ANALYSIS OF PREDICTIVE AND PROGNOSTIC FACTORS IN PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK) REARRANGED EARLY STAGE LUNG CANCER ADENOCARCINOMA (LUAD): A MULTICENTRIC ANALYSIS

OBJECTIVES Rearrangements of the anaplastic lymphoma kinase (ALK) gene characterize 6-7% of NSCLC affecting predominantly never-smokers and young patients with adenocarcinoma more. Due to the widespread of alk-directed TKIs and the rarity of the data on the molecular expressions in a non-metastatic setting, their prognostic and predictive role alk-rearrangements in alkdirected-TKIs naïve patients is mostly unknown. In this study, we aim to analyze the clinical and biological factors associated with recurrence in patients with early-stage, ALK rearranged LUAD without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. METHODS Patients who underwent radical treatment for clinical stage I and II LUAD with ALK rearrangement in five high volume centers were evaluated. Univariable and multivariable logistic regression was used to quantify the association between clinical and biological variables and the risk of recurrence, in addition to hazard ratios and their 95% confidence intervals. RESULTS A total of 60 patients were included. Most of the patients underwent minimally invasive surgery. The majority of the patients were female (56.1%) and never or light smokers (57.6%). More than half of the patients showed nodal upstaging after surgery (56.2%), and 72.7% of the patients with nodal upstaging had tumors less than 3 cm (OR 2.788; 1.331-5.929, p=0.008). Recurrence was reported in 28 patients, of whom 8 had brain metastases. In the multivariate analysis, the PD-L1 status showed a significant correlation with recurrence (HR 13.5, CI 3.53- 52.1; p= 0.0001). CONCLUSIONS Our results demonstrated a high rate of upstaging and brain recurrence in patients with stage I and II LUAD who had the ALK rearrangement. Additionally, we found a significant correlation between the PD-L1 status and recurrence.