Objectives: This study is aimed at examining the synergistic impact of motion and acquisition/reconstruction parameters on ¹⁸ F-FDG PET image radiomic features in non-small cell lung cancer (NSCLC) patients, and investigating the robustness of features performance in differentiating NSCLC histopathology subtypes.

Methods: An in-house developed thoracic phantom incorporating lesions with different sizes was used with different reconstruction settings, including various reconstruction algorithms, number of subsets and iterations, full-width at half-maximum of post-reconstruction smoothing filter and acquisition parameters, including injected activity and test-retest with and without motion simulation. To simulate motion, a special motor was manufactured to simulate respiratory motion based on a normal patient in two directions. The lesions were delineated semi-automatically to extract 174 radiomic features. All radiomic features were categorized according to the coefficient of variation (COV) to select robust features. A cohort consisting of 40 NSCLC patients with adenocarcinoma (n = 20) and squamous cell carcinoma (n = 20) was retrospectively analyzed. Statistical analysis was performed to discriminate robust features in differentiating histopathology subtypes of NSCLC lesions.

Results: Overall, 29% of radiomic features showed a COV ≤5% against motion. Forty-five percent and 76% of the features showed a COV ≤ 5% against the test-retest with and without motion in large lesions, respectively. Thirty-three percent and 45% of the features showed a COV ≤ 5% against different reconstruction parameters with and without motion, respectively. For NSCLC histopathological subtype differentiation, statistical analysis showed that 31 features were significant (p-value < 0.05). Two out of the 31 significant features, namely, the joint entropy of GLCM (AUC = 0.71, COV = 0.019) and median absolute deviation of intensity histogram (AUC = 0.7, COV = 0.046), were robust against the motion (same reconstruction setting).

Conclusions: Motion, acquisition, and reconstruction parameters significantly impact radiomic features, just as their synergies. Radiomic features with high predictive performance (statistically significant) in differentiating histopathological subtype of NSCLC may be eliminated due to non-reproducibility.