Non-invasive decision support for clinical treatment of non-small cell lung cancer using a multiscale radiomics approach

Background: Selecting therapeutic strategies for cancer patients is typically based on key target-molecule biomarkers that play an important role in cancer onset, progression, and prognosis. Thus, there is a pressing need for novel biomarkers that can be utilized longitudinally to guide treatment selection. Methods: Using data from 508 non-small cell lung cancer (NSCLC) patients across three institutions, we developed and validated a comprehensive predictive biomarker that distinguishes six genotypes and infiltrative immune phenotypes. These features were analyzed to establish the association between radiological phenotypes and tumor genotypes/immune phenotypes and to create a radiological interpretation of molecular features. In addition, we assessed the sensitivity of the models by evaluating their performance at five different voxel intervals, resulting in improved generalizability of the proposed approach. Findings: The radiomics model we developed, which integrates clinical factors and multi-regional features, outperformed the conventional model that only uses clinical and intratumoral features. Our combined model showed significant performance for EGFR, KRAS, ALK, TP53, PIK3CA, and ROS1 mutation status with AUCs of 0.866, 0.874, 0.902, 0.850, 0.860, and 0.900, respectively. Additionally, the predictive performance for PD-1/ PD-L1 was 0.852. Although the performance of all models decreased to different degrees at five different voxel space resolutions, the performance advantage of the combined model did not change. Conclusions: We validated multiscale radiomic signatures across tumor genotypes and immunophenotypes in a multi-institutional cohort. This imaging-based biomarker offers a non-invasive approach to select patients with NSCLC who are sensitive to targeted therapies or immunotherapy, which is promising for developing personalized treatment strategies during therapy.