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.

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.

CD147 expression correlates with lymph node metastasis in T1-T2 squamous cell carcinoma of the tongue.

Cervical lymph node metastasis causes a poor prognosis in cases of stage T1-T2 squamous cell carcinoma (SCC) of the tongue. Recent studies have reported that cluster of differentiation (CD)147, also known as extracellular matrix metalloproteinase inducer, contributes to tumor progression. The present study evaluated the role of CD147 in the tumorigenesis of SCC of the tongue in vitro, as well as the association between CD147 expression and cervical lymph node metastasis in clinical samples of SCC of the tongue. Tongue SCC cell lines were used to evaluate in vitro tumorigenesis. In addition, 41 patients with clinical stage T1-T2 tongue SCC were assessed with a histopathological analysis. Univariate and multivariate analysis were performed to investigate the risk of cervical lymph node metastasis associated with histopathological findings. In the in vitro study, cell invasiveness was upregulated by S100 calcium-binding protein A9 (S100A9) stimulation and downregulated following CD147-blocking antibody treatment. The univariate and multivariate analyses identified CD147 expression in the invasive tumor front as an independent risk factor for metastasis. It was concluded that CD147 induces tongue carcinoma cell invasion through its interaction with S100A9. Thus, an evaluation of the extent of CD147 expression in cancer cell nests at the invasive tumor front may help in predicting cervical lymph node metastasis in patients with clinical N0 T1-T2 tongue SCC.

ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction.

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.