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It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor-node-metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) have a significantly better treatment response and overall survival (OS) rates than non-HPV-associated OPSCC. Objectives: We conducted the present study to further characterize the interplay between lifestyle risk factors, which are not only HPV status, but also smoking history and alcohol consumption, and the OS to optimize the treatment of patients with OPSCC. Materials and Methods: Between January 2006 and December 2013, 94 patients newly diagnosed with OPSCC were treated with curative intent at Aichi Cancer Center Hospital (Nagoya, Japan). To determine negative prognostic factors associated with the OS, univariate and multivariable Cox regression analyses were performed. Results: Of the 94 OPSCC patients, 53 (56.4%) were positive for HPV. The univariate analysis revealed that T classification, smoking history, alcohol consumption, and HPV status were significant determinants of the OS. In the multivariate analysis, adjusted for the clinical stage, smoking history, alcohol consumption, HPV status, and a smoking history of >10 pack-years was an independent negative prognostic factor for the OS among patients with OPSCC (HR: 10.4, 95 %CI: 1.34−80.6, p < 0.05). Conclusions: Smoking is a very important negative prognostic factor even in cases of HPV-associated OPSCC. The impact of smoking needs to be reaffirmed when deciding on treatment plans and de-escalation trials in OPSCC, even in cases of HPV-associated OPSCC.

Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a variety of biologic behaviors. Salivary gland malignancies are known as chemo-resistant tumors, which render optimal treatment challenging. This review summarizes the role of systemic therapy for salivary gland malignancies. To date, the advantage of adding concurrent chemotherapy has remained undefined for both postoperative and inoperable locally advanced salivary gland malignancy patients undergoing radiotherapy. For recurrent/metastatic disease, local and/or systemic treatment options should be discussed in a multidisciplinary setting with consideration to both patient needs and tumor factors. For symptomatic patients or those who may compromise organ function, palliative systemic therapy can be a reasonable option based on the results of phase II studies. Platinum combination regimens as first-line therapy have been widely accepted. Personalized therapies have become established options, particularly for androgen receptor-positive, HER2-positive and NTRK fusion-positive salivary gland malignancies (i.e. androgen receptor and HER2 in salivary duct carcinoma and NTRK3 in secretory carcinoma). For patients with adenoid cystic carcinoma, multi-targeted tyrosine kinase inhibitors have also been developed. Anti-PD1 checkpoint inhibitors have shown limited activity to date. Investigation of active systemic treatments for salivary gland malignancy remains a significant unmet need. Future directions might include a more comprehensive genomic screening approach (usually next-generation sequencing-based) and combination strategies using immune checkpoint inhibitors. These are rare malignancies that require ongoing effort in the conduct of high-quality clinical trials., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: During the COVID-19 pandemic, pedicle flaps instead of free flap transfer were recommended for head and neck reconstruction to reduce infection risk. Boron neutron-capture therapy in Japan was clinically approved in 2020 as a salvage radiotherapy for recurrent head and neck cancer following chemoradiotherapy. The efficacy and safety of salvage surgery following boron neutron-capture therapy remain unclear., Case Report: We describe a 57-year-old male with crT4aN0M0 oral cancer after three different forms of radiotherapy including boron neutron-capture therapy, treated by salvage partial maxillectomy with both buccal fat pad and nasoseptal flaps. His postsurgical course was successful, without tracheostomy, and he had no Clavien- Dindo grade 3 or 4 complications. The pathological diagnosis was T4a squamous cell carcinoma with a negative surgical margin. No recurrence or metastasis had occurred at 113 days postoperatively. No opioid consumption was needed postoperatively., Conclusion: Pathological negative margins were achieved in this case and there were no severe complications. Further accrual of cases salvage surgery following boron neutron-capture therapy is required to clarify treatment strategies for recurrent head and neck cancer., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 68-year-old woman was admitted with a persistent cough and dyspnea that had persisted for 4 months prior. Chest computed tomography revealed a tumor protruding from the membranous portion of the trachea. She underwent tumor resection via rigid and flexible bronchoscopy to relieve the symptoms and obtain a diagnosis. After the procedure, she was diagnosed with tracheal liposarcoma. Three months after the procedure, she underwent complete surgical tumor resection. Liposarcoma is a mesenchymal tumor that usually develops in the extremities and the retroperitoneum. Tracheal liposarcoma is extremely rare. To the best of our knowledge, this is only the second reported case.

Background: The importance of supraclavicular lymph node (SCLN) metastases in esophageal cancer (EC) remains unknown. Few studies have reported on the prognostic impact of SCLN metastases on patients with cervical EC (CEC). This study aimed to investigate whether SCLNs should be considered regional lymph nodes and be dissected in patients with CEC., Methods: This retrospective study enrolled 835 consecutive patients who underwent radical esophagectomy. Of these patients, 67 underwent radical surgery for CEC. These 67 patients were divided into three groups based on the presence of lymph node metastases with or without metastatic SCLNs or the absence of lymph node metastases., Results: Of the 67 patients, 23 (34.3%) did not have metastatic lymph nodes (pN-negative group), 27 (40.3%) had metastatic lymph nodes except for metastatic SCLNs (pN-positive group without metastatic SCLN), and 17 (25.4%) had metastatic lymph nodes including metastatic SCLNs (pN-positive group with metastatic SCLNs). The 5-year overall survival rate was 58.4% for the pN-negative group, 46.2% for the pN-positive group without metastatic SCLNs, and 7.8% for the pN-positive group with metastatic SCLNs. The pN-positive group with metastatic SCLNs tended to show residual tumor cells and complications after surgery. The presence of metastatic SCLNs was a significantly poor prognostic factor (p = 0.004). The efficacy index was lowest for the lymph nodes in the supraclavicular region., Conclusions: The prognosis of the CEC patients with metastatic SCLNs was dismal. Although the cervical esophagus is located adjacent to the SCLNs, the SCLNs may be considered extra-regional lymph nodes in patients with CEC., (© 2021. Society of Surgical Oncology.)

Background: During the coronavirus disease 2019 (COVID19) pandemic, pedicle flaps (instead of free flaps) were recommended for reconstruction following wide resection for patients with head and neck cancer, in order to reduce the use of medical resources. Currently, there are no established treatment guidelines for patients with head and neck cancer with synchronous esophageal cancer., Case Report: We present a 68-year-old male with cT4aN2cM0 oral floor and synchronous cT1bN1M0 esophageal cancers who had defective reconstruction following oral tumor resection before esophagectomy during the pandemic. At the initial surgery, the oral resected defect was reconstructed using supraclavicular artery flap. The subsequent esophagectomy was reconstructed by gastric tube reconstruction. Both postoperative courses were successful, without the need for postoperative ventilator use. The days from initial or second surgery to discharge were 14 or 16 days, respectively., Conclusion: This case had achieved negative surgical margins and recovered oral intake with tracheostomy decannulation. Further case accruement using supraclavicular artery flap is required for patients with head and neck cancer and synchronous esophageal cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives/hypothesis: The present study aimed to investigate the efficacy of transarterial embolization (TAE) for bleeding in patients with head and neck cancer (HNC) and to evaluate the prognostic factors after TAE., Study Design: Outcome study., Methods: This retrospective study included 31 consecutive patients (27 men and 4 women; median age, 61 years) who presented uncontrollable hemorrhage associated with HNC and underwent emergency TAE at our institution during a 10-year period (January 2011-December 2020). This corresponded to 40 TAE procedures, including 27 cases with an unstable status (circulatory and/or respiratory insufficiency) and 10 cases with carotid blowout syndrome. The technical success rate and adverse events were analyzed on a per-procedure basis. The rebleeding and overall survival (OS) rates were analyzed on a per-patient basis, and the factors related to OS were evaluated., Results: The technical success rate was 100%. As an adverse event, cerebral infarction was found in three cases with carotid blowout syndrome. The rebleeding rate at 30 days after TAE and in the follow-up period (range, 9-3,004 days) was 17.2% and 35.5%, respectively. The median survival time was 263 days (95% confidence interval: 124.0-402.0 days). In the log-rank test, complete remission (CR) of the primary cancer at the time of the first TAE was identified as a significant influencing factor of survival., Conclusion: TAE is effective for the treatment of hemorrhage associated with HNC even in patients with an unstable status. Patients with CR can gain a long life span., Level of Evidence: 4 Laryngoscope, 131:E2777-E2783, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: This study aimed to reveal the influence of the invasion site of external auditory canal (EAC) cancer by analyzing the outcome of patients with advanced tumor., Methods: A total of 111 patients with T4 EAC cancer were enrolled in this study. Of these patients, 79 underwent chemoradiotherapy and 32 underwent surgery under curative intent. Univariate and multivariate analyses and the Kaplan-Meier method were used to focus on the tumor invasion sites and overall survival of the patients., Results: The 3-year overall survival rate of all patients was 55.0%. In multivariate analysis, the only significant invasion site for overall survival was the facial nerve, with the dura mater being the next most influential site. When Kaplan-Meier survival curve was calculated, facial nerve and dura mater were the significant factors resulting in poor patient outcomes., Conclusion: The facial nerve and dura mater are crucial sites of EAC cancer for patient outcomes., (© 2021 Wiley Periodicals LLC.)

Background: Preoperative diagnosis of parotid tumor is mainly performed via imaging and cytology to avoid both facial nerve injury and tumor seeding. Synchronous resection of solitary parotid metastasis with esophagectomy for esophageal squamous cell carcinoma is rarely performed., Case Report: This is a case report of a 58-year-old male patient with a left preauricular tumor, which was cytologically diagnosed as squamous cell carcinoma. Esophageal squamous cell carcinoma was pathologically diagnosed following 18 F-fluorodeoxyglucose positron emission tomography with computed tomography. His diagnosis was cT2N0M0 esophageal squamous cell carcinoma with cT3N0M0 parotid carcinoma. Esophagectomy for esophageal cancer, as well as parotidectomy were performed. Pathological diagnosis of pT1bN1M1 (parotid) esophageal squamous cell carcinoma was based on exclusion diagnosis of no primary tumor from several specialists and pathological findings including immunohistochemical staining., Conclusion: Reporting of more cases of rare synchronous metastasectomy and esophagectomy is needed to clarify treatment strategies., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The objective of our study was to clarify the clinical features of EGFR-mutated sinonasal squamous cell carcinoma (SNSCC) and human papilloma virus (HPV)-related SNSCC. Patients with SNSCC treated from April 2008 to June 2019 at our institution were retrospectively reviewed. We examined EGFR mutation and HPV status for all patients. Main outcomes were overall survival, recurrence, and outcome of each treatment modality. A total of 85 patients with SNSCC were enrolled in this study. EGFR mutations and HPV DNA were detected in 24 (28%) and 7 (8%) patients, respectively. Patients with EGFR-mutated SNSCC showed a worse overall survival (OS) than those with EGFR wild-type in the multivariate analysis (p = 0.037). No death was observed in HPV-positive SNSCC. The cumulative incidence of local recurrence was significantly higher in EGFR mutant than EGFR wild-type tumors (p = 0.03). In patients with EGFR mutations, treatment with induction chemotherapy significantly improved OS (p = 0.01). EGFR-mutated SNSCC have a high-risk feature for recurrence and requires intensive attention for treatment and observation. A new treatment approach, such as EGFR tyrosine kinase inhibitors, may be needed., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives : There is evidence or consensus on the use of 18F-2-fluorodeoxyglucose-positron emission tomography with computed tomography (PET-CT) in evaluating the effects of treatment at 12 weeks after chemoradiotherapy for head and neck squamous cell carcinoma with cervical lymph node metastasis. However, the use of imaging to evaluate the effects of treatment within 12 weeks after chemoradiotherapy is controversial. The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of lymph nodes metastasis after chemoradiotherapy according to the criteria of the "Evaluation of the effects of treatment on metastatic cervical lymph nodes using ultrasonography", which evaluated lymph nodes metastasis based on size change and presence of degeneration. Materials and methods : This prospective study included 34 head and neck squamous cell carcinoma patients with cervical lymph nodes metastasis. Thirty-two patients who completed treatment were analyzed. Ultrasonography was performed at 4 and 8 weeks after chemoradiotherapy and we judged whether a favorable prognosis could be expected or whether additional treatments should be considered. Ultrasonography and PET-CT were performed at 12 weeks after chemoradiotherapy. Neck dissection was performed if residual disease was suspected based on the PET-CT findings. Results : The accuracy and negative predictive value of ultrasonography were 81.3% and 96.3%, respectively. According to the Ultrasonography findings, the size of lymph nodes metastasis after chemoradiotherapy was significantly smaller than those before chemoradiotherapy ( p < 0.05). The fluid and blood flow of lymph nodes metastasis showed a significantly reduced at 12 weeks after chemoradiotherapy ( p < 0.05, p < 0.05, respectively). The echo density significantly changed from low to high echoic density after chemoradiotherapy ( p < 0.05). Conclusions : Ultrasonography was useful for evaluating cervical lymph nodes metastasis after chemoradiotherapy for head and neck squamous cell carcinoma.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice., Methods: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records., Results: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1-27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2-12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141., Conclusions: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141., Trial Registration Number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).

Background: The present study evaluated the 2-year survival of the Asian population in the CheckMate 141 trial., Methods: The CheckMate 141 trial included patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). In the present study, 34 Asian patients (nivolumab group: 23 patients; investigator's choice of therapy [IC] group: 11 patients) were analyzed., Results: The median overall survival (OS) was 12.1 and 6.2 months for the nivolumab and IC groups, respectively. The estimated 2-year OS rates were 22.7% and 0% for the nivolumab and IC groups, respectively. In the nivolumab group, the patients with any treatment-related adverse events (TRAEs), including skin-related disorders, showed better OS than the patients without any TRAEs., Conclusions: Nivolumab demonstrated prolonged OS benefits in the Asian population with platinum-refractory R/M SCCHN and a favorable safety profile. TRAEs, including skin-related disorders, may be favorable prognostic factors for nivolumab efficacy., Clinical Trial Registration: NCT02105636., (© 2020 The Authors. Head & Neck published by Wiley Periodicals LLC.)

The aim of the present study is to investigate the association of treatment package time with the survival outcomes and clinical parameters in patients with oropharyngeal squamous cell carcinoma.A total of 49 patients who underwent definitive treatment were enrolled. The treatment package time was calculated in days from the start of any treatment to the completion of all treatments, including postoperative treatment and salvage surgery for residual tumor.On univariate analyzes, treatment package time ≥118 days, sake index ≥60, Brinkman index ≥450, maximum standardized uptake value ≥42.45, and the presence of synchronous cancer were significantly associated with shorter oropharyngeal squamous cell carcinoma-specific survival. Moreover, a treatment package time of ≥118 days was significantly correlated with shorter overall survival and distant metastasis-free survival. On multivariate analyzes, Brinkman index ≥450 was significantly associated with shorter oropharyngeal squamous cell carcinoma-specific and locoregional recurrence-free survival, and the presence of synchronous cancer was significantly associated with shorter overall and distant metastasis-free survival.In conclusion, a relatively long treatment package time was a predictor of low survival outcomes in oropharyngeal squamous cell carcinoma by univariate analysis.

Background and Objective: This study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis., Methods: Sixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes., Results: An LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS., Conclusion: Results demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis., (Copyright © 2019. Published by Elsevier Inc.)

An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in patients with ALK-positive IMT. Here, we report the first case of a 46-year-old man with IMT harboring a novel SQSTM1-ALK fusion gene who demonstrated marked response to alectinib. The patient presented a right neck mass (5-cm diameter) that progressively enlarged and expanded to the upper mediastinum. ALK-rearranged IMT was diagnosed after complete tumor resection. Spindle cells displayed diffuse cytoplasmic staining for ALK on immunohistochemistry. A fluorescence in situ hybridization analysis revealed the translocation of a part of the ALK gene locus at chromosome 2p23. FoundationOne CDx™ assay identified an SQSTM1-ALK gene fusion. After a year, right cervical, subclavian, and mediastinal lymph node metastases, considered unresectable, developed. Notably, the patient exhibited a marked response to alectinib treatment and has sustained for 17 months following systemic therapy initiation without significant adverse events. This report highlights the possibility of alectinib being a reasonable option for advanced IMT with the SQSTM1-ALK fusion.

A number of major modifications were made to the classification of head and neck carcinomas in the eighth edition of the American Joint Committee on Cancer, Cancer Staging Manual and Union for International Cancer Control TNM classification of Malignant Tumors. These modifications were aimed at improving the prognosis prediction accuracy of the system. In this article, we review the new edition of the TNM classification system. Among the several changes in the new system, a separate algorithm for p16-positive oropharyngeal carcinoma was included, as were new chapters on 'Head and Neck Skin Carcinoma' and 'Unknown Primary Carcinoma-Cervical Nodes.' Changes to Tumor (T) classification were made by introducing the depth of invasion of oral carcinoma, whereas changes to Node (N) classification were made by adding extra-nodal extension. It is believed that these changes will help improve the accuracy of the system in the prediction of prognosis. However, it is necessary to verify their validity through further clinical research., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To investigate whether 18 F-fluorodeoxyglucose uptake is associated with overall survival in patients with major salivary gland cancer using univariate and multivariate analyses after adjusting for pathological stage (eighth edition of the International Union Against Cancer)., Patients and Methods: A total of 32 patients with major salivary gland cancer treated with curative surgery were enrolled. Parameters for 18 F-fluorodeoxyglucose uptake were assessed by positron-emission tomography combined with computed tomography., Results: Using univariate and multivariate analyses after adjusting for pathological stage, a maximum standardized uptake value ≥26, peak standardized uptake value ≥20.3, metabolic tumor volume ≥9.7, and total lesion glycolysis ≥263 were significantly correlated with shorter overall survival., Conclusion: Parameters of 18 F-fluorodeoxyglucose uptake in major salivary gland cancer are predictive of overall survival after adjusting for the pathological stage., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments., Material and Methods: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months., Results: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort., Conclusion: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Backgroud: Laryngeal preservation is an important consideration when treating cervical esophageal cancers (CECs) such as laryngeal cancer. The standard treatment for CEC allowing laryngeal preservation is chemoradiotherapy. However, in cases of laryngeal cancer, chemoselection has also been applied as a treatment strategy that promotes larynx preservation. This strategy involves assigning the appropriate radical treatment according to the primary tumor's response to induction chemotherapy. Since there have been no studies of the application of chemoselection in CEC cases, the present study compared the results, including laryngeal preservation rates, obtained upon applying chemoselection and chemoradiotherapy to CEC., Study Design: This was a retrospective cohort study of cervical esophageal squamous cell carcinoma patients treated using chemoselection or chemoradiotherapy at Aichi Cancer Center Hospital between January 2000 and March 2013. A total of 42 patients were enrolled., Results: The 2-year overall survival and laryngeal preservation rates for the chemoselection group versus the primary radiotherapy group were 65.1 and 57.3 versus 40 and 83.3%, respectively (P = 0.017 and P = 0.122, respectively). The 2-year locoregional control rates for the chemoselection and primary radiotherapy groups were 68 and 25%, respectively (P = 0.045)., Conclusion: The chemoselection group achieved favorable results. Therefore, chemoselection can be applied as a treatment strategy for CEC.

Objective: The clinical importance of neoadjuvant chemotherapy (NAC) followed by definitive surgery was retrospectively investigated in clinical Stage III/IV oral squamous cell carcinoma (OSCC)., Methods: Surgery was performed for OSCC in 164 patients, including 72 patients who had received NAC (two cycles of cisplatin and fluorouracil) prior to surgery from January 2004 to December 2014. The clinical characteristics and survival parameters of the groups that received and did not receive NAC were evaluated. The pathological response was classified as Grade 0 (no effect), 1a (very slight effect), 1b (slight effect), 2 (moderate effect) or 3 (marked effect), and its correlation with prognosis was investigated., Results: There were no statistical differences in survival indicators between patients who received NAC and those who did not (overall survival, P = 0.75). The proportion of patients who received NAC in the effective NAC group (Grades 1b, 2, and 3) was 52.8%. After a median follow-up of 35 months, overall survival (P = 0.01), disease-free survival (P = 0.002), locoregional disease-free survival (P = 0.003), and distant disease-free survival (P = 0.01) were significantly better in the effective NAC group than in the less effective NAC group (Grades 0 and 1a)., Conclusion: Although NAC had a limited effect on disease prognosis in OSCC, the pathological response to NAC could be an important prognostic indicator for advanced OSCC., (Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: We investigated a possible correlation between the maximum standardized uptake value (SUV max ), which is assessed by pretreatment 18 F-fluorodeoxyglucose positron emission tomography with computed tomography, and the overall survival (OS) in patients with hypopharyngeal squamous cell carcinoma from two institutions on long-term follow-up, and examined whether SUV max is correlated with several survival outcomes, including lung metastasis-free survival., Methods: A total of 81 patients were enrolled. The survival rate was calculated by the Kaplan-Meier method. Both univariate and multivariate survival analyses were assessed by a Cox proportional hazards model., Results: SUV max ≥15.2 in institution A (p = 0.0306) or SUV max ≥8 in institution B (p = 0.0132) was significantly predictor of a lower OS. We disaggregated the data by high SUV max (SUV max ≥15.2 from institution A and SUV max ≥8 from institution B) and low SUV max (SUV max <15.2 from institution A and SUV max <8 from institution B). Patients with a high SUV max exhibited a significantly lower OS in both univariate (p = 0.001) and multivariate (p = 0.0046) analyses for adjusted for the clinical stage and treatment group. The patients with a high SUV max exhibited significantly shorter disease-specific (p = 0.0068), distant metastasis-free (p = 0.0428), and lung metastasis-free (p = 0.0328) survivals., Conclusions: High SUV max was significantly correlated with a lower OS, disease-specific survival, distant metastasis-free survival, and lung metastasis-free survival in a multi-institutional retrospective study.

Purpose: Changes in acoustic features in the perioperative phase for elucidating the mechanisms of articulation disorder and the effect of perioperative rehabilitation were studied prospectively., Materials and Methods: Sixty-two patients with 62 tongue cancer were divided into a partial glossectomy group (n = 40) and a reconstruction group (n = 22). Acoustic characteristics were analyzed during the preoperative and postoperative periods and after rehabilitation using the first and second formants of the vowels /a/, /i/, and /u/; the triangular vowel space area (tVSA); and the slopes of formant transitions., Results: In the 2 groups, decreases in the tVSA and formant slopes were found from the preoperative to the postoperative period, and the acoustic characteristics of the reconstruction group especially improved to preoperative values after rehabilitation. Analysis of the postoperative period showed that acoustic characteristics were altered at the site of surgical resection., Conclusion: Changes of acoustic variables are related to excision size and site, suggesting the distinctive tongue portion for the articulation of each speech sound. Perioperative rehabilitation could activate the articulators and increase the range of movement of the remaining tongue, especially the preserved anterior tongue., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The present study investigated the possible correlation between 18 F-2-fluorodeoxyglucose ( 18 F-FDG)-uptake parameters and clinicopathological parameters in hypopharyngeal squamous cell carcinoma (HPSCC). A total of 53 patients, newly diagnosed with HPSCC, received pretreatment 18 F-FDG-positron emission tomography/computed tomography (PET/CT). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) were calculated as 18 F-FDG-uptake parameters of the primary tumor. Tumor thickness, depth of invasion and pathological tumor volume were pathologically measured. Upon univariate survival analysis, SUVmax ≥28.5, SUVpeak ≥19, MTV ≥12 and TLG ≥42 were significantly associated with a shorter overall survival (OS) time, and MTV ≥12 and TLG ≥42 were significantly associated with a shorter distant metastasis-free survival (DMFS) time. Upon multivariate analysis with adjustment for clinical T category and treatment group, patients with SUVmax ≥28.5 exhibited a significantly shorter OS time, while TLG ≥42 was significantly correlated with shorter OS and DMFS times. Upon simple regression analysis, TLG was found to be significantly associated with tumor thickness and depth of invasion, while MTV was found to be closely associated with pathological tumor volume. In conclusion, pretreatment 18 F-FDG-PET/CT is likely to provide valuable prognostic parameters in HPSCC.

Background: The significance of neoadjuvant chemotherapy followed by definitive surgery for sinonasal squamous cell carcinoma (SCC) was investigated using surgical specimens., Methods: Surgery was performed in 58 patients, including 43 patients who had received neoadjuvant chemotherapy. The pathological response was classified as grades 0 (no effect), 1 (slight effect), 2 (moderate effect), and 3 (marked effect), and its correlation with prognosis was investigated., Results: Grade 2 or 3 response was observed in 34.9% of cases that received neoadjuvant chemotherapy. Overall survival (OS), disease-free survival (DFS), locoregional control, and freedom from distant metastasis were significantly better in the effective neoadjuvant chemotherapy group (grades 2 and 3) than in the less effective neoadjuvant chemotherapy group (grades 0 and 1) and the non-neoadjuvant chemotherapy group combined., Conclusion: Pathological response to neoadjuvant chemotherapy in sinonasal SCC was related to disease prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1305-E1311, 2016., (© 2016 Wiley Periodicals, Inc.)

Aim: Recurrence rates of oral cancer following primary treatment have been reported in the range of 25-48%. However, salvage therapy remains a critical challenge to improving outcomes. Here, we investigated prognostic factors and outcomes for salvage surgery in patients with recurrent oral tongue squamous cell carcinoma (OTSCC)., Methods: We retrospectively reviewed patients who were referred to Aichi Cancer Center, Japan, for the treatment of recurrent OTSCC. All patients included in the present study had undergone salvage surgery. Data to identify the predictive value of prognostic factors were available from 69 patients. Prognostic factors were assessed using Cox's proportional hazards regression analysis. Differences in overall survival between groups of patients were assessed by the log-rank test., Results: In all, 36 patients (52%) developed second recurrence or died, of which 21 (58%) occurred within 12 months of salvage surgery. Univariate analysis indicated that survival was significantly worse in patients with recurrent stage III or IV tumors, two or more positive cervical lymph nodes, levels IV or V positive cervical lymph nodes, extracapsular spread (ECS) of positive cervical lymph nodes and a disease-free interval from initial treatment of less than 12 months. On multivariate analysis, ECS was an independent prognostic factor for overall survival after salvage surgery., Conclusion: Neck status at the time of salvage surgery, particularly ECS is a significant prognostic factor for surgical salvage. Survival was also influenced by the stage of the recurrent tumor and disease-free interval, suggesting that the biological features of recurrent tumors might impact on prognosis., (© 2013 Wiley Publishing Asia Pty Ltd.)

Aim: High [18F]-2-fluorodeoxyglucose (18F-FDG) -uptake of primary tumor, assessed by pretreatment positron emission tomography combined computed tomography (PET/CT), has indicated poor overall survival (OS) in head and neck cancer (HNC).We investigated the correlation between 18F-FDG-uptake and in vitro chemosensitivity of cisplatin using histoculture drug response assay in HNC., Patients and Methods: Twenty-eight patients were evaluated. The maximum standardized uptake value (SUVmax) and inhibition index (I.I.) cisplatin were calculated as 18F-FDG-uptake and in vitro chemosensitivity of cisplatin., Results: Each SUVmax10.5 or I.I.cisplatin<50 could significantly differentiate shorter survival group by OS analyses. I.I.cisplatin of patients with SUVmax≥10.5 was significantly greater. In 19 patients with SUVmax≥10.5, those who received treatment with cisplatin-based chemotherapy exhibited a significant correlation with longer OS., Conclusion: Cisplatin hasthe potential to improve OS for HNC patients that were predicted as shorter OS by 18F-FDG-PET/CT., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A phase I/II study of postoperative chemoradiotherapy with weekly cisplatin for head and neck squamous cell carcinoma was conducted. The eligiblity of patients were the high risk features, i. e., multiple lymph nodes metastasis(2 or more), extracapusular extension of nodal disease(ECE), or the presence of tumor at the surgical section margins(at 5mm or less). The recommended dose of CDDP in a phase I study was 30mg/m2. We performed a phase II study to assess toxicity and tolerability. We assessed 13 patients, 10 of whom were enrolled in a phase II study, and 3 patients in phase I were given the RD. Acute adverse events were rather mild, including grade 1-2 anemia(50%), mucositis(43%)and nausea/vomiting(43%). One patient required administration of CDDP to be discontinued due to grade 1 renal toxicity. The compliance rate was markedly high(85%: 11/13 patients). We consider weekly CDDP of 30mg/m2 to be a safe regimen in the setting of postoperative adjuvant chemoradiotherapy.

A Phase I / II study of docetaxel (DOC) and cisplatin (CDDP) combination therapy was conducted. The respective recommended dose (RD) in a phase I study was DOC 60 mg/m(2) and CDDP 80 mg/m(2). We performed a multicenter phase II study to assess the antitumor activity and toxicity of this RD. Patients with recurrent or unresectable squamous cell carcinoma of the head and neck were eligible. For inclusion in this study, patients were required to be >or=20<70 years of age with a Performance Status of 0 to 2. Adequate bone marrow as well as adequate renal and liver function were required. We assessed 22 patients, 13 of whom were enrolled in the phase II study, and 9 patients in phase I were given the RD. Grade 3 or higher neutropenia occurred in 12 patients (55%). There was no episode of febrile neutropenia of more than 3 days or grade 4 neutropenia of more than 3 days receiving G-CSF. Nausea was the most frequent toxicity, but only one patient experienced vomiting of more than grade 3. Pneumonia (grade 3), thrombocytopenia (grade 4) and emphysema (grade 2) were observed. No one achieved a complete response (CR) and 5 achieved a partial response (PR), for an overall response rate of 22.7% (5/22). Stable disease (SD) was seen in 11 and progressive disease (PD) in 6. In 21 of 22 patients, a relapse occurred despite previous treatment. For this population, the response rate was 19.0% (4/21).

We have been using the Groningen voice prosthesis as a method of voice restoration after total laryngectomy for approximately five years. During this period, the Groningen voice prosthesis has been used in 19 patients and a total of 125 unit replacements have been performed. No serious complications have occurred to date. Upon examination of the voice restoration results, exchange frequency, and complications, we noted that 15 out of 19 patients (78.9%) were able to maintain a good voice quality, including cases with long-term observation periods. Voice restoration was difficult in the remaining 4 cases. The overall mean exchange period was 4.5 months, with 2.5 months being the shortest exchange interval in cases without complications. The mean exchange period for cases without complications was 6.1 months. No serious complications, such as a foreign body in the trachea, were encountered. However, several problems with water leakage occurred and were managed appropriately. Aspiration pneumonia from repeated water leakage did not occur, and no cases of TE shunt closure were encountered. These problems may occur with further aging. Thorough follow-ups will be continued in the future.