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Background: In recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), local therapy (LT) such as surgery or radiotherapy can be treatment options for improved survival or quality of life. To date, however, few reports have addressed the efficacy of LT for sites of disease progression after immune checkpoint inhibitors, including other cancers., Methods: We conducted a retrospective analysis of patients with R/M SCCHN originating from the oral cavity, oropharynx, hypopharynx, and larynx and treated with nivolumab. We extracted patients undergoing salvage LT or palliative radiotherapy (RT) to the selected progressive lesion at any time after initiation of nivolumab., Results: Twenty-four patients received LT. Salvage LT was performed in 9 (37.5%) patients, including surgery and definitive RT in 5 and 4 patients, respectively. Palliative RT was performed in 15 (62.5%) patients. LT was provided in 10 (41.7%) patients for oligoprogressive disease. Twelve (50.0%) patients received subsequent systemic therapy immediately after LT. Classification based on patient treatment divided the population into four subgroups with different prognoses (salvage LT followed by subsequent systemic therapy [n = 3], salvage LT alone [n = 6], palliative RT followed by subsequent systemic therapy [n = 9], and palliative RT alone [n = 6]). Median OS in this order was 24.5, 9.0, 7.3, and 2.4 months (p = 0.001). All patients in the salvage LT followed by subsequent systemic therapy group continued nivolumab., Conclusion: In R/M SCCHN patients who have received nivolumab, salvage LT for the selected progressive lesion with continuation of nivolumab potentially provides an excellent survival prognosis., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

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.)

Background: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015., Methods: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities., Results: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less)., Conclusions: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem., (© 2022. The Author(s).)

Objectives: Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers., Methods: Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy., Results: A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers., Conclusions: This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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: Prediction of the invasive depth is the objective of endoscopic observation for digestive cancer. In superficial esophageal cancer, a close relationship between microvascular patterns observed by magnifying endoscopy with narrow-band imaging (M-NBI) and pathological depth of invasion is well known. The ability of M-NBI to predict the invasion depth in superficial pharyngeal squamous cell carcinoma (SPSCC) has been seldom evaluated. This study aimed to clarify the relationship between the microvasculature patterns and pathological depth in SPSCC., Methods: SPSCC lesions evaluated with M-NBI followed by endoscopic resection were analyzed between April 2010 and March 2017. Endoscopic images were classified as microvasculature tumor types B1, B2, and B3 according to the Japan Esophageal Society classification. The pathological depth of invasion was described as either squamous cell carcinoma in situ (Tis) or invasive subepithelial cancer, and the tumor thickness of all lesions was examined. Data were analyzed using the unpaired t, χ 2 , or Mann-Whitney U test., Results: Type B1 and type B2/B3 (35/3) microvessels were found in 180 lesions (82%) and 39 (18%), respectively. Of the flat lesions, 115 (83%) were classified as Tis and 23 (17%) as subepithelial cancer. Positive and negative predictive values of the B1 vessels were 77% and 82%, respectively. Additional analysis showed that the positive predictive value of the B1 vessels for the flat-type lesions was 87%; the negative predictive value for the elevated lesions was 93%., Conclusions: Microvascular patterns observed by M-NBI are an important factor in predicting the pathological depth of invasion.

Background: In treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN), the use of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by high-dose cisplatin chemoradiotherapy (CRT) carries concerns over toxicity. We evaluated the feasibility of TPF as induction chemotherapy (IC) to Japanese patients and the tolerability of CRT with fractionated administration of cisplatin after IC., Methods: Patients with unresectable stage III, IV SCCHN received IC followed by CRT. IC consisted of three 3-week cycles of docetaxel 70-75 mg/m 2 on day 1, cisplatin 70-75 mg/m 2 on day 1, and 5-fluorouracil 750 mg/m 2 on days 1-5. Patients subsequently received IMRT concomitant with fractionated administration of cisplatin (20 mg/m 2 ) on days 1-4, repeated every 3 weeks. The primary endpoint was completion of the three cycles of IC., Results: Forty-eight patients were enrolled. The IC treatment completion rate was 85%. Grade 3-4 toxicities of TPF were neutropenia (79%) and febrile neutropenia (15%). Thirty-eight patients (79%) achieved a response after IC. Forty patients subsequently underwent CRT. Thirty-three patients (83%) completed the planned cycles of fractionated administration of cisplatin, but seven (18%) did not. Grade 3-4 toxicities during CRT were neutropenia (23%), mucositis (53%), and dysphagia (33%). With a median follow-up of 36.1 months, 3-year overall survival was 65%., Conclusion: TPF IC is feasible and CRT with fractionated administration of cisplatin after IC is tolerable. IC followed by CRT appears to be a useful and safe sequential treatment. (Trial registration no. UMIN000024686).

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.

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.)

Background: S-1 is a combination of tegafur [metabolized to 5-fluorouracil (5-FU)] with the modulators gimeracil (5-chloro-2,4-dihydroxypyridine) and oteracil potassium. 5-Chloro-2,4-dihydroxypyridine maintains plasma 5-FU concentrations by inhibiting dihydropyrimidine dehydrogenase, a pyrimidine catabolism enzyme that degrades 5-FU. As 50% of 5-chloro-2,4-dihydroxypyridine is excreted in urine, renal insufficiency may increase its blood level, increasing 5-FU concentrations. We investigated whether special dose modification is needed in the presence of renal insufficiency., Objective: We compared steady state pharmacokinetics of 5-FU for the initial S-1 dose and reduced doses in patients with head and neck cancer requiring dose reduction due to renal and non-renal toxicities., Methods: Chemoradiotherapy with S-1 and cisplatin was administered every 5 weeks for two courses with a radiation dose totaling 70 Gy over 33-35 fractions. Two additional courses of adjuvant chemotherapy were administered in the case of an objective response. The S-1 and/or cisplatin dose was reduced in response to renal, hematologic or other toxicities. The primary endpoint was the change in area under the plasma concentration-versus-time curve from time 0-10 hours (5-FU AUCss 0-10) between the initial and reduced S-1 doses., Results: Although the mean 5-FU levels in patients with non-renal toxicities significantly decreased between the full and reduced dose, the full-dose and reduced-dose mean maximum 5-FU plasma concentrations at steady state (Css max) and AUCss 0-10 in patients with renal insufficiency were similar., Conclusions: Standard S-1 dose reduction for renal toxicity did not result in a significant decrease in 5-FU levels at steady state. A greater reduction to lower plasma 5-chloro-2,4-dihydroxypyridine may be necessary in patients with renal insufficiency., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the feasibility of postoperative intensity-modulated radiotherapy for head and neck cancer by investigating the patterns of failure after this therapy., Methods: A retrospective chart review was performed., Results: Between March 2006 and December 2013, 122 consecutive patients with head and neck squamous cell carcinoma were treated by surgery followed by postoperative intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59 (48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The median follow-up period of the surviving patients was 54 months (range, 25-115). Concurrent chemotherapy was administered in 76 patients (62%). The median prescribed radiation dose was 66 Gy. The 3-year overall survival, progression-free survival, distant metastasis free survival and loco-regional control rates were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed loco-regional recurrence as the initial recurrence, including in-field recurrence in 26 patients, marginal recurrence in five patients and out-field recurrence in seven patients. Of the five patients with marginal recurrence, four have had two or more surgeries before the intensity-modulated radiotherapy and three had oral cavity cancer. Severe adverse events were not frequent, occurring at a frequency of <5%, except for mucositis. No severe toxicities associated with the flap reconstruction were observed either., Conclusion: Postoperative intensity-modulated radiotherapy appears to be effective and feasible for patients with head and neck squamous cell carcinoma., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: We conducted a retrospective analysis to evaluate the efficacy and safety of cetuximab plus radiation with or without prophylactic percutaneous endoscopic gastrectomy in locally advanced squamous cell carcinoma of the head and neck patients who were not suitable to receive platinum., Patients and Methods: We reviewed the case records of 27 locally advanced squamous cell carcinoma of the head and neck patients treated with cetuximab plus radiation (RT) between January 2013 and July 2014. No patient was able to receive platinum because of renal dysfunction or other contraindications. Patients received an initial dose of cetuximab of 400 mg/m(2), followed by weekly doses of 250 mg/m(2). The total dose of radiotherapy was 66-70 Gy in five daily fractions of 2-2.12 Gy per week., Results: The incidence of leukopenia was significantly higher in patients without percutaneous endoscopic gastrectomy placement than in those with (67.5% vs. 7%, P = 0.002). The incidence of Grade 3 or 4 mucositis tended to be higher in patients without percutaneous endoscopic gastrectomy placement than in those with (83% vs. 47%, P = 0.058). Five of twelve patients without percutaneous endoscopic gastrectomy placement required interruption of treatment. More patients without percutaneous endoscopic gastrectomy placement had significantly >10% weight loss than patients with (75% vs. 27%, P = 0.013). The overall response rate was 56% in all patients. The 1-year progression-free survival rate was 30.6% in all patients., Conclusions: Prophylactic percutaneous endoscopic gastrectomy-feeding tube placement could reduce the incidence of severe toxicities, including mucositis and weight loss, and avoid RT interruption. These results require confirmation in a larger study., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Radiation dermatitis is one of the most common acute toxicities of both radiotherapy and chemoradiotherapy. Many clinical trials have evaluated the level of toxicity using the Common Terminology Criteria for Adverse Events ver. 4.03. This criterion accounts for severity in a single sentence only, and no visual classification guide has been available. Thus, there is a risk of subjective interpretation by the individual investigator. This contrasts with the situation with hematologic toxicities, which can be interpreted objectively. The aim of this prospective picture collection study was to develop a grading tool for use in establishing the severity of radiation dermatitis in clinical trials. A total of 118 patients who were scheduled to receive definitive or postoperative radiotherapy or chemoradiotherapy were enrolled from the four participating cancer centers. All researchers in our group used the same model of camera under the same shooting conditions to maintain consistent photographic quality. In all, 1600 photographs were collected. Of these, 100 photographs qualified for the first round of selection and were then graded by six experts, basically in accordance with the CTCAE ver. 4.03 (JCOG ver. in Japanese). After further study, 38 photographs were selected as representing typical models for Grade 1-4 radiation dermatitis; the radiation dermatitis grading atlas was produced from these photographs. The atlas will play a major role in ensuring that the dermatitis rating system is consistent between the institutions participating in trials. We hope that this will contribute to improving the quality of clinical trials, and also to improving the level of routine clinical practice., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Calibrating the dose per monitor unit (DMU) for individual patients is important to deliver the prescribed dose in radiation therapy. We have developed a DMU calculation method combining measurement data and calculation with a simplified Monte Carlo method for the double scattering system in proton beam therapy at the National Cancer Center Hospital East in Japan. The DMU calculation method determines the clinical DMU by the multiplication of three factors: a beam spreading device factor FBSD, a patient-specific device factor FPSD, and a field-size correction factor FFS(A). We compared the calculated and the measured DMU for 75 dose fields in clinical cases. The calculated DMUs were in agreement with measurements in ± 1.5% for all of 25 fields in prostate cancer cases, and in ± 3% for 94% of 50 fields in head and neck (H&N) and lung cancer cases, including irregular shape fields and small fields. Although the FBSD in the DMU calculations is dominant as expected, we found that the patient-specific device factor and field-size correction also contribute significantly to the calculated DMU. This DMU calculation method will be able to substitute the conventional DMU measurement for the majority of clinical cases with a reasonable calculation time required for clinical use.

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.)

Objective: We evaluated the clinical characteristics of a Dermatitis Control Program based on a moderately absorbent surgical pad for head and neck cancer patients undergoing (chemo)radiotherapy., Methods: We retrospectively reviewed patients who underwent definitive radiotherapy or post-operative radiotherapy and were treated during radiotherapy with a Dermatitis Control Program using a moderately absorbent surgical pad from May 2011 through April 2012. The main protocol was the 'Dermatitis Control Program', a systematic program which consists of a three-step ladder. When radiation dermatitis reached Grade 2, the irradiated area was covered with a moderately absorbent surgical pad. All outpatients and their families were instructed on how to cover and moisten the irradiated area. Radiation dermatitis was evaluated by physicians or nurses at an outpatient clinic and reviewed from photographs., Results: A total of 116 head and neck cancer patients were treated by definitive or adjuvant (chemo)radiotherapy in our hospital from May 2011 through April 2012. Of these, 85 patients managed their dermatitis using a new device and they were reviewed. Fifty-five patients received chemoradiotherapy, of whom 22 received induction chemotherapy before chemoradiotherapy. Median radiation dose at the onset of Grade 2 dermatitis was 60.0 Gy (range 40-71.2 Gy). Median time to recover from the end of radiotherapy was 10.5 days (range 0-25 days). The rate of recovery from Grade 2 dermatitis within 2 weeks after the end of radiotherapy was 89.4%. The rate of Grade 3 dermatitis was 7.1, with 6.7% in radiotherapy and 7.3% in chemoradiotherapy., Conclusions: This study suggests that the DeCoP protocol with a moderately absorbent surgical pad might be useful for the treatment of radiation dermatitis in clinical practice., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Accelerated fractionation radiotherapy (RT) was administered in an attempt to improve the local control rates in patients with T1/T2 N0 glottic cancer., Methods: Medical charts of 148 consecutive patients who had undergone RT using 2.4 Gray (Gy) once-daily fractionation between July 1999 and April 2007 were reviewed., Results: Of 104 patients with T1 disease treated by RT, 82 received 60 Gy/25 fractions, and the remaining 22 with large tumor volumes and/or slow response to RT received 64.8 Gy/27 fractions. All 44 patients with T2 disease received 64.8 Gy/27 fractions. The 5-year local control and overall survival (OS) rates were 93% and 96%, respectively, in patients with T1 disease, and 77% and 91%, respectively, in patients with T2 disease. No severe acute toxicities were observed, although 2 patients (1%) developed severe late toxicity., Conclusion: Accelerated RT for early glottic cancer is feasible, with encouraging local control rates., (© 2014 Wiley Periodicals, Inc.)

Objective: Post-operative concurrent chemoradiotherapy significantly improves the rates of locoregional control and disease-free survival in high-risk patients but has significant adverse effects. Percutaneous endoscopic gastrostomy and opioid-based pain control increase treatment completion rates but can result in dysphagia., Methods: The rate and duration of use of prophylactically placed percutaneous endoscopic gastrostomies were evaluated in 43 patients who underwent post-operative radiotherapy or chemoradiotherapy from April 2007 through March 2010. All patients completed treatment and received 60 Gy or more of radiotherapy., Results: Thirty four of 43 patients (79.1%) used percutaneous endoscopic gastrostomies, which could later be removed in 25 of 34 patients. The median period of use was 108 days. Only one disease-free patient was permanently dependent on percutaneous endoscopic gastrostomy feeding. The frequency of percutaneous endoscopic gastrostomy use among patients with oral, oropharyngeal and hypopharyngeal cancer was 91.7, 100 and 54.5%, respectively., Conclusions: Prolonged percutaneous endoscopic gastrostomy use is not required in patients receiving post-operative chemoradiotherapy and will not lead to dysphagia., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Accurate dose delivery is essential for the success of intensity-modulated radiation therapy (IMRT) for patients with head-and-neck (HN) cancer. Reproducibility of IMRT dose delivery to HN regions can be critically influenced by treatment-related changes in body contours. Moreover, some set-up margins may not be adaptable to positional uncertainties of HN structures at every treatment. To obtain evidence for appropriate set-up margins in various head and neck areas, we prospectively evaluated positional deviation (δ values) of four bony landmarks (i.e. the clivus and occipital protuberance for the head region, and the mental protuberance and C5 for the neck region) using megavoltage cone-beam computed tomography during a treatment course. Over 800 δ values were analyzed in each translational direction. Positional uncertainties for HN cancer patients undergoing IMRT were evaluated relative to the body mass index. Low positional accuracy was observed for the neck region compared with the head region. For the head region, most of the δ was distributed within ± 5 mm, and use of the current set-up margin was appropriate. However, the δ values for the neck region were within ± 8 mm. Especially for overweight patients, a few millimeters needed to be added to give an adequate set-up margin. For accurate dose delivery to targets and to avoid excess exposure to normal tissues, we recommend that the positional verification process be performed before every treatment.

Background: We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck., Methods: Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m(2) initial dose then 250 mg/m(2) weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2-7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule)., Results: Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85-100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60-95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each)., Conclusions: Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck.

Background: The aim of this multi-center phase II study was to clarify the clinical benefit of an opioid-based pain control program for head and neck cancer patients during chemoradiotherapy., Patients and Methods: Head and neck cancer patients who were to receive definitive or postoperative chemoradiotherapy were enrolled. The opioid-based pain control program consisted of a three-step ladder, with basic regimens of: The primary endpoint of this study was compliance with radiotherapy., Results: A total of 101 patients from 10 institutions were registered between February 2008 and May 2009 and included in the analysis. The major combination chemotherapy regimen was cisplatin alone (76%). The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13% (13/101, 90% confidence interval: 9.9-16.5%). Median maximum quantity of morphine used per day was 35 mg (range 0-150 mg)., Conclusions: Use of a systematic pain control program may improve compliance with CRT., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A Phase II study was started in Japan to evaluate the efficacy and safety of concurrent chemoradiotherapy with S-1 plus cisplatin in patients with unresectable locally advanced squamous cell carcinoma of the head and neck. This study began in July 2008, and a total of 45 patients will be accrued from 13 institutions within 2 years. The primary endpoint is the clinical complete remission rate. The secondary endpoints are local progression-free survival, overall survival, progression-free survival, time to treatment failure, proportion of patients who achieve nutritional support-free survival and adverse events.

Background: The aim of this study was to evaluate the impact of dysadherin and E-cadherin expression on the clinical outcomes, including the treatment outcomes and recurrence pattern, in patients with head and neck cancer., Patients and Methods: Tumor specimens were obtained from 48 head and neck cancer patients who were treated by radiation therapy and the specimens were immunohistochemically stained for dysadherin and E-cadherin. The expressions were graded according to the percentage area occupied by cancer cells showing positive staining for E-cadherin and dysadherin as follows: grade 0, less than 10%; grade 1, 10-50%; grade 2, more than 50%. The correlations between the expression of E-cadherin and dysadherin and the clinical outcomes, including the treatment outcomes and recurrence pattern, were analyzed., Results: The complete response (CR) rate in the patients with a dysadherin expression grade of 0 or 1 was 70% and that in the patients with dysadherin expression grade of 2 was 38%; the difference was significant (p < 0.05). Regarding the pattern of recurrence, the expression grade of dysadherin or E-cadherin alone was not correlated with the recurrence pattern; however, patients with a difference in the expression grade between dysadherin and E-cadherin (Dys-Ecad value) of 1 or 2 showed a significantly higher rate of lymph node and/or distant metastasis (55%) as compared with those with a Dys-Ecad value of < 1 (22%) (p < 0.05)., Conclusion: Dysadherin and E-cadherin expression might serve as useful prognostic factors in patients with head and neck cancer treated by definitive radiation therapy.

Objective: To examine the feasibility and efficacy of concurrent weekly docetaxel and radiation therapy as a definitive treatment for head and neck cancer (HNC)., Methods: Thirty-two patients with primary HNC, who were treated with concurrent weekly docetaxel and radiation therapy, were analysed. The distribution of the disease stage was as follows: Stage II, 18 patients; Stage III, 3 patients; Stage IVA, 7 patients; Stage IVB, 3 patients; the patient of cervical lymph node metastasis with unknown primary tumor was not assessable. The average total dose of radiotherapy was 67.5 Gy. Docetaxel (10 mg/m(2), intravenously, once a week) was given to all patients up to four cycles, and cisplatin (6 mg/m(2), intravenously, five times a week) was also administered to all patients for up to 3 weeks from the beginning of the radiation therapy., Results: Only in two patients did the radiotherapy need to be temporarily interrupted due to the development of acute mucositis. Grade 3 toxicity was observed in six patients. Grade 4 acute mucositis was seen in one patient. The response rate was 100%, and complete response (CR) was observed in 30 patients (94%). At the time of the analysis, the 2 year local control and relapse-free rates in the 30 patients showing CR were 90 and 76%, respectively., Conclusions: Concurrent weekly docetaxel and radiation therapy did not affect the compliance of the patients for the radiation therapy, indicating that the acute toxicities were within acceptable limits.