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Trastuzumab emtansine increases the risk of stereotactic radiosurgery-induced radionecrosis in HER2 + breast cancer

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Abstract

Introduction

In this study, we investigate factors associated with radionecrosis (RN) in HER2 + (human epidermal growth factor receptor 2) patients with brain metastases (BrM) treated with stereotactic radiosurgery (SRS).

Methods

Patients with HER2 + breast cancer BrM treated with SRS (2010–2020) were identified from an institutional database. The incidence of RN was determined per treated BrM according to serial imaging and/or histology. Factors associated with RN such as age, RT dose, BrM volume, and initiation of Trastuzumab Emtansine (T-DM1) were investigated with univariate and multivariable analyses (MVA).

Results

67 HER2 + patients with 223 BrM were identified. 21 patients (31.3%) were treated with T-DM1 post-SRS, including 14 patients (20.9%) who received T-DM1 within 12 months of SRS. The median follow-up was 15.6 (interquartile range (IQR) 5.4–35.3) months. The overall probability of RN post-SRS was 21.6% (95% confidence interval (CI) 2.7–10.7), and the 1 and 2 year risk was 6.7% (95% CI 2.7–10.7) and 15.2% (95% CI 9.2–21.3). MVA identified T-DM1 treatment post-SRS (hazard ratio (HR) 2.5, 95% CI 1.2–5.3, p = 0.02) and equivalent dose in 2 Gy fractions (EQD2) > 90 Gy2 (HR 2.4, 95% CI 1.1–5.1, p = 0.02) as predictors of RN. Patients treated with T-DM1 and SRS had a 29.9% (95% CI 15.3–44.6%) probability of RN, with a 25.2% (95% CI 12.8–37.6%) risk at 1- and 2 years post-T-DM1. The majority of RN were symptomatic (71%), with a median time to RN of 4.8 months.

Conclusion

T-DM1 exposure post-SRS was associated with a higher risk of RN among patients with HER2 + BrM.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, 2075 Bayview Ave., T2 181, Toronto, ON, M4N 3M5, Canada

    Badr Id Said, Hanbo Chen, Sten Myrehaug, Chia-Lin Tseng, Jay Detsky, Zain Husain, Arjun Sahgal & Hany Soliman

  2. Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada

    Katarzyna J. Jerzak & Ellen Warner

Authors
  1. Badr Id Said
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by BIS, HC, KJ and HS. The first draft of the manuscript was written by BIS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hany Soliman.

Ethics declarations

Conflict of interest

BI (none), HC (none), KJJ (advisor: Amgen, AzstraZeneca, Apo Biologix, Eli Lily, Esai, Genomic Health, Knight Therapeutics,Merck. Myriad Genetics Inc, Noveratis, Purdue Pharma, Pfizer, Roche, Seagen; grant: Aztra Zeneca, Eli Lilly, Seagen), EW (none), SM (none), CLT (advisor: Sanofi, Elekta MR-linac consortium), JD (none), ZH (none), AJ (advisor: Gamma Knife Icon, honoraria: Astra Zeneca, BrainLAB, Elekta AB; grant: Elekta, BrainLAB, Varian), HS (none)

Ethical approval

This study received REB approval prior to study initiation.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Id Said, B., Chen, H., Jerzak, K.J. et al. Trastuzumab emtansine increases the risk of stereotactic radiosurgery-induced radionecrosis in HER2 + breast cancer. J Neurooncol 159, 177–183 (2022). https://doi.org/10.1007/s11060-022-04055-y

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