Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Endocrinology, Chui Yang Liu Hospital affiliated to Tsinghua University, Beijing, China.
Thorac Cancer. 2021 Sep;12(17):2388-2399. doi: 10.1111/1759-7714.14083. Epub 2021 Jul 20.
Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS).
We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan-Meier analysis was conducted to identify risk factors for tumor progression.
Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan-Meier analysis (p = 0.002). Additionally, response duration to crizotinib <1 year and liver metastasis were adversely associated with PFS. The combined model, composed of clinicopathological signature and CT radiomic signature, showed good prediction ability with the area under the receiver operating characteristic curve being 0.85, and 0.89 in the training and validation dataset respectively.
Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features.
在这里，我们旨在评估 NSCLC 中 ALK 变体和改变与恩沙替尼反应持续时间的关联，并探索计算机断层扫描 (CT) 放射组学特征在预测无进展生存期 (PFS) 方面的潜在价值。
我们在一项多中心 2 期试验中招募了 88 名经鉴定的 ALK 变体 NSCLC 患者，并评估了 ALK 变体和次要 ALK 改变对接受恩沙替尼治疗的患者临床结局（反应持续时间）的影响。我们还建立了一个多因素的临床病理和定量 CT 放射组学特征模型，以预测 PFS 和风险分层。Kaplan-Meier 分析用于确定肿瘤进展的危险因素。
单因素分析表明，在三种分类（V1、V3 和其他变体）中，ALK 变体的 PFS 存在统计学差异（p=0.035）。次要 ALK 改变与 PFS 无论是在单因素（p=0.008）还是多因素（p=0.04）分析中均呈负相关，并且在 Kaplan-Meier 分析中可以识别出早期进展风险较高的患者（p=0.002）。此外，克唑替尼的反应持续时间<1 年和肝转移与 PFS 呈负相关。由临床病理特征和 CT 放射组学特征组成的联合模型在训练数据集和验证数据集中的 AUC 分别为 0.85 和 0.89，具有良好的预测能力。
我们的研究表明，次要 ALK 改变与恩沙替尼疗效呈负相关，而 ALK 变体可能与 PFS 无关。定量放射组学特征为临床病理特征提供了附加的预后预测价值。
