monotherapy were used for a subgroup analy- sis. Three different drugs used in monotherapy were the topic of more than one study. Figure 5A shows the forest plot for the OR of toxicity in low SMM and non-low SMM patients treated with cisplatin or carboplatin. Cisplatin and carboplatin have an apparent volume of distribu - tion which approximately equals total body water (40–60 L). 53,54 These drugs were used as monotherapy in two studies 8,24 and showed an association between low SMM and toxicity (OR 3.06; 95% CI 1.45–6.44, p = 0.003) with moderate heterogeneity ( χ 2 = 1.98; I2 = 49%). Figure 5B shows the forest plot for low SMM and non-low SMM patients treated with sorafenib as a monotherapy, which has an apparent volume of distribution of 213 L 55 . These two studies 33,42 demonstrated an association between low SMM and toxicity (OR 5.60; 95% CI 2.01–15.59; p = 0.001) with low heterogeneity ( χ 2 = 0.33; I2 = 0%). Figure 5C shows the forest plot for low SMM and non-low SMM patients treated with sunitinib as a monotherapy, which has an appar- ent volume of distribution of 2230 L 56 . These two studies 7,45 showed no association between low SMM and toxicity (OR 1.27; 95%CI 0.08–20.94; p = 0.87) with high heterogeneity ( χ 2 = 5.62; I2 = 82%). 13