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230 CHAPTER 12 the measurement of CSA on CT imaging and MRI imaging. 8 Measurement of skeletal muscle CSA at the level of L3 can, therefore, be assessed using skeletal muscle CSA measurement at the level of C3 on CT or MRI. Several studies show that low SMM is a prognostic factor in HNSCC patients. 16–18 In the present study, low SMM showed no significant prognostic value in the multivariate cox regression analysis. The populations in studies showing low SMM as prognostic factor consisted of elder - ly 16 , cisplatin fit 17 and advanced stage disease patients 18 . Some reasons for this difference in prognostic value of the present study with highly selected patients compared to other studies can be hypothesized. First, this study consists of a limited number of patients. Secondly, these patients were unfit for cisplatin-based chemotherapy, mainly because of comorbidity which can affect overall survival as well. The poor condition of these selected patients is illustrated by the very high prevalence of low SMM. Finally, in our study only patients with locoregional advanced stage disease with generally already a poor prognosis were included. This is the first study on the predictive value of low SMM for cetuximab DLT in HNSCC patients. There is only one study that previously looked at the predictive value of low SMM for DLT in cancer patients treated with cetuximab. 10 In this study, Barret et al. showed that in metastatic colorectal cancer patients treated with cetuximab low SMMwas a significant predictive factor for grade 3-4 toxicity. This is in contradiction with our results, which show that low SMM is not a predictive factor for cetuximab DLT. However, the patients in the study by Barret et al. received cetuximab in combination with another chemotherapeutic agent, most commonly oxaliplatin. Thismakes it difficult to determine whether the predictive value of lowSMMapplies to cetuximab treatment or the chemotherapeutic treatment it was combined with. Both stud - ies differ substantially in patient, tumor and treatment characteristics. In our study patients received concomitant radiotherapy which may also affect toxicity. Patients in the colorectal cancer study hadmetastatic disease and patients in our head and neck cancer study were unfit for cisplatin chemotherapy. These differences could be responsible for the fact that Barret et al ., contrary to our study, concluded that low SMMwas a predictive factor for DLT. 10 There are several hypotheses explaining the influence of low SMM on the occurrence of chemotherapy toxicity. Some hypothesize that the altered fat-to-lean body composition may influence the pharmacokinetics of chemotherapeuticals. 19 In HNSCC patients, low SMM appears to be inde - pendently associated with frailty 20 , which describes a general state of increased vulnerability to stressors, such as cancer and anticancer treatment, and a higher risk of adverse events. 13,19,20 However, the hypothesis most supported in literature is based on the influence of low SMM on the drug distribution. The body is comprised of two major compartments, fat mass (FM) and lean body mass (LBM). Distribution of hydrophilic drugs, e.g., cisplatin, occurs mostly in the LBM, of which muscle mass is a large contributor. 19,21 Therefore, a decrease in LBM due to low SMM may result in increased plasma levels and thereby increased risk of toxicity. 17,19,21–23 Low SMMhas been demonstrated to have different predictive value for a variety of chemotherapeu - tical agents. This difference in predictive value could be explained by the mechanismof action by which low SMM causes an increased risk for toxicity. Platinum-based chemotherapies, such