Jun Furusawa

Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells.

Mitochondria are key organelles for apoptosis, and mitochondrial DNA (mtDNA) content can regulate cancer progression. Increases in mtDNA mutations and deletions have been reported in cancer; however, a detailed investigation of mtDNA content in cancer cells has not yet been conducted.

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer

Background:The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS).Methods:Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100–120 mg m−2 per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65–70 Gy).Results:One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions.Conclusion:We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

Superselective arterial cisplatin infusion with concomitant radiation therapy for base of tongue cancer

The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success.

Comparison of acute toxicities associated with cetuximab-based bioradiotherapy and platinum-based chemoradiotherapy for head and neck squamous cell carcinomas : A single-institution retrospective study in Japan

Abstract Conclusion: Grade ≥ 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well. Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation. Method: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m2 was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m2 of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m2 weekly during the definitive radiotherapy. Results: The BRT group had a higher incidence of Grade ≥ 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade ≥ 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).

Distinct Epigenetic Profiling in Head and Neck Squamous Cell Carcinoma Stem Cells

Objective. To identify unique epigenetic signature in cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC). Study Design. Molecular and microarray studies. Setting. Tertiary referral center. Subjects and Methods. Head and neck CSCs were isolated in HNSCC cells by CD44 staining and flow cytometry sorting. CSCs with highest CD44 expression (CD44hi) and non–stem cells (non-SCs) with lowest CD44 expression (CD44low) were then characterized for stemness gene expression and their responses to chemotherapeutic agents, followed by high-throughput epigenetic profiling using the Illumina BeadChip Array, targeting 28,544 CpG sites covering more than 14,956 genes. Results. CD44hi CSCs expressed higher levels of stem cell markers and were more resistant to chemotherapeutic agents as compared to CD44low non-SCs. By DNA methylation microarray analysis, 17 hypomethylated and 9 hypermethylated genes were identified in CD44hi CSCs as compared to non-SCs in most HNSCC cell lines. Cluster analysis using these 26 genes showed that CD44hi CSCs were epigenetically distinct from the CD44low non-SCs in all 5 HNSCC cell lines. Conclusion. A unique epigenetic profile consisting of 17 hypomethylated and 9 hypermethylated genes was seen in HNSCC CSCs. These genes may be critically required in maintaining the stemness or pluripotency of CSCs and may represent novel molecular targets for anticancer therapies aimed at eradicating CSCs in HNSCC.

Combined modality therapy for laryngeal cancer with superselective intra-arterial cisplatin infusion and concomitant radiotherapy

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.

Indications for superselective intra-arterial cisplatin infusion and concomitant radiotherapy in cases of hypopharyngeal cancer

OBJECTIVE We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC). METHODS Between April 2000 and March 2013, 41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100-120mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65-70Gy). RESULTS During the median follow-up period of 5.5 years, a statistically significant difference in the 5-year overall survival was noted between patients with N0-1 (n=14) and N2b-3 disease (n=27). One-half of deaths were observed to be the result of distant metastasis. The 5-year local control and overall survival were significantly better in patients with unilateral than in those with bilateral primary tumors. All the patients with T4b disease (n=3) died of disease within 2 years. CONCLUSION Indications for RADPLAT in patients with HPC were defined as patients with unilateral tumors staged as T3-4a and N0-1.

Management for squamous cell carcinoma of the nasal cavity and ethmoid sinus: A single institution experience

OBJECTIVE Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes. METHODS A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No patient had lymph node metastasis. RESULTS Twelve patients were treated with surgery with/without radiotherapy and with/without chemotherapy. Of these, 4 underwent endoscopic surgery without an open approach and 3 required an anterior skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy alone, and 4 and 8 with intravenous and intra-arterial chemotherapy, respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%, 71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a, and T4b disease was 74.1%, 71.4%, and 29.0%, respectively. CONCLUSION Our treatment policy for patients with SCC of NC&ES, which basically follows the NCCN guideline, was considered to be appropriate. However, several points in terms of surgery and non-surgical approach remain to be solved through further research.

Salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy.

Our aim was to evaluate the feasibility of salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively analysed the records of 61 patients with cancer of the maxillary sinus who were treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra-arterial infusions of cisplatin given a median of 4 times weekly (range 2-5). Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy). Persistent or recurrent cancer of the maxillary sinus was found in 17 patients, of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7 of the 11 survived with no evidence of disease. Their 5-year overall survival was 61%. Two of the 11 developed serious operative complications. Salvage surgery for patients with persistent or recurrent cancer of the maxillary sinus treated by superselective chemoradiotherapy is both safe and successful. Salvage surgery is a good option when this sort of persistent or recurrent cancer is followed up after the regimen of chemoradiotherapy described.

p53 expression in concurrent chemoradiotherapy with docetaxel for head and neck squamous cell carcinoma

BACKGROUND The current study aimed to evaluate the significance of an immunohistochemical assessment of tumor suppressor p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) patients treated with docetaxel and radiotherapy. METHODS The expression of tumor suppressor p53 and its phosphorylated form at the Ser392 residue was retrospectively evaluated by immunohistochemistry in 51 Stage T1-3N0-2M0 (except T1N0 glottis) HNSCC patients who were treated with 10mg/m(2)/week docetaxel four to six times and received concurrent chemoradiotherapy. RESULTS Kaplan-Meier univariate analysis revealed that no difference in rates for overall and disease-free survival (DFS) between patients with p53-positive and -negative tumors (p=0.786 and p=0.924, respectively). The prognostic significance of phosphorylated p53 at the Ser392 residue was neither observed. CONCLUSIONS An immunohistochemical assessment of the expression of p53 and its phosphorylated form might not be of clinical use in defining subgroups of patients with poor prognosis.