非小细胞肺癌淋巴结的无创分期评价

目的 本研究通过对经胸部CT解剖显像后的非小细胞肺癌(NSCLC)患者进行18F-FDG PET全身扫描及经食管超声解剖显像，着重评估无创检查对NSCLC术前分期准确性及价值。方法 56例经病理证实的NSCLC术前患者经CT扫描、全身^18F-FDG PET显像，并与手术病理结果进行回顾性的分析。结果 所有56例NSCLC患者肺部及相应转移部位^18F-FDG摄取增高，^18F-FDG PET对预测NSCLC纵隔淋巴结转移的灵敏度为83％，特异性为91％，CT扫描纵隔淋巴结转移的灵敏度为58％，特异性为78％，其中38例行经食管超声解剖显像纵隔淋巴结转移的灵敏度为77％，特异性为72％。^18F-FDG PET对NSCLC对纵隔淋巴结优于胸部CT解剖显像和经食管超声解剖显像。结论 ^18F-FDG PET在对NSCLC的术前分期均优于CT等常规检查，但PET在精确定位方面仍然需要结合解剖显像，图像融合技术等是发展的方向。     

机器人手术和胸腔镜手术治疗早期非小细胞肺癌的临床效果Meta分析

目的使用Meta分析评估机器人手术和胸腔镜手术治疗早期非小细胞肺癌的临床效果。方法利用计算机在PubMed、Embase、万方、知网等数据库中进行检索,检查时限为建库至2020年5月,对筛选文献进行质量评价,利用RevMan5.3软件对纳入文献进行Meta分析。结果共纳入8篇文献,在早期非小细胞肺癌的治疗中,机器人手术比胸腔镜手术术中切除淋巴结数量更多[MD=2.84,95%CI(0.37,5.32),P=0.02],出血量更少[MD=-53.31,95%CI(-90.20,-16.42),P=0.005],总费用更多[MD=40.01,95%CI(35.71,44.31),P<0.00001]。两种手术方式在术后并发症、手术时间、术后住院时间、术后引流时间、中转开胸方面无统计学差异(P>0.05)。结论在临床早期非小细胞肺癌的治疗中,机器人手术相比胸腔镜手术具有一定优势,相信机器人手术将更多应用于临床早期肺癌的治疗。     

Pembrolizumab for the treatment of non-small cell lung cancer

ABSTRACT

Introduction: Immune checkpoint inhibitors targeting programmed death protein 1 (PD-1) receptor and its ligand, PD-L1, have recently led to significant and durable improvements in the clinical outcomes of some types of cancers including lung cancer.

Areas covered: Pembrolizumab was approved by the US FDA for the treatment of advanced or metastatic NSCLC whose disease has progressed after other treatments and with tumors that express PD-L1. In the phase I KEYNOTE-001 trial, the overall response rate (ORR) was 19.4%, the median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 12.0 months for 495 unselected NSCLC patients. Strong PD-L1 expression (≥ 50%) was associated with higher ORR, longer PFS, and longer OS. The phase II/III randomized KEYNOTE-010 trial demonstrated that pembrolizumab improved OS versus docetaxel in patients with previously treated NSCLC.

Expert opinion: Pembrolizumab, demonstrated durable response and prolonged OS especially in NSCLC patients with high expression of PD-1, thereby suggests a new treatment paradigm. However, many issues remain to be explored, including the identification of other robust biomarkers that can accurately predict the immune-responsiveness of tumors. Along with the identification of predictive biomarkers, further understanding of the tumor microenvironment is necessary to improve treatment outcomes through combinations of immunotherapy or combined with other targeted therapies.     

单孔与三孔胸腔镜下肺叶切除术治疗非小细胞肺癌的临床疗效对比

目的对比分析非小细胞肺癌患者行单孔和三孔胸腔镜肺叶切除术(VATS)治疗后的围术期状况及远期生存状况。方法选取2013年1月-2016年11月该科同一术者收治的行VATS的141例非小细胞肺癌患者为研究对象。其中单孔VATS治疗肺癌52例(单孔组),同期三孔法VATS手术89例(三孔组),统计并对比分析两组手术时间、术中出血量、术中清扫淋巴结数目、胸腔引流时间、术后引流量、术后住院时间及术后并发症情况。结果单孔组与三孔组相比,两组在术后胸腔引流时间、引流量、术中清扫淋巴结数目及术后并发症等方面差异均无统计学意义(P0.05);两组平均手术时间分别为(196.1±19.6)和(162.7±18.9)min,差异有统计学意义(P=0.000);两组平均术中出血量分别为(100.3±13.6)和(176.5±15.9)ml,差异有统计学意义(P=0.000);两组术后住院时间分别为(7.5±1.7)和(9.2±1.3)d,差异有统计学意义(P=0.000)。结论单孔VATS能够达到三孔胸腔镜手术的治疗效果,虽然手术时间增加,但能避免多余切口对胸壁肌肉、肋间神经或血管的损伤,进一步降低手术创伤,缩短术后住院时间,是可选择的安全有效的肺癌根治性手术方式。     

全胸腔镜肺叶切除与开胸肺叶切除治疗非小细胞肺癌疗效对比研究

目的 比较全胸腔镜肺叶切除与开胸肺叶切除治疗非小细胞肺癌的临床疗效.方法 68例非小细胞肺癌患者根据手术方式不同分为2组,全胸腔镜肺叶切除组38例,开胸肺叶切除术组30例,观察比较2组在手术时间、术中出血量、术后引流量、术后引流管拔除时间、淋巴结清扫数、术后哌替啶使用次数、术后住院时间以及术后并发症方面的差异.结果 全胸腔镜肺叶切除组的术中出血量、术后放置引流时间、引流量、哌替啶使用次数及术后住院时间明显小于开胸肺叶切除术组,差别均有统计学意义(P＜0.01),而手术时间则明显高于开胸肺叶切除术组,差别也有统计学意义(P＜0.01);全胸腔镜肺叶切除组的术后并发症发生率明显低于开胸肺叶切除术组,差别有统计学意义(P＜0.01).结论 全胸腔镜肺叶切除术是较为安全、可靠的治疗非小细胞肺癌的方法.     

非小细胞肺癌患者血清Tenascin-C水平及诊断价值

目的探讨非小细胞肺癌(NSCLC)患者血清细胞外基质蛋白Tenascin-C水平及诊断价值。方法收集该院2017年1月至2019年1月收治的NSCLC患者80例作为NSCLC组,同期年龄和性别相匹配的健康者80例为对照组,采用酶联免疫吸附试验法检测2组血清Tenascin-C水平,电化学发光免疫法检测血清癌胚抗原(CEA)水平。绘制受试者工作特征曲线(ROC曲线)分析血清Tenascin-C、CEA对NSCLC的诊断价值。结果NSCLC组血清Tenascin-C水平高于对照组[(5.08±3.33)ng/mL vs.(1.51±1.07)ng/mL,P=0.001],NSCLC组血清CEA水平高于对照组[(15.64±7.18)ng/mL vs.(3.58±1.72)ng/mL,P=0.003]。NSCLC组血清Tenascin-C水平与患者年龄、性别和组织类型无显著相关性(P>0.05),患者TNM分期越高、存在淋巴结和远处转移患者血清Tenascin-C水平显著性增高(P<0.05)。当临界值为2.07 ng/mL时,血清Tenascin-C水平诊断NSCLC的ROC曲线下面积为0.743(95%CI:0.688~0.817,P<0.001),灵敏度和特异度分别为71.1%和76.0%,高于CEA诊断NSCLC患者ROC曲线下面积0.715(95%CI:0.683~0.838,P<0.001);二者联合使用诊断NSCLC患者的ROC曲线下面积为0.892(95%CI:0.788~0.917,P<0.001),灵敏度和特异度为81.0%和91.0%。Ⅰ+Ⅱ期NSCLC组患者血清Tenascin-C水平高于对照组(P<0.001)。当临界值为1.73 ng/mL时,血清Tenascin-C诊断早期(Ⅰ+Ⅱ期)NSCLC的ROC曲线下面积为0.743(95%CI:0.688~0.846,P<0.001),灵敏度和特异度分别为68.6%和83.0%。结论NSCLC患者血清Tenascin-C水平显著高于健康人群,对NSCLC患者具有一定早期诊断价值。     

~(18)F-FDG PET-CT显像对恶性淋巴瘤诊断和分期中的临床应用价值

目的探讨18F-FDG PET-CT显像在恶性淋巴瘤诊断、疗效评价及临床分期中的应用价值。方法对30例疑诊为淋巴瘤并进行18F-FDG PET-CT显像28例经病理证实为淋巴瘤,其中HD6例,NHL22例。图像分析采用视图分析及测量病灶平均标准摄取值方法相结合。结果 30例疑诊淋巴瘤患者中,14例治疗前行PET-CT检查,11例确诊为淋巴瘤,2例假阳性,1例假阴性;5例手术治疗后,2例术后复发及转移;11例放疗/化疗的患者,4例复发,4例见局部有病灶残存,3例未见异常;5例患者于治疗前及放化疗后检查,4例肿瘤明显受抑制1。8F-FDG PET-CT诊断符合率为93.3%。检测淋巴瘤病灶敏感性为89.4%。特异性为95.5%。结论 18F-FDG PET-CT显像对淋巴瘤病灶有较高的敏感性、特异性,有助于临床更准确的分期从而指导治疗。     

周围型非小细胞肺癌组织间近距离放疗的精准护理

目的探讨行CT引导下肺癌组织间插植近距离放疗患者的精准护理。方法根据预计划对行CT引导下肺癌组织间插植近距离放疗的患者进行知识宣教、心理疏导、体位训练以及呼吸配合,观察治疗期间医患配合满意度以及并发症。结果经过护理的干预,医生对患者满意度达92.3%,患者对精准护理服务的满意度达94.1%。本组患者插植后CT扫描发现小量气胸8例,大量气胸3例,痰中带血8例,穿刺点轻度纤维化3例,未发现血胸、胸膜肺休克和剧烈疼痛。结论对风险较高且治疗精度要求严格的有创操作治疗,治疗前护理的知识宣教、心理疏导以及相应的患者配合训练,有利于提高患者的操作依从性以及治疗满意度。     

CIMAvax-EGF,a therapeutic non-small cell lung cancer vaccine

Introduction: Lung cancer represents the most common cause of cancer death worldwide. While the prognosis remains poor, immunotherapy is giving a positive impact on survival. Cancer vaccines represent a form of active immunotherapy that historically has given modest results in terms of efficacy.

The overexpression of the EGFR by tumor cells was reported in more than half of cases of lung cancer, representing a mechanism of cancerogenesis. CIMAvax-EGF, a therapeutic vaccine for non-small cell lung cancer (NSCLC) developed in Cuba, consists of a human recombinant EGF able to induce antibodies against the autologous EGF, resulting in serum EGF withdrawal and lower EGF-EGFR interaction.

Area covered: We critically reviewed the existing literature about CIMAvax-EGF, from the Pilot studies to the efficacy controlled studies. We also overviewed the ongoing trials.

Expert opinion: CIMAvax-EGF demonstrated to be safe and immunogenic. In a phase III randomized study CIMAvax-EGF, used as a switch maintenance treatment after platinum-based chemotherapy, did not significantly improve survival. Current data are not sufficient to recommend CIMAvax-EGF as a treatment option for advanced stage NSCLC. Further studies, conducted in a context of worldwide standardized clinical practice, are needed to better define if a subpopulation of patients can benefit from the vaccination.     

Representativeness of nodal sampling with endobronchial ultrasonography in non-small-cell lung cancer staging

The objective of our study was to determine the procedure-related requirements of mediastinal node sampling with endobronchial ultrasonography with real-time transbronchial needle aspiration (EBUS-TBNA) that would provide negative predictive value (NPV) for the identification of stage III disease in non-small-cell lung cancer (NSCLC) high enough to consider the technique equivalent to cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and 7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the results of postsurgical staging in patients who underwent surgery as a reference. Two-hundred ninety-six patients staged with EBUS-TBNA were included. Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in 150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the representativeness criteria required for sampling was attained in 248 of the participating patients (83.8%). The NPV of the procedure in this setting was 93.6%, with false-negative results only found in 5 patients, four of them with nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more than 80% of patients staged using EBUS-TBNA, and in the procedures that attain this requirement a NPV >90% for mediastinal malignancy is reached, a figure equivalent to cervical mediastinoscopy.     

厄洛替尼治疗晚期非小细胞肺癌的临床研究

目的观察厄洛替尼治疗晚期非小细胞肺癌的疗效和毒副作用。方法38例经病理组织学检查确诊的晚期非小细胞肺癌患者，给予厄洛替尼150mg做，1次／d。结果38例患者均可以评价疗效，获CR1例（2．6％），PR11例（28．9％），SD19例（50．0％），PD7例（18．5％）。有效率（CR＋PR）为31．6％，疾病控制率（CR＋PR＋SD）为81．6％。腺癌的有效率优于鳞癌（P〈0．05），ECOG体力状况评分0～1分较2～3分的有效率高（P〈0．05）。中位疾病进展时间（1vrP）304d（95％CI：109-498d）；中位生存时间333d（95％CI：212--453d）。女性、腺癌、ECOG评分0～1分的TTP分别优于男性、鳞癌、ECOG评分2～3分者。腺癌、ECOG评分0～1分的中位生存时间分别优于鳞癌、ECOG评分2～3分者。经Cox风险比例模型分析，体力状况评分是服用厄洛替尼后TTP（HR：0．037，95％CI：0．010-0．147）和中位生存时间（HR：0．014。95％CI：0．002-0．125）独立的预测因素。最常见的毒副反应是皮疹和腹泻，对症处理后缓解。结论厄洛替尼治疗晚期非小细胞肺癌有一定的疗效．安全性高，在国人中女性、腺癌、体力状况好的患者将有可能更多获益。     

厄洛替尼治疗晚期非小细胞肺癌的临床研究

目的观察厄洛替尼治疗晚期非小细胞肺癌的疗效和毒副作用。方法38例经病理组织学检查确诊的晚期非小细胞肺癌患者,给予厄洛替尼150 mg/次,1次/d。结果38例患者均可以评价疗效,获CR 1例(2.6%),PR 11例(28.9%),SD 19例(50.0%),PD 7例(18.5%)。有效率(CR+PR)为31.6%,疾病控制率(CR+PR+SD)为81.6%。腺癌的有效率优于鳞癌(P<0.05),ECOG体力状况评分0~1分较2~3分的有效率高(P<0.05)。中位疾病进展时间(TTP)304 d(95%CI:109~498 d);中位生存时间333 d(95%CI:212~453 d)。女性、腺癌、ECOG评分0~1分的TTP分别优于男性、鳞癌、ECOG评分2~3分者。腺癌、ECOG评分0~1分的中位生存时间分别优于鳞癌、ECOG评分2~3分者。经Cox风险比例模型分析,体力状况评分是服用厄洛替尼后TTP(HR:0.037,95%CI:0.010~0.147)和中位生存时间(HR:0.014,95%CI:0.002~0.125)独立的预测因素。最常见的毒副反应是皮疹和腹泻,对症处理后缓解。结论厄洛替尼治疗晚期非小细胞肺癌有一定的疗效,安全性高,在国人中女性、腺癌、体力状况好的患者将有可能更多获益。     

同步放化疗治疗非小细胞肺癌的临床研究

目的观察同步放化疗治疗非小细胞肺癌的疗效及毒性反应。方法 32例Ⅱ~Ⅲb期非小细胞肺癌患者接受同步放化疗。6MVX线加速器常规分割放射治疗,2 Gy/次,5次/周,总计量为60~66 Gy(6~7周)。放疗开始后同步进行EP方案:VP-16 100 mg/m2,第1~3天;DDP 30 mg/m2,第1~3天,3周为1个周期,共化疗4个周期。结果近期有效率为84.38%,1年生存率为68.75%。主要的毒副反应为骨髓抑制(71.88%),胃肠道反应(75.00%),放射性食管炎(56.25%)和放射性肺炎(21.88%)。结论 EP方案同步放疗治疗非小细胞肺癌疗效确切,毒副反应可耐受,值得在临床上进一步推广。     

立体定向放射治疗非小细胞肺癌脑转移患者的护理

非小细胞肺癌约占肺癌的75%～80%,脑转移总的发生率为20%,尸检为40%[1]。脑转移是非小细胞肺癌晚期及病情严重的标志之一,如不积极治疗,患者的中位生存时间仅为4周,是导致患者死亡的主要原因[2-3]。随着立体定向放疗技术的不断发展,对于提高非小细胞肺癌脑转移患者的     

多西他赛单药一线治疗晚期非小细胞肺癌临床研究

目的探讨多西他赛单药一线治疗晚期非小细胞肺癌临床疗效及不良反应。方法48例晚期非小细胞肺癌患者,多西他赛75m4g／lm2静脉滴注,第1天。21d为1个周期,治疗2～4个周期后评价临床疗效及不良反应。结果48例患者共化疗140个周期,中位化疗2．9个周期。RR为25．O％,DCR为56．3％,中位无进展生存期5．3个月,中位生存期8．6个月,1年生存率35．4％。不良反应以粒细胞减少、贫血、腹泻、脱发为主。结论多西他赛单药一线治疗晚期非小细胞肺癌临床疗效良好,患者耐受性较好。     

紫杉醇联合奈达铂治疗晚期非小细胞肺癌的临床观察

目的观察紫杉醇（PTX）联合奈达铂（NDP）治疗晚期非小细胞肺癌的疗效及不良反应。方法 48例晚期非小细胞肺癌患者应用紫杉醇（PTX）联合奈达铂（NDP）方案化疗：PTX 135~175 mg/m2,静脉滴注,第1天;NDP 80~100 mg/m2,静脉滴注,第2天,21 d为1个周期。结果全组48例患者中,完全缓解率（CR）3例（6.3%）,部分缓解率（PR）16例（33.3%）,稳定（SD）22例（45.8%）,病情进展（PD）7例（14.6%）。有效率（RR）为39.6%,疾病控制率（DCR）为85.4%。主要不良反应为骨髓抑制及胃肠道反应,肝、肾毒性较轻。结论紫杉醇联合奈达铂治疗晚期非小细胞肺癌不良反应轻,疗效较好,值得临床推广。     

1例晚期非小细胞肺癌患者的全程管理

山西省肿瘤医院呼吸一病区收治1例IV期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者。患者,男,50岁,于2012年10月初无明显诱因出现刺激性咳嗽、咳痰。正电子发射计算机断层显像(positron emission tomography-computed tomography,PET-CT)提示:右肺上叶癌,右锁区、纵隔及右肺门肿大淋巴结转移。全身多发骨质破坏。病理(右肺穿刺物)检查示腺癌。变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)示EGFR19外显子突变。一线治疗给予培美曲塞二钠联合顺铂全身化疗6周期,无进展生存期(progression-free survival,PFS)为8个月;二线治疗予吉非替尼,PFS为42个月;三线治疗继续口服吉非替尼,PFS为4个月;四线治疗予口服AZD9291,PFS为11个月;五线治疗予吉非替尼联合阿帕替尼,PFS为2个月;六线治疗行右上肺楔形切除术,术后病理示:BRAF V600E突变,出现头颅转移,给予培美曲塞二钠+顺铂全身化疗2周期,并予同步左侧额叶、左侧顶叶转移灶大分割调强放疗,PFS为3个月;液滴式数字聚合酶链式反应(droplet digital polymerase chain reaction,ddPCR):T790M(+),七线治疗口服奥希替尼联合培美曲塞单药化疗2周期,疗效评估为部分缓解(partial response,PR),目前仍在随访中。     

Necitumumab for non-small cell lung cancer

Introduction: Targeting the EGFR pathway is a rational approach to treat patients with advanced NSCLC. Necitumumab, a second-generation recombinant fully human immunoglobulin G1 monoclonal antibody directed against EGFR, has recently been assessed in combination with first-line cisplatin-based chemotherapy.

Areas covered: This article reviews literature on necitumumab development, from preclinical data to results of Phase III clinical trials, either published or presented in international scientific conferences. Ongoing clinical trials were searched with the clinical-trials.gov website.

Expert opinion: During the last decade, advances in treatment of metastatic NSCLC have been exclusively achieved in patients with non-squamous histology. In this context, any treatment improvement, even modest, was eagerly awaited for patients with squamous NSCLC. In this patient’s population, the SQUIRE Phase III study demonstrated a relatively small, but statistically significant survival benefit in patients treated with necitumumab in combination with standard chemotherapy (cisplatin and gemcitabin) compared with those treated with chemotherapy alone. However, the identification of predictive biomarker for treatment outcome is still needed to select the patients who will experience a large benefit from the targeted treatment.     

Prognostic significance of gamma-glutamyl transferase in patients with metastatic non-small cell lung cancer

Background: The prognostic significance of serum gamma-glutamyl transferase (GGT) level at diagnosis in patients with metastatic non-small lung cancer (NSCLC) is not clear. We aimed to assess the relationship between serum GGT level and overall survival (OS) and progression-free survival (PFS) in this patient population.

Methods: Data of patients with metastatic NSCLC who were admitted to the medical oncology clinic of our hospital during April 2013–December 2017 were retrospectively analyzed. Patients were divided into two groups based on GGT levels, normal and high (as defined by normal reference levels), and then compared.

Results: Significant differences between the high and normal GGT level groups were found regarding female sex, Eastern Cooperative Oncology Group performance score, weight loss at the time of diagnosis, and lactate dehydrogenase level (p < 0.05). The high GGT group had a shorter median OS (11.5 vs. 3.4 months, p < 0.001) and PFS (7.8 vs. 3.0 months, p = 0.001). High GGT level is an independent risk factor for OS (hazard ratio [HR] 2.270; 95% confidence interval [CI], 1.398–3.686; p < 0.001) and PFS (HR 2.489; 95% CI, 1.323–4.684; p = 0.005).

Conclusions: High serum GGT level is an independent prognostic factor for OS and PFS in metastatic NSCLC patients.     

非小细胞肺癌纤维支气管镜活检物中microRNA21的表达及意义

目的探讨非小细胞肺癌纤维支气管镜活检物中microRNA21的表达及意义。方法选取30例非小细胞肺癌患者为病例组,另外选取同期体检的同龄健康人群30例为对照组。实时荧光定量PCR检测microRNA21表达水平。结果病例组microRNA21表达水平显著高于对照组(P0.001);腺癌患者microRNA21表达水平显著高于鳞癌患者(P0.001)。非小细胞肺癌组织中microRNA21表达水平与TNM分期有关(P=0.004),与性别、年龄、分化程度和淋巴转移无关(P0.05)。结论 microRNA21在非小细胞肺癌纤维支气管镜活检物中表达上调,且与病理类型和临床分期相关,可作为肺腺癌的特异性的肿瘤标志物。