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245 Systemic therapy: skeletal muscle mass and anti-cancer drug toxicity Figure 4A shows the forest plot for the OR of 6 studies that used toxicity ≥ grade 3 according to the CTCAE as the measure for toxicity. Patients with low SMM had a significantly higher risk of ≥grade 3 toxicity compared to patients without low SMM (OR 4.08; 95% CI 2.48–6.70; p < 0.01). Heterogeneity across studies was low ( χ 2 of 1.14 and I2 of 0%). Figure 4B shows the forest plot for the OR of 3 studies that besides using the same toxicity description also used the same cut-off value, namely that established by Martin et al., 2013 47 , as well as the same measurement technique on CT at the L3 vertebrae. Patients with low SMM had a significantly higher risk of ≥grade 3 toxicity compared to patients without low SMM (OR 3.81; 95% CI 2.07- 6.98; p <0.001). Heterogeneity across studies was low ( χ 2 of 0.13 and I2 of 0%). Of the 31 studies included in this review, 19 were included in the meta-analysis. Six studies were excluded because there was not sufficient statistical data published to determine an OR. 22,26,32,37,39,41 Of these six, five concluded that there was no association between SMI and toxicity 22,26,32,37,39 and one concluded that a lower SMI was related to a higher risk of toxicity. 41 Four studies were excluded because they did not dichotomize SMI and instead performed the analysis with SMI as a continuous variable. 28,29,34,36 Of these four, one concluded no associa - tion 28 , and three concluded that lowSMI was related to increased toxicity occurrence. 29,34,36 Two studies were excluded from the meta-analysis because the toxicity endpoint did not match any of the other studies. 6,38 Of these two, one showed a negative association between toxicity occurrence and SMI 6 , and one showed no association 38 . Of the seven studies excluded that demonstrated no association between sarcopenia, several provided a theory as to why this association was not demonstrated. Some of these studies hypothesized that the distribution of the anti-cancer drug investigated was not influenced by low SMM, because of the hydro- philic characteristics of the drug or because of the route of administration. 22,26,32 Other studies mentioned the variety of cut-off values used for low SMM, which originated in populations that differ from the investigated population and can be observed in the varying prevalence of low SMM between studies. 28,37 Although these studies did not find an association between low SMM and toxicity, some did observe other associations related to low SMM and toxicity. These associations include the association between sarcopenic obesity and toxicity 22 ; muscle quality and toxicity 26 ; muscle loss during treatment and toxicity 39 ; and low SMM and survival 38 . 13