Pretherapy 18F-fluorodeoxyglucose positron emission tomography/computed tomography robust radiomic features predict overall survival in non-small cell lung cancer
Authors: Mostafa Rehab , Abdelsamie Kandeel Ahmed , Abd Elkareem Maha , Nardo Lorenzo , Abdelhafez Yasser G. 
Published: February 2022

Objective
To extract robust radiomic features from staging positron emission tomography/computed tomography (18F- fluroodeoxyglucose PET/CT) in patients with non-small cell lung cancer from different segmentation methods and to assess their association with 2-year overall survival.

Methods
Eighty-one patients with stage I–IV non-small cell lung cancer were included. All patients underwent a pretherapy 18F-FDG PET/CT. Primary tumors were delineated using four different segmentation methods: method 1, manual; method 2: manual with peripheral 1 mm erosion; method 3: absolute threshold at standardized uptake value (SUV) 2.5; and method 4: relative threshold at 40% SUVmax. Radiomic features from each method were extracted using Image Biomarker Standardization Initiative-compliant process. The study cohort was divided into two groups (exploratory and testing) in a ratio of 1:2 (n = 25 and n = 56, respectively). Exploratory cohort was used to identify robust radiomic features, defined as having a minimum concordance correlation coefficient ≥0.75 among all the 4-segmentation methods. The resulting texture features were evaluated for association with 2-year overall survival in the testing cohort (n = 56). All patients in the testing cohort had a follow-up for 2 years from the date of staging 18F-FDG PET/CT scan or till death. Cox proportional hazard models were used to evaluate the independent prognostic factors.

Results
Exploratory and validation cohorts were equivalent regarding their basic characteristics (age, sex, and tumor stage). Ten radiomic features were deemed robust to the described four segmentation methods: SUV SD, SUVmax, SUVQ3, SUVpeak in 0.5 ml, total lesion glycolysis, histogram entropy log 2, histogram entropy log 10, histogram energy uniformity, gray level run length matrix-gray level non-uniformity, and gray level zone length matrix-gray level non-uniformity. At the end of 2-year follow-up, 41 patients were dead and 15 were still alive (overall survival = 26.8%; median survival = 14.7 months, 95% confidence interval: 10.2–19.2 months). Three texture features, regardless the segmentation method, were associated with 2-year overall survival: total lesion glycolysis, gray level run length matrix_gray level non-uniformity, and gray level zone length matrix_run-length non-uniformity. In the final Cox-regression model: total lesion glycolysis, and gray level zone length matrix_gray level non-uniformity were independent prognostic factors. The quartiles from the two features were combined with clinical staging in a prognostic model that allowed better risk stratification of patients for overall survival.

Conclusion
Ten radiomic features were robust to segmentation methods and two of them (total lesion glycolysis and gray level zone length matrix_gray level non-uniformity) were independently associated with 2-year overall survival. Together with the clinical staging, these features could be utilized towards improved risk stratification of lung cancer patients.