New treatment options for patients with brain metastases from ovarian cancer

Brain metastases from ovarian cancer are quite rare: they affect no more than 0.5–3.0 % of patients according to the literature. However, the incidence of brain metastasis is increasing, which is attributed to longer survival of ovarian cancer patients and more accurate diagnosis. It is not possible to predict metastasis to the central nervous system, because reliable prognostic biomarkers have not been identified so far, although there have been some achievements in the treatment of such patients. Novel pathological and molecular tumor markers allow doctors to plan individual treatment for each patient and ensure good outcome. Many authors recommend combination treatment that includes surgical resection of the cerebral lesion followed by local radiotherapy alone or in combination with pharmacotherapy. The majority of these patients had high-grade serous ovarian carcinoma (HGSOC) and initially responded to chemotherapy with platinum and taxanes, while brain metastases were detected 2 to 4 years after treatment initiation. Mutations in the BRCA1 and BRCA2 genes, as well as expression of androgen receptors in the primary tumor, may be the risk factors for metastases to the central nervous system and, therefore, should determine further treatment strategy. In this article, we analyzed 3 cases of ovarian cancer with brain metastases.

1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7–30.

2. Malignant tumors in Russia in 2019. Ed. by A.D. Kaprin, V.V. Starinskiy, A.O. Shakhzodova. Moscow: P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center of Ministry of Health of Russia, 2020. 252 p. (In Russ.).

3. Van Baal J., van Noorden C.J.F., Nieuwland R. et al. Development of peritoneal carcinomatosis in epithelial ovarian cancer: A review. J Histochem Cytochem 2018;66:67–83. DOI: 10.1369/0022155417742897.

4. Nayak L., Lee E.Q., Wen P.Y. Epidemiology of brain metastases. Curr Oncol Rep 2012;14:48–54. DOI: 10.1007/s11912-011-0203-y.

5. Borella F., Bertero L., Morrone A. et al. Brain metastases from ovarian cancer: current evidence in diagnosis, treatment, and prognosis. Cancers 2020;12:2156. DOI: 10.3390/cancers12082156.

6. Shaw E., Scott C., Souhami L. et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 2000;47:291–8. DOI: 10.1016/s0360-3016(99)00507-6.

7. Pakneshan S., Safarpour D., Tavassoli F., Jabbari B. Brain metastasis from ovarian cancer: A systematic review. J Neurooncol 2014;119:1–6. DOI: 10.1007/s11060-014-1447-9.

8. Sehouli J., Pietzner K., Harter P. et al. Prognostic role of platinum sensitivity in patients with brain metastases from ovarian cancer: Results of a German multicenter study. Ann Oncol 2010;21:2201–5.

9. Da Costa A., Dos Santos E.S., Cotrim D.P. et al. Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis. BMC Cancer 2019;19:1194.

10. Marchetti C., Ferrandina G., Cormio G. et al. Brain metastases in patients with EOC: Clinico-pathological and prognostic factors. A multicentric retrospective analysis from the MITO group (MITO 19). Gynecol Oncol 2016;143:532–38. DOI: 10.1016/j.ygyno.2016.09.025.

11. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609–15. DOI: 10.1038/nature10166.

12. Xu K., Yang S., Zhao Y. et al. Prognostic significance of BRCA mutations in ovarian cancer: An updated systematic review with meta-analysis. Oncotarget 2017;8:285–302.

13. Ratner E., Bala M., Louie-Gao M. et al. Increased risk of brain metastases in ovarian cancer patients with BRCA mutations. Gynecol Oncol 2019;153:568–73. DOI: 10.1016/j.ygyno.2019.03.004.

14. Kim M., Kizilbash S.H., Laramy J.K. et al. Barriers to effective drug treatment for brain metastases: A multifactorial problem in the delivery of precision medicine. Pharm Res 2018;35:177. DOI: 10.1007/s11095-018-2455-9.

15. Tentori L., Leonetti C., Scarsella M. et al. Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res 2003;9:5370–9.

16. O’Sullivan C.C., Davarpanah N.N., Abraham J., Bates S.E. Current challenges in the management of breast cancer brain metastases. Semin Oncol 2017;44:85–100.

17. Ray-Coquard I., Pautier P., Pignata S. et al. Olaparib plus bevacizumab as firstline maintenance in ovarian cancer. N Engl J Med 2019;381:2416–28. DOI: 10.1056/NEJMoa1911361.