Providence Health, Portland, OR.
Earle A. Chiles Research Institute, Portland, OR.
JCO Oncol Pract. 2024 Nov;20(11):1523-1532. doi: 10.1200/OP.24.00226. Epub 2024 Nov 12.
Precision therapies and immunotherapies have revolutionized cancer care, with novel genomic biomarker-associated therapies being introduced into clinical practice rapidly, resulting in notable gains in patient survival. Despite this, there is significant variability in the utilization of tumor molecular profiling that spans the timing of test ordering, comprehensiveness of gene panels, and clinical decision support through therapy and trial recommendations.
To standardize testing, we designed a pathologist-directed test ordering system at the time of diagnosis using a 523-gene DNA/RNA hybrid comprehensive genomic profiling (CGP) panel and extensive clinical decision support tools. To comprehensively characterize the clinical impact of this protocol, we developed a novel natural language processing (NLP)-based approach to extract clinical features from physician chart notes. We assessed test actionability rates, therapy choice, and outcomes across a set of 3,216 patients with advanced cancer.
We observed 49% of patients had at least one actionable genomic biomarker-driven-approved and/or guideline-recommended targeted or immunotherapy (IO) and 53% of patients would have been eligible for a precision therapy clinical trial from three large basket trials. When assessing CGP versus an in silico 50-gene panel, 67% of tumors compared with 33% harbored actionable alterations including clinical trials. Among patients with 6 months or more of follow-up, over 52% received a targeted therapy (TT) or IO, versus 32% who received conventional chemotherapy alone. Furthermore, patients receiving TT had significantly improved overall survival compared with patients receiving chemotherapy alone ( < .001).
Overall, these data represent a major shift in standard clinical practice toward molecularly guided treatments (targeted and immunotherapies) over conventional systemic chemotherapy. As guidelines continue to evolve and more precision therapeutics gain approval, we expect this gap to continue to widen.
精准治疗和免疫疗法彻底改变了癌症治疗模式，新型基因组生物标志物相关疗法迅速被引入临床实践，显著提高了患者的生存率。尽管如此，肿瘤分子谱检测的应用仍存在显著差异，包括检测时机、基因检测panel 的全面性以及通过治疗和临床试验建议提供的临床决策支持。
为了标准化检测，我们在诊断时设计了一个由病理学家指导的检测系统，使用了一个包含 523 个基因的 DNA/RNA 混合综合基因组分析（CGP）panel 和广泛的临床决策支持工具。为了全面描述该方案的临床影响，我们开发了一种新的基于自然语言处理（NLP）的方法，从医生的图表记录中提取临床特征。我们评估了一组 3216 名晚期癌症患者的检测可操作性、治疗选择和结果。
我们观察到 49%的患者至少有一种基于基因组生物标志物驱动的获批靶向治疗和/或免疫治疗（IO），53%的患者将有资格参加三项大型篮子试验中的一项精准治疗临床试验。与基于 50 个基因的计算 panel 相比，67%的肿瘤存在可操作的改变，包括临床试验，而只有 33%的肿瘤存在可操作的改变。在随访时间至少 6 个月的患者中，超过 52%的患者接受了靶向治疗（TT）或 IO，而单独接受传统化疗的患者为 32%。此外，接受 TT 治疗的患者总生存期明显长于单独接受化疗的患者（<0.001）。
总体而言，这些数据代表了向基于分子指导的治疗（靶向和免疫治疗）转变的重大转变，而不是传统的全身化疗。随着指南的不断发展和更多的精准治疗方法获得批准，我们预计这一差距将继续扩大。
