Introduction
Body composition increasingly is a subject of interest in medical research. An abnormal body composition, such as a decreased lean body mass and/or increased adipose tissue mass, may have a profound influence on treatment outcome and (disease free) survival of patients with a variety of illnesses [
1‐
3]. Skeletal muscle mass (SMM) is the largest component of lean body mass [
4]. In cancer patients, a low SMM, sometimes referred to as sarcopenia, has specifically been associated with a higher incidence of chemotherapy-related toxicity, postoperative complications, longer hospital stay, increased healthcare-related expenditures, and lower disease free and overall survival [
5‐
10]. This relationship has been shown in breast, colorectal, hepato-pancreatico-biliary, renal, and lung cancer, amongst others [
11‐
15].
In cancer patients, SMM is most often assessed on abdominal computed tomography (CT) imaging at the level of the third lumbar vertebra (L3) [
16]. This method is based on research using whole-body magnetic resonance imaging (MRI), in which has been shown that cross-sectional skeletal muscle area (CSMA) on a single transversal slice at the level of L3 is strongly correlated with total skeletal muscle volume as measured using whole-body MRI [
17,
18]. The CSMA at the level of L3 is commonly normalized for stature, which results in the lumbar skeletal muscle index (lumbar SMI) [
11]. This value is used as an indication of total SMM.
Abdominal CT imaging is often routinely performed in most types of cancer during diagnostic work-up and follow-up. In these patients, SMM measurement can be performed on abdominal CT imaging without the need for additional imaging or other diagnostics. However, abdominal CT imaging is not routinely performed in head and neck cancer (HNC) patients [
19]. Recently, a novel method to assess SMM on a single transversal CT slice at the level of the third cervical vertebra (C3) was published [
20]. Using this method, skeletal muscle mass is assessed measuring the CSMA of the paravertebral muscles and the sternocleidomastoid muscles at the level of the C3 vertebra. This method allows for evaluation of SMM in HNC patients on routinely performed imaging, in a similar manner as is used in patients with other types of cancer. This measurement method for SMM was recently used in three studies in head and neck cancer patients [
21‐
23].
To be clinically useful, the C3 measurement method of SMM has to provide similar results when used by different observers. The aim of this study was to evaluate the interobserver agreement of SMM measurement at the level of C3. The robustness of the C3 measurement method was investigated in terms of the vertebra selection, the exact single slice selection, and the correspondence in CSMA measurements between all observers.
Discussion
This study aimed to examine the robustness of the C3 measurement method for SMM in terms of interobserver agreement and specific vertebra and single slice selection by multiple observers. This study was performed without a training data set and limited formal training, to simulate the use of the C3 measurement method for SMM as if it were adopted from an external research paper.
The interobserver agreement for all different CSMA measurements was excellent. The measurement of CSMA of PVM appears to be most uniform. There is some difference between observers in measurement of the CSMA of the SCM muscles; however, actual differences remain small. The previous research has shown that total CSMA at C3 was significantly better correlated with CSMA at L3 than the CSMA of the PVM only with CSMA at L3 [
20].
The level of C3 is easily identifiable for both researchers and clinicians, with only incidental selection of a different level. There was more variation in the actual single slice selection, perhaps due to the lack of a training data set and little informal training received prior to delineation of scans. This may also be due to the thin slices (1 mm) and small (2 mm) interslice gaps of the CT imaging used in this study. In most cases, where an observer had selected a different slice than the majority of the observers, the different slices were indeed directly above or below of the slice the majority chose, which corresponds with a 3 mm difference in location. Probably, in these cases, the accidental selection of a different slice should not greatly influence CSMA measurements. However, it may still be advisable to include a training data set when starting to use the C3 measurement method to allow for a learning period in delineation of skeletal muscle and single slice selection.
In recent years, SMM has widely been researched in cancer patients, using a measurement of skeletal muscle area at the level of L3 on CT imaging as an indicator of total SMM [
11]. Imaging at the level of L3 is not routinely performed in HNC patients, so SMM measurement at the level of L3 is not always clinically applicable in HNC [
19]. The SMM measurement method at the level of C3 provides a reliable and robust alternative to SMM measurement at the level of L3, allowing for broad research into the predictive and prognostic effect of sarcopenia in HNC.
Patients with HNC often present with signs of malnutrition and as such are at risk of developing sarcopenia [
29]. Adverse outcomes associated with sarcopenia, such as chemotherapy-related toxicity and wound healing problems, are highly prevalent in HNC [
30]. It can be anticipated that both are at least partly related to sarcopenia. The first study using the C3 measurement method to assess SMM in HNC patients undergoing chemoradiotherapy found that low SMM was an independent predictor of the occurrence of chemotherapy dose-limiting toxicity [
21]. A recent study in HNC patients undergoing laryngectomy for laryngeal cancer showed that low SMM, as measured at the level of L3, was an independent predictor of the occurrence of a pharyngocutaneous fistula and of the occurrence of any wound complication [
31]. In this study, 122 patients who had undergone a total laryngectomy were retrospectively evaluated for inclusion; 70 (57%) had abdominal imaging available for analysis. It is likely that all or almost all HNC patients will undergo CT or MRI imaging of the head and neck area during the diagnostic process and follow-up [
19]. The C3 measurement method allows the investigation of body composition in nearly all HNC patients without the need for extra diagnostics. A recent study in patients undergoing laryngectomy, where SMM was measured at the level of C3, showed that low SMM was a predictor of the occurrence of a pharyngocutaneous fistula [
23]. Preoperative low SMM also was a strong negative prognostic factor for overall survival after laryngectomy [
23]. In this retrospective study, 235 out of 245 patients could be included for analysis due to measurement of SMM at the level of C3.
Future research is still needed to clarify whether the adverse effects of low SMM are prognostic only, or if these adverse effects can be overturned. In the future, HNC patients at high risk of adverse outcomes related to low SMM or sarcopenia might benefit from additional supportive treatment or individualized primary treatment. Several possible interventions may be considered, such as altered chemotherapy dosing [
32], prehabilitation before surgery [
33], enhanced recovery after surgery [
34], intensive physiotherapy [
35], and additional nutritional support [
36]. A measurement of SMM at the level of C3 might be used as a screening tool for low SMM in HNC cancer patients at diagnosis.
Limitations
There are some limitations to this study that need to be addressed. No training data set or formal training was given to the observers in this study. Although this study setup was chosen, because it may best mimic the clinical adaptation and use of the C3 measurement method by other institutions, it may also explain some of the differences in the measurements and in the vertebra and single slice selections. For further use in research and clinical work, a training data set for researchers learning skeletal muscle area measurement may limit these differences. Second, only CT imaging was used in this study to assess SMM, as is usually done in other studies in cancer patients that assess SMM at the level of L3. Some HNC patients will only undergo MRI imaging of the head and neck area during the diagnostic process. It should still be evaluated whether CT and MRI can be used interchangeably for SMM assessment or that some form of modification of the method is necessary. Finally, most variation in CSA measurements was seen in the SCM muscles. This can at least partially be explained by lymph node metastasis close to or invading in the SCM muscles. Most patients included in this study had advanced, lymph node positive disease, which may make accurate delineation of the muscle more difficult. In daily clinical practice, approximately two-thirds of HNC patients present with advanced stage disease (large tumor and/or lymph node positive) [
37]. Thus, this study population provides an accurate reflection of the clinical use of the C3 measurement method. Because previous research showed that the addition of the CSA of the SCM muscles was beneficial for a prediction model, and because actual differences were small and ICCs could still be classified as excellent, it is justified to include the CSA of the SCM muscles in the total CSA at C3 in patients with lymph node positive disease.