定量影像学作为生物标记物在早期肺腺癌中的应用研究

Adenocarcinoma is the most frequent histopathologic type of lung cancer, and more early stage (clinical Ⅰa/ cT1N0M0) lung adenocarcinoma were detected with the extensive CT application. The different biological information of each type lesion determines different treatment and prognosis. Modern medical quantitative imaging can evaluate early stage lung adenocarcinoma from morphological structure to the metabolic function objectively and accurately, as an imaging biomarker, which may decide or predict the malignant biological behavior and information (local invasion, metastasis, growth kinetics and oncogene) of early stage lung adenocarcinoma prior to surgery. Our previous study work also showed that some imaging features might identify the lung adenocarcinoma invasive classification and predict the tumor metastasis accurately, so as to guide the surgical operation mode. So we furthermore study the preoperative multimoding imaging ( HRCT, spectral CT and/or PET-CT) findings, then acquire quantitative imaging information, to estimate the invasive types, growth kinetics or oncogene of clinicalⅠa stage lung adenocarcinoma, and analyze the risk and protective factors of lymph node metastasis, aims to investigate the effectiveness and accuracy of quantitative imaging to evaluate or predict the malignant biological behavior of early lung adenocarcinoma, in order to afford scientific guiding information for clinical individual precision therapy.

随着CT筛查和诊断的广泛应用，越来越多的早期肺腺癌（临床Ⅰa期/cT1N0M0）被检出。不同亚型的肺腺癌承载的生物学信息有很大异质性，决定着临床转归有显著差异。定量影像学能够精确地反映肿瘤的形态结构、代谢功能和生长速度等，作为一种客观无创的生物学指标，使术前预测早期肺腺癌的生物学行为和信息（局部浸润性、转移、生长动力学和基因表达）成为可能。我们的前期工作证明影像学可以对早期肺腺癌浸润类型和淋巴结转移进行准确判断和预测，从而指导治疗方案和手术计划。据此本研究通过CT（HRCT和/或能谱CT）和部分PET-CT的多模态影像学检查，综合较大样本量数据，获得体积、密度、能谱曲线、放射性摄取值、倍增时间等可量化影像学参数，试图客观精确地判断早期肺腺癌的局部浸润性、淋巴结转移危险、生长动力学和基因表达，建立早期肺腺癌生物学行为恶性等级及相应临床转归的预测模型，为临床精准个体化治疗提供科学依据。

随着CT筛查和诊断的广泛应用，越来越多的早期肺腺癌（Ⅰ期）被检出。肺腺癌承载的生物学信息有很大异质性，决定着临床转归有显著差异。本研究的主要内容是通过CT（HRCT和/或能谱CT）和部分PET-CT的可量化影像学参数分析，术前预测早期肺腺癌的生物学行为和信息（局部浸润性、转移、预后和基因表达）。研究结果表明（1）影像学定量分析可以预测早期肺腺癌浸润性：A、病理Ⅰ期浸润性肺腺癌GGO定量分析与病理附壁样生长成分有相关性，三维CT值定量分析可更好地对浸润性肺腺癌附壁样生长成分的比例进行量化评估；B、影像学特征可预测肺腺癌浸润性，其中病灶的实性成分比例是首选的诊断指标，诊断界值为实性成分比例 > 25.2%；C、术前影像学定量分析能在一定程度上对腺癌组织学亚型进行预判，从而为患者术前评估及个体化手术治疗方案的制定提供帮助。（2）三维CT值定量分析所得GGO成分和实性成分比例对I期肺腺癌术后疾病进展有较高预测价值，界值分别为0.13和0.40，可以作为预后判断的重要指标。（3）肺腺癌原发病灶实性成分比例为临床I期肺腺癌淋巴结转移的独立危险因素；当原发灶实性成分比例 ≤16.1%时，所有临床I期肺腺癌均无淋巴结转移，该部分患者在手术中可以避免无效系统淋巴结清扫。（4）能谱CT定量参数结合临床信息能够预测早期肺腺癌分子基因表型，为个体化内科靶向治疗提供依据。A、吸烟史和能谱CT参数NIC是肺腺癌EGFR突变的两个影响因素；NIC可能是预测肺腺癌患者EGFR突变的一个潜在的定量参数。B、对于实性肺腺癌，能谱CT可无创性预测其分子表型：70keVCT值与临床因素吸烟史可预测EGFR突变；ALK重排只与年龄相关；有效原子序数可预测KRAS突变。总之，本研究的结果证明了定量影像学分析能够判断早期肺腺癌的局部浸润性、淋巴结转移、预后和基因表达，可以作为一种客观无创的影像生物学标记物反映肺腺癌的肿瘤异质性，为肺腺癌的临床精准个体化治疗提供科学依据。