Background: More than 40% of NSCLCs are diagnosed in patients older than 70 years. Elderly have more comorbidities and are less tolerant to chemio-radiotherapies than younger but targeted treatments such as epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors could be well tolerated. Here, we sought to define the genetic profile of NSCLCs in patients older than 70 years Methods: In this single-institution study, we evaluated EGFR, KRAS mutations and ALK rearrangements in 880 pulmonary adenocarcinomas (ADK) occurring in patients older than 70 years (median 75 yrs) compared to a consecutive series of 409 patients younger than 60 years (range 18-60, median 55 yrs). Mutational status was analyzed with bi-directional Sanger sequencing and ALK rearrangement was evaluated by fluorescence in-situ hybridization (FISH). Statistical analysis was performed by Pearson's chi-square test Results: There was no difference in the prevalence of EGFR mutations between elderly and younger patients. Nevertheless, both ALK rearrangements and KRAS mutations occurred less frequently in the elderly. Moreover, statistically significant differences in KRAS codons involved and gender prevalence of KRAS mutations were found (Table) Conclusions: Though KRAS and ALK alterations are less frequent in elderly patients, no significant differences in EGFR mutations prevalence were found. Routine molecular tests driving targeted therapies should be offered to all ADK patients regardless of age.

F = Female M = Male MUT = Mutation REARR = Rearrangement * p < 0.05