Boron neutron capture therapy (BNCT) is a radiation therapy that utilizes the alpha rays produced by the thermal neutron capture reaction of boron nuclei. With BNCT, only unresectable head and neck cancer (HNC) is currently covered by medical insurance in Japan. Some authors have reported the outcomes of BNCT for HNC, but individual case reports are lacking; therefore, the detailed clinical course of such patients remains poorly understood. Herein, we report a case of BNCT treatment for an unresectable residual lesion of external auditory canal carcinoma. A 59-year-old man was diagnosed with squamous cell carcinoma of the right auditory canal. He underwent right lateral temporal bone resection surgery followed by additional chemoradiotherapy; however, a residual preauricular lesion and an unresectable residual lesion deep in the middle ear were identified 2 months later. BNCT was administered for the middle ear and preauricular lesion. Although the preauricular lesion required an additional surgical excision, the middle ear lesion remained locally controlled at the 3-year follow-up. Grade 3 brain radiation necrosis and skin disorders occurred as late adverse events, however, the patient continued his daily activities without any impairment in his quality of life.
{"title":"Boron neutron capture therapy for unresectable residual external auditory canal carcinoma","authors":"Hideto Shigemi , Yoshinori Kadowaki , Teruhito Aihara , Satoshi Takeno , Misaki Iwata , Kaoru Hashimoto , Shohei Iwano , Kazuhiro Yoshinaga , Yumi Kizu , Masashi Suzuki , Takashi Hirano","doi":"10.1016/j.anl.2025.12.007","DOIUrl":"10.1016/j.anl.2025.12.007","url":null,"abstract":"<div><div>Boron neutron capture therapy (BNCT) is a radiation therapy that utilizes the alpha rays produced by the thermal neutron capture reaction of boron nuclei. With BNCT, only unresectable head and neck cancer (HNC) is currently covered by medical insurance in Japan. Some authors have reported the outcomes of BNCT for HNC, but individual case reports are lacking; therefore, the detailed clinical course of such patients remains poorly understood. Herein, we report a case of BNCT treatment for an unresectable residual lesion of external auditory canal carcinoma. A 59-year-old man was diagnosed with squamous cell carcinoma of the right auditory canal. He underwent right lateral temporal bone resection surgery followed by additional chemoradiotherapy; however, a residual preauricular lesion and an unresectable residual lesion deep in the middle ear were identified 2 months later. BNCT was administered for the middle ear and preauricular lesion. Although the preauricular lesion required an additional surgical excision, the middle ear lesion remained locally controlled at the 3-year follow-up. Grade 3 brain radiation necrosis and skin disorders occurred as late adverse events, however, the patient continued his daily activities without any impairment in his quality of life.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 50-54"},"PeriodicalIF":1.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To assess the impact of WeChat applet-based myofunctional therapy (MFT) on the efficacy and adherence of patients with obstructive sleep apnea (OSA) compared to conventional hospital-guided programs.
Methods
A parallel-group randomized controlled trial was conducted, enrolling 78 patients with OSA who declined continuous positive airway pressure (CPAP) or surgical treatment (mean age 39.44 ± 9.82 years). Participants were randomly allocated to either the mini-program intervention group (n = 39) or the non-intervention group (n = 39). Both groups underwent a 12-week oropharyngeal muscle training program that targeted the soft palate, tongue, lips, and buccal muscles. The intervention group received video-based guidance, real-time feedback, and automated compliance monitoring via a customized WeChat application, whereas the non-intervention group maintained their records using paper diaries. Outcomes, including polysomnography results, sleep scale scores, and compliance rates, were subsequently compared between the two groups.
Results
Sixty-six patients completed the study (32 in the intervention group and 34 in non-intervention group). Improvement in AHI was significantly better in the intervention group than in the non-intervention group (Δ8.92±9.27 vs. Δ2.66±6.80 beats/hour, P < 0.001), and adherence rates were higher at all time points (12 weeks: 73 % vs. 66 %, P = 0.002).
Conclusions
Mobile health guided MFT significantly improved treatment adherence in patients with OSA and outperformed traditional modality in terms of improvement in the core metric AHI, providing a digital solution for CPAP-intolerant patients.
目的：评估b微信苹果肌功能疗法（MFT）对阻塞性睡眠呼吸暂停（OSA）患者疗效和依从性的影响，并与传统的医院指导方案进行比较。方法：采用平行组随机对照试验，纳入78例持续气道正压通气（CPAP）或手术治疗下降的OSA患者（平均年龄39.44±9.82岁）。参与者被随机分配到小程序干预组（n = 39）和非干预组（n = 39）。两组都进行了为期12周的口咽肌肉训练计划，目标是软腭、舌头、嘴唇和颊肌。干预组通过定制的微信应用程序接受基于视频的指导、实时反馈和自动依从性监测，而非干预组使用纸质日记进行记录。随后比较两组的结果，包括多导睡眠图结果、睡眠量表得分和依从率。结果：66例患者完成研究，其中干预组32例，非干预组34例。干预组的AHI改善明显优于非干预组（Δ8.92±9.27 vs. Δ2.66±6.80次/小时，P < 0.001），坚持率在所有时间点都更高（12周：73% vs. 66%, P = 0.002）。结论：移动健康引导下的MFT显著提高了OSA患者的治疗依从性，在改善核心指标AHI方面优于传统模式，为cpap不耐受患者提供了数字化解决方案。
{"title":"Efficacy and adherence of mobile health-based myofunctional therapy for obstructive sleep apnea","authors":"Liqun Zhu , Wenqian Zhong , Meihong Zhang , Chucheng Wu , Yuxiang Zhou , Jing Tao , Beiping Miao , Zhenzhang Lu","doi":"10.1016/j.anl.2025.12.003","DOIUrl":"10.1016/j.anl.2025.12.003","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the impact of WeChat applet-based myofunctional therapy (MFT) on the efficacy and adherence of patients with obstructive sleep apnea (OSA) compared to conventional hospital-guided programs.</div></div><div><h3>Methods</h3><div>A parallel-group randomized controlled trial was conducted, enrolling 78 patients with OSA who declined continuous positive airway pressure (CPAP) or surgical treatment (mean age 39.44 ± 9.82 years). Participants were randomly allocated to either the mini-program intervention group (<em>n</em> = 39) or the non-intervention group (<em>n</em> = 39). Both groups underwent a 12-week oropharyngeal muscle training program that targeted the soft palate, tongue, lips, and buccal muscles. The intervention group received video-based guidance, real-time feedback, and automated compliance monitoring via a customized WeChat application, whereas the non-intervention group maintained their records using paper diaries. Outcomes, including polysomnography results, sleep scale scores, and compliance rates, were subsequently compared between the two groups.</div></div><div><h3>Results</h3><div>Sixty-six patients completed the study (32 in the intervention group and 34 in non-intervention group). Improvement in AHI was significantly better in the intervention group than in the non-intervention group (Δ8.92±9.27 vs. Δ2.66±6.80 beats/hour, <em>P</em> < 0.001), and adherence rates were higher at all time points (12 weeks: 73 % vs. 66 %, <em>P</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>Mobile health guided MFT significantly improved treatment adherence in patients with OSA and outperformed traditional modality in terms of improvement in the core metric AHI, providing a digital solution for CPAP-intolerant patients.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 19-26"},"PeriodicalIF":1.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.anl.2025.11.003
Akiko Uchida , Takeshi Igarashi , Miki Nozawa, Tomohiko Yamauchi, Kota Matsuyama, Ryutaro Onaga, Mari Dias Shimada, Takahiro Fukuhara, Hiroshi Nishino, Makoto Ito, Takeharu Kanazawa
Objective
We aimed to evaluate whether early surgical intervention remains the optimal treatment strategy for primary hyperparathyroidism (PHPT), in light of recent advances in conservative management, by assessing surgical outcomes and examining the clinicopathological factors associated with preoperative intact parathyroid hormone (iPTH) levels.
Methods
We retrospectively analyzed 80 patients (19 men and 61 women; mean age, 56.8 years) who underwent parathyroidectomy for PHPT between 2014 and 2023. Clinical subtypes were classified as renal, biochemical, or skeletal. Collected data included preoperative and postoperative serum calcium and iPTH levels, imaging findings from ultrasonography and 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy, pathological diagnoses, and immunohistochemical expression of Cyclin D1 and Ki-67.
Results
Renal-type PHPT was the most common subtype (52.5%), followed by biochemical (26.3%) and skeletal (21.2%) types. Parathyroid adenomas accounted for the majority of pathological diagnoses (79.6%). The concordance rate for gland localization using combined ultrasonography and MIBI scintigraphy was 72.1%. Surgery led to significant reductions in serum calcium (from 11.1 to 9.1 mg/dL) and iPTH levels (from 201.8 to 37.5 pg/mL). Tumor size was positively correlated with preoperative iPTH levels, whereas Cyclin D1 and Ki-67 expression were not.
Conclusion
Parathyroidectomy yields favorable biochemical outcomes in patients with PHPT and remains the most effective strategy for preventing disease progression. Tumor size was the only factor associated with elevated preoperative iPTH levels. Persistent postoperative iPTH elevation in some patients underscores the importance of early diagnosis and timely surgical intervention, particularly before irreversible systemic complications arise.
{"title":"Surgical outcome of primary hyperparathyroidism and factors correlated with preoperative serum iPTH concentration","authors":"Akiko Uchida , Takeshi Igarashi , Miki Nozawa, Tomohiko Yamauchi, Kota Matsuyama, Ryutaro Onaga, Mari Dias Shimada, Takahiro Fukuhara, Hiroshi Nishino, Makoto Ito, Takeharu Kanazawa","doi":"10.1016/j.anl.2025.11.003","DOIUrl":"10.1016/j.anl.2025.11.003","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to evaluate whether early surgical intervention remains the optimal treatment strategy for primary hyperparathyroidism (PHPT), in light of recent advances in conservative management, by assessing surgical outcomes and examining the clinicopathological factors associated with preoperative intact parathyroid hormone (iPTH) levels.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 80 patients (19 men and 61 women; mean age, 56.8 years) who underwent parathyroidectomy for PHPT between 2014 and 2023. Clinical subtypes were classified as renal, biochemical, or skeletal. Collected data included preoperative and postoperative serum calcium and iPTH levels, imaging findings from ultrasonography and 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy, pathological diagnoses, and immunohistochemical expression of Cyclin D1 and Ki-67.</div></div><div><h3>Results</h3><div>Renal-type PHPT was the most common subtype (52.5%), followed by biochemical (26.3%) and skeletal (21.2%) types. Parathyroid adenomas accounted for the majority of pathological diagnoses (79.6%). The concordance rate for gland localization using combined ultrasonography and MIBI scintigraphy was 72.1%. Surgery led to significant reductions in serum calcium (from 11.1 to 9.1 mg/dL) and iPTH levels (from 201.8 to 37.5 pg/mL). Tumor size was positively correlated with preoperative iPTH levels, whereas Cyclin D1 and Ki-67 expression were not.</div></div><div><h3>Conclusion</h3><div>Parathyroidectomy yields favorable biochemical outcomes in patients with PHPT and remains the most effective strategy for preventing disease progression. Tumor size was the only factor associated with elevated preoperative iPTH levels. Persistent postoperative iPTH elevation in some patients underscores the importance of early diagnosis and timely surgical intervention, particularly before irreversible systemic complications arise.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 35-40"},"PeriodicalIF":1.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunotherapy using immune checkpoint inhibitors is a standard treatment option for many types of malignancies but is not effective for differentiated thyroid cancer (DTC). Regulatory T-cells (Tregs), which are one of the main suppressive factors in the tumor microenvironment, are another important target for immunotherapy. This study investigated the characteristics of Tregs in DTC with the aim of further developing immunotherapy.
Methods
Peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) were obtained from 12 patients with DTC and 12 patients with goiter (benign control group) who underwent primary surgery between February 2017 and September 2022. Flow cytometry analyses were performed for CD4, CD45RA, FOXP3, CC chemokine receptor 4 (CCR4; a candidate Treg-targeting molecule), and immune checkpoint molecules in order to characterize the features of Tregs.
Results
In the DTC patients, age ranged from 39 to 84 years, and the male:female ratio was 7:5. Pathological staging was pT1 or pT2 in 4 patients, pT3 in 8, pN0 in 5, and pN1 in 7, and extrathyroidal extension was observed in 5 patients. Effector Treg (eTreg) frequency in CD4+T-cells in TILs and PBLs was significantly higher in DTC than in goiter. Extrathyroidal extension was associated with a higher eTreg frequency in TILs. A positive correlation was found between eTreg frequency and the expression of immune checkpoint molecules (PD-1, TIM3, GITR, and OX40) on eTregs in TILs from DTC patients. These findings suggest that Tregs are activated in DTC and are important in the creation of an immunosuppressive microenvironment. In addition, the mean positive rate (±standard deviation) of CCR4 on eTregs was high in PBLs (95.8 % ± 3.8 %) and TILs (92.8 % ± 9.8 %) from DTC patients, suggesting that CCR4 is a potential target for eTreg-depletion immunotherapy for DTC.
Conclusion
Tregs were increased and activated in DTC tumor tissue, indicating that they play an important role in creating an immunosuppressive microenvironment in DTC. The results suggest that eTreg-depletion immunotherapy using an anti-CCR4 antibody (mogamulizumab) might be effective for treating DTC.
{"title":"C-C chemokine receptor 4 is a candidate for regulatory T-cell-depletion immunotherapy in differentiated thyroid cancer","authors":"Rui Sano , Hiromu Nakamura , Susumu Suzuki , Daisuke Inukai , Hiroki Okamoto , Shunpei Yamanaka , Taishi Takahara , Akira Satou , Yasushi Fujimoto , Toyonori Tsuzuki , Ryuzo Ueda , Tetsuya Ogawa","doi":"10.1016/j.anl.2025.12.004","DOIUrl":"10.1016/j.anl.2025.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>Immunotherapy using immune checkpoint inhibitors is a standard treatment option for many types of malignancies but is not effective for differentiated thyroid cancer (DTC). Regulatory T-cells (Tregs), which are one of the main suppressive factors in the tumor microenvironment, are another important target for immunotherapy. This study investigated the characteristics of Tregs in DTC with the aim of further developing immunotherapy.</div></div><div><h3>Methods</h3><div>Peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) were obtained from 12 patients with DTC and 12 patients with goiter (benign control group) who underwent primary surgery between February 2017 and September 2022. Flow cytometry analyses were performed for CD4, CD45RA, FOXP3, C<img>C chemokine receptor 4 (CCR4; a candidate Treg-targeting molecule), and immune checkpoint molecules in order to characterize the features of Tregs.</div></div><div><h3>Results</h3><div>In the DTC patients, age ranged from 39 to 84 years, and the male:female ratio was 7:5. Pathological staging was pT1 or pT2 in 4 patients, pT3 in 8, pN0 in 5, and pN1 in 7, and extrathyroidal extension was observed in 5 patients. Effector Treg (eTreg) frequency in CD4<sup>+</sup> <em>T</em>-cells in TILs and PBLs was significantly higher in DTC than in goiter. Extrathyroidal extension was associated with a higher eTreg frequency in TILs. A positive correlation was found between eTreg frequency and the expression of immune checkpoint molecules (PD-1, TIM3, GITR, and OX40) on eTregs in TILs from DTC patients. These findings suggest that Tregs are activated in DTC and are important in the creation of an immunosuppressive microenvironment. In addition, the mean positive rate (±standard deviation) of CCR4 on eTregs was high in PBLs (95.8 % ± 3.8 %) and TILs (92.8 % ± 9.8 %) from DTC patients, suggesting that CCR4 is a potential target for eTreg-depletion immunotherapy for DTC.</div></div><div><h3>Conclusion</h3><div>Tregs were increased and activated in DTC tumor tissue, indicating that they play an important role in creating an immunosuppressive microenvironment in DTC. The results suggest that eTreg-depletion immunotherapy using an anti-CCR4 antibody (mogamulizumab) might be effective for treating DTC.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 27-34"},"PeriodicalIF":1.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1016/j.anl.2025.12.001
Hiroshi Sakaida, Kazuhiko Takeuchi
Objective
Subtotal petrosectomy (STP) is a standard procedure for intractable middle ear disease in Western countries, but reports from Japan are scarce. This report describes the clinical experience, patient characteristics, and surgical outcomes of STP at a tertiary center in Japan.
Methods
We retrospectively reviewed the medical records of all patients who underwent STP in our department between January 2018 and April 2022. We analyzed patient demographics, underlying pathology, preoperative findings, postoperative complications, and the cholesteatoma recurrence rate.
Results
The cohort included 11 patients (7 male, 4 female) with a median age of 75 years. The primary indication was extensive cholesteatoma (11 cases), which was often complicated by dural exposure (6 cases) and labyrinthine fistula (6 cases). Postoperative complications occurred in 1 patient (9 %), who developed a fistula at the blind sac closure site. There were no instances of postoperative facial nerve palsy or inner ear complications. MRI surveillance revealed a residual cholesteatoma recurrence rate of 27 % (3 cases).
Conclusion
STP is an option for managing extensive primary cholesteatoma where hearing reconstruction is not feasible, particularly in the elderly population. However, the risk of residual cholesteatoma is significant, as evidenced by a 27 % recurrence rate in this series, and careful surgical indication is essential to avoid potential over-indication. This finding highlights the critical importance of meticulous surgical technique and rigorous postoperative imaging surveillance to ensure long-term disease control.
{"title":"Subtotal petrosectomy for extensive cholesteatoma: A case series from Japan","authors":"Hiroshi Sakaida, Kazuhiko Takeuchi","doi":"10.1016/j.anl.2025.12.001","DOIUrl":"10.1016/j.anl.2025.12.001","url":null,"abstract":"<div><h3>Objective</h3><div>Subtotal petrosectomy (STP) is a standard procedure for intractable middle ear disease in Western countries, but reports from Japan are scarce. This report describes the clinical experience, patient characteristics, and surgical outcomes of STP at a tertiary center in Japan.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the medical records of all patients who underwent STP in our department between January 2018 and April 2022. We analyzed patient demographics, underlying pathology, preoperative findings, postoperative complications, and the cholesteatoma recurrence rate.</div></div><div><h3>Results</h3><div>The cohort included 11 patients (7 male, 4 female) with a median age of 75 years. The primary indication was extensive cholesteatoma (11 cases), which was often complicated by dural exposure (6 cases) and labyrinthine fistula (6 cases). Postoperative complications occurred in 1 patient (9 %), who developed a fistula at the blind sac closure site. There were no instances of postoperative facial nerve palsy or inner ear complications. MRI surveillance revealed a residual cholesteatoma recurrence rate of 27 % (3 cases).</div></div><div><h3>Conclusion</h3><div>STP is an option for managing extensive primary cholesteatoma where hearing reconstruction is not feasible, particularly in the elderly population. However, the risk of residual cholesteatoma is significant, as evidenced by a 27 % recurrence rate in this series, and careful surgical indication is essential to avoid potential over-indication. This finding highlights the critical importance of meticulous surgical technique and rigorous postoperative imaging surveillance to ensure long-term disease control.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 13-18"},"PeriodicalIF":1.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The intracranial antitumor efficacy of combination therapy with BRAF and MEK inhibitors in BRAF-mutated thyroid cancer has not been reported. Here, we describe a case of anaplastic thyroid cancer harboring BRAF V600E mutation with brain metastases which was treated with encorafenib plus binimetinib. The patient was initially diagnosed with T4bN1bM1 and experienced disease progression following surgery and lenvatinib treatment. Encorafenib plus binimetinib was initiated as second-line treatment seven months after the surgery. After achieving sustained disease stabilization, a solitary asymptomatic brain metastasis was detected following a three-week interruption due to COVID-19 infection. The lesion shrank after only two weeks of resumed encorafenib plus binimetinib, and additional stereotactic radiosurgery was performed without significant adverse events. This case suggests that the combination of BRAF and MEK inhibitors may be a viable treatment option for brain metastasis in BRAF-mutated thyroid cancer, despite general prioritization of local treatments. In addition, encorafenib plus binimetinib treatment may suppress the growth of microscopic metastasis. This possibility is supported by reliable evidence for the use of BRAF plus MEK inhibitor for brain metastasis from BRAF-mutated malignant melanoma. We conclude that encorafenib plus binimetinib treatment for brain metastasis from BRAF-mutated thyroid cancer is a safe and effective treatment choice.
{"title":"Intracranial antitumor efficacy of combination treatment with encorafenib plus binimetinib in BRAF V600E-mutated anaplastic thyroid carcinoma","authors":"Ryutaro Onaga , Tomohiro Enokida , Toshifumi Tomioka , Shingo Sakashita , Masanobu Sato , Nobukazu Tanaka , Yuta Hoshi , Takuma Kishida , Ryo Kuboki , Takao Fujisawa , Susumu Okano , Kazuto Matsuura , Makoto Tahara","doi":"10.1016/j.anl.2025.11.007","DOIUrl":"10.1016/j.anl.2025.11.007","url":null,"abstract":"<div><div>The intracranial antitumor efficacy of combination therapy with BRAF and MEK inhibitors in <em>BRAF</em>-mutated thyroid cancer has not been reported. Here, we describe a case of anaplastic thyroid cancer harboring <em>BRAF</em> V600E mutation with brain metastases which was treated with encorafenib plus binimetinib. The patient was initially diagnosed with T4bN1bM1 and experienced disease progression following surgery and lenvatinib treatment. Encorafenib plus binimetinib was initiated as second-line treatment seven months after the surgery. After achieving sustained disease stabilization, a solitary asymptomatic brain metastasis was detected following a three-week interruption due to COVID-19 infection. The lesion shrank after only two weeks of resumed encorafenib plus binimetinib, and additional stereotactic radiosurgery was performed without significant adverse events. This case suggests that the combination of BRAF and MEK inhibitors may be a viable treatment option for brain metastasis in <em>BRAF</em>-mutated thyroid cancer, despite general prioritization of local treatments. In addition, encorafenib plus binimetinib treatment may suppress the growth of microscopic metastasis. This possibility is supported by reliable evidence for the use of BRAF plus MEK inhibitor for brain metastasis from <em>BRAF</em>-mutated malignant melanoma. We conclude that encorafenib plus binimetinib treatment for brain metastasis from <em>BRAF</em>-mutated thyroid cancer is a safe and effective treatment choice.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 7-12"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarcopenia and systemic inflammatory markers predict prognosis in various cancers, including head and neck cancer (HNC) treated with surgery or chemoradiotherapy. Their significance in patients receiving immune checkpoint inhibitors (ICIs), however, remains unclear. This study aims to determine whether skeletal muscle loss and systemic inflammation influence treatment response and survival in ICI-treated HNC, and whether composite indices provide prognostic value.
Methods
A retrospective cohort of 179 patients with histologically confirmed recurrent or metastatic (R/M) HNC who received ICI therapy between April 2017 and July 2024 was analyzed. Sarcopenia was assessed using the lumbar skeletal muscle index (LSMI), calculated from cervical CT images. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were derived from pre-treatment blood samples. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan–Meier estimates, and prognostic factors were identified through Cox regression analysis.
Results
Among the 179 patients, 98 (54.7%) were classified as sarcopenic. These patients had significantly shorter median OS compared to non-sarcopenic patients (12.1 vs. 39.8 months; p < 0.001). Univariate analysis identified sarcopenia, BMI, NLR, and PLR as significant predictors of OS. However, multivariate Cox analysis revealed that only sarcopenia remained an independent prognostic factor for both OS (HR 1.94; 95% CI: 1.15–3.27; p = 0.013) and PFS (HR 1.92; 95% CI: 1.33–2.75; p < 0.001). Inflammatory markers and their composite indices failed to retain prognostic significance in adjusted models.
Conclusion
Sarcopenia independently predicts poor survival outcomes in patients with R/M HNC undergoing ICI therapy, whereas conventional inflammatory markers such as NLR, PLR, and LMR, alone or in combination with sarcopenia, lack independent prognostic value. Routine pre-treatment evaluation of skeletal muscle mass using CT imaging may offer a practical and effective tool for patient risk stratification.
目的通过心肌减少和全身炎症标志物预测包括头颈癌（HNC）手术或放化疗治疗后的预后。然而，它们在接受免疫检查点抑制剂（ICIs）治疗的患者中的意义尚不清楚。本研究旨在确定骨骼肌损失和全身炎症是否影响ici治疗的HNC的治疗反应和生存，以及复合指标是否具有预后价值。方法回顾性分析2017年4月至2024年7月期间接受ICI治疗的179例组织学证实的复发或转移性（R/M） HNC患者。通过颈椎CT图像计算腰椎骨骼肌指数（LSMI）评估骨骼肌减少症。炎症标志物如中性粒细胞与淋巴细胞比率（NLR）、血小板与淋巴细胞比率（PLR）和淋巴细胞与单核细胞比率（LMR）均来自预处理前的血液样本。采用Kaplan-Meier估计评估总生存期（OS）和无进展生存期（PFS），并通过Cox回归分析确定预后因素。结果179例患者中，98例（54.7%）为肌少症。与非肌肉减少症患者相比，这些患者的中位生存期显著缩短（12.1个月vs 39.8个月；p < 0.001）。单因素分析发现肌肉减少症、BMI、NLR和PLR是OS的重要预测因子。然而，多变量Cox分析显示，只有肌肉减少症仍然是OS（风险比1.94;95% CI: 1.15-3.27; p = 0.013）和PFS（风险比1.92;95% CI: 1.33-2.75; p < 0.001）的独立预后因素。在调整后的模型中，炎症标志物及其复合指数未能保留预后意义。结论肌少症单独预测接受ICI治疗的R/M HNC患者的不良生存结果，而传统的炎症标志物如NLR、PLR和LMR单独或联合肌少症缺乏独立的预后价值。常规治疗前骨骼肌量CT成像评估可为患者风险分层提供实用有效的工具。
{"title":"The prognostic impact of sarcopenia and systemic inflammation in head and neck cancer patients treated with immune checkpoint inhibitors","authors":"Ken Kasahara , Takeyuki Kono , Yoichiro Sato , Keisuke Okubo , Ayaka Sasaki , Ko Hentona , Yutaro Mokudai , Keigo Oguchi , Motoki Izawa , Seiichi Shinden , Hiroyuki Ozawa","doi":"10.1016/j.anl.2025.11.006","DOIUrl":"10.1016/j.anl.2025.11.006","url":null,"abstract":"<div><h3>Objective</h3><div>Sarcopenia and systemic inflammatory markers predict prognosis in various cancers, including head and neck cancer (HNC) treated with surgery or chemoradiotherapy. Their significance in patients receiving immune checkpoint inhibitors (ICIs), however, remains unclear. This study aims to determine whether skeletal muscle loss and systemic inflammation influence treatment response and survival in ICI-treated HNC, and whether composite indices provide prognostic value.</div></div><div><h3>Methods</h3><div>A retrospective cohort of 179 patients with histologically confirmed recurrent or metastatic (R/M) HNC who received ICI therapy between April 2017 and July 2024 was analyzed. Sarcopenia was assessed using the lumbar skeletal muscle index (LSMI), calculated from cervical CT images. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were derived from pre-treatment blood samples. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan–Meier estimates, and prognostic factors were identified through Cox regression analysis.</div></div><div><h3>Results</h3><div>Among the 179 patients, 98 (54.7%) were classified as sarcopenic. These patients had significantly shorter median OS compared to non-sarcopenic patients (12.1 vs. 39.8 months; p < 0.001). Univariate analysis identified sarcopenia, BMI, NLR, and PLR as significant predictors of OS. However, multivariate Cox analysis revealed that only sarcopenia remained an independent prognostic factor for both OS (HR 1.94; 95% CI: 1.15–3.27; p = 0.013) and PFS (HR 1.92; 95% CI: 1.33–2.75; p < 0.001). Inflammatory markers and their composite indices failed to retain prognostic significance in adjusted models.</div></div><div><h3>Conclusion</h3><div>Sarcopenia independently predicts poor survival outcomes in patients with R/M HNC undergoing ICI therapy, whereas conventional inflammatory markers such as NLR, PLR, and LMR, alone or in combination with sarcopenia, lack independent prognostic value. Routine pre-treatment evaluation of skeletal muscle mass using CT imaging may offer a practical and effective tool for patient risk stratification.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"53 1","pages":"Pages 1-6"},"PeriodicalIF":1.5,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145625061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Japanese cedar pollinosis (JCP) is the most prevalent seasonal allergic rhinitis in Japan. Many JCP patients are also sensitized to Japanese cypress pollen (JCyP), and their symptoms become exacerbated and prolonged during the JCyP dispersal period after JCP. To date, there have been no reports on the development of JCyP-specific allergen immunotherapy. For the future development of a JCyP-specific skin test and immunotherapy, we sought to develop a reference extract for future standardization of JCyP extract determined by the average threshold dilution eliciting a positive response in the intradermal skin test.
Methods
A 1:20 antigen extract (Lot AA) was prepared from JCyP grains by the glycerin extraction method. The protein and allergen concentrations in the extract were determined. After confirming its safety, 3-fold serially diluted solutions of JCyP extract were prepared from Lot AA. The average threshold dilution eliciting a positive response in the intradermal skin test was determined among Japanese subjects with serum JCyP-specific IgE class of 2 or higher according to ImmunoCAP IgE assays or View39 IgE assays.
Results
The protein concentration in Lot AA was 4.7 mg/mL, and the allergen concentration was 18.8 μg/mL for Cha o 1 and 1.1 μg/mL for Cha o 3. In total, 85 individuals were registered for this study and finally, 55 subjects were left for the analysis. The threshold dilution for an intradermal reaction was 36 in 32 individuals (58.2 %), 37 in 8 individuals (14.6 %), 38 in 4 individuals (7.3 %), and 39 in 1 individual (1.8 %); no reaction was seen in 10 individuals (18.2 %). The average threshold dilution was 36.4, which is equivalent to a 1131-fold dilution. No serious adverse events were observed at any of the tested dilutions.
Conclusion
The results showed that Lot AA of JCyP extract exhibited in vivo allergic potency and was safe. Thus, it may be useful as a future standardized antigen of JCyP or a reference antigen for standardizing other JCyP extracts for the diagnosis and treatment of JCyP pollinosis.
目的：杉木花粉症是日本最常见的季节性变应性鼻炎。许多JCP患者也对日本柏树花粉（JCyP）敏感，在JCP后的JCyP弥散期，其症状加重和延长。迄今为止，还没有关于jcp特异性过敏原免疫疗法发展的报道。对于JCyP特异性皮肤试验和免疫治疗的未来发展，我们试图开发一种参考提取物，用于未来标准化的JCyP提取物，该提取物由皮内皮肤试验中引起阳性反应的平均阈值稀释来确定。方法：采用甘油提取法制备1:20抗原提取物（Lot AA）。测定提取液中蛋白质和过敏原的浓度。在确认其安全性后，从Lot AA中制备3倍连续稀释的JCyP提取物溶液。根据ImmunoCAP IgE检测或View39 IgE检测，在血清jcp特异性IgE等级为2或更高的日本受试者中，确定皮内皮肤试验中引起阳性反应的平均阈值稀释。结果：Lot AA蛋白浓度为4.7 mg/mL， Cha o 1和Cha o 3的过敏原浓度分别为18.8和1.1 μg/mL。共有85人登记参加本研究，最后，55人被留作分析。皮内反应的阈值稀释度为32例36(58.2%)，8例37(14.6%)，4例38(7.3%)，1例39 (1.8%)；无反应10例（18.2%）。平均阈值稀释度为36.4，相当于稀释1131倍。在任何测试的稀释度下均未观察到严重的不良事件。结论：JCyP提取物AA批次具有体内过敏效力，安全性好。因此，它可以作为未来JCyP的标准化抗原或其他JCyP提取物的标准化参考抗原，用于JCyP授粉病的诊断和治疗。
{"title":"Trial for developing a reference extract for future standardization of Japanese cypress pollen extracts","authors":"Kengo Kanai , Aiko Oka , Hideaki Kouzaki , Kento Kawakita , Takuya Murao , Takeshi Shimizu , Takaya Higaki , Aya Murai , Mizuo Ando , Kojiro Hirano , Isao Suzaki , Hitome Kobayashi , Minoru Gotoh , Kimihiro Okubo , Mitsuhiro Okano","doi":"10.1016/j.anl.2025.10.001","DOIUrl":"10.1016/j.anl.2025.10.001","url":null,"abstract":"<div><h3>Objective</h3><div>Japanese cedar pollinosis (JCP) is the most prevalent seasonal allergic rhinitis in Japan. Many JCP patients are also sensitized to Japanese cypress pollen (JCyP), and their symptoms become exacerbated and prolonged during the JCyP dispersal period after JCP. To date, there have been no reports on the development of JCyP-specific allergen immunotherapy. For the future development of a JCyP-specific skin test and immunotherapy, we sought to develop a reference extract for future standardization of JCyP extract determined by the average threshold dilution eliciting a positive response in the intradermal skin test.</div></div><div><h3>Methods</h3><div>A 1:20 antigen extract (Lot AA) was prepared from JCyP grains by the glycerin extraction method. The protein and allergen concentrations in the extract were determined. After confirming its safety, 3-fold serially diluted solutions of JCyP extract were prepared from Lot AA. The average threshold dilution eliciting a positive response in the intradermal skin test was determined among Japanese subjects with serum JCyP-specific IgE class of 2 or higher according to ImmunoCAP IgE assays or View39 IgE assays.</div></div><div><h3>Results</h3><div>The protein concentration in Lot AA was 4.7 mg/mL, and the allergen concentration was 18.8 μg/mL for Cha o 1 and 1.1 μg/mL for Cha o 3. In total, 85 individuals were registered for this study and finally, 55 subjects were left for the analysis. The threshold dilution for an intradermal reaction was 3<sup>6</sup> in 32 individuals (58.2 %), 3<sup>7</sup> in 8 individuals (14.6 %), 3<sup>8</sup> in 4 individuals (7.3 %), and 3<sup>9</sup> in 1 individual (1.8 %); no reaction was seen in 10 individuals (18.2 %). The average threshold dilution was 3<sup>6.4</sup>, which is equivalent to a 1131-fold dilution. No serious adverse events were observed at any of the tested dilutions.</div></div><div><h3>Conclusion</h3><div>The results showed that Lot AA of JCyP extract exhibited <em>in vivo</em> allergic potency and was safe. Thus, it may be useful as a future standardized antigen of JCyP or a reference antigen for standardizing other JCyP extracts for the diagnosis and treatment of JCyP pollinosis.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"52 6","pages":"Pages 805-810"},"PeriodicalIF":1.5,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.anl.2025.10.013
Akihisa Tanaka , Kohtaro Eguchi , Mitsuhiko Katoh , Tatsuya Ito , Azusa Sakai , Toshihiko Sakai , Chihiro Fushimi , Go Omura , Taisuke Mori , Seiichi Yoshimoto
Radiotherapy (RT) is a cornerstone management strategy for head and neck cancer (HNC); however, local recurrence often requires salvage surgery, which is associated with an elevated risk of complications, particularly in previously irradiated fields. Boron neutron capture therapy (BNCT) has broadened treatment options; however, the safety and feasibility of salvage surgery after BNCT remain unclear owing to the limited case number. Herein, we describe a rare case of hypopharyngeal squamous cell carcinoma initially treated with RT, followed by BNCT for local recurrence, and ultimately with successful salvage surgery. The patient experienced no significant intraoperative or postoperative complications, and has remained recurrence-free for three years while maintaining adequate activities of daily living. Histopathological examination revealed no abnormal fibrosis exceeding that typically observed following standard RT alone throughout the resected specimen. Instead, edematous changes predominated over fibrotic alterations exclusively within the tumor region, presumed to be most affected by BNCT, accompanied by strong expression of L-type amino acid transporter 1, a potential surrogate marker of BNCT indication, suggesting the tumor-specific therapeutic effect of BNCT. This is the first report of salvage surgery for an organ previously treated with RT and BNCT, which provides valuable clinical and histopathological insights into this condition.
{"title":"Salvage surgery following boron neutron capture therapy in a case of recurrent hypopharyngeal cancer after radiotherapy: Surgical and pathological insights","authors":"Akihisa Tanaka , Kohtaro Eguchi , Mitsuhiko Katoh , Tatsuya Ito , Azusa Sakai , Toshihiko Sakai , Chihiro Fushimi , Go Omura , Taisuke Mori , Seiichi Yoshimoto","doi":"10.1016/j.anl.2025.10.013","DOIUrl":"10.1016/j.anl.2025.10.013","url":null,"abstract":"<div><div>Radiotherapy (RT) is a cornerstone management strategy for head and neck cancer (HNC); however, local recurrence often requires salvage surgery, which is associated with an elevated risk of complications, particularly in previously irradiated fields. Boron neutron capture therapy (BNCT) has broadened treatment options; however, the safety and feasibility of salvage surgery after BNCT remain unclear owing to the limited case number. Herein, we describe a rare case of hypopharyngeal squamous cell carcinoma initially treated with RT, followed by BNCT for local recurrence, and ultimately with successful salvage surgery. The patient experienced no significant intraoperative or postoperative complications, and has remained recurrence-free for three years while maintaining adequate activities of daily living. Histopathological examination revealed no abnormal fibrosis exceeding that typically observed following standard RT alone throughout the resected specimen. Instead, edematous changes predominated over fibrotic alterations exclusively within the tumor region, presumed to be most affected by BNCT, accompanied by strong expression of L-type amino acid transporter 1, a potential surrogate marker of BNCT indication, suggesting the tumor-specific therapeutic effect of BNCT. This is the first report of salvage surgery for an organ previously treated with RT and BNCT, which provides valuable clinical and histopathological insights into this condition.</div></div>","PeriodicalId":55627,"journal":{"name":"Auris Nasus Larynx","volume":"52 6","pages":"Pages 785-789"},"PeriodicalIF":1.5,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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