Stereotactic Radiosurgery for a Patient With 94 Brain Metastases in the Setting of Prior Whole Brain Radiation

The current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. Here, we present our experience treating a young patient with 94 intact brain metastases with SRS in the setting of prior WBRT. A 37-year-old male with metastatic lung adenocarcinoma (PD-L1 5%, EGFR exon 19 deletion) initially presented with a seizure and numerous intracranial metastases and previously completed a course of WBRT to a total dose of 3000 cGy in 10 fractions at an outside hospital. He subsequently started first-line oral osimertinib therapy, with baseline PET/CT showing multiple sites of disease. After 18 months from initial diagnosis and WBRT, the patient presented with 94 new brain metastases while on maintenance osimertinib. He had a Karnofsky performance score of 90, no neurological deficits, and only occasional headaches. His baseline cognitive objective Patient-Reported Outcome Measurement Information System (PROMIS) score was 29/40. Given his age, failure of EGFR-targeted therapy, and prior WBRT, he was planned for single-isocenter multiple target (SIMT) fractionated SRS to all lesions to a total dose of 2400 cGy in three fractions to 91 lesions and 1800 cGy to three brainstem metastases. He was simulated with a Qfix© Encompass mask (Qfix, Avondale, PA, USA) and treated on a Varian Edge linear accelerator utilizing HyperArc (Varian, Palo Alto, CA, USA), a 6DOF robotic couch with daily CBCT, and a Varian Optical Surface Monitoring System. A planning target volume (PTV) was created using a 2 mm margin around the GTV, with a smaller margin of 1 mm for brainstem metastases. The total GTV was 8.6 cc and PTV was 40.1 cc. He tolerated SRS well with no acute side effects. Due to progressive systemic disease, he transitioned to atezolizumab, paclitaxel, carboplatin, and bevacizumab combination therapy. Follow-up MRI imaging at two and five months was consistent with post-treatment changes, with no increase in the volume or number of brain metastases. His serial PROMIS scores were 29, 29, and 26 at three, six, and nine months of follow-up, respectively. At the last follow-up, 11 months after SRS, he remained free of headaches or new neurological symptoms. Due to the systemic progression of the disease, he transitioned to comfort care 30 months after BM diagnosis and 11 months after SRS. This case illustrates one of the largest numbers of metastases treated in a single course of SRS, and this treatment was well tolerated, with no significant cognitive decline, resulting in a comparable survival outcome to contemporary studies evaluating WBRT in this population.