Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated With Stereotactic Radiosurgery

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jun 7

PMID 35669439

Authors

Christine Park

Evan D Buckley

Amanda E D Van Swearingen

Will Giles

James E Herndon

John P Kirkpatrick

Carey K Anders

Scott R Floyd

Affiliations

Soon will be listed here.

Abstract

Background: There is a concern that HER2-directed systemic therapies, when administered concurrently with stereotactic radiosurgery (SRS), may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ breast cancer brain metastasis (BCBrM).

Methods: This was a single-institution, retrospective study including patients >18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 and with at least 12-month post-SRS follow-up. Presence of RN was determined imaging at one-year post-SRS, with confirmation by biopsy in some patients. Demographics, radiotherapy parameters, and timing ("during" defined as four weeks pre- to four weeks post-SRS) and type of systemic therapy (e.g., chemotherapy, HER2-directed) were evaluated.

Results: Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not based on imaging criteria. Of the 11 patients who underwent biopsy, 10/10 (100%) who were diagnosed with RN on imaging were confirmed to be RN positive on biopsy and 1/1 (100%) who was not diagnosed with RN was confirmed to be RN negative on biopsy. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (including total dose, fractionation, CTV and size target volume, all >0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, =0.97) did not differ between patients who did or did not develop RN. However, there was a trend for patients who developed RN to have received more than one agent of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, =0.08). Moreover, a significantly higher proportion of those who developed RN received more than one agent of HER2-directed therapy SRS treatment compared to those who did not develop RN (35.7% vs 5.6%, =0.047).

Conclusions: Patients with HER2 BCBrM who receive multiple HER2-directed therapies during SRS for BCBrM may be at higher risk of RN. Collectively, these data suggest that, in the eight-week window around SRS administration, if HER2-directed therapy is medically necessary, it is preferable that patients receive a single agent.

Citing Articles

Neurotoxicity from Old and New Radiation Treatments for Brain Tumors.

Soffietti R, Pellerino A, Bruno F, Mauro A, Ruda R Int J Mol Sci. 2023; 24(13).

PMID: 37445846 PMC: 10342178. DOI: 10.3390/ijms241310669.

Novel Mechanisms and Future Opportunities for the Management of Radiation Necrosis in Patients Treated for Brain Metastases in the Era of Immunotherapy.

Vaios E, Winter S, Shih H, Dietrich J, Peters K, Floyd S Cancers (Basel). 2023; 15(9).

PMID: 37173897 PMC: 10177360. DOI: 10.3390/cancers15092432.

Radiotherapeutic Strategies to Overcome Resistance of Breast Cancer Brain Metastases by Considering Immunogenic Aspects of Cancer Stem Cells.

Hintelmann K, Petersen C, Borgmann K Cancers (Basel). 2023; 15(1).

PMID: 36612206 PMC: 9818478. DOI: 10.3390/cancers15010211.

References

Kim J, Miller J, Kotecha R, Chao S, Ahluwalia M, Peereboom D . Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis. Neuro Oncol. 2019; 21(5):659-668. PMC: 6502492. DOI: 10.1093/neuonc/noz006. View

Blonigen B, Steinmetz R, Levin L, Lamba M, Warnick R, Breneman J . Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2009; 77(4):996-1001. DOI: 10.1016/j.ijrobp.2009.06.006. View

Geraud A, Xu H, Beuzeboc P, Kirova Y . Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer. J Neurooncol. 2016; 131(1):69-72. DOI: 10.1007/s11060-016-2265-z. View

Sayan M, Mustafayev T, Balmuk A, Mamidanna S, Kefelioglu E, Gungor G . Management of symptomatic radiation necrosis after stereotactic radiosurgery and clinical factors for treatment response. Radiat Oncol J. 2020; 38(3):176-180. PMC: 7533401. DOI: 10.3857/roj.2020.00171. View

Shah R, Vattoth S, Jacob R, Manzil F, OMalley J, Borghei P . Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence. Radiographics. 2012; 32(5):1343-59. DOI: 10.1148/rg.325125002. View

Quigley M, Fukui O, Chew B, Bhatia S, Karlovits S . The shifting landscape of metastatic breast cancer to the CNS. Neurosurg Rev. 2012; 36(3):377-82. DOI: 10.1007/s10143-012-0446-6. View

Kennecke H, Yerushalmi R, Woods R, Chon U Cheang M, Voduc D, Speers C . Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010; 28(20):3271-7. DOI: 10.1200/JCO.2009.25.9820. View

Tabouret E, Chinot O, Metellus P, Tallet A, Viens P, Goncalves A . Recent trends in epidemiology of brain metastases: an overview. Anticancer Res. 2012; 32(11):4655-62. View

Murthy R, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz S . Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2019; 382(7):597-609. DOI: 10.1056/NEJMoa1914609. View

10.

Vellayappan B, Tan C, Yong C, Khor L, Koh W, Yeo T . Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases. Front Oncol. 2018; 8:395. PMC: 6172328. DOI: 10.3389/fonc.2018.00395. View

11.

Nieder C, Grosu A, Gaspar L . Stereotactic radiosurgery (SRS) for brain metastases: a systematic review. Radiat Oncol. 2014; 9:155. PMC: 4107473. DOI: 10.1186/1748-717X-9-155. View

12.

Gori S, Rimondini S, De Angelis V, Colozza M, Bisagni G, Moretti G . Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist. 2007; 12(7):766-73. DOI: 10.1634/theoncologist.12-7-766. View

13.

Lin N, Gaspar L, Soffietti R . Breast Cancer in the Central Nervous System: Multidisciplinary Considerations and Management. Am Soc Clin Oncol Educ Book. 2017; 37:45-56. DOI: 10.1200/EDBK_175338. View

14.

Modi S, Saura C, Yamashita T, Park Y, Kim S, Tamura K . Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2019; 382(7):610-621. PMC: 7458671. DOI: 10.1056/NEJMoa1914510. View

15.

Giglio P, Gilbert M . Cerebral radiation necrosis. Neurologist. 2003; 9(4):180-8. DOI: 10.1097/01.nrl.0000080951.78533.c4. View

16.

Nonoguchi N, Miyatake S, Fukumoto M, Furuse M, Hiramatsu R, Kawabata S . The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles. J Neurooncol. 2011; 105(2):423-31. DOI: 10.1007/s11060-011-0610-9. View

17.

Sneed P, Mendez J, Vemer-van den Hoek J, Seymour Z, Ma L, Molinaro A . Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. J Neurosurg. 2015; 123(2):373-86. DOI: 10.3171/2014.10.JNS141610. View

18.

SHELINE G, Wara W, Smith V . Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980; 6(9):1215-28. DOI: 10.1016/0360-3016(80)90175-3. View

19.

Minniti G, Clarke E, Lanzetta G, Osti M, Trasimeni G, Bozzao A . Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011; 6:48. PMC: 3108308. DOI: 10.1186/1748-717X-6-48. View

20.

Chin L, Ma L, DiBiase S . Radiation necrosis following gamma knife surgery: a case-controlled comparison of treatment parameters and long-term clinical follow up. J Neurosurg. 2001; 94(6):899-904. DOI: 10.3171/jns.2001.94.6.0899. View