Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study.

BACKGROUND: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. METHODS: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. RESULTS: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT. CONCLUSION: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

Surgery-based versus radiation-based treatment strategy for a high metabolic volume laryngeal cancer.

OBJECTIVE/HYPOTHESIS: We previously reported that the metabolic tumor volume (MTV) of a primary tumor was an independent prognostic factor for survival in laryngeal carcinoma treated by radiotherapy (RT)-based protocol. The purpose of this study was to evaluate the difference in survival outcomes between surgery-based and RT-based treatment in patients with a MTV laryngeal cancer. STUDY DESIGN: An individual retrospective cohort study. METHODS: We reviewed the records of 63 patients with laryngeal cancer showing a primary tumor with a high MTV value (≥ 4.9 mL). The patients were separated into two groups by primary treatment strategy: 22 patients were included in the surgery group, and 41 patients were included in the RT group. Clinical factors and treatment modalities were analyzed for their association with survival. RESULTS: Multivariate analysis, including age, sex, subsite, T classification, nodal metastasis, and treatment modality, showed that the subsite (hazard ratio [HR] 2.55, P = 0.043) and treatment modality (HR 3.98, P = 0.019) were independent predictors for survival. The Kaplan-Meier curves for 2-year relapse-free survival rates and overall survival rates for patients in the surgery and RT groups were 74.2% versus 38.8% (P = 0.025) and 80.1% versus 66.7% (P = 0.078). CONCLUSIONS: Patients with a high metabolic volume laryngeal cancer treated by a surgery-based protocol showed better relapse-free survival and overall survival than did those undergoing RT-based treatment. Pretreatment MTV assessment could be useful in planning the treatment strategy for patients with a laryngeal cancer. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:862-867, 2017.

Symmetric Lipomatosis Arising in the Tongue Presenting as Macroglossia and Articulatory Disorder.

Symmetric lipomatosis is definitively characterized by symmetric, tumorous lipomatous proliferation of adipose tissue that often develops in the head and neck, shoulders, and upper trunk. However, in the oral region, symmetric lipomatosis of the tongue (SLT) is an extremely rare condition related to generalized lipidosis that is often caused by chronic alcoholism. It is characterized by multiple symmetric lipomatous nodules and diffuse bilateral swelling located within the tongue. We report an extremely rare case of SLT arising in an 80-year-old man with a long history of alcoholic liver cirrhosis. He exhibited multiple soft nodular protrusions on the bilateral margin of the tongue presenting as macroglossia for years. Although MR imaging showed multiple fatty masses on both sides of the tongue, there was no elevated tumor mass on the bilateral margin. The patient underwent bilateral partial glossectomy under general anesthesia. Histopathologically, the resected tumor exhibited diffuse infiltration with mature adipose tissue lacking a fibrous capsule. Due to the lipidosis and the unusual presentation of multiple lesions, the lesion was ultimately diagnosed as SLT. At present, after surgery, the patient wears a full-denture and is in excellent condition, with no sign of recurrence, improved QOL, and recovery of masticatory, articulatory, and speech intelligibility functions.

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma.

PURPOSE: Although locally advanced head and neck squamous cell carcinoma (HNSCC) can be effectively treated using chemoradiotherapy (CRT) with docetaxel (DTX), and cisplatin (CDDP) plus 5-fluorouracil (TPF-CRT), severe adverse events (especially neutropenia) can limit treatment adherence. Therefore, we evaluated the safety and efficacy of a new chemotherapy regimen that consisted of DTX and CDDP plus cetuximab (Cmab) with concurrent radiotherapy. METHODS: Bio-chemoradiotherapy (B-CRT) using DTX, CDDP, and Cmab was administrated to patients with locally advanced HNSCC, and its safety and efficacy were evaluated. RESULTS: Interim analysis of nine patients revealed severe neutropenia in five patients (56 %) and leukopenia in seven patients (78 %); hence, the study was terminated. One patient experienced disease-free survival using only B-CRT. CONCLUSIONS: Neutropenia was equally severe for B-CRT, compared to TPF-CRT. Based on the limited sample size, it is impossible to conclude that B-CRT has non-inferior efficacy, compared to TPF-CRT.

Prognostic significance of metabolic tumor volume in patients with piriform sinus carcinoma treated by radiotherapy with or without concurrent chemotherapy.

BACKGROUND: The purpose of this study was to elucidate the prognostic significance of the pretreatment metabolic tumor volume (MTV) in patients with piriform sinus carcinoma treated by radiation-based therapy. METHODS: This retrospective study included 100 patients with piriform sinus carcinomas who had received treatment by radiation-based therapy. The MTV values were obtained from pretreatment positron emission tomography (PET). The association between clinical factors, including the MTV, and survival was analyzed. RESULTS: Kaplan-Meier estimates revealed the 5-year disease-free survival (DFS) rates were significantly poorer for patients with a high MTV compared to those with a low MTV. In the multivariate analysis, MTV (p < .001), nodal metastasis (p = .011), and applied chemotherapy regimen (p = .004) were found to be independent prognostic factors for DFS. CONCLUSION: The locoregional MTV is a prognostic factor for DFS in patients with piriform sinus carcinoma treated by radiation-based therapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the head and neck treated with salvage surgery after concurrent chemoradiotherapy.

BACKGROUND: For primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival. METHODS: The records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed. RESULTS: A total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5 %, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5 %). CONCLUSIONS: Salvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

Predictive markers, including total lesion glycolysis, for the response of lymph node(s) metastasis from head and neck squamous cell carcinoma treated by chemoradiotherapy.

BACKGROUND: Chemoradiotherapy (CRT) is used to treat cervical lymph node(s) metastatic head and neck cancer patients. Evaluation and treatment of lymph node(s) after CRT is important to improve the prognosis. METHODS: Prior to CRT, we determined the TNM stage by visual and imaging examinations. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated from the results of fluorodeoxyglucose-positron emission tomography (FDG-PET). After CRT, the patients were divided in two groups-complete response (CR) and non-CR-and their responses were compared with the clinical characteristics. RESULTS: T4, N2b, N2c and TLG2.5 ≥ 18.8 were statistically significant predictive indices before CRT. The odds ratio, 95 % confidence interval and p value were, respectively-T4: 2.73, 1.15-6.51, 0.0230; N2b: 6.96, 1.50-32.3, 0.0132; N2c: 11.80, 2.37-58.50, 0.00258; and TLG2.5 ≥ 18.8: 6.25, 2.17-18.00, 0.000672. CONCLUSIONS: TLG was found to be a good predictive factor for metastatic lymph node(s) prior to CRT treatment. After CRT treatment, FDG-PET was found to be highly specific and useful for negative screening.

Imaging strategy for response evaluation to chemoradiotherapy of the nodal disease in patients with head and neck squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (CRT) is used to treat lymph node metastatic head and neck cancer patients. Regional control of the neck disease is important to improve the prognosis, and the accuracy of the method used to evaluate the metastatic lymph node(s) after CRT is crucial to the decision-making process for any following salvage surgery. METHODS: Patients undergoing CRT were divided in two groups of patients of those showing complete clinical response (CR) and those showing clinical non-response (non-CR), as assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI), ultrasonography, fluorodeoxyglucose-positron emission tomography (FDG-PET), and fine needle aspiration cytology. The responses (CR vs. non-CR) were compared with the actual clinical outcomes. For the interim analysis, the study period was broken down into two periods, namely, the exploratory phase (patients treated between January 2002 and April 2012) and the validating phase (patients treated between May 2012 and January 2014). RESULTS: The sensitivity, specificity, and accuracy were as follows: CT and/or MRI, 66.7, 73.8, and 72.8 %, respectively, in the exploratory phase; ultrasonography, 91.7, 70.6, and 73.4 %, respectively, in the exploratory phase and 80.0, 82.8, and 82.4 %, respectively, in the validating phase; FDG-PET, 50.0, 97.5, and 91.3 %, respectively, in the exploratory phase and 60.0, 100, and 94.1 %, respectively, in the validating phase; cytology, 68.4, 95.9, and 90.3 %, respectively, in the exploratory phase and 66.7, 100, and 85.7 %, respectively, in the validating phase. CONCLUSIONS: Based on our results, CT and/or MRI appear to be inadequate methods for the evaluation of the response of lymph node(s) to CRT. In contrast, ultrasonography appears to be a highly sensitive and useful tool for positive screening at 6-8 weeks after CRT, and FDG-PET appears to be a highly specific and useful tool for negative screening at 8-12 weeks after CRT.

Concurrent Chemoradiotherapy with Docetaxel, Cisplatin and 5-Fluorouracil (TPF) in Patients with Nasopharyngeal Carcinoma.

BACKGROUND/AIM: Several randomized trials have shown that concurrent chemoradiotherapy (CCRT) either with or without adjuvant chemotherapy is more effective than radiotherapy-alone for treating nasopharyngeal carcinoma (NPC). The present study retrospectively evaluated the efficacy and toxicity of CCRT with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy in patients with NPC. PATIENTS AND METHODS: The study regimen consisted of two cycles of TPF chemotherapy [docetaxel (90 mg/m(2)), cisplatin (60 mg/m(2)), and continuous 5-fluorouracil (600 mg/m(2)/day: 5 days)] during definitive radiotherapy. Radiotherapy was performed 5 days a week with a single daily fraction of 1.8 or 2.0 Gy totalling to 70-Gy doses. A total of 24 patients with NPC were enrolled and evaluated. RESULTS: Treatment completion rate was 70.8%, with an overall response rate of 100%. The 5-year overall survival rate was 82.4%, and 5-year progression-free survival rate was 78.3%. CONCLUSION: CCRT with TPF resulted in excellent survival rates for patients with NPC.

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.

Predictive and prognostic value of metabolic tumor volume (MTV) in patients with laryngeal carcinoma treated by radiotherapy (RT) / concurrent chemoradiotherapy (CCRT).

PURPOSE: To evaluate the predictive and prognostic value of pretreatment metabolic tumor volume (MTV) in patients with treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: We reviewed the records of 118 patients with newly diagnosed laryngeal carcinoma, who had been treated by RT or CCRT. Pretreatment positron emission tomography (PET) was performed, and MTV values were obtained by contouring margins of standardized uptake value. Clinical factors and MTV were analyzed for their association with survival. RESULTS: Patients with residual disease showed a significantly higher MTV than those with a complete response (CR) after primary treatment. Univariate analysis showed that the patients with a high MTV had a significantly lower disease-free survival (DFS) (p < 0.001). Subsite (p = 0.010), T-stage (p < 0.001), nodal metastasis (p < 0.001) and clinical stage (p < 0.001) also correlated significantly with DFS. In the multivariate analysis, MTV and clinical stage were both found to be independent prognostic factors for DFS (p = 0.001, p = 0.034, respectively). The 3-year DFS for patients with a high MTV were significantly poorer than those with a low MTV (p < 0.001). CONCLUSIONS: MTV of the primary tumor is a significant prognostic factor for DFS in patients with laryngeal carcinoma treated by RT or CCRT. The results imply that MTV could be an important factor when planning treatment and follow-up for patients with laryngeal carcinoma.

Definitive chemo-radiotherapy for squamous cell carcinoma of the pharynx: impact of baseline low hemoglobin level (<12 g/dL) and post-radiation therapy F-18 FDG-PET/CT.

OBJECTIVE: To identify reliable predictors of overall survival (OS), locoregional control (LC), and metastasis-free survival (MFS) after definitive concurrent chemo-radiotherapy (CCRT) for squamous cell carcinoma (SCC) of the pharynx (nasopharynx, oropharynx and hypopharynx), we examined 16 potential prognostic factors, including pre-treatment hemoglobin level and pre- and post-treatment [(18)F]fluorodeoxyglucose positron emission tomography CT (F-18 FDG-PET/CT) maximum standardized up-take values (SUVmax) of primary sites and lymph node (LN) regions. METHODS: We retrospectively reviewed records of 70 patients treated with definitive CCRT for pharyngeal cancer in our institution during July 2006-April 2012, with particular regard to 16 prognostic factors: age, sex, T stage, N stage, retropharyngeal LN (RPLN) involvement, existence of multiple primary cancer, treatment interruptions, overall treatment time, chemotherapy type, pre-treatment hemoglobin level, pre-treatment body mass index, enteral feeding period, and pre- and post-treatment F-18 FDG-PET/CT SUVmax of primary site and LN region. All patients in our cohort underwent pre- and post-treatment F-18 FDG-PET/CT. RESULTS: Multivariate analysis associated improved OS with pre-treatment hemoglobin level (≥12 g/dL; hazard ratio [HR] 3.902; 95 % confidence interval [CI] 1.244-12.236; P = 0.020) and post-treatment SUVmax (primary site) (SUVmax <5.00; HR 4.237; 95 % CI 1.072-16.747; P = 0.039). Improved LC was associated with pre-treatment hemoglobin level (≥12 g/dL; HR 2.983; 95 % CI 1.123-7.920; P = 0.028), and post treatment SUVmax (primary site) (SUVmax <5.00; HR 5.233; 95 % CI 1.582-17.309; P = 0.007). No variable was found to be significant for improved MFS. CONCLUSIONS: Significant predictors for outcome in pharyngeal SCC treated with definitive CCRT were pre-treatment baseline hemoglobin level and post-treatment F-18 FDG-PET/CT SUVmax for primary site. Patients who have hemoglobin level lower than 12 g/dL may tend to have dismal prognosis. Additional treatment should be considered in those who have higher SUVmax at primary site in post-treatment F-18 FDG-PET/CT finding.

Phase II study of concurrent chemoradiotherapy with S-1 in patients with stage II (T2N0M0) squamous cell carcinoma of the Pharynx or Larynx.

OBJECTIVE: The goals of treatment for head and neck cancer are cure and organ-function preservation. For organ preservation, primary treatment via radiotherapy alone is thought to be insufficient for Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx. The objective of the present study was to investigate the efficacy and safety of concurrent chemoradiotherapy with S-1 for patients with Stage II squamous cell carcinoma of the pharynx or larynx for primary organ preservation. METHODS: Previously untreated patients with Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx received three courses of S-1 (40 or 50 mg twice a day; 2 weeks of administration followed by 1 week of rest every 3 weeks) during conventional radiotherapy (a single daily fraction of 1.8 Gy) to a total dose of 70.2 Gy. The primary endpoint was the local control rate at 3 years. RESULTS: From August 2009 to October 2012, 37 patients were evaluated for the study. The overall response rate was 100%. The 3-year local control rate was 89.0% (95% confidence interval, 78.9-99.2%), and the 3-year overall survival rate was 97.2% (95% confidence interval, 91.8-100%). Mucositis and dermatitis in the radiation field were the most common acute adverse events observed. The rates of Grade 3 mucositis and dermatitis were 27 and 35%, respectively. No patients experienced Grade 4 acute adverse events. The treatment completion rate was 89.2%. CONCLUSION: Concurrent chemoradiotherapy with S-1 was safe and effective in improving local control for Stage II squamous cell carcinoma of the pharynx or larynx.

[The accuracy of evaluating the response of metastatic lymph nodes after concurrent chemoradiotherapy in patients with head and neck squamous cell carcinoma].

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is used to treat advanced head and neck cancer. The accuracy of evaluating lymph nodes metastases following CCRT is important for subsequent therapy. PATIENTS AND METHODS: Patients were divided into two groups according to the nodal status, the complete response (CR) and the non-CR groups, as determined by imaging and fine-needle aspiration cytology (FNAC) performed 4-8 weeks after the CCRT, and the findings were compared with the status 6 months after the treatment completion. RESULTS: The sensitivity, the specificity, positive predictive value, negative predictive value and accuracy of each evaluation method were as follows: 66.7%, 73.5%, 26.7%, 93.8% and 72.5%, respectively, for computer tomography (CT) and magnetic resonance imaging (MRI); 91.7%, 69.9%, 30.6%, 98.3% and 72.6% for ultrasonography (US) ; 50.0%, 96.4%, 66.7%, 93.0% and 90.5% for fluorodeoxyglucose-positron emission tomography (FDG-PET) or PET-CT; and 68.4%, 96.1%, 81.3%, 92.5% and 90.6% for FNAC. CONCLUSION: To evaluate the response of lymph node(s) treated by CCRT, US is useful as a positive screening tool and FDG-PET and PET-CT as negative screening tools. FNAC is useful in evaluating suspicious lymph nodes in both positive and negative cases.

[Nuclear translocation of epidermal growth factor receptor and its relation to clinicopathological factors in oral squamous cell carcinomas].

The epidermal growth factor receptor (EGFR) is one of the receptor tyrosine kinases. Some EGFRs are transferred from membrane to nucleus upon ligand binding and an increase of this translocation causes high-level expression of nuclear EGFR. The high-level expression of nuclear EGFR was reported to be a poor prognostic factor in various cancers such as breast cancer, ovarian cancer, gallbladder cancer, prostate cancer and oropharyngeal cancer. Regarding oral cancers, one report indicated that nuclear EGFR is detected in oral squamous cell carcinoma (OSCC) on immunohistochemical staining, but did not mention the clinicopathological prognostic value in detail. Therefore, we investigated the expression of nuclear EGFR in OSCC cell lines and primary tumor specimens of tongue SCCs to see whether nuclear EGFR could be a useful prognostic value. We verified the expression level of nuclear EGFR in OSCC cell lines and observed an increase in the amount of nuclear EGFR upon EGF stimulation with the expression level reaching its peak after 15 minutes. Nuclear EGFR positive tumors were found in 23 patients (28.0%) with tongue SCCs. However, we could not find any correlation between clinicopathological factors and the expression of nuclear EGFR in patients with tongue SCCs.

Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: Compared with radiotherapy alone, concurrent chemoradiotherapy significantly improves survival rates for patients with squamous cell carcinoma of the head and neck. The aim of this study was to retrospectively evaluate the efficacy, toxicity and long-term prognosis of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil chemotherapy. METHODS: A total of 140 patients were enrolled and evaluated. Patients were received two cycles of docetaxel, cisplatin and 5-fluorouracil chemotherapy (docetaxel [50 mg/m(2): Day 1], cisplatin [60 mg/m(2): Day 4] and continuous 5-fluorouracil [600 mg/m(2)/day: Days 1-5]) during definitive radiotherapy. RESULTS: The overall response rate was 97.1%. The 3 and 5-year overall survival rates were 83.3 and 79.2%, respectively. The 3 and 5-year disease-specific survival rates were 84.2 and 80.0%, respectively. Among patients with laryngeal or hypopharyngeal carcinoma, the 5-year laryngectomy-free survival rate was 64.9%. CONCLUSIONS: Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil showed excellent survival and organ preservation rates for the patients with locally advanced squamous cell carcinoma of the head and neck.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the hypopharynx treated with concurrent chemoradiotherapy.

PURPOSE: The purpose of the study is to review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma(SCC) of the hypopharynx and to evaluate the factors affecting survival and larynx preservation. STUDY DESIGN: Retrospective study. METHODS AND MATERIALS: T he records of 102 patients with Stage III or IV resectable SCC of the hypopharynx treated with CCRT between January 1998 and August 2010 were reviewed. Of the 102 patients, 62 were treated with high dose regimens including cisplatin, 5-fluorouracil, methotrexate, leucovorin or docetaxel, cisplatin, and 5-fluorouracil. The remaining 40 were treated with low-dose regimens including carboplatin and uracil-tegafur, weekly docetaxel, or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8­2.0 Gray (Gy), to a total dose of 64.8­70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan­Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for OS, DSS, and DSS with larynx preservation. RESULTS: The 5-year OS and DSS for all patients treated with CCRT were 51.3 and 64.3 %, respectively. The 5-year DSS with larynx preservation was 55.5 %. On multivariate analysis, the content of chemotherapy was a significant predictor of OS and DSS for patients undergoing CCRT ; N stage was a significant prognostic factor for DSS and larynx preservation. CONCLUSION: T he treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the N stages of SCC of the hypopharynx.

Telomerase-specific oncolytic adenovirus: antitumor effects on radiation-resistant head and neck squamous cell carcinoma cells.

BACKGROUND: Radioresistance remains a critical issue in the use of radiotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy of combination treatment with OBP-301, a telomerase-specific replication-selective adenovirus, and radiotherapy in overcoming radioresistance by examining its effect on radiation-resistant HNSCC cells. METHODS: Radiation-resistant HNSCC cells were treated with OBP-301 and radiation in vitro and in an orthotopic nude mouse model in vivo and synergism was assessed. Apoptosis and expression of MRN complex, which plays a key role in DNA repair machinery, were also analyzed. RESULTS: Infection with OBP-301 was found to enhance the antitumor efficacy of radiation both in vitro and in vivo by inhibiting MRN complex expression and increasing apoptosis induction. CONCLUSION: Combined OBP-301 and radiation therapy seems to overcome radioresistance in HNSCC cells by inhibiting DNA repair machinery, and may thus be a novel therapeutic strategy for treating HNSCC.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy.

OBJECTIVE: To review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and to evaluate the factors affecting survival and larynx preservation. STUDY DESIGN: Retrospective study. SUBJECTS AND METHODS: The records of 102 patients with stage III or IV resectable SCC of the larynx treated with CCRT between February 1994 and March 2009 were reviewed. Of 102 patients, 59 were treated with high-dose regimens, including cisplatin, 5-fluorouracil (5-FU), methotrexate, and leucovorin or docetaxel, cisplatin, and 5-FU, and 43 were treated with low-dose regimens, including carboplatin and uracil-tegafur or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8­2.0 Gray (Gy), to a total dose of 66.0­70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan­Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for DSS and DSS with larynx preservation. RESULTS: The 5-year OS and DSS for all patients treated with CCRT were 63.9 and 70.7 %, respectively. The 5-year DSS with larynx preservation was 54.1 %. On multivariate analysis, N stage, synchronous multiple primary cancers, and the contents of chemotherapy were significant predictors of OS for patients undergoing CCRT; T stage, N stage, and the contents of chemotherapy were significant prognostic factors for larynx preservation. CONCLUSION: The treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the T and N stages of laryngeal SCC. It is important to diagnose multiple synchronous primary cancers before CCRT.