Caratterizzazione epidemiologica, clinica e molecolare "real life" del tumore polmonare early- stage con mutazioni dei geni EGFR e KRAS in pazienti del Sud Italia

Objective The identification of driver mutations in NSCLC has revolutionized the understanding and management of many lung cancer patients and has opened new scenario in the in the early disease stages. Data on prevalence rates and stage distribution of EGFR and KRAS mutations in surgically resected NSCLC are growing, but in Southern Italy are limited, since KRAS screening is not jet common practice in resected NSCLC. In this real-life study of a single Institution of Puglia Region, we provide an overview of the epidemiological distribution of EGFR and KRAS mutations in Southern Italy patients with resected NSCLC, highlighting their prevalence, clinical significance, and correlation with demographic and pathological factors. Patients and Methods: The study involved a total of 149 patients with surgically resected stage I–IIIA NSCLC, who underwent curative radical surgery during a period of 16 years at the Thoracic and Pulmonary Surgery Department of the Casa Sollievo della Sofferenza Hospital in Southern Italy (Puglia Region). All patients included in this study underwent anatomical resection of the lung parenchyma with an open or minimally invasive approach (VATS or robotic) or an atypical resection. For all patients, clinical and pathological information were collected. Mutation screening were performed using both sequencing techniques or hot spot techniques. Results: In our study, about 48% of the 149 patients had a genetic change in one of the two EGFR and KRAS genes. More specifically, 24/149 NSCLC (16%) harbored an EGFR mutation. Frequencies of exon 19 deletions and missense p.(L858R) mutations of EGFR gene were quite similar (46%) and were more frequent in never smoker (p<0.001) female (p<0.001) patients with adenocarcinoma histology. KRAS gene mutations were observed in 31.5% of cases, with missense p.G12C (32%), p.G12V (28%) and p.G12D (17%) mutations as the most frequent ones. Neither EGFR, nor KRAS mutational status were found to impact on overall survival (OS) in our study cohort. Conclusions: Our findings improve our understanding of lung cancer genetics in a small and homogeneous area of Southern Italy and guide future research. The EGFR and KRAS mutations in NSCLC resected patients from Southern Italy showed a global similar incidence in comparison with other just described Italian cohorts of advanced and early-stage NSCLC, with a higher frequency of exon19 EGFR deletions. No prognostic impact was observed for both EGFR and KRAS status, but additional investigations on a larger cohort are needed to confirm our conclusions.