Molecular Profiling and Dynamic Changes of ctDNA in Unresectable Locally Advanced NSCLC

Tumor samples will be collected as standard diagnostic procedure at diagnosis. Plasma samples from whole blood extractions will also be collected at diagnosis, after chemoradiotherapy, and every 3 months from there until completing one year of follow-up.

Genomic alterations of tumor tissue samples will be analyzed locally by next-generation sequencing when material is adequate, as standard diagnostic procedure.

Patients will be treated with standard chemotherapy (following the clinical practice at each institution). Radiotherapy will be delivered concurrently when feasible with a total dose of 60-66 Gy. In selected cases, due to frailty of the patient or impaired pulmonary function, radiotherapy will be delivered sequentially. In tumors with positive PD-L1 expression, a year of durvalumab 10 mg/m2 every 2 weeks will be administered if there are no contraindications.

"Blood samples for ctDNA genomic and methylation analysis (4 mL of plasma for each sample) will be sent to the Guardant Health Laboratories in the US and analyzed after Contractual Agreement signature, using the Guardant Reveal test.~This liquid biopsy test uses ctDNA to detect presence of MRD and monitor for recurrence after definitive surgical/systemic therapy for patients with cancer. It has been validated in early-stage colorectal cancer and integrates assessment of somatic alterations with an epigenomic cancer signature to identify the presence of methylation signatures associated with cancer versus normal DNA."