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Background: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan., Methods: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied., Results: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN., Conclusion: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data., Materials and Methods: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism., Results: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism., Conclusion: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.)

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.)

Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details., Competing Interests: Declaration of interests AML reports uncompensated consultancy for Eisai; support from a Peter MacCallum Cancer Centre Discovery Partner Fellowship, and institutional research funding support from Sanofi/Regeneron Pharmaceuticals. LM has participated in an advisory board for Merck Sharp & Dohme (MSD). CLT has participated in advisory boards for MSD, Roche, Merck Serono, ALX Oncology, Excientia, Seagen, Kumar Therapeutics, MaxiVax, BMS, PCI Biotech, Nanobiotix, Onxeo, MVX-ONCO, Seattle Genetics, Rakuten, GSK, Celgene, and AstraZeneca. AH has received grants and personal fees from ONO, Taiho, KYORIN, Eisai, and Mitsubishi Tanabe Pharma; grants from Otsuka Pharmaceutical Factory, Iwasakidenshi, and Torii; and personal fees from Bristol Myers Squibb, Bayer Yakuhin, Merck Biopharma, Eli Lilly, Sanofi, Rakuten Medical, Meiji Pharma, Demant, and MSD, outside the submitted work. DJT reports consulting fees from MSD; advisory board participation for Merck Serono; and research grants from Cancer Research UK. AM-P has participated in advisory boards for MSD and Norgine; and has received clinical trial research grants from MSD and Intuitive Surgical, outside the submitted work. CHu has participated in advisory boards for EMD Serono. PS has advisory relationships with Merck Serono, Servier, and MSD. ATD reports grants from the National Health Institute and the Cancer Prevention Institute of Texas. JEB has participated in advisory boards for Galera Therapeutics and Castle Biosciences. AP has participated in advisory boards for MSD, Roche, Merck Serono, BMS, Nanobiotics, GSK, and Seagen; reports honoraria for editorial work from Elsevier; research grants from KURA, BMS, and Ipsen; and received travel grants from Ipsen. HM reports grants from UK National Institute of Health research, Cancer Research UK, the UK Medical Research Council, and AstraZeneca; advisory board fees from AstraZeneca, MSD, Merck, Nanobiotix, and Seagen; and is Director of Warwickshire head and neck clinic and Docspert Health. SSY reports clinical trial research grants from Bristol Myers Squibb, EMD Serono, and Nanobiotix; honoraria for editorial work from Elsevier and ASTRO; and publishing royalties from Springer and Up To Date. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: To investigate the utility of deep learning (DL)-based image reconstruction using a model-based approach in head and neck diffusion-weighted imaging (DWI)., Materials and Methods: We retrospectively analyzed the cases of 41 patients who underwent head/neck DWI. The DWI in 25 patients demonstrated an untreated lesion. We performed qualitative and quantitative assessments in the DWI analyses with both deep learning (DL)- and conventional parallel imaging (PI)-based reconstructions. For the qualitative assessment, we visually evaluated the overall image quality, soft tissue conspicuity, degree of artifact(s), and lesion conspicuity based on a five-point system. In the quantitative assessment, we measured the signal-to-noise ratio (SNR) of the bilateral parotid glands, submandibular gland, the posterior muscle, and the lesion. We then calculated the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle., Results: Significant differences were observed in the qualitative analysis between the DWI with PI-based and DL-based reconstructions for all of the evaluation items (p < 0.001). In the quantitative analysis, significant differences in the SNR and CNR between the DWI with PI-based and DL-based reconstructions were observed for all of the evaluation items (p = 0.002 ~ p < 0.001)., Discussion: DL-based image reconstruction with the model-based technique effectively provided sufficient image quality in head/neck DWI., (© 2023. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to high-dose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort., Methods and Materials: Patients received 100 mg/m 2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%)., Results: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported., Conclusions: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan., Methods: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included., Results: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05)., Conclusion: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: Silicon photomultiplier-based positron emission tomography/computed tomography (SiPM-PET/CT) has the superior spatial resolution to conventional PET/CT (cPET/CT). This head-to-head comparison study compared the images of physiological 18 F-fluorodeoxyglucose (FDG) accumulation in small-volume structures between SiPM-PET/CT and cPET/CT in patients scanned with both modalities, and we investigated whether the thresholds that are reported to be useful for differentiating physiological accumulations from malignant lesions can also be applied to SiPM-PET/CT., Methods: We enrolled 21 consecutive patients with head and neck malignancies who underwent whole-body FDG-PET/CT for initial staging or a follow-up evaluation (October 2020 to March 2022). After being injected with FDG, all patients underwent PET acquisition on both Vereos PET-CT and Gemini TF64 PET-CT systems (both Philips Healthcare) in random order. For each patient, the maximum standardized uptake value (SUVmax) was measured in the pituitary gland, esophagogastric junction (EGJ), adrenal glands, lumbar enlargement of the spinal cord, and epididymis. We measured the liver SUVmean and the blood pool SUVmean to calculate the target-to-liver ratio (TLR) and the target-to-blood ratio (TBR), respectively. Between-groups differences in each variable were examined by a paired t-test. We also investigated whether there were cases of target uptake greater than the reported threshold for distinguishing pathological from physiological accumulations., Results: Data were available for 19 patients. Ten patients were in Group 1, i.e., the patients who underwent SiPM-PET first, and the remaining nine patients who underwent cPET first were in Group 2. In the SiPM-PET results, the SUVmax of all targets was significantly higher than that obtained by cPET in all patients, and this tendency was also observed when the patients were divided into Groups 1/2. The TLRs of all targets were significantly higher in SiPM-PET than in cPET in all patients, and SiPM-PET also showed significantly higher TBRs for all targets except the EGJ (p = 0.052)., Conclusions: The physiological uptake in the small structures studied herein showed high accumulation on SiPM-PET. Our results also suggest that the thresholds reported for cPET to distinguish pathological accumulations likely lead to false-positive findings in SIPM-PET evaluations., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments., (Copyright © 2023. Published by Elsevier B.V.)

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66 Gy in 33 fractions for T1 disease and 70 Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0 to 2.5 Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9 months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Eyelid squamous cell carcinoma is a major type of rare eyelid cancer, together with basal cell carcinoma and sebaceous gland carcinoma. It is a painless disease that progresses slowly and is often detected by the appearance of nodules or plaques. Risk factors include exposure to ultraviolet light, fair skin, radiation and human papillomavirus infection. The standard treatment is surgical removal, and in cases of orbital invasion, orbital content removal is required. If sentinel node biopsy reveals a high risk of lymph node metastasis, adjuvant radiotherapy may be considered. Local chemotherapy, such as imiquimod and 5-fluorouracil, may be used for eyelid squamous cell carcinoma in situ. When surgery or radiotherapy is not recommended for distant metastases or locally advanced disease, drug therapy is often according to head and neck squamous cell carcinoma in Japan. The treatment often requires a multidisciplinary team to ensure the preservation of function and cosmetic appearance., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN., Methods: This study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m 2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score., Discussion: If the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT., Trial Registration: This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 ( https://jrct.niph.go.jp/latest-detail/jRCTs031210100 ). Date of Registration: May 2021., (© 2023. The Author(s).)

Background: Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT)., Methods: A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score., Results: A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1 year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04)., Conclusion: This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Given the low incidence, variety of histological types, and heterogeneous biological features of head and neck sarcomas, there is limited high-quality evidence available to head and neck oncologists. For resectable sarcomas, surgical resection followed by radiotherapy is the principle of local treatment, and perioperative chemotherapy is considered for chemotherapy-sensitive sarcomas. They often originate in anatomical border areas such as the skull base and mediastinum, and they require a multidisciplinary treatment approach considering functional and cosmetic impairment. Moreover, head and neck sarcomas may exhibit different behaviour and characteristics than sarcomas of other areas. In recent years, the molecular biological features of sarcomas have been used for the pathological diagnosis and development of novel agents. This review describes the historical background and recent topics that head and neck oncologists should know about this rare tumour from the following five perspectives: (i) epidemiology and general characteristics of head and neck sarcomas; (ii) changes in histopathological diagnosis in the genomic era; (iii) current standard treatment by histological type and clinical questions specific to head and neck; (iv) new drugs for advanced and metastatic soft tissue sarcomas; and (v) proton and carbon ion radiotherapy for head and neck sarcomas., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: Esophageal cancer is the most common second primary cancer (SPC) in patients with head and neck cancer (HNC). Esophageal SPC has a negative impact on survival. Elevated mean corpuscular volume (MCV) is an accepted predictor of esophageal cancer risk. The aim of this study was to elucidate the usefulness of elevated MCV as an indicator of a high risk for esophageal SPC., Methods: We retrospectively reviewed the medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma who underwent chemoradiotherapy between 2003 and 2012. We excluded patients younger than 20 years or who had received treatment for esophageal cancer and who had a histologically unproven lesion. Patients were divided into two groups according to their MCV. The cut-off for MCV was defined by receiver operating characteristics curve analysis. The primary endpoint was the cumulative incidence of esophageal SPC., Results: A total of 295 patients were included. The median follow-up period for surviving patients was 7.4 years and the optimal cut-off point was 99.0 fL. One hundred ninety-five patients (66%) had an MCV < 99.0 fL and 100 (34%) had an MCV ≥ 99.0 fL. The 5-year cumulative incidence in patients with an MCV < 99.0 fL and ≥ 99.0 fL was 8.7% and 27%, respectively. In the multivariate analysis, an MCV ≥ 99.0 fL (HR=2.2; 95%CI, 1.1-4.2) was an independent risk factor., Conclusion: MCV ≥ 99.0 fL was found to be a risk factor for esophageal SPC. We, therefore, recommend that patients with an MCV ≥ 99.0 fL should undergo intensive monitoring., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Sequential boost intensity-modulated radiotherapy (SQB-IMRT) uses two different planning CTs (pCTs) and treatment plans. SQB-IMRT is a form of adaptive radiotherapy that allows for responses to changes in the shape of the tumour and organs at risk (OAR). On the other hand, dose accumulation with the two plans can be difficult to evaluate. The purpose of this study was to analyse patterns of loco-regional failure using deformable image registration (DIR) in hypopharyngeal cancer patients treated with SQB-IMRT., Methods: Between 2013 and 2019, 102 patients with hypopharyngeal cancer were treated with definitive SQB-IMRT at our institution. Dose accumulation with the 1st and 2nd plans was performed, and the dose to the loco-regional recurrent tumour volume was calculated using the DIR workflow. Failure was classified as follows: (i) in-field (≥95% of the recurrent tumour volume received 95% of the prescribed dose); (ii) marginal (20-95%); or (iii) out-of-field (<20%)., Results: After a median follow-up period of 25 months, loco-regional failure occurred in 34 patients. Dose-volume histogram analysis showed that all loco-regional failures occurred in the field within 95% of the prescribed dose, with no marginal or out-of-field recurrences observed., Conclusion: The dosimetric analysis using DIR showed that all loco-regional failures were within the high-dose region. More aggressive treatment may be required for gross tumours., (© 2022 Royal Australian and New Zealand College of Radiologists.)

Background: Radiotherapy plus cetuximab (bioradiotherapy: BRT) is a standard option in the treatment of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Published data on its safety and efficacy in real-world settings is limited. Here, we conducted a prospective multi-institutional observational study to evaluate clinical outcomes of BRT in patients with LA-SCCHN., Methods: We analyzed real-world data of all patients who underwent BRT from 2013 to 2016. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were 1-year locoregional PFS (LPFS), treatment completion rate (TCR), and adverse events (AEs)., Results: A total of 171 patients with a minimum 1-year follow-up were analyzed. Median age was 67 (36-85) years, and 37 patients (21.6%) were aged 75 years or older. 1-year PFS and LPFS were 51.5 and 56.1%, respectively. N stage (p = 0.049) was significantly associated with PFS. TCR was 77.2%. Cetuximab was definitively discontinued in 30 patients (17.5%), in 15 cases due to severe mucositis. N stage, T stage, and comorbidity were significantly associated with TCR. Major AEs of grade 3 or higher were pharyngeal mucositis (48.5%), radiation dermatitis (45.6%), and oral mucositis (40.4%). Pneumonitis was observed in 12 patients (7.0%); 6 cases (3.5%) were grades 3-4 and 2 (1.2%) were grade 5., Conclusion: As a result of the large number of elderly patients in clinical practice,　toxicity reduced TCR. BRT-induced pneumonitis, which is sometimes fatal, was found to be more frequent than with chemotherapy plus cetuximab., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC)., Methods: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0., Results: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC., Conclusion: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III)., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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.)

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.

There are no established guidelines for managing older patients with head and neck cancer. Most clinical trials that define current standard therapy included few elderly patients. On the other hand, there is great variability in patients' comorbidities, physical functions, cognitive function, familial and financial background and values. The key point appears to be appropriate geriatric assessment, clarifying the patients' outcomes and a multidisciplinary team approach, including the treatment decision-making policy. Although these processes should be scientific in nature, the evidence for the treatment of elderly head and neck patients is very limited. This review summarizes the evidence available regarding the management of geriatric assessment, each treatment modality and the multidisciplinary team approach for older patients with head and neck cancers., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorexia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients., Methods: We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC., Results: A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to enhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome., Conclusion: Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients., (© 2022. The Author(s).)

Background: We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy., Methods: In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs)., Results: Overall, 256 patients received a median of 6.0 doses (range: 1-52) of nivolumab over a median duration of 72.5 days (range: 1-736). Median OS was 9.5 months [95% confidence interval (CI) 8.2-12.0] and median PFS was 2.1 months (95% CI 1.8-2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9-11.9) and 3.5 months (95% CI 2.3-5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis., Conclusions: Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up., (© 2021. The Author(s).)

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Radiation dermatitis is one of the most common acute toxicities induced by chemoradiation therapy (CRT) for head and neck cancer (HNC). The benefit of topical steroids in the management of radiation dermatitis is still unclear. This phase 3, multi-institutional, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of topical steroids for radiation dermatitis in patients with locally advanced HNC receiving CRT., Methods and Materials: Eligible patients were scheduled to receive bilateral neck irradiation (≥66 Gy) with concurrent cisplatin (≥200 mg/m 2 ) as definitive or postoperative CRT. Patients were randomly assigned to receive either topical steroid or placebo when grade 1radiation dermatitis was observed or the total radiation dose reached 30 Gy. Basic skin care including gentle washing and moistening in the head and neck region was performed in both groups. The primary endpoint was the frequency of grade ≥2 radiation dermatitis, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grading of radiation dermatitis was performed by independent central review using photographs taken weekly., Results: A total of 211 patients were enrolled (intention to treat: steroid 101 and placebo 102). The frequency of grade ≥2 radiation dermatitis was not significantly reduced with the steroid (73.3%; 95% confidence interval, 64.6%-81.9%) compared with the placebo (80.4%; 95% confidence interval, 72.7%-88.1%; P = .23), whereas the steroid significantly reduced the frequency of grade ≥3 radiation dermatitis (13.9% vs 25.5%; P = .034). No significant differences in adverse events, including local infection or compliance with CRT, were observed between the groups., Conclusions: Topical steroid may reduce the severity of radiation dermatitis in patients with HNC and thus may become an important therapeutic tool in the management of radiation dermatitis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We investigated whether prophylactic percutaneous endoscopic gastrostomy (PEG) is used effectively for patients treated with definitive concurrent chemoradiotherapy (CCRT) and the predictors of the need for PEG., Methods: 326 patients with laryngeal, oropharyngeal or hypopharyngeal cancers were retrospectively reviewed., Results: The PEG tube use group had more favorable results than the total parenteral nutrition and nasogastric tube groups in terms of rate of serum albumin loss, incidence of severe fever and aspiration pneumonia, CCRT completion rate and hospitalization period. However, it was inferior to oral intake. Analysis of the relative risk of requiring enteral or parenteral nutrition revealed that performance status (PS) 2, primary site (supraglottis, oropharynx, or hypopharynx), N3 disease, and cisplatin were predictors of the need for nutritional support., Conclusions: Prophylactic PEG is effective for patients treated with definitive CCRT and is especially required for patients with PS2 or oropharyngeal cancer.

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 aims of this study are to evaluate the efficacy and safety of first-line treatment with chemotherapy plus cetuximab in real-world patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) and to identify prognostic factors for overall survival (OS)., Methods: This is a prospective observation study involving 20 oncology institutions in Japan. Patients with RM-SCCHN treated with a first-line therapy consisting of cetuximab plus any chemotherapy regimen between December 2013 and February 2017 were enrolled. The primary objective of the study was 1-year OS. Secondary objectives included response rate and adverse events., Results: Of 120 patients recruited, 114 patients were analyzed. Median age was 64 years. Cetuximab in combination with platinum plus 5-FU (EXTREME regimen) was chosen in 86 patients (75.4%). The median OS was 12.4 months. A point estimate of the 1-year survival rate was 51.1%. Overall response rate was 26.3%. Grade 3 or worse adverse events included neutropenia (22.8%), hypokalemia (9.6%), acneiform rash (7.0%), pneumonitis (1.8%), and infusion-related reaction (0.9%). On multivariate analysis, regional lymph node metastasis, absence of intervention by dermatologists, lack of response to therapy, skin metastasis, and non-EXTREME regimen were identified as independent unfavorable prognostic factors for OS., Conclusion: The combination of cetuximab plus chemotherapy was tolerable and efficacious in patients with RM-SCCHN in a real-world setting. Clinical outcomes and prognostic factors extracted from this study provide a reference of the current clinical practice as well as for the future development of novel therapy in RM-SCCHN.

Background: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab., Methods: Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m 2 /day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m 2 , followed by 250 mg/m 2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR)., Results: Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%)., Conclusions: Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number: UMIN000015123.

Purpose : To predict local control / failure by a multiparametric approach using magnetic resonance (MR)-derived tumor morphological and functional parameters in pharynx squamous cell carcinoma (SCC) patients. Materials and Methods : Twenty-eight patients with oropharyngeal and hypopharyngeal SCCs were included in this study. Quantitative morphological parameters and intratumoral characteristics on T2-weighted images, tumor blood flow from pseudo-continuous arterial spin labeling, and tumor diffusion parameters of three diffusion models from multi-b-value diffusion-weighted imaging as well as patients' characteristics were analyzed. The patients were divided into local control / failure groups. Univariate and multiparametric analysis were performed for the patient group division. Results : The value of morphological parameter of 'sphericity' and intratumoral characteristic of 'homogeneity' was revealed respectively significant for the prediction of the local control status in univariate analysis. Higher diagnostic performance was obtained with the sensitivity of 0.8, specificity of 0.75, positive predictive value of 0.89, negative predictive value of 0.6 and accuracy of 0.79 by multiparametric diagnostic model compared to results in the univariate analysis. Conclusion : A multiparametric analysis with MR-derived quantitative parameters may be useful to predict local control in pharynx SCC patients. J. Med. Invest. 68 : 354-361, August, 2021.

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.)

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA-SCCHN., Methods: Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration-time curve = 1.5, PTX 80 mg/m 2 and Cmab with an initial dose of 400 mg/m 2 followed by 250 mg/m 2 for 8 weeks. Following IC, CDDP (20 mg/m 2 , 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%., Results: Thirty-five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m 2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment-related death was seen., Conclusions: PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA-SCCHN., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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.)

Background: Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment., Methods: We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015., Results: Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0-1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis., Conclusions: CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.

Background: Oral mucositis and body weight loss are the most critical conditions known to lead to the discontinuation of chemoradiotherapy for head and neck cancer. We investigated the effect of a nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)on body weight loss, oral mucositis, and the completion rate of chemoradiotherapy in patients with oropharyngeal and hypopharyngeal cancer., Patients and Methods: The study group comprised patients with oropharyngeal and hypopharyngeal cancer who were treated with concomitant cisplatin and 70 Gy of radiotherapy. These patients received 2 packs of Prosure®per day during chemoradiotherapy., Results: A total of 17 patients were included in this study. The reduction in body weight was significantly improved compared with that in the historical control group that did not receive Prosure®(7.3% vs 10.3%, p<0.01), and the rate of Grade 3-4 oral mucositis was significantly reduced for the patient groups that received Prosure®(CTCAE v3.0 GradeB3; 24% vs 58%, p<0.05). The completion rate of chemoradiotherapy was not significantly different between both groups(77% vs 60%, NS)., Conclusions: A nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)had effects on oral mucositis and body weight loss in head and neck cancer patients treated with chemoradiotherapy.

: TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated. Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of TRIM29 . Depletion of TRIM29 increased cancer cell migration and invasion; conversely, overexpression of TRIM29 suppressed these. Comprehensive proteomics and immunoprecipitation analyses identified keratins and keratin-interacting protein FAM83H as TRIM29 interactors. Knockdown of TRIM29 led to ectopic keratin localization of keratinocytes. In primary tumors, lower TRIM29 expression correlated with the altered expression of keratins. Our findings reveal an unexpected role for TRIM29 in regulating the distribution of keratins, as well as in the migration and invasion of SCC. They also suggest that the TRIM29-keratin axis could serve as a diagnostic and prognostic marker in stratified epithelial tumors and may provide a target for SCC therapeutics. SIGNIFICANCE: These findings identify TRIM29 as a novel diagnostic and prognostic marker in stratified epithelial tissues., (©2018 American Association for Cancer Research.)

Background: A fluorescent probe glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG), which becomes fluorescent after cleavage by dipeptidyl peptidase-IV (DPP-IV), has been reported to be useful for the detection of esophageal cancer. Thus, we investigated whether head and neck squamous cell carcinoma (HNSCC) can be detected by spraying EP-HMRG., Methods: Fluorescence imaging of 17 cases of HNSCCs resected using endoscopic or surgical resection was performed ex vivo after spraying EP-HMRG, and then the fluorescence intensity of the tumors and normal mucosa were measured., Results: Iodine-voiding lesions became fluorescent within a few minutes after the application of EP-HMRG in 12 resected tumors without a history of radiotherapy but this was not observed in the normal mucosa. Fluorescence intensity in tumor lesions was significantly higher than normal lesions. However, 5 other tumors that developed after radiotherapy did not have sufficient contrast against normal mucosa., Conclusion: Fluorescence imaging with EP-HMRG would be useful for rapid detection of superficial HNSCC without a history of radiotherapy., (© 2018 Wiley Periodicals, Inc.)

Purpose: To evaluate the diagnostic power of hybrid intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model parameters in pretreatment for the prediction of future distant metastasis in head and neck squamous cell carcinoma (HNSCC) patients., Materials and Methods: We retrospectively evaluated 49 HNSCC patients who underwent curative chemoradiation therapy. Diffusion-weighted image (DWI) acquired by single-shot spin-echo echo-planar imaging with 12 b-values (0-2000) was performed in all patients before any treatment. We calculated the IVIM-DKI parameters and the conventional apparent diffusion coefficient (ADC) in the ROI placed on the primary lesion. The presence of future distant metastasis was determined by histological findings or clinical follow-up., Results: A univariate analysis revealed significant differences between the patients with distant metastasis and those without in slow diffusion coefficient (D) and kurtosis value (K). Highest diagnostic accuracy was obtained by the D value. In addition, a multivariate analysis revealed that the D value was an independent predictor of future distant metastasis., Conclusion: The D and K values obtained by this hybrid IVIM-DKI model can be one of the diagnostic tools for the prediction of future distant metastasis in HNSCC patients.

Objective: The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification., Methods: 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members., Results: Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function., Conclusions: In this article, we described most relevant guidelines and CQs for the diagnosis and treatment of head and neck cancer in Japan. These guidelines are not intended to govern therapies that are not shown here, but rather aim to be used as a guide in searching for the most appropriate treatment for individual patient., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: A recent study identified a survival benefit with prophylactic neck dissection (ND) at the time of primary surgery as compared with watchful waiting followed by therapeutic neck dissection for nodal relapse, in patients with cN0 oral squamous cell carcinoma (OSCC). Alternative management of cN0 neck cancer is recommended to minimize the adverse effects of ND, indicating the need for sentinel node biopsy (SNB) and limited neck dissection. We conducted a multicenter Phase II study to examine the feasibility of SNB for clinically N0 OSCC., Methods: Previously untreated N0 OSCC patients (n=57) with clinical late-T2 or T3 tumors were enrolled across 10 institutions. SNB navigated with multislice frozen section analysis of sentinel nodes (SNs) and SNB supported sentinel node lymphatic basin dissection (SN basin dissection) were performed in a one-stage procedure. The endpoint was to investigate the rate of false-negative metastases after SN basin dissection and SNB alone., Results: Most tumors were late-T2 lesions (n=50; 87.7%). SNs were identified in all patients. A total of 196 SNs were detected. Among these SNs, 35 (17.8%) were positive for metastasis (9 in level I, 12 in level II, 12 in level III, 1 in level V and 2 in the contralateral region of the neck). The false-negative rate of SNB supported by SN basin dissection and SNB alone was 4.5% and 9.1%, respectively. The concordance of the SN status in intraoperative frozen sections with the permanent histopathology was 97.4% (191/196). The sensitivity and specificity of intraoperative pathological evaluation were 85.7% (30/35) and 100% (30/30), respectively. The 3-year overall survival (OS) and disease-free survival was 89.5% and 82.5%, respectively. The OS of SN-negative patients was significantly longer than that of SN-positive patients (P=0.047)., Conclusion: The current study verified that SN basin dissection was a useful back-up procedure for SNB performed as a one-stage procedure, showing a low false-negative rate. SNB alone is an appropriate staging method for patients with clinical N0 staging, and a reliable procedure to determine the appropriate levels for neck dissection., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We assessed parameters of advanced diffusion weighted imaging (DWI) models for the prediction of the tumor growth rate in 55 head and neck squamous cell carcinoma (HNSCC) patients. The DWI acquisition used single-shot spin-echo echo-planar imaging with 12 b-values (0-2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, tri-exponential, stretched exponential and diffusion kurtosis imaging models. We directly measured the tumor growth rate from two sets of different-date imaging data. We divided the patients into a discovery group (n = 40) and validation group (n = 15) based on their MR acquisition dates. In the discovery group, we performed univariate and multivariate regression analyses to establish the multiple regression equation for the prediction of the tumor growth rate using diffusion parameters. The equation obtained with the discovery group was applied to the validation group for the confirmation of the equation's accuracy. After the univariate and multivariate regression analyses in the discovery-group patients, the estimated tumor growth rate equation was established by using the significant parameters of intermediate diffusion coefficient D2 and slow diffusion coefficient D3 obtained by the tri-exponential model. The discovery group's correlation coefficient between the estimated and directly measured tumor growth rates was 0.74. In the validation group, the correlation coefficient (r = 0.66) and intra-class correlation coefficient (0.65) between the estimated and directly measured tumor growth rates were respectively good. In conclusion, advanced DWI model parameters can be a predictor for determining HNSCC patients' tumor growth rate.

Purpose: To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy., Materials and Methods: We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0-1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up., Results: Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (D s ) obtained by the SDM. The multivariate analysis revealed that the D s and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour., Conclusion: DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: We assessed advanced fitting models of diffusion weighted imaging (DWI) in head/neck squamous cell carcinoma (HNSCC) patients to determine the best goodness of fit and correlations among diffusion parameters. We compared these results with those of dynamic contrast-enhanced (DCE) perfusion parameters., Materials and Methods: We retrospectively evaluated 32 HNSCC patients (12 sinonasal, 20 pharynx/oral cavity). The DWI acquisition used single-shot spin-echo echo-planar imaging (EPI) with 12 b-values (0-2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, and tri-exponential models, stretched exponential model (SEM) and diffusion kurtosis imaging (DKI) models. We compared each model's goodness of fit using the residual sum of squares (RSS), Akaike Information Criterion (AIC) and Bayesian information criterion (BIC) value. We determined the correlation between each pair of DWI parameters and between each DWI parameter and DCE perfusion parameter., Results: The tri-exponential fit's RSS, AIC and BIC values were significantly smaller than those for bi-exponential fit. The RSS, AIC and BIC values of the SEM fit and DKI fit were significantly smaller than mono-exponential model. Significant correlations were observed in 30 pairs (sinonasal cavity) and 31 (sinonasal cavity group) among 91 DWI parameter combinations. Significant correlations were also observed in nine pairs (both sinonasal cavity and pharynx/oral cavity group) among 64 DWI/DCE perfusion parameter pairs, in particular, high positive correlations between the tri-exponential model's intermediate diffusion fraction (f 2 ) and the volume of the extracellular extravascular space per unit volume of tissue (v e ) were observed in both patient groups., Conclusion: We identified several correlations between DWI parameters by advanced fitting models and correlations between DWI and DCE parameters. These will help determine HNSCC patients' detailed tissue structures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers., Methods: The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated., Results: Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor., Conclusion: Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247-253, 2017., (© 2016 Wiley Periodicals, Inc.)

Objective: To determine the relationship between tumor glucose metabolism and tumor blood flow (TBF) in head and neck squamous cell carcinoma (HNSCC)., Methods: We retrospectively analyzed 57 HNSCC patients. Tumor glucose metabolism was assessed by maximum and mean standardized uptake values (SUVmax and SUVmean) obtained by 18F-fluorodeoxyglucose positron-emission tomography. TBF values were obtained by arterial spin labeling with 3-tesla MRI. The correlations between both SUVs and TBF were assessed in the total series and among patients divided by T-stage (T1-T3 and T4 groups) and tumor location (pharynx/oral cavity and sinonasal cavity groups). Pearson's correlation coefficients were calculated for significant correlations., Results: Significant correlations were detected: a negative correlation in the advanced T-stage group (TBF and SUV max: r, -0.61, SUVmean: r, -0.62), a positive correlation in the non-advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, 0.70, SUVmean: r, 0.73), a negative correlation in the advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, -0.62, SUVmean: r, -0.65), and a negative correlation in the advanced T-stage sinonasal cavity group (TBF and SUVmax: r, -0.61, SUVmean: r, -0.65)., Conclusion: Significant correlations between glucose uptake and TBF in HNSCC were revealed by the division of T-stage and tumor location., Competing Interests: The authors have declared that no competing interests exist.

We sought to evaluate the efficacy and feasibility of superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed. The ascending pharyngeal artery was targeted for the treatment of RPLN metastasis in 9 patients. The median total dose of cisplatin was 26.6 mg/m(2) (mean 31.5 mg/m(2), range 11.7-87.9 mg/m(2)). In the remaining patient, the RPLN was supplied by the ascending palatine artery. As grade 3 and 4 adverse effects, leukopenia was observed in three, mucositis in four and nausea in one patient. No neurological complications were observed in any patients. Metastatic RPLNs were evaluated as a complete response in all patients. There was no recurrence of RPLN metastasis in any patients. Four patients remain alive without any evidence of disease and six patients died of disease. The 5-year overall survival rate was 50 %. We have shown that superselective intra-arterial cisplatin infusion for RPLNs was a feasible and effective approach for HNSCC patients with RPLN metastasis.

Background: Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples., Methods: gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured., Results: All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application., Conclusions: Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.