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Background: Recurrent or metastatic squamous cell carcinoma of the head and neck (R/MHNSCC) is a challenging malignancy with a poor prognosis and limited treatment options. Nivolumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) pathway, has emerged as a promising therapy for these patients. However, identifying biomarkers predictive of response to nivolumab remains critical for optimizing treatment strategies. Previous studies have suggested that PD-L1 expression, as determined by the Combined Positive Score (CPS) and other clinical factors, may influence treatment outcome. This study aims to retrospectively examine whether CPS can be a biomarker by staining PD-L1 with 22 C3 antibody in R/MHNSCC patients treated with nivolumab. Methods: This retrospective study reviewed the medical records of R/MHNSCC patients treated with ICIs at Tokai University Hospital from April 2017 to December 2022. We examined the relationship between response rate to ICI therapy, PD-L1 staining, biomarkers, and survival. Statistical analyses included t -test, chi-square test, and Cox regression. Results: This study included 92 nivolumab-treated patients. Combined Positive Score was evaluable in 53 of these patients. Patients with a CPS of 15 or higher had better progression-free survival (PFS) ( P = .0171), with a median PFS) of 13 months. In the Various Definitions analysis, cisplatin-sensitive patients also had good PFS ( P = .0295). The cisplatin-sensitive patient population with a CPS of 15 or higher had the best PFS, with a median of 14 months ( P = .006). There was no significant difference in overall survival (OS) by CPS value. Immune-related adverse events did not affect OS or PFS. Conclusions: CPS ⩾ 15 and cisplatin sensitivity are promising prognostic markers for nivolumab therapy in R/MHNSCC. Considering these biomarkers in patient selection could maximize the therapeutic benefits of nivolumab. This finding may help to optimize ICI therapy strategies.

Abstract Objective This study aimed to evaluate the clinical effectiveness of chemotherapy following immune checkpoint inhibitors (ICI). The association between inflammatory and nutritional factors and prognosis has also been investigated. Methods We retrospectively reviewed the medical records of recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) patients who received chemotherapy following ICI therapy. The response rate and survival after chemotherapy, and nutritional and inflammatory factors, were examined. Results The ICI before chemotherapy was nivolumab in 36 patients (70.6%) and pembrolizumab in 15 patients (29.4%). The chemotherapy regimens consisted of PTX in 32 patients (62.7%), PTX + Cmab in 9 (17.6%), and S1 in 10 (19.6%). The median overall survival (OS) was 20 months (95% CI 12–25), the estimated 12-month OS rate was 63.3%, the median progression-free survival (PFS) was 5 months (CI 4–6), and the 12-month PFS estimate was 8.9%. Univariate analysis significantly correlated Neutrophil-to-Lymphocyte Ratio (NLR), platelet-to-lymphocyte ratio (PLR), controlling nutritional status score (CONUT), and prognostic nutrition index (PNI) with OS and PFS. Additionally, these factors were significantly correlated with OS and PFS in the log-rank tests. Conclusions Chemotherapy following ICI is highly effective. There were no significant differences in the chemotherapy regimens. Inflammatory and nutritional factors may associate with patient prognosis after chemotherapy.

Abstract Background The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood. Case Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation. Conclusion This report was reviewed to examine the synergistic effects of ICI and radiotherapy and to identify optimal strategies to enhance the abscopal effect in clinical practice. It has also touched on various ongoing debates and clinical trials aimed at understanding and exploiting this effect to improve cancer treatment. The exact mechanisms and optimal treatment protocols remain areas for future research.

Abstract Background Transoral salvage surgery has the potential to preserve a patient's quality of life. Therefore, we investigated the outcomes, safety, and risk factors for postoperative complications of salvage transoral videolaryngoscopic surgery (TOVS) for recurrent hypopharyngeal carcinoma after radiotherapy (RT) or chemoradiotherapy (CRT). Methods This retrospective analysis enrolled patients with hypopharyngeal cancer who had a history of RT or CRT and underwent TOVS from January 2008 to June 2021. The factors related to postoperative complications, postoperative swallowing functions and survival rates were analyzed. Results Seven patients (36.8%) of the 19 patients developed complications. Severe dysphagia was the primary complication, and post‐cricoid resection was a complication risk factor. The FOSS score was significantly lower in the salvage treatment group. The survival rates were: 3‐year overall survival: 94.4%; disease‐specific survival: 94.4%; 5‐year overall survival: 62.3%; and disease‐specific survival: 86.6%. Conclusions Salvage TOVS for hypopharyngeal cancer was feasible, and oncologically and functionally reasonable. Level of Evidence: 2b.

Abstract Objectives With the advent of new optical technologies, early pharyngolaryngeal cancerous lesions can be better visualized. Although the conventional transnasal approach offers great views of the hypopharynx and larynx, the visualization of the oropharynx and palatine tonsils is limited. Through the transoral insertion of a flexible video‐laryngoscope, direct views of the oropharynx and oral cavity can be obtained. Thus, transoral examination may contribute to primary detection of cancers of unknown primary (CUP). Methods Eighty‐five CUP patients from Tokai University were included retrospectively in this study, from 2006 to 2017. Starting in 2010, we employed the transoral examination in addition to our conventional method. The primary detection rates were compared before and after 2010. Oropharyngeal primaries were further analyzed for tumor subsite and p16 status. Results The overall primary detection rate did not improve with the addition of transoral examination. However, greater numbers of oropharyngeal primaries were detected. The oropharyngeal lesions detected by transoral examination were mainly p16 positive, located on the palatine tonsil. Conclusion Transoral examination is a noninvasive, easy method to adopt in an outpatient setting, and a promising technique to improve tumor detection in this era of human papillomavirus‐associated head and neck cancers. Level of Evidence 3.

Abstract Background Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN. Methods Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. Results Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen. Conclusions PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN.

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Eagle syndrome is characterized by an elongated styloid process. However, the time frame over which the styloid process becomes elongated and extends is unknown. How the condition worsens over time is also unclear. To date, there has been no report describing the chronologic change that occurs in the styloid process in Eagle syndrome. We describe a 53-year-old patient with Eagle syndrome in whom the styloid process enlarged progressively over time and the elongated styloid process fused with the hyoid bone. The styloid process was resected via a transcervical approach, and the patient’s subjective symptoms improved. This is the first report showing how the styloid process can enlarge over a few years in a patient with Eagle syndrome. Surgical resection via a transcervical approach is an appropriate treatment for a patient in whom the styloid process has become excessively enlarged and elongated.

Background. The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy. Methods and Results. We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy. Conclusion. To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.

Background and study aims: Early detection of superficial pharyngeal squamous cell carcinoma (SPSCC) using narrow-band imaging as well as the increasing use of ER for gastrointestinal cancers may increase the number of ER for SPSCC. The aims of this study were to clarify the feasibility of ER for SPSCC and its long-term outcomes. Patients and methods: In total, 84 patients with 115 lesions were treated by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) between March 2004 and August 2012. We retrospectively assessed the en bloc and R0 resection rates, complications, lymph node metastasis (LNM), local recurrence, metachronous pharyngeal and esophageal SCC, 5-year overall and cause-specific survival rates. Results: Higher proportions of en bloc and R0 resection were achieved with ESD compared to EMR (en bloc 100 % vs. 60 %, P

A Ga-Sn-O (GTO) thin-film memristor has been developed, and an analog plasticity characteristic has been observed. First, GTO thin-film memristors are fabricated by depositing three GTO layers in a stacked structure using sputtering. Next, the current-voltage characteristics are measured by varying the maximum applied voltage after a certain negative voltage, the hysteresis is observed, and the switching characteristics are evaluated, which is regarded as that an analog plasticity characteristic is observed. The parametric study is done for the stacked structure and deposition process, and the proposed operating mechanism is that oxygen vacancies reciprocate by applying negative and positive voltages. Finally, the pulse application characteristic shows the long-term potentiation and depression, which presents a practical possibility to utilize the GTO thin-film memristor for neuromorphic systems.

Background The longitudinal relationship between cancer-related fatigue (CRF) and physical function remains unclear. This study evaluated the association between pre-treatment physical functions and CRF exacerbation following concurrent chemoradiotherapy (CCRT). Methods The study included 42 cancer patients undergoing CCRT. Poor physical function was de ned as the presence of either or both low grip strength (3 points. A multivariate logistic regression analysis was performed to identify the association between poor physical function and exacerbation of CRF. Results Seventeen (40.5%) patients developed CRF exacerbation following CCRT. More patients had poor physical function in the CRF exacerbation group (58.8% vs. 20.0%; p=0.02). Poor physical function was an independent risk factor for exacerbation of CRF following CCRT after adjusting for confounders. Conclusions Poor physical function was a risk factor for exacerbation of CRF following CCRT. Assessing physical function may be useful in determining patients at high risk for CRF exacerbation following CCRT.