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Background: Concurrent chemoradiotherapy (CCRT) is an important therapeutic strategy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). We evaluated the efficacy and toxicity of two CCRT regimens in treating LA-SCCHN. Materials and Methods: LA-SCCHN patients receiving CCRT with either a modified 3-weekly cisplatin 75 mg/m2 (Group A, n = 86) or 5-day continuous infusion of cisplatin 12 mg/m2 plus 5-fluorouracil (5-FU) 600 mg/m2 (Group B, n = 87) were enrolled. The Kaplan−Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRFS). Univariate and multivariate analyses were performed using Cox proportional hazard models to assess correlations between clinical parameters and survival. Results: With a median of 35.8 months' follow-up, the median OS and PFS in Group A and Group B were 65.9 versus 55.0 months (P = 0.546) and 34.6 versus 33.3 months (P = 0.948), respectively. LRFS was not reached in either group. Group B patients had more Grade 3−4 mucositis (53.7% vs. 32.28%, P= 0.001) and dermatitis (49.8% vs. 21.5%, P= 0.0001). Trends of higher incidence rates of Grade 3−4 hematologic and renal toxicity were observed in Group A. After statistical adjustment, higher disease stage (Stage IVb) (hazard ratio [HR] = 6.657, 95% confidence interval [CI] 1.786−24.81, P= 0.005) and pretreatment anemia (hemoglobin

The epidermal growth factor (EGF) receptor (EGFR) overexpressed in many cancers, including lung and head and neck cancers, and is involved in cancer cell progression and survival. PD-L1, increases in tumor cells to evade and inhibit CD8+ T cells, is a clinical immunotherapeutic target. This study investigated the molecular mechanism of EGF on regulating PD-L1 in EGFR-positive cancers and determined potential agents to reduce PD-L1 expression. RNA sequencing (RNAseq) and bioinformatics analysis were performed to determine potential driver genes that regulate PD-L1 in tumor cells-derived tumorspheres which mimicking cancer stem cells. Then, the specific inhibitors targeting EGFR were applied to reduce the expression of PD-L1 in vitro and in vivo. We validated that EGF could induce PD-L1 expression in the selected EGFR-positive cancers. RNAseq results revealed that STAT1 increased as a driver gene in KOSC-3-derived tumorspheres; these data were analyzed using PANTHER followed by NetworkAnalyst. The blockade of EGFR by afatinib resulted in decreased STAT1 and IRF-1 levels, both are transcriptional factors of PD-L1, and disabled the IFNr-STAT1-mediated PD-L1 axis in vitro and in vivo. Moreover, STAT1 knockdown significantly reduced EGF-mediated PD-L1 expression, and ruxolitinib, a JAK1/JAK2 inhibitor, significantly inhibited STAT1 phosphorylation to reduce the IFNr-mediated PD-L1 axis. These results indicate that EGF exacerbates PD-L1 by increasing the protein levels of STAT1 to enforce the IFNr-JAK1/2-mediated signaling axis in selected EGFR-positive cancers. The inhibition of EGFR by afatinib significantly reduced PD-L1 and may be a potential strategy for enhancing immunotherapeutic efficacy.