Mu Wei, Tunali Ilke, Gray Jhanelle E, Qi Jin, Schabath Matthew B, Gillies Robert J
Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Eur J Nucl Med Mol Imaging. 2020 May;47(5):1168-1182. doi: 10.1007/s00259-019-04625-9. Epub 2019 Dec 5.
Immunotherapy has improved outcomes for patients with non-small cell lung cancer (NSCLC), yet durable clinical benefit (DCB) is experienced in only a fraction of patients. Here, we test the hypothesis that radiomics features from baseline pretreatment F-FDG PET/CT scans can predict clinical outcomes of NSCLC patients treated with checkpoint blockade immunotherapy.
This study included 194 patients with histologically confirmed stage IIIB-IV NSCLC with pretreatment PET/CT images. Radiomics features were extracted from PET, CT, and PET+CT fusion images based on minimum Kullback-Leibler divergence (KLD) criteria. The radiomics features from 99 retrospective patients were used to train a multiparametric radiomics signature (mpRS) to predict DCB using an improved least absolute shrinkage and selection operator (LASSO) method, which was subsequently validated in both retrospective (N = 47) and prospective test cohorts (N = 48). Using these cohorts, the mpRS was also used to predict progression-free survival (PFS) and overall survival (OS) by training nomogram models using multivariable Cox regression analyses with additional clinical characteristics incorporated.
The mpRS could predict patients who will receive DCB, with areas under receiver operating characteristic curves (AUCs) of 0.86 (95%CI 0.79-0.94), 0.83 (95%CI 0.71-0.94), and 0.81 (95%CI 0.68-0.92) in the training, retrospective test, and prospective test cohorts, respectively. In the same three cohorts, respectively, nomogram models achieved C-indices of 0.74 (95%CI 0.68-0.80), 0.74 (95%CI 0.66-0.82), and 0.77 (95%CI 0.69-0.84) to predict PFS and C-indices of 0.83 (95%CI 0.77-0.88), 0.83 (95%CI 0.71-0.94), and 0.80 (95%CI 0.69-0.91) to predict OS.
PET/CT-based signature can be used prior to initiation of immunotherapy to identify NSCLC patients most likely to benefit from immunotherapy. As such, these data may be leveraged to improve more precise and individualized decision support in the treatment of patients with advanced NSCLC.
免疫疗法改善了非小细胞肺癌(NSCLC)患者的治疗结果,但只有一小部分患者能获得持久的临床获益(DCB)。在此,我们检验了这样一个假设,即基线预处理F-FDG PET/CT扫描的放射组学特征可预测接受检查点阻断免疫疗法的NSCLC患者的临床结果。
本研究纳入了194例经组织学确诊为IIIB-IV期NSCLC且有预处理PET/CT图像的患者。基于最小Kullback-Leibler散度(KLD)标准,从PET、CT和PET+CT融合图像中提取放射组学特征。来自99例回顾性患者的放射组学特征用于训练多参数放射组学特征(mpRS),以使用改进的最小绝对收缩和选择算子(LASSO)方法预测DCB,随后在回顾性(N = 47)和前瞻性测试队列(N = 48)中进行验证。利用这些队列,mpRS还通过纳入额外临床特征的多变量Cox回归分析训练列线图模型来预测无进展生存期(PFS)和总生存期(OS)。
mpRS能够预测将获得DCB的患者,在训练队列、回顾性测试队列和前瞻性测试队列中,受试者操作特征曲线(AUC)下面积分别为0.86(95%CI 0.79 - 0.94)、0.83(95%CI 0.71 - 0.94)和0.81(95%CI 0.68 - 0.92)。在相同的三个队列中,列线图模型预测PFS的C指数分别为0.74(95%CI 0.68 - 0.80)、0.74(95%CI 0.66 - 0.82)和0.77(95%CI 0.69 - 0.84),预测OS的C指数分别为0.83(95%CI 0.77 - 0.88)、0.83(95%CI 0.71 - 0.94)和0.80(95%CI 0.69 - 0.91)。
基于PET/CT的特征可在免疫疗法开始前用于识别最有可能从免疫疗法中获益的NSCLC患者。因此,这些数据可用于改善晚期NSCLC患者治疗中更精确和个性化的决策支持。