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Background/aim: Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications., Patients and Methods: We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement., Results: Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups., Conclusion: The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear., Patients and Methods: We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders., Results: In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response., Conclusion: Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Nivolumab is expected to further prolong survival and improve the quality of life (QOL) of patients with a poor prognosis of head and neck cancer. However, only a few studies have been conducted regarding the QOL of recurrent or metastatic head and neck cancer patients treated with nivolumab using real-world data. This study aimed to examine the effect of nivolumab on the QOL of these patients using real-world data., Patients and Methods: This study included patients with recurrent metastatic head and neck cancer who received nivolumab at the Department of Otolaryngology and Head and Neck Surgery, Tokyo Medical University Hospital from May 1, 2017, to December 31, 2021. Among them, 50 patients who self-assessed their QOL were included in this study. The primary endpoint was the QOL evaluation score, and secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate, and immune-related adverse events. OS and PFS were evaluated using the Kaplan-Meier method., Results: No significant reduction in QOL was observed before or after nivolumab administration. The median OS time was 20.1 months, and 1-year OS rate was 76.4%. The median PFS time was 4.2 months, and 1-year PFS rate was 31.0%., Conclusion: The comparison of patient QOL before and after nivolumab use suggested that patient QOL was not compromised. The results were not inferior to those of other studies in terms of treatment efficacy and safety., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection., Methods: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated., Results: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections., Conclusions: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy., (© 2023 Wiley Periodicals LLC.)

Background/aim: Head and neck photoimmuno-therapy (HN-PIT) has been an insured treatment in Japan for approximately three years. The number of treatments has gradually increased to over 350 cases. However, there are still various questions in actual clinical practice, including laryngeal edema. Therefore, it is vital to carefully explain in advance to patients the possibility of laryngeal edema occurring and obtaining consent for tracheostomy as a prophylactic or emergency measure. At our institution, 44 HN-PIT cycles were performed in 23 patients between January 2021 and October 2023. Of these, we experienced two cases in which preventive tracheostomy was not performed because the risk of laryngeal edema was considered low; however, laryngeal edema developed after treatment, and an emergency tracheostomy had to be performed., Case Report: Case 1 was a patient in his 70s with a local recurrence of mandibular gingival carcinoma. HN-PIT using cylindrical diffusers was performed on the target lesion, extending from the lateral wall of the oropharynx to the soft palate. Case 2 was also a patient in his 70s with carcinoma of the mid-pharynx. HN-PIT was performed using a frontal diffuser to target lesions extending from the soft palate to the buccal mucosa. Notably, both patients developed laryngeal edema after HN-PIT, and an emergency tracheostomy had to be performed., Conclusion: HN-PIT treatment is still being established through a trial-and-error method and is still incomplete., Competing Interests: Isaku Okamoto received lecturer fees from Rakuten Medical KK. The Authors declare no conflicts of interest in relation to this study., (Copyright 2024, International Institute of Anticancer Research.)

Background/aim: A pharyngeal fistula is the most common complication of total laryngectomy; thus, accurate diagnosis and treatment are important. Diagnosis is usually made by the finding of leakage of the contrast agent outside the pharynx during swallowing contrast examination. Herein, we encountered a case in which fine leaks not detected on contrast examination during swallowing were visualized and diagnosed by computed tomography (CT) imaging with oral contrast media with the patient in a prone position., Case Report: During imaging in a prone position, the contrast agent entered the sutures on the cephalocaudal and ventral sides of the surgical site, which were particularly prone to leaks due to gravity, and it was possible to diagnose minute leaks. When there is a high risk of postoperative pharyngeal fistula, such as in reconstructive cases with a pedunculated flap or with overlapping risk factors such as preoperative irradiation, CT imaging with contrast medium in a prone position is considered useful when swallowing contrast examination does not provide a clear diagnosis. However, suture failure is possible, and this should be evaluated., Conclusion: This case suggests that routine prone CT may lead to the early detection of postoperative pharyngeal fistula in high-risk cases. Further accumulation of cases is required to confirm our findings., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC)., Patients and Methods: Platinum-sensitive patients with R/M-HNSCC were selected at Tokyo Medical University Hospital from May 1, 2017, to June 30, 2022. Patients with a history of treatment with nivolumab or pembrolizumab were included. Nivolumab was used in 21 cases and pembrolizumab in 15 cases., Results: The median overall survival (OS) was 16.9 months in the nivolumab group and 19.2 months in the pembrolizumab group and no significant differences were observed between the two groups. The median progression-free survival (PFS) was 4.8 months in the nivolumab group and 9.3 months in the pembrolizumab group. No significant differences were observed between the two groups. The objective response rates (ORR) were 38% and 47% in the nivolumab and pembrolizumab groups, respectively., Conclusion: Nivolumab as well as pembrolizumab were found to be effective in platinum-sensitive patients with R/M-HNSCC. Nivolumab can be considered a potential treatment option for platinum-sensitive R/M-HNSCC in the future., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities., Patients and Methods: Data of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022 were analyzed. The endpoint was overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). OS and PFS were analyzed comparatively with and without irAEs, and complete response (CR) or partial response (PR), and stable disease (SD) or progressive disease (PD) were compared., Results: One hundred thirty-five patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. For the pembrolizumab only group, the median OS and PFS were 22.7 and 5.1 months, respectively. There were significant differences in OS and PFS between CR or PR and SD or PD (p<0.01, p<0.01, respectively). For pembrolizumab with chemotherapy, the OS was not reached and median PFS was 7.0 months. There was a significant difference in PFS between CR or PR and SD or PD (p<0.01). There was a significant difference in PFS between patients with and without irAEs (p=0.02)., Conclusion: The real-world therapeutic effect of pembrolizumab for R/M SCCHN was comparable to that observed in the KEYNOTE048 trial. In addition, irAEs and best overall response were considered as prognostic factors., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Nivolumab has antitumor efficacy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who relapse within 6 months after platinum-based therapy; however, the efficacy of nivolumab for platinum-sensitive R/M HNSCC has not been shown. Therefore, this study compared the efficacy and safety of nivolumab for platinum-refractory and platinum-sensitive R/M HNSCC., Patients and Methods: This was a retrospective study of patients who received nivolumab for R/M HNSCC who had been previously treated with platinum-based anticancer drugs. Patients were divided into a platinum-sensitive and a platinum-refractory group, and progression-free survival (PFS), overall survival (OS), the overall response rate (ORR) [complete response (CR) + partial response (PR)], the disease control rate (DCR) (CR + PR + stable disease), and the incidence of immune-related adverse events (irAEs) were compared between the two groups., Results: We included 88 patients with squamous cell carcinoma: 60 with platinum-refractory disease and 28 with platinum-sensitive disease. The median PFS in the platinum-refractory and platinum-sensitive groups were 2.7 months and 5.3 months, respectively (p=0.03), and the median OS were 8.8 months and 17.1 months, respectively (p=0.06). There were no significant differences in the ORR, DCR, or incidence of irAEs between the two groups (p>0.99, p=0.11, and p>0.99, respectively)., Conclusion: Nivolumab is a safe and effective treatment for platinum-sensitive R/M HNSCC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method., Patients and Methods: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities., Results: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%., Conclusion: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Head and neck photoimmunotherapy (HN-PIT), a new treatment developed for local control of head and neck carcinoma, uses cetuximab sarotalocan sodium with a laser system to specifically destroy only tumor cells. No studies have examined the impact of HN-PIT on the quality of life (QOL) of patients with head and neck cancer. This study assessed the QOL of patients with unresectable locally advanced or locally recurrent head and neck carcinoma (LA/LR-HNC) treated with HN-PIT. Nine eligible patients with unresectable LA/LR-HNC who underwent HN-PIT at our institution between 20 January 2021 and 30 April 2022 were included in the study. They completed a QOL evaluation form. The primary endpoint was QOL assessment. The secondary endpoints were overall response rate, overall survival (OS), progression-free survival, and adverse events. QOL was compared before and 4 weeks after HN-PIT. There were no significant changes in all QOL assessment parameters after treatment with HN-PIT. The overall response rate was 89%, and safety was acceptable. For patients with unresectable LA/LR-HNC, HN-PIT provided good local control without decreasing the QOL. The addition of HN-PIT to conventional head and neck carcinoma treatment may lead to the prolongation of OS in head and neck carcinoma., Competing Interests: The authors declare no conflict of interest.

A 30-year-old man presented with swelling in the lower left ear. Close examination led to a diagnosis of parotid gland cancer, T4N0M0 Stage IVA, so total resection of the left parotid gland and left neck dissection were performed. Pathological examination led to a diagnosis of high-grade malignant-type mucoepidermoid, and chemoradiotherapy was performed as postoperative treatment. Fourteen days after completion of chemoradiotherapy, the patient was admitted to the hospital with headache and lack of appetite. Echocardiography showed a pericardial effusion and complete collapse of the right ventricle; cardiac tamponade was diagnosed, and pericardiocentesis was performed. The pericardial effusion was bloody, and a metastatic lesion was suspected, but cytological examination showed class IIIa. On day 33 of the illness, respiratory distress and hypotension were observed. A clot was seen covering the lower wall of the heart, and dilatation of the lower wall was significantly impaired. Pericardiotomy was performed on day 36. Pathological examination diagnosed cardiac metastasis of mucoepidermoid carcinoma of the parotid gland. Although only 4 cases of parotid cancer have been reported as primary lesions of metastatic heart tumors, this case represents the world's first description of isolated parenchymal metastasis of mucoepidermoid carcinoma of the parotid gland diagnosed by pericardial biopsy., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest, potential conflicts, or financial relationships to disclose., (Copyright © 2021 Japanese Society of Otorhinolaryngology-Head and Neck Surgery, Inc. Published by Elsevier B.V. All rights reserved.)

This study compared the incidence of perioperative complications and swallowing function between free jejunal flap reconstruction and cutaneous free tissue flap construction. We included 223 patients who underwent hypopharyngeal reconstruction using free flap. At discharge, +the free jejunal flap was associated with a Functional Oral Intake Scale (FOIS) score of 1-6 in 132 cases (70%) and a score of 7 in 56 cases (30%). Regarding the cutaneous free tissue flaps, FOIS scores of 1-6 were observed in 18 cases (51%), and a score of 7 was noted in 17 cases (49%). Donor site complications occurred in 12% of the patients who underwent free jejunal flap procedures and in none of the patients who underwent cutaneous free tissue flap procedures. We found that the free jejunal flap had a regular dietary intake rate in 56 patients (30%), whereas cutaneous free tissue flaps had a regular dietary intake rate in 17 patients (49%). Cutaneous free tissue flaps had a significantly higher regular dietary intake rate at discharge and a significantly lower incidence of donor site complications than free jejunal flaps. In conclusion, free-flap reconstruction may be a better method than free jejunal flap reconstruction for the treatment of hypopharyngeal cancer.

Background/aim: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data., Patients and Methods: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety., Results: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups., Conclusion: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)