151751-Najiba-Chargi

191 Systemic therapy: skeletal muscle mass and chemoradiotherapy Several hypotheses have been proposed in literature to explain the underlying mechanism of this important finding in several types of cancers. 22,23 Themost accepted hypothesis is based on the influence of low SMM on the volume of distribution of anti-cancer drugs and assumes that dosing of anti-cancer drugs on body surface area is insufficient to capture body composition differences. Dosing cytotoxic agents on body surface areawas initially derived fromobservations that basal metabolic rates non-linearly differed between species (humans, animals) according to weight. 6 These observations also showed that themaximum tolerated dose expressed asmg/m 2 was similar in different species. 6 Therefore, in the 1950’s, body surface area (m 2 ) calculatedwith patient’s body weight and body height was used as an estimate for safe starting doses in phase 1 human trials based on preclinical animal toxicology studies. 6 However, the use of body sur - face area for predicting a safe starting dose was extended as a dosing tool for cytotoxic agents. Prado et al. showed that LBMhas a poor associationwith body surface area (r 2 = 0.37) in patients with solid tumors of the respiratory or gastro-intestinal tract. 24 Prado et al. estimated that the individual variation in LBM could account for up to a threefold variation in volume distribution for anticancer drugs dosed per unit body surface area. Currently, the best tool used to predict who will benefit from chemotherapy is the perfor- mance status of the patient, which can be measured by the Eastern Cooperative Oncology group (ECOG) or the Karnofsky performance status. Besides the performance status, patients’ comorbidities such as renal conditions and otologic conditions are taken into consideration as objectivemeasures to classify a cisplatin-fit patient. However, the assessment of performance status by the clinician may be a subjective measure. In our study, also partly because unfit patients do not receive cisplatin, the performance status was, as expected, not an independent predictor for DLT. Besides performance status, BMI is mostly used as surrogate measure of patients’ physical fitness or nutritional status in clinical oncology practice. We found that low BMI at diagnosis was not associated with an increased risk of DLTs. BMI is not an appropriate measurement tool to identify patient at risk for DLTs and may unjustly reassure oncologists about patients’ nutritional status and risk for experiencing adverse treatment effects. Ideally in the future, the body composition rather than the body weight should be taken into account during the diagnostic, treatment and surveillance stages of phases in oncology. A need for a more objective and integrated measurement tool, such as SMM assessment, is needed. This enables an individualized patient approach, as wide variations in body composition, especially SMM, are reported in many populations. 25 SMM can be determined on routinely performed diagnostic imaging and therefore may be useful in clinical practice to identify patients at risk for DLTs without additional patient burden. Our study had some limitations. First, due to the retrospective design of this study no infor - mation was available on nutritional status and physical exercise, which may influence the relationship between SMM and DLT. Second, due to the observative nature of this study no causal relationship between cisplatin pharmacokinetics and body surface area or SMM could be drawn from this study and further prospective studies are needed to elucidate this rela- tionship. 10