背景:NSCLC的分子谱分析对于优化治疗决策至关重要,但往往是不完整的。在荷兰的一项前瞻性观察研究中,我们评估了当前标准护理(SoC)中蛋白质化分子谱分析的功效,并测量了提供标准化诊断程序的效果。我们还探索了基于血浆的分子谱分析在主要诊断环境中的潜力。
方法:这项多中心前瞻性研究旨在探索使用局部SoC组织谱分析程序在磨合阶段的当前临床实践表现。设计后续阶段以研究通过使肿瘤轮廓化可以使综合分子轮廓(CMP)最大化的程度。成功的分子谱分析被定义为至少完成EGFR和ALK测试。此外,探索PD-L1肿瘤比例评分。最后,我们评估了使用液滴数字PCR集中血浆检测EGFR和KRAS突变的额外价值.
结果:总计878名患者,22.0%为鳞状细胞癌,78.0%为非鳞NSCLC。Ⅰ-Ⅲ期54.0%,第四阶段为46.0%。在纳入磨合期的136例患者中,有69.9%进行了EGFR和ALK的分析。显著高于真实世界数据估计的55%(p<0.001)。脱色的分子谱分析将比率提高到77.0%(p=0.049)。在非鳞状NSCLC中,EGFR和ALK谱分析率从77.9%增加到82.1%,在鳞状NSCLC中从43.8%增加到57.5%。基于血浆的测试在98.4%的患者中是可行的,并且在7.1%的患者中确定了癌基因驱动突变,这些患者的组织谱分析是不可行的。
结论:这项研究表明,基于组织的分子谱分析的成功率很高,通过采用protocolised方法得到了显着改善。对于相当比例的患者,基于组织的分析仍然不可行。肿瘤组织和循环肿瘤DNA的联合分析是一种有前途的方法,可以对更多患者进行适当的分子谱分析。
BACKGROUND: Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting.
METHODS: This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated.
RESULTS: Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible.
CONCLUSIONS: This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.