High Terminal Hemorrhage Risk From Cardiac Angiosarcoma Brain Metastases Warrants Frequent Brain Imaging and Early Intervention

Abstract

<h3>Purpose/Objective(s)</h3> Cardiac angiosarcomas (CA) often develop early distant disease with risk of brain metastases (BM) and have recognized hemorrhagic risk. However, limited data exists characterizing this presentation. Therefore, we evaluated a cohort of patients with CA who developed BM to better define outcomes and intracranial hemorrhage (IH) risk. <h3>Materials/Methods</h3> We reviewed 26 consecutive patients with BM treated between 1988 and 2020 identified from a departmental CA (n = 103) database. Institutional practice has shifted over the decades to include a CT head at diagnosis but with infrequent serial imaging. Causes of death were recorded, and a terminal hemorrhage (TH) was defined as an IH that caused death during hospitalization or prompted transfer to hospice. <h3>Results</h3> The prevalence of BM was 25% (n = 26/103) among patients with CA at a median age of 37 years (IQR 26-50). All primary tumors involved the right heart (atrium: n = 20, 77%), and 20 patients (77%) presented with metastases at initial diagnosis, of which only 4 had BM. The median time between initial CA diagnosis to BM was 11 m (IQR 3-18) resulting in a 6-m BM free survival of 65%. There was a median of 3 lesions (IQR 1-7), and a majority had 1-4 (n = 15, 58%). The median follow-up from the time of BM was short at 2 m (IQR 1-6.5) due to a high rate of TH. Nearly all patients died of disease (n = 23, 88%). The 6-m OS from the time of BM was 21%, and most patients died from TH (n = 13, 57%). TH occurred at BM presentation in 6 (46%) patients, whereas 3 (23%) had TH from known and untreated lesions, 2 (15%) had continued uncontrolled IH during RT, and 2 (15%) from new BM. The only factor associated with TH as the cause of death was platelet count as a continuous variable (median 162 vs 360k, <i>P</i> = 0.02; platelet count < 50 vs. ≥50, <i>P</i> = 0.25). Only 18 patients (69%) received treatment for BM due to a high rate of TH at presentation: RT alone in 10 (55%; WBRT n = 6; SRS n = 4), surgery for 4 (22%), surgery + RT for 2 (11%), and chemotherapy for 2 (11%). One patient (6%) developed local failure following surgery alone and 5 (28%) developed distant brain failure. A total of 23 patients (88%) had IH, including 21 (81%) at initial BM diagnosis, of which 18 (86%) required hospitalization. The median platelet count at the time of IH was 235k (IQR, 108-338k). Only 4 patients (17%) had a platelet count < 50k at the time of IH, whereas the majority were above 200k (n = 12, 71%). Subsequent IH occurred in 9 patients (35%), but in only 1 that completed RT, which was minor. No patients who completed RT for BM died from TH. <h3>Conclusion</h3> Patients with CA frequently develop BM, and the risk of IH is high resulting in an alarming rate of TH despite normal platelet counts. Therefore, early diagnosis and intervention is warranted. We recommend incorporating MRI brain imaging into the standard q2-3 month staging evaluation. And importantly, once BM are detected, prompt local therapy is recommended to try and mitigate the risk of TH.