Primary Management of Non-Seminomatous Germ Cell Brain Metastases with Stereotactic Radiosurgery: A Case Series

Abstract

Non-seminomatous germ cell tumors (NSGCT) are a clinically rare entity, mainly occurring in otherwise healthy young men. While standard of care for brain metastases has shifted to stereotactic radiosurgery (SRS) for many histologies, in NSGCT patients with brain metastases, it remains whole brain radiation therapy (WBRT). Radiation-induced neurocognitive deficits have been documented in patients with NSGCT brain metastases treated with WBRT. This is further complicated by the fact that these patients typically receive neuro-toxic high dose chemotherapy. There remain no published reports evaluating the efficacy of SRS as the primary treatment of NSGCT brain metastases. We hypothesize that SRS is a feasible alternative to WBRT for the treatment of NSGCT metastases to the brain. The available records of patients with various non-seminomatous germ cell tumor histologies treated between 2011 and 2018 at a single institution were retrospectively reviewed. All of the 26 male patients received initial gamma knife or Linac based radiosurgery without WBRT. Five of the patients underwent SRS to a post-surgical resection cavity. Nearly 75% of patients received adjuvant tandem stem cell transplant with high dose chemotherapy. The median follow-up of the cohort was 42 months (range 17-107 months) with a median age of 27 years old (range, 17-56) and a mean of 3 (range, 1-14) lesions treated. At the time of SRS, patients had received a median of 5 prior lines of chemotherapy, with a median of 3 disease relapses. The 1-year OS was 73% with a median survival of 23 months. Only one treated lesion was observed with local progression, resulting in a 2-year LC rate of 99% (this recurrence was salvaged successfully with repeat SRS). Only one neurologically related death occurred, leading to a neuro-specific EFS rate of 96%. A total of 23% of patients experienced distant brain recurrence at a median time of 2.7 months, which resulted in a 1-year distant brain control of 77%. Of the 6 patients with distant failure, 4 were successfully salvaged with repeat SRS treatment without additional relapse on follow-up imaging. Only one patient received salvage WBRT 19 months post initial SRS, leading to a 2-year WBRT free survival of 96%. Radiosurgical management of brain metastases has demonstrated feasibility in the management of several cancer histologies, but this has yet to be determined for NSGCTs. Brain metastases from NSGCTs are often limited in number, and mainly affect young men with good functional status. Avoidance of WBRT in patients receiving adjuvant high dose chemotherapy may provide control of intracranial disease with the goal of preserving neurocognitive function in these young patients. Our preliminary results suggest that SRS may safely replace WBRT as an initial treatment of choice in patients with NSGCT brain metastases receiving adjuvant high dose chemotherapy.