Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

[Significant factors for surgical site infection: analysis of 203 head and neck surgeries].

Surgical site infection (SSI) is a common complication in head and neck surgeries. The aim of this study was to assess the rate of, and risk factors for SSI following surgical procedures of the head and neck. The study population comprised 206 patients who underwent surgery of head and neck region in NTT West Osaka Hospital between 2009 and 2011. The incidence rate and risk factors were estimated by the chi-square test and a logistic regression analysis. SSI occurred in 22 cases (10.8%) of 203 patients. A broad range of putative risk factors was recorded in each patient and statistically analyzed to elucidate SSI related factors. Univariate analysis indicated that low BMI, diabetes mellitus, anemia, hypoalbuminemia, surgical wound classification, duration of operation, blood loss, left implants and preoperative radiotherapy were risk factors associated with SSI. Multivariate statistics revealed four independent risk factors: surgical wound classification (odds ratio (OR) 5.88, p = 0.02), hypoalbuminemia (OR 11.48, p < 0.01), duration of operation (OR 18.66, p < 0.01) and left implants (OR 20.24, p < 0.01). Thus, to achieve a reduction in SSI, we need to take care of not only the factors related with surgical technique such as the duration of the operation or left implants, but the preoperative nutrition status.

[Treatment outcome and failure pattern of olfactory neuroblastoma: a clinical analysis of 14 cases and meta-analysis of Japanese cases].

The olfactory neuroblastoma, first described in 1924, is a rare tumor arising from the olfactory epithelium. Because of its rarity, it is difficult to accrue a large individual series. To elucidate the characteristics of olfactory neuroblastomas in Japan, we report herein on our institutional experience of 14 cases and reviewed 104 cases reported from Japan. In our cases, one out of nine surgically treated patients died during treatment and the remaining 8 patients are alive without disease. Among the five non-surgically treated patients, four patients experienced local treatment failure and the other one patient died of metastasis. In the 104 Japanese cases, 54 patients were treated with multimodality treatment including surgery and radiation. The 3-year overall survival rates for surgically treated patients and non-surgically treated patients were 85% and 73%, respectively. The prognostic factors for survival were modified Kadish stage, Hyams' grade and surgical treatment. Further investigation is required for the validation of endoscopic resection.

Incidence and predictors of febrile neutropenia during chemotherapy in patients with head and neck cancer.

PURPOSE: Febrile neutropenia (FN) is an oncologic emergency, and its management is critical during chemotherapy. However, little is known about FN in patients with head and neck cancer. The purpose of this study was to investigate the incidence and predictors of FN in patients with head and neck cancer. METHODS: We performed a retrospective study in a university hospital in Japan between January 2008 and December 2012. Head and neck cancer patients treated with a platinum-based regimen were included in the analysis. RESULTS: FN occurred in 47 out of 138 cycles, and the incidence of FN was highest during the first cycle. Severe sepsis or more serious events were observed in 46 % of FN episodes. Patients treated with TPF (docetaxel, cisplatin, and fluorouracil) were more susceptible to FN than those treated with DC (docetaxel, cisplatin). The patient-specific risk factors revealed using univariate analysis were tube feeding, the presence of diabetes mellitus, and gastrointestinal adverse effects. Of these, logistic regression analysis demonstrated tube feeding and diabetes mellitus as independent predictors of FN. CONCLUSIONS: The incidence of FN in head and neck cancer patients in the community setting is higher than previously reported. Patients receiving enteral nutrition and those with diabetes are at high risk for FN.

[Head and neck soft tissue sarcoma].

Soft tissue sarcoma arising as a head and neck lesion is very rare in adults. Therefore, no standardized treatment exists for this entity of disease. We retrospectively analyzed 11 cases of head and neck soft tissue sarcomas treated at Osaka University Hospital from 1991 to 2011. They were pathologically classified as follows: 5 cases with rhabdomyosarcoma, 2 cases with liposarcoma, 2 cases with undifferentiated sarcoma and one each of epithelioid hemangioendothelioma and malignant fibrous histocytoma. Rhabdomyosarcomas were treated with multimodality therapy. Other sarcomas were treated mainly with surgery. The prognosis of patients with sarcoma depended on the histology, histological grade, tumor size and tumor stage. Patients with larger tumors, high grade tumors and advanced stage tumors had a poor prognosis, while those with rhabdomyosaracoma had a better prognosis. Further investigation is required to establish the new treatment protocol for adult soft tissue sarcoma and to improve survival.

Atypical soft tissue perineurioma in the tongue of a young girl.

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue perineuriomas arise in a wide anatomic distribution and mostly in patients older than 20 years of age. We report an atypical perineurioma in a 7-year-old girl. The tumor, located in the tongue, was uniformly hypercellular. The tumor cells were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process formation and wavy elongated nuclei, and the architecture was composed of predominantly short fascicles with areas exhibiting a vague storiform pattern. Although the tumor cells generally appeared bland, the tumor showed worrisome features including an infiltrative pattern and occasional mitotic figures. Psammoma bodies were observed in the periphery of the tumor. Immunohistochemically, the cells were positive for epithelial membrane antigen, vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type IV collagen. The authors document a case of soft tissue perineurioma with atypical histological features that occurred in the tongue of a child.

Age-adjusted Charlson comorbidity index as a prognostic factor of hypopharyngeal cancer treated with chemoradiation therapy.

CONCLUSION: The age-adjusted Charlson comorbidity index (ACCI) was associated with overall survival, disease-specific survival, and non-cancer death in patients treated with chemoradiation therapy (CRT) for hypopharyngeal cancer (HPC). Further studies using other CRT regimens are required. OBJECTIVE: To investigate the impact of the ACCI on survival in patients with HPC. METHODS: This study reviewed 128 patients with HPC who received CRT between 2004-2012. The survival rates and the cumulative incidence of non-cancer death according to the ACCI were estimated. A Cox proportional hazard model was used to assess the hazard ratio (HR) of the ACCI. RESULTS: The disease-specific survival rates at 3 years for the low ACCI group, moderate group, and high group were 80.1%, 45.8%, and 54.8%, respectively (p = 0.007). The laryngectomy-free survival rates at 3 years were 61%, 39.7%, and 37.1%, respectively (p = 0.137). The cumulative incidences of non-HPC death were 5% for the low/moderate ACCI group and 15.5% for the high ACCI group (p = 0.031). The HRs compared to the low ACCI group for overall survival, disease-specific survival, and laryngectomy-free survival were 2.61 and 2.74, 2.55 and 2.27, and 1.75 and 1.97 in the moderate and high ACCI groups, respectively.

Transaminase Activity Predicts Survival in Patients with Head and Neck Cancer.

Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected. The effect of the AST/ALT ratio on overall survival was analyzed using a Cox proportional hazard model. Moreover, recursive partitioning analysis (RPA) was used to divide the patients into groups on the basis of the clinical stage and AST/ALT ratio. The prognostic ability of this grouping was validated using an independent data set (N = 167). The AST/ALT ratio ranged from 0.42 to 4.30 (median, 1.42) and was a prognostic factor for overall survival that was independent of age, primary sites, and tumor stage (hazard ratio: 1.36, confidence interval: 1.08-1.68, P = 0.010). RPA divided patients with stage IVA into the following two subgroups: high AST/ALT (≥2.3) and low AST/ALT (<2.3) subgroups. The 5-year survival rate for patients with stage III, stage IVA with a low AST/ALT ratio, stage IVA with a high AST/ALT ratio, and stage IVB were 64.8%, 49.2%, 28.6%, and 33.3%, respectively (p < 0.001). Compared with the low AST/ALT group, the adjusted hazard ratio for death was 2.17 for high AST/ALT group (confidence interval: 1.02-.22 P = 0.045). The AST/ALT ratio was demonstrated to be a prognostic factor of HNSCC. The ratio subdivided patients with stage IVA into low- and high-risk groups. Moreover, intensified treatment for the high-risk group may be considered.

Docetaxel, cisplatin, and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: The first-line treatment for inoperable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has long been the combination of cisplatin and fluorouracil (PF). Recently, cetuximab has been shown to provide an additional survival benefit to PF. It remains unknown whether docetaxel adds additional benefits to PF. Therefore, we sought to evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) for inoperable recurrent or metastatic HNSCC. METHODS: A retrospective chart review from January 2005 to March 2013 identified patients who were treated with docetaxel 60 mg/m(2) on day 1, followed by cisplatin 60 mg/m(2) on day 1, and fluorouracil 600 mg/m(2)/day on days 1-5 (modified TPF) every 4 weeks for inoperable recurrent or metastatic HNSCC. RESULTS: Twenty-four patients were identified; seven and five patients had locoregional disease only and distant metastasis only, respectively, while 12 patients had locoregional disease and distant metastasis simultaneously. Of the 17 patients with distant metastasis, multiple organs were affected in 9 patients, with the most frequently affected organ being the lung (n=11). Three patients had no prior treatment, whereas 21 patients underwent intensive prior treatment. In 17 of 21 patients who had received prior treatment, the treatment included chemoradiotherapy and/or chemotherapy. The median number of cycles of modified TPF was two (range, 1-5). One patient showed complete response, four patients showed partial response, two patients had stable disease, and 17 patients had progressive disease. Overall, the rate of objective response was 21%, with a 95% confidence interval (CI) of 9-40%. Median overall survival was 8.0 months (95%CI, 4.4-10.6 months). The treatment efficacy differed significantly according to extent of disease. Objective response in patients with distant metastasis alone was better than in patients with locoregional disease with or without distant metastasis (60% vs. 11%, respectively; P=0.02). Median overall survival in the former patients was longer than in the latter patients (not reached vs. 7.0 months, respectively; P=0.02). Fifteen patients (63%) had Grades 3-4 neutropenia, and seven patients (29%) developed Grade 3 febrile neutropenia. There were no toxic deaths. CONCLUSION: The efficacy of modified TPF in the setting of first-line treatment for recurrent or metastatic HNSCC is not very high, while the toxicity is acceptable with extensive care. The development of more efficacious chemotherapeutic regimen is required.

Chemoradiation therapy for squamous cell carcinoma of the external auditory canal: A meta-analysis.

BACKGROUND: The standard treatment for advanced external auditory canal squamous cell carcinoma (SCC) is subtotal temporal bone resection and postoperative radiation therapy (RT), whereas chemoradiation therapy (CRT) is used in some institutions to improve patient prognosis. The purpose of this study was to evaluate the efficacy of CRT in external auditory canal SCC treatment. METHODS: Meta-analyses of external auditory canal SCC studies were performed. We extracted 5-year overall survival rates and number of patients for aggregate patient data, and types of treatment and outcomes for individual patient data. RESULTS: The 5-year overall survival rate of 752 patients was 57%. In the individual patient data meta-analysis, the 5-year overall survival rates of patients who received surgery ± RT, preoperative CRT, definitive CRT, and postoperative CRT were 53.5%, 85.7%, 43.6%, and 0%, respectively. CONCLUSION: Our data suggest that preoperative CRT may improve the survival of surgically treated patients with external auditory canal SCC and that definitive CRT may be equivalent to surgical resection.

Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer.

CONCLUSIONS: Serum squamous cell carcinoma antigen (SCC-Ag) level was an independent prognostic factor for survival in patients with head and neck squamous cell carcinoma (HNSCC), and the prognostic value depended on the carcinoma site. OBJECTIVES: To assess the value of SCC-Ag as a prognostic indicator in patients with HNSCC and to determine the effect of primary tumor site on prognosis. METHODS: We reviewed 493 patients with HNSCC between 2004 and 2012. The chi-squared test was used to assess associations between SCC-Ag levels and TNM classification. A Cox proportional hazard model was used to assess the hazard ratio of SCC-Ag at different sites for death, and it was analyzed as a continuous variable. RESULTS: The median serum level of SCC-Ag was 1.1 ng/ml (range 0-20). SCC-Ag was significantly higher in patients with advanced T and N classification tumors. Primary sites in the oral cavity, in the hypopharynx, advanced T and N classification, distant metastasis, and SCC-Ag were negatively associated with survival in univariate analysis. Multivariate analysis revealed that SCC-Ag was a significant risk factor for overall survival in cancers of the oral cavity, hypopharynx, and larynx, but not in oropharyngeal cancer.

Factors predicting severe infections during chemotherapy in head and neck cancer patients.

CONCLUSIONS: The head and neck cancer patients with more co-morbidities and those dependent on tube feeding are at a high risk of severe infections during chemotherapy. Therefore, prophylaxis with colony-stimulating factors and/or antibiotics should be considered for those patients. OBJECTIVES: To investigate the risk factors for severe infection during chemotherapy in head and neck cancer patients. METHODS: A retrospective study was conducted of 129 patients with head and neck cancer who received taxane-based and platinum-based chemotherapy between 2008-2013. Logistic regression models were used to evaluate risk factors. RESULTS: Febrile neutropenia occurred in 50 patients out of the 129 (39%), severe infections occurred in 24 patients (19%), and bacteremia in two patients (2%). In univariate analysis, low serum albumin levels and tube feeding were significantly associated with severe infections (p = 0.015 and < 0.001, respectively). In multivariate analysis, the odds ratios for a higher modified Charlson co-morbidity index and tube feeding were 2.80 and 9.74, respectively. These two were independent predictive factors for severe infections (p = 0.020 and 0.001, respectively).

Prognostic significance of body mass index before treatment for head and neck cancer.

BACKGROUND: Patients with head and neck cancer frequently experience malnutrition. The purpose of this study was to examine the impact of nutritional status on prognosis and its association with treatment modalities. METHODS: This retrospective study included 706 patients with head and neck cancer diagnosed between 2004 and 2012. The effects of pretreatment body mass index (BMI) on overall survival were analyzed using the Kaplan-Meier method and Cox regression model. RESULTS: BMI ranged from 11.6 to 38.0 kg/m2 (median, 21.5) and was a prognostic factor for survival, independent of primary site, and tumor stage. The 5-year survival rates for underweight, normal, and overweight groups were 32.2%, 62.7%, and 73.5%, respectively. The hazard ratios of BMI in the surgery, chemoradiation, and radiation groups were 0.95, 0.91, and 0.79, respectively, and the latter two were statistically significant. CONCLUSION: The impact of BMI is determined by the types of cancer treatment. Pretreatment BMI should be considered while deciding treatment.

Factors associated with malnutrition in patients with head and neck cancer.

CONCLUSIONS: Comorbidities as well as T classification were the primary determinants for the nutritional status of patients with head and neck cancer. OBJECTIVES: We aimed to elucidate the underlying conditions of malnutrition in patients with head and neck cancer. METHODS: We retrospectively reviewed 726 patients diagnosed with head and neck cancer between 2004 and 2013. Associations between malnutrition and clinical parameters were assessed using univariate and multivariate analyses. RESULTS: Median body mass index was 21.5 (range 11.6-38.0). According to World Health Organization criteria, the nutritional status of these patients was classified into four groups: underweight (18%), normal (63%), overweight (17%), and obese (1%). Comorbidities were detected in 40% of patients. Multivariate analysis revealed the following factors to be independent factors associated with malnutrition: advanced T stage, metachronous cancer, collagen disease, gastrointestinal disease, and pulmonary disease.