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Impact of concurrent antibody–drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study

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Abstract   

Aim

We aimed to investigate the impact of concurrent antibody–drug conjugates (ADC) and radiotherapy on symptomatic radiation necrosis (SRN) in breast cancer patients with brain metastases (BM).

Methods

This multicenter retrospective study uses four institutional data. Eligibility criteria were histologically proven breast cancer, diagnosed BM with gadolinium-enhanced MRI, a Karnofsky performance status of 60 or higher, and radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. Concurrent ADC was defined as using ADC within four weeks before or after radiotherapy. The cumulative incidence of SRN until December 2023 with death as a competing event was compared between the groups with and without concurrent ADC. Multivariable analysis was performed using the Fine-Gray model.

Results

Among the 168 patients enrolled, 48 (29%) received ADC, and 19 (11%) had concurrent ADC. Of all, 36% were HER2-positive, 62% had symptomatic BM, and 33% had previous BM radiation histories. In a median follow-up of 31 months, 18 SRNs (11%) were registered (11 in grade 2 and 7 in grade 3). The groups with and without concurrent ADC had 5 SRNs in 19 patients and 13 SRNs in 149, and the two-year cumulative incidence of SRN was 27% vs. 7% (P = 0.014). Concurrent ADC was associated with a higher risk of SRN on multivariable analysis (subdistribution hazard ratio, 3.0 [95% confidence interval: 1.1–8.3], P = 0.030).

Conclusions

This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.

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Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

We acknowledge the integral contribution of all participating patients, researchers, and institutions. We also extend our sincere thanks to the Global Breast Cancer Conference (GBCC) for inspiring this work and for their support in our pursuit of advancing knowledge in the field.

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS, Grant Number 23K14669).

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Authors and Affiliations

  1. Department of Radiation Oncology, Aichi Cancer Center Hospital, Kanokoden 1–1, Chikusa-Ku, Nagoya, Aichi, Japan

    Yutaro Koide, Naoya Nagai, Yurika Shindo, Takahiro Aoyama, Hidetoshi Shimizu, Shingo Hashimoto, Hiroyuki Tachibana & Takeshi Kodaira

  2. Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Naoya Nagai & Mariko Kawamura

  3. Department of Radiology, Aichi Medical University Hospital, Nagakute, Japan

    Sou Adachi & Makoto Ito

  4. Department of Radiation Oncology, Fujita Health University School of Medicine, Toyoake, Japan

    Masayuki Ito & Fumitaka Ito

Authors
  1. Yutaro Koide
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  2. Naoya Nagai
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Contributions

Y.K. wrote the main manuscript text and prepared figures and tables. Y.K., N.N., S.A., and M.I. prepared the research data. All authors reviewed the manuscript.

Corresponding author

Correspondence to Yutaro Koide.

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Competing interests

YK has a speaker’s bureau for Hitachi Co., Global Breast Cancer Conference (GBCC), and received research funding from Japan Society for the Promotion of Science (JSPS, Grant Number 23K14669). MK has a research grant from Accuray Co. and speaker’s bureau for Accuray Co., Chugai Pharmaceutical, and leadership/fiduciary roles in Japanese Society for Radiation Oncology (educational committee, public relations committee, international committee), Japanese Breast cancer society (educational committee, guideline committee), and Japan Radiological Society (international committee, diversity committee). TK has a speaker’s bureau for Hitachi Co., Bristol Myers Squibb., Accuray Co., Elekta Co., Ono Pharmaceutical Co., AstraZeneca Co., Taiho Pharmaceutical Co., Canon Co., and Janssen Pharmaceutical Co.

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Koide, Y., Nagai, N., Adachi, S. et al. Impact of concurrent antibody–drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study. J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04681-8

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