Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.
Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.
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DOI：
10.1016/j.ctarc.2021.100486
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发表时间：
2021
影响因子：
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通讯作者：
Rieger-Christ KM
中科院分区：
文献类型：
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作者：
Burks EJ;Zhang J;Sullivan TB;Shi X;Sands JM;Regis SM;McKee BJ;McKee AB;Zhang S;Liu H;Liu G;Spira A;Beane J;Lenburg ME;Rieger-Christ KM
尽管三项随机对照试验已经证明了CT肺癌筛查（CTLS）的死亡率益处，但<5%的合格美国吸烟者接受了筛查。一些人将其归因于对共同决策访视中传达的伤害的恐惧，包括对惰性BAC样腺癌过度诊断/过度治疗的伤害。由于CTLS和常规检测队列之间的惰性癌症的频率尚未比较，我们比较了86例NCCN高风险CTLS受试者与83例高风险（HR-R）和51例低风险（LR-R）常规检测患者的病理学和RNA表达。惰性腺癌的定义与先前描述的低恶性潜能（LMP）腺癌沿着AIS/MIA相同。对高风险（CTLS和HR-R）FFPE肿瘤样品的子集进行外显子组RNA测序。惰性腺癌（AIS、MIA和LMP）显示100%的疾病特异性生存期（DSS），CTLS（18%）和HR-R（20%）的频率相似，但相对低于LR-R（33%）。尽管有这种观察结果，CTLS表现出介于HR-R和LR-R之间的中间DSS（5年DSS：88%CTLS，82% HR-R，和95% LR-R，p=0.047），可能反映了与HR-R相比小0.4cm的中值肿瘤大小和较低的肿瘤坏死频率。来自TCGA肺腺癌的WGCNA基因模块与侵袭性组织学类型、有丝分裂活性和肿瘤侵袭特征相关，但CTLS和HR-R之间未观察到显著差异表达。与常规临床实践中发现癌症的风险匹配患者相比，CTLS受试者的惰性腺癌（AIS，MIA和LMP）过度诊断风险并不更高。改善的结果可能反映了更小尺寸的检测和治疗。
Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. Since the frequency of indolent cancers has not been compared between CTLS and routinely detected cohorts, we compare pathology and RNA expression of 86 NCCN high-risk CTLS subjects to 83 high-risk (HR-R) and 51 low-risk (LR-R) routinely detected patients. Indolent adenocarcinoma was defined as previously described for low malignant potential (LMP) adenocarcinoma along with AIS/MIA. Exome RNA sequencing was performed on a subset of high-risk (CTLS and HR-R) FFPE tumor samples. Indolent adenocarcinoma (AIS, MIA, and LMP) showed 100% disease-specific survival (DSS) with similar frequency in CTLS (18%) and HR-R (20%) which were comparatively lower than LR-R (33%). Despite this observation, CTLS exhibited intermediate DSS between HR-R and LR-R (5-year DSS: 88% CTLS, 82% HR-R, & 95% LR-R, p=0.047), possibly reflecting a 0.4 cm smaller median tumor size and lower frequency of tumor necrosis compared to HR-R. WGCNA gene modules derived from TCGA lung adenocarcinoma correlated with aggressive histologic patterns, mitotic activity, and tumor invasive features, but no significant differential expression between CTLS and HR-R was observed. CTLS subjects are at no greater risk of overdiagnosis from indolent adenocarcinoma (AIS, MIA, and LMP) than risk-matched patients whose cancers are discovered in routine clinical practice. Improved outcomes likely reflect detection and treatment at smaller size.