Recently immune-checkpoint inhibitors have demonstrated promising clinical efficacy in patients with advanced non-small cell lung cancer (NSCLC). However, the response rates to immune checkpoint blockade drugs remain modest (45% in the front line setting and 20% in the second line setting). Consequently, there is an unmet need to develop accurate, validated biomarkers to predict which NSCLC patients will benefit from immunotherapy. While there has been recent interest in evaluating the role of texture and shape patterns of the nodule on CT scans to predict response to checkpoint inhibitors for NSCLC, our group has shown that nodule vessel morphology might also play a role in determining tumor aggressiveness and behavior. In this work we present a new approach using quantitative vessel tortuosity (QVT) radiomics, to predict response to checkpoint inhibitors and overall survival for patients with NSCLC treated with Nivolumab (a PD1 inhibitor) on a retrospective data set of 111 patients (D1) including 56 responders and 45 non-responders. Patients who did not receive Nivolumab after 2 cycles due to a lack of response or progression as per Response Evaluation Criteria in Solid Tumors (RECIST) were classified as non-responders, patients who had radiological response or stable disease as per RECIST were classified as responders. On D1, in conjunction with a linear discriminant analysis (LDA) classifier the QVT features were able to predict response to immunotherapy with an AUC of 0.73_0.04. Kaplan Meier analysis showed significant difference of overall survival between patients with low risk and high risk defined by the radiomics classifier (p-value = 0.004, HR= 2.29, 95% CI= 1.35 - 3.87).
Immune checkpoint inhibitors targeting the programmed cell death (PD)1/ L1 axis have been approved for treatment of chemotherapy refractory advanced non-small cell lung cancer (NSCLC) for a few years. While higher PD-L1 expression is associated with better outcomes after monotherapy with immune checkpoint inhibitors, it is not a perfect predictive biomarker for clinical benefit from immunotherapy, because some patients with low PD-L1 expression have sustained responses. In clinical practice, using radiological tools like Response Evaluation Criteria in Solid Tumors (RECIST), tends to underestimate the benefit of therapy. For instance, some patients treated with immunotherapy suffer from pseudoprogression while actually having a favorable response, RECIST in this setting is inadequate to capture the response. In this study we sought to explore whether radiomic texture features extracted from both inside and outside of the tumor from baseline CT scans were associated with overall patient survival (OS) in 139 NSCLC patients being treated with IO from two separate sites. Patients were divided into a discovery (D1 = 50; nivolumab from Cleveland Clinic) and two validation sets (D2 = 62 from Cleveland Clinic, D3 = 27 from University of Pennsylvania Health System. Patients in the validation sets had been treated with different types of checkpoint inhibitor drugs including nivolumab, pembrolizumab, and atezolizumab. 454 radiomic texture features from within (intra-tumoral) and outside the tumor (peri-tumoral) were extracted from baseline contrast CT images. Following feature selection on the discovery set, a radiomic risk-score signature was generated by using least absolute shrinkage and selection operator. Using a Cox regression model, the association of the radiomic signature with overall survival (OS) was evaluated in the discovery and two validation sets. In addition, 95% confidence intervals (CI) and relative hazard ratios (HR) were calculated. Our results revealed that the radiomics signature was significantly associated with OS, both in the discovery set (HR = 5.06, 95%CI = 3, 8.55; p-value < 0.0001) and the two validation data sets (D2: HR = 5.88, 95% CI = 2.19, 21.63, p-value = 0.0009; D3: HR = 5.37, 95% CI = 1.74, 16.57, p-value = 0.0034). Our initial results appear to suggest that our radiomic signature could serve as a non-invasive way of predicting and monitoring response to checkpoint inhibitors for patients with non-small cell lung cancer.
Differentiation between benign and malignant nodules is a problem encountered by radiologists when visualizing computed tomography (CT) scans. Adenocarcinomas and granulomas have a characteristic spiculated appearance and may be fluorodeoxyglucose avid, making them difficult to distinguish for human readers. In this retrospective study, we aimed to evaluate whether a combination of radiomic texture and shape features from noncontrast CT scans can enable discrimination between granulomas and adenocarcinomas. Our study is composed of CT scans of 195 patients from two institutions, one cohort for training (N = 139) and the other (N = 56) for independent validation. A set of 645 three-dimensional texture and 24 shape features were extracted from CT scans in the training cohort. Feature selection was employed to identify the most informative features using this set. The top ranked features were also assessed in terms of their stability and reproducibility across the training and testing cohorts and between scans of different slice thickness. Three different classifiers were constructed using the top ranked features identified from the training set. These classifiers were then validated on the test set and the best classifier (support vector machine) yielded an area under the receiver operating characteristic curve of 77.8%.
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