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...     

免疫治疗——开启肺癌治疗的新时代

以免疫检查点抑制剂为代表的免疫治疗已成为晚期非小细胞肺癌二线标准治疗方案,其一线治疗的适应证也在逐步获批,肺癌免疫治疗正向着早期新辅助治疗方向推进.在免疫单药治疗取得突破性进展后,免疫联合放疗、化疗及双免疫治疗使患者的疗效进一步提高,强强联合是肺癌治疗的大势所趋.免疫治疗在非小细胞肺癌领域疗效显著,并向小细胞肺癌领域扩展,使越来越多的患者受益.肺癌免疫治疗同时面临诸多挑战,如何筛选肺癌免疫治疗的获益人群,如何优化免疫治疗的方案,如何评估免疫治疗的疗效,如何克服免疫治疗的耐药,以及如何监测管理免疫相关不良反应等一系列问题亟待解决.我国自主研发的免疫检查点抑制剂也在临床研究或审批中,肺癌免疫治疗将会给我国肺癌患者带来更多的福音.     

免疫检查点抑制剂在肺癌治疗中的应用研究进展

免疫检查点抑制剂是一类针对细胞程序性死亡受体1(PD-1)、程序性死亡配体1(PD-L1)以及毒性T淋巴细胞抗原4(CTLA-4)的人源化单克隆抗体药物。在非小细胞肺癌患者的治疗方面,免疫检查点抑制剂表现出了显著且更加持久的疗效。本文就当前这类药物在肺癌治疗中的作用机制、临床研究最新进展以及相关生物标志物的预后和预测作用进行综述。     

免疫检查点抑制剂联合放化疗治疗非小细胞肺癌的疗效预测标志物研究进展

肺癌已成为我国死亡率最高的恶性肿瘤,其中非小细胞肺癌占肺癌的85%~90%,且发病率呈逐年增高趋势[1]。大多数非小细胞肺癌诊断时已出现远处转移,无法手术治疗。放疗、化疗、靶向治疗和抗血管生成治疗是晚期非小细胞肺癌患者的主要治疗方法。而肿瘤免疫治疗在肺癌中的应用既往一直未有突破性的进展,其治疗策略主要集中于直接提高抗肿瘤主动免疫(如过继性细胞免疫治疗)[2]。随着对肿瘤免疫微环境研究的深入,免疫检查点(immune checkpoint)在肿瘤免疫逃逸中的作用逐渐被重视,而针对免疫检查点的抑制剂(immune checkpoint inhibitors,ICIs)开始进入临床应用,并显示出一定的治疗效果。其中,程序性死亡受体-1/配体-L1(programmed cell death 1,PD-1/Programmed cell death 1 ligand 1,PD-L1)抑制剂已经获批应用于晚期非小细胞肺癌的治疗。     

免疫检查点抑制剂在驱动基因阳性非小细胞肺癌治疗中的研究进展

近年来, 免疫检查点抑制剂显著改善了部分肺癌患者的生存和预后。驱动基因阳性非小细胞肺癌患者免疫疗法往往效果不佳, 且常伴随免疫治疗相关不良反应, 因此争议较大。近来一些研究证明伴有驱动基因改变的肺癌患者也可受益于免疫治疗, 这可能为相关患者提供更多治疗选择, 值得进一步研究。本文对免疫检查点抑制剂在驱动基因阳性非小细胞肺癌患者治疗中的研究进展进行综述。     

非小细胞肺癌免疫检查点抑制剂相关性肺炎的研究进展

近年来, 肺癌的发病率逐年上升, 手术及放化疗作为肺癌的传统治疗手段, 临床效果较为有限, 免疫检查点抑制剂改变了晚期非小细胞肺癌患者的治疗格局。然而, 免疫检查点抑制剂也会引发与免疫相关的不良事件, 免疫检查点抑制剂相关性肺炎(CIP)是其中较为严重的不良反应, 并且在很大程度上影响了癌症患者的治疗和预后。因此, 进一步认识CIP就显得至关重要, 本文旨在对CIP的发病机制、危险因素、临床表现、分型、诊断及治疗进行系统性的综述。     

肺癌免疫检查点抑制剂治疗的不良反应及其防治

肺癌免疫检查点抑制剂(主要为抗PD-1或PD-L1类药物)可显著提升晚期肺癌患者的5年生存率,目前在晚期肺癌一线及二线治疗中占据重要地位,未来将成为肺癌治疗的主要措施之一,而呼吸领域的临床医生对其不良反应还缺乏足够的认识.本文简要介绍肺癌免疫检查点抑制剂治疗的不良反应及其防治.     

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。     

可手术切除的局部进展期非小细胞肺癌患者新辅助治疗研究进展

肺癌是全球范围内发病率和死亡率最高的恶性肿瘤.对于可手术切除的局部进展期非小细胞肺癌(NSCLC)患者,当前国内外相关指南建议采取多模式联合治疗,包括手术、放化疗、靶向治疗及免疫治疗等.术前新辅助治疗指在恶性肿瘤手术切除前给予化疗或放疗,近年随着靶向药物与免疫检查点抑制剂(ICI)的快速发展,新辅助治疗又延伸出新辅助靶...     

人工智能和影像组学在免疫检查点抑制剂治疗非小细胞肺癌中的应用进展

肺癌是我国发病率和死亡率居首位的恶性肿瘤,非小细胞肺癌为其主要病理类型,免疫检查点抑制剂使非小细胞肺癌的治疗模式进入了新的阶段。随着人工智能和影像组学的发展,医学影像中所包含的高维度特征信息作为生物标志物为术前无创评估肿瘤免疫信息、评估肿瘤异质性、预测免疫治疗反应及预后、预测及鉴别不良反应等方面提供了更多可靠的信息,从而实现精准选择免疫治疗受众以改善患者预后。本文对上述人工智能和影像组学的研究现状作一综述。     

Translation of clinical trials into clinical practice

The results of well-conducted clinical trials should be translated into practice but there is good evidence that this is not happening. There are a number of reasons for this - ignorance of doctors and patients, uncertainty as to the applicability of trials to individual patients, indolence and inefficiency on the part of practitioners, and financial considerations. More attention needs to be paid to correct all these factors.     

Liraglutide: from clinical trials to clinical practice

Liraglutide, a once-daily glucagon-like peptide-1 receptor agonist, is approved for use as monotherapy in the USA and Japan (but not in Europe or Canada) and in combination with selected oral agents (all regions) for the treatment of patients with type 2 diabetes. Guidance from local advisory bodies is emerging on the most appropriate place for liraglutide in the treatment pathway. It is apparent from its phase 3 clinical trial programme that liraglutide provides superior glycaemic control compared with that achieved with other antidiabetic agents used early in the treatment pathway (e.g. glimepiride and sitagliptin). Key additional benefits include a low incidence of hypoglycaemia and clinically relevant weight loss, although these benefits may be ameliorated by concomitant sulphonylurea (SU) treatment and, in the case of hypoglycaemia, reduction of the SU dose may be necessary. Overall, the profile of liraglutide is similar and, in some aspects, superior to twice-daily exenatide. The implementation of liraglutide therapy is straightforward, with simple dose titration from the starting dose of 0.6 to 1.2 mg/day after 1 week; some patients may benefit from additional titration to 1.8 mg/day. Treatment is self-administered by subcutaneous injection. This contrasts with other agents used early in the treatment pathway, but clinical data suggest patients' overall treatment satisfaction with liraglutide is similar (1.2 mg) or better (1.8 mg) than that with sitagliptin despite differing administration methods. Some patients may experience nausea when initiating liraglutide treatment, but the titration regimen is designed to improve tolerability and clinical data indicate nausea is transient.     

Measuring clinical performance using routinely collected clinical data

Following the well-publicized problems with paediatric cardiac surgery at the Bristol Royal Infirmary, there is wide public interest in measures of hospital performance. The Kennedy report on the BRI events suggested that such measures should be meaningful to the public, case-mix-adjusted, and based on data collected as part of routine clinical care. We have found that it is possible to predict in-hospital mortality (a measure readily understood by the public) using simple routine data-age, mode of admission, sex, and routine blood test results. The clinical data items can be obtained at a single venesection, are commonly collected in the routine care of patients, are already stored on hospital core IT systems, and so place no extra burden on the clinical staff providing care. Such risk models could provide a metric for use in evidence-based clinical performance management. National application is logistically feasible.     

Pitavastatin - from clinical trials to clinical practice

Managing dyslipidaemia is central to the management of cardiovascular disease. Most statins can reduce the 5-year incidence of major vascular events by 20%. In Europe, however, up to 53% of statin-treated patients fail to attain their low-density lipoprotein-cholesterol (LDL-C) target and residual risk remains high, even when targets are reached. Reasons for this include under-treatment due to insufficient starting doses/failure to uptitrate; poor persistence with therapy due to adverse events (AEs) or drug-drug interactions (DDIs); and failure to treat non-LDL-C risk factors, such as high triglycerides (TGs) and low high-density lipoprotein-C (HDL-C). Phase III and IV studies demonstrate that pitavastatin 1-4 mg has a similar or greater lipid-lowering efficacy to atorvastatin 10-20 mg, simvastatin 20-40 mg and pravastatin 10-40 mg, and is well-tolerated with a low incidence of adverse events (AEs). The SmPC recommends a usual starting dose of 1 mg, with dose-escalation if required. However, since the lower doses (1-2 mg) bring the majority of people with hypercholesterolaemia or combined dyslipidaemia to LDL-C target, the need for pitavastatin uptitration and the risk of under-treatment is low. In addition to reducing LDL-C, pitavastatin has a sustained beneficial effect on other atherogenic lipids, including TGs and HDL-C. Recent studies reveal that pitavastatin reduces coronary atheroma plaque volume as efficiently as atorvastatin and can improve the composition of coronary plaques, effects that are likely to reduce the risk of CV endpoints in patients with acute coronary syndrome. Moreover, pitavastatin has a number of pleiotropic effects that can reduce inflammation and lipid oxidation, improve endothelial function, reduce the metabolic changes associated with adiposity, and improve glucose metabolism and renal function. Compared to other statins, pitavastatin has a unique metabolic profile that could reduce the risk of DDIs, thereby providing a clear benefit in patients receiving polypharmacy. Overall, pitavastatin is a well tolerated and effective treatment for patients with hypercholesterolaemia and combined dyslipidaemia, especially in those with low HDL-C, and it should help improve LDL-C-target attainment rates by reducing the risk of under-treatment, minimising AE rates, and reducing the risk of DDIs in people requiring polypharmacy. Future and ongoing studies will directly compare the effects of pitavastatin vs. other statins on hard clinical endpoints.     

Loose connections between peer-reviewed clinical journals and clinical practice

Many important advances in medical care are first reported in the biomedical literature, but physicians find the literature overwhelming and, therefore, are often unaware of advances. This article examines the ways in which peer-reviewed clinical journals contribute to this problem and proposes some solutions for both their editors and clinical readers. Peer-reviewed clinical journals impede the dissemination of validated advances to practitioners by mixing a few rigorous studies (communications from scientists to practitioners) with many preliminary investigations (communications from scientists to scientists). Journals wishing to improve communication with practitioners should feature rigorous studies of the nature, cause, prognosis, diagnosis, prevention, and treatment of disease and should feature sound clinical review articles (communications from practitioners to practitioners). Additional strategies for improving communication between medical scientists and practitioners include improving publication standards for clinical journals, proving more informative abstracts for clinical articles, fostering the development of derivative literature services, and enhancing practitioners' skills in critically appraising the medical literature.     

Quantitative assessment of rheumatoid arthritis in standard clinical care: turning clinical care into clinical science

Patient questionnaires are a valuable method of monitoring the health status of patients with musculoskeletal conditions as part of daily clinical practice. Quantitative clinical monitoring improves the physician's ability to detect and document changes in patients' health conditions and thus leads to greater precision in clinical decisions. Furthermore, routine data collection on consecutive patients facilitates the analysis of groups of patients, providing more information than can be obtained from randomized clinical trials.