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Abstract：
Liquid biopsy has recently emerged as an important tool in clinical practice particularly for lung cancer patients. We retrospectively evaluated cell-free DNA analyses performed at our Institution by next generation sequencing methodology detecting the major classes of genetic alterations. Starting from the graphical representation of chromosomal alterations provided by the analysis software, we developed a support vector machine classifier to automatically classify chromosomal profiles as stable (SCP) or unstable (UCP). High concordance was found between our binary classification and tumor fraction evaluation performed using shallow whole genome sequencing. Among clinical features, UCP patients were more likely to have ≥ 3 metastatic sites and liver metastases. Longitudinal assessment of chromosomal profiles in 33 patients with lung cancer receiving immune checkpoint inhibitors (ICIs) showed that only patients that experienced early death or hyperprogressive disease retained or acquired an UCP within 3 weeks from the beginning of ICIs. UCP was not observed following ICIs among patients that experienced progressive disease or clinical benefit. In conclusion, our binary classification, applied to whole copy number alteration profiles, could be useful for clinical risk stratification during systemic treatment for non-small cell lung cancer patients.
摘要：
液体活检最近已成为临床实践中的重要工具，特别是对于肺癌患者。我们回顾性评估了我们机构通过下一代测序方法进行的无细胞DNA分析，检测了主要的遗传改变类别。从分析软件提供的染色体改变的图形表示开始，我们开发了一个支持向量机分类器，将染色体谱自动分类为稳定（SCP）或不稳定（UCP）。在我们的二元分类和使用浅全基因组测序进行的肿瘤分数评估之间发现高度一致性。在临床特征中，UCP患者更可能有≥3个转移部位和肝转移。对接受免疫检查点抑制剂（ICIs）的33例肺癌患者的染色体谱的纵向评估表明，只有经历过早期死亡或过度进行性疾病的患者在ICIs开始后3周内保留或获得UCP。在经历进行性疾病或临床益处的患者中，ICI后未观察到UCP。总之,我们的二元分类，应用于整个拷贝数更改配置文件，可用于非小细胞肺癌患者全身治疗期间的临床风险分层。
