Objectives: In non-small cell lung cancer (NSCLC), non-invasive alternatives to biopsy-dependent driver mutation analysis are needed. We reviewed the effectiveness of radiomics alone or with clinical data and assessed the performance of artificial intelligence (AI) models in predicting oncogene mutation status.

Materials and methods: A PRISMA-compliant literature review for studies predicting oncogene mutation status in NSCLC patients using radiomics was conducted by a multidisciplinary team. Meta-analyses evaluating the performance of AI-based models developed with CT-derived radiomics features alone or combined with clinical data were performed. A meta-regression to analyze the influence of different predictors was also conducted.

Results: Of 890 studies identified, 124 evaluating models for the prediction of epidermal growth factor-1 (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma virus (KRAS) mutations were included in the systematic review, of which 51 were meta-analyzed. The AI algorithms' sensitivity/false positive rate (FPR) in predicting mutation status using radiomics-based models was 0.754 (95% CI 0.727-0.780)/0.344 (95% CI 0.308-0.381) for EGFR, 0.754 (95% CI 0.638-0.841)/0.225 (95% CI 0.163-0.302) for ALK and 0.475 (95% CI 0.153-0.820)/0.181 (95% CI 0.054-0.461) for KRAS. A meta-analysis of combined models was possible for EGFR mutation, revealing a sensitivity of 0.806 (95% CI 0.777-0.833) and a FPR of 0.315 (95% CI 0.270-0.364). No statistically significant results were obtained in the meta-regression.

Conclusions: Radiomics-based models may offer a non-invasive alternative for determining oncogene mutation status in NSCLC. Further research is required to analyze whether clinical data might boost their performance.

Key points: Question Can imaging-based radiomics and artificial intelligence non-invasively predict oncogene mutation status to improve diagnosis in non-small cell lung cancer (NSCLC)? Findings Radiomics-based models achieved high performance in predicting mutation status in NSCLC; adding clinical data showed limited improvement in predictive performance. Clinical relevance Radiomics and AI tools offer a non-invasive strategy to support molecular profiling in NSCLC. Validation studies addressing clinical and methodological aspects are essential to ensure their reliability and integration into routine clinical practice.