A meta-analysis showed that chemoradiotherapy (CCRT) improved survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). CCRT has become widely used in treating such patients. The purpose of CCRT in the treatment of resectable HNSCC is to improve survival while preserving organs and functions, and so CCRT is a potential alternative to surgery. However, problems regarding CCRT were revealed such as severe dysphasia and difficulty of salvage surgery.
Recently, induction chemotherapy has attracted attention again, the purpose of which is to predict the response of subsequent CCRT or to improve outcomes. Moreover, chemotherapy is concurrently used with postoperative radiotherapy or definitively used for recurrent or metastatic HNSCC.
In this article, we review the current state of chemotherapy for HNSCC and consider the problems in Japan.

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In western countries, the development of new drugs including molecular targeted agents for head and neck cancer patients is very active, whereas it remains difficult in Japan. In order to catch up with western countries, we need education on EBM, medical oncology, medical ethics, medical statistics and clinical trials. We also need infrastructure development of clinical trial groups, support systems for clinical trials and global development teams. After we solve these challenges, we will be able to shorten the phenomenon known as “drug lag”.
The Japan Society for Head and Neck Cancer is one of the most important academic societies for head and neck cancer in Japan and I hope to contribute to this society through education and infrastructure development of head and neck oncology research.

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Recently, the development of molecular-targeted drugs for the treatment of head and neck cancer has progressed, but there are no drugs available for head and neck cancer in Japan. This time difference is known as “drug lag”.
This article discusses how to reduce the drug lag for head and neck cancer. In head and neck oncology in Japan, there are many problems including a small number of physicians who are familiar with chemotherapy for head and neck cancer, poor infrastructure for clinical trials and great differences in treatment strategy among institutions. From personal experience in studying medical oncology at the National Cancer Center Hospital East for two years, I am convinced that the first step to reduce the drug lag is to increase the number of physicians who are familiar with chemotherapy for head and neck cancer.

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In order to present good clinical data with conclusive evidence, a multi-institutional cooperative clinical study is essential. In this paper we report on how to conduct a multi-institutional clinical study in Japan. When constructing a study group of investigator-initiated clinical trials, standardization of diagnosis, indication, and treatment is very important. Support systems for clinical trials at Tokai University are presented and problems in cooperation among multiple institutes are discussed. Preparation of the infrastructure, motivation of researchers, and funding are the most important factors.

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The data of 14 patients with squamous cell carcinoma of the maxillary sinus who were admitted to our hospital and received radiation therapy and concurrent superselective intraarterial infusion therapy between 1998 and 2008 were analyzed to determine the effect of the primary treatment and the adverse events. The subjects were between 43 and 79 years old (median, 61 years old), and there were 10 male and 4 female patients.
Superselective intraarterial infusion therapy was administered using the Seldinger method, and CDDP was administered by intraarterial infusion at a total of 200 mg/m². 5-FU was systemically administered by intravenous infusion at the dose of 800 mg/m² from day 2 to day 5. In addition, radiation therapy was given concurrently, beginning on day 2. At 4 weeks after completion of the scheduled radiation therapy combined with superselective intraarterial infusion therapy, the treatment effect was judged based on macroscopic, radiological and histopathological findings. The response rates to the primary treatment were as follows: 57.1%, CR (8 patients) and 42.9%, PR (6 patients). Thus, the overall response rate was 100%. As for the adverse events, while grade 4 cerebral infarction occurred in one patient, all of the other adverse events were reversible and not serious. The safety of the treatment was therefore considered to be acceptable. We are planning to investigate the long-term outcomes in a future study.

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Recently, superselective intra-arterial chemotherapy concurrent with radiotherapy has become popular in advanced head and neck carcinoma treatment. Twenty patients with advanced oral cancers were treated by radiation (66 Gy) and chemotherapy with superselective intra-arterial docetaxel (40 mg/mm²) - nedaplatin (80 mg/mm²) infusion between 2003 and 2009. Complete response in the primary and regional cervical region was obtained in 17 (85%) out of the 20 patients. Five-year survival rate was 74.1% and major adverse effects were leukopenia and mucositis. Five patients (25%) developed distant metastasis post-treatment.
Intra-arterial docetaxel-nedaplatin infusion concurrent with radiotherapy is an effective treatment for advanced oral cancers but severe complications and distant metastasis are problems that need to be solved.

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We evaluated patients with oral tongue cancer suffering from recurrence, which develops in the intervening area between the primary site and the neck. Lesions in the area around the greater cornu of the hyoid bone (‘para-hyoid’ area) involve the hypoglossal nerve and the root of the lingual artery and often extend to the parapharyngeal space, resulting in treatment failure and death. This area is beyond the limits of neck dissection. We assume that metastases in occult lymph nodes along the lingual artery might be responsible for such lesions, though the clinical importance of these small nodes in cancer therapy has been underestimated so far. Once a para-hyoid lesion becomes clinically evident, salvage may appear to be difficult even with radical surgery using a microvascular free-tissue flap. We believe that a dissection of occult nodes along the lingual artery, which correspond to the draining course of the lateral lingual nodes, should be included intraoperatively in any type of neck dissection (elective or therapeutic) for patients with oral tongue cancer. This could be the key to improving the regional control rate of patients with small oral tongue cancer.

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Background: We have previously proposed the CAT classification system, a simple and clear-cut system for classifying segmental mandibular defects after oncological surgery: “C” refers to the loss of the condylar head of the mandible, “A” the mandibular angle and “T” the mental tubercle. Here, we report a statistical and mathematical taxonomical study on the validity and utility of the classification system.
Methods: Data were collected from 17 medical institutions in Japan on 259 patients who had undergone surgical ablation and simultaneous microsurgical oromandibular reconstruction (osteocutaneous free flap or soft tissue free flap with reconstruction-plate) attributed to head and neck cancer. The mandibular defects were classified according to the CAT system and the two commonly used systems HCL and Urken, and the validity and utility of the CAT system were tested as follows: 1) the tendency among the numbers of the three reference points of the CAT system (C, A and T) and the esthetic outcome of each patient were analyzed by Jonckheere's trend test, 2) each of the classified patterns of the three systems was analyzed by cluster analysis based on the esthetic results using Ward's method.
Results: 1) There was a statistically significant trend among the numbers of the three reference points in the CAT system and the esthetic outcome, 2) each of the grouped clusters in the CAT system was clinically explicable and demonstrated a significant difference in the esthetic outcome; the two other systems did not yield such information.
Conclusion: The CAT classification system is valid and useful for oncological segmental mandibular defects.

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A fibrosarcoma is a malignant mesenchymal tumor of fibroblasts that seldom affects the mandible and less often in children. We describe a case of fibrosarcoma in the right mandible of an 8-year-old boy. He was referred to our Oral-Maxillofacial Surgery Division because of a pressure pain in the molar gingiva of the right mandibular body. Panoramic tomography showed a relatively well-defined, unilocular, radiolucent area at the apical region of the second deciduous molar of the right mandible. We suspected an odontogenic tumor/cyst, and after administering local anesthesia with intravenous sedation, we performed an excisional biopsy, enucleating the white solid mass found in the mandible. Pathological tissue analysis revealed fibrosarcoma. As there was no evidence of metastasis after systemic fluoro-deoxy-glucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), we performed radical ablative surgery, comprising segmental resection of the right mandible with submandibular neck dissection, and temporary bridging with a reconstruction plate, under general anesthesia. Postoperatively, one course of combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide was administered. Two years after treatment, the patient's physical condition is good, with no evidence of recurrence or metastasis.

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A clinical study was made of 179 patients with previously untreated glottic carcinoma registered in our department between 1998 and 2004. In our facility, T1 glottic cancer was treated by radiotherapy, T2 glottic cancer by radiotherapy or chemoradiotherapy using low-dose CDDP, and T3 and T4 glottic cancer by laryngectomy.
The five-year cause-specific survival rate for glottic carcinoma was 95.1%, 96.5% for stage I, 96.6% for stage II, 92.9% for stage III, and 68.6% for stage IV. The five-year local control rate for early glottic carcinoma treated by radiotherapy was 83.1% for T1a, 60.7% for T1b, and 62.5% for T2. In T2 cases, the local control rate was 49.2% for treatment by radiotherapy, and 83.6% for low-dose CDDP with radiotherapy. Low-dose CDDP with radiotherapy contributes to high local control rate in T2 cases.

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Adenocarcinoma of the larynx is a very rare neoplasm, accounting for 0.7% of all laryngeal malignant neoplasms. Laryngeal adenocarcinoma arises from minor salivary glands under the mucous membrane. We experienced two cases of laryngeal adenocarcinoma in the subglottic region. Herein, we report one case of laryngeal adenoid cystic carcinoma and another of adenocarcinoma, NOS. The first case was a 67-year-old man who was admitted to our hospital with the diagnosis of laryngeal adenoid cystic carcinoma in the subglottic region, which was stage T4aN0M0, for invasion of the cricoid cartilage. Partial laryngectomy was performed and the larynx was preserved. The other case was a 76-year-old female, who was admitted to our hospital with the diagnosis of laryngeal adenocarcinoma, NOS in the subglottic region. Tumor volume had already been reduced by resection with the laryngofissure approach by her previous doctor. She refused total laryngectomy and so received 70 Gy of irradiation therapy. There has been no evidence of recurrence for 16 months.

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We analyzed prognostic factors of 38 cases with nasopharyngeal carcinoma. The 3-year disease-specific survival rate was 50%, and the 3-year locoregional control rate was 58%. The survival rate in the elderly group was low, but there was no significant difference. In terms of T stage, advanced cases did not show reduced survival rate and locoregional control rate. Regarding N stage, advanced cases showed low survival and locoregional control rates, but there was no significant difference. In terms of stage classification, there was also no significant difference. The group of WHO type 1 showed lower survival rate compared to the group of WHO types 2 & 3, but there was no significant difference. On the other hand, the group of WHO type 1 showed a lower locoregional control rate with a significant difference. Based on these findings, age, T, N, stage, and histological type were not unfavorable prognostic factors, however, WHO type 1 was a poor prognostic factor in the locoregional control rate of neopharyngeal carcinoma.

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We investigated the prevalence of high-risk human papillomavirus (HR-HPV) in squamous cell carcinoma of the tonsil and tongue-base region, and evaluated its clinical features and prognostic implications according to HPV status and p16 and p53 expression. HR-HPV was positive in 16 (53%) of 30 samples. Of these positive cases, 15 (94%) carried HPV 16 sequences and only 1 (6%) carried a HPV58 sequence. Among the HPV-positive patients, the frequency of heavy smokers and drinkers was significantly lower than among the HPV-negative patients. Among the 30 patients, p16 was overexpressed in 16 (53%), and this overexpression was strongly associated with the presence of HR-HPV (P < 0.0001). In contrast, HPV-negative patients were more likely to have p53 overexpression (75%). On univariate analysis, both HPV-positive status (86% vs. 48%; P = 0.029) and p16 overexpression (100% vs. 31%; P < 0.001) significantly improved the overall survival (OS), respectively. On the other hand, p53 overexpression was significantly associated with inferior OS (42% vs. 83%; P = 0.004). These results indicate that it will be necessary to use these HPV-related biomarkers for decisions on staging and therapeutic strategy.

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We report an investigation into the effects of concurrent chemoradiotherapy (CCRT) on cervical lymph node metastases in cases of head and neck squamous cell carcinoma occurring with cervical lymph node metastasis. The subjects were 32 patients receiving CCRT simultaneously for both the primary tumor and cervical lymph node metastases over a five-year period, from January 2005 to December 2009.
A complete response (CR) was observed in 71.9% of cases, increasing to 87.5% when cases with no residual viable tumor cells in excised specimens of radical neck dissection were included. Although no relationship existed between primary tumor location, N classification, and the therapeutic effect on cervical lymph node, the actual ratio of CR for cervical lymph node metastases tended to decrease with advanced stages of T classification. Considering that positive results are obtained without planned neck dissection, recurrence occurs only in a few cases, and there are no serious complications of radical neck dissection after CCRT, we believe that a planned neck dissection procedure is not necessarily required in all cases. However, evaluation is difficult with regard to cervical lymph nodes subsequent to CCRT, and therefore, future studies are needed to investigate a test method or a combination of test methods that provide a definite assessment of the presence or absence of residual cervical lymph node metastasis.

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One of the most important prognostic factors in head and neck squamous cell carcinoma is to control and manage regional metastasis. A few studies reported that real-time elastography (elastography) was used in the examination of lymph node metastasis. The purpose of the present study was to evaluate the efficacy of elastography in order to diagnose cervical lymph node metastasis in head and neck cancer. Our study included 253 lymph nodes in 37 patients with head and neck squamous cell carcinoma who underwent neck dissection from October 2007 to December 2008. Grade of the elastographic findings was determined by the hardness of the lymph node based on Furukawa's classification. The patterns of images were compared with the histopathological diagnosis obtained by neck dissection. Elastographic pattern 3 and 4 were considered metastatic. The precision of diagnosis was as follows: sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of elastography were 81.0%, 90.8%, 88.5%, 72.3% and 94.1%, respectively. The combined evaluation of elastography and ultrasonography, PPV and NPV were improved to 95.6% and 95.6%, respectively. The combination of elastography with ultrasonography might improve the precision of diagnosis of cervical lymph node metastasis in head and neck squamous cell carcinoma.

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Recently, the use of chemoradiotherapy for preserving organs in the treatment of head and neck cancer is increasing. However, there is controversy about advanced neck node management in post-chemoradiation cases. We retrospectively analyzed our 119 cases of chemoradiotherapy for oropharyngeal and hypopharyngeal cancer to examine the effectiveness and indications of planned neck dissection.
Regional control rate and survival rate were superior in the neck dissection group. If the cases did not achieve CR in imaging, planned neck dissection improved the regional control rate significantly. We should perform planned neck dissection immediately rather than “wait and see” for this persistent disease.
However, in the cases achieving radiological CR, it is possible to omit planned neck dissection because of the high salvage rate of neck disease. However, in these cases, careful observation is essential.
We clarified that the presence of pathologically positive lymph node is a prognostic factor. For evaluating persistent disease of cervical lymph nodes, PET-CT was the most accurate method of imaging.

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This study involved 46 patients, aged 75 years or more, with malignant tumors of the head and neck who visited our department during 2 years, from April 2006 to March 2008, and who underwent close investigation and medical treatment. We investigated age and gender, primary site, histopathological classification, staging classification (2002 TNM classification), complications, performance status (PS), follow-up period, treatment, outcome, cumulative survival rate, and disease-specific survival rate.
As a result, complications were observed in 76.1% of cases, and treatment reduction or non-treatment in 32.6% of cases. With regard to treatment in the elderly, we believe that treatment must be chosen after considering various factors such as complications, patient's standby capacity, PS, life expectancy, and family environment. Furthermore, although the number of cases in this study was small, we considered that in more than half of the patients, treatment was a trigger that worsened life prognosis, even if palliative treatment was performed, and that sufficient examination and informed consent are necessary in case of palliative treatment.

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Purpose: The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with 3DCRT (three-dimensional conformal radiation therapy) and alternate-day administration of S-1 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Materials and methods: Between 2006 and 2010, eleven patients with previously untreated SCCHN were included. The patients were administered oral S-1 (40 mg) twice daily on alternate days during the course of radiation treatment. 3DCRT was performed concurrently, using a combination of the rectangular arc fields and static fields techniques for the involved field which was defined based on endoscopic findings and CT and/or PET-CT. The median total dose was 69 Gy (66-70 Gy).
Results: All the patients received the planned radiotherapy without interruption. Grade 2 mucositis occurred in two of the patients. No cases experienced other grade 2 or greater acute or late adverse events. Eight patients achieved complete response (CR) after the primary treatment, and no recurrence has been seen yet in any of the primary sites for CR cases.
Conclusions: CCRT with 3DCRT and alternate-day administration of S-1 showed efficacy in the patients with SCCHN.

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The goals of head and neck reconstruction after malignant tumor resection include obtaining good postoperative function and appearance and minimizing operative invasiveness. However, the most important goals are reducing local postoperative complications and discharging the patient early, because patients requiring head and neck reconstruction tend to have poorer prognoses. Local complications delay wound healing, postoperative treatment, and postoperative recovery of eating and speech functions. Thus, when shown to be necessary by clinical observation and imaging findings, we open the wound area promptly and attempt to diagnose the complication. In this way, we can discover cervical infections and minimize wound contamination before more serious complications, such as total flap necrosis, develop. We review measures for preventing local complications in patients undergoing head and neck reconstruction at our institution and divide them into preoperative, intraoperative, and postoperative measures.

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