BRAF突变型黑色素瘤治疗进展

BRAF基因在黑色素瘤的发生发展中起重要作用,中国黑色素瘤患者中BRAF突变率为25.9%,最常见的突变位点是BRAF V600E,BRAF突变型黑色素瘤预后更差。随着新型靶向及免疫治疗药物,包括BRAF抑制剂、MEK抑制剂、程序性死亡受体-1（programmed death receptor-1,PD-1）/程序性死亡受体-1配体（programmed death receptor-1 ligand,PD-L1）抑制剂、细胞毒性T淋巴细胞相关蛋白- 4 （cytotoxic T-lymphocyte antigen- 4 ,CTLA-4 ）抑制剂等的出现,近年来BRAF V600突变型黑色素瘤在辅助治疗及系统治疗中取得了很大的突破,本文旨在对BRAF突变型黑色素瘤的治疗进展进行综述。      

头颈部黏膜恶性黑色素瘤的临床诊治现状及进展

头颈部黏膜恶性黑色素瘤是一类少见的恶性肿瘤,主要发生在鼻窦和口腔,5年生存率不到30%。目前治疗模式尚存争议。多数回顾性研究结果显示术后放疗可以提高LC,但OS率未见明显获益。本文旨在加强对头颈部黏膜恶性黑色素瘤的认识,包括其临床特点、诊断、分期、治疗模式和疗效等。     

转移性恶性黑色素瘤分子靶向及免疫治疗进展

黑色素瘤是恶性程度最高的皮肤肿瘤,基于对黑色素瘤细胞的基因突变和免疫系统研究的深入,分子靶向和免疫治疗药物为晚期黑色素瘤带来了新的契机。全文总结近年治疗恶性黑色素瘤靶向药物及相关治疗通路的研究进展。     

头颈部黏膜恶性黑色素瘤诊断与治疗进展

头颈部黏膜恶性黑色素瘤常发生于眼内、口腔、下咽、鼻腔鼻旁窦、鼻咽等部位。睫状体或脉络膜黏膜恶性黑色素瘤诊断基础是临床检查，CT，MRI，细针穿刺抽吸活检利于确诊，治疗方法为观察和局部治疗方法，如放疗、光照疗法、冷冻疗法、超声高温疗法、局部切除以及眼球摘除术。鼻腔鼻旁窦黏膜恶性黑色素瘤组织学检查是首要的诊断依据，治疗可采取：手术、化疗、免疫治疗、局部复发后采用包括外科手术切除、补充放疗、化疗、免疫治疗。口腔、鼻咽及下咽黏膜恶性黑色素瘤主要依据内窥镜及病理活检诊断，CT扫描及MRI检查利于明确病变范围及分期，可采用手术、放疗和化疗综合治疗。     

恶性黑色素瘤生物治疗研究进展

黑色素瘤是较常见的恶性肿瘤,近年来已经成为发病率增长最快的肿瘤之一.自2011年依匹单抗等药物经FDA批准上市后,黑色素瘤相关治疗的研究与发展就一直处于各类肿瘤研究的前列.现我国黑色素瘤患者死亡病例与新发病例的比例明显高于全球平均水平,但治疗情况却与国外差距悬殊,生存率相差甚远,8种FDA批准的药物在我国也均未上市.文章就目前黑色素瘤治疗相关药物临床应用进展、耐药机制研究及新型免疫药物的开发予以综述.     

恶性黑色素瘤的免疫治疗现状与进展

恶性黑色素瘤是一种高度恶性,易转移,预后差,对化疗放疗均不敏感的恶性肿瘤。随着肿瘤免疫学、分子生物学技术的迅速发展,过继免疫治疗、生物化学治疗、肿瘤疫苗、靶向治疗以及佐剂等治疗恶性黑色素瘤的方法显示了良好的应用前景。免疫治疗已逐渐成为肿瘤综合治疗的一个重要组成部分,文章就该方面的研究进展进行综述。     

恶性黑色素瘤的免疫治疗现状与进展

恶性黑色素瘤是一种高度恶性,易转移,预后差,对化疗放疗均不敏感的恶性肿瘤。随着肿瘤免疫学、分子生物学技术的迅速发展,过继免疫治疗、生物化学治疗、肿瘤疫苗、靶向治疗以及佐剂等治疗恶性黑色素瘤的方法显示了良好的应用前景。免疫治疗已逐渐成为肿瘤综合治疗的一个重要组成部分,文章就该方面的研究进展进行综述。     

头颈部恶性黑色素瘤28例的治疗及预后因素

目的：探讨影响恶性黑色素瘤的治疗及其预后因素。方法：本院头颈外科1984年-1994年10年间诊断28例恶性黑色素瘤,治疗方法分广泛切除,广泛切除加预防性颈清扫术,广泛切除加治疗性颈清扫术3组,并作回顾性分析。结果：28例患者外院局部切除23例,残留率34.8%。原发灶切除范围分≤2cm组及＞2cm组,五年生存率分别为58%及40%。上述3组的五年生存率分别为80%、80%及39%。结论：原发灶的处理要规范,切除范围2cm以内。对颈淋巴结未及肿大的患者可暂不行颈淋巴结清扫术。颈洒巴结阳性患者可依原发灶的部位不同施行不同方式的颈清扫术,并强调颈清扫术中皮片分离应在颈阔肌浅面进行,以减少术后复发。     

头颈部恶性黑色素瘤45例临床分析

头颈部恶性黑色素瘤临床少见,是恶性程度高、易转移、复发率高和预后差的恶性肿瘤之一。我院自1984年～1996年共收治45例,现报告如下: 1 临床资料 1.1 一般资料 全组45例恶性黑素瘤(以下简称恶黑)患者,男31例,女14例;年龄18岁～72岁,平均45岁。病程7天～1年,平均6个月。本组头颈部皮肤恶黑11例(男6例,女5例),头颈部粘膜恶黑30例(男16例,女14例),腮腺、颌下腺各2例。其中头颈部皮肤恶黑伴有颌下或颈部淋巴结转移者3例,头颈部粘膜恶黑伴有颌下及颈部淋巴结转移者16例。 1.2 诊断 本组45例患者的手术切除标本经病理学检查和免疫组化方法确诊均为恶性黑色素瘤,其中12例为无色素性黑色素瘤。 1.3 治疗 头颈部皮肤恶黑11例患者中,8例术前及术后均给予DTIC、CCNU、VCR、CTX或PDD方案化疗;术中对病灶采取扩大切除,术后行放疗或免疫治疗;对于有颈部淋巴结或颌下淋巴结转移的患者,予以行颈部清扫术或颌下三角清扫术。头颈部粘膜恶黑30例中,有18例于术前或术后以上述方法化疗。术中对病灶采取扩大切除,术后行放疗或免疫治疗。腮腺及颌下腺各2例仅行病灶扩大切除。     

Current management of mucosal melanoma of the head and neck

While mucosal-based melanomas of the head and neck region are uncommon lesions, when they do arise they usually follow an inexorably aggressive course. Experience with these tumors is, necessarily, limited; as such, well-worked out treatment protocols for the treatment of such lesions are in short supply. It appears as though mucosal melanomas (MuMs) develop more frequently in the nasal cavity and paranasal sinus region, and less often in the oral cavity. It seems that the incidence of nodal metastasis is significantly lower for sinonasal MuMs than it is for MuMs of the oral cavity; this observation may influence decisions about performing neck dissection as a function of location of the primary MuM. At present, surgical excision remains the mainstay of treatment; however, anatomical complexities within the region can hamper attempts at complete excision. Radiotherapy has not traditionally been relied on for routine treatment of MuM, although some recent reports have challenged this view. Chemotherapy is, at present, employed principally in the treatment of disseminated disease and for palliation. As a diagnostic matter, MuM belongs to the class of tumors that, on light microscopy, may with some regularity be confused with other malignancies (including sarcomas, plasmacytomas, and carcinomas); as a consequence, this is a diagnosis which is often best confirmed by way of ancillary testing via immunohistochemical studies. A better grasp of the best means of treating MuM will likely come only when large referral centers are able to pool their experiences with these uncommon yet virulent malignancies.     

Optimizing treatments for recurrent or metastatic head and neck squamous cell carcinoma

Introduction: The majority of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) will recur. The treatment of patients with recurrent/metastatic (R/M HNSCC) is rapidly evolving.

Areas covered: This article will comprehensively review the current systemic treatment of R/M HNSCC.

Expert commentary: For the time being, the EXTREME regimen (cetuximab in combination with platinum and 5-fluorouracil) still remains standard of care in previously untreated R/M HNSCC patients who are candidates for combination chemotherapy. Single agents with well documented activity in HNSCC include methotrexate, cisplatin, 5-FU, docetaxel, and paclitaxel. The anti-PD-1 monoclonal antibody nivolumab can be considered the current standard of care in patients with R/M HNSCC progressing after platinum-based therapy based on the results of CheckMate 141 showing a survival benefit over standard of care drugs, such as single agent weekly cetuximab, methotrexate, or docetaxel.

Multiple randomized phase III trials comparing anti-PD(L)-antibodies either as single agent or in combination with chemotherapy or an anti-CTLA-4 with the EXTREME as fist line treatment are ongoing or planned. The outcome of these trials might change the current treatment paradigm in previously untreated R/M HNSCC. Immunotherapeutic agents under active investigation include Toll-like receptor 8 agonists and inhibitors of IDO1.     

Targeting DDR2 in head and neck squamous cell carcinoma with dasatinib

Squamous cell carcinoma of the head and neck (HNSCC) is the tenth most common tumor entity in men worldwide. Nevertheless therapeutic options are mostly limited to surgery and radio‐chemotherapy resulting in 5‐year survival rates of around 50%. Therefore new therapeutic options are urgently needed. During the last years, targeting of receptor tyrosine kinases has emerged as a promising strategy that can complement standard therapeutical approaches. Here, we aimed at investigating if the receptor tyrosine kinase DDR2 is a targetable structure in HNSCC. DDR2 expression was assessed on a large HNSCC cohort (554 patients) including primary tumors, lymph node metastases and recurrences and normal mucosa as control. Subsequently, DDR2 was stably overexpressed in two different cell lines (FaDu and HSC‐3) using lentiviral technology. Different tumorigenic properties such as proliferation, migration, invasion, adhesion and anchorage independent growth were assessed with and without dasatinib treatment using in‐vitro cell models and in‐vivo zebrafish xenografts. DDR2 was overexpressed in all tumor tissues when compared to normal mucosa. DDR2 overexpression led to increased migration, invasion, adhesion and anchorage independent growth whereas proliferation remained unaltered. Upon dasatinib treatment migration, invasion and adhesion could be inhibited in‐vitro and in‐vivo whereas proliferation was unchanged. Our data suggest treatment with dasatinib as a promising new therapeutic option for patients suffering from DDR2 overexpressing HNSCC. Since dasatinib is already FDA‐approved we propose to test this drug in clinical trials so that patients could directly benefit from this new treatment option.     

头颈部原发性黏膜恶性黑色素瘤患者PD－L 1表达及其临床相关因素分析

目的：探讨头颈部原发性黏膜恶性黑色素瘤患者程序性细胞死亡配体1（PD－L1）表达及其临床意义。方法：研究采用免疫组化检测45例头颈部原发性黏膜恶性黑色素瘤样本PD－L1表达,分析其表达与患者临床病理学特征及疾病预后的关系。结果：所有患者均接受手术切除治疗联合干扰素治疗。随访患者5年生存率为44．4％（20／45）,平均生存期为51个月,无复发生存期为23个月。免疫组化染色证实57．8％（26／45）肿瘤样本为 PD －L1高表达,显著多与临近非肿瘤组织（P＝0．0037）。PD－L1表达与患者年龄（P＝0．09）、性别（P＝0．16）、肿瘤分布（P＝0．08）无关,而PD－L1阳性患者的无复发生存期显著短于阴性患者（P＝0．027）。多变量分析证实PD－L1高表达是头颈部原发性黏膜恶性黑色素瘤患者预后不良独立标志物。结论：PD－L1高表达与头颈部原发性黏膜恶性黑色素瘤进展和预后不良密切相关,可以作为该疾病的预后标志物。     

头颈部鳞状细胞癌靶向治疗进展

每年全世界大约有65万例新的头颈癌病例出现,其中绝大多数是头颈部鳞状细胞癌。晚期头颈部鳞状细胞癌的治疗需要综合治疗,尽管放化疗及手术治疗手段在不断发展,但是预后仍不理想且具有一定的毒副反应。靶向治疗是目前治疗研究头颈部鳞癌的热点,其在针对头颈部鳞癌的治疗特别是对局部晚期或复发/转移性头颈部鳞癌治疗中展现出了希望。本文综述了靶向治疗的最新进展。     

Sentinel lymph node biopsy is accurate and prognostic in head and neck melanoma

BACKGROUND:

Sentinel lymph node biopsy (SLNB) has emerged as a widely used staging procedure for cutaneous melanoma. However, debate remains around the accuracy and prognostic implications of SLNB for cutaneous melanoma arising in the head and neck, as previous reports have demonstrated inferior results to those in nonhead and neck regions. Through the largest single‐institution series of head and neck melanoma patients, the authors set out to demonstrate that SLNB accuracy and prognostic value in the head and neck region are comparable to other sites.

METHODS:

A prospectively collected database was queried for cutaneous head and neck melanoma patients who underwent SLNB at the University of Michigan between 1997 and 2007. Primary endpoints included SLNB result, time to recurrence, site of recurrence, and date and cause of death. Multivariate models were constructed for analyses.

RESULTS:

Three hundred fifty‐three patients were identified. A sentinel lymph node was identified in 352 of 353 patients (99.7%). Sixty‐nine of the 353 (19.6%) patients had a positive SLNB. Seventeen of 68 patients (25%) undergoing completion lymphadenectomy after a positive SLNB result had at least 1 additional positive nonsentinel lymph node. Patients with local control and a negative SLNB failed regionally in 4.2% of cases. Multivariate analysis revealed positive SLNB status to be the most prognostic clinicopathologic predictor of poor outcome; hazard ratio was 4.23 for SLNB status and recurrence‐free survival (P < .0001) and 3.33 for overall survival (P < .0001).

CONCLUSIONS:

SLNB is accurate and its results are of prognostic importance for head and neck melanoma patients. Cancer 2012;. © 2011 American Cancer Society.