Clinical, Pathological and Molecular Predictive Factors for the Development of Brain Metastasis in Patients with Lung Adenocarcinoma
Kirtee Raparia, Celina Villa, Minesh Mehta, Philip Cagle. Northwestern University, Chicago, IL; Methodist Hospital, Houston, TX
Background: Metastasis to brain comprises 24-45% of all cancer patients, of which the most common primary site is lung. It is important to predict which lung cancer patients are at higher risk of developing brain metastases, so that prophylactic therapies can be better directed. We hypothesize that lung adenocarcinomas, which metastasize to the brain show distinct morphologic and molecular features and outcomes.
Design: We evaluated clinical and pathological feature of patients with Stage 4 lung adenocarcinoma with known epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement status, diagnosed at our institution between 2008 and 2011. Overall survival (OS) was analyzed using the Kaplan-Meier and Cox proportional hazard methods.
Results: 58 of 126 patients with stage 4 lung cancer (46%) had brain metastases. Of the patients with brain metastases, 37 (64%) were women and had a median age of 62 years (range 32-92 years). 26% patients had solitary, and 74% had multiple lesions in the brain. Majority of these patients (52%) had metastatic deposits at other sites including bone, adrenal, contralateral lung, liver, choroid and peritoneum. Patients with brain metastasis had larger lung nodules (p=0.006) and were slightly older in age (68 vs. 64 years, p=0.044). Lung primaries, which developed brain metastases had predominant acinar pattern. 25% of these patients had EGFR mutation and 28% patients harbored KRAS mutation. G12V in codon 12 was the most common KRAS mutation and E746 mutation in exon 19 was most common EGFR mutation in this subgroup. 2 patients had ALK gene rearrangements. Trend for increased survival was seen in patients with EGFR mutation (Log rank, p=0.067), but no difference in survival was seen in patients with KRAS mutation.
Conclusions: G12V is the most common KRAS mutation and E746 is the most common EGFR mutation in the patients with lung adenocarcinoma with brain metastasis. Patients with EGFR mutation had a trend for increased survival than those patients with EGFR wild type tumors.
Monday, March 4, 2013 1:15 PM
Proffered Papers: Section D, Monday Afternoon