Skip to main content

Advertisement

SpringerLink
Log in

Comparison of initial and sequential salvage brain-directed treatment in patients with 1–4 vs. 5–10 brain metastases from breast cancer (KROG 16–12)

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1–4 brain metastases (BMs) and those with 5–10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients.

Methods

Between 2008 and 2014, 471 patients were diagnosed with 1–10 BMs. They were divided into two groups based on the number of BM: 1–4 BMs (n = 337) and 5–10 BMs (n = 134). Median follow-up duration was 14.0 months.

Results

Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1–4 BMs group. In contrast, 80% (n = 107) of patients with 5–10 BMs were treated with WBRT. The median OS of the entire cohort, 1–4 BMs, and 5–10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months.

Conclusion

The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

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

References

  1. Jeon W, Jang BS, Jeon SH et al (2018) Analysis of survival outcomes based on molecular subtypes in breast cancer brain metastases: a single institutional cohort. Breast J 24:920–926. https://doi.org/10.1111/tbj.13111

    Article  CAS  PubMed  Google Scholar 

  2. Kim JS, Kim IA (2020) Evolving treatment strategies of brain metastases from breast cancer: current status and future direction. Ther Adv Med Oncol 12:175883592093611. https://doi.org/10.1177/1758835920936117

    Article  Google Scholar 

  3. Quigley MR, Fukui O, Chew B et al (2013) The shifting landscape of metastatic breast cancer to the CNS. Neurosurg Rev 36:377–382. https://doi.org/10.1007/s10143-012-0446-6

    Article  PubMed  Google Scholar 

  4. Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044. https://doi.org/10.1016/S1470-2045(09)70263-3

    Article  PubMed  Google Scholar 

  5. Aoyama H, Shirato H, Tago M et al (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. J Am Med Assoc 295:2483–2491. https://doi.org/10.1001/jama.295.21.2483

    Article  CAS  Google Scholar 

  6. Kocher M, Soffietti R, Abacioglu U et al (2011) 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 29:134–141. https://doi.org/10.1200/JCO.2010.30.1655

    Article  PubMed  Google Scholar 

  7. Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial. JAMA - J Am Med Assoc 316:401–409. https://doi.org/10.1001/jama.2016.9839

    Article  Google Scholar 

  8. Chaung KV, Sloan AE, Choi S (2021) Limited brain metastases: a narrative review. Ann Palliat Med 10:6016–6027. https://doi.org/10.21037/apm-21-363

    Article  PubMed  Google Scholar 

  9. Gondi V, Bauman G, Bradfield L et al (2022) Radiation therapy for brain metastases: an ASTRO clinical practice guideline. Pract Radiat Oncol 12:265–282. https://doi.org/10.1016/j.prro.2022.02.003

    Article  PubMed  Google Scholar 

  10. Kim JS, Kim K, Jung W et al (2022) The pattern of care for brain metastasis from breast cancer over the past 10 years in Korea: a multicenter retrospective study (KROG 16–12). Cancer Res Treat 54:1121–1129. https://doi.org/10.4143/crt.2021.1083

    Article  PubMed  Google Scholar 

  11. Kim JS, Kim K, Jung W et al (2020) Survival outcomes of breast cancer patients with brain metastases: a multicenter retrospective study in Korea (KROG 16–12). The Breast 49:41–47. https://doi.org/10.1016/j.breast.2019.10.007

    Article  PubMed  Google Scholar 

  12. Kim JS, Kim K, Jung W et al (2021) New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16–12). Breast Cancer Res Treat 186:453–462. https://doi.org/10.1007/s10549-020-06043-0

    Article  CAS  PubMed  Google Scholar 

  13. Kim JS, Kim K, Jung W et al (2021) Novel prognostic classification predicts overall survival of patients receiving salvage whole-brain radiotherapy for recurrent brain metastasis from breast cancer: a recursive partitioning analysis (KROG 16–12). The Breast 60:272–278. https://doi.org/10.1016/j.breast.2021.11.005

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yamamoto M, Serizawa T, Shuto T et al (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:387–395. https://doi.org/10.1016/S1470-2045(14)70061-0

    Article  PubMed  Google Scholar 

  15. Rogers S, Baumert B, Blanck O et al (2022) Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the radiosurgery and stereotactic radiotherapy working group of the German association for radiation oncology (DEGRO). Strahlentherapie und Onkol 198:919–925. https://doi.org/10.1007/s00066-022-01991-6

    Article  CAS  Google Scholar 

  16. Khan M, Lin J, Liao G et al (2017) Comparison of WBRT alone, SRS alone, and their combination in the treatment of one or more brain metastases: review and meta-analysis. Tumor Biol 39:101042831770290. https://doi.org/10.1177/1010428317702903

    Article  CAS  Google Scholar 

  17. Yan H, Li X, Peng Y et al (2020) Apatinib and fractionated stereotactic radiotherapy for the treatment of limited brain metastases from primary lung mucoepidermoid carcinoma. Medicine (Baltimore) 99:e22925. https://doi.org/10.1097/MD.0000000000022925

    Article  PubMed  Google Scholar 

  18. Hendriks LEL, Schoenmaekers J, Zindler JD et al (2015) Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: a systematic review. Cancer Treat Rev 41:634–645. https://doi.org/10.1016/j.ctrv.2015.05.005

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by grants from Korean Ministry of Science and Information & Communication Technology (NRF#2023R1A2C3003782) to In Ah Kim.

Author information

Author notes

  1. Jae Sik Kim and Kyubo Kim contributed equally to this study.

Authors and Affiliations

  1. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea

    Jae Sik Kim, Kyung Hwan Shin, Kyung Su Kim & In Ah Kim

  2. Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Korea

    Kyubo Kim & Wonguen Jung

  3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

    Seock-Ah Im & Jee Hyun Kim

  4. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

    Hee-Jun Kim

  5. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea

    Yong Bae Kim & Jee Suk Chang

  6. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Doo Ho Choi

  7. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Yeon Hee Park

  8. Proton Therapy Center, National Cancer Center, Seoul, Korea

    Dae Yong Kim & Tae Hyun Kim

  9. Department of Radiation Oncology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

    Byung Ock Choi & Sea-Won Lee

  10. Department of Radiation Oncology, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

    Sea-Won Lee

  11. Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

    Suzy Kim

  12. Department of Radiation Oncology, Chungnam National University College of Medicine, Daejeon, Korea

    Jeanny Kwon

  13. Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Korea

    Ki Mun Kang

  14. Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea

    Woong-Ki Chung

  15. Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea

    Kyung Su Kim

  16. Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan-Si, Korea

    Won Sup Yoon

  17. Department of Radiation Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea

    Jin Hee Kim

  18. Department of Radiation Oncology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju-Si, Korea

    Jihye Cha

  19. Department of Radiation Oncology, Chosun University Medical School, Gwangju, Korea

    Yoon Kyeong Oh

  20. Department of Radiation Oncology, Seoul National University Bundang Hospital, Gumi-Ro 173, 82 Beon-Gil, Bundang Gu, Seongnam, 13620, Republic of Korea

    In Ah Kim

Authors
  1. Jae Sik Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyubo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wonguen Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyung Hwan Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seock-Ah Im
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hee-Jun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Bae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jee Suk Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jee Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Doo Ho Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yeon Hee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dae Yong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tae Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Byung Ock Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sea-Won Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Suzy Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jeanny Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ki Mun Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Woong-Ki Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Kyung Su Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Won Sup Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Jin Hee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Jihye Cha
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Yoon Kyeong Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. In Ah Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JSK contributed to formal analysis, methodology, visualization, writing of the original draft, and writing, reviewing, and editing of the manuscript. KK contributed to formal analysis, methodology, supervision, writing of the original draft, and writing, reviewing, and editing of the manuscript. WJ, KHS, SAI, HJK, YBK, JSC, JHK, DHC, YHP, DYK, THK, BOC, SWL, SK, JK, KMK, WKC, KSK, WSY, JHK, JC, and YKO contributed to investigation and writing, reviewing, and editing of the manuscript. IAK contributed to conceptualization, supervision, and writing, reviewing, and editing of the manuscript. All the authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to In Ah Kim.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The Institutional Review Board of each institution approved this study. This study was conducted in accordance with the principles of the Declaration of Helsinki.

Consent to participate

The requirement for informed consent was waived because of the retrospective design.

Consent to publish

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Jae Sik Kim currently working at the Department of Radiation Oncology in Soonchunhyang University Seoul Hospital.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, J.S., Kim, K., Jung, W. et al. Comparison of initial and sequential salvage brain-directed treatment in patients with 1–4 vs. 5–10 brain metastases from breast cancer (KROG 16–12). Breast Cancer Res Treat 200, 37–45 (2023). https://doi.org/10.1007/s10549-023-06936-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-023-06936-w

Keywords

Search

Navigation