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【35under35】吴创炎医生:磨玻璃影/贴壁成分对肺腺癌预后的影响

2022年07月31日
作者:吴创炎
医院:华中科技大学同济医学院附属协和医院 

   

               
吴创炎
医学博士、主治医师

华中科技大学同济医学院附属协和医院 胸外科 医学博士 主治医师
湖北省临床肿瘤学会(ESCO)肺癌专家委员会第一届青年委员会委员 湖北省微循环学会胸部微创外科青年委员会委员
Journal of Clinical and Translational Hepatology青年编委
临床工作:熟练掌握肺癌的规范化诊治原则,在肺癌的外科及综合治疗有所体会
科研工作:主要从事肺癌的综合诊疗、新靶点预测及小分子药物研究 主持国自然青年基金一项,省自然基金一项
第一作者发表SCI文章10篇,累积影响因子40

《2015年WHO肺、胸膜、胸腺及心脏肿瘤分类》提示微乳头状成分、实体型成分为高级别成分,腺体型的筛状模式与实体型腺癌类似,与更差的预后相关[1-4]。而后2021年的分类更新,将包括实体状、微乳头、筛状或复杂腺体成分定义为高级别成分,并引入浸润性非黏液性肺腺癌(手术切除标本)的IASLC( InternationalAssociation for the Study of Lung Cancer)分级系统,明确地将含有超过20%高级别成分的腺癌定义为低分化腺癌,而以贴壁成分为主的腺癌,若高级别成分少于20%则被定义为预后相对良好的高分化腺癌[5]

第八版TNM分期对肺腺癌T分期的评估进行了调整,将非黏液腺癌的大小定义为浸润性成分的大小,贴壁成分不再计算在内。根据 2011 年国际肺癌研究协会、美国胸科学会、欧洲呼吸学会和 2015 年 WHO 肺腺癌分类,贴壁成分的生长模式被认为是一种非浸润性的生长模式[6]。该概念的临床意义得到多项研究的支持,这些研究认为相较于肿瘤总的大小,浸润性成分的大小能准确地预测患者的临床预后[7-9]。在CT检查中,组织学上的贴壁成分往往呈现为磨玻璃样变 (GGO),而浸润性成分则通常表现为的实性成分[10]。因此,从影像学的角度来看,部分实性结节(PSN)中只有实性成分的大小会影响临床 T分期。

近年,有研究者提出肺腺癌影像学中的GGO成分或病理学中的贴壁成分可能是良好预后的独立预测因素。在最近的一些研究中,根据浸润性成分大小分层,PSN与实性肺腺癌相比具有更好的预后[11-14]。因此也有学者提议将 GGO (G) 或 贴壁成分(lepidic,L)用作T分期的附加前缀[13-15]。可以预见的是该提议在下一版 TNM 分期中将是争论的焦点。

就这一主题Okubo团队展开了研究评估GGO/贴壁成分对肺腺癌的预后影响[16]。该研究纳入了 380 例手术切除的早期肺腺癌患者(临床 IA 期),并将肿瘤分为贴壁成分阳性(存在任何贴壁模式)和贴壁成分阴性。研究将纯贴壁状病变(即原位腺癌,AIS)、微浸润腺癌(MIA)及手术切缘阳性的病例排除在外。病变的影像学特征包括肿瘤的大小、实性成分的大小以及 GGO 比率。结果显示虽然贴壁型成分阳性组的无复发生存期 (RFS) 有所提高(5年 RFS 95.4% v.s. 87.0%, p=0.005),但在亚组分型里(pT1a、pT1b和pT1c)中RFS没有统计学意义。经多因素模型分析,贴壁成分的存在并不足以成为独立预测因素(HR,hazard ratio =0.46,95%的CI:0.19-1.14,p=0.09)。随后在多因素分析时把贴壁成分比率提高到大于0.1时,也未能得到阳性结果(p=0.05),而当 GGO比率提高到大于0.1时,在多因素分析中显示出更好的预后(HR=0.30,95%CI:0.12-0.81,p=0.02)。

该研究的亮点只要体现在两个方面:一、由于AIS和 MIA在完全切除时可表现出100%的RFS,该研究排除了两种亚类,避免了结果的偏倚。二、考虑到实性成分、浸润性成分的大小及行为模式之间存在很强的单因素关联,因此研究者进行了多因素分析。

而该研究局限性也是不可回避的,首先是每个亚组纳入的患者数量相对较少,降低了预测效率。这也解释了研究中一些明确的预后预测因子,例如影像学中的实体成分的大小和病理学中的浸润成分的大小,在多因素模型中未能产生统计学意义(分别为p=0.13和p=0.16)。此外,本研究中纳入了浸润性黏液腺癌(n=24)而浸润性黏液腺癌的行为模式、对预后的影响以及影像学特征与非黏液腺癌不同,可能会影响整体结果。

该研究为含GGO/贴壁成分的肺腺癌的临床结局研究提供了思路。与过去一些研究类似,该研究发现贴壁成分对预后的影响没有统计学意义[17-19],但最近也有研究表明CT提示GGO成分是早期肺腺癌良好预后的独立预测因素[12-14, 19-20]

随着高分辨CT的普及,越来越多的肺癌得到早期发现。尽管许多文献表明GGO/贴壁成分可能对预后有独立预测作用,但研究设计可能影响最终结果。Okubo团队的研究提醒我们,在T分期中加入GGO/贴壁成分信息前,需进行大规模、多中心的临床研究以进一步证实GGO/贴壁成分对肺腺癌的预后影响[16]

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