Are brain metastases a special issue in POLE mutated endometrial cancer? A case series

Christoph Ebner^1*Kristina Lindemann^2,3Gunnar Kristensen^2,4Alice Frosch⁵Hanne Askautrud⁴Gianpaolo Di Santo⁶Katharina Leitner¹Christian Marth¹Alain G. Zeimet^1*

• ¹Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria
• ²Department of surgical oncology, Section for gynecologic oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
• ³Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
• ⁴Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway
• ⁵INNPATH GmbH, Institute of Pathology, Innsbruck, Austria
• ⁶Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria

POLE mutated endometrial cancers have repeatedly shown to harbor an excellent prognosis. Recurrences or primary advanced disease are rare events in this subgroup. We report three cases of POLE mutated endometrioid ECs with brain metastases. While patients with CNS metastases from endometrial cancers are very uncommon and generally confer a poor prognosis and limited survival, all cases presented here, survived substantially longer than the median survival time of patients with brain metastasis published in the literature. All patients responded well to systemic -and radiotherapy. Additionally, we present one case with complete response to only four cycles of pembrolizumab monotherapy. These cases suggest that even in the setting of brain metastases or recurrent disease, a pathogenic POLE mutation remains a marker for excellent clinical outcome. The question of why these tumors metastasized to the brain in the first place remains to be answered by further research.