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Salvage resection of recurrent previously irradiated brain metastases: tumor control and radiation necrosis dependency on adjuvant re-irradiation

Abstract

Purpose

The efficacy of salvage resection (SR) of recurrent brain metastases (rBrM) following stereotactic radiosurgery (SRS) is undefined. We sought to describe local recurrence (LR) and radiation necrosis (RN) rates in patients undergoing SR, with or without adjuvant post-salvage radiation therapy (PSRT).

Methods

A retrospective cohort study evaluated patients undergoing SR of post-SRS rBrM between 3/2003–2/2020 at an NCI-designated cancer center. Cases with histologically-viable malignancy were stratified by receipt of adjuvant PSRT within 60 days of SR. Clinical outcomes were described using cumulative incidences in the clustered competing-risks setting, competing risks regression, and Kaplan–Meier methodology.

Results

One-hundred fifty-five rBrM in 135 patients were evaluated. The overall rate of LR was 40.2% (95% CI 34.3–47.2%) at 12 months. Thirty-nine (25.2%) rBrM treated with SR + PSRT trended towards lower 12-month LR versus SR alone [28.8% (95% CI 17.0–48.8%) versus 43.9% (95% CI 36.2–53.4%), p = .07 by multivariate analysis]. SR as re-operation (p = .03) and subtotal resection (p = .01) were independently associated with higher rates of LR. On univariate analysis, tumor size (p = .48), primary malignancy (p = .35), and PSRT technique (p = .43) bore no influence on LR. SR + PSRT was associated with an increased risk of radiographic RN at 12 months versus SR alone [13.4% (95% CI 5.5–32.7%) versus 3.5% (95% CI 1.5–8.0%), p = .02], though the percentage with symptomatic RN remained low (5.1% versus 0.9%, respectively). Median overall survival from SR was 13.4 months (95% CI 10.5–17.7).

Conclusion

In this largest-known series evaluating SR outcomes in histopathologically-confirmed rBrM, we identify a significant LR risk that may be reduced with adjuvant PSRT and with minimal symptomatic RN. Prospective analysis is warranted.

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Data availability

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Code availability

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Funding

This study was supported in part by the National Institutes of Health and National Cancer Institute Cancer Center Support Grant P30 CA008748 to Craig B. Thompson.

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Affiliations

Authors

Contributions

Conception and design: JAW, NSM. Collection and assembly of data: JAW, JC, WCM. Neuropathology review: TAB, MKR. Neuroradiology review: JAW, RJY. Data analysis and interpretation: JAW, SB, ASR, KSP, NSM. Manuscript writing and final approval: JAW, SB, ASR, RJY, JC, TAB, MKR, WCM, KB, CWB, KSP, VT, NSM.

Corresponding author

Correspondence to Nelson S. Moss.

Ethics declarations

Conflict of interest

NSM has consulted for AstraZeneca and has received trial support from GT Medical Technologies (to institution). RJY has consulted for Agios, Puma, ICON and NordicNeuroLab, and received grant funding (to institution) from Agios.

Ethical approval

The Memorial Sloan Kettering Institutional Review Board approved this study and granted a waiver of consent.

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Not applicable.

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Each author (JAW, SB, ASR, RJY, JC, TAB, MKR, WCN, CWB, VT, KB, NSM) approves of the content and provides consent to publish.

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Wilcox, J.A., Brown, S., Reiner, A.S. et al. Salvage resection of recurrent previously irradiated brain metastases: tumor control and radiation necrosis dependency on adjuvant re-irradiation. J Neurooncol (2021). https://doi.org/10.1007/s11060-021-03872-x

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Keywords

  • Brain metastasis
  • Radiation necrosis
  • Local recurrence
  • Salvage resection
  • Stereotactic radiosurgery