RESULTS OF RADIOSURGICAL AND DRUG TREATMENT OF PATIENTS WITH BRAIN METASTASES

The study objective is to study overall survival and the rate of intracranial recurrences in patients with brain metastases after radiosurgery as single treatment.

Materials and methods. The results of radiosurgical treatment of 579 patients with brain metastases (248 men and 331 women) were analyzed. The sources of brain metastases were breast cancer (164 patients), non-small-cell lung carcinoma (162), melanoma (123), kidney cancer (87), colorectal cancer (43). Median cumulative tumor volume, maximal lesion volume, number of brain metastases in the studied patient group were 5.4 cm3, 3.6 cm3, and 4, respectively. Mean marginal dose of ionizing radiation was 22 Gy (15–24 Gy). Mean follow-up duration was 13.4 months.

Results. Overall survival of patients at 12 and 24 months was 42.8 and 24.8 %, respectively, with median overall survival after radiosurgery of 9.8 months (95 % confidence interval: 8.5–11.3). Local control of metastatic lesions was achieved in 81.3 % patients. Survival without local recurrence at 12 months was 66.7 %. Distant metastases developed in 235 (52.4 %) of 449 patients for whom radiological data was available. Survival without distant metastases at 12 and 24 months was 41.5 and 20.9 %, respectively. Multifactor analysis has shown that prognostic factors for long-term survival in patients with brain metastases were presence of breast cancer metastases in the brain, limited (4 lesions or less) number of brain metastases, high functional status, and absence of extracranial metastases. Increased survival duration was also associated with targeted therapy (p = 0.0412) and repeated radiosurgery to treat intracranial recurrences (р <0.0001).

Conclusion. Radiosurgical treatment of patients with brain metastases confers higher median overall survival (up to 9.8 months) than the same criterion (7.1 months) in the 1st class patients (per the recursive partitioning analysis scale) who received irradiation of the whole brain as single treatment. Repeated radiosurgery in cases of intracranial recurrences and targeted therapy confer increased overall survival of patients with brain metastases.

1. Barnholtz-Sloan J. S., Sloan A. E., Davis F. G. et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004;22(14):2865–72. DOI: 10.1200/JCO. 2004.12.149. PMID: 15254054.

2. Lippitz B., Lindquist C., Paddick I. et al. Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Canc Treat Rev 2014;40(1):48–59. DOI: 10.1016/j.ctrv.2013.05.002. PMID: 23810288.

3. Lo S. S., Clarke J. W., Grecula J. C. et al. Stereotactic radiosurgery alone for patients with 1–4 radioresistant brain metastases. Med Oncol 2011;28(1):439–44. DOI: 10.1007/s12032-010-9670-5.

4. Голанов А. В., Банов С. М., Ветлова Е. Р. Метастатическое поражение головного мозга: изменение парадигмы лучевого лечения. Вопросы онкологии 2015;61 (4):530–45. [Golanov A. V., Banov S. M., Vetlova E. R. Metastatic brain lesion paradigm shift in radiation therapy. Voprosy onkologii = Problems in Oncology 2015;61(4):530–45. (In Russ.)].

5. Vogelbaum M. A., Suh J. H. Resectable brain metastases. J Clin Oncol 2006;8(24):1289–1294. DOI: 10.1200/JCO.2005.04.6235. PMID: 16525184.

6. Yamamoto M., Serizawa T., Shuto T. et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 2014; 15(4):387–95. DOI: 10.1016/S1470–2045(14)70061–0. PMID: 24621620.

7. Andrews D. W., Scott C. B., Sperduto P. W. et al. Whole Brain Radiation Therapy with or Without Stereotactic Radiosurgery Boost for Patients with One to Three Brain Metastases: Phase III Results of the RTOG 9508 Randomised Trial. Lancet (London, England) 2004;363(9422):1665–72. DOI: 10.1016/S0140–6736 (04)16250–8.

8. Muacevic A., Wowra B., Siefert A. et al. Microsurgery Plus Whole Brain Irradiation Versus Gamma Knife Surgery Alone for Treatment of Single Metastases to the Brain: a Randomized Controlled Multicentre Phase III Trial. J Neurooncol 2008;87(3):299–307. DOI: 10.1007/s11060-007-9510-4.

9. Serizawa T., Yamamoto M., Sato Y et al. Gamma Knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study. J Neurosurg 2010;113:48–52. DOI: 10.3171/2010.8. GKS10838. PMID: 21121787.

10. Tendulkar R. D., Liu S. W., Barnett G. H. et al. RPA classification has prognostic significance for surgically resected single brain metastasis. Int J Radiat Oncol Biol Phys 2006;66(3):810–7. DOI: 10.1016/j.ijrobp.2006.06.003. PMID: 17011454.

11. Patchell R. A., Regine W. F. The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases. Technol Cancer Res Treat 2003;2(2):111–5. DOI: 10.1177/153303460300200206. PMID: 12680791.

12. Yu C. P., Cheung J. Y., Chan J. F. et al. Prolonged survival in a subgroup of patients with brain metastases treated by gamma knife surgery. J Neurosurg 2005;102(Suppl.):262–5. DOI: 10.3171/jns.2005.102.s_supplement.0262. PMID: 28306476.

13. Golden D. W., Lamborn K. R., McDermott M.W. et al. Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site. J Neurosurg 2008;109:77–86. DOI: 10.3171/JNS/2008/109/12/S13.

14. Karlsson B., Hanssens P., Wolff R. et al. Thirty years» experience with Gamma Knife surgery for metastases to the brain. J Neurosurg 2009;111(3): 449–57. DOI: 10.3171/2008.10.JNS08214. PMID: 19199505.

15. Lagerwaard F. J., Levendag P. C., Nowak P. J. et al. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 1999;43(4):795–803. PMID: 10098435.

16. Sperduto P. W., Berkey B., Gaspar L. E. et al. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 2008;2(70):510–4. DOI: 10.1016/j.ijrobp.2007.06.074. PMID: 17931798.

17. Aoyama H., Shirato H., Tago M. et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 2006:21(295):2483–91. DOI: 10.1001/jama. 295.21.2483. PMID: 16757720.

18. Kocher M., Soffietti R., Abacioglu U. et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952– 26001 study. J Clin Oncol 2011;2(29):134–41. DOI: 10.1200/JCO. 2010.30.1655. PMID: 21041710.

19. Kwon K. Y., Kong D. S., Lee J. I. et al. Outcome of repeated radiosurgery for recurrent metastatic brain tumors. Clin Neurol Neurosurg 2007;109(2):132–41. DOI: 10.1016/j.clineuro.2006.06.007. PMID: 16930821.

20. Голанов А. В., Банов С. М., Ильялов С. Р. и др. Радиохирургическое лечение метастазов в головной мозг. Факторы прогноза общей выживаемости и интракраниальных рецидивов. Вопросы нейрохирургии им. Н. Н. Бурденко 2016;80(2):35–46. [Golanov A. V., Banov S. M., Ilyalov S. R. et al. Overall survival and intracranial relapse in patients with brain metastases after gamma knife radiosurgery alone. Voprosy neyrokhirurgii imeni N. N. Burdenko = Burdenko»s Journal of Neurosurgery 2016;80(2):35–46. (In Russ.)].

21. Shen C. J., Rigamonti D., Redmond K. J. et al. The strategy of repeat stereotactic radiosurgery without whole brain radiation treatment for new brain metastases. Pract Radiat Onco 2016;6(6):409–16. DOI: 10.1016/j.prro.2016.04.004. PMID: 27687187.

22. Yomo S., Hayashi M., Cho N. Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer. J Neurooncol 2013;112(2):199–207. DOI: 10.1007/s11060-013-1046-1. PMID: 23296546.

23. Johung K. L., Yao X., Li F. et al. A clinical model for identifying radiosensitive tumor genotypes in non-small cell lung cancer. Clin Cancer Res 2013;19(19):5523–32. DOI: 10.1158/1078–0432.CCR-13–0836. PMID: 23897899.

24. Patel K. R., Chowdhary M., Switchenko J. M. et al. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res 2016;26(4):387–94. DOI: 10.1097/CMR. 0000000000000268. PMID: 27223498.

25. Kiess A. P., Wolchok J. D., Barker C. A. et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys 2015;92(2):368–75. DOI: 10.1016/j.ijrobp.2015.01.004. PMID: 25754629.