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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.

We encountered a case involving a brain abscess in the right frontal lobe of a 12-year-old girl who was diagnosed with a chief complaint of headache and nausea. Left maxillary sinusitis, a dental infection related to dental caries and apical periodontitis, was observed in the left maxillary first molar in addition to left frontal sinusitis also being present. In addition to administering antibacterial agents, extraction of the left maxillary first molar and drainage of the paranasal sinuses and brain abscess were performed. Follow-up over the course of 1 year and 5 months indicated that the patient had progressed without any sequelae; therefore, the prognosis was good. In this case, although bone destruction was observed in the posterior wall of the frontal sinus, which could be a route for bacteria to enter the skull, we considered the possibility of direct invasion from the same site to be low because the brain abscess occurred on the opposite side. We believe that a route for hematogenous invasion from apical periodontitis, in addition to sinusitis, is also possible. Regardless of the route, the outset was an infection in the dental field; therefore, this case reaffirmed the importance of dental cavity treatment in childhood. [ABSTRACT FROM AUTHOR]

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.

Magnetic resonance imaging (MRI) is a more useful diagnostic modality for detecting paranasal tumors compared with computed tomography (CT). We encountered a case of malignant lymphoma of the maxillary sinus. Although CT findings suggested malignancy, MRI findings indicated an inflammatory disease. The patient was a 51-year-old man with a chief complaint of right maxillary toothache. Edema in the right middle meatus and bloody rhinorrhea were observed. CT revealed r ight maxillary s inus shadow with partial bone loss, suggesting malignancy. However, MRI performed two weeks later showed an internal homogeneous lesion with neither contrast effect, nor invasion outside the maxillary sinus. The patient also had no fever, weight loss, or night sweats. Additionally, no palpable cervical lymphadenopathy was observed. Endoscopic sinus surgery was performed to confirm the diagnosis. Upon opening the maxillary sinus, highly viscous retention and a large amount of yellowish-white debris were observed. Allergic fungal rhinosinusitis was suspected. However, histopathological analysis of the debris established a diagnosis of malignant lymphoma. The debris exhibited pathological findings of necrosis. The patient remained in remission after undergoing radiochemotherapy. Malignant lymphomas of the paranasal sinuses, which have a minimal tendency for invasion but with considerable predominance of necrosis, may be diagnosed as an inflammatory disease, based on MRI findings. In cases in which a thorough physical examination could not rule out malignant lymphomas, an endoscopic biopsy should be immediately considered. [ABSTRACT FROM AUTHOR]

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

Background/Aim: In December 2019, pembrolizumab was approved in Japan for the treatment of head and neck cancer with recurrence or distant metastasis, making it a new option for first-line treatment. However, there are still many unanswered questions about Overall survival (OS), Progression free survival (PFS), adverse events including immune-related adverse events (irAEs), and biomarkers. Aims/Objectives: The aim of this study was to retrospectively review first-line treatment of head and neck cancer with recurrence or distant metastasis treated with pembrolizumab and to determine whether Combined positive score (CPS) is still useful as a biomarker in the clinical practice. Material and Methods: We retrospectively reviewed clinical records of 20 patients who received pembrolizumab as first-line treatment for head and neck cancer with recurrence or distant metastasis between December 2019 and March 2021. Results: Age ranged from 45 to 83 years (median 66 years), 17 male patients and 3 female patients. The response rate was 40%, and the disease control rate was 60%. OS and PFS in patients with CPS < 1 were significantly worse than those with CPS ≤ 1 (CPS-positive patients). The OS and PFS of patients with CPS < 1 were s ignificantly worse than those of p atients with 1 < = CPS (CPS-positive p atients), and there was no significant difference between the group with CPS between 1 and 20 and the group with CPS over 20. And we experiences several CR cases with high CPS. Conclusion: CPS is a useful biomarker for pembrolizumab. Significance: There are no reported cases of CR after two courses of pembrolizumab in head and neck cancer. There are no reports of pembrolizumab in patients with head and neck cancer in Japan. [ABSTRACT FROM AUTHOR]

Methods: A 42-year-old woman presented to our clinic with tongue pain and dysarthria. She had a smoking history of 22 pack-years and no history of alcohol consumption. A deep ulcer at the left side of the tongue and induration across the whole tongue were observed. The bilateral cervical lymph nodes were palpable. A biopsy from the ulcer revealed squamous cell carcinoma. PET/CT showed sternal bone metastasis resulting in the final diagnosis of left-sided oral tongue cancer (cT4aN2cM1). Systemic chemotherapy treatment involving 6 courses of the EXTREME regimen followed by weekly cetuximab administration was indicated. Results: After the first two courses, diminished tongue pain and improved dysarthria were observed; complete response was obtained after 6 courses. Re-examination of the biopsy specimen showed that the tumor was p16 positive. The p16 protein is a surrogate marker for HPV, but in this case HPV in-situ hybridization was negative. Locoregional or distant failure were not observed during the 5-year follow-up period. Conclusions: The treatment regimen unexpectedly proved successful. It may be beneficial to examine p16 expression in oral tongue cancer to identify patients that are more likely to benefit from the EXTREME treatment regimen. [ABSTRACT FROM AUTHOR]

Background: The correlation between genomic mutations (or the overexpression of abnormal proteins) and prognosis in temporal bone squamous cell carcinoma (TBSCC) is not clear. We investigated the overexpression of EGFR and p53 as a pathological biomarker for predicting the clinical course of patients with TBSCC. Methods: We performed a retrospective review of 22 TBSCC cases treated in Tokai University Hospital between January 2005 and October 2016. We assessed the overexpression of EGFR and p53 in TBSCC patients through immunohistochemical staining. We also evaluated the association between the overexpression of these proteins and clinicopathological variables, including survival outcomes. Results: The primary lesion in all patients was the external auditory canal. Nine (40.9%) patients were EGFR positive, and 9 (40.9%) were p53 positive. The 5-year overall survival rate for EGFR-positive patients (55.6%) was significantly lower (p = 0.043) than that of the EGFR-negative patients (92.3%). Conclusion: EGFR overexpression in TBSCC patients may be a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Lacrimal sac tumors are rare and difficult to diagnose. We present a case of coexisting lacrimal sac adenocarcinoma and transitional cell carcinoma in a 73-year-old woman who presented with swelling of the inner canthus. Biopsy identified the growth as an adenocarcinoma. After dissection of the lacrimal carcinoma via a lateral rhinotomy, histopathologic examination confirmed the adenocarcinoma and identified a coexisting transitional cell carcinoma. A recurrence developed, but only of the adenocarcinoma component. For the recurrence, the patient was treated with wide resection, including the orbital contents, and subsequent irradiation. At 49 months postoperatively, the patient remained alive but with a lung metastasis. Wide resection was the key to treatment. [ABSTRACT FROM AUTHOR]

The glass dosemeter, which is a component of the glass badge (GB), is used on the basis of radiophotoluminescence phenomenon. Chiyoda Technol Corporation has been providing it for personal monitoring services since the year 2000. Through the experience acquired over 15 y, Chiyoda Technol Corporation has developed the New GB, which was brought into service in Japan for radiation monitoring in January 2014. The New GB was developed with the aim of improving radiation measurement methods, streamlining the provision of GB monitoring services and realising a user-friendly dosemeter. As the result, in this study, the measurable energy range covered for beta rays was expanded to include those emitted from 147Pm, the directional dependency was improved, a film was designed to remove secondary electrons arising from interactions between incident photons and the metallic filters, and the arrangement of the metallic filters was optimised. [ABSTRACT FROM AUTHOR]