MON-554 Brain Metastases in Thyroid Cancer: Molecular Profile and Institutional Experience of a Single Tertiary Referral Center in the Era of Kinase Inhibitor Therapy

Background: Historical data suggests differentiated thyroid cancer (DTC) patients (pts) with brain metastases (mets) have overall survival (OS) of approximately 1 year; other reports refer median OS of 33months. Little is known about the mutation profile these pts. The TCGA indicates a median of 1 mutation in pts with PTC, most of which were low risk cases. Methods: We retrospectively studied clinical characteristics including number of lesions, therapeutic modalities, OS and mutational profile of TC pts with brain mets at a single cancer center between 2013-2018. Cases were identified by ICD-9 & -10 codes for TC and secondary neoplasm of brain but excluded if a separate malignancy accounted for brain mets. Somatic mutations were tested by targeted next-generation sequencing in the majority of cases. Results: Of 105 cases reviewed, 52 met entry criteria. Median age at diagnosis of brain mets was 62.5 years (4-85years); 31/52 (59.6%) were males. DTC accounted for the majority of the pts, 37/52 (71%) [papillary thyroid cancer 55.8%(PTC; 29/52); poorly differentiated thyroid cancer (PDTC; 5/52) 9.6%; follicular thyroid cancer 5.8% (3/52); Hurthle cell 0/52]; anaplastic thyroid cancer (ATC) 21.1% (11/52) & medullary thyroid cancer 7.7% (4/52). Symptoms were present in 50%, predominantly weakness 9/26 (34.6%), headaches 6/26 (23.1%), altered mental status 5/26 (19.2%), visual changes 5/26 (19.2%) and seizures 4/26 (15.4%). 47 pts received systemic therapy as follows: antiangiogenic drug 26/47 (55%); BRAF inhibitor alone or in combination with MEK inhibitor 22/47 (46.8%) and checkpoint inhibitors 16/47 (34%). Molecular testing was available in 50 cases. Known oncogenic driver mutations were noted in 86%(43/50); BRAF V600E mutated in 25/50 (50%), RAS 14/50 (28%; NRAS n=11, HRAS n=2, KRAS n=1), RET mutated in 4 cases. Of 25 pts tested for TERT promoter mutation 8 (32%) were positive. Mean number +/- SD of somatic mutations was 2.14 +/- 1.15 in PTC; 2.6 +/-1.62 in PDTC; and 5.45 +/- 4.6 in ATC. In terms of number of brain lesions, 38.5% had ≥3 metastatic foci. Treatment consisted of radiation [stereotactic radiosurgery 22/50 (44%), whole brain radiation 10/50 (20%)] and 13/50 (26%) surgical intervention. Median OS was 29.7 months (95% CI 12.5-NR) after brain mets diagnosis. 1-year survival by number of brain metastases was 76% for single focus (n=17), 66% for 2 (n=15) and 50% (n=20) for ≥3 (p=0.034). One year OS for surgically treated vs radiation was not statistically different. 1-year OS for DTC was 65% (95% CI 51%, 82%) vs 53% in ATC (95% CI 30%, 94%) p-value=0.996. The OS in symptomatic vs silent brain mets was 19.9 months vs 29.6 months (p value= 0.45). Conclusions: Mutation burden appears to be higher in TC pts with brain mets compared to TCGA. In TC pts with brain mets, survival decreases as number of lesions increases. The OS was slightly shorter in pts with symptomatic brain mets but not statistically significant.