Purpose: To evaluate ability of radiomic (computer-extracted imaging) features to distinguish non-small cell lung cancer adenocarcinomas from granulomas at noncontrast CT. Materials and Methods: For this retrospective study, screening or standard diagnostic noncontrast CT images were collected for 290 patients (mean age, 68 years; range, 18–92 years; 125 men [mean age, 67 years; range, 18–90 years] and 165 women [mean age, 68 years; range, 33–92 years]) from two institutions between 2007 and 2013. Histopathologic analysis was available for one nodule per patient. Corresponding nodule of interest was identified on CT axial images by a radiologist with manually annotation. Nodule shape, wavelet (Gabor), and texture-based (Haralick and Laws energy) features were extracted from intra- and perinodular regions. Features were pruned to train machine learning classifiers with 145 patients. In a test set of 145 patients, classifier results were compared against a convolutional neural network (CNN) and diagnostic readings of two radiologists. Results: Support vector machine classifier with intranodular radiomic features achieved an area under the receiver operating characteristic curve (AUC) of 0.75 on the test set. Combining radiomics of intranodular with perinodular regions improved the AUC to 0.80. On the same test set, CNN resulted in an AUC of 0.76. Radiologist readers achieved AUCs of 0.61 and 0.60, respectively. Conclusion: Radiomic features from intranodular and perinodular regions of nodules can distinguish non-small cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT. Summary Perinodular and intranodular radiomic features corresponding to texture and shape (radiomics) were evaluated to distinguish nonsmall cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT.

No predictive biomarkers can robustly identify patients with non-small cell lung cancer (NSCLC) who will benefit from immune checkpoint inhibitor (ICI) therapies. Here, in a machine learning setting, we compared changes ("delta") in the radiomic texture (DelRADx) of CT patterns both within and outside tumor nodules before and after two to three cycles of ICI therapy. We found that DelRADx patterns could predict response to ICI therapy and overall survival (OS) for patients with NSCLC. We retrospectively analyzed data acquired from 139 patients with NSCLC at two institutions, who were divided into a discovery set (D 1 ¼ 50) and two independent validation sets (D 2 ¼ 62, D 3 ¼ 27). Intranodular and perinodular texture descriptors were extracted, and the relative differences were computed. A linear discriminant analysis (LDA) classifier was trained with 8 Del-RADx features to predict RECIST-derived response. Association of delta-radiomic risk score (DRS) with OS was determined. The association of DelRADx features with tumor-infiltrating lymphocyte (TIL) density on the diagnostic biopsies (n ¼ 36) was also evaluated. The LDA classifier yielded an AUC of 0.88 AE 0.08 in distinguishing responders from nonresponders in D 1 , and 0.85 and 0.81 in D 2 and D 3. DRS was associated with OS [HR: 1.64; 95% confidence interval (CI), 1.22-2.21; P ¼ 0.0011; C-index ¼ 0.72). Peritumoral Gabor features were associated with the density of TILs on diagnostic biopsy samples. Our results show that DelRADx could be used to identify early functional responses in patients with NSCLC.

To identify the role of radiomics texture features both within and outside the nodule in predicting (a) time to progression (TTP) and overall survival (OS) as well as (b) response to chemotherapy in patients with non-small cell lung cancer (NSCLC). Materials and Methods:Data in a total of 125 patients who had been treated with pemetrexed-based platinum doublet chemotherapy at Cleveland Clinic were retrospectively analyzed. The patients were divided randomly into two sets with the constraint that there were an equal number of responders and nonresponders in the training set. The training set comprised 53 patients with NSCLC, and the validation set comprised 72 patients. A machine learning classifier trained with radiomic texture features extracted from intraand peritumoral regions of non-contrast-enhanced CT images was used to predict response to chemotherapy. The radiomic risk-score signature was generated by using least absolute shrinkage and selection operator with the Cox regression model; association of the radiomic signature with TTP and OS was also evaluated. Results:A combination of radiomic features in conjunction with a quadratic discriminant analysis classifier yielded a mean maximum area under the receiver operating characteristic curve (AUC) of 0.82 ± 0.09 (standard deviation) in the training set and a corresponding AUC of 0.77 in the independent testing set. The radiomics signature was also significantly associated with TTP (hazard ratio [HR], 2.8; 95% confidence interval [CI]: 1.95, 4.00; P < .0001) and OS (HR, 2.35; 95% CI: 1.41, 3.94; P = .0011). Additionally, decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics signature had a higher overall net benefit in prediction of high-risk patients to receive treatment than the clinicopathologic measurements. Conclusion:This study suggests that radiomic texture features extracted from within and around the nodule on baseline CT scans are (a) predictive of response to chemotherapy and (b) associated with TTP and OS for patients with NSCLC.

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PurposeHyperprogression is an atypical response pattern to immune checkpoint inhibition that has been described within non-small cell lung cancer (NSCLC). The paradoxical acceleration of tumor growth after immunotherapy has been associated with significantly shortened survival, and currently, there are no clinically validated biomarkers to identify patients at risk of hyperprogression.Experimental designA total of 109 patients with advanced NSCLC who underwent monotherapy with Programmed cell death protein-1 (PD1)/Programmed death-ligand-1 (PD-L1) inhibitors were included in the study. Using RECIST measurements, we divided the patients into responders (n=50) (complete/partial response or stable disease) and non-responders (n=59) (progressive disease). Tumor growth kinetics were used to further identify hyperprogressors (HPs, n=19) among non-responders. Patients were randomized into a training set (D1=30) and a test set (D2=79) with the essential caveat that HPs were evenly distributed among the two sets. A total of 198 radiomic textural patterns from within and around the target nodules and features relating to tortuosity of the nodule associated vasculature were extracted from the pretreatment CT scans.ResultsThe random forest classifier using the top features associated with hyperprogression was able to distinguish between HP and other radiographical response patterns with an area under receiver operating curve of 0.85±0.06 in the training set (D1=30) and 0.96 in the validation set (D2=79). These features included one peritumoral texture feature from 5 to 10 mm outside the tumor and two nodule vessel-related tortuosity features. Kaplan-Meier survival curves showed a clear stratification between classifier predicted HPs versus non-HPs for overall survival (D2: HR=2.66, 95% CI 1.27 to 5.55; p=0.009).ConclusionsOur study suggests that image-based radiomics markers extracted from baseline CTs of advanced NSCLC treated with PD-1/PD-L1 inhibitors may help identify patients at risk of hyperprogressions.