Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Multicenter Study of Congenital Middle Ear Anomalies. Report on 246 Ears.

OBJECTIVES/HYPOTHESIS: Congenital middle ear anomalies represent a relatively rare condition. This study aimed to describe the characteristics and the surgical outcomes for patients with middle ear anomalies. METHODS: A multicenter study was conducted of consecutive patients with congenital middle ear anomalies who underwent primary surgical treatment between January 2008 and December 2017. Demographics, surgical procedures, and audiometric data were registered into the institutional database. Hearing changes and postoperative air-bone gap (ABG) were evaluated 1 year after surgery. RESULTS: A total of 246 patients (246 ears) (median age: 14 years, range: 4-75 years old) were included in this study. Anomalies were subdivided using the Teunissen and Cremers classification: 53 ears (22%) were categorized as class I, comprising only stapes ankylosis; 35 ears (14%) as class II, having ossicular chain anomalies with stapes ankylosis; 139 ears (57%) as class III, having ossicular chain anomalies with a mobile stapes-footplate; and 19 ears (8%) as class IV, with aplasia of the oval window. Evaluation of hearing outcomes for 198 ears with more than 1 year of follow-up revealed that good postoperative ABG (≤20 dB) was achieved in 82% of class I, 68% of class II, 74% of class III, and 23% of class IV anomalies. The postoperative ABG in class IV was significantly worse than in class I (P < .001) or class III (P < .01). CONCLUSIONS: This study demonstrated that class III anomalies comprised the majority of middle ear anomalies and surgical outcomes for class IV anomalies are unfavorable. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2323-E2328, 2021.

Efficacy of chemotherapy after progression with nivolumab in squamous cell carcinoma of the head and neck.

Nivolumab, a programmed death-1 (PD-1) inhibitor, has shown promising results against squamous cell carcinoma of the head and neck (SCCHN) in cases of recurrence or in a metastatic setting after platinum-based therapy. However, treatment alternatives for patients with nivolumab-refractory are limited, and a constant opinion is not provided. Recently, accumulating studies have demonstrated that chemotherapy after immune checkpoint inhibitor treatment may induce better objective responses in patients with advanced non-small cell lung cancer. However, there are few reports on the increased effect of chemotherapy after nivolumab treatment in SCCHN. Therefore, cases must be accumulated to identify patients with nivolumab-refractory SCCHN who may benefit from chemotherapy. Here, we present patients with SCCHN who exhibited a significant response to chemotherapy after nivolumab treatment.

Facial nerve neuroma in the geniculate ganglion extending into the internal auditory canal: A case report.

Facial nerve schwannoma is a very rare benign tumor representing less than 1% of intrapetrous lesions. Our patient is a forty-one year old female who has suffered from recurrent right facial palsy for the last six years. She was first misdiagnosed as having Bell's palsy and received corticosteroids which resulted in little improvement. She then had facial nerve decompression surgery which resulted in a partial improvement. Since then, she has suffered from recurrent attacks of facial palsy. Two years ago, she came to our hospital seeking further treatment options. The final diagnosis made by MRI was a possible facial nerve tumor. To obtain a better facial outcome, total tumor removal was performed through the middle cranial fossa approach along with facial-hypoglossal nerve end-to-side anastomosis through transmastoid approach. Her hearing was preserved, and she obtained a better facial outcome than that of her preoperative level. In conclusion, facial nerve schwannoma has the potential to be misdiagnosed as Bell's palsy which might lead to a delay in diagnosis, and end-to-side neurorrhaphy may be an effective alternative in a selected case.

Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion.

The plasminogen activator/plasmin system is one of the main protease systems involved in tumor cell invasion and metastasis. Our previous study has shown that plasmin degrades E-cadherin and promotes cell dissemination by downregulation of E-cadherin-mediated cell-cell adhesion in oral squamous cell carcinoma (SCC) cells. To examine the effect of downregulation of the plasminogen activator/plasmin system by alpha2-antiplasmin (alpha2-AP) on cell-cell adhesion mediated by E-cadherin in oral SCC cells, the oral SCC cell line SCCKN was stably transfected with alpha2-AP cDNA. Induction of alpha2-AP expression led to the inhibition of the proteolysis of E-cadherin by plasminogen activator/plasmin in SCC cells, resulting in the enhancement of the cell aggregation and the suppression of the cell motility. Moreover, alpha2-AP also reduced the ability of SCC cells to invade type I collagen gel, and suppressed tumorigenicity in vivo. These results suggested that downregulation of the plasminogen activator/ plasmin system by alpha2-AP might be a potent therapeutic approach to prevent the progression of oral SCC.

Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin.

The participation of plasminogen activator/plasmin system in the expression and function of E-cadherin was examined in oral squamous cell carcinoma (SCC) cells. Treatment of SCC cells with plasminogen reduced the Ca2+-dependent cell aggregation. SCC cells expressed E-cadherin at the cell membrane, and released a small amount of soluble E-cadherin at 80 kDa in the culture medium. Addition of plasminogen to SCC cells led to a decrease in the amount of E-cadherin of the cell membrane and the enhancement of the shedding of E-cadherin ectodomain. Plasmin directly cleaved E-cadherin of SCC cells and enhanced the motility of SCC cells. These results suggested that plasminogen activator/plasmin system might directly mediate the proteolytic processing of E-cadherin in oral SCC cells and that might facilitate the progression of oral SCC by downregulation of E-cadherin-mediated cell-cell adhesion.

Role of stromal thrombospondin-1 in motility and proteolytic activity of oral squamous cell carcinoma cells.

The immunohistochemical localization of thrombospondin-1 (TSP-1) in human normal oral mucosa and oral squamous cell carcinoma (SCC) was examined. The immunostaining of TSP-1 was mainly localized in the connective tissues adjacent to the epithelium of oral mucosa, whereas epithelial cells showed negligible immunoreactivity for TSP-1. TSP-1 expression was striking in the stroma of SCC. TSP-1 synthesis by SCC cells and fibroblasts in culture was examined by immunoprecipitation with anti-TSP-1 antibody. Fibroblasts produced a large amount of TSP-1, whereas SCC cells secreted little amount of TSP-1. Treatment of fibroblasts by the conditioned medium of SCC cells led to an increase in TSP-1 synthesis. TSP-1 induced haptotactic migration and stimulated the production of matrix metalloproteinase-9 (MMP-9) in SCC cells. These results suggest that TSP-1 in the stroma of oral SCC might be synthesized by mesenchymal cells but not by epithelial cells, and that the synthesis of TSP-1 might be regulated by interaction with SCC cells. TSP-1 accumulated in the stroma might promote the progression of oral SCC by enhancing the motility and proteolytic activity in a paracrine manner.