Stereotactic radiosurgery for pancreatic neuroendocrine tumor brain Metastases: Systematic review and Illustrative case presentation

Abstract

Background: Neuroendocrine tumor (NET) brain metastases (BM) are rare malignancies which frequently bear a poor prognosis and have the potential to secrete hormones. The optimal treatment approach for these metastases remains unclear, with significant heterogeneity occurring both across and within primary tumor types, and outcome data are limited. Pancreatic neuroendocrine tumor (pNET) BM may be particularly aggressive. While stereotactic radiosurgery (SRS) for other NET BM has previously been described, no report has specifically investigated SRS for management of pNET BM.

Methods: A comprehensive literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms included ("neuroendocrine tumor" OR "neuroendocrine neoplasm" OR "neuroendocrine carcinoma" OR "NET") AND ("brain metastasis" OR "brain metastases" OR "intracranial metastases") AND ("stereotactic radiosurgery" OR "stereotactic body" OR "CyberKnife" OR "GammaKnife").

Results: Our search strategy yielded 230 articles. After screening, a total of 16 articles with 256 patients were identified. Number of patients per study cohort ranged from 1 to 101 (mean = 16). Ten articles were single case reports. The most commonly investigated primary site was lung (5 studies), followed by skin (2 case reports), and uterine cervix (2 case reports). Median survival post-SRS ranged from 5 to 42 months. Median tumor volume ranged from 0.08 cm³ to 33.62 cm³. Local control rate was provided in 3 of 6 of the reviewed retrospective analyses. A pulmonary cohort of 101 patients reported a recurrence rate of 13.8 % at 12 months. A pulmonary case series similarly reported local progression in only 1 of 8 patients. The mixed primary cohort (33 patients) had a long-term local failure rate of 16.7 %. In addition, we describe a first reported individual case of pNET BM treated with SRS. Nearly 6-years after initial pNET diagnosis, multiple intracranial enhancing lesions were found, which were subsequently treated with SRS. Follow-up imaging demonstrated a statistically significant decrease in lesion diameter (p < 0.001), with none of the 18 BM progressing.

Conclusion: Given the recently increase in age-adjusted incidence of NET BM, determining an optimal treatment approach for these malignancies is of growing importance. Prognosis generally remains poor, with BM being a significant predictor of overall survival. Our review indicated large variability in outcomes both between and within primary tumor types, suggesting a need for further investigation of predictive molecular biomarkers. In addition, to the authors' knowledge, this represents the first reported case of pNET BM successfully treated with SRS.

Keywords: Brain metastases; Neuroendocrine tumor; Pancreatic neuroendocrine tumor; Stereotactic radiosurgery.