基因治疗联合放射治疗恶性肿瘤

肿瘤治疗是目前医学研究的重点之一,基因治疗与放射治疗方法的结合倍受重视,根据技术特点这种联合治疗方法主要有:免疫基因治疗联合放疗、直接杀伤或抑制肿瘤细胞的基因治疗联合放疗、抗肿瘤血管生成的基因治疗联合放疗以及辐射保护性基因治疗.综述了近年来基因治疗联合放射治疗恶性肿瘤的研究现状以及可能的作用机制.     

免疫检查点抑制剂联合TACE在肝癌治疗中的研究进展北大核心CSCD

近年来,免疫检查点抑制剂(ICI)是肝细胞癌(HCC)系统治疗的研究热点,ICI是指针对免疫系统中抑制性的信号通路和受体的阻断剂。经动脉导管化疗栓塞术(TACE)和ICI的疗效及适应证有一定差异,部分临床试验发现TACE联合ICI有协同抗肿瘤作用,能提高肿瘤应答率。这些临床试验主要是评估联合治疗的长期生存率和安全性。本文就ICI联合TACE在治疗HCC中的协同抗肿瘤机制和疗效进行简要综述。     

食管癌放疗联合免疫治疗专家共识(2023年版)

放疗是食管癌综合治疗的重要组成部分。近年来, 免疫联合化疗已经成为晚期食管癌一线标准治疗, 局部晚期食管癌多项Ⅲ期免疫联合放疗研究正在进行中, 免疫联合放化疗作为局部晚期食管癌患者的一种新的治疗策略, 尚缺乏充分的循证医学证据。因此, 结合食管癌免疫联合放化疗最新的研究数据, 组织中国抗癌协会肿瘤放射治疗专业委员会、中华医学会放射肿瘤治疗学分会、中国医师协会放射肿瘤治疗医师分会专家组成员深入研究讨论, 共同制定了该共识。详尽阐述了可手术食管癌、不可手术局部晚期食管癌以及晚期食管癌放疗联合免疫治疗推荐及疗效评价方法, 同时对放疗联合免疫治疗常见并发症及放疗相关问题进行讨论, 以期指导临床实践。     

甘露聚糖肽对鼻咽癌患者免疫指标和临床疗效的影响

目的观察甘露聚糖肽辅助治疗对Ⅱ~Ⅳa期鼻咽癌患者免疫指标和临床疗效的影响。方法将40例Ⅱ~Ⅳa期鼻咽癌患者,随机分为治疗组(单用放疗或同步放化疗,加注射甘露聚糖肽)和对照组(单用放疗或同步放化疗),分别检测患者T淋巴细胞亚群,同时观察疗效和副作用。结果治疗组与对照组的近期临床控制率相近,但治疗组治疗前后T淋巴细胞亚群有显著改善,发生白细胞下降、恶心呕吐、口腔黏膜炎症的病例也较对照组减少,且程度减轻。结论注射甘露聚糖肽与放疗或放化疗联合应用虽不能明显提高Ⅱ~Ⅳa期鼻咽癌的临床疗效,但能提高患者的免疫功能,并减轻放化疗或放疗引起的不良反应。     

老年脑转移瘤患者再次放疗联合替莫唑胺化疗疗效分析

目的探讨老年脑转移瘤患者再次放疗联合替莫唑胺治疗的临床疗效及安全性。方法将辽宁省肿瘤医院2009年1月至2011年12月收治52例老年脑转移瘤患者随机分为放疗组(n=24)和联合治疗组(n=28)。放疗组采用三维适形放疗,联合治疗组在放疗组基础上口服替莫唑胺治疗。治疗后对两组患者的疗效、生存质量以及不良反应情况进行评价与比较。结果联合治疗组总有效率为89.3%(25/28),放疗组为75.0%(18/24),两组间比较,差异有统计学意义(P<0.05)。联合治疗组中位生存时间为13.1个月,较放疗组(10.5个月)明显延长(P<0.05)。联合治疗组日常生活活动能力量表评分明显低于放疗组,而简易智力状态检查量表评分则显著高于放疗组(P<0.05);两组间各不良反应发生率比较,差异无统计学意义(P>0.05)。结论三维适形放疗联合替莫唑胺治疗老年脑转移瘤疗效确切,安全性好,对患者生活质量有显著提高作用。     

免疫检查点抑制剂PD-1免疫相关不良反应的临床分析

目的 探讨程序性细胞死亡蛋白-1(PD-1)免疫检查点抑制剂(ICI)临床应用中的免疫相关不良反应(irAE)及临床处理.方法 回顾性分析自2019年1月至12月共194例/473次接受PD-1治疗恶性肿瘤的患者,观察治疗期间患者发生的irAE,包括不良反应的类别、分级、发生时间、持续时间、处理方案、预后等指标.结果 ...     

诱导加同步时辰化疗联合调强放射治疗鼻咽癌的前瞻性随机对照研究

目的 分析诱导化疗加同步时辰化疗与同步常规化疗联合调强放疗治疗局部晚期鼻咽癌的不良反应、淋巴免疫功能及疗效.方法 将60例局部晚期鼻咽癌患者采用信封法随机分组,试验组为诱导化疗加同步时辰化疗联合调强放疗,对照组为诱导化疗加同步常规化疗联合调强放疗.两组均采用2个周期多西他赛+顺铂+5-氟尿嘧啶诱导化疗,同步化疗均采用顺铂,试验组采用时辰给药方式,对照组采用常规静脉给药方式.观察两组的不良反应、淋巴免疫功能及疗效.结果 同步放化疗期间试验组恶心(Z=2.50,P＜0.05)、呕吐(Z=3.31,P＜0.05)较对照组轻.同步放化疗后试验组CD4 +/CD8+高于对照组(t=3.34,P＜0.05).两组诱导化疗加同步放化疗的疗效差异无统计学意义(P＞0.05).结论 在不降低疗效的情况下,时辰给药方式能减轻恶心、呕吐不良反应,改善免疫功能,有可能成为鼻咽癌一种更合理的治疗方式.     

免疫检查点在肿瘤放疗中的应用进展

放射治疗诱导DNA损伤与细胞死亡,并且通过改变肿瘤表型、肿瘤微环境,参与内源性免疫反应的调节。免疫检查点信号途径在抗微生物免疫反应中参与维持自身耐受,限制组织损伤,但其在抗肿瘤免疫中抑制细胞毒T细胞活化与功能,增强免疫抑制细胞作用,导致免疫逃逸。阻断免疫检查点信号能够恢复抗肿瘤免疫,延缓肿瘤进程。近年来,放疗与免疫治疗联合应用已成为基础与临床研究的热点。在此就放疗对机体免疫系统的作用、免疫检查点的负性调控机制以及放疗联合阻断免疫检查点用于肿瘤治疗的研究进展进行总结,以期为拓展肿瘤综合治疗提供新思路。     

肿瘤相关巨噬细胞在放疗中的研究进展

肿瘤相关巨噬细胞（TAMs）与肿瘤的发生、发展、转移和复发密切相关。TAMs可根据表型及功能的不同分为M1型和M2型,分别与抗肿瘤免疫和促进肿瘤进展有关。放疗是大多数实体瘤的主要治疗方式之一,其可以直接杀伤肿瘤细胞,也可以间接调控肿瘤免疫微环境（包括TAMs）,导致TAMs向放疗抵抗型或放疗敏感型发展,从而影响放疗的疗效。靶向TAMs来抑制其促肿瘤作用以及促进TAMs向M1型复极化已经成为极有希望的肿瘤治疗方式。靶向TAMs与放疗联合治疗能够协同抑制肿瘤进展、增强疗效并减少放疗抵抗。笔者就TAMs在肿瘤放疗中的角色和相互作用机制以及靶向TAMs与放疗联合治疗的最新进展进行综述。     

免疫检查点抑制剂治疗可能增加脑转移立体定向放射手术后治疗相关坏死的发生率：系统综述和荟萃分析

正摘要目的比较立体定向放射手术(SRS)+免疫检查点抑制剂(ICI)联合治疗和单纯 SRS 治疗在黑色素瘤脑转移和非小细胞肺癌(NSCLC)病人中治疗相关坏死的发生率。方法     

Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

ObjectiveImmune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis.Materials and MethodsA systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes.ResultsEleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44–61%); DCR, 57% (95% CI, 49–66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31–54%]; DCR, 85% [95% CI, 63–95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11–20%]; DCR, 26% [95% CI, 21–32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52–67%) compared to ICI monotherapy (11%; 95% CI, 8–17%) and ICI combined with radiotherapy (4%; 95% CI, 1–19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy).ConclusionICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.     

A review of the imaging manifestations of immune check point inhibitor toxicities

The past decade has witnessed a paradigm shift in cancer therapy owing to the introduction of immune checkpoint inhibitors (ICIs) and it is now commonplace for radiologists to image patients on therapy with these agents. The purpose of this review is to detail the mechanism, radiological manifestations and clinical significance of ICI related toxicities, according to the organ system involved.ICI related toxicities that have known imaging manifestations include colitis, enterocolitis, pancreatitis, hepatitis, endocrine toxicities, pneumonitis, cardiovascular toxicity and musculoskeletal toxicity. These toxicities may be acute, recurrent or chronic in nature. Radiologists must be aware of the imaging features and clinical significance of these toxicities in order to effectively participate in personalized cancer therapy.     

High-dose interleukin-2 therapy related adverse events and implications on imaging

High-dose interleukin-2 (HDIL-2) therapy was initially approved by the U.S. Food and Drug Administration for metastatic renal cell carcinoma (mRCC) and metastatic melanoma. IL-2 is able to promote CD8+ T cell and natural killer (NK) cell cytotoxicity to increase tumoricidal activity of the innate immune system. HDIL-2 therapy is associated with a wide spectrum of immune-related adverse events (irAEs) that can be radiologically identified. HDIL-2 toxicity can manifest in multiple organ systems, most significantly leading to cardiovascular, abdominal, endocrine, and neurological adverse events. The collective impact of the irAEs and the rise of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors led to the demise of HDIL-2 as a primary therapy for mRCC and metastatic melanoma. However, with innovation in ICIs and the creation of mutant IL-2 conjugates, there has been a drive for combination therapy. Knowledge of the HDIL-2 therapy and HDIL-2 related adverse events with radiology relevance is critical in diagnostic image interpretation.

High-dose interleukin-2 (HDIL-2) was initially approved for the treatment of metastatic renal cell carcinoma (mRCC) and metastatic melanoma in 1992 and 1998, respectively. IL-2 was discovered as a cytokine, known as T cell growth factor. The majority of IL-2 is produced by CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and activated dendritic cells. IL-2 has numerous functions which include differentiation of CD4+ T cells, promoting CD8+ T cell cytotoxicity, and promoting NK cell cytotoxicity (1). When given intravenously at high doses, IL-2 therapy gained success in a subset of patients with metastatic melanoma or mRCC who achieved complete and durable responses (1). However, the high toxicity profile of HDIL-2 restricted this therapy to a minority of patients in highly specialized centers.Currently HDIL-2 has been relegated to a limited role in systemic therapy of mRCC and metastatic melanoma patients. Based on National Comprehensive Cancer Network (NCCN) guidelines, HDIL-2 has been useful for patients with favorable, intermediate, and poor risk clear cell mRCC patients who have excellent performance and normal organ function (2). Additionally, HDIL-2 is recommended as a second line regimen for metastatic or unresectable melanoma. HDIL-2 is contraindicated in patients with inadequate organ reserve, poor performance status, or with untreated/active brain metastases (3).Although HDIL-2 was more commonly used in 1990s, with the innovation in immune checkpoint inhibitors (ICIs), there has been a reemergence of HDIL-2 treatment as a combination therapy. The leading theory with including ICIs is the fact that these agents work downstream during the effector phase in a tumor. With IL-2 secretion activating tumor-specific T cells, HDIL-2 therapy could potentially work synergistically with ICIs (4). One study found that there was durable antitumor activity in metastatic melanoma and mRCC patients with HDIL-2 therapy after the patient had received programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor compared to patients who had just received IL-2. Thus, HDIL-2 remains an option for patients who have progressed on ICIs (5). With additional data, combination therapy may be the new norm for metastatic melanoma and mRCC treatment.New innovations to make HDIL-2 therapy safer has also surfaced with the creation of IL-2 conjugated with 6 releasable polyethylene glycol (PEG) chains (4). The mechanism behind PEGylated IL-2 revolves around the idea that the drug selectively binds to the IL-2Rabg isoform which preferentially activates effector T cells, which limits the side effect profile. Unfortunately, there has been mixed data revolving around this therapy. There were attempts to look at the relationship between adverse events observed with HDIL-2 and treatment effectiveness. Curti et al. (6) concluded that those who experienced adverse events had increased survival and better tumor control following treatment with HDIL-2.The purpose of this pictorial review is to describe typical and atypical HDIL-2 related adverse events that can be identified on imaging. It is crucial for radiologists to be familiar with the adverse events associated with HDIL-2 therapy, which has a potential to be more commonly used in the future.     

尤瑞克林和依达拉奉联合治疗脑梗死的疗效及对神经功能的影响

目的观察尤瑞克林和依达拉奉联合治疗脑梗死的疗效及对神经功能的影响。方法选择2010年9月～2012年3月在神经内科就诊的急性脑梗死患者94例,随机分为联合治疗组和依达拉奉组,联合治疗组在依达拉奉治疗基础上给予尤瑞克林,观察两组的神经功能评分和疗效及不良反应。结果两组BI评分比较,治疗后联合治疗组高于依达拉奉组,并且治疗后均高于治疗前。两组NIHSS评分比较,治疗后联合治疗组低于依达拉奉组,并且治疗后均低于治疗前。联合治疗组有效率改善更明显。两组只有轻微的不良反应,未见与药物相关的出血性事件。结论达拉奉联合尤瑞克林具有协同作用,达到快速治疗脑梗死的目的,疗效确切,不良反应轻微．安全有效。     

A review of Magnetic Resonance Enterography classification and quantitative evaluation of active disease in patients with Crohn's disease

Crohn's disease (CD) is a chronic inflammation of the gastro-intestinal system in which episodes of clinical worsening alternate with episodes of clinical regression. Monitoring of disease is mandatory to evaluate the efficacy of therapy and it is usually performed using a combination of clinical symptoms, laboratory tests, endoscopy and radiological exams, such as MR enterography or CT enterography. MR enterography should be preferred to CT enterography because of the absence of ionizing radiation, a very high soft tissue contrast, and a lower incidence of adverse events. In 2003, Maglinte introduced a radiological classification to identify patients in different stages of disease (active inflammatory, fibrostenotic and fistulising/perforating subtypes), based on following parameters: oedema, ulcers, stenosis, mural thickening, stratified contrast enhancement, engorged vasa recta, fistulae/abscess and mesenteric inflammation. In general, medical therapy is efficient in reducing inflammation while fibrotic disease and fistulising subtypes usually require surgery. Moreover, in patients with active CD it is important to quantify disease activity in order to adequately plan therapy and to monitor drug effects, by using some MR enterography indexes such as MaRIA score, Clermont index, and others. In this review we describe how to apply Maglinte's classification in MR enterography exams and how to quantify active disease.     

甲亢眼病大剂量糖皮质激素冲击加免疫抑制剂治疗疗效及不良反应的临床研究

目的:了解大剂量甲强龙冲击加小剂量免疫抑制剂治疗甲亢眼病的临床疗效和不良反应情况,以评估该治疗方案的临床应用价值。方法:选取我院2006-01～2010-01住院及门诊治疗的甲亢眼病64例,随机分为大剂量甲强龙冲击加免疫抑制剂治疗组(A组)和单纯大剂量甲强龙冲击治疗组(B组)及常规口服糖皮质激素治疗组(C组)。结果:①治疗半年后A组的有效率及显效率显著高于其他两组,且组间比较有显著性差异(P<0.05);②A组不良反应的发生情况与B组无统计学差异(P>0.05),但A、B组与C组比较不良反应有下降,且有统计学差别(P<0.05)。结论:大剂量甲强龙联合小剂量免疫抑制剂治疗甲亢突眼临床治疗效果显著提高,不良反应较单一治疗无明显增加,较常规口服激素治疗有下降,是值得临床广泛应用的治疗方法。     

Imaging manifestations of immune-related adverse effects in checkpoint inhibitor therapies: A primer for the radiologist

Immune checkpoint inhibitors are monoclonal antibodies directed against cellular pathways on T-cells to treat different types of malignancies. This new therapy can cause immune-related adverse events that can involve almost any organ system. This article will review clinical presentations, molecular mechanisms and imaging manifestations of adverse events caused by checkpoint inhibitors and also illustrate the pseudoprogression tumor response pattern.     

Thermal Ablation,Embolization, and Selective Internal Radiation Therapy Combined with Checkpoint Inhibitor Cancer Immunotherapy: Safety Analysis

PurposeTo describe interventional oncology therapies combined with immune checkpoint inhibitor (ICI) therapy targeting the programmed death 1 pathway in patients with different neoplasms.Materials and MethodsThis was a retrospective cohort study of patients who underwent tumor-directed thermal ablation, embolization, or selective internal radiation therapy (SIRT) between January 1, 2011, and May 1, 2019, and received anti–programmed death 1/PD-L1 agents ≤ 90 days before or ≤ 30 days after the interventional procedure. Immune-related adverse events (irAEs) and procedural complications ≤ 90 days after the procedure were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The study included 65 eligible patients (49% female; age 63 years ± 11.1). The most common tumors were metastatic melanoma (n = 28) and non–small cell lung cancer (NSCLC) (n = 12). Patients underwent 78 procedures (12 patients underwent > 1 procedure), most frequently SIRT (35.9%) and cryoablation (28.2%). The most common target organs were liver (46.2%), bone (24.4%), and lung (9.0%). Most patients received ICI monotherapy with pembrolizumab (n = 30), nivolumab (n = 22), and atezolizumab (n = 6); 7 patients received ipilimumab and nivolumab.ResultsSeven (10.8%) patients experienced an irAE (71.4% grade 1–2), mostly affecting the skin. Median time to irAE was 33 days (interquartile range, 19–38 days). Five irAEs occurred in patients with melanoma, and no irAEs occurred in patients with NSCLC. Management required corticosteroids (n = 3) and immunotherapy discontinuation (n = 1); all irAEs resolved to grade ≤ 1. There were 4 intraprocedural and 32 postprocedural complications (77.8% grade < 3). No grade 5 irAEs and/or procedural complications occurred.ConclusionsNo unmanageable or unanticipated toxicities occurred within 90 days after interventional oncology therapies combined with ICIs.     

原发性支架植入术治疗自发性急性心肌梗死疗效分析

目的 比较原发性支架植人术和药物治疗自发性急性心肌梗死的临床疗效。方法选取2002年5月-2012年5月我院治疗的自发性急性心肌梗死患者102例作为研究对象。接受原发性支架植入术的患者为实验组,未接受原发性支架植入术的患者为对照组,两组采用相同且适当的护理方法,比较两组治疗前后的疗效差异,比较患者1、3年生存率、主要不良心脑血管事件（MACCE）发生率、心脏射血分数（EF）等项目差异。结果两组比较发现,术后3年生存率、主要不良心脑血管事件（MACCE）发生率、心脏射血分数（EF）差异有统计学意义（P均〈0．05）,原发性支架植入术的疗效明显强于药物治疗。结论原发性支架植入术治疗自发性急性心肌梗死的临床疗效强于药物治疗,各疗效评价指标显著优于对照组,临床应用更具有优势。