Radiological, Radiomics, and Metastatic Patterns Associated with Targetable Oncogenic Drivers on CT-Scan of Newly Diagnosed NSCLC Patients: A Comprehensive Radiogenomics Review

The management of non-small cell lung cancer (NSCLC), including lung adenocarcinomas (LUAD), has been revolutionized with the advent of precision oncology. While advanced cancers often carry poor prognosis, those harboring specific molecular alterations sensitive to targeted therapy (notably tyrosine kinase inhibitor [TKI]) have experienced improved response to treatment and survival outcomes. Consequently, detecting these alterations through molecular screening panel has become standard in several countries, although this necessitates high-quality tissue sampling to inform optimal therapeutic decisions. Oncologic imaging occupies a pivotal role in the routine care of patients, in particular at diagnosis, with a wealth of information gathered but underutilized, as medical imaging reflects the disease in its entirety at a given time point. Moreover, recent advancements in imaging quantitative analysis, including radiomics and artificial intelligence, could aid in better integration and understanding of this information that has been overlooked for years. Several radiological phenotypes (or radiophenotypes) have been linked to tumor genomic alterations, both in standard radiology relying on semantic features and metastatic patterns, and in radiomics. Ultimately, understanding the relationships between imaging and targetable genomic alterations via accurate imaging biomarkers could complement ambiguous tumor or liquid biopsy, detect emerging new alterations, and even substitute biopsy through 'virtual biopsy'. During the past decade, there has been a surge in research focused on radiogenomic assessment of NSCLC and especially LUAD. However, due to the low prevalence of many oncogenic drivers, the scientific literature may lack clarity or present conflicting findings. This comprehensive review aims to provide a summary of the current state of this research, offering insights into the complex interplay between imaging and genomic alterations in lung adenocarcinoma.