吉非替尼、紫杉醇及放疗治疗局部晚期头颈癌的分子及临床效果初步报告

表皮生长因子（EGFR）在头颈鳞癌（HNSCC）中过表达，可刺激癌细胞增殖，抑制凋亡，并提高癌细胞对放疗和化疗的抵抗。该文旨在研究吉非替尼（GEF）、紫杉醇（PAc）联合放疗（RT）治疗局部晚期头颈癌（HNSCC）的毒性、安全性及该治疗方法对治疗组织EGFR信号通路的影响。将临床Ⅲ到Ⅳ期的患者纳入研究范围，年龄大于（或等于）18岁，无放化疗史，脏器功能正常。     

头颈癌放疗后无症状颈动脉狭窄的发生率及危险因素

头颈癌放疗(RT)后无症状颈动脉狭窄的发生率及危险因素尚不清楚。该文对2000-2009年头颈癌接受放疗患者颈动脉超声检查结果进行回顾分析。在纳入的224例患者中,主要为临床Ⅲ-Ⅳ期并接受过顺铂化疗的患者。放疗完成到颈     

头颈癌的靶向治疗：2007年发展及临床应用进展

头颈部鳞癌患者的肿瘤复发、第二原发及并发症导致肿瘤治疗失败，且各种治疗方法都有其自身的局限性。靶向治疗的应用，使肿瘤治疗方法的选择逐渐增多。表皮生长因子受体（EGFR）参与肿瘤的发生及发展，并与患者的不良预后有关，因此，第一个靶向治疗药物抗表皮生长因子受体的单克隆抗体西妥昔单抗应用而生。新近的研究资料表明，西妥昔单抗联合放疗能够提高晚期头颈癌患者的生存率及肿瘤局部控制率。单独应用西妥昔单抗，能够提高铂类耐药患者的生存率。最近的临床Ⅲ期实验结果表明，对复发性及转移性头颈癌，西妥昔单抗及铂类药物的联合应用能够提高患者生存率。西妥昔单抗的治疗副作用较其他细胞毒性药物轻，且不会加重放疗副作用。     

头颈癌放疗进展

放射治疗在头颈癌治疗中处于重要地位，该文旨在回顾头颈癌放射治疗的新进展及影像学在制定治疗计划时的作用。最新的Meta分析显示，同期化放疗是治疗局部晚期头颈癌的标准治疗模式。最近的2个大规模随机临床试验并没有说明加速放疗结合同期化放疗能够起到累加效应。近5年的Ⅲ期临床试验证实，西托昔结合放疗能提高疗效。     

西托昔单抗、紫杉醇、卡铂及放疗治疗头颈癌的毒性分析

该文旨在评价西托昔单抗、紫杉醇、卡铂及同期放疗治疗头颈癌的可行性并分析其毒性。方法：将无远处转移的临床Ⅲ或Ⅳ期头颈癌患者纳入研究范围。患者先接受4周西托昔单抗诱导化疗,再接受同期化放疗（西托昔、紫杉醇、卡铂）。结果：32例出现放化疗毒性,3级和4级黏膜炎的发生率分别为53％和16％,3级及4级皮炎的发生率分别为44％和9％。     

3头颈癌的新辅助化疗：是否应对之重新评价？

通常．局部晚期头颈癌应用放疗、化疗和（或）手术进行联合治疗。化疗时间一直是学者长期争论的问题，但Meta分析显示，同期化放疗可将患者2年、5年生存率提高8％，因此．化放疗是局部晚期头颈癌的标准治疗模式，并被广泛采用。术前诱导化疗有其独特的优点，如可以评估肿瘤对药物的反应。继而选择可以保存器官的患者，避免过度治疗。[第一段]     

术前诱导化疗在头颈肿瘤治疗中的角色转变

化疗是局部晚期头颈癌的重要治疗手段之一,但其使用方案仍待探讨。联合应用顺铂与5-氟尿嘧啶一直被视为标准新辅助治疗,并被证明有利于保存手术患者的器官,提高可手术切除及不可手术切除患者的远期生存效果。新近的研究发现,在顺铂与5-氟尿嘧啶的标准诱导化疗中增加紫杉烷(taxane)、多烯紫杉醇(docetaxel)或紫杉醇(paclitaxel),可进一步改善有效率和生存结果。越来越多的Ⅲ期临床试验资料支持在顺铂与5-氟尿嘧啶的标准诱导化疗方案中增加多烯紫杉醇或紫杉醇,使之成为疗效更好、毒性更小的诱导化疗方案。将诱导化疗与同期化放疗结合的序列治疗方案也在研究之中,旨在进一步提高远期生存效果。在顺铂与5-氟尿嘧啶方案中增加多烯紫杉醇或紫杉醇的诱导方案也在评价之中,序列治疗方案与标准治疗的疗效比较的随机试验也在进行中,有望为局部晚期头颈癌患者提供新的治疗方案。     

同期化放疗治疗晚期头颈癌

头颈癌虽仅占成人恶性肿瘤的 5 % ,但其危害甚大。 1 995年 ,美国有新发头颈癌病人 3 975 0例 ,1 2 4 6 0例死于该病。早期头颈癌经手术和 (或 )放射治疗 ,多数可获治愈。但遗憾的是 ,大多数病人就诊时 ,已属局部 -区域晚期。过去 ,手术和 (或 )放疗被视为治疗局部 -区域晚期头颈癌的标准方法 ,但其治愈率不足 40 % ,远处转移率在 3 0 %以上。对于无法手术切除的病人 ,单纯放疗的局部复发率高达 5 0 % ,五年生存率不足 2 0 %。手术或放疗可导致广泛而严重的机体损害 ,包括畸形、功能损害和社交心理障碍 ;与单纯放疗相比 ,手术结合放疗对机体…     

经动脉和经静脉化放疗治疗晚期头颈癌的效果分析：Ⅲ期随机试验结果

化放疗是晚期头颈癌的首选治疗方法。大剂量化疗在体内外都可达到良好治疗效果，该文旨在比较头颈癌经动脉和经静脉化放疗的效果。将239例无法切除的头颈癌患者纳入研究范围，进行随机Ⅲ期临床试验，比较经动脉（IA）和经静脉（IV）化放疗的效果。IV组在第1、22、43天时给予顺铂300mg／m^2，并同时给以35天总量70Gy的放疗。     

头颈癌放疗、化疗及靶向治疗新进展

在首次就诊的上消化道鳞状细胞癌患者中，约60％处于l临床晚期（UICC，Ⅲ—Ⅳ期）。多学科综合治疗使患者总生存率高达50％。近期的研究证实，诱导化疗后肿瘤的远处转移率低于放疗和放化疗。加速超分割放疗效果优于传统放疗。调强放疗是调整放射剂量分布的一种新方法。应用特异性抗体，如表皮生长因子受体抗体（EGFR）进行靶向治疗，效果优于放疗，但与化放疗的效果比较仍悬而未决。针对血管内皮生长因子的靶向治疗，     

晚期口腔颌面-头颈部鳞癌靶向治疗的进展浅析

晚期口腔颌面-头颈部鳞癌的治疗仍然是个巨大的挑战。尽管传统的手术、放疗及化疗已取得了很大的进展,但晚期口腔颌面-头颈部鳞癌的预后仍然较差,分子靶向药物为此带来了新的希望。目前针对口腔颌面-头颈部鳞癌的靶向治疗的靶点主要有表皮生长因子受体及血管内皮生长因子受体。前者的代表药物有西妥昔单抗及尼妥珠单抗,他们无论是单药治疗,还是与放化疗结合治疗,均表现出了良好的前景;后者的代表药物主要是贝伐单抗,也已经进行到临床Ⅲ期实验。靶向治疗为晚期口腔颌面-头颈部鳞癌的治疗提供了新的机遇。     

Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck

Background:  Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35 000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical.
Methods:  Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described.
Results:  Postoperative chemoradiation is used in patients with high-risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity-modulated radiation treatment have proven to decrease some debilitating side effects from radiation treatment.
Conclusions:  Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long-term side effects can be minimized with the use of newer technologies and with careful treatment planning.     

Impact of epidermal growth factor receptor,mesenchymal–epithelial transition factor,and insulin-like growth factor receptor 1 expression on survival of patients with oral and oropharyngeal cancer

The aim of this study was to evaluate the impact of expression of epidermal growth factor receptor (EGFR), mesenchymal–epithelial transition factor (c-Met), and insulin-like growth factor receptor 1 (IGF-1R) protein on response to treatment and survival in patients with oral and oropharyngeal squamous cell carcinoma (SCC). EGFR, c-Met, and IGF-1R immunohistochemical (IHC) scores were generated based on the incidence and intensity of expression of the biomarkers evaluated in paraffin-embedded sections of biopsy specimens taken before treatment from 113 patients given neoadjuvant chemoradiotherapy followed by resection for primary locally advanced oral and oropharyngeal SCC. Correlations were assessed between the IHC of the biomarkers and the patients’ clinicopathological variables using Spearman's rank test. Cox's regression models were used to evaluate the impact of EGFR, c-Met, and IGF-1R, expression on survival.     

The increasing clinical relevance of human papillomavirus type 16 (HPV-16) infection in oropharyngeal cancer

Human papillomavirus type 16 (HPV-16) has been established beyond doubt as a causative agent in oropharyngeal squamous cell carcinoma (SCC). The incidence of oropharyngeal cancer has risen in recent decades, as has the proportion of patients who have a biologically relevant HPV-16 infection. Combined data from 14 recently published studies (2006-2010) show that 57% of 1316 reported cases of oropharyngeal SCC were HPV-16 positive. They had significantly better prognosis (hazard ratio (HR) for 5-year overall survival range 0.05-0.64), although smoking and higher T stage often appear as confounding factors to this favourable prognostic benefit. HPV-16 therefore has increasing importance as a clinically useful prognostic biomarker, but a benefit in survival has been seen in the use of surgery, radiotherapy, and chemotherapy, so specific changes in the preferred methods of treatment are hard to justify. Future trials that include oropharyngeal SCC will consider HPV-16 routinely as a stratification factor, and its use as a predictive biomarker awaits the development of effective targeted treatments. The undeniable and impressive prognostic significance of HPV-16 should hasten its addition to standard pathological reporting of oropharyngeal SCC, and ultimately to its inclusion in TNM staging systems of the American Joint Committee on Cancer (AJCC) and the International Union against Cancer (UICC).     

What patients consider important: Temporal variations by early and late stage oral,oropharyngeal and laryngeal subsites

Functional outcomes are of high priority to cancer patients and are relevant when considering treatment strategies. This study aimed to collate and analyse importance rankings of UW-QOL over time for patients treated with curative intent for primary head and neck squamous cell carcinoma between 2000 and 2010, and to compare early and late stage oral, oropharyngeal and laryngeal subsites. There were 1614 patients comprising oral cavity 47% (751), oropharyngeal 24% (382), laryngeal 20% (320) and other HNC locations 10% (161). Items of importance remained relatively stable within clinical groups but there were notable differences between groups. For patients with early oral tumours no domain was especially dominant, whereas for late oral tumours swallowing, chewing, speech and saliva were selected more often. Swallowing and saliva were more important in oropharyngeal tumours, as was taste with more advanced oropharyngeal tumours. Speech and activity were important for those with early laryngeal tumours, as were swallowing and speech for more advanced laryngeal tumours. Swallowing and saliva were more important in advanced tumours for all sites. This data confirms the priority patients place on swallowing, chewing, speech, and saliva, therefore curative treatments should optimise these functions wherever possible and provide access to post-treatment interventions as required.     

Human papillomavirus and oral disease – emerging evidence: a review

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart‐like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non‐smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.     

Survey of the use of tests for human papilloma virus and epidermal growth factor receptor for squamous cell carcinoma of the head and neck in UK head and neck multidisciplinary teams

Human papilloma virus (HPV), usually type 16, has emerged as an aetiological and prognostic marker of oropharyngeal carcinomas, and epidermal growth factor receptor (EGFR) has been associated with poor prognosis in patients with carcinoma of the head and neck. This makes the identification of cancers associated with these biomarkers important in the management of patients. We surveyed UK head and neck multidisciplinary teams by email using an online form to assess the use of biomarker testing. Overall 33 cancer networks were contacted and 28 (85%) responded. HPV tests were used in departments by 22 (79%) of our respondents, while only 3 (11%) used EGFR tests. The commonest reasons for not using them were lack of availability and lack of clinical indication.     

2019年NCCN口腔口咽癌诊疗指南更新解读

美国癌症联合委员会2017年第8版《AJCC肿瘤分期手册》出版,口腔及口咽癌TNM分期标准中新增侵袭深度（DOI）、淋巴结外扩展（ENE）、人乳头瘤病毒（HPV）等指标,并将口咽癌分为HPV阳性（p16+）与HPV阴性（p16-）,分别制定了不同的TNM分期标准。2018年,美国国立综合癌症网（NCCN）首次为HPV阳性（p16+）口咽癌制定了诊疗指南。2019年第1版NCCN头颈癌诊疗指南已经发布,其中对口腔口咽癌指南做了部分修订。为临床工作需要,本文结合2版变化进行部分解读。     

A systematic review of the management of oral candidiasis associated with HIV/AIDS.

The purpose of this review was to investigate the management of oral candidiasis in HIV/AIDS patients and to evaluate the different guidelines available for its management. A number of topical and systemic antifungal medications are used to treat oral candidiasis in HIV-positive patients. Milder episodes of oral candidiasis respond to topical therapy with nystatin, clotrimazole troches or oral ketoconazole. Fluconazole has been extensively evaluated as a treatment for candidiasis. With HIV-infection, a cure rate of 82% has been achieved with a daily oral dose of 50 mg. Fluconazole was found to be a better choice of treatment for relapsing oropharyngeal candidiasis, resulting in either better cure rates or better prevention of relapse. Intravenous amphotericin B has been found to be effective in azole-refractory candidiasis and is well tolerated. Topical therapies are effective for uncomplicated oropharyngeal candidiasis; however, patients relapsed more quickly than those treated with oral systemic antifungal therapy. Nystatin appeared less effective than clotrimazole and the azoles in the treatment of oropharyngeal candidiasis. Clotrimazole was found to be just as effective for resolution of clinical symptoms as the azoles, except when patient compliance was poor. Fluconazole-treated patients were more likely to remain disease-free during the fluconazole follow-up period than those treated with other antifungal agents.     

In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines.

BACKGROUND: Intraarterial chemotherapy of oral and oropharyngeal cancer with cisplatin (cis-diamminedichloroplatinum [II]) has experienced a revival in the last decade. Side-effects of the therapy were very low with concomitant systemic infusion of the neutralizing agent sodium thiosulphate. The requisite dose of the chemotherapeutic agent which safely leads to apoptosis of oral cancer cells has not yet been assessed in vitro, nor has the combination of cisplatin and sodium thiosulphate been examined for the potential reduction of cytotoxicity in oral cancer cells. STUDY DESIGN: In a panel of two tongue squamous cancer cell lines and an oesophageal cancer cell line as control and comparison, cisplatin (0.2-10 microgram/ml) was combined with sodium thiosulphate (0-0.5 mg/ml). RESULTS: 10 microgram/ml of cisplatin proved to be 100% antiproliferative, while any additional concentration of sodium thiosulphate decreased this effect. At the maximum dose of cisplatin, a sodium thiosulphate/cisplatin concentration relation of less than 6:1 still effected cytotoxic activity of >80%. An increase of cisplatin concentration led to higher cytotoxicity irrespective of sodium thiosulphate concentration. The oesophageal cell line was more sensitive to cisplatin and to sodium thiosulphate than the tongue cell lines. CONCLUSIONS: In this study, it was found that high concentrations of cisplatin are necessary in oral cancer to reach cytotoxic levels which support high-dose intraarterial chemotherapy by which these levels might be reached. A sodium thiosulphate/cisplatin concentration ratio within the tumour of less than 6:1 may be allowed without compromising the cytotoxic activity of cisplatin.