In this study we investigate the novel approach of using radiomic phenotypes from the lung parenchyma and tumor region of PET/CT images in non-small cell lung cancer (NSCLC) patients to predict overall survival (OS) and progression free survival (PFS) after tumor resection. We used 144 publicly available fluorodeoxyglucose ([18]F-FDG) PET/CT images from The Cancer Imaging Archive (TCIA) NSCLC Radiogenomics dataset. We extract features using the cancer phenomics imaging toolkit (CaPTk) to extract radiomic features from each of four image source regions: PET imaging of the tumor, PET imaging of the non-tumor lung parenchyma, CT imaging of the tumor, and CT of the parenchyma. Using each of the four sets of features, we independently clustered patients into phenotypes using unsupervised hierarchical clustering. The four phenotyping schemes individually, together, and in combination with clinical variables were assessed for association with time to OS and PFS via Cox proportional-hazards modeling, assessing covariate association via the log-rank p-value and model predictive performance via the C statistic. The clinical variables divided high from low hazard groups with p ≤ 0.05 for OS (p = 0.002, C = 0.62) but not for PFS (p = 0.098, C = 0.58). For PFS, radiomic phenotype derived from PET lung parenchyma performed better than the clinical variables both alone (p = 0.014, C = 0.59) and in conjunction with the clinical variables (p = 0.014, C = 0.62). Radiomic phenotypes from the lung parenchyma of PET/CT images can improve outcomes prediction for PFS after tumor resection in patients with NSCLC. Radiomic phenotypes from the non-cancerous parenchyma may derive prognostic value by detecting differences in the tissue linked to the biology of recurrence.
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