A proposed methodology for detecting the malignant potential of pulmonary nodules in sarcoma using computed tomographic imaging and artificial intelligence-based models

The presence of lung metastases in patients with primary malignancies is an important criterion for treatment management and prognostication. Computed tomography (CT) of the chest is the preferred method to detect lung metastasis. However, CT has limited efficacy in differentiating metastatic nodules from benign nodules (e.g., granulomas due to tuberculosis) especially at early stages (<5 mm). There is also a significant subjectivity associated in making this distinction, leading to frequent CT follow-ups and additional radiation exposure along with financial and emotional burden to the patients and family. Even 18F-fluoro-deoxyglucose positron emission technology-computed tomography (18F-FDG PET-CT) is not always confirmatory for this clinical problem. While pathological biopsy is the gold standard to demonstrate malignancy, invasive sampling of small lung nodules is often not clinically feasible. Currently, there is no non-invasive imaging technique that can reliably characterize lung metastases. The lung is one of the favored sites of metastasis in sarcomas. Hence, patients with sarcomas, especially from tuberculosis prevalent developing countries, can provide an ideal platform to develop a model to differentiate lung metastases from benign nodules. To overcome the lack of optimal specificity of CT scan in detecting pulmonary metastasis, a novel artificial intelligence (AI)-based protocol is proposed utilizing a combination of radiological and clinical biomarkers to identify lung nodules and characterize it as benign or metastasis. This protocol includes a retrospective cohort of nearly 2,000-2,250 sample nodules (from at least 450 patients) for training and testing and an ambispective cohort of nearly 500 nodules (from 100 patients; 50 patients each from the retrospective and prospective cohort) for validation. Ground-truth annotation of lung nodules will be performed using an in-house-built segmentation tool. Ground-truth labeling of lung nodules (metastatic/benign) will be performed based on histopathological results or baseline and/or follow-up radiological findings along with clinical outcome of the patient. Optimal methods for data handling and statistical analysis are included to develop a robust protocol for early detection and classification of pulmonary metastasis at baseline and at follow-up and identification of associated potential clinical and radiological markers.