Shigemichi Iwae

Retropharyngeal node metastasis from papillary thyroid carcinoma

Papillary thyroid carcinomas commonly metastasize to paratracheal and jugular lymph nodes. Metastasis to the retropharyngeal node is rare for this tumor.

Multicenter phase II study of an opioid-based pain control program for head and neck cancer patients receiving chemoradiotherapy

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.

Randomized Phase III Trial of Adjuvant Chemotherapy with S-1 after Curative Treatment in Patients with Squamous-Cell Carcinoma of the Head and Neck (ACTS-HNC)

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

Matched-pair analysis in patients with advanced oropharyngeal cancer: surgery versus concurrent chemoradiotherapy.

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

Effect of local extension sites on survival in locally advanced maxillary sinus cancer.

We analyzed the effects of local extension sites on survival in patients with locally advanced maxillary sinus cancer.

Expression of amphiregulin in mucoepidermoid carcinoma of the major salivary glands: a molecular and clinicopathological study

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

Multi-institutional retrospective study for the evaluation of ocular function-preservation rates in maxillary sinus squamous cell carcinomas with orbital invasion

The purpose of this retrospective analysis was to evaluate ocular function and survival rates among treatment modalities in patients with maxillary sinus cancer with orbital invasion.

A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141

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

The role of initial neck dissection for patients with node-positive oropharyngeal squamous cell carcinomas.

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

Phase II trial of chemoradiotherapy with S-1 plus cisplatin for unresectable locally advanced head and neck cancer (JCOG0706)

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/m2/day and cisplatin at 20 mg/m2/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.