The results of the study indicated that baseline musculature (both myosteatosis and low muscle mass) was predictive of all-cause mortality in this cohort of HNC patients. Low muscle mass has been tied to chemotoxicity through a number of mechanisms. Chemotherapy and radiation can cause muscle wasting via inflammation and activation of the NF-κB pathway [12, 13]. Those patients with less dense muscle or, less muscle mass at the beginning of therapy may be less likely to tolerate full therapy and therefore more likely to succumb to their cancer [14].
The study population was in accord with HNC populations typical of the United States: the study population was predominately male, non-Hispanic white, with an oropharyngeal primary tumor site [15]. Our measure of SMD was slightly higher than a prior study of myosteatosis and sarcopenia in HNC patients (38.6 vs 30.5 HU at baseline) [7]. Our measure of SMD was in accord with other studies of different cancer patients prior to treatment [16, 17]. A systematic review found a wide range of prevalence in sarcopenic and low muscle mass definitions. Pre-treatment prevalence ranged from 6.6–70% in HNC patients [18]. The review found that low muscle mass was associated with decreased overall survival but that more studies were needed to verify the findings.
A recent prospective cohort study by Thureau et al. examined the relationship between pre-treatment sarcopenia (determined solely through CT evaluation at the L3 level) and both treatment-related toxicities and overall survival [19]. The current study was in accord with the prospective cohort study’s findings. The Thureau et al. study found that although sarcopenia did not have an association with treatment related toxicity there was a significant association with overall survival HR 1.9 (95% CI 1.1, 3.25) which is in line with the findings of the current study.
A similarly sizedstudy (matched sample n = 100 vs n = 99) by Findlay et al. indicated that treatment completion was similar for those HNC patients with and without pre-treatment myosteatosis while including a much higher percentage of stage IV cancers (62%) [7]. The same study found not significant association between pre-treatment myosteatosis and unplanned hospitalization (OR 3.45; 95% CI 0.93, 12.64; p = 0.063). The Findlay et al. study performed a survival analysis and also found similar associations to the current study between overall survival, baseline LMM (HR 3.87; 95% CI 1.22, 12.24; p = 0.02) and myosteatosis (HR 8.86; 95% CI 1.12, 69.88; p = 0.038).
A retrospective cohort study was conducted at the University Medical Center Utrecht on locally advanced HNC patients treated with chemoradiation. The study was conducted in a similar timeframe to this study from 2012 to 2018. Chargi et al. also found that low skeletal muscle mass at diagnosis was prognostic for overall survival (HR 2.1; 95% CI 1.1–4.1; p = 0.03).
Muscle density and myosteatosis are still relatively new areas of exploration in HNC and so comparable studies are limited. A study by Murnane et al. examined the rate of overall survival and complications following radical surgery in oesophageal and gastric cancer patients. Those with myosteatosis compared to normal musculature had a reduced 5 year overall (54.1 vs. 83%, p = 0.004) and disease-free (55.2 vs. 87.2%, p = 0.007) survival.
A study by Charette et al. performed a post-hoc analysis of two clinical trials on colorectal cancer patients [20]. The post-hoc analysis indicated that myosteatosis was indicative of poor survival which is similar to the findings of this study. Charette et al. also found that the factor with the most negative impact on survival was visceral adipose tissue and those are the persons in the current study who were hospitalized at a higher percent.
A recent study by Schaffler-Schaden et al. failed to find a significant association between visceral adiposity, BMI, myosteatosis, and complications following surgery with curative intent in colorectal cancer patients [21]. The Schaffler-Schaden et al. study indicated that in the non-obese population the only statistically significant predictor was lean muscle mass. It is possible that the effect of myosteatosis is different in the non-obese population.
The study had a number of strengths. The study was a cohort design allowing for the exposure to be ascertained prior to the outcome. Only patients with imaging of L3 were included which allowed for consistency in the measurement of body composition parameters and served to decrease measurement bias. Patient scans were only be used if they were full-body CT scans thus improving rigor and reproducibility. All patients were managed by one radiation oncologist which allowed for consistency in care decisions.
The study also had some limitations. The study contains patients with multiple cancer sites, however an attempt was made to control for this by including it in the final model. The study is also a single-center study and so its findings may not be broadly applicable.
The pre-treatment prevalence of myosteatosis and low muscle mass was 37.2 and 33.5%, respectively. Both myosteatosis and low muscle mass were significantly associated with mortality. The question of musculature and treatment effects requires more study so as to determine an appropriate and feasible response. Diagnostic and planning imaging could potentially be utilized to give early and specific body composition and malnutrition information to the healthcare team in an effort to improve outcomes.