新辅助免疫治疗在头颈部鳞状细胞癌中的研究进展

头颈部鳞状细胞癌(HNSCC)是全球第八大常见癌症,超过一半的HNSCC患者可出现局部复发或远处转移。随着医学的发展,免疫治疗药物的陆续问世为复发/转移性HNSCC患者带来了新的希望。目前多项研究已经证实,以程序性死亡受体1(PD-1)检查点抑制剂为代表的新辅助免疫治疗具有较好的疗效,且安全性良好,而以新辅助免疫治疗为基础的联合治疗也成为研究热点,包括新辅助免疫治疗联合化疗、放疗、放化疗、靶向治疗以及新辅助双免疫联合治疗等新型治疗模式。本文将对新辅助免疫治疗在HNSCC中的研究进展作一综述。     

头颈鳞癌靶向放疗进展

<正>近年来随着影像、放疗技术及分子靶向治疗的研究,使得作为头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)三大传统治疗方式之一的放疗得到了发展。靶向放疗作为HNSCC新的治疗手段进入了人们的视野,它主要通过放疗设备及技术将放射线高效的靶向作用于肿瘤组织细胞同时减少放射线对正常组织细胞的伤害,保护肿瘤组织周围的重要器官和组织。主要方式包括调     

头颈鳞状细胞癌乏氧微环境与放疗抵抗相关性的研究进展

头颈鳞状细胞癌(HNSCC)的治疗方式有手术和放化疗.治疗后HSNCC的高复发率及其显著的转移能力是影响HNSCC患者预后的主要因素,且放化疗存在各种并发症,包括放射性口腔黏膜炎、局部软组织损伤等,严重影响患者生活质量.而肿瘤局部组织内乏氧造成的乏氧微环境与肿瘤治疗抵抗和复发的关系密切相关,如果能采取措施改善肿瘤微环境...     

整合素αvβ6在头颈部鳞状细胞癌中的作用研究

头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)起源于口腔、鼻腔、鼻窦和咽的黏膜上皮,为头颈部常见恶性肿瘤。许多患者以局部晚期病变为特征,经过手术联合放化疗后生存率仍然较低。局部复发、颈淋巴结转移、远处转移是影响HNSCC患者预后的重要因素。识别与复发和转移相关的肿瘤标志物,对预测肿瘤生物学行为和治疗策略的方向具有重要意义。大量研究证实整合素αvβ6在HNSCC中表达显著上调,而且能通过多种机制介导HNSCC肿瘤细胞的侵袭与转移。其表达的增加与HNSCC的疾病进展和较差的预后有关。因此,整合素αvβ6有望成为HNSCC预后的预测指标和治疗靶点。     

局部晚期头颈部鳞状细胞癌的化疗及靶向进展

局部晚期头颈部鳞状细胞癌目前主要采用手术、放疗和化疗相结合的综合治疗,但是器官功能保留率和5年生存率没有显著提高。从20世纪70年代末开始,以顺铂为基础的化疗药开始应用于局部晚期头颈部鳞状细胞癌治疗中,研究表明,顺铂联合氟尿嘧啶作为诱导化疗方案提高了喉功能保全率。后来随着紫杉醇的应用,有研究证实在PF方案基础上加用紫杉醇可提高诱导化疗的疗效。与PF方案相比,TPF方案在局部控制率及无进展生存期上有显著的优越性,因此,成为诱导化疗的首选方案。20世纪90年代初期,同步放化疗成为非手术治疗及保喉的新方式,因其在总体生存率、保喉率、局部控制率上有明确的优势,已被列入局部晚期头颈部肿瘤非手术治疗的标准治疗方案。2006年分子靶向治疗药物西妥昔单抗经美国食品和药物管理局批准运用于临床,因其预后的优势及较少的不良反应成为无法耐受化疗药物的新选择。就局部晚期头颈部鳞状细胞癌的化疗药物及靶向药物治疗进展进行综述。     

化疗应用于头颈部鳞状细胞癌治疗的新动向

近年来，随着同步放化疗、序贯化疗等方案的兴起，化疗在头颈部鳞状细胞癌治疗中的作用已不仅限于姑息治疗，与放疗联合提高了肿瘤的局部控制率，较单纯放疗相比有更好的疗效。但治疗病例选择问题和较高的严重副反应发生率仍制约其成为头颈部鳞状细胞癌的常规治疗。     

线粒体自噬与头颈部鳞状细胞癌关系的研究进展

头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)是全球最常见的6种癌症之一,很多晚期患者因肿瘤复发或对化疗药物耐药而死亡。努力开拓治疗HNSCC新策略,对于HNSCC患者的预后具有重大意义。线粒体自噬是一种选择性的宏观自噬形式,通过相关通路蛋白或者药物调控减轻氧化应激和预防癌的发生,又或者在一些不利条件下促进肿瘤细胞的存活。目前大量研究证明,线粒体自噬是控制癌细胞质量的关键因素,与肿瘤发生发展密切相关。线粒体功能障碍促进细胞癌变;线粒体自噬功能失调可诱导癌细胞凋亡;新型药物的出现开拓了靶向线粒体治疗肿瘤的新方法,线粒体自噬对于肿瘤的防治展现出巨大潜能。论文将从线粒体自噬的调控机制、线粒体自噬与肿瘤的关系、HNSCC防治及临床耐药性等方面进行综述,旨在为HNSCC治疗提供新的方向和靶点。     

rAd-p53联合放化疗治疗晚期头颈部鳞状细胞癌

p53基因是迄今为止发现与人类肿瘤相关性最高的基因,在头颈部癌中,p53基因在喉癌、上颌窦癌、唾液腺癌、鼻咽癌等中均可见到阳性表达,而以复制缺陷型重组腺病毒为载体的p53基因替代疗法作为一种肿瘤治疗的新方法在头颈部鳞状细胞癌（鳞癌）中取得了很好的疗效,且临床应用安全。自2006年3月至2006年12月,我科应用重组人p53腺病毒（recombinant adenovirus—p53,rAd—p53,商品名为今又生）注射液对14例局部晚期或复发性头颈部鳞癌联合放化疗进行治疗,获得了较好的近期疗效,报道如下。     

纠正肿瘤微环境乏氧相关方法研究进展

治疗头颈部鳞状细胞癌(HNSCC)的手段尽管不断改善,患者生活质量水平有所提高,但患者术后5年生存率并没有得到明显提高.治疗抵抗和复发一直是头颈鳞癌治疗中的难题,但局部组织内缺氧造成的乏氧微环境与肿瘤治疗抵抗和复发的关系密不可分.如果能采取有效措施改善肿瘤微环境乏氧状况,就可能提高HNSCC的治疗效果.     

TGFBI在头颈部鳞状细胞癌中的表达及其临床意义

目的 探索转化生长因子β诱导基因(transforming growth faetor β indured gene, TGFBI)在头颈部鳞状细胞癌(head and neck souamous cell carcinoma, HNSCC)中的表达及其临床意义。方法 采用NCBI数据库中的单细胞RNA-Seq测序数据分析TGFBI在免疫细胞中的表达,并通过Bulk RNA-Seq探索HNSCC肿瘤微环境的浸润情况。使用TCGA数据库分析TGFBI在HNSCC中的基因表达量及预后价值,并用临床标本验证。根据TGFBI表达量分组后HNSCC患者对靶向治疗和免疫治疗的响应进行TCGA数据评估,分析基因突变对TGFBI表达的影响。结果 TGFBI高表达于M2型巨噬细胞。TGFBI高表达与HNSCC患者不良预后相关。TGFBI低表达患者潜在响应免疫治疗,而TGFBI高表达的患者潜在响应靶向治疗。TP53突变与TGFBI高表达相关。结论 TGFBI可作为HNSCC患者生存与治疗反应的潜在生物标志物。     

免疫检查点抑制剂在复发或转移性头颈鳞癌的治疗进展

以铂类为基础的化疗联合西妥昔单抗是复发或转移性头颈鳞状细胞癌（R/M HNSCC）的标准治疗方式，然而治疗后有易复发、中位生存期短等问题。以PD-1/PDL-1单抗为主的免疫检查点抑制剂（ICIs）开始成为R/M HNSCC新的临床治疗方案，且pembrolizumab和nivolumab都已被FDA批准用于经铂类治疗失败的R/M HNSCC。现就ICIs在R/M HNSCC的临床试验进行系统汇总，并对药物的不良反应及生物标志物进行阐述，为未来在R/M HNSCC中使用ICIs提供理论基础。     

Therapie der Rezidiv- und Fernmetastasen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs

In many cases squamous cell carcinoma of the head and neck is already in an advanced stage when initially diagnosed. Despite definitive treatment, loco-regional recurrences and metastases are common and patients ultimately require systemic treatment. Epidermal growth factor receptor (EGFR) inhibitors have proven to significantly prolong survival and have therefore become the first line treatment in recurrent and metastatic squamous cell carcinoma of the head and neck in addition to platinum and 5-FU treatment. Good results have also been reported for EGFR inhibitors in cases where platinum-based treatment has failed. Further strategies, such as salvage surgery, platinum-based chemotherapy, targeted therapy, chemoradiation and reirradiation are currently under investigation to reduce toxicity and improve survival and health-related quality of life.     

Aktuelle Therapieoptionen bei rezidivierenden Kopf-Hals-Tumoren

Recurrent disease is one of the main reasons for the persistently poor prognosis of squamous cell carcinoma of the head and neck (HNSCC; European 5-year survival, 42%). The main treatment option for primary and secondary malignancy as well as recurrent disease is surgical therapy. If R0 resection (resection margin >5 mm) for a primary tumor is not viable, survival probability is reduced by 50%. In recurrent or secondary tumors with R1- or -2 resection or in the presence of non-resectable metastases, a palliative situation results in more than 80% of cases. In the case of surgery following radiotherapy or radiochemotherapy, attention should be paid to the criteria for salvage surgery (tissue perfusion, fibrosis, wound healing) and the procedure adapted to focus on functionality. In the case of relapse, primary surgery can potentially be supplemented with adjuvant therapy protocols such as (re-) irradiation, as well as possibly with chemotherapeutic agents or targeted therapies. Interdisciplinary collaboration and case discussions should take place in the context of a tumor board.     

Systemic therapy strategies for head-neck carcinomas: current status

Head and neck cancers, most of which are squamous cell tumours, have an unsatisfactory prognosis despite intensive local treatment. This can be attributed, among other factors, to tumour recurrences inside or outside the treated area, and metastases at more distal locations. These tumours therefore require not only the standard surgical and radiation treatments, but also effective systemic treatment. The main option here is antineoplastic chemotherapy, which is firmly established in the palliative treatment of recurrent or metastatic stages of disease, and is used with curative intent in the form of combined simultaneous or adjuvant chemoradiotherapy in patients with inoperable or advanced tumour stages. Neoadjuvant treatment strategies for tumour reduction before surgery have yet to gain acceptance. Induction chemotherapy protocols before radiotherapy have to date been used in patients at high risk of distant metastases or as an aid for decision-making ("chemoselection") in those with extensive laryngeal cancers, prior to definitive chemoradiotherapy or laryngectomy. Triple-combination induction therapy (taxanes, cisplatin, 5-fluorouraeil) shows high remission rates with significant toxicity and, in combination with (chemo-)radiotherapy, is currently being compared with simultaneous chemoradiotherapy the current gold standard with regards to efficacy and long-term toxicity. A further systemic treatment strategy, called 'targeted therapy', has been developed to help increase specificity and reduce toxicity. An example of targeted therapy, EGFR-specific antibodies, can be used in palliative settings and, in combination with radiotherapy, to treat advanced head and neck cancers. A series of other novel biologicals such as signal cascade inhibitors, genetic agents, or immunotherapies, are currently being evaluated in large-scale clinical studies, and could prove useful in patients with advanced, recurring or metastatic head and neck cancers. When developing a lasting, individualised systemic tumour therapy, the critical evaluation criteria are not only efficacy and acute toxicity but also (Iong-term) quality-of-life and the identification of dedicated predictive biomarkers.     

The chemotherapy of head and neck cancer

Chemotherapy in head and neck cancer can be given in metastatic disease at presentation, in locally far advanced disease not amendable for curative treatment with surgery and/or radiotherapy, in the neo-adjuvant setting, in recurrent disease after previous surgery and radiotherapy and either concurrent or alternating with radiotherapy. Most data are gathered in the recurrent and locally far advanced disease setting. Combination therapy (with agents such as cisplatinum, 5-FU and methotrexate) have shown some improvements in response rate, however no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck has been observed. In the neo-adjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New compounds and approaches are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease are the taxanes. With monotherapy docetaxel, response rates of 23%-42% are seen, and, when used in combination with cisplatinum and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neo-adjuvant therapy with cisplatinum and 5-FU is now underway.     

Occult nodal metastasis in head and neck carcinoma patients treated with chemoradiotherapy

Background and aimNeck lymph node metastasis plays an important role in the prognosis of patients with squamous cell carcinoma of the head and neck. The aim of this study was to evaluate the occult nodal metastasis in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemo radiotherapy.MethodsIn this 5-year prospective study, patients with recurrent head and neck squamous cell carcinomas (HN-SCC) after primary treatment with chemoradiotherapy or radiotherapy that candidate for surgery were enrolled. In total, 50 patients with squamous cell carcinomas of the head and neck with N0 neck were included in the study. Age, initial location of recurrent tumor, T staging in primary and recurrent tumors, neck condition (N0 or N+), and pathology report for neck metastasis, number of affected lymph nodes and duration of tumor recurrence were examined.ResultsOut of 50 patients with mean age of 57.04 ± 14.4 years, 13 were female (26%) and 37 (74%) were male. In terms of primary tumor size, 52% (26 patients) were in T2 stage. The primary and recurrent tumor was located in the oral cavity in 33 patients (66%). Nine 0f 50 patients (18%) had occult metastases.ConclusionIt seems that END surgery is necessary for treatment the occult lymph node neck metastasis of recurrent head and neck cancers with N0 neck. Therefore, it is possible that END surgery has reduced cervical recurrence in these patients.     

Studienergebnisse zur Primärtherapie von Kopf-Hals-Tumoren

At the annual meeting of the American Society of Clinical Oncology (ASCO) 2016, results of current trials dealing with primary therapy for head and neck squamous cell carcinoma (HNSCC) were presented. Current trials investigate in particular therapy regimens for the treatment of locally advanced HNSCC. Concomitant chemoradiotherapy (CRT) remains the standard therapy approach. Current trials focus on sequential chemoradiation with modifications in induction chemotherapy (ICT) or the subsequent CRT schedule. Studies investigating the combination of targeted therapy with the epidermal growth factor receptor (EGFR) antibody cetuximab and concomitant, sequential, or adjuvant therapy were presented. The most important trials are summarized in this article.     

Neue Aspekte zur aktuellen Therapie von Oropharynxkarzinomen

Beside the surgical treatment of head and neck cancer, the concept of organ and function preserving therapy of locally advanced HNSCC (head and neck squamous cell carcinoma) especially of oropharyngeal origin is becoming increasingly important. The comparison of induction chemotherapy plus chemoradiation and primary concomitant chemoradiation has recently been the subject of randomized clinical trials. New combinations of different (chemo)radiation regimens and targeted therapies are also under investigation for HNSCC. Molecular markers predicting treatment efficacy as well as new potential targets are also being evaluated in several clinical trials. The good prognosis of HPV-associated HNSCC has sparked efforts to deintensify treatment to minimize therapy-related toxicities. The impact of specific therapies is growing due to the increasing incidence of young patients with HPV-positive carcinomas.