Establishment and Validation of Pre-Therapy Cervical Vertebrae Muscle Quantification as a Prognostic Marker of Sarcopenia in Patients With Head and Neck Cancer

Abstract Importance Sarcopenia, or diminished skeletal muscle mass, is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging for patients without computed tomography (CT) images that capture the abdomen or lower thorax. Objectives To (1) define sarcopenia thresholds at the C3 vertebral level using previously established thresholds derived from abdominal CT imaging and (2) determine if C3-defined sarcopenia is associated with survival in patients with HNC. Design, setting, and participants This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment and treated between January 2005 and December 2017. Data analysis was completed from December 2018 to April 2021. Exposures Measurement of the cross-sectional muscle area at the third lumbar and cervical vertebral levels using CT imaging. Main outcomes and measures Primary study outcome was overall survival. Results In a cohort of 253 HNC patients with CT imaging that captures both L3 and C3 vertebral levels, skeletal muscle cross-sectional area at C3 was strongly correlated with the L3 level in both men (n = 188; r = 0.77; p < 0.001) and women (n = 65; r = 0.80; p < 0.001), and C3-defined sarcopenia thresholds of 14.0 cm 2 /m 2 (men) and 11.1 cm 2 /m 2 (women) were best predictive of previously established L3-defined sarcopenia thresholds. Applying these defined C3 sarcopenia thresholds in a cohort of 536 HNC patients with neck imaging alone revealed that C3-defined sarcopenia was independently associated with reduced overall survival in men (HR = 2.63; 95% CI, 1.79, 3.85) but not women (HR = 1.18, 95% CI, 0.76, 1.85) with HNC. Conclusions and relevance This study identifies sarcopenia thresholds at the C3 level that best predict L3-defined sarcopenia in both men and women. In HNC, C3-defined sarcopenia is associated with poor survival outcomes in men, but not women, suggesting sarcopenia may differentially affect men and women with HNC. Key Points Question Is cervical vertebrae muscle wasting a reliable predictor of sarcopenia-related mortality in patients with head and neck cancer (HNC)? Findings (1) We established sex-specific sarcopenia thresholds (men, 14.0 cm 2 /m 2 ; women, 11.1 cm 2 /m 2 ) at the third cervical vertebrae (C3) level through statistical modelling that correlates with previously established lumbar thresholds. (2) Applying these defined C3 sarcopenia thresholds in a large cohort of HNC patients with neck imaging alone revealed that C3-defined sarcopenia was associated with reduced overall survival in men (HR = 2.63; 95% CI, 1.79, 3.85), but not women (HR = 1.18, 95% CI, 0.76, 1.85) with HNC. Meaning The C3 sarcopenia thresholds established herein may be a useful prognostic and risk-stratification tool; the influence of sarcopenia on patient outcomes should be assessed in a sex-specific manner.