Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Health and Rehabilitation Sciences

Supervisor

Theurer, Julie A.

2nd Supervisor

Doyle, Philip C.

Affiliation

Stanford University School of Medicine

Joint Supervisor

Abstract

Introduction: In head and neck cancer (HNC), loss of skeletal muscle mass (SMM), or sarcopenia, is a strong prognostic factor for outcomes. However, inconsistencies in its assessment limit our understanding of the relationship between sarcopenia and nutrition-related outcomes. This project evaluated the significance of sarcopenia as described in the literature and as demonstrated in a cohort of HNC patients.

Methods: A scoping review was first conducted followed by a retrospective cohort study with data collected from 194 oropharyngeal carcinoma patients treated with definitive radiation/chemoradiation. Sarcopenia was assessed from computed tomography (CT) imaging at the third cervical vertebra (C3) and the fourth thoracic vertebra (T4). To determine the predictive nature of pre-treatment sarcopenia and its association with feeding tube (FT) outcomes, logistic and linear regression were performed.

Results: Seventy-six studies on sarcopenia in HNC published from 2016 to 2021 were included in the scoping review. Approximately two-thirds of studies used CT imaging to assess sarcopenia. Skeletal muscle index (SMI) at the third lumbar vertebra (L3) was the most prevalent metric used to identify sarcopenia, followed by SMI at the level of C3. Of the 194 eligible patients included in the retrospective cohort study, 30.9% received a FT at some point during treatment. Sarcopenia was identified at baseline in 72.7% of patients based on C3 measurements and in 41.7% based on measures at the level of T4. Those with sarcopenia were significantly more likely to receive a FT and had significantly worse freedom from FT placement compared to patients without sarcopenia. Sarcopenia assessed at T4 was a significant predictor of FT placement and age was the only significant predictor of duration of FT placement.

Conclusions: The most effective strategy to assess sarcopenia in HNC depends on access to resources, patient and treatment characteristics, and the prognostic significance of outcomes used to represent sarcopenia. SMI measured at T4 may represent a practical and valid biomarker for sarcopenia detection that is associated with the need for FT placement. These findings suggest that detection of baseline sarcopenia could guide decision-making related to the progression of treatment and the need for nutritional support.

Summary for Lay Audience

Individuals who are diagnosed with head and neck cancer (HNC) are likely to experience substantial issues related to related to swallowing and oral intake resulting from their cancer treatment. These challenges will often lead to weight loss, reductions in quality of life (QoL), and poor survival. Sarcopenia, or the loss of muscle mass, has the potential to be used as a pre-treatment marker to identify which patients are at a high risk of developing significant impairments. However, because the assessment of sarcopenia is inconsistent, and because little is known about the relationship between muscle mass and nutrition-related outcomes, it is difficult to understand the true impact of this condition. This study gathered information on the definition, measurement, and identification of sarcopenia for individuals undergoing treatment for HNC, investigated the relationship between sarcopenia and nutrition-related outcomes, and identified factors associated with muscle loss after treatment.

The information gathered indicated that best strategy to measure muscle mass and identify individuals with sarcopenia may depend on access to resources, the characteristics of each patient and their treatment, and the predictive value of the outcome used to represent sarcopenia. Muscle mass assessed on computed tomography scans at fourth thoracic vertebra (T4) is relatively simple to measure, convenient, non-invasive, and predictive of feeding tube (FT) placement. Therefore, this information may provide care providers with essential information about the risk for FT placement and in turn guide decision-making in HNC.

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