P11.06.A PATTERNS OF PSTAT3 EXPRESSION IN REACTIVE ASTROCYTES OF BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER AND CORRELATIONS WITH OUTCOME

Abstract BACKGROUND pSTAT3 expression in peritumoral reactive astrocytes (RA) of brain metastases (BrM) from breast cancer may favor a pro-metastatic environment and negatively affect the intracranial progression-free survival (i-PFS) (Pellerino, Neurooncol Adv. 2023). We aim to evaluate whether pSTAT3 plays the same role also in BrM from NSCLC. MATERIAL AND METHODS Seventy-two BrM specimens from NSCLC were identified from the biobank of Pathology Unit of University of Turin and Berlin. pSTAT3 expression was scored in RA of peritumoral tissue according to Priego et al. (Nat Med 2018). Clinical and molecular data, and i-PFS were retrospectively retrieved. RESULTS Median age was 64 years (95%CI 59-67). Immunohistochemistry for GFAP and pSTAT3 was feasible in 66/72 (91,6%). 42/66 (63,6%) had BrM with druggable mutations, while 24/66 (36,4%) did not show any actionable mutations. Druggable mutations were as follows: 8/42 (19,1%) KRAS G12C, 6/42 (14,3%) EGFR, 5/42 (11,9%) ALK, 1/42 (2,4%) BRAFv600E, 31/42 (73,8%) PDL1 expression. Overall, 53/66 (80,3%) showed positive staining of pSTAT3: 22/66 (33,3%) with score 3, 21/66 (31,8%) with 2, 10/66 (15,1%) with 1, and 12/66 (19.8%) with 0 (negative). High pSTAT3 expression (score 2-3) was observed in 32/42 (76,2%) BrM with actionable mutations and in 12/24 (50%) without actionable mutations (p 0,031). PDL1 expression was significantly correlated with high pSTAT3 expression (29/31, 93,5%), while most of BrM without PDL1 (20/35 - 57,1%) had low or absent pSTAT3 (score 0-1) (p<0,0001). Median i-PFS was 12 months (95%CI 8-23): low pSTAT3 BrM had a median i-PFS of 18 months (95%CI 14-28) versus 9 months (95%CI 8-12) for high pSTAT3 BrM (HR 5,3;p 0,0001). CONCLUSION pSTAT3 overexpression in RA is associated with PDL1 expression and may negatively impact the i-PFS in BrM from NSCLC. These data support the investigation of STAT3 inhibitor silibinin in preventing intracranial recurrence in a clinical trial (NCT05689619).