High-dose radiation therapy is needed for intracranial control and long-term survival in patients with non-seminomatous germ cell tumor brain metastases

J Neurooncol. 2019 May;142(3):523-528. doi: 10.1007/s11060-019-03123-0. Epub 2019 Feb 15.

Abstract

Purpose: 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 patients with NSGCT BM, there is a paucity of data on the optimal regimen. We sought to investigate the impact of RT on clinical outcomes in patients with NSGCT BM.

Methods: Patients with NSGCT BM who received RT at our institution from 2002 to 2017 were included. Sixty-three consecutive patients were identified. Clinical factors associated with intracranial control (ICC) and overall survival (OS) were evaluated using cox regression analysis and Kaplan Meier method.

Results: Median age was 31 years and number of BM was three. Fifteen patients presented with BM at diagnosis, while 48 developed BM at a median time of 8.4 months from diagnosis. At a median follow-up of 3.6 years, ICC and OS were 39.7% and 30.1%. On multivariate analysis, ICC (hazard ratio [HR] = 0.93, p = 0.03) and OS (HR = 0.93, p = 0.005) were both significantly associated with biologically effective dose (BED) of RT. The 4-year OS of patients who received BED < 39Gy, 39 Gy, 40-50 Gy, and ≥ 50 Gy were 0%, 14.7%, 34.1%, and 70.0%, respectively. Patients who achieved ICC after RT were able to achieve long-term survival (4-year OS 68.1% vs. 0%, p < 0.0001).

Conclusions: Our data supports that a higher BED is required for durable ICC, and that ICC 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.

Keywords: Brain metastases; Dose–response relationship; Non-seminomatous germ cell tumor; Stereotactic radiosurgery; Whole brain radiation therapy.

MeSH terms

  • Adolescent
  • Adult
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary
  • Cranial Irradiation / mortality*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / mortality*
  • Neoplasms, Germ Cell and Embryonal / radiotherapy
  • Neoplasms, Germ Cell and Embryonal / secondary
  • Prognosis
  • Radiation Dose Hypofractionation
  • Retrospective Studies
  • Salvage Therapy*
  • Survival Rate
  • Testicular Neoplasms / mortality*
  • Testicular Neoplasms / radiotherapy
  • Testicular Neoplasms / secondary
  • Young Adult

Supplementary concepts

  • Nonseminomatous germ cell tumor