151751-Najiba-Chargi

426 CHAPTER 21 patients described in chapter 10 and 11 (58% and 54.9%, respectively). Although previous studies showed a predictive impact of low skeletal muscle mass for cisplatin dose-limiting toxicity, no predictive impact of low skeletal muscle mass for cetuximab dose-limiting toxic- ity (OR 0.83, p=0.74) could be found. To evaluate the findings in Chapter 10-12, a systematic review and meta-analysis was performed on the predictive impact of low skeletal muscle for anti-cancer drug toxicity in all types of cancer (head and neck cancer and non-head and neck cancer), this study is presented in Chapter 13 . In total, 31 studies were included in the sys - tematic review, sample size ranged from 21 to 414 patients and the occurrence of low skeletal muscle mass ranged from 12.2% to 89.0%. Most research on low skeletal muscle mass and anti-cancer drug toxicity was performed in esophageal, renal, colorectal, breast and head and neck cancer. Patients with low skeletal muscle mass had a higher risk of severe toxicity (OR 4.08, p < 0.001) and dose-limiting toxicity (OR 2.24, p < 0.001) compared to patients without low skeletal muscle mass. This shows that the predictive value of low skeletal muscle mass for anti-cancer drug toxicity can be observed across cancer types. The mechanisms as to why low skeletal muscle mass is associated with the occurrence of cisplatin dose-limiting toxicity in head and neck cancer patients undergoing chemoradiotherapy is unknown. A hypothesis for this phenomenon is that the pharmacokinetics of cisplatin is altered with respect to the distributional volume in patients with a low skeletal muscle mass and normal to high adipose tissue mass. Cisplatin is a hydrophilic chemotherapeutical agent, and mainly distributes into the fat-free body mass, of which skeletal muscle mass is the largest component. 5–7 Cisplatin is dosed using the body surface area of a patient, and does not take into account individual body composition. 8,9 It was therefore hypothesized that patients with low skeletal muscle mass and normal or high adipose tissue mass may actually receive a relatively high dose of cisplatin. Data on the relationship between body composition and pharmacokinetic charac - teristics of cisplatin was not yet available. Therefore, Chapter 14 presents the prospective observational PLATISMA study performed in 45 patients with locally advanced head and neck cancer in which patients skeletal muscle mass was measured before treatment and blood cisplatin levels were measured during the first cycle of treatment. A pharmacokinetic analysis was performed to assess the relationship between cisplatin pharmacokinetics and skeletal muscle mass. As hypothesized, a significant relationship between cisplatin pharmacokinetics and skeletal muscle mass was found. However, this relationship was also seen between cis - platin pharmacokinetics and body weight. Further studies are needed to evaluate whether cisplatin dosing based on skeletal muscle mass is superior to dosing based on body surface area with regards to the occurrence of toxicities and overall and disease-free survival. Besides the role of skeletal muscle mass in cisplatin toxicity, cisplatin itself is thought to cause muscle wasting. Therefore, Chapter 15 presents a study performed in 235 patients with locally ad- vanced head and neck cancer undergoing cisplatin-based chemoradiotherapy to investigate the patterns, predictors and prognostic value of skeletal muscle mass loss after treatment. Skeletal muscle mass was measured on pre-chemoradiotherapy and post-chemoradiother- apy imaging, the skeletal muscle area was significantly lower than before treatment (31.62cm 2 versus 33.34 cm 2 , p<0.01). Majority of patients (54.9%) experienced moderate loss of skeletal muscle mass, 38.7% had stable skeletal muscle mass, 13% had a moderate gain of skeletal