151751-Najiba-Chargi

275 Systemic therapy: skeletal muscle mass changes and chemoradiotherapy INTRODUCTION Head and neck cancer (HNC) accounts worldwide for approximately 550.000 cases annually. 1 Locally advanced HNC (LA-HNC) is the most prevailing clinical manifestation of HNC and has poor prognosis with a 5-year disease-free survival (DFS) of approximately 40-50%. Although the addition of the cytotoxic compound cisplatin to radiotherapy (RT) improved 5-years PFS from36% to 47%and 5-years overall survival (OS) from40% to 53%, it also caused a significant increase in severe functional mucosal adverse effects from 21% to 40%. 2 Due to the increased risk of side-effects, full compliance of chemoradiotherapy (CRT) is seen in only about two thirds of the initially eligible patients. 3–5 Ongoing research evaluates and compares different systemic treatment regimens and novel therapeutic approaches with consideration of po- tential patient-related (i.e., HPV-status) and treatment-related factors (i.e., dose regimen) in order to improve treatment tolerance and survival in LA-HNC patients. An emerging patient-related predictive and prognostic factor in the management of HNC is patients’ skeletal muscle mass (SMM). SMM quantification can be easily performed with the use of computed tomography (CT) or magnetic resonance imaging (MRI) images, which are routinely performed in the diagnostic work-up prior to treatment. Low SMM is common in HNC and especially in LA-HNC patients. 6 Patients with LA-HNC frequently experience dysphagia due to tumor site and adverse effects caused by CRT. This leads to weight loss and nutritional deficiencies which are the major contributors to low SMM. Low SMM has shown to be a sig - nificant predictive factor for failure of the treatment plan due to toxicities in various types of cancer. 7,8,9,10 Also in LA-HNC patients, low SMM at diagnosis has shown to be predictive for platinum dose-limiting toxicities. 11,12 Moreover, previous studies suggest that chemotherapy itself may induce SMM loss, also referred to as muscle wasting, in patients with cancer by increasing lipolysis and fatty acid B-oxidation. 13 It has also been suggested that patients with low SMM have higher blood levels of cytotoxic agents compared to patients without low SMM, which together with the previous mentioned mechanismmay cause a vicious circle of muscle wasting. 12 In addition, various studies in other types of cancers have shown that loss of SMM during systemic chemotherapy is prognostic for decreased survival in patients with several types of cancer including colorectal and pancreatic cancer 14–17 . For HNC, several studies have shown that low SMM at diagnosis is prognostic for decreased survival. 18,19,20,21 However, little is known about the patterns and prognostic impact of changes in SMM after cisplatin-based CRT in LA-HNC patients. In HNC, one previous study investigated the prognostic impact of changes in SMM after (C)RT in patients with nasopharyngeal carci - noma and showed that loss of SMM was associated with decreased OS 22 . Nasopharyngeal carcinoma is, however, a distinctive entity in HNC. Furthermore, patients were treated with different treatment strategies (induction CRT as well as concurrent CRT) and SMM segmenta - tion was performed on CT scans with a wide time interval (median: 110 days, range 41-1083 days). As regards to squamous cell carcinomas of other anatomical head and neck subsites, no evidence is published yet. If loss of SMM after CRT is indeed a prognostic factor, it can be 15