The VIGILANCE Study Protocol: An Innovative Study to Identify Prognostic and Response Biomarkers in Patients with Stage III Non-Small-Cell Lung Cancer Treated with Curative-Intent Radiotherapy

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574.