Impatto del DNA tumorale circolante e DNA libero circolante su diagnosi precoce di tumore al polmone in pazienti con riscontro radiologico di ground glass opacity (GGO)

Background: Pulmonary Ground Glass Nodules (GGNs) are often detected accidentally but may be indicative of early-stage lung cancer in up to 37% of cases. Currently, the standard of care includes long-term radiological follow-up. This study explores the potential diagnostic role of circulating free DNA (cfDNA) and circulating tumor DNA (ctDNA) in peripheral blood of patients with GGNs. Methods: This pilot study included 28 patients (mean age 67.5 years) diagnosed with GGNs via CT scan. Blood samples were collected before any treatment and plasma was stored at -80°C. cfDNA was extracted and quantified, while ctDNA was analyzed using the Myriapod® NGS Cancer Panel. Patients were monitored through radiological or histological biopsy following international guidelines. Findings were compared with DNA results to evaluate cfDNA and ctDNA’s role in diagnosing malignant GGNs. Results: Of the 28 patients, seventeen (60.7%) had malignant GGNs, and eleven (39.3%) had benign or transitory nodules. Pure GGNs were more likely to be benign than mixed GGNs (p value=0.023). ctDNA analysis detected mutations in HRAS and KIT (40%), NRAS (30%), IDH-2 (20%), RET (20%), and PIK3CA (20%), but no consistent mutations were found between ctDNA and tissue analysis in the first 10 patients, therefore the examination was stopped. The cfDNA analysis showed a mean concentration of 1.37 ng/μL, with malignant GGNs showing lower cfDNA levels (1.149 ng/μL) compared with inflammatory lesions (1.414 ng/μL), even if it not reached the statistical significance. Conclusions: The study suggests that early-stage lung cancer does not release significant ctDNA into the blood, limiting its role in early diagnosis of GGNs. However, lower cfDNA levels in malignant GGNs compared with inflammatory lesions may offer new insights into lung cancer biology and detection.