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78 CHAPTER 5 best predictor for mortality. Martin et al. also utilized optimum stratification analysis for low SMM as a predictor of mortality in a population of 1.473 patients with lung or gastrointestinal malignancies and incorporated both gender-specific and BMI-specific cutoffs: 41.0 cm 2 /m 2 for women and 43.0 cm 2 /m 2 for men with a BMI <25 kg/m 2 and 53.0 cm 2 /m 2 for men with a BMI > 25 kg/m 2 . These cut-off values are based on SMA at the level of L3 and are not applicable for patients with HNC in whom SMM segmentation at the level of C3 is performed. The European Working Group of Sarcopenia in Older People (EWGSOP) recommends that low SMM should be defined as SMM less than 2 standard deviations (SD) below the mean SMM of typical healthy adults. 1 It is unknown whether this recommendation also implies to patients with cancer, but reference values may provide a better direct comparison in between patients. Recently a study in a Dutch cohort of healthy persons revealed gender- and BMI-specific refer- ence values for SMM at the level of L3 19 , which may be used to uniformly identify patients with a significantly lower SMM than a reference patient of the same gender and BMI. The aim of this study is to provide gender- and BMI-specific cut-off values for low SMM as measured at the level of C3 in a large cohort of patients diagnosed with HNC. This information will contribute to the knowledge about the distribution of low SMM in HNC patients and will provide more uniformity in the definition of low SMM in HNC research. METHODS ETHICAL CONSIDERATIONS The design of this study was approved by the Medical Ethical Research Committee of the University Medical Center Utrecht (approval ID 16/595 C and 17-365/C). All data was retrieved retrospectively and used in an anonymized fashion. STUDY POPULATION Patient data collected in several earlier retrospective studies of our group that evaluated skeletal muscle mass in head and neck cancer patients were combined in a new database. Patients were diagnosed and treated with a curative intent at the University Medical Center Utrecht, The Netherlands between 2008 and 2018 with a primary head and neck cancer and include cohorts of patients planned for microvascular free-flap mandibular reconstruction 9 , patients undergoing chemoradiotherapy 7 or bioradiotherapy 20 , elderly patients with HNC 10 and patients with oropharyngeal cancer 11 . Relevant parameters, including length and weight at the time of imaging, sex, age, tumor localization and clinical TNM stage (7 th and 8 th edition) were retrospectively retrieved. After completion of the new database, the database was checked for duplicates and all duplicate patients were removed.