Patterns, Predictors, and Prognostic Value of Skeletal Muscle Mass Loss in Patients with Locally Advanced Head and Neck Cancer Undergoing Cisplatin-Based Chemoradiotherapy

Abstract

Low skeletal muscle mass (SMM) is associated with toxicities and decreased survival in head and neck cancer (HNC). Chemoradiotherapy (CRT) may exaggerate loss of SMM. We investigated the changes in SMM, their predictors, and prognostic impact of SMM in patients treated with CRT between 2012 and 2018. Skeletal muscle area (SMA) segmentation was performed on pre- and post-CRT imaging. Observed changes in SMM were categorized into: (I) Stable, (II) moderate gain (III), moderate loss, (IV) large gain, and (V) large loss. In total, 235 HNC patients were included, of which 39% had stable SMM, 55% moderate loss, 13% moderate gain, 0.4% large loss, and 0.4% large gain of SMM. After CRT, SMA decreased compared to pre-CRT (31.6 cm2 versus 33.3 cm2, p < 0.01). The key predictor was a body mass index (BMI) of ≥30 kg/m2 (OR 3.6, 95% CI 1.4–9.3, p < 0.01). Low SMM at diagnosis (HR 2.1; 95% CI 1.1–4.1, p = 0.03) and an HPV-positive oropharyngeal tumor (HR 0.1; 95% CI 0.01–0.9, p = 0.04) were prognostic for overall survival. Changes in SMM were not prognostic for survival. Loss of SMM is highly prevalent after CRT and a high BMI before treatment may aid in identifying patients at risk.

Influence of fat-free mass index on the survival of patients with head and neck cancer

“…Furthermore, the FFMI of our patients also did not correlate with sex, PS, primary tumor location, overall disease stage, or type of treatment (definitive or postoperative (chemo)radiotherapy). This also contradicts the findings of some other authors, i.e., the relationship between low muscle mass and female sex [ 15 , 38 , 39 ] or higher overall disease stage [ 14 , 38 ]. However, we observed an association between reduction of muscle mass and smoking, as did Bril et al [ 38 ] but not also Wendrich et al [ 15 ] and Huiskamp et al [ 40 ], possibly reflecting the problem of the reliability of data obtained from patients.…”

“…An additional, albeit related, reason was the high prevalence of low muscle mass (56.3%) in our patients, which turned out to be an independent adverse prognostic factor for OS (but not also for DFS) in multivariate analysis. Several other studies demonstrated a negative prognostic impact of low muscle mass on the survival of HNSCC patients [ 14 , 19 , 39 ]. Moreover, despite the statistically significant correlation between FFMI and BMI values measured in individual patients, only FFMI proved to be of significance for predicting OS in multivariate analysis.…”

Cut-off values for low skeletal muscle mass at the level of the third cervical vertebra (C3) in patients with head and neck cancer

“…Secondly, due to heterogeneity of tumor site, tumor characteristics and tumor stages included in this cohort study, no reliable cutoff value of low SMM for mortality could be provided. Our previous study in patients with HNC treated with curative intent cisplatin-based chemoradiotherapy showed that low SMM at diagnosis is a significant prognostic for decreased survival, changes in SMM after treatment were however not prognostic (32). Further studies are needed to validate the prognostic impact of the cut-off values for low SMM provided in the present study.…”

The predictive and prognostic value of weight loss and body composition prior to and during immune checkpoint inhibition in recurrent or metastatic head and neck cancer patients

“…The findings concern head and neck cancer, lung cancer as well as other cancer sites. 37 , 38 , 39 , 40 The catabolic effects of chemotherapy probably play a major role here. For example, cisplatin is known to activate nuclear factor kappa‐B cells (NFκB), a key player in inflammation and a trigger for muscle wasting.…”