A new study published in Nature: Precision Oncology introduces a radiogenomics approach to predict and characterize pneumonitis in patients with stage III non-small cell lung cancer (NSCLC) undergoing chemoradiation followed by consolidative durvalumab. The research combines radiomic features extracted from CT scans with clinical data and genomic information to develop predictive and discriminative models for pneumonitis. This approach aims to improve risk stratification and personalize treatment strategies for NSCLC patients.
Predicting Pneumonitis Risk
The study, conforming to HIPAA guidelines and approved by Institutional Review Boards at Cleveland Clinic Foundation and Emory Healthcare, retrospectively analyzed data from 226 patients at Cleveland Clinic and 67 patients at Emory Healthcare. Researchers extracted 555 radiomic features from pre-treatment CT scans and developed a predictive radiomic signature (PRS) using multivariable logistic regression. This PRS, combined with clinical features such as age, smoking status, tumor histology, and PD-L1 expression, was used to create a nomogram for predicting pneumonitis likelihood.
The predictive model (M1) demonstrated promising results in both internal and external validation cohorts. The area under the receiver operating characteristic curve (AUC) for M1 in the training cohort (D1) was not explicitly stated, but the model showed good calibration power, suggesting its reliability in predicting pneumonitis risk. Bootstrapping with 500 resamples was employed to quantify model overfitting.
Distinguishing Between Radiation-Induced and Immunotherapy-Induced Pneumonitis
In addition to predicting pneumonitis risk, the researchers developed a discriminative model (M2) to differentiate between radiation-induced pneumonitis (RTP) and immunotherapy-induced pneumonitis (IIP). This model utilized a discriminating radiomic signature (DRS) derived from post-treatment CT scans. The ability to distinguish between these two types of pneumonitis is crucial for tailoring treatment strategies, as they may require different management approaches.
The discriminative model (M2) was trained on a subset of patients from Cleveland Clinic (D4) and validated on a combined cohort from Cleveland Clinic and Emory Healthcare (D5). The AUC for M2 in distinguishing between RTP and IIP was not explicitly stated, but the model's development suggests its potential clinical utility.
Correlating Radiomic Features with Tumor Genomics
The study also explored the correlation between radiomic features and tumor genomics. Gene set enrichment analysis (GSEA) was performed using Spearman's correlation on mRNA sequencing data from The Cancer Imaging Archive (TCIA) dataset. This analysis aimed to identify gene pathways associated with the predictive (PRS) and discriminative radiomic signature (DRS), potentially revealing molecular mechanisms linked to pneumonitis development.
Clinical Implications
The findings suggest that radiogenomics can play a significant role in predicting and characterizing pneumonitis in stage III NSCLC patients. By integrating radiomic features with clinical and genomic data, clinicians can potentially identify high-risk patients before treatment initiation and tailor their management strategies accordingly. Furthermore, the ability to distinguish between RTP and IIP can guide treatment decisions and improve patient outcomes.
Study Limitations
The study acknowledges several limitations, including its retrospective design and the potential for selection bias. The reliance on manual segmentation of CT scans also introduces a degree of subjectivity. Future prospective studies with larger patient cohorts are needed to validate these findings and further refine the radiogenomics approach.
