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Simple parameters to solve a complex issue: predicting response to checkpoint inhibitor therapy in lung cancer. 简单的参数解决一个复杂的问题:预测肺癌对检查点抑制剂治疗的反应。
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-11-23 DOI: 10.2217/lmt-2020-0024
James Newman, Isabel Preeshagul, Nina Kohn, Craig Devoe, Nagashree Seetharamu

Background: Noninvasive biomarkers predicting immune checkpoint inhibitor (ICI) response are urgently needed. We evaluated the predictive value of pretreatment neutrophil-to-lymphocyte ratio (NLR), smoking history, smoking intensity, BMI and programmed death ligand 1 (PD-L1) expression in non-small-cell lung cancer (NSCLC) patients treated with ICIs.

Materials & methods: Single-center retrospective study included 137 patients from July 2015 to February 2018. Outcomes included 3-month disease control rate, progression-free survival, and overall survival. Predictive value of biomarkers was assessed independently and in a multivariable model.

Results: NLR was associated with all outcomes. Smoking history was predictive of progression-free survival and smoking intensity was predictive of disease control rate. BMI and PD-L1 were not associated with any outcome. High BMI was associated with low NLR.

Conclusion: Simple clinical biomarkers can predict response to ICIs. A score incorporating both clinical factors and established tissue/serum biomarkers may be useful in identifying NSCLC patients who would benefit from ICIs.

背景:迫切需要预测免疫检查点抑制剂(ICI)反应的无创生物标志物。我们评估了预处理中性粒细胞与淋巴细胞比率(NLR)、吸烟史、吸烟强度、BMI和程序性死亡配体1 (PD-L1)表达在非小细胞肺癌(NSCLC)患者接受ICIs治疗中的预测价值。材料与方法:2015年7月至2018年2月,单中心回顾性研究纳入137例患者。结果包括3个月疾病控制率、无进展生存期和总生存期。在多变量模型中独立评估生物标志物的预测价值。结果:NLR与所有结果相关。吸烟史可预测无进展生存,吸烟强度可预测疾病控制率。BMI和PD-L1与任何结果无关。高BMI与低NLR相关。结论:简单的临床生物标志物可预测ICIs的疗效。结合临床因素和已建立的组织/血清生物标志物的评分可能有助于识别将受益于ICIs的非小细胞肺癌患者。
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引用次数: 3
Efficacy and safety of tyrosine kinase inhibitors in advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutation: a network meta-analysis. 酪氨酸激酶抑制剂治疗表皮生长因子受体突变晚期非小细胞肺癌的疗效和安全性:一项网络荟萃分析。
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-11-23 DOI: 10.2217/lmt-2020-0011
Abdullah Alanazi, Ismaeel Yunusa, Khaled Elenizi, Abdulaziz I Alzarea

Aim: To compare the efficacy and safety of tyrosine kinase inhibitors (TKIs) as first-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with positive EGFR mutation.

Materials & methods: Following a systematic literature review until December 2019, we conducted a random-effects pairwise and network meta-analyses (NMA). We ranked treatments for efficacy and safety based on the surface under the cumulative ranking curve (SUCRA).

Results: Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) improved survival outcomes with fewer grade 3 or higher adverse events compared to chemotherapy. Overall survival results suggest that osimertinib has the highest probability of being the most efficacious (SUCRA, 79.9%), followed by dacomitinib (SUCRA, 75.8%). Adverse events results suggest that osimertinib (SUCRA, 84.3%) and gefitinib (SUCRA, 78.9%) has the highest probability of being the safest.

Conclusion: In this NMA, we found that osimertinib is the most efficacious and safest EGFR-TKI. These results may guide clinicians in choosing the most appropriate treatment option among EGFR-TKIs for their patient's individual clinical characteristics.

目的:比较酪氨酸激酶抑制剂(TKIs)作为EGFR阳性突变的局部晚期或转移性非小细胞肺癌(NSCLC)患者一线治疗的疗效和安全性。材料与方法:在系统文献综述之后,我们进行了随机效应配对和网络荟萃分析(NMA)。我们根据累积排名曲线(SUCRA)下的表面对治疗的疗效和安全性进行排名。结果:与化疗相比,表皮生长因子受体(EGFR-TKI)酪氨酸激酶抑制剂改善了生存结果,减少了3级或更高的不良事件。总体生存结果显示,奥西替尼最有效的概率最高(SUCRA, 79.9%),其次是dacomitinib (SUCRA, 75.8%)。不良事件结果显示,奥西替尼(SUCRA, 84.3%)和吉非替尼(SUCRA, 78.9%)最安全的概率最高。结论:在本次NMA中,我们发现奥西替尼是最有效、最安全的EGFR-TKI。这些结果可以指导临床医生根据患者的个体临床特征在egfr - tki中选择最合适的治疗方案。
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引用次数: 18
Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform. 间变性淋巴瘤激酶阳性非小细胞肺癌的人文生活负担:来自ALKConnect患者洞察网络和研究平台的研究结果
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-11-20 DOI: 10.2217/lmt-2020-0018
Huamao M Lin, Xiaoyun Pan, Alyssa Biller, Kyla J Covey, Hui Huang, Rebecca Sugarman, Fatima Scipione, Howard West

Aim: Evaluate real-world patient preferences, experiences and outcomes (health-related quality of life [HRQoL]) from patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) utilizing the ALKConnect Patient Insight Network.

Patients & methods: Demographics, disease history/status/treatment, patient preferences and HRQoL (MD Anderson Symptom Inventory lung cancer module, reported as symptom severity and interference) were evaluated for US adults with ALK+ NSCLC.

Results: Among 104 patients (median age: 53.0 years, 67.3% female, 40.0% employed), HRQoL and 3-month delay in disease progression were important treatment attributes. Burdensome symptoms included fatigue and disturbed sleep. Symptoms interfered most with work and day-to-day activity. Higher HRQoL was associated with ALK tyrosine kinase inhibitor (TKI) treatment and employment.

Conclusion: ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC.

目的:利用ALKConnect患者洞察网络评估间变性淋巴瘤激酶阳性(ALK+)非小细胞肺癌(NSCLC)患者的现实世界患者偏好、经历和结果(健康相关生活质量[HRQoL])。患者和方法:对美国成年ALK+ NSCLC患者的人口统计学、病史/状态/治疗、患者偏好和HRQoL (MD安德森症状量表肺癌模块,报告为症状严重程度和干扰)进行评估。结果:104例患者(中位年龄:53.0岁,67.3%为女性,40.0%为在职),HRQoL和疾病进展延迟3个月是重要的治疗属性。繁重的症状包括疲劳和睡眠紊乱。症状对工作和日常活动的影响最大。较高的HRQoL与ALK酪氨酸激酶抑制剂(TKI)的治疗和使用有关。结论:ALKConnect表明ALK+ NSCLC的疾病进展、HRQoL、疲劳/睡眠、ALK TKIs和就业相关。
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引用次数: 0
Diagnosis and management of small pulmonary atypical carcinoid tumor associated with Cushing syndrome. 与库欣综合征相关的肺部小型非典型类癌的诊断和治疗。
IF 0.9 Q4 RESPIRATORY SYSTEM Pub Date : 2020-09-14 DOI: 10.2217/lmt-2020-0010
Dathe Z Benissan-Messan, Robert E Merritt, Konstantin Shilo, Desmond M D'Souza, Peter J Kneuertz

Ectopic adrenocorticotropic hormone (ACTH) syndrome is rare and identification of its source is often challenging. We report the case of an ectopic Cushing syndrome in a young adult male secondary to an occult ACTH producing atypical carcinoid tumor. Extensive biochemical and imaging workup was unrevealing. The diagnosis was aided by Ga-DOTA PET scan demonstrating a suspicious left upper lobe lung nodule. The patient underwent video-assisted thoracoscopic exploration with wedge resection and mediastinal lymphadenectomy of a T2aN2M0 atypical carcinoid, resulting in the normalization of ACTH levels and complete resolution of symptoms. The role of a Ga-DOTA PET scan in diagnosing pulmonary carcinoid tumors and their management are discussed.

异位促肾上腺皮质激素(ACTH)综合征非常罕见,而确定其病源往往具有挑战性。我们报告了一例继发于隐匿性促肾上腺皮质激素分泌非典型类癌的异位库欣综合征病例。广泛的生化和影像检查均未发现异常。Ga-DOTA正电子发射计算机断层扫描显示左上肺叶有可疑结节,有助于诊断。患者接受了视频辅助胸腔镜探查、楔形切除术和纵隔淋巴结切除术,切除了一个T2aN2M0非典型类癌,结果促肾上腺皮质激素(ACTH)水平恢复正常,症状完全缓解。本文讨论了Ga-DOTA PET扫描在诊断肺类癌及其治疗中的作用。
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引用次数: 0
Biopsy frequency and complications among lung cancer patients in the United States. 美国肺癌患者的活检频率和并发症
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-08-17 DOI: 10.2217/lmt-2020-0022
Yichen Zhang, Lizheng Shi, Michael J Simoff, Oliver J Wagner, James Lavin

Objective: This study aimed to describe the frequency and distribution of biopsy procedures for patients diagnosed and treated for primary lung cancer.

Study design: Retrospective cohort study within an administrative database.

Materials & methods: This observational study used data from the IBM MarketScan® Databases between 2013 and 2015.

Results: The total number of lung biopsies performed among eligible subjects was 32,814; an average of 1.7 biopsies per patient. Bronchoscopy and percutaneous approaches accounted for 95% of all procedures. Complication rates by procedure are remarkably similar irrespective of biopsy frequency.

Conclusion: Nearly half (46%) of patients in this population experienced multiple biopsies prior to diagnosis. Further, biopsy choice or sequence in patients receiving multiple procedures was unpredictable.

目的:本研究旨在描述诊断和治疗原发性肺癌的患者活检手术的频率和分布。研究设计:在行政数据库中进行回顾性队列研究。材料与方法:本观察性研究使用了2013年至2015年IBM MarketScan®数据库中的数据。结果:符合条件的受试者进行肺活检的总次数为32,814次;每位患者平均做1.7次活检。支气管镜检查和经皮入路占所有手术的95%。无论活检频率如何,手术并发症的发生率都非常相似。结论:该人群中近一半(46%)的患者在诊断前进行了多次活检。此外,在接受多种手术的患者中,活检的选择或顺序是不可预测的。
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引用次数: 16
The role of palliative care in the management of patients with lung cancer. 姑息治疗在肺癌患者管理中的作用。
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-07-29 DOI: 10.2217/lmt-2020-0016
Irena Tan, Kavitha Ramchandran

Palliative care (PC) is the care of patients and their families with serious illness and is rapidly becoming an important part of the care of cancer patients. Patients with advanced lung cancer are a highly symptomatic population of patients and clearly experience benefits in quality of life and potentially benefits in overall survival when PC is incorporated early on after diagnosis. However, referrals to PC are still reliant on clinical judgment of patient prognosis and symptom burden. Moving forward, improving the integration of PC and lung cancer care will require more efficient real-time screening of patient symptoms, which may be accomplished through the use of patient-reported outcomes.

姑息治疗(Palliative care, PC)是对患有严重疾病的患者及其家属的护理,正迅速成为癌症患者护理的重要组成部分。晚期肺癌患者是一个高度症状化的患者群体,如果在诊断后早期合并PC,显然会在生活质量和总生存期方面获益。然而,转介到PC仍依赖于临床对患者预后和症状负担的判断。展望未来,改善PC和肺癌治疗的整合将需要更有效地实时筛查患者症状,这可以通过使用患者报告的结果来实现。
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引用次数: 1
Choosing the best first-line therapy: NSCLC with no actionable oncogenic driver. 选择最佳一线治疗:无可操作的致癌驱动因素的非小细胞肺癌。
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-07-24 DOI: 10.2217/lmt-2020-0003
So Yeon Kim, Balazs Halmos

Combination platinum-based therapy has been the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC). Immunotherapy has emerged and demonstrated to show benefit in the treatment of patients with advanced NSCLC. In this review, we discuss the pivotal trials that led to the US FDA approval of specific immunotherapy regimens in particular patient populations. We discuss the optimal use of immunotherapy as monotherapy based on the KEYNOTE-024, KEYNOTE-042 and IMpower110 trials, chemo-immunotherapy based on KEYNOTE-189, KEYNOTE-407, IMpower150 and IMpower130 trials, and as doublet immunotherapy based on CheckMate-227. We also discuss the role and limitations of PD-L1 expression and tumor mutational burden as predictive biomarkers in response to single-agent immunotherapy and combination chemoimmunotherapy. Furthermore, we discuss emerging resistance markers such as STK11 and KEAP1 mutations in immunotherapy response and briefly discuss the role of immunotherapy in elderly patients and in patients with actionable mutations.

以铂为基础的联合治疗已成为晚期非小细胞肺癌(NSCLC)的标准治疗方案。免疫疗法已经出现,并证明在治疗晚期非小细胞肺癌患者中显示出益处。在这篇综述中,我们讨论了导致美国FDA批准特定患者群体的特异性免疫治疗方案的关键试验。基于KEYNOTE-024, KEYNOTE-042和IMpower110试验,基于KEYNOTE-189, KEYNOTE-407, IMpower150和IMpower130试验的化学免疫治疗,以及基于CheckMate-227的双重免疫治疗,我们讨论了免疫治疗作为单一治疗的最佳使用。我们还讨论了PD-L1表达和肿瘤突变负担作为单药免疫治疗和联合化疗免疫治疗反应的预测性生物标志物的作用和局限性。此外,我们讨论了新出现的耐药标志物,如STK11和KEAP1突变在免疫治疗反应中的作用,并简要讨论了免疫治疗在老年患者和具有可操作突变的患者中的作用。
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引用次数: 13
Computed tomography texture analysis of response to second-line nivolumab in metastatic non-small cell lung cancer. 转移性非小细胞肺癌对二线纳武单抗反应的计算机断层扫描结构分析。
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-07-22 DOI: 10.2217/lmt-2020-0002
Rahul Ladwa, Kate E Roberts, Connor O'Leary, Nicole Maggacis, Kenneth J O'Byrne, Kenneth Miles

Objectives: Assess computed tomography texture analysis of patients likely to benefit from nivolumab.

Materials & methods: Texture analysis was used to quantify heterogeneity within the largest tumor before immunotherapy. Histogram analysis was classified as hyperdense (positive skewness) or hypodense (negative skewness) and subclassified on median standard deviation value or entropy measurement.

Results: 47 patients were included. At a median follow-up of 18 months, statistical significant differences in progression-free survival were observed when stratified by positive skewness with low entropy, hazard ratio: 0.43 (0.19-0.95); p = 0.036, and positive skewness with low standard deviation, hazard ratio: 0.42 (0.18-0.96); p = 0.04.

Conclusion: Patients who derive a clinical benefit to Nivolumab show a computed tomography texture of a hyperdense yet homogenous tumor.

目的:评估可能受益于纳武单抗的患者的计算机断层结构分析。材料与方法:使用质地分析来量化免疫治疗前最大肿瘤内的异质性。直方图分析分为高密度(正偏度)或低密度(负偏度),并根据中位标准差值或熵测量进行细分。结果:纳入47例患者。在中位随访18个月时,采用低熵正偏度分层时,观察到无进展生存的统计学差异,风险比:0.43 (0.19-0.95);P = 0.036,正偏度标准差低,风险比为0.42 (0.18-0.96);p = 0.04。结论:从Nivolumab获得临床益处的患者显示出高密度但均质肿瘤的计算机断层结构。
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引用次数: 8
Prognostic significance of the neutrophil/lymphocyte ratio in patients undergoing treatment with nivolumab for recurrent non-small-cell lung cancer. 中性粒细胞/淋巴细胞比值在接受纳武单抗治疗复发性非小细胞肺癌患者中的预后意义
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-07-20 DOI: 10.2217/lmt-2020-0014
Bernardo L Rapoport, Annette J Theron, Daniel A Vorobiof, Lizanne Langenhoven, Jacqueline M Hall, Ronwyn I Van Eeden, Teresa Smit, Sze-Wai Chan, Michael C Botha, Johann I Raats, Margriet De Necker, Ronald Anderson

Aim: We investigated the prognostic potential of pretherapy measurement of the neutrophil/lymphocyte ratio (NLR) in patients (n = 56) with non-small-cell lung cancer deemed suitable for treatment with nivolumab.

Materials & methods: This was a multicenter, noninterventional, retrospective data analysis, involving five oncology centers.

Results: Patients with prenivolumab NLR values of <5 and ≥5 had respective median overall survival (OS) values of 14.5 and 7.02 months (p = 0.0026). Patients with ≤2 and >2 metastatic sites had median OS values of 11.4 and 6.1 months, respectively (p = 0.0174). A Cox multiple regression model revealed baseline NLR ≥5 as the only variable significantly associated with decreased OS (p < 0.0447).

Conclusion: Pretreatment elevated NLR values are associated with poor outcomes in patients with recurrent metastatic non-small-cell lung cancer treated with nivolumab.

目的:我们研究了治疗前测量中性粒细胞/淋巴细胞比率(NLR)对56名非小细胞肺癌患者(n = 56)的预后潜力,这些患者被认为适合用纳武单抗治疗。材料与方法:这是一项涉及五个肿瘤中心的多中心、非介入性、回顾性数据分析。结果:2个转移部位的prenivolumab NLR值患者的中位OS值分别为11.4和6.1个月(p = 0.0174)。Cox多元回归模型显示,基线NLR≥5是唯一与OS降低显著相关的变量(p)。结论:预处理升高的NLR值与纳沃单抗治疗的复发性转移性非小细胞肺癌患者预后不良相关。
{"title":"Prognostic significance of the neutrophil/lymphocyte ratio in patients undergoing treatment with nivolumab for recurrent non-small-cell lung cancer.","authors":"Bernardo L Rapoport,&nbsp;Annette J Theron,&nbsp;Daniel A Vorobiof,&nbsp;Lizanne Langenhoven,&nbsp;Jacqueline M Hall,&nbsp;Ronwyn I Van Eeden,&nbsp;Teresa Smit,&nbsp;Sze-Wai Chan,&nbsp;Michael C Botha,&nbsp;Johann I Raats,&nbsp;Margriet De Necker,&nbsp;Ronald Anderson","doi":"10.2217/lmt-2020-0014","DOIUrl":"https://doi.org/10.2217/lmt-2020-0014","url":null,"abstract":"<p><strong>Aim: </strong>We investigated the prognostic potential of pretherapy measurement of the neutrophil/lymphocyte ratio (NLR) in patients (n = 56) with non-small-cell lung cancer deemed suitable for treatment with nivolumab.</p><p><strong>Materials & methods: </strong>This was a multicenter, noninterventional, retrospective data analysis, involving five oncology centers.</p><p><strong>Results: </strong>Patients with prenivolumab NLR values of <5 and ≥5 had respective median overall survival (OS) values of 14.5 and 7.02 months (p = 0.0026). Patients with ≤2 and >2 metastatic sites had median OS values of 11.4 and 6.1 months, respectively (p = 0.0174). A Cox multiple regression model revealed baseline NLR ≥5 as the only variable significantly associated with decreased OS (p < 0.0447).</p><p><strong>Conclusion: </strong>Pretreatment elevated NLR values are associated with poor outcomes in patients with recurrent metastatic non-small-cell lung cancer treated with nivolumab.</p>","PeriodicalId":43551,"journal":{"name":"Lung Cancer Management","volume":"9 3","pages":"LMT37"},"PeriodicalIF":2.8,"publicationDate":"2020-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/lmt-2020-0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38245943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Lung cancer screening guidelines are clear but are they being followed? 肺癌筛查指南很明确,但是否得到了遵守?
IF 2.8 Q4 RESPIRATORY SYSTEM Pub Date : 2020-06-22 DOI: 10.2217/lmt-2020-0015
Coral Olazagasti, Carolina Bernabe, Nagashree Seetharamu
Lung cancer is the second most common cause of cancer worldwide and the leading cause of cancer death in the USA [1]. The American Cancer Society (NY, USA) estimated a total of 228,150 new cases of lung cancer with 142,670 deaths from lung cancer in the USA for 2019 [1]. Smoking is the main cause of lung cancer and contributes to 80% of lung cancer deaths in women and 90% in men [2]. Lung cancer is typically diagnosed at advanced stages and carries a high mortality rate, with a 5-year survival rate of only 18% [3]. Randomized controlled trials targeted toward lung cancer screening started in the 1970s when the US National Cancer Institute (NCI; MD, USA) sponsored several clinical trials to evaluate the benefit of adding sputum cytology to annual chest radiography (CXR) [4,5]. However, none of the trials showed a reduction in lung cancer mortality (Supplementary Table 1). Decades later, the NCI initiated the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), a large randomized controlled trial that aimed to reduce disease-specific cancer mortality by evaluating the use of CXR for screening [6]. The study found that 2% of participants that had a positive radiographic findings were diagnosed with lung cancer within 12 months of the screen, 44% of whom were diagnosed with stage I disease [6]. Pertinent findings that paved the road for future guidelines included the discovery that high incidences of lung cancer were noted in active smokers or those that had quit within 15 years of randomization [6]. In the 2000s, prospective studies were created throughout the world to evaluate the role of low-dose computed tomography (LDCT) for screening. The Lung Screening Study compared LDCT and CXR as screening modalities and revealed that LDCT was twice as effective as CXR in detecting lung cancer [7]. It also showed that 48% of lung cancers detected by LDCT screening were diagnosed at stage I [7]. Inspired by the Lung Screening Study, a large scale study called the National Lung Screening Trial (NLST), which enrolled 53,456 participants, was created. Participants were randomized to LDCT or CXR at a 1:1 ratio. The study demonstrated a 20% relative reduction in mortality in patients screened with LDCT compared with CXR [8]. Results from this trial were updated in 2013 and confirmed the benefit of LDCT for lung cancer screening in specific patient populations [9]. Similar results were showcased from The Dutch–Belgian Randomized Lung Cancer Screening Trial (NELSON) which began in Europe in 2003 [10]. More than 15,000 participants were enrolled and assigned to either computer tomography (CT) screening or to the control group with no screening [10]. The study reported a 41% positive predictive value with screening and 50% of the cancers diagnosed in the screening arm were found at early stages of the disease [10]. During a 10-year follow-up, there was a 26% mortality rate reduction in men and 39% in women [10]. Updated results published in the New E
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引用次数: 1
期刊
Lung Cancer Management
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