151751-Najiba-Chargi

231 Systemic therapy: skeletal muscle mass and bioradiotherapy as cisplatin, carboplatin, and oxaliplatin, mostly distribute to the LBM and are therefore affect - ed by the decrease in LBM in patients with low SMM. 3 Although cetuximab is also hydrophilic it has a very high molecular weight, and therefore, cetuximab distributes less towards the LBM and is mostly present in the plasma levels. 24 In the case of a patient with low SMM, it is possible that the decrease in LBMwill not affect the plasma levels of cetuximab and therefore not increase the risk of toxicity. To be able to confirm this hypothesis additional research is needed. Currently, it is unknown what the underlying pathophysiology of decreased SMM is, although there is a range of theories. Firstly, it is hypothesized that age plays an important role in the mechanism of sarcopenia and decreasing SMM. This could be explained by the decrease of physical activity, the decrease of food intake, or the hormonal changes which are associated with aging. 25 Secondly, intracellular oxidative stress is speculated to be of influence on the occurrence of sarcopenia, specifically the increased concentration of inflammatory cytokines. 12,25 Lastly, there are theories about genetic components that could cause a de- crease in SMM or muscle function. 25 Additional research into the mechanisms causing loss of muscle mass could progress the strategies for improving muscle mass and function, thereby improving overall survival. Further knowledge regarding drug distribution of chemothera - peutic agents could provide a better understanding of the process by which low SMM could cause an increased risk of toxicity. If there is a link between the distribution of a drug and the predictive value of low SMM for DLT, it would be possible to select a chemotherapeutic agent with less distribution towards the LBM or adapt the dose for patients with low SMM. This could result in less toxicity for patients with low SMM, however, it should not reduce the efficacy of the treatment. In order to ensure that efficacy is not reduced further research is required. To accurately determine whether patients with low SMMwould profit more from treatment with cetuximab as opposed to cisplatin, a randomized controlled trial with endpoints toxicity and survival would be required. CONCLUSION In conclusion, in contrast with cisplatin dose-limiting toxicity, low SMM has no predictive value for cetuximab dose-limiting toxicity in HNSCC patients treated with cetuximab and ra - diotherapy, probably attributable to the difference in lean body mass distribution of these chemotherapeutical agents. This study showed no significant prognostic value of low SMM for overall survival in HNSCC patients treated with cetuximab and radiotherapy unfit for pla - tin-based chemotherapy. 12