放疗联合免疫检查点抑制剂在非小细胞肺癌中的研究进展

非小细胞肺癌(non-small-cell lung cancer, NSCLC)是一种常见且致命的恶性肿瘤。放疗(radiation treatment, RT)是NSCLC一种有效的局部治疗方式。免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)在NSCLC患者治疗方面显示出了持久、显著的疗效，为NSCLC患者带来了新的希望，但需要采取策略将其疗效进一步扩大。初步证据表明，RT可能会调节患者的免疫系统，与全身免疫治疗药物具有协同作用，而且随着RT技术的改进及不同ICIs的研发，这种协同作用愈发显著。RT联合ICIs使远隔效应发生率增加，这引起研究人员的广泛关注。二者的结合已显示出对控制肿瘤进展和延长NSCLC患者生存期的改善效果。联合治疗虽取得了一定成果，但仍有一些问题需进一步解决，如RT联合ICIs的协同作用机制、ICIs种类、RT剂量与分割、联合治疗顺序、疗效与安全性、可靠的预测性生物标志物等，本文就RT联合ICIs治疗NSCLC患者的研究进展进行综述，为临床选择提供参考。     

晚期非小细胞肺癌靶向治疗的研究进展

随着测序技术的发展,不同分子靶点药物的研发,实体肿瘤的靶向治疗水平不断提高,给非小细胞肺癌(NSCLC)患者尤其是晚期患者带来希望。分子靶向治疗精确作用于肿瘤组织,减轻对正常组织的损伤,抗肿瘤作用准确,不良反应少,可明显改善患者预后,延长其生存期。目前,已有5类NSCLC靶向药物经美国食品药品管理局批准上市,分别为表皮生长因子受体抑制剂吉非替尼、埃克替尼及阿法替尼等,血管内皮生长因子抑制剂贝伐珠单抗和重组人血管内皮抑制素等,间变性淋巴瘤激酶抑制剂克唑替尼、色瑞替尼及艾乐替尼等,免疫靶向治疗药物派姆单抗和阿特朱单抗,     

非小细胞肺癌EGFR靶向治疗的研究进展

肺癌是目前世界上发病率和病死率最高的癌症,其中非小细胞肺癌(NSCLC)占肺癌的85％以上.近10年来,随着对肿瘤生物学的深入研究,作为NSCLC治疗靶点的多个基因突变已被识别,其中表皮生长因子受体(EGFR)基因的突变频率最高,因此,EGFR基因的靶向治疗也逐渐成为NSCLC治疗的主力军.本文将就目前NSCLC中的EGFR基因突变及其靶向治疗药物进行简要阐述.     

非小细胞肺癌的分子靶向治疗进展

近年来分子靶向治疗药物成了肿瘤治疗领域的研究热点之一,目前研究最为广泛的靶向治疗药物主要有表皮生长因子受体（EGFR）家族抑制剂、血管生成抑制剂、多靶点抑制剂、信号传导抑制剂等。现将非小细胞肺癌（NSCLC）分子靶向治疗的研究进展情况综述如下。     

小细胞肺癌免疫治疗的研究进展

小细胞肺癌(SCLC)虽然对放化疗敏感,但易在短时间内复发、转移,患者后期治疗效果极差.SCLC的免疫治疗包括免疫检查点抑制剂、肿瘤疫苗、干扰素、免疫调节剂、细胞因子等,免疫检查点抑制剂主要包括程序性死亡受体1(PD-1)/程序性死亡配体(PD-L1)抑制剂和细胞毒性T淋巴细胞相关抗原4(CTLA-4)抑制剂.CTLA...     

PCSK9及其抑制剂在非小细胞肺癌中的研究进展

目前针对非小细胞肺癌(non-small cell lung cancer, NSCLC)患者的内科治疗主要包括靶向基因治疗和免疫抑制剂治疗,然而对于靶向基因阴性的晚期非小细胞肺癌患者来说,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗临床获益有限,近年来有研究发现前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(propmtein convertase subtilisin/kexin 9,PCSK9)抑制剂在某些恶性肿瘤有一定的治疗作用。本文通过系统检索目前PCSK9与NSCLC的相关研究可发现PCSK9在肺癌细胞的迁移、凋亡及化学耐药中均发挥调节作用。抑制PCSK9或可成为治疗NSCLC的一种可行方法。     

非小细胞肺癌分子靶向治疗策略

<正>肺癌治疗已迈向分子分型(molecular classification)的新时代,在生物标志物(biomarker)指导下的个体化治疗将成为肺癌治疗的发展方向。"患者、路径、进展(Patients,Pathways,Progress)"是现阶段肺癌个体化治疗策略的最佳总结。在肺腺癌中已发现若干个驱动基因,如表皮生长因子受体(EGFR)活化突变、K-Ras突变、c-Met扩增、HER2突变和EML4/ALK的表达增加等,而不同的肺癌个体存在不同的驱动基因或靶点,通过检测     

非小细胞肺癌的联合靶向治疗

虽然化疗对于晚期非小细胞肺癌患者的预后有一定疗效,但已进入一个平台期.特别对于化疗无效的患者,亟需新的、更有效的治疗方法.随着研究人员对肿瘤细胞生长、运动、转移以及肿瘤血管生成机制的深入了解,靶向治疗成为研究的热点.本文综述了现在主要使用的分子靶向药物及重要的临床试验,并对联合靶向治疗进行了阐述.     

老年晚期非小细胞肺癌患者免疫检查点抑制剂研究进展

肺癌是最常见的老年恶性肿瘤之一,以免疫检查点抑制剂为代表的免疫治疗利用机体免疫系统达到有效的抗肿瘤效应。在晚期非小细胞肺癌(NSCLC)患者中,免疫检查点抑制剂单药治疗及联合治疗已成为重要的治疗手段,现对免疫检查点抑制剂类药物在老年晚期NSCLC患者中应用的效果、不良反应、超进展情况进行综述,为老年NSCLC免疫治疗策...     

非小细胞肺癌的靶向治疗和免疫治疗进展

肺癌是全球最常见、病死率最高的恶性肿瘤,除传统的手术、放疗、化疗外,近20年肺癌的治疗发生了巨大变化,针对驱动基因阳性的靶向治疗和针对免疫检查点的免疫治疗显著提高了晚期非小细胞肺癌(NSCLC)患者的生存期。多项临床随机对照试验数据的发布使靶向治疗和免疫治疗在肺癌综合治疗中的地位逐渐提高。如何更加精准地使用靶向治疗和免疫治疗、选择真正获益的患者需要更深入的研究探索。本文从肺癌靶向治疗和免疫治疗的临床研究、精准人群筛选、耐药机制等方面进行综述。     

晚期非小细胞肺癌脑转移的靶向治疗

脑转移是非小细胞肺癌(NSCLC)常见的转移部位,出现脑转移的患者生活质量下降,预后不佳.目前脑转移的主要治疗方式为全脑放疗,常规化疗对脑转移治疗效果不佳.近期多个个案报道和小规模的回顾性研究发现以吉非替尼和厄洛替尼为代表的表皮生长因子受体-酪氨酸激酶抑制剂对NSCLC脑转移体现出良好治疗效果.特别是对于存在表皮生长因子受体基因突变的患者,效果更加显著.提示该类药物可能是治疗NSCLC脑转移的一个好选择.     

非小细胞肺癌免疫治疗进展

目前非小细胞肺癌仍是癌症死亡的主要原因。近年来,随着多项免疫治疗药物在临床试验中呈现出良好的治疗效果,非小细胞肺癌的免疫治疗目前正受到越来越多的关注。本文就当前非小细胞肺癌免疫疗法的原理、相关药物临床试验以及评价标准作一概述。     

晚期非小细胞肺癌化学治疗的新进展

非小细胞肺癌的治疗在过去的20多年里有了相当大的进步,化疗相比支持治疗更能使总体受益.第三代以铂类为基础的两药联用方案已经确立.无铂方案也在发展.化疗已经广泛用于那些以前被认为不适用化疗的患者,化疗持续时间也变得更短,而疗效相当.在认识到化疗所带来的益处之后,出现了一些具有新颖作用机制的新药.本文就目前化疗的概况,方案,以及靶向治疗、新化疗药物的进展作一综述.     

晚期非小细胞肺癌免疫检查点抑制剂相关性肌炎的临床病理学特征

目的:报道晚期非小细胞肺癌免疫检查点抑制剂（ICI）相关性肌炎的临床病理学特征与治疗转归。方法:回顾性分析2019年6月至2020年12月广州医科大学附属第一医院呼吸病理中心数据库的肌肉活检标本及患者的住院病历,纳入7例晚期非小细胞肺癌ICI相关性肌炎,均为男性,中位年龄64岁,年龄范围42~79岁,总结其临床特点。结...     

肺癌免疫治疗预测指标在非小细胞肺癌免疫治疗中的预测价值

目的:探索由中性粒细胞淋巴细胞比率(NLR)联合乳酸脱氢酶(LDH)得出的新型肺癌免疫治疗预测指标(IOPI)在非小细胞肺癌(NSCLC)免疫检查点抑制剂治疗中的预测价值。方法:对2018年1月至2019年7月来自空军军医大学第一附属医院和空军军医大学第二附属医院共5个科室的88例使用PD-1/PD-L1抑制剂的NSC...     

Active-specific immunotherapy for non-small cell lung cancer

Non-small cell lung cancer constitutes about 85% of all newly diagnosed cases of lung cancer and continues to be the leading cause of cancer-related deaths worldwide. Standard treatment for this devastating disease, such as systemic chemotherapy, has reached a plateau in effectiveness and comes with considerable toxicities. For all stages of disease fewer than 20% of patients are alive 5 years after diagnosis; for metastatic disease the median survival is less than one year. Until now, the success of active-specific immunotherapy for all tumor types has been sporadic and unpredictable. However, the active-specific stimulation of the host’s own immune system still holds great promise for achieving non-toxic and durable antitumor responses. Recently, sipuleucel-T (Provenge^®; Dendreon Corp., Seattle, WA) was the first therapeutic cancer vaccine to receive market approval, in this case for advanced prostate cancer. Other phase III clinical trials using time-dependent endpoints, e.g. in melanoma and follicular lymphoma, have recently turned out positive. More sophisticated specific vaccines have now also been developed for lung cancer, which, for long, was not considered an immune-sensitive malignancy. This may explain why advances in active-specific immunotherapy for lung cancer lag behind similar efforts in renal cell cancer, melanoma or prostate cancer. However, various vaccines are now being evaluated in controlled phase III clinical trials, raising hopes that active-specific immunotherapy may become an additional effective therapy for patients with lung cancer. This article reviews the most prominent active-specific immunotherapeutic approaches using protein/peptide, whole tumor cells, and dendritic cells as vaccines for lung cancer.     

非小细胞肺癌疫苗的研究现状及进展

在世界范围内,肺癌已占所有癌症病死率的首位,十分迫切地需要新的治疗方法.肿瘤疫苗代表了一种低毒、高特异性的新治疗方法,作为一种极具发展前景的治疗方式有望为肺癌的治疗带来新的希望.近年来,越来越多的临床研究结果表明,免疫治疗应用于肺癌可以获得显著的临床疗效.本文就非小细胞肺癌的疫苗的研究现状及进展作一综述.     

Predictability of early changes in derived neutrophil-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors

BackgroundAs association between systemic inflammation and disease progression has been suggested, early changes in neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) may have accurate predictability for prognosis in non-small cell lung cancer (NSCLC) treated with ICI therapy.MethodsComplete blood count (CBC) was measured immediately before the first and second cycles of ICI therapy in patients with advanced NSCLC. Differences in NLR and dNLR were measured. When the increase in NLR was ≥1, the patient was classified into the increased NLR group. Similarly, when the increase in dNLR was ≥1, the patient was classified into the increased dNLR group; otherwise, they were classified into the non-increased NLR or dNLR group.ResultsA total of 89 patients was selected for evaluation. Median progression-free survival (PFS) was significantly shorter in the increased NLR group than in the non-increased NLR group (2.6 vs. 9.5 months, P<0.001). The increased dNLR group showed significantly shorter median PFS than the non-increased dNLR group (4.2 vs. 9.2 months, P=0.001). Association with PFS was analyzed using the Cox regression model. In model 1, increase ≥1 in NLR showed significant association (HR =3.085, 95% CI, 1.657–5.742, P<0.001). In model 2, increase ≥1 in dNLR showed significant association (HR =2.826, 95% CI, 1.436–5.561, P=0.003).ConclusionsEarly changes in dNLR were shown to have prognostic value in patients undergoing immunotherapy. It can be an accurate and a comprehensive biomarker for predicting ICI response.     

Neoadjuvant immunotherapy in non-small cell lung cancer: a narrative review on mechanisms,efficacy and safety

Background and ObjectiveImmune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.MethodsRelevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms “non-small-cell lung cancer”, “NSCLC”, “neoadjuvant”, “immunotherapy”, “immune checkpoint inhibitors”, “mechanisms”, and “toxicity”. The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.Key Content and FindingsAfter reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83–86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.ConclusionsNeoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.