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Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m 2 ) was non-inferior to 3-weekly cisplatin (100 mg/m 2 ) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS)., Methods: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5-fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test., Results: The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m 2 vs. 239.2 mg/m 2 ; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/m 2 vs. 297.4 mg/m 2 ; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21)., Conclusions: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m 2 in this setting., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC., Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing., Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53 , CDKN2A , and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses., Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles., Competing Interests: TT received lecture honoraria, consulting fees, and grants from Ono Pharmaceutical Co., Ltd. and lecture honoraria from Bristol Myers Squibb, and Merck Sharp & Dohme Corp. KO received grants from Ono Pharmaceutical Co., Ltd. HO and SS were employed by SCREEN Holdings Co., Ltd. YaS received lecture honoraria from Bristol Myers Squibb, Merck Sharp & Dohme Corp, and Ono Pharmaceutical Co., Ltd. RH received lecture honoraria from Rakuten Medical Inc. YuS received grants from Merck Sharp & Dohme Corp. KT received lecture honoraria from Bristol Myers Squibb, Merck Sharp & Dohme Corp, and Ono Pharmaceutical Co., Ltd. NO received lecture honoraria and grants from Ono Pharmaceutical Co., Ltd and lecture honoraria from Bristol-Myers Squibb. NH received lecture honoraria from Bristol Myers Squibb, and Ono Pharmaceutical Co., Ltd. KN received lecture honoraria from Merck Sharp & Dohme Corp, and Ono Pharmaceutical Co., Ltd. SI received lecture honoraria and grants from Ono Pharmaceutical Co., Ltd and lecture honoraria from Bristol Myers Squibb. KI received grants from SCREEN Holdings Co., Ltd. TAs received grants from Ono Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tsujikawa, Ohno, Morita, Saburi, Mitsuda, Yoshimura, Kimura, Morimoto, Ogi, Shibata, Akashi, Kurata, Imoto, Shimizu, Kano, Watanabe, Yamazaki, Asada, Hayashi, Saito, Ozawa, Tsukahara, Oridate, Sano, Horii, Ueki, Maruo, Mukoyama, Hanai, Fukusumi, Iwai, Fujisawa, Fujii, Nibu, Iwae, Ueda, Chikuie, Yasumatsu, Matsuo, Umeno, Ono, Masuda, Toh, Itoh, Hirano and Asakage.)

Objectives: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008., Materials and Methods: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m 2 (weekly arm) or 3-weekly cisplatin at 100 mg/m 2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration., Results: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %., Conclusions: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshinori Imamura Speakers' Bureau - Daiichi Sankyo/UCB Japan; MSD Naomi Kiyota Honoraria - AstraZeneca; Bayer; Bristol-Myers Squibb Japan; Eisai; Lilly Japan; Merck Serono; MSD; Ono Pharmaceutical Consulting or Advisory Role - Adlai Nortye; Ono Pharmaceutical; Shift Zero Research Funding - Adlai Nortye (Inst); Bayer (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); Lilly (Inst); Ono Pharmaceutical (Inst); Rakuten Medical (Inst) Makoto Tahara Honoraria - Bayer; Bristol-Myers Squibb; Eisai; Lilly; Merck Serono; MSD; Ono Pharmaceutical Consulting or Advisory Role - Astellas Pharma; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Eisai; Genmab; Janssen; Lilly; MSD; Nanobiotix; Nektar; Ono Pharmaceutical; Pfizer; Rakuten Medical Research Funding - AstraZeneca (Inst); Bayer (Inst); Bristol-Myers Squibb (Inst); GlaxoSmithKline (Inst); Lilly (Inst); Merck Serono (Inst); Merck Sharp & Dohme (Inst); Novartis (Inst); Ono Pharmaceutical (Inst); Pfizer (Inst); Rakuten Medical (Inst) Takeshi Kodaira Speakers' Bureau - Accuray; AstraZeneca; Bristol-Myers Squibb; Chugai Pharma; Hitachi; Janssen; Merck Serono; Ono Pharmaceutical; Reason Why Co. Ryuichi Hayashi Consulting or Advisory Role - Rakuten Medical Japan Research Funding - Japan Agency for Medical Research and Development Hiroshi Nishino No Relationships to Disclose Yukinori Asada No Relationships to Disclose Hiroki Mitani No Relationships to Disclose Shigemichi Iwae Consulting or Advisory Role - Merck (Inst) Speakers' Bureau - Bristol-Myers Squibb Japan; Merck; MSD; Ono Pharmaceutical Research Funding - Ascent Development Services (Inst); GlaxoSmithKline (Inst); Merck (Inst); MSD (Inst); Ono Pharmaceutical (Inst) Nobuhiro Hanai Honoraria - Bristol-Meyers Squibb; Covidien; Eisai; Merck; MSD K.K; Ono Pharmaceutical; Rakuten Medical Research Funding - MSD K.K Hiroki Hara Honoraria - Asahi Kasei; Bayer; Bristol-Myers Squibb; Chugai Pharma; Daiichi Sankyo/UCB Japan; Lilly; Merck Serono; MSD; Ono Pharmaceutical; Taiho Pharmaceutical; Takeda; Yakult Honsha Consulting or Advisory Role - Boehringer Ingelheim; Bristol-Myers Squibb Japan; Chugai Pharma; MSD; Ono Pharmaceutical Research Funding - ALX Oncology (Inst); Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bayer (Inst); BeiGene (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb Japan (Inst); Chugai Pharma (Inst); Daiichi Sankyo (Inst); Dainippon Sumitomo Pharma (Inst); Eisai (Inst); Janssen Oncology (Inst); Merck Serono (Inst); MSD (Inst); Ono Pharmaceutical (Inst); Taiho Pharmaceutical (Inst) Akihiro Homma Speakers' Bureau - Bayer Yakuhin; Bristol-Myers Squibb; Demant; Eisai; Kyorin; Lilly Japan; Meiji Seika Kaisha; Merck; Mitsubishi Tanabe Pharma; MSD K.K; Ono Pharmaceutical; Rakuten Medical Japan; Sanofi; Taiho Pharmaceutical Research Funding - Eisai; Iwasaki Denshi; Kyorin; Mitsubishi Tanabe Pharma; Ono Pharmaceutical; Otsuka; Taiho Pharmaceutical; Torii Pharmaceutical Others had no relationships to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background:  Salivary fistula formation is a common and serious complication following head and neck reconstruction. Because it can cause delayed wound healing and infection and carotid artery rupture in severe cases, hence, early detection and treatment are crucial. This study was designed to identify early predictors of postoperative fistula formation., Methods:  We conducted a retrospective analysis of patients who underwent head and neck reconstruction between 2015 and 2022. Body temperature, serum white blood cell (WBC) count, and serum C-reactive protein (CRP) levels were assessed until postoperative day (POD) 14 and compared between patients with and without fistula., Results:  In this study, 200 patients were included. No significant differences in body temperature and WBC count were observed between the two groups during the entire study period. CRP levels after POD2 were higher in the fistula group than in the without fistula group. From the receiver operating characteristic curves comparing the two groups, the best cutoff level for CRP was 6.27 mg/dL from POD7 to POD8, with 77.1% sensitivity, 69.8% specificity, and 90.1% negative predictive value., Conclusion:  CRP is a valuable predictor of fistula formation following head and neck reconstruction. The course of CRP levels in patients with fistulas remains consistently elevated compared to patients without fistulas, and it is particularly useful for the exclusion diagnosis of fistula., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: For patients with recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), platinum-free interval (PFI)-based differences in the effectiveness of rechallenge with platinum-based chemotherapy (PBCT) remain unknown. We aimed to evaluate the difference in platinum sensitivity based on PFI in R/MHNSCC., Methods: We retrospectively examined 80 patients with R/MHNSCC who underwent PBCT between 2001 and 2020. Treatment efficacy was compared between patients with prior PBCT for treatment of recurrence/metastasis or concurrent chemoradiotherapy during radical treatment (rechallenge group) and those without (control group). Patients with prior PBCT (rechallenge group) were stratified by PFI. PFI was defined as the period from the last dosing date with the previous platinum agent to rechallenge with PBCT., Results: Of 80 patients, 55 had been with prior PBCT (rechallenge group) and 25 had been without prior PBCT (control group). The rechallenge group was divided into three groups: PFI <6 months (10), PFI 6-11 months (17), and PFI ≥12 months (28). The PFI <6-month group had shorter overall survival (p=0.047, the log-rank test) and lower disease control rate (p=0.02, Fisher's exact test) than the control group. The PFI 6-11- and ≥12-month group outcomes did not significantly differ from those of the control group., Conclusions: Patients with PFI <6 months tend to have a poorer prognosis after rechallenge with PBCT than patients without prior PBCT, suggesting that PFI 6 months may be considered as a threshold of platinum resistance and rechallenge with PBCT may be a valid option in PFI ≥6 months., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The frequency of metastasis to level VI lymph nodes in advanced pyriform sinus squamous cell carcinoma (PSSCC) is unknown. We intended to analyze the clinical features and pathological presence or absence of level VI lymph node metastasis in patients with PSSCC., Methods: The data of 270 patients with previously untreated hypopharyngeal squamous cell carcinoma from 2006 to 2016 were obtained. Patients who underwent pharyngolaryngectomy for the pyriform sinus subsite with a curative intent with level VI dissection were included. We retrospectively analyzed the clinical Tumor-Node (TN) status (TNM classification of malignant tumors, eighth edition) and the presence or absence of pathological level VI lymph node metastasis., Results: A total of 34 patients were included. Eight patients (24%) had pathological level VI lymph node metastasis. The rate of pathological level VI lymph node metastasis was directly proportional to the clinical N status ( P  = .0002, Chi-square test for trend). In all, 5 patients with cN2b- 3 were classified as cN3b. Ipsilateral pathological level VI lymph node metastasis was observed in 1 patient, and bilateral metastasis was observed in 3 patients. There was no association between clinical T status or pyriform sinus apex invasion and pathological level VI metastasis (both P  > .99, Fisher's exact test)., Conclusions: PSSCC with cN3b is prone to bilateral level VI metastasis. We recommend that patients with PSSCC with cN3b should undergo bilateral level VI lymph node dissection.

Purpose: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2 ). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m 2 ) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown., Patients and Methods: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2 ) or with weekly cisplatin (40 mg/m 2 ) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32., Results: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm., Conclusion: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients., Competing Interests: Naomi KiyotaHonoraria: Ono Pharmaceutical, Bristol Myers Squibb Japan, Bayer, Chugai Pharma, Merck Serono, MSD, Eisai, AstraZenecaConsulting or Advisory Role: Shift Zero, Ono Pharmaceutical, Ascent Development ServicesSpeakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Serono, Eisai, Bayer, MSD, Chugai PharmaResearch Funding: Ono Pharmaceutical (Inst), Bristol Myers Squibb (Inst), Pfizer (Inst), Roche (Inst), Rakuten Medical (Inst), Adlai Nortye (Inst) Makoto TaharaHonoraria: Merck Serono, Bristol Myers Squibb, Eisai, Ono Pharmaceutical, MSDConsulting or Advisory Role: Ono Pharmaceutical, MSD, Pfizer, Bristol Myers Squibb, Rakuten Medical, Bayer, LillyResearch Funding: Merck Sharp & Dohme (Inst), AstraZeneca (Inst), Ono Pharmaceutical (Inst), Novartis (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Rakuten Medical (Inst), Bayer (Inst), GlaxoSmithKline (Inst), Lilly (Inst) Junki MizusawaHonoraria: Chugai Pharma, Taiho Pharmaceutical Takeshi KodairaConsulting or Advisory Role: Ono Pharmaceutical, Chugai PharmaSpeakers' Bureau: Merck Serono, Hitachi, Bristol Myers Squibb Japan, Accuray, Elekta, Ono Pharmaceutical, Canon USA, AstraZeneca, Chugai Pharma Nobuhiro HanaiHonoraria: Ono Pharmaceutical, Bristol Myers Squibb, Merck, MSD K.K, Eisai, Ethicon/Johnson & Johnson, AmcoConsulting or Advisory Role: SanwaResearch Funding: Ono Pharmaceutical, Chugai Pharma, Rakuten Medical, Bristol Myers Squibb/Ono Pharmaceutical, GlaxoSmithKline K.K, MSD K.K Hiroki HaraHonoraria: Chugai Pharma, Taiho Pharmaceutical, Merck Serono, Yakult Honsha, Lilly, Ono Pharmaceutical, Takeda, Bristol Myers Squibb, Sanofi, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, BayerConsulting or Advisory Role: Ono Pharmaceutical, MSD, Lilly, Boehringer Ingelheim, Dainippon SumitomoResearch Funding: AstraZeneca (Inst), Chugai Pharma (Inst), Merck Serono (Inst), MSD (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Boehringer Ingelheim (Inst), Dainippon Sumitomo Pharma (Inst), Daiichi Sankyo (Inst), Pfizer (Inst), Eisai (Inst), Incyte (Inst), BeiGene (Inst), Astellas Pharma (Inst), Bayer (Inst), Elevar Therapeutics (Inst) Kaoru TanakaHonoraria: AstraZeneca, Merck Serono, Ono Pharmaceutical, Bristol Myers Squibb, Eisai, MSD, Kyowa Kirin Co, Ltd Akihiro HommaConsulting or Advisory Role: Rakuten Medical Japan, Olympus Medical SystemsSpeakers’ Bureau: Bristol Myers Squibb Japan, Mitsubishi Tanabe Pharma, Eisai, Makichie, Merck Serono, MSD K.K, Ono Pharmaceutical, Sanofi, Nobelpharma, BayerResearch Funding: Taiho Pharmaceutical (Inst), Kyorin Pharmaceutical (Inst), Otsuka Pharmaceutical Factory (Inst), Eisai (Inst) Nobuhiko OridateSpeakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Biopharma/Japan, Taiho Pharmaceutical, MSDResearch Funding: Ono Pharmaceutical, Merck biopharma/Japan, Taiho Pharmaceutical, Daiichi Sankyo Japan Tsutomu UedaHonoraria: Mitsubishi Tanabe Pharma, Bayer, Taiho Pharmaceutical, MSD, Ono PharmaceuticalResearch Funding: Ono Pharmaceutical Kenichi NakamuraHonoraria: Bayer Yakuhin, Chugai Pharma, Taiho PharmaceuticalResearch Funding: Astellas Pharma (Inst), Eisai (Inst), Otsuka (Inst), Ono Pharmaceutical (Inst), Kyorin (Inst), Daiichi Sankyo (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), Chugai/Roche (Inst), Novartis (Inst), Pfizer (Inst), Bayer (Inst), Bristol Myers Squibb Japan (Inst), Boehringer Ingelheim Seiyaku (Inst) Ryuichi HayashiConsulting or Advisory Role: Rakuten Medical JapanNo other potential conflicts of interest were reported.

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.)

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0-1. Patients received docetaxel (75 mg/m 2 on day 1) and cisplatin (75 mg/m 2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24-68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options.This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012]., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients., Methods: This is a multi-institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent., Results: Overall 5-year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5-fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups., Conclusion: Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes., Level of Evidence: 4 Laryngoscope, 131:E870-E874, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

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.)

Background: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date., Methods: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality., Results: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m 2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m 2 ; 17 patients)., Conclusions: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m 2 ., (© 2020 American Cancer Society.)

Objectives: To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272)., Methods: Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome., Results: With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose., Conclusions: This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Objectives: To evaluate the clinical impact of cachexia, defined by the combination of albumin and C-reactive protein levels, in patients with unresectable locally advanced head and neck squamous cell carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706., Methods: Forty-five patients received radiation for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. The present analysis was conducted in 44 patients with available data. The association between treatment efficacy and cachexia was investigated. Pretreatment cachexia was defined as a serum albumin level of less than 3.5 mg/dl and C-reactive protein level of more than 0.5 mg/dl., Results: Among the 44 patients, 5 patients had cachexia. On comparison with the cachexic and non-cachexic patients, the percentage of clinical complete remission (20% vs 72%), time to treatment failure at 3 years, (20% vs 53%) and proportion of treatment completion (20% vs 79%) were statistically worse in the cachexic patients, while overall survival, progression-free survival and local progression-free survival at 3 years tended to be worse in cachexic patients., Conclusions: This supplementary analysis from a prospective study suggests that a pretreatment status of cancer cachexia is a prognostic factor for treatment outcomes and compliance in patients with locally advanced head and neck squamous cell carcinomas treated with chemoradiotherapy, and a candidate stratification factor in future prospective trials in this population.

Background: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study., Methods: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival., Results: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT., Conclusion: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive., Competing Interests: A. Kubota has received honoraria from AstraZeneca, Otsuka Pharmaceutical, and Taiho Pharmaceutical; and research funding from Taiho. K. Tsukahara has received honoraria from Covidien Japan, FUJIFILM Medical, Johnson & Johnson, KYORIN Pharmaceutical, Kyowa Hakko Kirin, Merck Serono, Mitsubishi Tanabe Pharma Corporation, and Sanofi. T. Terada has received honoraria from GlaxoSmithKline, KYORIN, Merck Serono, and Ono Pharmaceutical. T. Taguchi has received an honorarium from Taiho. K. Nagahara has received honoraria from Kowa Pharmaceutical and Taisho Toyama Pharmaceutical. S. Iwae has received honoraria from Ono and Otsuka. K. Tomita has received an honorarium from KYORIN. S. Teramukai has received consulting fees from Bristol-Myers Squibb, Daiichi Sankyo, Sanofi, Sysmex Corporation, and Taiho; and research funding from Daiichi Sankyo. M. Fujii has received honoraria from Bristol-Myers Squibb, Merck Serono, and Taiho; and research funding from Taiho. The other authors have declared no conflicts of interest. We confirm that our potential interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background/objective: The Amatsu tracheoesophageal shunt (ATES) represents a nonprosthesis surgical option for voice restoration in laryngectomized patients. However, data regarding the long-term efficacy of ATES are lacking., Study Design: Retrospective, single-institution study., Methods: Between 2001 and 2010, 16 patients with laryngeal cancer underwent total laryngectomy with ATES at the Hyogo Cancer Center (Akashi, Hyogo, Japan). Of these, 11 achieved long-term tracheoesophageal speech that was maintained for a follow-up exceeding 5 years (range 75-161 months; median 95 months). All patients were male and ranged from 46 to 74 years of age at the time of ATES surgery., Results: Of 11 eligible patients, eight were able to speak intelligibly with ATES at last follow-up. Regarding aspiration, three patients experienced no leakage, and six experienced mild leakage of saliva without medical intervention at last follow-up. Almost all patients maintained an unchanged degree of voice quality (9 of 11) and leakage (8 of 11)., Conclusion: The favorable voice restoration and low aspiration rates achieved in this study appear to support the long-term efficacy of ATES., Level of Evidence: 4. Laryngoscope, 128:1395-1397, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer., Methods: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates., Results: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups., Conclusions: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

Objectives: To assess efficacy and safety of nivolumab versus investigator's choice of therapy (IC) in Asian patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)., Materials and Methods: Thirty-four patients from Japan, Taiwan, Hong Kong, and Korea received nivolumab 3mg/kg (n=23) every 2weeks or IC (n=11), as part of a global trial (n=361), until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS)., Results: Median OS was 9.5months (95% confidence interval [CI] 9.1-NR) with nivolumab and 6.2months (95% CI 2.6-NR) with IC. Seven (30.4%) patients receiving nivolumab and six (54.5%) receiving IC died. The hazard ratio (HR) for risk of death (nivolumab vs. IC) was 0.50 (95% CI 0.17-1.48). Median progression-free survival was 1.9months (95% CI 1.6-7.5) with nivolumab and 1.8months (95% CI 0.4-6.1) with IC (HR 0.57 [95% CI 0.25-1.33]). Objective response rates (complete+partial responses) were 26.1% (6/23 patients; 95% CI 10.2-48.4) for nivolumab and 0% (0/11 patients; 95% CI 0.0-28.5) for IC. Sixteen (69.6%) nivolumab-treated patients and 10 (90.9%) patients receiving IC had a treatment-related adverse event, most commonly decreased appetite (21.7%), pruritus, rash, and fatigue (17.4% each) with nivolumab, and nausea, stomatitis, and decreased appetite (27.3% each) with IC., Conclusion: Nivolumab demonstrated a survival advantage compared with conventional treatments in Asian patients with platinum-refractory recurrent or metastatic SCCHN, and was well tolerated. Clinical trial registration NCT02105636., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In mucoepidermoid carcinoma (MEC), CRTC1-MAML2 fusion indicates a favorable prognosis. Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, has been shown to be a downstream target of CRTC1-MAML2 fusion, and to play a role in tumor growth and survival in CRTC1-MAML2-positive MEC cell lines. The aim of this study was to characterize the AREG and EGFR expression in the fusion-positive and fusion-negative MEC of the major salivary gland. The AREG and EGFR expression were studied by immunochemistry in 33 MEC cases of the major salivary glands. CRTC1-MAML2 fusion was tested by reverse-transcription polymerase chain reaction (23 CRTC1-MAML2 fusion-positive, 10 fusion-negative). Of 23 fusion-positive cases, AREG and EGFR overexpression were detected in 17 (73.9%) and 14 (60.9%) cases, respectively. Of 10 fusion-negative cases, AREG and EGFR overexpression were detected in 1 (10%) and 3 (30.0%) cases, respectively. There was a positive correlation between CRTC1-MAML2 fusion and AREG overexpression (P < .01), but not between CRTC1-MAML2 fusion and EGFR overexpression. The AREG overexpression was associated with a longer disease-free survival of the MEC patients (P = .042), but EGFR overexpression was not. In this study, we showed that AREG overexpression was detected more frequently in the CRTC1-MAML2 fusion-positive tumors than in fusion-negative tumors. Detection of AREG expression may be useful for identifying CRTC1-MAML2-positive MECs and as a marker for favorable prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Renal function influences decisions regarding treatment for patients with oropharyngeal squamous cell carcinoma (SCC). However, the importance of renal function in oropharyngeal SCC has not yet been reported., Methods: Four hundred sixty patients with oropharyngeal SCC treated with curative intent between April 2005 and March 2007 in 12 institutions in Japan were analyzed retrospectively., Results: Four hundred three patients (87.6%) showed a creatinine clearance (CrCl) ≥50 mL/min and 57 (12.4%) with a CrCl <50 mL/min. Age was associated with worse overall survival (OS), whereas stage IVB, radiotherapy (RT), and CrCl <50 were associated with worse OS on univariate analyses. Surgery and hypertension were associated with better OS on univariate analyses. On multivariate analysis, age, stage, hypertension, and CrCl were also found to be significantly associated with OS., Conclusion: Based on this retrospective study, impaired renal function is an independent predictor of increased risk of death in patients with oropharyngeal SCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1500, 2016., (© 2016 Wiley Periodicals, Inc.)

We conducted a phase II study to evaluate the efficacy and safety of chemoradiotherapy concurrent with S-1 plus cisplatin in patients with unresectable locally advanced squamous cell carcinoma of the head and neck. Chemotherapy consisted of S-1 twice daily on days 1-14 at 60 mg/m(2) /day and cisplatin at 20 mg/m(2) /day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently starting on day 1. For patients achieving an objective response after chemoradiotherapy, two additional cycles of chemotherapy were administered. Of the 45 enrolled patients, the percentage of clinical complete remission, the primary endpoint, was 64.4% (8 complete response, 21 good partial response) on central review. After a median follow-up of 3.52 years, 3-year local progression-free survival was 62.2%, with 3-year progression-free survival of 60.0%, 3-year overall survival of 64.4%, and 3-year time to treatment failure of 48.9%. Grade 3 or 4 toxicity included pharyngeal mucositis (46.7%), oral mucositis (44.4%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%), and febrile neutropenia (4.4%). No treatment-related deaths were observed. This combination showed promising efficacy with acceptable toxicities., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Background: The purpose of this retrospective analysis was to evaluate ocular function and survival rates among treatment modalities in patients with maxillary sinus cancer with orbital invasion., Methods: Eighty-seven patients were classified according to the main treatment modality. Ocular function preservation rates and survival rates were evaluated for each therapeutic modality., Results: The 5-year overall survival rate for the en bloc resection, conservative surgery, superselective intra-arterial chemotherapy, and radiotherapy (RADPLAT), intravenous chemoradiotherapy (IV-CRT) was 70%, 35%, 49%, and 31%, respectively. The ocular function preservation rate for each group was 15%, 27%, 30%, and 17%, respectively. In the en bloc resection group, there was no significant difference in the 5-year overall survival rate between patients with orbital exenteration and those without orbital exenteration (72% vs 71%; p = .9321)., Conclusion: The en bloc resection group showed a favorable survival rate but a low preservation rate. Preservation of orbital contents did not reduce the survival rate., (© 2014 Wiley Periodicals, Inc.)

Background: We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN)., Patients and Methods: Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety., Results: A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group., Conclusions: Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN., Trial Registration: ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947.

Background: We analyzed the effects of local extension sites on survival in patients with locally advanced maxillary sinus cancer., Methods: The criteria for inclusion in this study were as follows: (1) previously untreated maxillary sinus cancer; (2) squamous cell carcinoma; (3) T4 disease; and (4) curative-intent treatment. The data for 118 patients were obtained from 28 institutions across Japan and analyzed for overall survival and local control rates by local extension site., Results: Sites with a poor prognosis included the cribriform plate, dura, nasopharynx, middle cranial fossa, and cranial nerves other than V2. There was a significant correlation among these sites, except for the cranial nerves. Additionally, the hard palate was the only site that correlated with nodal involvement and showed a poor treatment outcome., Conclusion: Even in cases presenting with similar T4 maxillary sinus cancer, treatment should be performed in consideration of the local extension site., (© 2013 Wiley Periodicals, Inc.)

Background: The current study sought to assess the role of initial neck dissection (ND) for patients with node-positive oropharyngeal squamous cell carcinomas (OPSCC)., Methods: The data for 202 patients with previously untreated node-positive OPSCC were gathered from 12 institutions belonging to the Head and Neck Cancer Study Group in the Japan Clinical Oncology Group. These patients were categorized into two groups, consisting of the initial ND group and the wait-and-see group, according to treatment policy., Results: Regional recurrence was observed in 17 of 93 patients undergoing initial ND, whereas, recurrent or persistent diseases were observed in 40 of 109 patients who did not undergo initial ND. The 4-year overall survival rates (OS) for the wait-and-see group and initial ND groups were 74.0% and 78.7%, respectively, and the 4-year regional control rates (RC) for each group were 77.6% and 84.9%. There were no significant differences in either OS or RC (p=0.3440 and p=0.2382, respectively). However, for patients with N3 disease, the 4-year OS of the initial ND group (100%) was favorable. For patients with N2a disease, the 4-year RC of the initial ND group was higher than that of the wait-and-see group statistically (100% vs 62.5%, p=0.0156)., Conclusions: The role of initial ND was limited in patients with node-positive OPSCC. The treatment strategy not involving initial ND is considered feasible and acceptable when nodal evaluation after definitive radiotherapy or chemoradiotherapy is applied adequately. However, it is possible that initial ND improves outcomes in patients with resectable large-volume nodal disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to evaluate the incidence of lymph node metastasis among patients with T4 maxillary sinus squamous cell carcinoma (MS-SCC) as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC., Methods: Consecutive series of all patients (n = 128) with previously untreated T4 maxillary sinus SCC between 2006 and 2007 were obtained from 28 institutions belonging to or cooperating in the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group., Results: Of the 128 patients, 28 (21.9 %) had lymph node metastasis, and six patients (4.7 %) had distant metastasis at diagnosis. Among the 111 patients who were treated with curative intent, 98 had clinically N0 neck disease and did not receive prophylactic neck irradiation. A total of 11 patients (11.2 %) subsequently developed evidence of lymph node metastasis, of whom eight were among the 83 patients with an N0 neck and had not received elective neck treatment. There were 15 patients who received an elective neck dissection as part of the initial treatment, of whom three had pathologically positive for lymph node metastases. Of 11 patients, six patients with nonlateral retropharyngeal lymph node metastasis without primary or distant disease were successfully salvaged., Conclusions: This study identified the incidence of lymph node metastasis among patients with T4 MS-SCC as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. These results will be of assistance in selecting treatment strategy for T4 MS-SCC in the future.

Background: The current study aimed to assess the role of salvage surgery for failure cases of oropharyngeal cancer (OPC) undergoing initial chemoradiotherapy (CRT)., Methods: The data for 523 patients with previously untreated OPC were gathered from 12 institutions belonging to the Head and Neck Cancer Study Group in Japan Clinical Oncology Group (JCOG)., Results: Of the 170 patients who received CRT, 35 patients (21%) had local recurrence or residual disease. Only 11 patients underwent further salvage surgery, and 24 patients received nonsurgical treatment. There were statistically significant differences between the two groups in terms of patient age and the presence of a simultaneous regional recurrence. The 5-year overall survival rates for the patients who underwent salvage surgery were 49.1%, whereas those for the patients who received nonsurgical treatment were 16.3%., Conclusion: The initial treatment method for OPC should be decided carefully and the limitations of salvage surgery should be fully considered.

Objective: The current study aimed to compare the therapeutic outcomes of surgery with those of chemoradiation for patients with advanced oropharyngeal cancer (OPC)., Methods: The data for 523 patients with previously untreated OPC were obtained from 12 institutions belonging to the Head and Neck Cancer Study Group in the Japan Clinical Oncology Group from April 2005 to March 2007. In this study, we matched a group of patients who underwent surgery with a second group treated with chemoradiation according to age, gender, subsite, and T and N classification, and analyzed the overall survival, progression-free survival, local control and swallowing function., Results: The final matched-pair analysis included 186 patients. The 5-year overall survival, progression-free survival and local control rates were 69.8 and 71.4% (p = 0.762), 51.0 and 54.4% (p = 0.531), and 75.2 and 80.3% (p = 0.399), respectively, in patients treated with surgery and those treated with chemoradiation. Swallowing function in patients treated with chemoradiation was significantly better than that in patients treated with surgery (p = 0.015)., Conclusion: Although this study was not randomized, this matched-pair analysis of patients treated with surgery or chemoradiation showed that chemoradiation is as effective as surgery in the treatment of OPC., (Copyright © 2013 S. Karger AG, Basel.)