Gregg Jeffrey P, Li Tianhong, Yoneda Ken Y
Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, CA, USA.
Division of Hematology & Oncology, Department of Internal Medicine, School of Medicine, University of California, Davis Comprehensive Cancer Center, CA, USA.
Transl Lung Cancer Res. 2019 Jun;8(3):286-301. doi: 10.21037/tlcr.2019.04.14.
Molecular testing identifies patients with advanced non-small cell lung cancer (NSCLC) who may benefit from targeted therapy or immunotherapy (i.e., immune checkpoint inhibitor treatment for patients with high tumor mutational burden (TMB), microsatellite instability-high or mismatch repair-deficient tumors). Current guidelines state that molecular testing should be conducted at the time of initial diagnosis and tumor progression on targeted therapy. In real-world clinical practice in the United States (US), molecular testing is often not conducted or happens late in the diagnostic journey, resulting in delayed or inappropriate treatment. Herein, we review the rationale for molecular testing in advanced NSCLC, along with best-practice guidelines based on published recommendations and our own clinical experience, including a case study. We propose three strategies to optimize molecular testing in newly diagnosed patients with advanced NSCLC: (I) pulmonologists, interventional radiologists, or thoracic surgeons order molecular tests as soon as advanced NSCLC with an adenocarcinoma component is suspected; (II) liquid biopsies conducted early in the diagnostic pathway; and (III) pathologist-directed reflex testing, as conducted in other areas of oncology. To help facilitate these strategies, we outline our recommendations for optimal sample collection techniques and stewardship. In summary, we believe that implementation of these individual strategies will allow clinicians to effectively leverage available treatment options for advanced NSCLC, reducing the time to optimal treatment and improving patient outcomes.
分子检测可识别出可能从靶向治疗或免疫治疗中获益的晚期非小细胞肺癌（NSCLC）患者（即对肿瘤突变负荷（TMB）高、微卫星高度不稳定或错配修复缺陷肿瘤患者进行免疫检查点抑制剂治疗）。当前指南指出，分子检测应在初始诊断时以及靶向治疗出现肿瘤进展时进行。在美国的实际临床实践中，分子检测往往未进行或在诊断过程后期才进行，导致治疗延迟或不恰当。在此，我们回顾了晚期NSCLC分子检测的基本原理，以及基于已发表建议和我们自身临床经验的最佳实践指南，包括一个案例研究。我们提出了三种优化新诊断晚期NSCLC患者分子检测的策略：（I）一旦怀疑患有具有腺癌成分的晚期NSCLC，肺科医生、介入放射科医生或胸外科医生应立即开具分子检测医嘱；（II）在诊断途径早期进行液体活检；（III）如肿瘤学其他领域所开展的那样，进行病理学家指导的反射性检测。为帮助实施这些策略，我们概述了关于最佳样本采集技术和管理的建议。总之，我们认为实施这些个体化策略将使临床医生能够有效利用晚期NSCLC的现有治疗选择，减少达到最佳治疗的时间并改善患者预后。
