Optimal Management of Brainstem Metastases

A Narrative Review

Joan Y. Lee; Danielle A. Cunningham; Erin S. Murphy; Samuel T. Chao; John H. Suh


Chin Clin Oncol. 2022;11(2):15 

In This Article


Surgical resection of brainstem metastases is seldom attempted due to high risks of operating on the brainstem, as it is critical for neurologic function and injury can result in severe neurologic symptoms or death.[31–33] Brainstem metastases have largely been excluded from prospective trials of SRS for treatment of brain metastases due to concern that brainstem toxicity would result from radiation doses that are acceptable in the remainder of the brain.[34,35]

Whole-brain and targeted radiation therapy techniques were initially utilized as the primary treatment options for brainstem metastases. A single-institution study of SRS for metastatic melanoma in 1993 described four cases of brainstem SRS.[36] Subsequent case series presented evidence of efficacy and safety of SRS for brainstem metastases.[37–39] Single-institution retrospective studies have provided useful information on local control, median survival, and adverse events.[8,9,18,24,40–47] Koyfman and colleagues at Cleveland Clinic described a series of 43 patients with single brainstem metastases who underwent SRS as the first local treatment (21 patients) or as salvage after previous WBRT (22 patients).[47] These patients were treated at a median prescription dose of 15 (range, 9.6–24) Gy with a mean conformality index of 1.7 and mean heterogeneity index of 1.9. Of the 33 patients with post-treatment MRI scans, radiographic radionecrosis was demonstrated in 2 (6%) patients. No grade 3 or 4 toxicities were observed. Grade 1 or 2 weakness, ataxia, and bleeding from a pin site were noted in 3 patients.

At the time of this review, two multi-institutional analyses of brainstem metastases treated with SRS have been conducted. Trifiletti and colleagues[47] obtained and analyzed the data of 547 patients with 596 SRS-treated brainstem metastases from collaborators in the International Gamma Knife Research Foundation. This cohort had a median dose of 16 Gy prescribed to the 50% isodose line and a median maximum dose of 30 Gy. At 1 year after SRS, local control was achieved in 81.8% of tumors and overall survival at 1 year after SRS was 32.7%. 7.4% of patients experienced treatment-related grade 3 or higher toxicities.[47] Most recently, Chen and colleagues[7] conducted a meta-analysis of data from 32 retrospective studies that included 1,446 patients with 1,590 brainstem metastases, not including the patients described in the 2016 multicenter retrospective study by Trifiletti and colleagues.[47] The brainstem metastases were treated with a median marginal dose of 16 (range, 11–39) Gy in a median of 1 (range, 1–13) fraction. Local control was achieved in 86% of lesions at 1 year in 1,410 patients across 31 studies, and the 1-year overall survival rate was 33% in 1,254 patients across 27 studies. Grade 3 to 5 treatment related toxicities were noted in 2.4% of 1,421 patients across 31 studies. The objective response rate was 59% in 642 patients across 17 studies and 55% of patients had improvement in their symptoms in 323 patients across 13 studies.[7] Figures 2,3 illustrate treatment plans of solitary brainstem metastases.

Figure 2.

T1-weighted MRI images of metastasis in close proximity to midbrain and pons. (A) Sagittal and axial images of patient with melanoma metastatic to the cerebral aqueduct posterior to the midbrain and pons. (B) This lesion was treated with 27 Gy in 3 fractions of linear accelerator-based radiosurgery. MRI, magnetic resonance imaging.

Figure 3.

T1-weighted MRI images of patient with a metastatic lesion in midbrain, before and after radiosurgery. (A) Sagittal and axial images of patient with lung adenocarcinoma metastatic to the central midbrain, (B) treated with 27 Gy in 3 fractions of linear accelerator-based radiosurgery. (C) Significant decrease in size and gadolinium enhancement was noted 6 months following radiosurgery. MRI, magnetic resonance imaging.