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Immune checkpoint inhibitor therapy may increase the incidence of treatment-related necrosis after stereotactic radiosurgery for brain metastases: a systematic review and meta-analysis

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Abstract

Objectives

To compare the incidence of treatment-related necrosis between combination SRS+ICI therapy and SRS therapy alone in patients with brain metastases from melanoma and non-small cell lung cancer (NSCLC).

Methods

A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to August 10, 2020. The difference in the pooled incidence of treatment-related necrosis after SRS+ICI or SRS alone was evaluated. The cumulative incidence of treatment-related necrosis at the specific time point after the treatment was calculated and plotted. Subgroup and meta-regression analyses were additionally performed.

Results

Sixteen studies (14 on melanoma, 2 on NSCLC) were included. In NSCLC brain metastasis, the reported incidences of treatment-related necrosis in SRS+ICI and SRS alone ranged 2.9–3.4% and 0–2.9%, respectively. Meta-analysis was conducted including 14 studies on melanoma brain metastasis. The incidence of treatment-related necrosis was higher in SRS+ICI than SRS alone (16.0% vs. 6.5%; p = 0.065; OR, 2.35). The incidence showed rapid increase until 12 months after the SRS when combined with ICI therapy (14%; 95% CI, 8–22%) and its pace of increase slowed thereafter. Histopathologic diagnosis as the reference standard for treatment-related necrosis and inclusion of only symptomatic cases were the source of heterogeneity in SRS+ICI.

Conclusions

Treatment-related necrosis tended to occur 2.4 times more frequently in the setting of combination SRS+ICI therapy compared with SRS alone in melanoma brain metastasis showing high cumulative incidence within the first year. Treatment-related necrosis should be considered when SRS+ICI combination therapy is used for melanoma brain metastasis, especially in the first year.

Key Points

• Treatment-related necrosis occurred 2.4 times more frequently in the setting of combination SRS+ICI therapy compared with SRS alone in melanoma brain metastasis.

• Treatment-related necrosis more frequently occurred in brain metastases from melanoma than NSCLC.

• Reference standard for treatment-related necrosis and inclusion of only symptomatic treatment-related necrosis were a significant source of heterogeneity, indicating varying definitions of treatment-related necrosis in the literature need to be unified.

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Abbreviations

CI:

Confidence interval

ICI:

Immune checkpoint inhibitor

KM curve:

Kaplan-Meier curve

NSCLC:

Non-small cell lung cancer

SRS:

Stereotactic radiosurgery

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The authors state that this work has not received any funding.

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Author notes

  1. Jeffrey P. Guenette and Raymond Y. Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Olympic-ro 33, Seoul, 05505, Republic of Korea

    Pyeong Hwa Kim, Chong Hyun Suh, Ho Sung Kim & Kyung Won Kim

  2. Department of Quarantine, Incheon Airport National Quarantine Station, Incheon, Republic of Korea

    Dong Yeong Kim

  3. Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA

    Ayal A. Aizer & Rifaquat Rahman

  4. Division of Neuroradiology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Jeffrey P. Guenette & Raymond Y. Huang

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  1. Pyeong Hwa Kim
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Correspondence to Chong Hyun Suh.

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Kim, P.H., Suh, C.H., Kim, H.S. et al. Immune checkpoint inhibitor therapy may increase the incidence of treatment-related necrosis after stereotactic radiosurgery for brain metastases: a systematic review and meta-analysis. Eur Radiol 31, 4114–4129 (2021). https://doi.org/10.1007/s00330-020-07514-0

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