Objectives Sarcopenia and systemic inflammation can affect survival of advanced‐stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated. Study Design Retrospective review at a tertiary cancer center. Methods Patients with stage III‐IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex‐specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C‐reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models. Results A total of 174 patients were included in the study. The cut‐off values for sarcopenia were set at SMI <52.4 cm2/m2 (men) and < 36.2 cm2/m2 (women) corresponding to the lowest sex‐specific tertile. An mGPS 1–2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06–3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1–2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17–3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7–16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1–2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01–46.99; P < .001). Conclusions Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced‐stage OSCC patients. Level of Evidence 4 Laryngoscope, 131:E1530–E1538, 2021

Oral squamous cell carcinoma often causes bone invasion resulting in poor prognosis and affects the quality of life for patients. Herein, we combined radiation with sorafenib, to evaluate the combination effect on tumor progression and bone erosion in an in situ human OSCC-bearing mouse model. Treatment procedure were arranged as following groups: (a) normal (no tumor); (b) control (with tumor); (c) sorafenib (10 mg/kg/day); (d) radiation (single dose of 6 Gy); (e) pretreatment (sorafenib treatment for 3 days prior to radiation), and (f) concurrent treatment (sorafenib and radiation on the same day). The inhibition of tumor growth and expression level of p65 of NF-κB in tumor tissues were the most significant in the pretreatment group. EMSA and Western blot showed that DNA/NF-κB activity and the expressions of NF-κB-associated proteins were down-regulated. Notably, little to no damage in mandibles and zygomas of mice treated with combination of sorafenib and radiation was found by micro-CT imaging. In conclusion, sorafenib combined with radiation suppresses radiation-induced NF-κB activity and its downstream proteins, which contribute to radioresistance and tumorigenesis. Additionally, bone destruction is also diminished, suggesting that combination treatment could be a potential strategy against human OSCC.

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