Chemotherapy in head and neck cancer treatment has advanced by multimodality therapy combined with surgery and radiation. CDDP has been used in a variety of multidisciplinary approaches as a key drug. Furthermore, taxanes and anti-EGFR antibody have been developed as new treatment options. Recently, the efficacy and safety profile of the immune checkpoint inhibitor for head and neck cancer has been reported, and it will be possible to use it in the near future. Chemotherapy for head and neck cancer will become more complex and its management will become more difficult, thus requiring the development of a broader multidisciplinary medical team.

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There are still few comparison reports regarding the safety of salvage surgery for recurrence and persistence following platinum-based chemoradiotherapy (CRT) and cetuximab-based bioradiotherapy (BRT), which are frequently used as non-surgical therapies for advanced head and neck carcinomas. This study compared the safety of salvage surgery following CRT against that following BRT for advanced hypopharyngeal cancer. The study examined 34 cases who underwent salvage surgery following CRT and 7 cases who underwent salvage surgery following BRT from September 2002 to December 2015. The number of cases that were able to undergo salvage surgery was 34 among 67 recurrence and persistence cases following CRT and 7 of 8 cases following BRT. In terms of the surgical procedure, salvage neck dissection was conducted for 22 cases in the CRT group and 5 cases in the BRT group, with no significant differences observed between both including the surgical time and amount of bleeding, and with no major complications in either group. Total hypopharynx or total laryngectomy resection for salvage was conducted for 19 cases in the CRT group and 3 cases in the BRT group, upon which we observed anastomotic leakage in 3 cases in the CRT group and 1 case in the BRT group; however, there was no significant difference in the onset frequency.
There was no clear difference regarding safety between salvage surgery following CRT and following BRT for locally advanced hypopharyngeal cancer. However, regarding the adaptation of salvage surgery, the possibility of limitations in the CRT group was suggested in comparison with the BRT group.

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Most head and neck cancer patients are advanced stage when first diagnosed and about half of them receive chemoradiotherapy (CRT) because the cancer is unresectable or there is hope of functional preservation. In subsequent treatment for recurrence after CRT, many of them receive chemotherapy with or without reirradiation.
There are three situations when chemotherapy is used for recurrence after CRT: 1. Re-chemoradiotherapy (Re-CRT) in the adjuvant setting after salvage surgery. 2. Re-CRT for cases who cannot receive salvage surgery. 3. Chemotherapy for cases who cannot receive salvage surgery or Re-CRT.
In the first situation, Re-CRT is expected to yield a better outcome, but there is concern about severe adverse events, so special care in selecting patients is required. In the second situation, there are some negative comments about Re-CRT, and so cases must be judged individually. In the third situation, there are some choices of treatment, but EBM is based on past large clinical trials, so the treatment based on a guideline or guidance is recommended.
Recently, new drugs have been invented and approved in the world, though their cost is increasing rapidly. It is necessary to provide the best treatment that also takes cost-effectiveness into consideration.

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We retrospectively studied the long-term outcome of oropharyngeal cancer. We evaluated the clinical records of 157 oropharyngeal cancer patients who underwent surgery as primary treatment, from April 1992 through December 2005 at the National Cancer Research Center East Hospital.
The number of patients with stage I, II, III and IV were 12, 27, 26 and 92, respectively. The number of patients with lateral wall, anterior wall, posterior wall and superior wall subsites were 84, 52, 4 and 17, respectively. 81 patients underwent reconstruction surgery with free flap, and 19 patients underwent postoperative therapy.
The 5-year and 10-year overall survival rates were 51.0 and 44.7%, respectively. 66 patients died due to oropharyngeal cancer and 25 patients died due to other causes. 53 patients developed multiple cancers. Functional laryngeal preservation rate was 78.3%. Laryngeal function was impaired by recurrence or other cancers. After oropharyngeal cancer therapy, long-term observation is necessary.

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We retrospectively analyzed the long-term prognosis, postoperative complications and quality of life of patients with hypopharyngeal squamous cell carcinoma who underwent total pharyngolaryngectomy as the primary treatment. The subjects were 295 patients who were operated on during the nine years from April 2005 to the present. Ten subjects (3.4%) were classified as stage II, 46 (15.6%) as stage III and 239 (81.0%) as stage IV. The three-year and five-year overall survival rates (disease-specific survival rates) were 63.1% and 53.6% (66.7%/58.9%), respectively. The disease-specific 3-year and 5-year survival rates by disease stage were 85.2% and 78.6%, respectively, for stage III and 65.5% and 56.6%, respectively, for stage IV. Postoperative complications were neck abscess or wound infection (33 cases; 11.2%), fistula formation (21 cases; 7.1%), sepsis (13 cases; 4.4%), thrombus in the vascular anastomosis sites (11 cases; 3.7%), and partial tracheal necrosis (10 cases; 3.4%). Most of these complications could be relieved by local or conservative treatment or salvage surgery. In total, 250 cases (95.0%) were capable of total oral intake. A total of 51 cases (17.3%) underwent secondary insertion of a voice prosthesis and recovered good vocal function.

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Three hundred ninety patients with head and neck cancer aged over 75 years old were referred to our center between April 2011 and December 2015. Of these, 208 patients with oral, oropharyngeal, hypopharyngeal and laryngeal cancer were enrolled and evaluated for operative indications based on comorbidity and postoperative complications. It is important to decide operative indications based on performance status, degree of general comorbidity and adequate informed consent; elderly patients should not be denied treatment because of their age. Moreover, the treatment strategy and overall survival rate were both similar to those of younger counterparts. Finally, we examined whether operative extent decreased or not in elderly patients, and found no difference between near-elderly patients and younger patients.

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Skull base surgery is a procedure for en-bloc resection of head and neck tumors which extend to the skull base area. We retrospectively analyzed 13 patients with head and neck tumors who underwent skull base surgery at our hospital from 2007 to 2014. Ten patients underwent frontal and/or front-temporal craniotomy and 3 patients underwent subtotal temporal bone resection. The 5-year disease specific survival (DSS) rates by the Kaplan-Meier method were 65% in frontal and front-orbital craniotomy and 100% in subtotal temporal bone resection. The 5-year DSS rates classified by histological findings were 100% in squamous cell carcinoma (SCC) and 33% in non-SCC (p=0.03). The positive surgical margin status and dural invasions were important factors of poor prognosis (p=0.02, p=0.07). Although patients with paranasal sinus or external ear SCCs were all recurrence cases, their postoperative courses were favorable. Paranasal sinus and external ear SCCs were good indicators for skull base surgery even in cases of recurrence after primary surgery or chemoradiotherapy, provided there is no intracranial invasion and the SCC is resectable with a free margin.

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We report a case of stage I basaloid squamous cell carcinoma (BSCC) which showed pulmonary metastasis. A 69-year-old man was referred to our hospital by his physician because of a tumor of the tongue. At the first visit to our hospital, physical examination revealed a mass measuring 10 mm in diameter in the ventral surface of the tongue on the right side. Under general anesthesia, the tumor was excised with a tentative diagnosis of a benign submucosal tumor. Pathological diagnosis was BSCC of the tongue. Seven months after excision of the tongue tumor, a nodular lesion was detected in the left lower lobe of his lung on CT scans. The lung lesion, excised by respiratory surgeons, was diagnosed as metastatic BSCC. Thereafter, two pulmonary metastatic foci appeared, and four courses of a combination of chemotherapy of DOC (60mg/m²) and NDP (90mg/m²) were carried out. Therapeutic effect was assessed as CR. Two months after the fourth course of chemotherapy, the patient was found deceased at his home due to an unknown cause. Prior to his death, no locoregional recurrence was observed throughout the follow-up.

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Extracapsular spread (ECS) of metastatic lymph node in oral cancer is the most significant prognostic predictor of poor treatment outcome. However, only a few reports on prognostic indicators in ECS positive cases have been published. The purpose of this study was to determine the prognostic factors of oral squamous cell carcinoma (OSCC) with ECS in metastatic lymph nodes. In this study, the cases of 77 patients with primary OSCC, who attended our hospital from 2008 to 2013 and had at least one pathologically metastatic node with ECS, were reviewed. Patients with primary recurrence during follow up were excluded from the present study. Univariate analyses revealed that many kinds of cervical metastatic factor, including number of ECS positive lymph nodes, were significantly associated with recurrence and poor outcome. Moreover, multivariate analyses indicated that the number of ECS positive metastatic lymph nodes is the only significant factor predicting regional recurrence and poor outcome. In conclusion, the number of ECS positive lymph nodes is the most important prognostic indicator for OSCC with ECS in metastatic lymph nodes. Thus, classification of ECS status using the number of ECS positive lymph nodes may be useful for further prediction of poorer prognosis in OSCC cases. However, standardization of ECS diagnosis and a larger multicenter prospective study for refining the present finding are required.

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We retrospectively analyzed 36 local advanced oropharyngeal cancer (OPC) patients to examine the feasibility of induction chemotherapy (IC). Nineteen and 17 patients underwent PF chemotherapy (CDDP+5-FU) and TPF chemotherapy (TXT+CDDP+5-FU) for one cycle, respectively. The 5-year local control rate (LC), progression-free survival rate (PFS), disease-specific survival rate (DSS), and overall survival rate (OS) in patients with posterior wall involvement (n=3) were all 0%, and worse than those in patients with lateral (n=29) or anterior wall involvement (n=4). The 5-year PFS and 5-year DSS of T4a and T4b cases were worse than those T3 tumor cases. The 5-year LC, 5-year PFS, 5-year DSS, and 5-year OS in the TPF (n=17) and PF groups (n=19) were 93.3% and 66.8% (p=0.0040), 49.9% and 45.9% (p=0.019), 77.8% and 53.3% (p=0.084), and 53.9% and 50.3% (p=0.222), respectively. The 5-year LC, 5-year PFS, 5-year DSS, and 5-year OS of the CRT group (n=20) who underwent chemoselection were better than those of the extended surgery group (n=16), but the difference was not statistically significant. In comparisons between patients receiving the two IC types (TPF or PF) followed by CRT or surgery, the prognosis and LC of TPF responders who underwent CRT were better than those of the other groups. These results indicate that TPF for chemoselection is a more feasible option.

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The prognosis for childhood cancer has improved drastically recently due to advances in anti-tumor therapy. The current 5-year survival rate is over 70%; hence, childhood cancer is curable. However, secondary malignant neoplasms are a late effect of primary cancer therapy. The patient was an 8-year-old girl. When she was 2 years old, she suffered from neuroblastoma (stage IV). Chemotherapy, hematopoietic stem cell transplantation, surgery, and radiotherapy brought about complete remission. However, 6 years later a right parotid gland tumor appeared. A tumorectomy was then conducted, and intraoperative consultation revealed inflammation of the parotid gland. The final pathological diagnosis was low-grade mucoepidermoid carcinoma of the parotid gland, so we performed an additional operation. This cancer seemed to be secondary malignant neoplasm induced later following childhood cancer therapy. Eighteen months have passed since her final operation, and there is no recurrence of cancer.

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Differentiated thyroid carcinoma (DTC) generally has a good prognosis, though systemic metastasis slowly progresses in some cases. Among such cases, brain metastasis is reportedly present with an unusual clinical picture and markedly reduces QOL, resulting in poor outcomes. We treated two cases who developed brain metastasis after thyroid gland surgery and who achieved marked QOL improvement of their home lives following tumor resection via craniotomy. Unlike other malignant tumors, progression of DTC is slow due to its biological characteristics. Life expectancy and QOL can be improved with proactive treatment by considering prognostic determinants for metastatic brain tumor development and general condition.

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Differentiated thyroid cancer (DTC) refractory to radioactive iodine has a very poor prognosis, and treatment options are limited. Recently, however, small-molecular tyrosine kinase inhibitors (TKI) have shown clinical benefits in advanced thyroid cancer.
The efficacy and safety of lenvatinib (lenvima^®) were evaluated in locally recurrent and metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer in the SELECT trial, and the drug was approved in 2015 in Japan. The most common side effects of lenvatinib were hypertension, fatigue, diarrhea, and appetite loss. Reported serious side effects included thromboembolic events, liver damage, fistula formation, and others. Some side effects of TKI are new, and not previously experienced with chemotherapy. Given that these side effects have not been seen with traditional cytotoxic anticancer drugs, a clear understanding of their expression and measures against them are important. Optimal management includes measures to deal with side effects as well as dose modification or interruption.
Cooperation with co-workers, including nurses, pharmacists and dentists, should include education about side effects and management of lenvatinib administration.
Here, we report the history of lenvatinib until approval, and describe its main adverse effects and their management.

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We compared the outcome of concomitant chemoradiotherapy using two different schedules of cisplatin, 100mg/m² or 80mg/m² cisplatin once every 3 weeks (3-Weekly) and 40mg/m² cisplatin once per week (Weekly), for patients with previously untreated squamous cell carcinoma of the head and neck. From November 2007 to March 2015, 34 patients with previously untreated squamous cell carcinoma of the head and neck were included in this study. Twenty-six received 3-Weekly cisplatin, and 8 received Weekly cisplatin. 65% of patients in the 3-Weekly group and 88% of those in the Weekly group received a total cisplatin dose of more than 200mg/m². In patients 75 years old and over, no patients in the 3-Weekly group and 75% of those in the Weekly group received a total cisplatin dose of more than 200mg/m². Weekly cisplatin treatment can achieve higher compliance compared to 3-Weekly cisplatin treatment in patients with older age at diagnosis.

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Background: A Phase III EXTREME trial showed that the addition of cetuximab to platinum-based chemotherapy (CTx) had significantly improved overall survival (median overall survival: 7.4 versus 10.1 months) in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated the efficacy of CTx plus cetuximab in Japanese patients. Patients and methods: We retrospectively reviewed the medical records of 43 patients with R/M HNSCC treated with CTx with or without cetuximab as first-line therapy between April 2008 and June 2015. Results: The patients were 38 men and 5 women with a median age of 63 years. The most frequent primary tumor site was the hypopharynx (37%), and most patients had metastatic disease (67%). Prior CTx and radiotherapy were received for 49% and 60%. 23 patients were treated with CTx alone and 20 were treated with CTx plus cetuximab. With a median follow-up period of 12.1 months, median overall survival was 9.6 months and 10.4 months (p=0.67), and median progression-free survival was 3.5 months and 3.0 months (p=0.54), respectively. Overall response rates were 39% and 35%, respectively. Univariate analysis failed to reveal any prognostic factor for survival except for subsequent therapies. However, in the patients treated by platinum-fluorouracil chemotherapy, CTx plus cetuximab appeared to be more effective than CTx alone (median overall survival: 10.4 versus 7.0 months). Conclusions: Survival data in this retrospective analysis appeared to be reproducible with the EXTREME trial.

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