Radiation therapy is a cornerstone of brain metastasis (BrM) management but carries the risk of radiation necrosis (RN), which can require resection for palliation or diagnosis. We sought to determine the relationship between extent of resection (EOR) of pathologically-confirmed RN and postoperative radiographic and symptomatic outcomes.
A single-center retrospective review was performed at an NCI-designated Comprehensive Cancer Center to identify all surgically-resected, previously-irradiated necrotic BrM without admixed recurrent malignancy from 2003 to 2018. Clinical, pathologic and radiographic parameters were collected. Volumetric analysis determined EOR and longitudinally evaluated perilesional T2-FLAIR signal preoperatively, postoperatively, and at 3-, 6-, 12-, and 24-months postoperatively when available. Rates of time to 50% T2-FLAIR reduction was calculated using cumulative incidence in the competing risks setting with last follow-up and death as competing events. The Spearman method was used to calculate correlation coefficients, and continuous variables for T2-FLAIR signal change, including EOR, were compared across groups.
Forty-six patients were included. Most underwent prior stereotactic radiosurgery with or without whole-brain irradiation (N = 42, 91%). Twenty-seven operations resulted in gross-total resection (59%; GTR). For the full cohort, T2-FLAIR edema decreased by a mean of 78% by 6 months postoperatively that was durable to last follow-up (p < 0.05). EOR correlated with edema reduction at last follow-up, with significantly greater T2-FLAIR reduction with GTR versus subtotal resection (p < 0.05). Among surviving patients, a significant proportion were able to decrease their steroid use: steroid-dependency decreased from 54% preoperatively to 15% at 12 months postoperatively (p = 0.001).
RN resection conferred both durable T2-FLAIR reduction, which correlated with EOR; and reduced steroid dependency.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
The datasets generated during and/or analyzed during the current study are not publicly available to decrease the risk of breach of patient privacy but available from the corresponding author on reasonable request.
Extent of resection
Gross total resection
Laser interstitial thermal therapy
Whole brain radiation therapy
Shah R, Vattoth S, Jacob R et al (2012) Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence. Radiographics 32(5):1343–1359. https://doi.org/10.1148/rg.325125002
Loganadane G, Dhermain F, Louvel G et al (2018) Brain radiation necrosis: current management with a focus on non-small cell lung cancer patients. Front Oncol 8:336. https://doi.org/10.3389/fonc.2018.00336
Minniti G, Clarke E, Lanzetta G et al (2011) Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 6:48. https://doi.org/10.1186/1748-717X-6-48
Kohutek ZA, Yamada Y, Chan TA et al (2015) Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases. J Neurooncol 125(1):149–156. https://doi.org/10.1007/s11060-015-1881-3
Chin LS, Ma L, DiBiase S (2001) Radiation necrosis following gamma knife surgery: a case-controlled comparison of treatment parameters and long-term clinical follow up. J Neurosurg 94(6):899–904. https://doi.org/10.3171/jns.2001.94.6.0899
Varlotto JM, Flickinger JC, Niranjan A, Bhatnagar AK, Kondziolka D, Lunsford LD (2003) Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 57(2):452–464. https://doi.org/10.1016/s0360-3016(03)00568-6
Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC (2010) Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 77(4):996–1001. https://doi.org/10.1016/j.ijrobp.2009.06.006
Telera S, Fabi A, Pace A et al (2013) Radionecrosis induced by stereotactic radiosurgery of brain metastases: results of surgery and outcome of disease. J Neurooncol 113(2):313–325. https://doi.org/10.1007/s11060-013-1120-8
Chao ST, Ahluwalia MS, Barnett GH et al (2013) Challenges with the diagnosis and treatment of cerebral radiation necrosis. Int J Radiat Oncol Biol Phys 87(3):449–457. https://doi.org/10.1016/j.ijrobp.2013.05.015
Vellayappan B, Tan CL, Yong C et al (2018) Diagnosis and management of radiation necrosis in patients with brain metastases. Front Oncol 8:395. https://doi.org/10.3389/fonc.2018.00395
Patel U, Patel A, Cobb C, Benkers T, Vermeulen S (2014) The management of brain necrosis as a result of SRS treatment for intra-cranial tumors. Transl Cancer Res 3(4):373–382. https://doi.org/10.21037/2950
Kohshi K, Imada H, Nomoto S, Yamaguchi R, Abe H, Yamamoto H (2003) Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy. J Neurol Sci 209(1–2):115–117. https://doi.org/10.1016/s0022-510x(03)00007-8
Williamson R, Kondziolka D, Kanaan H, Lunsford LD, Flickinger JC (2008) Adverse radiation effects after radiosurgery may benefit from oral vitamin E and pentoxifylline therapy: a pilot study. Stereotact Funct Neurosurg 86(6):359–366. https://doi.org/10.1159/000163557
Tye K, Engelhard HH, Slavin KV et al (2014) An analysis of radiation necrosis of the central nervous system treated with bevacizumab. J Neurooncol 117(2):321–327. https://doi.org/10.1007/s11060-014-1391-8
Kotsarini C, Griffiths PD, Wilkinson ID, Hoggard N (2010) A systematic review of the literature on the effects of dexamethasone on the brain from in vivo human-based studies: implications for physiological brain imaging of patients with intracranial tumors. Neurosurgery 67(6):1799–1815. https://doi.org/10.1227/NEU.0b013e3181fa775b (discussion 1815)
Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K (2013) Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol 15(9):1257–1263. https://doi.org/10.1093/neuonc/not085
Sujijantarat N, Hong CS, Owusu KA et al (2020) Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases. J Neurooncol 148(3):641–649. https://doi.org/10.1007/s11060-020-03570-0
Rao MS, Hargreaves EL, Khan AJ, Haffty BG, Danish SF (2014) Magnetic resonance-guided laser ablation improves local control for postradiosurgery recurrence and/or radiation necrosis. Neurosurgery 74(6):658–667. https://doi.org/10.1227/NEU.0000000000000332 (discussion 667)
Rahmathulla G, Recinos PF, Valerio JE, Chao S, Barnett GH (2012) Laser interstitial thermal therapy for focal cerebral radiation necrosis: a case report and literature review. Stereotact Funct Neurosurg 90(3):192–200. https://doi.org/10.1159/000338251
Grkovski M, Kohutek ZA, Schöder H et al (2020) 18F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases. Eur J Nucl Med Mol Imaging 47(6):1446–1457. https://doi.org/10.1007/s00259-019-04628-6
Hatzoglou V, Yang TJ, Omuro A et al (2016) A prospective trial of dynamic contrast-enhanced MRI perfusion and fluorine-18 FDG PET-CT in differentiating brain tumor progression from radiation injury after cranial irradiation. Neuro Oncol 18(6):873–880. https://doi.org/10.1093/neuonc/nov301
Shah AH, Mahavadi AK, Morell A et al (2020) Salvage craniotomy for treatment-refractory symptomatic cerebral radiation necrosis. Neurooncol Pract 7(1):94–102. https://doi.org/10.1093/nop/npz028
Kimura T, Sako K, Tohyama Y et al (2003) Diagnosis and treatment of progressive space-occupying radiation necrosis following stereotactic radiosurgery for brain metastasis: value of proton magnetic resonance spectroscopy. Acta Neurochir (Wien) 145(7):557–564. https://doi.org/10.1007/s00701-003-0051-0 (discussion 564)
Wong S-T, Loo K-T, Yam K-Y et al (2010) Results of excision of cerebral radionecrosis: experience in patients treated with radiation therapy for nasopharyngeal carcinoma: clinical article. J Neurosurg 113(2):293–300. https://doi.org/10.3171/2010.1.JNS091039
Grossman R, Shimony N, Hadelsberg U et al (2016) Impact of resecting radiation necrosis and pseudoprogression on survival of patients with glioblastoma. World Neurosurg 89:37–41. https://doi.org/10.1016/j.wneu.2016.01.020
Mou Y, Sai K, Wang Z et al (2011) Surgical management of radiation-induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: report of 14 cases. Head Neck 33(10):1493–1500. https://doi.org/10.1002/hed.21639
Miyatake S-I, Nonoguchi N, Furuse M et al (2015) Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain. Neurol Med Chir (Tokyo) 55(1):50–59. https://doi.org/10.2176/nmc.ra.2014-0188
McPherson CM, Warnick RE (2004) Results of contemporary surgical management of radiation necrosis using frameless stereotaxis and intraoperative magnetic resonance imaging. J Neurooncol 68(1):41–47. https://doi.org/10.1023/b:neon.0000024744.16031.e9
Bander ED, Yuan M, Carnevale JA et al (2021) Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies. Cancer. https://doi.org/10.1002/cncr.33459
Bander ED, Yuan M, Reiner AS et al (2021) Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control. Neuro-Oncol Pract. https://doi.org/10.1093/nop/npab005
Niwińska A, Tacikowska M, Murawska M (2010) The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys 77(4):1134–1139. https://doi.org/10.1016/j.ijrobp.2009.06.030
Giles AJ, Hutchinson M-KND, Sonnemann HM et al (2018) Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. https://doi.org/10.1186/s40425-018-0371-5
Petrelli F, Signorelli D, Ghidini M et al (2020) Association of steroids use with survival in patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Cancers 12(3):546. https://doi.org/10.3390/cancers12030546
Tawbi HA, Forsyth PA, Algazi A et al (2018) Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med 379(8):722–730. https://doi.org/10.1056/NEJMoa1805453
Iorgulescu JB, Gokhale PC, Speranza MC et al (2021) Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma. Clin Cancer Res 27(1):276–287. https://doi.org/10.1158/1078-0432.CCR-20-2291
This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.
Conflict of interest
NSM has consulted for AstraZeneca and received grant support from GT Medical Technologies. RJY has consulted for Agios, Puma, NordicNeuroLab and ICON plc, and received grant support from Agios, unrelated to this report.
This study was approved by the institutional review board (IRB# 16-1531) and performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Consent to participate
The institutional review board (IRB# 16-1531) granted this study a wavier of consent.
Consent for publication
The institutional review board (IRB# 16-1531) granted this study a wavier of consent. No patient identifiers are presented in this study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Newman, W.C., Goldberg, J., Guadix, S.W. et al. The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes. J Neurooncol 153, 507–518 (2021). https://doi.org/10.1007/s11060-021-03790-y
- Brain metastasis
- Radiation necrosis
- Radiation therapy
- Surgical resection