151751-Najiba-Chargi

286 CHAPTER 15 DISCUSSION This study is the first to evaluate the patterns of changes in SMM in LA-HNC patients treated with cisplatin-based CRT. After CRT, the majority of the patients (n=129, 55%) had moderate loss of SMM and one patient (0.4%) had large loss of SMM after CRT. A minority of the patients (n=13, 6%) had moderate gain of SMM after CRT and one patient (0.4%) had large gain of SMM after CRT. Of the 235 LA-HNC patients who underwent CRT only 91 patients (39%) had stable SMM. Mean SMA at follow-up (31.62 cm 2 , SD 8.69) was significantly lower than mean SMA at initiation of CRT (33.34 cm 2 , SD 9.11). The prevalence of low SMM increased after CRT from 60% of the study population to 63%. As reported in many studies, low SMM prior to initiation of CRT seemed to have a negative prognostic impact on overall survival, but this finding was not statistically significant. Previous research has shown that low SMM is a significant negative prognostic factor for survival. 19,21 Because we also included patients who were treated as recently as in 2018, right-censoring of these cases might explain why we did not find a prognostic impact of low SMM for survival. Another explanation for this finding might be that tumor stage itself as a prognostic factor outweighs the prognostic impact of low SMM. In a previous study in elderly HNC patients we also showed that low SMM had prognostic impact in patients with stage I-III HNC, but lost its prognostic impact in patients with stage IV HNC. 21 In this study we included patients with LA-HNC, stage III-IV, and it is possible that low SMM does not have a prognostic impact in this group of patients. The mechanism underlying the relation between low SMM and decreased survival is yet to be elucidated. Low SMM may impact survival by causing treatment-related toxicities, which may lead to ineffective cancer treatment. In a previous study, although low SMM was not prognostic for the whole group of HNC patients treated with primary CRT, pa - tients who experienced cisplatin dose limiting toxicity, significantly more frequently observed in patients with low SMM, had a worse prognosis. 12 Moreover, malignancies also cause a state of hyper catabolism and inflammation which negatively impacts SMM causing a negative vi- cious circle. 27 The loss of SMM after treatment, also referred to as muscle wasting, is the net result of a combination of an imbalance between protein synthesis and protein degradation, cell death of muscle cells and a decrease in the muscle’s capability of regenerating news muscle cells. Previous research also underlines the role of oxidative stress and inflammation in the devel- opment of muscle wasting. 28 In this study, patients with an oropharyngeal carcinoma had a significantly higher risk of a loss of SMM after CRT. Patients with oropharyngeal carcinoma are especially prone tomalnutrition due to the localization of the tumor impairing oral intake. This may explain the higher risk of a loss in SMM and may advocate for early nutritional support for these patients at high-risk for loss in SMM. Being overweight or obese at diagnosis also showed to be a significant predictive factor for loss of SMM in our study population. Although this may feel counterintuitive, BMI