Abstract
Radiomics has traditionally focused on individual tumors, often neglecting the integration of metastatic disease, particularly in patients with non-small cell lung cancer. This study sought to examine intra-patient inter-tumor lesion heterogeneity indices using radiomics, exploring their relevance in metastatic lung adenocarcinoma. Consecutive adults newly diagnosed with metastatic lung adenocarcinoma underwent contrast-enhanced CT scans for lesion segmentation and radiomic feature extraction. Three methods were devised to measure distances between tumor lesion profiles within the same patient in radiomic space: centroid to lesion, lesion to lesion, and primitive to lesion, with subsequent calculation of mean, range, and standard deviation of these distances. Associations between HIs, disease control rate, objective response rate to first-line treatment, and overall survival were explored. The study included 167 patients (median age 62.3 years) between 2016 and 2019, divided randomly into experimental (N = 117,546 lesions) and validation (N = 50,232 tumor lesions) cohorts. Patients without disease control/objective response and with poorer survival consistently systematically exhibited values of all heterogeneity indices. Multivariable analyses revealed that the range of primitive-to-lesion distances was associated with disease control in both cohorts and with objective response in the validation cohort. This metrics showed univariable associations with overall survival in the experimental. In conclusion, we proposed original methods to estimate the intra-patient inter-tumor lesion heterogeneity using radiomics that demonstrated correlations with patient outcomes, shedding light on the clinical implications of inter-metastases heterogeneity. This underscores the potential of radiomics in understanding and potentially predicting treatment response and prognosis in metastatic lung adenocarcinoma patients.