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


Edema, hemorrhage, and radionecrosis are the underlying mechanisms of adverse events following SRS. The most frequently reported toxicities after brainstem SRS are postprocedure headache (which may be associated with head frame placement), fatigue, nausea, vomiting, which are usually self-limited or effectively treated with corticosteroids.[40,48] Confusion, ataxia, weakness, focal neurologic deficits, and seizures have also been reported.[24,41,42,45] Yoo and colleagues reported one death from a hemorrhagic tumor following Gamma Knife SRS to a pontine lesion treated with 14.8 Gy.[22] Adverse effects that were reported in the literature are summarized in Table 3. A case of radiation necrosis after WBRT with SRS boost to brainstem metastasis is described in Figure 4. Despite steroids, there was progression of the presumed radiation necrosis. She subsequently passed away with an abrupt decline in her functional and neurologic status.

Figure 4.

A 52-year-old female with 1.2 cm diameter midbrain metastasis from squamous cell lung cancer, treated with WBRT to 37.5 Gy with SRS boost of 15 Gy to the brainstem metastasis. (A) MRI at diagnosis of brain metastasis. (B) MRI at time of SRS boost. (C) MRI 4 months post-SRS shows improvement. (D) MRI and (E) MR perfusion images consistent with radiation necrosis after patient developed worsening headaches (note negative cerebral blood volume). WBRT, whole-brain radiation therapy; SRS, stereotactic radiosurgery; MRI, magnetic resonance imaging; MR, magnetic resonance.

Rates of adverse events after brainstem SRS ranged from 0% to 27% in 31 single-institution retrospective studies analyzed by Chen and colleagues, with an overall 5.6% rate of symptomatic adverse effects and 2.4% rate of grade 3 to 5 toxicities in 1,421 patients.[7]

Trifiletti and colleagues[47] reported that 7.4% of their cohort experienced grade 3–5 toxicities. These rates are comparable to the 3–8% toxicity rates reported in prospective randomized/observational trials for SRS for all brain metastases. However, brainstem SRS appears to have a shorter median time to development of toxicity (3 months) compared to cerebral lesions (4.5 months).[53]

Individual risk factors, particularly prior WBRT, may influence the incidence of posttreatment toxicities. Of the 44 patients in the Trifiletti study[47] who developed a severe toxicity, 84% had undergone WBRT before brainstem SRS. The authors also found that an interval of at least 4.5 months between WBRT and brainstem SRS was associated with lower risk of toxicity (odds ratio, 0.116). Increased tumor volume and higher margin dose have also been reported as risk factors.[18]