J Korean Neurosurg Soc.  2013 Oct;54(4):329-335. 10.3340/jkns.2013.54.4.329.

Clinical Outcome in Gamma Knife Radiosurgery for Metastatic Brain Tumors from the Primary Breast Cancer : Prognostic Factors in Local Treatment Failure and Survival

• Choi SW
• Kwon DH
• Kim CJ

• KMID: 1499339
• DOI: http://doi.org/10.3340/jkns.2013.54.4.329

Abstract

OBJECTIVE
Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer.
METHODS
From March 2001 to May 2011, 124 women with metastatic brain lesions originating from a primary breast cancer underwent GKRS at a tertiary medical center in Seoul, Korea. All patients had radiosurgery as a primary treatment or salvage therapy. We retrospectively reviewed their clinical outcomes and radiological responses. The end point of this study was the date of patient's death or the last follow-up examination.
RESULTS
In total, 106 patients (268 lesions) were available for follow-up imaging. The median follow-up time was 7.5 months. The mean treated tumor volume at the time of GKRS was 6273 mm3 (range, 4.5-27745 mm3) and the median dose delivered to the tumor margin was 22 Gy (range, 20-25 Gy). Local recurrence was assessed in 86 patients (216 lesions) and found to have occurred in 36 patients (83 lesions, 38.6%) with a median time of 6 months (range, 4-16 months). A treated tumor volume >5000 mm3 was significantly correlated with poor local tumor control through a multivariate analysis (hazard risk=7.091, p=0.01). Overall survival was 79.9%, 48.3%, and 15.3% at 6, 12, and 24 months, respectively. The median overall survival was 11 months after GKRS (range, 6 days-113 months). Multivariate analysis showed that the pre-GKRS Karnofsky performance status, leptomeningeal seeding prior to initial GKRS, and multiple metastatic lesions were significant prognostic factors for reduced overall survival (hazard risk=1.94, p=0.001, hazard risk=7.13, p<0.001, and hazard risk=1.46, p=0.046, respectively).
CONCLUSION
GKRS has shown to be an effective and safe treatment modality for treating brain metastases of primary breast cancer. Most metastatic brain lesions initially respond to GKRS, though, many patients have further CNS progression in subsequent periods. Patients with poor Karnofsky performance status and multiple metastatic lesions are at risk of CNS progression and poor survival, and a more frequent and strict surveillance protocol is suggested in such high-risk groups.

Keyword

Breast cancer; Metastases; Gamma knife radiosurgery; Prognosis

MeSH Terms

Brain Neoplasms*
Brain*
Breast Neoplasms*
Breast*
Female
Follow-Up Studies
Humans
Karnofsky Performance Status
Korea
Mortality
Multivariate Analysis
Neoplasm Metastasis
Prognosis
Radiosurgery*
Recurrence
Retrospective Studies
Salvage Therapy
Treatment Failure*
Tumor Burden

Reference

1. Altundag K, Bondy ML, Mirza NQ, Kau SW, Broglio K, Hortobagyi GN, et al. Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis. Cancer. 2007; 110:2640–2647. PMID: 17960791.

2. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases : a randomized controlled trial. JAMA. 2006; 295:2483–2491. PMID: 16757720.

3. Bartsch R, Berghoff A, Pluschnig U, Bago-Horvath Z, Dubsky P, Rottenfusser A, et al. Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. Br J Cancer. 2012; 106:25–31. PMID: 22127284.

4. Cairncross JG, Kim JH, Posner JB. Radiation therapy for brain metastases. Ann Neurol. 1980; 7:529–541. PMID: 7436358.

5. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation : a randomised controlled trial. Lancet Oncol. 2009; 10:1037–1044. PMID: 19801201.

6. Dawood S, Broglio K, Esteva FJ, Ibrahim NK, Kau SW, Islam R, et al. Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol. 2008; 19:1242–1248. PMID: 18334512.

7. DiStefano A, Yong Yap Y, Hortobagyi GN, Blumenschein GR. The natural history of breast cancer patients with brain metastases. Cancer. 1979; 44:1913–1918. PMID: 498057.

8. Dyer MA, Kelly PJ, Chen YH, Pinnell NE, Claus EB, Lee EQ, et al. Importance of extracranial disease status and tumor subtype for patients undergoing radiosurgery for breast cancer brain metastases. Int J Radiat Oncol Biol Phys. 2012; 83:e479–e486. PMID: 22704705.

9. Firlik KS, Kondziolka D, Flickinger JC, Lunsford LD. Stereotactic radiosurgery for brain metastases from breast cancer. Ann Surg Oncol. 2000; 7:333–338. PMID: 10864339.

10. Heitz F, Harter P, Lueck HJ, Fissler-Eckhoff A, Lorenz-Salehi F, Scheil-Bertram S, et al. Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. Eur J Cancer. 2009; 45:2792–2798. PMID: 19643597.

11. Kallioniemi OP, Holli K, Visakorpi T, Koivula T, Helin HH, Isola JJ. Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer. 1991; 49:650–655. PMID: 1682277.

12. Kelly PJ, Lin NU, Claus EB, Quant EC, Weiss SE, Alexander BM. Salvage stereotactic radiosurgery for breast cancer brain metastases : outcomes and prognostic factors. Cancer. 2012; 118:2014–2020. PMID: 21918959.

13. Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010; 28:3271–3277. PMID: 20498394.

14. Kondziolka D, Kano H, Harrison GL, Yang HC, Liew DN, Niranjan A, et al. Stereotactic radiosurgery as primary and salvage treatment for brain metastases from breast cancer. Clinical article. J Neurosurg. 2011; 114:792–800. PMID: 20887087.

15. Markesbery WR, Brooks WH, Gupta GD, Young AB. Treatment for patients with cerebral metastases. Arch Neurol. 1978; 35:754–756. PMID: 718475.

16. Matsunaga S, Shuto T, Kawahara N, Suenaga J, Inomori S, Fujino H. Gamma Knife surgery for metastatic brain tumors from primary breast cancer: treatment indication based on number of tumors and breast cancer phenotype. J Neurosurg. 2010; 113(Suppl):65–72. PMID: 21121788.

17. Nieder C, Marienhagen K, Astner ST, Molls M. Prognostic scores in brain metastases from breast cancer. BMC Cancer. 2009; 9:105. PMID: 19351389.

18. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain : a randomized trial. JAMA. 1998; 280:1485–1489. PMID: 9809728.

19. Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, et al. Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol. 2006; 17:935–944. PMID: 16603601.

20. Sneed PK, Lamborn KR, Forstner JM, McDermott MW, Chang S, Park E, et al. Radiosurgery for brain metastases : is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys. 1999; 43:549–558. PMID: 10078636.

21. Sundgren PC. MR spectroscopy in radiation injury. AJNR Am J Neuroradiol. 2009; 30:1469–1476. PMID: 19369613.

22. Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med. 2008; 49:694–699. PMID: 18413375.

23. Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer. 2006; 107:696–704. PMID: 16826579.

24. Tsuyuguchi N, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Takami T, et al. Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery : is a differential diagnosis possible? J Neurosurg. 2003; 98:1056–1064. PMID: 12744366.