Predicting recurrence risks in lung cancer patients using multimodal radiomics and random survival forests

Abstract

Purpose: We developed a model integrating multimodal quantitative imaging features from tumor and nontumor regions, qualitative features, and clinical data to improve the risk stratification of patients with resectable non-small cell lung cancer (NSCLC).

Approach: We retrospectively analyzed 135 patients [mean age, 69 years (43 to 87, range); 100 male patients and 35 female patients] with NSCLC who underwent upfront surgical resection between 2008 and 2012. The tumor and peritumoral regions on both preoperative CT and FDG PET-CT and the vertebral bodies L3 to L5 on FDG PET were segmented to assess the tumor and bone marrow uptake, respectively. Radiomic features were extracted and combined with clinical and CT qualitative features. A random survival forest model was developed using the top-performing features to predict the time to recurrence/progression in the training cohort ( $n=101$ ), validated in the testing cohort ( $n=34$ ) using the concordance, and compared with a stage-only model. Patients were stratified into high- and low-risks of recurrence/progression using Kaplan-Meier analysis.

Results: The model, consisting of stage, three wavelet texture features, and three wavelet first-order features, achieved a concordance of 0.78 and 0.76 in the training and testing cohorts, respectively, significantly outperforming the baseline stage-only model results of 0.67 ( $p<0.005$ ) and 0.60 ( $p=0.008$ ), respectively. Patients at high- and low-risks of recurrence/progression were significantly stratified in both the training ( $p<0.005$ ) and the testing ( $p=0.03$ ) cohorts.

Conclusions: Our radiomic model, consisting of stage and tumor, peritumoral, and bone marrow features from CT and FDG PET-CT significantly stratified patients into low- and high-risk of recurrence/progression.

Keywords: computed tomography; lung cancer; machine learning; positron emission tomography; radiomics.

Fig. 1

(a) One 1.25 mm slice of a preoperative diagnostic CT image of a patient with NSCLC. (b) The tumor segmentation is shown in pink, and the peritumoral segmentation is shown in cyan.

Fig. 2

(a) Transaxial and (b) sagittal preoperative diagnostic PET (left) and PET/CT fusion (right) images of a patient with NSCLC. (a) The metabolic tumor volume (MTV) is shown in pink, and the peritumoral segmentation is shown in blue. (b) The vertebral bodies L3 to L5 are shown segmented in pink to sample bone marrow uptake. These regions of interest are used to extract the local, regional, and distant PET imaging features.

Fig. 3

Coefficients for the selected features using LASSO in the training cohort showing the directionality of the association of each feature in descending order of feature contribution. MTV, metabolic tumor volume.

Fig. 4

Kaplan–Meier curves for the multivariate model risk scores in the (a) training cohort ($n=101$, $p<0.005$) and (b) testing cohort ($n=34$, $p=0.034$). Patients were stratified using the median risk score in the training cohort. The shaded regions show the 95% confidence intervals (CI), and + indicates censored data.