TNP方案在头颈部鳞状细胞癌中的疗效探讨

目的 比较头颈部鳞状细胞癌(SCCHN)治疗中TNP(紫杉醇+奈达铂+替加氟)与PF(氟尿嘧啶+顺铂)组的近期疗效以及不良反应。方法 分析2009年-2014年在襄阳市中心医院接受治疗的SCCHN患者的临床资料。根据治疗方案将患者划分为PF组和TNP组。比较两组患者的一般资料、临床特征、治疗疗效以及治疗不良反应。结果 本研究纳入患者54例,其中TNP组和PF组各27例,两组患者的临床资料并无统计学差异(P＞0.05);两组患者的肿瘤部位、临床分期及分化程度均无统计学差异(P＞0.05);TNP组患者的治疗疗效优于PF组,差异具有统计学意义(χ²=7.864,P=0.048);TNP组患者的胃肠道反应发生率显著低于PF组(χ²=4.854,P=0.028),其余不良反应均无统计学差异(P均＞0.05)。结论 在SCCHN治疗中,TNP方案疗效优于PF方案,且治疗过程中的胃肠道不良反应发生率更低。     

Hyperfractionated radiotherapy in advanced squamous cell carcinoma of the head and neck

From January, 1976 to January, 1980, 141 patients (135 males and 6 females) with Stage III and IV squamous cell carcinoma of the head and neck received a split course of hyperfractionated radiotherapy (HFR). In the first group, involving 91 patients, the therapeutic schedule was as follows: first and fourth week, 7.2 Gy per day in 8 sessions of .9 Gy from Monday to Friday, the second and third week no irradiation was given. Thus, patients were given 72 Gy total dose, fractionated into 80 sessions. Mucosal necrosis and severe hemorrhage were responsible for the death of 26 patiens (28%). Therefore the therapeutic protocol was altered for the 50 patients of the second group: during the first and sixth week 6.6 Gy per day in 6 sessions of 1.1 Gy from Monday to Friday. The total dose was thus reduced to 66 Gy fractionated into 60 sessions, resulting in the decrease of toxicity. Regardless of the therapeutic protocol and site of primary, 114 patients (80%) achieved a complete remission and 8 showed a partial remission (>50%), whereas no change was seen for the 19 remainders. Local recurrence appeared in 60 patients (48%). Acute mucositis and laryngeal edema regularly occurred a week after every course of HFR and were considered severe in 40 patients. In spite of toxicity, the median survival is 14 months and 22 patients are still alive in November 1981: 19 without disease, and 8 of these patients have a survival time of at least 3 years.     

Feasibility and tolerance of sequential chemoradiotherapy in squamous cell carcinoma of the head and neck

LOO S.W., GEROPANTAS K., TASIGIANNOPOULOS Z., MARTIN C. & ROQUES T.W. (2013) European Journal of Cancer Care 22 , 32–40 Feasibility and tolerance of sequential chemoradiotherapy in squamous cell carcinoma of the head and neck This paper evaluates the feasibility and tolerance of sequential chemoradiotherapy in patients with squamous cell carcinoma of the head and neck and ascertains whether the use of induction chemotherapy compromises delivery of subsequent radiotherapy with or without concurrent chemotherapy. We also compared sequential chemoradiotherapy treatment adherence between the elderly and younger patients with squamous cell carcinoma of the head and neck. One hundred and ninety-four patients with head and neck squamous cell carcinoma who received induction chemotherapy with cisplatin and 5-fluorouracil were included in this study. Treatment-related death rate from induction chemotherapy was 1.5%. One hundred and ninety-one patients (98.5%) proceeded to radical radiotherapy, with 90.1% also receiving planned concomitant chemotherapy. One hundred and seventy-eight patients (93.2%) completed radiotherapy with no prolongation of the treatment duration. There were no statistical differences in sequential chemoradiotherapy treatment adherence and tolerance between the elderly and younger patients apart from the proportion who required hospitalisation during radiotherapy. Induction chemotherapy in head and neck squamous cell carcinoma does not compromise delivery of definitive radiotherapy with or without concurrent chemotherapy. Elderly patients with head and neck squamous cell carcinoma are able to tolerate aggressive treatments such as sequential chemoradiotherapy. Treatment ‘deintensification’ based solely on chronological age is not recommended.     

头颈部鳞癌TNM分期的进展与展望

头颈部鳞癌的第8版TNM分期在前版基础上做出了许多重要改进,进一步提高了该分期在评估患者预后、指导治疗方案方面的价值.但很多研究表明,该分期的某些方面仍存在改进的空间.该文将对第8版与第7版TNM分期的主要差异、仍旧存在的不足之处,头颈部鳞癌分期的最新研究进展以及未来的发展方向作简要综述.     

Glutathione-associated enzymes in head and neck squamous cell carcinoma and response to cisplatin-based neoadjuvant chemotherapy

Glutathione S-transferases (GSTs) are metabolic phase II enzymes that promote reactive metabolite elimination by conjugating them to glutathione (GSH). Because of their important role in xenobiotic metabolism and detoxification, they have been implicated in carcinogenesis processes, especially epithelium transformation. Moreover, their influence on response to chemotherapy in cancer patients has been demonstrated. Genetic polymorphisms for GSTM1, GSTT1 and GSTP1 have been found in human populations and have been shown to have phenotypic consequences. To investigate the role of GST enzymes in carcinogenesis and in response to chemotherapy in patients with head and neck squamous cell carcinoma (HNSCC), GSTP1, GSTM1 and GSTT1 were studied prospectively in a large series of HNSCC patients. Correlations between GST alterations, p53 mutation status and clinical response to chemotherapy were investigated. We showed that the risk of developing laryngeal cancer was increased by 2.6-fold [95% CI 1.6--6.1] in patients with the GSTM1 null genotype and by 2.8-fold [95% CI 0.9--8.1] in patients with the homozygous GSTP1 val105 genotype. Furthermore, individuals with this latter genotype were over-represented in the p53 mutation group (p = 0.05). After storage duration and hemolysis adjustment, a significantly lower plasmatic GSTP1 level was observed in complete responders compared with partial and non-responders (mean: 4.4 +/- 0.06 microg/l, 4.7 +/- 0.06 microg/l and 4.7 +/- 0.07 microg/l; p = 0.05), respectively. The prevalence of p53-mutated tumors was significantly higher in the group of non-responders (81%) compared with partial (60%) and complete responders (64%) (p = 0.05). Two types of multivariate analysis were performed including parameters that have been shown to influence response to chemotherapy significantly in univariate analysis. p53 mutations and high tumor stage are independent factors of non-response to chemotherapy, whereas plasmatic GSTP1 levels and low tumor stage are independent factors of complete response. Our data suggest that GST enzymes are associated with larynx cancer and that their use as predictive factors and treatment targets should be further explored.     

头颈部鳞状细胞癌转移机制及其影响因素研究进展

头颈部鳞状细胞癌(Head and neck squamous cell carcinoma,HNSCC)是一种主要来源于上呼吸道、消化道的非角化上皮癌性增生的恶性肿瘤.癌症转移为HNSCC患者预后差及病死率高的常见原因,HNSCC转移机制近年来成为众多学者关注与研究的热点之一.HNSCC的转移常常为癌细胞经上皮间质转...     

Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing radiation

Background and purpose

There is a great need to improve the outcome of locoregionally advanced squamous cell carcinomas of the head and neck (HNSCC). Standard treatment includes a combination of surgery, radio- and chemotherapy. The addition of molecular targeting agents to conventional treatment may improve outcomes. In this study the Raf inhibitor sorafenib was used to increase the radiosensitivity of HNSCC cell lines.

Material and methods

In a panel of six cell lines (A549, FaDu, UTSCC 60A, UTSCC 42A, UTSCC 42B, UTSCC 29) radiosensitivity was measured by colony formation assay and apoptosis and cell cycle analysis were performed by flow cytometry. DNA repair was analyzed by 53BP1 immunohistochemistry.

Results

Sorafenib added prior to irradiation resulted in an increased cellular radiosensitivity (DEF_0.5 = 1.11–1.84). Radiosensitization was not caused by an enhanced rate of apoptosis or cell cycle effects. In contrast, sorafenib was shown for the first time to block the repair of DNA double-strand breaks (DSB).

Conclusion

Our data suggest that sorafenib may be used to overcome the radioresistance of HNSCC through the inhibition of DSB repair.     

Immune checkpoint inhibitors in head and neck squamous cell carcinoma: A systematic review of phase-3 clinical trials

BACKGROUNDThe outcomes of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal. A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors (ICIs). The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIMTo evaluate the evidence on the effectiveness of ICIs in HNSCC, based on published phase-3 clinical trials.METHODSWe searched PubMed, Cochrane Library, Embase, and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC (R/M HNSCC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC). We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma, recurrent, metastatic, locally advanced, immunotherapy, immune checkpoint inhibitors, monoclonal antibodies, programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T- lymphocyte associated protein-4 (CTLA-4), and phase-3 clinical trial. A sensitive search filter was used to limit our results to randomized controlled trials.RESULTSFive phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far: Four in R/M HNSCC and one in LAHNSCC. In patients with R/M HNSCC, anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care (standard single-agent systemic therapy). While the net gain in overall survival (OS) with nivolumab was 2.4 mo [hazard ratio (HR) = 0.69, P = 0.01], that with pembrolizumab was 1.5 mo (HR = 0.80 nominal P = 0.0161). The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T- lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes. In the first-line setting, in R/M HNSCC, pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo (HR = 0.77, P = 0.0034) in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive (combined positive score > 20) population compared to standard of care (EXTREME regime). In patients with PD-L1 positive R/M HNSCC, monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME. In LAHNSCC, immunotherapy using avelumab (an anti-PD-L1 agent) along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSIONAnti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings, with acceptable toxicity profiles compared to standard therapy. There is no proven efficacy in the curative setting to date.     

经颞浅动脉灌注PDD-Fudr/5Fu治疗头颈部鳞状细胞癌

 目的　观察经颞浅动脉灌注PDD +Fudr/ 5 Fu治疗头颈部鳞状细胞癌的疗效。方法　从 1996年 1月～ 2 0 0 0年 12月有 89例头颈部鳞状细胞癌给予动脉化疗 ,A组 4 9例予PDD +Fudr方案 ,B组 4 0例予PDD + 5Fu方案 ,方法与剂量两组相同。结果　A组的总有效率为 83.7% (41/ 4 9) ,其中CR10 .2 % ,PR73.5 % ,SD16 .3% ;B组的总有效率为 75 .0 % (30 / 4 0 ) ,其中CR2 .5 % ,PR72 .5 % ,SD2 5 % ,统计学上两组有效率无明显差异 (P >0 .0 5 )。而口腔溃疡在A组的发生率明显低于B组 ,经 χ2 检验 ,两组有显著差异。结论Fudr在头颈部鳞状细胞癌的辅助化疗中是安全、低毒、高效的 ,值得推荐。     

ErbB4 expression in squamous cell carcinoma of the head and neck

This study set out to delineate ErbB4 overexpression and its impact on prognosis in squamous cell carcinoma (SCC) of head and neck (H&N) origin. Thirty-six of the 47 evaluated SCC of H&N origin came from the larynx, oropharynx, or oral cavity. Twenty-four patients had stage III–IV, 17 had stage I–II, and 6 had recurrent disease. Immunohistochemical stains were performed on paraffin sections using the avidin–biotin–peroxidase method. Forty-five patients received radiation therapy, 24 primary treatment and 21 postoperatively. Nineteen patients with advanced stage disease received concomitant chemotherapy. ErbB4 was highly stained in 24/47 (51%) patients and weakly stained in another 13/47 (28%) patients. Age, gender, site, stage, and treatment approaches similarly distributed between the groups. Overall survival (OS) and disease-free survival (DFS) were similar in ErbB4-positive and ErbB4-negative groups. In conclusion, although ErbB4 is not a prognostic parameter for OS and DFS in H&N SCC, it is highly overexpressed. The high overexpression rate may lead to initiation of anti-ErbB4 targeted therapy in this cohort of patients.     

人乳头状瘤病毒相关头颈部鳞状细胞癌的研究进展

近年来,人乳头状瘤病毒（HPV）相关头颈部鳞状细胞癌的发病率呈上升趋势,尤其表现在口腔鳞状细胞癌中。HPV 相关头颈部鳞状细胞癌具有独特的临床特征、生物学特点及良好预后,且不暴露于吸烟、饮酒等危险因素,其生物标记物及治疗是国际的研究热点。     

HSP27在头颈鳞癌中的研究进展

HSP27是小分子量热休克蛋白(small heat stress proteirs,sHSP)家族中的重要一员,其重要的生物学功能是保护细胞免受各种应激因素的损伤.此外,HSP27也可参与细胞的增殖、分化及细胞凋亡的信号转导通路调节等.近年来,HSP27与临床疾病尤其是与肿瘤的关系日益受到重视,本文就HSP27在头颈鳞癌中的研究进展作一综述.     

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin-5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel-PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and overall response rates were demonstrated across the phase II trials in the range 42-82 and 71-100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and overall response of patients treated with docetaxel-based induction chemotherapy.     

Docetaxel in the management of patients with head and neck squamous cell carcinoma

The taxanes play a significant role in the treatment of various solid tumors of epithelial origin. Docetaxel is the most extensively studied taxane in prospective head and neck cancer trials and has been investigated as induction chemotherapy or in combination with radiotherapy in locally advanced squamous cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or metastatic disease. The data in locally advanced disease are particularly compelling. Three recently reported randomized trials, carried out in patients with locally advanced disease who were receiving induction chemotherapy followed by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the standard induction regimen of cisplatin/5-fluorouracil (PF) significantly improved survival compared with PF alone, without significantly increasing toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current standard induction regimen and TPF-based sequential therapy can be considered a standard treatment alternative to chemoradiotherapy alone in patients with locally advanced HNSCC. This review article discusses the current developments of docetaxel-based chemotherapy and the optimal use of this agent in patients with HNSCC.     

西妥昔单抗联合化疗在复发或转移头颈部鳞状细胞癌中的应用

复发或转移头颈部鳞状细胞癌(SCCHN)预后较差.西妥昔单抗是一种可抑制表皮生长因子(EGFR)的单克隆抗体,并可提高包括顺铂在内的多种化疗药物疗效.多项临床研究结果显示,西妥昔单抗联合化疗对复发或转移头颈部鳞癌有效,以其高疗效和低不良反应在治疗中显示出了优势.