High-Dose Radiation Therapy is Needed for Intracranial Control and Long-Term Survival in Patients with Non-Seminomatous Germ Cell Tumor Brain Metastases

Abstract

The presence of brain metastases (BM) in patients with non-seminomatous germ cell tumor (NSGCT) is associated with poor prognosis. While radiation therapy (RT) is an important treatment for NSGCT BM, there is limited data on the optimal RT regimen. We sought to investigate the impact of RT on intracranial control (IC) and overall survival (OS) in patients with NSGCT BM. Sixty-three consecutive patients with NSGCT and BM who underwent RT and were treated our institution from 2002-2017 were included. Kaplan-Meier method was used to estimate IC and OS following RT. Cox regression analysis was used to assess the impact of clinical factors including age, chemotherapy, surgery, RT fields (whole brain radiation therapy [WBRT], stereotactic radiosurgery [SRS]), and biologically effective dose (BED) of RT on IC and OS. The median age at BM diagnosis was 31 years (range 14-62) and median number of BM was 3 (range 1-11). Of the 63 patients, 15 (24%) presented with BM at the time of initial NSGCT diagnosis, while 48 patients (76%) developed BM at a median time of 8.4 months (range 3.7-222.9) after initial NSGCT diagnosis. The median follow up for the cohort was 3.6 years (range 0.4-15.8). ICC and OS at 3 years among the entire cohort were 39.7% (95% CI=26.1-53.3) and 30.1% (95% CI=18.2-42.0), respectively. On UVA, greater number of brain metastases was associated with worse IC (HR= 1.19, p=0.002). Patients who received a combination of WBRT with focal SRS boost (n=10) had better IC compared with patients who received SRS (n=7) or WBRT (n=46) alone (HR=0.25, p=0.06), and patients who received a higher BED of RT demonstrated better IC (HR=0.04, p=0.001). On MVA, higher BED remained a significant predictor of improved IC (HR=0.06, p=0.004): IC at 3-years was 0% in those who received a BED of <39 Gy, 17.9% in those who received a BED of 39 Gy (equivalent to 30 Gy in 10 fractions), 50.0% in those who received a BED of 40-50 Gy, and 77.9% in those who received a BED ≥ 50 Gy. On UVA, OS was found to be positively associated with a higher BED (HR=0.06, p<0.0001) and negatively associated with a greater number of brain metastases (HR=1.2, p=0.001). On MVA, higher BED remained a significant predictor of OS (HR=0.08, p<0.0001): 3-year OS of patients who received a BED <39Gy, 39Gy, 40-50 Gy, and ≥ 50 Gy was 0%, 14.7%, 34.1%, and 70.0%, respectively. Patients who achieved IC after RT were able to achieve long-term OS: 68.1% at 3 years in those without relapse in the brain compared with 0% in those who relapsed in the brain (p<0.0001). Brain metastases in NSGCT remain a clinically challenging entity. Our data supports that radiation regimens with a higher BED are needed for durable intracranial control. We also found that intracranial control after RT is needed for patients with NSGCT to achieve long-term survival. Prospective studies evaluating radiation dose escalation for the treatment of NSGCT BM should be considered.