locally advanced NSCLC

  • 文章类型: Journal Article
    背景:根据PACIFIC试验的结果,基于铂类的放化疗(CRT)后合并durvalumab是不可切除患者的全球标准治疗,III期非小细胞肺癌(NSCLC)。来自正在进行的PACIFIC-R研究(NCT03798535)的早期分析证明了该方案在无进展生存期(PFS)方面的有效性。这里,我们报告了首次计划总生存期(OS)分析.
    方法:PACIFIC-R是一种观察性/非干预性,无法切除的患者的回顾性研究,在2017年9月至2018年12月期间,在阿斯利康启动的早期接入计划内开始使用durvalumab(每2周静脉注射10mg/kg)的III期NSCLC.主要终点是OS和研究者评估的PFS,使用卡普兰-迈耶方法估计。
    结果:截至2021年11月30日,完整分析集包括来自10个国家的1154名参与者(审查患者的中位随访时间:38.7个月)。未达到OS中位数,3年OS率为63.2%(95%置信区间为60.3%~65.9%)。在程序性死亡配体1(PD-L1)表达≥1%与<1%的肿瘤细胞(TC;67.0%对54.4%)的患者中,三年OS率在数字上较高,同时接受CRT(cCRT)与序贯CRT(sCRT)(64.8%对57.9%)。
    结论:PACIFIC-R数据继续为CRT后合并durvalumab的有效性提供证据,多样化,现实世界的人口。在PD-L1TC≥1%的患者和接受cCRT的患者中观察到更好的结果。然而,在TC<1%的患者和接受sCRT的患者中仍观察到令人鼓舞的结果,支持在无法切除的广泛患者中使用巩固durvalumab,III期NSCLC。
    BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis.
    METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method.
    RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%).
    CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.
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  • 文章类型: Journal Article
    背景:局部晚期NSCLC治疗的最新进展导致了对该疾病的治疗标准的改变。为了为每位患者选择最佳的方法策略,诊断和治疗干预措施的同质化是必要的,以及多学科肿瘤学团队促进对患者的评估。
    目的:由西班牙肺癌组织GECP领导,为局部晚期非小细胞肺癌的方法和治疗提供建议。
    方法:在2023年3月至7月之间,组成了由28名专家组成的小组。在协调小组的指导下使用混合技术(Delphi/nominalgroup),分四个阶段达成共识:1。文献综述和讨论主题的定义2.第一轮投票3.传达结果和第二轮投票4.名义小组会议结论的定义。使用中位数和四分位数范围来合并响应。协议的门槛被定义为85%的选票。
    结果:根据证据和临床经验,对关于局部晚期NSCLC的诊断和治疗的新情况和有争议的情况进行分析和协调。讨论问题包括:分子诊断和生物标志物,放射学和外科诊断,纵隔分期,多学科胸科委员会的作用,新辅助治疗适应症,评估对新辅助治疗的反应,术后评估,和后续行动。
    结论:在最相关的情况下,如诊断,局部晚期肺癌的分期和治疗,这将有助于支持日常实践中的决策。
    BACKGROUND: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team.
    OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP.
    METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes.
    RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up.
    CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.
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  • 文章类型: Journal Article
    在安慰剂对照中,太平洋第三阶段试验,durvalumab显著延长了不可切除的III期NSCLC患者的无进展生存期(PFS)(p<0.0001)和总生存期(OS)(p=0.00251),且在铂类同步放化疗(cCRT)后无进展.肺炎或放射性肺炎(PRP)在两组中都很常见。我们报告了探索性分析,评估症状性(≥2级)PRP(G2+PRP)与基线因素和临床结果的关联。
    WHO表现状态为0或1的患者被随机(2:1)至12个月的durvalumab或安慰剂,cCRT后1~42天。使用单变量和多变量逻辑回归研究durvalumab治疗患者的基线因素与研究中G2+PRP之间的关联。使用Cox比例风险模型分析PFS和OS,该模型针对时间依赖性G2PRP加协变量进行了调整,用于没有和有其他基线因素的随机分层因素。
    研究中G2+PRP发生在使用durvalumab和安慰剂的475例患者中的94例(19.8%)和234例患者中的33例(14.1%),分别(中位随访,25.2个月);等级大于或等于3个PRP并不常见(4.6%和4.7%,分别)。G2+PRP的起效时间和消退时间与durvalumab和安慰剂相似。单变量和多变量分析确定了在亚洲接受治疗的患者,那些患有IIIA期疾病的人,表现状态为1的患者和未接受诱导化疗的患者G2+PRP风险较高.与时间依赖性G2+PRP无关,维持了Durvalumab相对于安慰剂的PFS和OS益处。
    确定了cCRT后与durvalumab的G2+PRP风险升高相关的因素。无论研究中的G2+PRP如何,临床获益均得到维持,提示该事件的风险不应阻止durvalumab用于符合条件的不可切除的III期NSCLC患者.
    UNASSIGNED: In the placebo-controlled, phase 3 PACIFIC trial, durvalumab significantly prolonged progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.00251) in patients with unresectable stage III NSCLC and no progression after platinum-based concurrent chemoradiotherapy (cCRT). Pneumonitis or radiation pneumonitis (PRP) was common in both arms. We report exploratory analyses evaluating the association of symptomatic (grade ≥2) PRP (G2+PRP) with baseline factors and clinical outcomes.
    UNASSIGNED: Patients with WHO performance status of 0 or 1 were randomized (2:1) to 12 months of durvalumab or placebo, 1 to 42 days after cCRT. Associations between baseline factors and on-study G2+PRP in durvalumab-treated patients were investigated using univariate and multivariate logistic regression. PFS and OS were analyzed using Cox proportional hazards models adjusted for time-dependent G2+PRP plus covariates for randomization stratification factors without and with additional baseline factors.
    UNASSIGNED: On-study G2+PRP occurred in 94 of 475 (19.8%) and 33 of 234 patients (14.1%) on durvalumab and placebo, respectively (median follow-up, 25.2 mo); grade greater than or equal to 3 PRP was uncommon (4.6% and 4.7%, respectively). Time to onset and resolution of G2+PRP was similar with durvalumab and placebo. Univariate and multivariate analyses identified patients treated in Asia, those with stage IIIA disease, those with performance status of 1, and those who had not received induction chemotherapy as having a higher risk of G2+PRP. PFS and OS benefit favoring durvalumab versus placebo was maintained regardless of time-dependent G2+PRP.
    UNASSIGNED: Factors associated with higher risk of G2+PRP with durvalumab after cCRT were identified. Clinical benefit was maintained regardless of on-study G2+PRP, suggesting the risk of this event should not deter the use of durvalumab in eligible patients with unresectable stage III NSCLC.
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  • 文章类型: Journal Article
    背景:同步放化疗(CRT)后的免疫检查点抑制剂(ICI)巩固显着改善了PACIFIC试验中的无进展生存期(PFS)和总生存期(OS),成为局部晚期的标准治疗,不可切除的非小细胞肺癌。KRAS突变可能影响对ICI的反应。
    方法:在这个单一机构中,回顾性分析,我们比较了2017年10月至2021年12月接受CRT治疗的不可切除KRAS突变(KRAS-mt)和野生型(KRAS-wt)NSCLC患者的治疗结局.Kaplan-Meier分析比较了所有KRAS-mt患者和KRAS-G12C突变患者的中位无进展生存期和完成放疗后的中位总生存期。结果也与没有ICI合并的情况进行了比较。
    结果:在156名患者中,42(26.9%)为KRAS-mt,114(73.1%)为KRAS-wt。基线特征仅在组织学上有所不同;KRAS-mtNSCLC更可能是腺癌。KRAS-mt患者PFS较差(中位数6.3vs.10.7个月,P=.041),但操作系统相似(中位数23.1与27.3个月,P=.237)。由于CRT后疾病进展迅速,KRAS-mt患者更有可能不接受ICI(23.8%vs.4.4%,P=.007)。在接受ICI的患者中(n=114),KRAS-mt与较差的PFS无关(8.1与11.9个月,P=.355)或OS(30.5vs.31.7个月,P=.692)。KRAS-G12C患者(n=22)的PFS和OS与其他KRAS-mt相似。
    结论:在发表的最大的CRT后KRAS-mt队列之一中,KRAS-mt与劣质PFS相关,主要是由于ICI合并之前的快速进展,但不影响操作系统。在接受ICI合并的人中,无论KRAS-mt状态如何,结局均具有可比性.
    BACKGROUND: Immune checkpoint inhibitor (ICI) consolidation following concurrent chemoradiotherapy (CRT) substantially improved progression free survival (PFS) and overall survival (OS) in the PACIFIC trial becoming the standard of care in locally-advanced, unresectable NSCLC. KRAS mutation may influence response to ICI.
    METHODS: In this single-institution, retrospective analysis, we compared treatment outcomes for patients with unresectable KRAS mutated (KRAS-mt) and wild-type (KRAS-wt) NSCLC treated with CRT between October 2017 and December 2021. Kaplan-Meier analysis was conducted comparing median progression free survival and median overall survival from completion of radiotherapy in all KRAS-mt patients and KRAS-G12C-mutated patients. Outcomes were also compared with and without ICI consolidation.
    RESULTS: Of 156 patients, 42 (26.9%) were KRAS-mt and 114 (73.1%) were KRAS-wt. Baseline characteristics differed only in histology; KRAS-mt NSCLC more likely to be adenocarcinoma. KRAS-mt patients had worse PFS (median 6.3 vs. 10.7 months, P = .041) but similar OS (median 23.1 vs. 27.3 months, P = .237). KRAS-mt patients were more likely to not receive ICI due to rapid disease progression post-CRT (23.8% vs. 4.4%, P = .007). Among patients who received ICI (n = 114), KRAS-mt was not associated with inferior PFS (8.1 vs. 11.9 months, P = .355) or OS (30.5 vs. 31.7 months, P = .692). KRAS-G12C patients (n = 22) had similar PFS and OS to other KRAS-mt.
    CONCLUSIONS: In one of the largest post-CRT KRAS-mt cohort published, KRAS-mt was associated with inferior PFS, largely due to rapid progression prior to ICI consolidation, but did not affect OS. Among those who received ICI consolidation, outcomes were comparable regardless of KRAS-mt status.
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  • 文章类型: Journal Article
    背景:伴有N1/N2淋巴结转移的局部晚期非小细胞肺癌(NSCLC)具有挑战性,生存率较差。新辅助化学免疫疗法在这些患者的一部分中获得了益处。然而,尚未证明特异性生物标志物在治疗前预测效果。此外,淋巴结状态与新辅助化学免疫疗法后生存的关系仍未得到很好的说明.
    方法:回顾性研究了75例接受新辅助化疗免疫疗法加手术治疗的N1/N2期可切除的NSCLC患者。临床特点,收集手术信息和安全参数.分析主要病理反应(MPR)和病理完全反应(pCR)与临床资料的相关性。通过病理反应和淋巴结状态评估无进展疾病(PFS)和总生存期(OS)。
    结果:在75例患者中,69例(92%)患者经历了治疗相关的不良反应,而3-4级不良反应发生在8例(10%)患者中。所有患者均接受手术R0切除,MPR率为60%,pCR率为36%。新辅助治疗后,67%的N1患者和77%的N2患者有淋巴结清除。随着年龄的增加,观察到病理反应之间存在显着差异。组织学及多发淋巴结转移。MPR队列中PFS较好。在12个月和18个月时,淋巴结清除组的PFS分别为90.1%和83.6%,与淋巴结残留组的70.1%和63.7%相比。
    结论:新辅助化疗治疗淋巴结阳性的局部晚期非小细胞肺癌是安全可行的。年龄较大、鳞状细胞癌(SCC)患者更容易有较好的病理反应,而多淋巴结转移是阴性预测因子。淋巴结的清除导致明显更长的PFS和OS。
    BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated.
    METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status.
    RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group.
    CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.
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  • 文章类型: Journal Article
    目的:尽管免疫治疗对非小细胞肺癌(NSCLC)的相关性与日俱增,关于局部晚期NSCLC的最佳治疗策略的共识有限.本研究评估了接受手术诱导化学免疫疗法(“CT/IO手术”)和明确的同步放化疗后免疫治疗(“cCRTIO”)的III-N2期非小细胞肺癌患者的总体生存率。
    方法:纳入国家癌症数据库(2013-2019)中的cT1-3,N2,M0NSCLC患者,并按治疗方案进行分层:CT/IO手术或cCRTIO。使用Kaplan-Meier分析评估总生存期,Cox比例风险建模,和10个预后变量的倾向评分匹配。
    结果:在满足研究资格标准的3,382名患者中,3,289(97.3%)接受cCRT+IO,93(2.8%)接受CT/IO+手术。整个队列的3年总生存率为58.2%(95%CI:56.2-60.1)。多变量校正Cox比例风险模型显示,CT/IO+手术后的生存率优于cCRT+IO(HR:0.52,95%CI:0.32-0.84,p=0.007)。在223例接受cCRT+IO的患者和76例接受CT/IO+手术的患者的3:1可变比率倾向评分匹配分析中,cCRT+IO术后3年总生存率为63.2%(95%CI:55.9-70.2),CT/IO+术后3年总生存率为77.2%(95%CI:64.6-85.7)(p=0.029)。
    结论:在这项国家分析中,包括免疫疗法在内的多模式治疗与所有III-N2期非小细胞肺癌患者的3年总生存率为58.2%相关,接受化学免疫疗法随后进行手术的患者为77.2%。这些结果应被认为是假设的产生,并证明了在现代免疫治疗时代,开发一项随机试验以评估手术与放化疗对局部晚期NSCLC的作用的重要性。
    OBJECTIVE: Despite the growing relevance of immunotherapy for non-small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for locally advanced NSCLC. This study evaluated the overall survival of patients with stage III-N2 NSCLC undergoing induction chemoimmunotherapy with surgery (CT/IO+Surgery) and definitive concurrent chemoradiation followed by immunotherapy (cCRT+IO).
    METHODS: Patients with cT1-3, N2, M0 NSCLC in the National Cancer Database (2013 to 2019) were included and stratified by treatment regimen: CT/IO+Surgery or cCRT+IO. Overall survival was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching on 10 prognostic variables.
    RESULTS: Of the 3382 patients who met the study eligibility criteria, 3289 (97.3%) received cCRT+IO and 93 (2.8%) received CT/IO+Surgery. The 3-year overall survival of the entire cohort was 58.2% (95% CI, 56.2% to 60.1%). Multivariable-adjusted Cox proportional hazards modeling demonstrated better survival after CT/IO+Surgery than after cCRT+IO (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.32 to 0.84; P = .007). In a 3:1 variable ratio propensity score-matched analysis of 223 patients who received cCRT+IO and 76 patients who received CT/IO+Surgery, 3-year overall survival was 63.2% (95% CI, 55.9% to 70.2%) after cCRT+IO and 77.2% (95% CI, 64.6% to 85.7%) after CT/IO+Surgery (P = .029).
    CONCLUSIONS: In this national analysis, multimodal treatment including immunotherapy was associated with a 3-year overall survival rate of 58.2% for all patients with stage III-N2 NSCLC and 77.2% for patients who underwent chemoimmunotherapy followed by surgery. These results should be considered hypothesis-generating and demonstrate the importance of developing a randomized trial to evaluate the role of surgery versus chemoradiation for locally advanced NSCLC in the modern immunotherapy era.
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  • 文章类型: Journal Article
    未经评估:那不勒斯预后评分(NPS)可以反映患者的营养和炎症状态,被确定为各种恶性肿瘤的预后指标。然而,目前尚不清楚其在接受新辅助治疗的切除局部晚期非小细胞肺癌(LA-NSCLC)患者中的意义.
    UNASSIGNED:回顾性调查了2012年5月至2017年11月手术治疗的165例LA-NSCLC患者。根据NPS评分将LA-NSCLC患者分为3组。进行受试者工作曲线(ROC)分析以揭示NPS和其他指标预测生存的辨别能力。通过单因素和多因素Cox分析进一步评估NPS和临床病理变量的预后价值。
    未经评估:NPS与年龄有关(P=0.046),吸烟史(P=0.004),东部肿瘤协作组(ECOG)评分(P=0.005),和辅助治疗(P=0.017)。NPS评分高的患者总生存期(OS)(第1组vs0,P=0.006;第2组vs0,P<0.001)和无病生存期(DFS)(第1组vs0,P<0.001;第2组vs0,P<0.001)较差。ROC分析表明,NPS比其他预后指标具有更好的预测能力。多因素分析显示,NPS是OS的独立预后指标(第1组vs0,风险比[HR]=2.591,P=0.023;第2组vs0,HR=8.744,P=0.001)和DFS(第1组vs0,HR=3.754,P<0.001;第2组vs0,HR=9.673,P<0.001)。
    UNASSIGNED:NPS可能是接受新辅助治疗的LA-NSCLC切除患者的独立预后指标,并且比其他营养和炎症指标更可靠。
    UNASSIGNED: The Naples Prognostic Score (NPS) can reflect patient\'s nutritional and inflammatory status, which is identified as a prognostic indicator for various malignant tumors. However, its significance in patients with resected locally advanced non-small cell lung cancer (LA-NSCLC) patients who receive neoadjuvant treatment remains unclear so far.
    UNASSIGNED: A total of 165 LA-NSCLC patients surgically treated from May 2012 to November 2017 were retrospectively investigated. The LA-NSCLC patients were divided into three groups according to NPS scores. The receiver operating curve (ROC) analysis was performed to reveal the discriminatory ability of NPS and other indicators for predicting the survival. The NPS and clinicopathological variables were further evaluated the prognostic value by univariate and multivariate Cox analysis.
    UNASSIGNED: The NPS was related to age (P = 0.046), smoking history (P = 0.004), Eastern Cooperative Oncology Group (ECOG) score (P = 0.005), and adjuvant treatment (P = 0.017). Patients with high NPS scores had worse overall survival (OS) (group 1 vs 0, P = 0.006; group 2 vs 0, P < 0.001) and disease-free survival (DFS) (group 1 vs 0, P < 0.001; group 2 vs 0, P < 0.001). The ROC analysis demonstrated that NPS had better predictive ability than other prognostic indicators. Multivariate analysis revealed that NPS was independent prognostic indicator of OS (group 1 vs 0, hazard ratio [HR] =2.591, P = 0.023; group 2 vs 0, HR = 8.744, P = 0.001) and DFS (group 1 vs 0, HR =3.754, P < 0.001; group 2 vs 0, HR = 9.673, P < 0.001).
    UNASSIGNED: The NPS could be an independent prognostic indicator in patients with resected LA-NSCLC receiving neoadjuvant treatment and more reliable than the other nutritional and inflammatory indicators.
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  • 文章类型: Journal Article
    背景:由于手术复杂性和预后差,侵入上腔静脉(SVC)的非小细胞肺癌(NSCLCs)的手术很少进行。已经描述了重建SVC的不同方法,如直接缝合,贴片使用或假体,根据其周围的参与。我们研究的目的是分析不同类型的SVC切除和重建治疗T4NSCLC的短期和长期结果。
    方法:在2000年1月至2019年12月之间,在这项多中心回顾性研究中,有80例患者接受了解剖性肺切除术和SVC手术。部分切除和直接缝合或补片重建组包括64例患者,而完整切除和假体重建组包括16例患者。主要终点如下:长期生存率和无病生存率。次要终点如下:围手术期并发症和30天和90天死亡率。非参数变量的非配对t检验或Mann-WhitneyU检验应用于离散或连续数据,对二分或分类数据进行卡方检验。使用Kaplan-Meier方法计算生存率,并使用对数秩检验进行比较。
    结果:两组在一般特征和手术方面没有发现差异,肿瘤和生存结果。特别是,在早期方面没有差异(50.0%与68.8%,p=0.178)和晚期并发症频率(12.5%vs.12.5%,p=1.000),30天和90天死亡率,R状态,复发,总生存率(33.89±40.35vs.35.70±51.43个月,p=0.432)和无病生存率(27.56±40.36vs.31.28±53.08个月,p=0.668)。多变量分析表明,年龄是总生存率的唯一独立预测因素。
    结论:根据我们的结果,SVC切除术具有良好的肿瘤和生存结果,无论圆周参与的比例和重建的类型。
    BACKGROUND: Surgery for non-small-cell lung cancers (NSCLCs) invading the superior vena cava (SVC) is rarely performed due to surgical complexities and reported poor prognoses. Different methods have been described to reconstruct the SVC, such as direct suture, patch use or prosthesis, according to its circumferential involvement. The aim of our study was to analyze the short- and long-term results of different types of SVC resection and reconstruction for T4 NSCLCs.
    METHODS: Between January 2000 and December 2019, 80 patients received an anatomical lung resection with SVC surgery in this multicenter retrospective study. The partial resection and direct suture or patch reconstruction group included 64 patients, while the complete resection and prosthesis reconstruction group included 16 patients. The primary endpoints were as follows: long-term survival and disease-free survival. The secondary endpoints were as follows: perioperative complications and 30- and 90-day mortality. Unpaired t-tests or Mann-Whitney U tests for non-parametric variables were applied to discrete or continuous data, and the chi-square test was applied to dichotomous or categorical data. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test.
    RESULTS: No differences were found between the two groups in terms of general characteristics and surgical, oncological and survival outcomes. In particular, there were no differences in terms of early (50.0% vs. 68.8%, p = 0.178) and late complication frequency (12.5% vs. 12.5%, p = 1.000), 30- and 90-day mortality, R status, recurrence, overall survival (33.89 ± 40.35 vs. 35.70 ± 51.43 months, p = 0.432) and disease-free survival (27.56 ± 40.36 vs. 31.28 ± 53.08 months, p = 0.668). The multivariate analysis demonstrated that age was the only independent predictive factor for overall survival.
    CONCLUSIONS: According to our results, SVC resection has good oncological and survival outcomes, regardless of the proportion of circumferential involvement and the type of reconstruction.
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  • 文章类型: Journal Article
    背景:3期PACIFIC试验确立了将durvalumab作为不可切除患者的标准治疗,明确放化疗(CRT)后III期NSCLC无疾病进展。PACIFIC-R观察性研究评估了durvalumab在早期接入项目患者中的真实世界有效性。这里,我们报告了治疗特征和对真实世界无进展生存期(rwPFS)的预先计划分析.
    方法:PACIFIC-R(NCT03798535)正在进行中,国际,在2017年9月至2018年12月期间在早期接入计划内开始使用durvalumab(静脉注射;每2周10mg/kg)的患者的回顾性研究.主要终点是研究者评估的rwPFS和总生存期(通过Kaplan-Meier方法分析)。
    结果:截至2020年11月30日,完整的分析集包括来自11个国家的1399名患者(中位随访时间,23.5个月)。患者接受durvalumab的中位时间为11.0个月。rwPFS中位数为21.7个月(95%置信区间:19.1-24.5)。在同时接受与序贯CRT的患者中,RwPFS在数值上更长(中位数,23.7对19.3mo),以及程序性细胞死亡-配体1表达大于或等于1%对小于1%(22.4对15.6mo)的患者。总的来说,16.5%的患者出现不良事件导致治疗中断;9.5%的患者因肺炎或间质性肺病而停止治疗。
    结论:明确的CRT后合并durvalumab在这种大的,无法切除的患者的真实世界队列研究,III期NSCLC。不出所料,同时接受与序贯CRT的患者和程序性细胞死亡-配体1表达较高的患者的rwPFS较长。然而,无论这些因素如何,均观察到有利的rwPFS结局.
    The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS).
    PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every 2 wk) within an early access program between September 2017 and December 2018. The primary end points are investigator-assessed rwPFS and overall survival (analyzed by Kaplan-Meier method).
    As of November 30, 2020, the full analysis set comprised 1399 patients from 11 countries (median follow-up duration, 23.5 mo). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% confidence interval: 19.1-24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 versus 19.3 mo) and among patients with programmed cell death-ligand 1 expression greater than or equal to 1% versus less than 1% (22.4 versus 15.6 mo). Overall, 16.5% of the patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis or interstitial lung disease.
    Consolidation durvalumab after definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was longer among patients who received concurrent versus sequential CRT and patients with higher programmed cell death-ligand 1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors.
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  • 文章类型: Journal Article
    背景:在局部晚期非小细胞肺癌(LA-NSCLC)的放射治疗中,报告了从内部目标体积到12至23mm范围内的计划目标体积的“余量”,避免暴露对侧肺是常见的做法。我们前瞻性地调查了一种边缘狭窄(7毫米)且最大程度保留同侧正常肺的方法。报告了第一个终点(肺炎)的成熟结果和进一步的毒性。
    方法:用VMAT治疗原发性肿瘤73.8-90.0Gy,与肿瘤体积呈正相关,具有61.2Gy的节点,选择性地限制了45Gy的节点体积。分数剂量为1.8Gybid,间隔8小时。放疗前,给予以铂为基础的2个周期化疗.12例患者完成Durvalumab维持治疗。所有患者的中位随访时间为19.4个月,对于存活27.0个月(3.4-66.5个月)的患者。
    结果:连续100次,纳入未选择的II期至IVA期LA-NSCLC患者(UICC/AJCC,第8版)。无急性4/5级毒性。在12%和2%的患者中观察到2级和3级肺炎,分别;与研究LA-NSCLC肺炎的文献中最大的研究相比,降低肺炎≥2级的风险,是显著的(p<0.0006)。急性食管毒性1级、2级和3级发生率为12%,57%和3%的患者,分别。两名患者表现为2级晚期支气管狭窄/肺不张。在两名致命性肺出血患者中,不能排除治疗相关性。所有III期患者的中位总生存期,对于那些具有“RTOG0617纳入标准”的人,分别为46.6和50.0个月,分别。
    结论:总体毒性低。与文献中的结果相比,最大限度地保留同侧正常肺可显著降低肺炎风险.
    背景:福拉尔贝格伦理委员会,奥地利;EK-0.04-105,注册04/09/2017-回顾性注册。http://www。ethikkommission-vorarlberg.在。
    BACKGROUND: In radiation treatment of locally advanced non-small cell lung cancer (LA-NSCLC), \'margins\' from internal target volumes to planning target volumes in the range of 12 to 23 mm are reported, and avoiding exposure of the contralateral lung is common practice. We investigated prospectively an approach with tight margins (7 mm) and maximal sparing of the ipsilateral normal lung. Mature results for the first endpoint (pneumonitis) and further toxicities are reported.
    METHODS: Primary tumors were treated by VMAT with 73.8-90.0 Gy in positive correlation to tumor volumes, nodes with 61.2 Gy, a restricted volume of nodes electively with 45 Gy. Fractional doses of 1.8 Gy bid, interval 8 h. Before radiotherapy, two cycles platin-based chemotherapy were given. 12 patients finished maintenance therapy with Durvalumab. Median follow up time for all patients is 19.4 months, for patients alive 27.0 months (3.4-66.5 months).
    RESULTS: 100 consecutive, unselected patients with LA-NSCLC in stages II through IVA were enrolled (UICC/AJCC, 8th edition). No acute grade 4/5 toxicity occurred. Pneumonitis grade 2 and 3 was observed in 12% and 2% of patients, respectively; lowering the risk of pneumonitis grade ≥ 2 in comparison to the largest study in the literature investigating pneumonitis in LA-NSCLC, is significant (p < 0.0006). Acute esophageal toxicity grade 1, 2 and 3 occurred in 12%, 57% and 3% of patients, respectively. Two patients showed late bronchial stricture/atelectasis grade 2. In two patients with lethal pulmonary haemorrhages a treatment correlation cannot be excluded. Median overall survival for all stage III patients, and for those with \'RTOG 0617 inclusion criteria\' is 46.6 and 50.0 months, respectively.
    CONCLUSIONS: Overall toxicity is low. In comparison to results in the literature, maximal sparing the ipsilateral normal lung lowers the risk for pneumonitis significantly.
    BACKGROUND: Ethics committee of Vorarlberg, Austria; EK-0.04-105, Registered 04/09/2017-Retrospectively registered. http://www.ethikkommission-vorarlberg.at.
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