Spine Stereotactic Radiosurgery in the Treatment of Metastatic Pheochromocytoma: An Updated Case Series

Abstract

Pheochromocytoma is a rare neuroendocrine tumor most frequently presenting with local disease. Despite aggressive primary treatment, up to 13.5% of patients may develop metastases with the axial skeleton as the most common site. Systemic therapy has historically been inadequate in controlling metastatic pheochromocytoma, thus local palliative radiotherapy has been explored to decrease local symptoms and disease burden. Potential radioresistance with standard fractionated radiation has led to increasing interest in stereotactic radiosurgery (SRS), which may provide more durable local control. Here we report an update on our institutional experience on spine stereotactic radiosurgery (SSRS) of pheochromocytoma spine metastases. A retrospective analysis on patients with metastatic pheochromocytoma treated with SSRS between 2000 and 2017 was performed. Seven patients with 16 treated spinal bone metastases were identified. Follow-up spine magnetic resonance imaging (MRI) was used to evaluate local control. Symptom data and imaging were reviewed to evaluate toxicity. Kaplan-Meier method was used to assess local control and overall survival (OS). Median follow up for treated lesions was 11 months (range 2.2 – 70.8 months). All patients underwent upfront surgical resection of their primary disease. Two patients presented with metastatic disease at the time of initial diagnosis, while the remaining five patients had a median time to first metastasis of 62.9 months (range 19.3 – 178 months). The median age at the time of SSRS treatment was 58 years (range 46 – 68 years). Most lesions were treated to a dose of 27Gy in 3 fractions (62.5%). Other fractionation schemes included 24Gy in 1 fraction (25%), 16Gy in 1 fraction (6.3%) and 18Gy in 3 fractions (6.3%). Treatment sites included the C-spine (18.8%), T-spine (37.5%), L-spine (31.3%) and sacrum (12.5%). The crude local control rate was 93.7%, with one thoracic spine lesion progressing 20.7 months after treatment with 24Gy in 1 fraction. Kaplan-Meier OS at 1 and 2 years after SSRS were 71.4% and 42.9% respectively. The most common toxicities included acute increase in pain and fatigue. There was one case of vertebral fracture in a C-spine lesion treated to 27Gy in 3 fractions, which was managed non-surgically. After updating our previous series with nearly double the number of patients and treated sites, the data continue to suggest SSRS is a safe and effective local treatment for spinal metastatic pheochromocytoma. The durable local control and short treatment course make this approach an attractive option for metastatic foci, where early treatment may manage local symptoms and potentially limit further disease spread. Future studies comparing SSRS with standard fractionation should be considered.