不同VATS切除术式对T1期NSCLC患者手术相关临床指标、肺功能及炎症反应水平的影响

目的:探讨VATS肺段和VATS肺叶切除术式对T1期NSCLC患者手术相关临床指标、肺功能及炎症反应水平的影响。方法:研究对象选取我院2015年6月至2017年6月收治T1期NSCLC患者共130例，根据手术方案不同分为肺叶切除组（65例）和肺段切除组（65例），分别采用VATS肺段和VATS肺叶切除术式治疗；比较两组患者手术相关临床指标水平、手术前后肺功能指标、炎症反应实验室指标水平及术后并发症发生率。结果:肺叶切除组患者手术操作时间和术中失血量均显著优于肺段切除组（P<0.05）；肺段切除组患者术后引流量、术后引流时间及总住院时间均显著优于肺叶切除组（P<0.05）；两组患者淋巴结数量比较差异无统计学意义（P>0.05）；肺段切除组患者术后肺功能指标水平均显著高于肺叶切除组（P<0.05）；肺段切除组患者术后炎症反应实验室指标水平均显著低于肺叶切除组（P<0.05）；两组患者术后并发症发生率比较差异无统计学意义（P>0.05）。结论:相较于VATS肺叶切除术式，VATS肺段切除术式治疗T1期NSCLC可有效加快病情康复进程，保护肺部通气功能，并有助于抑制术后全身炎症反应；而VATS肺叶切除术式则能够缩短手术用时，降低医源性创伤程度。     

Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC

IntroductionWe retrospectively analyzed the effects of crizotinib on serum creatinine and creatinine-based estimated glomerular filtration rate (eGFR) in patients with anaplastic lymphoma kinase–positive advanced NSCLC across four trials (NCT00585195, NCT00932451, NCT00932893, and NCT01154140).MethodsChanges from baseline data in serum creatinine and eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation, were assessed over time. eGFR was graded using standard chronic kidney disease criteria.ResultsMedian serum creatinine increased from 0.79 mg/dL at baseline to 0.93 mg/dL after 2 weeks of treatment (median percentage increase from baseline, 21.2%), was stable from week 12 (0.96 mg/dL) to week 104 (1.00 mg/dL), and decreased to 0.90 mg/dL at 28 days after last dose (median percentage increase from baseline, 13.1%). Median eGFR decreased over time (96.42, 80.23, 78.06 and 75.45 mL/min/1.73 m² at baseline, week 2, week 12, and week 104, respectively) and increased to 83.02 mL/min/1.73 m² at 28 days after the last dose. Median percentage decrease from baseline was 14.9%, 17.0%, and 10.4% at week 2, week 12, and 28 days after last dose of crizotinib, respectively. Overall, 12.6% of patients had a shift from eGFR grade less than or equal to 3a (≥45 mL/min/1.73 m²) at baseline to greater than or equal to 3b (<45 mL/min/1.73 m²) post-baseline.ConclusionsCrizotinib resulted in a decline in creatinine-based estimates of renal function mostly over the first 2 weeks of treatment. However, there was minimal evidence of cumulative effects with prolonged treatment and these changes were largely reversible following treatment discontinuation, consistent with previous reports suggesting this may be predominantly an effect on creatinine secretion as opposed to true nephrotoxicity.     

Local Control and Toxicity of Adaptive Radiotherapy Using Weekly CT Imaging: Results from the LARTIA Trial in Stage III NSCLC

IntroductionAnatomical change of tumor during radiotherapy contributes to target missing. However, in the case of tumor shrinkage, adaptation of volume could result in an increased incidence of recurrence in the area of target reduction. This study aims to investigate the incidence of failure of the adaptive approach and, in particular, the risk for local recurrence in the area excluded after replanning.MethodsIn this prospective study, patients with locally advanced NSCLC treated with concomitant chemoradiation underwent weekly chest computed tomography simulation during treatment. In the case of tumor shrinkage, a new tumor volume was delineated and a new treatment plan outlined (replanning). Toxicity was evaluated with the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Patterns of failures were classified as in field (dimensional and/or metabolic progression within the replanning planning target volume [PTV]), marginal (recurrence in initial the PTV excluded from the replanning PTV), and out of field (recurrence outside the initial PTV).ResultsReplanning was outlined in 50 patients selected from a total of 217 patients subjected to weekly simulation computed tomography in our center from 2012 to 2014. With a median follow-up of 20.5 months, acute grade 3 or higher pulmonary and esophageal toxicity were reported in 2% and 4% of cases and late toxicity in 4% and 2%, respectively. Marginal relapse was recorded in 6% of patients, and 20% and 4% of patients experienced in-field and out-of-field local failure, respectively.ConclusionsThe reduced toxicity and the documented low rate of marginal failures make the adaptive approach a modern option for future randomized studies. The best scenario to confirm its application is probably in neoadjuvant chemoradiation trials.     

新辅助化疗对局部晚期非小细胞肺癌患者临床疗效和手术切除率的影响

目的 探讨局部晚期非小细胞肺癌(NSCLC)患者手术前进行新辅助化疗的临床效果以及对患者的手术和生存情况的影响.方法 66例Ⅲ期NSCLC患者,其中36例患者在手术前进行2个周期全身化疗,为观察组;其余30例患者确诊后直接进行手术,为对照组.对2组患者的手术切除情况、手术相关指标、生存率以及T淋巴细胞亚群等指标进行收集整理.结果 新辅助化疗的有效率为58.3％,其中有13例患者病情下调,病情下调率为36.1％.观察组患者的手术切除率显著高于对照组(P＜0.05);在手术时,2组患者的术中出血量和手术时间均存在统计学差异,其中观察组均显著低于对照组(P＜0.05).术后随访3年,观察组和对照组患者的1年生存率、2年生存率和3年生存率分别是83.3％和60.0％、75.0％和50.0％、63.9％和40.0％,2组患者差异具有统计学意义(P＜0.05).手术前观察组患者的CD4+和CD4 +/CD8+显著高于对照组(P＜0.05).结论 在手术前进行新辅助化疗对NSCLC患者手术切除率以及生存率等情况都有提高的效果,可能与提高患者免疫水平和降低术中出血量有关.     

Targeting the MET pathway for potential treatment of NSCLC

Introduction: The mesenchymal-epithelial transition (MET) protein is the only known receptor for hepatocyte growth factor and has recently been identified as a novel promising target in several human cancers, including NSCLC. Activation of the MET signaling pathway can occur via different mechanisms. A number of compounds targeting MET have been evaluated in clinical trials, and recent clinical data have begun to afford some insight into the tumor types and patient populations that might benefit from treatment with MET pathway inhibitors.

Areas covered: We review recent publications and information disclosed at public conferences and summarize the epidemiology of dysregulation of MET signaling, and the associations thereof with other driver genes and therapeutic inhibitors useful to treat NSCLC.

Expert opinion: The MET pathway is emerging as a target for advanced NSCLC that is either resistant to EGFR tyrosine kinase inhibitors or that arises de novo. MET inhibitors currently being evaluated in clinical trials have yielded compelling evidence of clinical activities when used to treat various solid tumors, especially NSCLC. Remaining challenges are the identification of patient populations who might benefit from the use of MET inhibitors, and the most effective diagnostic methods for such patients.     

药物选择 剂量 分割 顺序对放疗联合免疫治疗晚期非小细胞肺癌疗效的影响

非小细胞肺癌(non-small cell lung cancer，NSCLC)约占肺癌总数的85%，53%的患者在确诊时即为晚期。近年来，免疫检查点抑制剂(immune checkpoint inhibitors，ICIs)在晚期肿瘤治疗中效果显著。放疗在晚期NSCLC主要用于局部姑息治疗。研究显示免疫治疗协同放疗治疗晚期NSCLC与单独放疗或免疫治疗相比，可改善患者的无进展生存(progression-free survival，PFS)和总生存(overall survival，OS)，且不增加3级以上不良反应发生率。但ICIs的选择、放疗剂量、分割方式及联合治疗顺序仍未完全阐明。本文就免疫治疗联合放疗在晚期NSCLC中的临床研究进展作一综述，为临床选择提供参考。