Comparison of high-dose Cisplatin-based chemoradiotherapy and Cetuximab-based bioradiotherapy for p16-positive oropharyngeal squamous cell carcinoma in the context of revised HPV-based staging

Aim: To perform a comparison of Cisplatin vs. Cetuximab in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) in the context of the revised HPV-based staging.Background: Previous reports comparing these agents in head and neck cancer have included heterogenous disease and p16-status.Materials and methods: A retrospective review was conducted from 2006 to 2016 of patients with p16-positive OPSCC who underwent definitive radiotherapy concurrent with either triweekly Cisplatin (n?=?251) or Cetuximab (n?=?40). AJCC 8th Edition staging was adapted.Results: Median follow-up for surviving patients was 40 months. On multivariate analysis for all-comers, comparing Cisplatin and Cetuximab, 3-year locoregional recurrence (LRR): 6% vs. 16% (p?=?0.07), 3-year distant metastasis (DM): 8% vs. 21% (p?=?0.04), 3-year overall recurrence rate (ORR): 11% vs. 29% (p?=?0.01), and 3-year cause-specific survival (CSS): 94% vs. 79% (p?=?0.06), respectively. On stage-based subgroup analysis, for stage III disease, 3-year LRR: 5% vs. 10% (p?=?0.51), 3-year DM: 7% vs. 16% (p?=?0.32), 3-year ORR: 10% vs. 23% (p?=?0.15), and 3-year CSS: 95% vs. 82% (p?=?0.38). For stage III disease, 3-year LRR: 10% vs. 40% (p?=?0.07), 3-year DM: 9% vs. 43% (p?=?0.07), 3-year ORR: 15% vs. 55% (p?=?0.04), and 3-year CSS: 94% vs. 57% (p?=?0.048).Conclusions: When given concurrently with radiotherapy, Cetuximab and triweekly Cisplatin demonstrated comparable efficacy for AJCC 8th Edition stage I–II p16-positive OPSCC. However, Cetuximab appeared to be associated with higher rates of treatment failure and cancer-related deaths in stage III disease. Upon availability of the RTOG 1016 trial results, analysis based on the revised HPV-based staging should be performed to confirm these findings.     

Clinical applications of palifermin: amelioration of oral mucositis and other potential indications

Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti‐neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high‐risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient‐reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft‐versus‐host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild‐to‐moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects.     

口咽部过路菌定植的微生态学防治研究

本文用ＳＰＦ级ＣＢＡ／Ｊ／Ｏｌａ近交系小鼠研究抗生素对咽部正常群的破坏与防治方法。观察发现小鼠咽部甲链菌群被破坏后咽部出现需氧革兰氏阴性杆菌定植。采用咽部人工接种甲链活菌的方法,成功地使小鼠咽部甲链菌群迅速恢复,并能有效防止咽部革兰氏阴性杆菌定植的发生、发展。为临床上应用微生态制品防止呼吸道二重感染提供了坚实的基础,具有重要理论和应用价值。     

Tongue pressure against hard palate during swallowing in post-stroke patients

Objectives: The tongue plays an important role in swallowing by contacting the palate. The aim of the present study was to investigate the characteristics of tongue pressure production during swallowing in post‐stroke patients using a newly developed sensor sheet. Materials and methods: Ten post‐stroke inpatients with hemiplegia and five healthy volunteers participated in this study. Magnitude of tongue pressure during a dry swallow was measured using a newly developed sensor sheet comprising five sensors applied directly to the palate or to the palatal surface of a maxillary denture using denture adhesive. Swallowing ability was evaluated by measuring the time taken to swallow 30 ml of water. The magnitude of tongue pressure was compared between the post‐stroke patients and healthy subjects as well as between each measuring point in both groups. The relationship between tongue pressure and swallowing ability and that between tongue pressure and state of occlusal support were also examined. Results: The magnitude of tongue pressure in the post‐stroke patients was smaller than that of the healthy subjects at the measuring points along the median line (Welch test, p < 0.05), larger in the non‐paralysed side than in the paralysed side (two‐way anova , p < 0.05), and was influenced by swallowing ability and occlusal support (Welch test, p < 0.05). Conclusions: Measurement of the magnitude of tongue pressure shows promise as a simple, non‐invasive and quantitative method by which tongue activity in post‐stroke patients, in whom swallowing ability is a concern, could be evaluated.     

Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland,Australia

BackgroundIncreases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia.MethodsIncidence data for 1982–2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression.ResultsThe incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50–69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC.ConclusionsIncidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males.     

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE)

BackgroundTobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk.MethodsWe analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models.ResultsWithout adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR_{<10 years vs. ≥30 years}: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR_{<10 years vs. ≥30 years}: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed.ConclusionsResults from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.