Vol 26, No 1 (2021)
Research paper
Published online: 2021-01-22

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Stereotactic radiosurgery for patients with breast cancer brain oligometastases — molecular subtypes and clinical outcomes

Ivica Ratosa1, Marija Skoblar Vidmar1
Rep Pract Oncol Radiother 2021;26(1):1-11.

Abstract

Background: We sought to determine the clinical outcomes of patients with breast cancer (BC) who had undergone stereotactic radiosurgery (SRS) for a limited number of brain metastases (BM) and to identify factors influencing overall survival (OS) and local control.

Materials and methods: The records of 45 patients who underwent SRS for 72 brain lesions were retrospectively evaluated. Statistics included the chi-squared test, Kaplan-Meier method, and the multivariate Cox model.

Results: The median number of treated BM was 2 (range 1–10). Median OS from BM diagnosis and post-SRS were 27.6 [95% confidence interval (CI): 14.8–40.5) and 18.5 months (95% CI: 11.1–25.8), respectively. One-year and two-year survival rates after BM diagnosis were 55% and 41%, respectively. In a univariate analysis, the Luminal-B-human-epidermal-growth-receptor-positive (HER2+) subtype had the longest median OS at 39.1 months (95% CI: 34.1–44.1, p = 0.004). In an adjusted analysis, grade 2 [hazard ratio (HR): 0.1; 95% CI: 0.1–0.6, p = 0.005), craniotomy (HR: 0.3; 95% CI: 0.1–0.7; p = 0.006), and ≥ 2 systemic therapies received (HR: 0.3; 95% CI: 0.1–0.9, p = 0.028) were associated with improved OS. One-year and two-year intracranial progression-free survival rates were 85% and 63%, respectively. Four factors for a higher risk of any intracranial recurrence remained significant in the adjusted analysis, as follows: age < 50 years (HR: 4.2; 95% CI: 1.3–36.3; p = 0.014), grade 3 (HR: 3.7; 95% CI: 1.1–13.2; p = 0.038), HER2+ (HR: 6.9; 95% CI: 1.3–36.3; p = 0.023), and whether the brain was the first metastatic site (HR: 4.7; 95% CI: 1.6–14.5; p = 0.006).

Conclusion: Intrinsic BC characteristics are important determinants for both survival and intracranial control for patients undergoing SRS for oligometastatic brain disease.

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References

  1. Berman AT, Thukral AD, Hwang WT, et al. Incidence and patterns of distant metastases for patients with early-stage breast cancer after breast conservation treatment. Clin Breast Cancer. 2013; 13(2): 88–94.
  2. Martin AM, Cagney DN, Catalano PJ, et al. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study. JAMA Oncol. 2017; 3(8): 1069–1077.
  3. Darlix A, Louvel G, Fraisse J, et al. Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort. Br J Cancer. 2019; 121(12): 991–1000.
  4. Znidaric T, Gugic J, Marinko T, et al. Breast cancer patients with brain metastases or leptomeningeal disease: 10-year results of a national cohort with validation of prognostic indexes. Breast J. 2019; 25(6): 1117–1125.
  5. Griguolo G, Jacot W, Kantelhardt E, et al. External validation of Modified Breast Graded Prognostic Assessment for breast cancer patients with brain metastases: A multicentric European experience. Breast. 2018; 37: 36–41.
  6. Cagney DN, Lamba N, Montoya S, et al. Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases. Breast Cancer Res Treat. 2019; 176(1): 171–179.
  7. Lee YT. Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol. 1983; 23(3): 175–180.
  8. Sundquist M, Brudin L, Tejler G. Improved survival in metastatic breast cancer 1985-2016. Breast. 2017; 31: 46–50.
  9. 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; 295(21): 2483–2491.
  10. 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; 29(2): 134–141.
  11. Shinde A, Akhavan D, Sedrak M, et al. Shifting paradigms: whole brain radiation therapy versus stereotactic radiosurgery for brain metastases. CNS Oncol. 2019; 8(1): CNS27.
  12. Grandhi R, Kondziolka D, Panczykowski D, et al. Stereotactic radiosurgery using the Leksell Gamma Knife Perfexion unit in the management of patients with 10 or more brain metastases. J Neurosurg. 2012; 117(2): 237–245.
  13. Brown PD, Gondi V, Pugh S, et al. for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020; 38(10): 1019–1029.
  14. 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(2): 291–298.
  15. Sobin LH, Gospodarowicz MK, Wittekind CH. Classification of Malignant Tumours. 7th ed. International Union Against Cancer. John Wiley and Sons 2009.
  16. Subbiah IM, Lei X, Weinberg JS, et al. Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases. J Clin Oncol. 2015; 33(20): 2239–2245.
  17. Senkus E, Kyriakides S, Ohno S, et al. ESMO Guidelines Committee. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5: v8–30.
  18. Abu-Khalaf M, Muralikrishnan S, Hatzis C, et al. Breast cancer patients with brain metastasis undergoing GKRS. Breast Cancer. 2019; 26(2): 147–153.
  19. Cagney DN, Lamba N, Montoya S, et al. Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases. Breast Cancer Res Treat. 2019; 176(1): 171–179.
  20. Cho E, Rubinstein L, Redman M, et al. Differentiation of overall survival by breast cancer tumor subtype following stereotactic radiosurgery for brain metastasis. J Clin Oncol. 2014; 32(15_suppl): e11584–e11584.
  21. Armstrong K, Ward J, Dunne M, et al. Linac-Based Radiosurgery for Patients With Brain Oligometastases From a Breast Primary, in the Trastuzumab Era-Impact of Tumor Phenotype and Prescribed SRS Dose. Front Oncol. 2019; 9: 377.
  22. Wilson TG, Robinson T, MacFarlane C, et al. Treating Brain Metastases from Breast Cancer: Outcomes after Stereotactic Radiosurgery. Clin Oncol (R Coll Radiol). 2020; 32(6): 390–396.
  23. Yang TJ, Oh JH, Folkert MR, et al. Outcomes and prognostic factors in women with 1 to 3 breast cancer brain metastases treated with definitive stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2014; 90(3): 518–525.
  24. Cho E, Rubinstein L, Stevenson P, et al. The use of stereotactic radiosurgery for brain metastases from breast cancer: who benefits most? Breast Cancer Res Treat. 2015; 149(3): 743–749.
  25. Chang E, Wefel J, Hess K, 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(11): 1037–1044.
  26. Kased N, Binder DK, McDermott MW, et al. Gamma Knife radiosurgery for brain metastases from primary breast cancer. Int J Radiat Oncol Biol Phys. 2009; 75(4): 1132–1140.
  27. Grubb CS, Jani A, Wu CC, et al. Breast cancer subtype as a predictor for outcomes and control in the setting of brain metastases treated with stereotactic radiosurgery. J Neurooncol. 2016; 127(1): 103–110.
  28. Abraham C, Garsa A, Badiyan SN, et al. Internal dose escalation is associated with increased local control for non-small cell lung cancer (NSCLC) brain metastases treated with stereotactic radiosurgery (SRS). Adv Radiat Oncol. 2018; 3(2): 146–153.
  29. Tomé W, Fowler J. Selective boosting of tumor subvolumes. Int J Radiat Oncol Biol Phys. 2000; 48(2): 593–599.
  30. Krop IE, Lin NU, Blackwell K, et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol. 2015; 26(1): 113–119.
  31. Stemmler HJ, Kahlert S, Siekiera W, et al. Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer. Breast. 2006; 15(2): 219–225.
  32. Parsai S, Miller JA, Juloori A, et al. Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases. J Neurosurg. 2019; 132(2): 503–511.
  33. Shah N, Mohammad AS, Saralkar P, et al. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. Pharmacol Res. 2018; 132: 47–68.
  34. Ma R, Levy M, Gui B, et al. Risk of leptomeningeal carcinomatosis in patients with brain metastases treated with stereotactic radiosurgery. J Neurooncol. 2018; 136(2): 395–401.
  35. Prabhu RS, Turner BE, Asher AL, et al. A Multi-Institutional Analysis of Presentation and Outcomes for Leptomeningeal Disease Recurrence After Surgical Resection and Radiosurgery for Brain Metastases. Neuro Oncol. 2019 [Epub ahead of print].



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