Research Article
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Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis

Year 2025, Volume: 38 Issue: 3, 235 - 241, 10.10.2025
https://doi.org/10.5472/marumj.1800032

Abstract

Objective: To investigate factors influencing the occurrence of radiation necrosis (RN) in patients receiving fractionated stereotactic
radiotherapy (fSRT) for brain metastases.
Patients and Methods: Forty patients underwent linear accelerator-based fSRT from January 2018 to December 2023. RN and treatment
response were monitored using magnetic resonance imaging (MRI), with toxicity graded by the Common Terminology Criteria for
Adverse Events (CTCAE) version 5.0 and oncological response was evaluated by the Response Evaluation Criteria in Solid Tumors
(RECIST) criteria.
Results: At a median follow-up of 12 months, RN occurred in 4 (10%) patients. Two patients had asymptomatic grade 1 RN, while
two required steroids for grade 2 RN. Univariate analysis showed significant factors for RN: history of repeated fSRT (p=0.020), >1
metastatic lesion (p=0.022), age (p=0.016), and brain V30 (p=0.022). Multivariate analysis confirmed that repeated fSRT (p=0.02) and
age (p=0.002) were significant.
Conclusion: Radiation necrosis is a major concern in fSRT for brain metastases. Repeated fSRT, multiple metastatic lesions, age, and
higher brain V30 values increase RN risk. Individualized treatment planning, especially considering dose-volume parameters, may
help reduce this risk. Larger prospective studies are needed to confirm these findings and optimize RN mitigation strategies.

References

  • Cagney DN, Martin AM, Catalano PJ, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro Oncol 2017;19:1511-21. doi: 10.1093/neuonc/nox077.
  • Chao ST, De Salles A, Hayashi M, et al. Stereotactic radiosurgery in the management of limited (1-4) brain metasteses: Systematic review and international stereotactic radiosurgery society practice guideline. Neurosurgery. 2018;83:345-53. doi: 10.1093/neuros/ nyx522. PMID: 29126142.
  • Le Chevalier T, Smith FP, Caille P, Constans JP, Rouesse JG. Sites of primary malignancies in patients presenting with cerebral metastases. A review of 120 cases. Cancer 1985;56:880-2.
  • Pannullo SC, Julie DAR, Chidambaram S, et al. Worldwide access to stereotactic radiosurgery. World Neurosurg 2019;130:608-14. doi: 10.1016/j.wneu.2019.04.031.
  • Suh JH, Kotecha R, Chao ST, Ahluwalia MS, Sahgal A, Chang EL. Current approaches to the management of brain metastases. Nat Rev Clin Oncol 2020;17:279-99.
  • Loo M, Pin Y, Thierry A, Clavier JB. Single fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: A comparative study. Clin Exp Metastasis 2020;37:425-34.
  • Lehrer EJ, Peterson JL, Zaorsky NG, et al. Single versus multifraction stereotactic radiosurgery for large brain metastases: An International meta-analysis of 24 trials. Int J Radiat Oncol Biol Phys 2019;103:618-30. doi: 10.1016/j.ijrobp.2018.10.038.
  • Marks JE, Baglan RJ, Prassad SC, Blank WF. Cerebral radionecrosis. Incidence and risk in relation to dose, time, fractionation and volume. Int J Radiat Oncol Biol Phys 1981;7:243-52. doi: 10.1016/0360-3016(81)90443-0.
  • Ruben JD, Dally M, Bailey M, Smith R, McLean CA, Fedele P. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 2006:65: 499-508.
  • Miller JA, Bennett EE, Xiao R, et al. Association between radiation necrosis and tumor biology after stereotactic radiosurgery for brain metastasis. Int J Radiat Oncol Biol Phys 2016;96:1060-9. doi: 10.1016/j.ijrobp.2016.08.039.
  • Minniti G, Clarke E, Lanzetta G, et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 2011;6:48. doi: 10.1186/1748-717X- 6-48.
  • Milano MT, Soltys SG, Marks LB, et al. The art of radiation therapy: The necessary risk of radiation necrosis for durable control of brain metastases. Int J Radiat Oncol Biol Phys 2023;115:294-6. doi: 10.1016/j.ijrobp.2022.07.036.
  • Dale R, Plataniotis G, Jones B. A generalised method for calculating repopulation-corrected tumour EQD2 values in a wide range of clinical situations, including interrupted treatments. Phys Med 2024;118:103294. doi: 10.1016/j.ejmp.2024.103294.
  • Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 2009;22:633-8. doi: 10.1097/WCO.0b013e328332363e.
  • National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health; 2017. Available from: https://ctep.cancer.gov/protocoldevelopment/ electronic_applications/ctc.htm#ctc_50 Accessed on: 03.04.2025
  • Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. doi: 10.1016/j. ejca.2008.10.026.
  • Andruska N, Kennedy WR, Bonestroo L, et al. Dosimetric predictors of symptomatic radiation necrosis after five-fraction radiosurgery for brain metastases. Radiother Oncol 2021;156:181- 7. doi: 10.1016/j.radonc.2020.12.011.
  • Balermpas P, Stera S, Müller von der Grün J, et al. Repeated in-field radiosurgery for locally recurrent brain metastases: Feasibility, results and survival in a heavily treated patient cohort. PLoS One 2018;13:e0198692. doi: 10.1371/journal.pone.0198692.
  • Terakedis BE, Jensen RL, Boucher K, Shrieve DC. Tumor control and incidence of radiation necrosis after reirradiation with stereotactic radiosurgery for brain metastases. J Radiosurg 2014;3:21-28.
  • Sayan M, Şahin B, Mustafayev TZ, et al. Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases. Neurocirugia (Astur : Engl Ed) 2021;32:261- 7. doi: 10.1016/j.neucie.2020.08.007.
  • Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2010;77:996-1001. doi: 10.1016/j. ijrobp.2009.06.006.
  • Milano MT, Grimm J, Niemierko A, et al. Single – and multifraction sereotactic radiosurgery dose/volume tolerances of the brain. Int J Radiat Oncol Biol Phys 2021;110:68-86. doi: 10.1016/j.ijrobp.2020.08.013.
  • Pham DQ, Sheehan DE, Sheehan KA, Katsos K, Fadul CE. Quality of life after stereotactic radiosurgery for brain metastasis: an assessment from a prospective national registry. J Neurooncol 2025;171:383-91. doi: 10.1007/s11060.024.04854-5.
  • Kohutek ZA, Yamada Y, Chan TA, et al. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases. J Neurooncol 2015;125:149-56. doi: 10.1007/ s11060.015.1881-3.
  • Korytko T, Radivoyevitch T, Colussi V, et al. 12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors. Int J Radiat Oncol Biol Phys 2006;64:419-24. doi: 10.1016/j.ijrobp.2005.07.980.
  • Masucci GL. Hypofractionated radiation therapy for large brain metastases. Front Oncol 2018;8:379. doi: 10.3389/fonc.2018.00379.
  • Ohguri T, Itamura H, Tani S, Shiba E, Yamamoto J. High incidence of radiation-induced brain necrosis in the periventricular deep white matter: stereotactic radiotherapy for brain metastases using volumetric modulated arc therapy. Radiat Oncol 2025; 9;20:4. doi: 10.1186/s13014.024.02579-3.

Year 2025, Volume: 38 Issue: 3, 235 - 241, 10.10.2025
https://doi.org/10.5472/marumj.1800032

Abstract

References

  • Cagney DN, Martin AM, Catalano PJ, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro Oncol 2017;19:1511-21. doi: 10.1093/neuonc/nox077.
  • Chao ST, De Salles A, Hayashi M, et al. Stereotactic radiosurgery in the management of limited (1-4) brain metasteses: Systematic review and international stereotactic radiosurgery society practice guideline. Neurosurgery. 2018;83:345-53. doi: 10.1093/neuros/ nyx522. PMID: 29126142.
  • Le Chevalier T, Smith FP, Caille P, Constans JP, Rouesse JG. Sites of primary malignancies in patients presenting with cerebral metastases. A review of 120 cases. Cancer 1985;56:880-2.
  • Pannullo SC, Julie DAR, Chidambaram S, et al. Worldwide access to stereotactic radiosurgery. World Neurosurg 2019;130:608-14. doi: 10.1016/j.wneu.2019.04.031.
  • Suh JH, Kotecha R, Chao ST, Ahluwalia MS, Sahgal A, Chang EL. Current approaches to the management of brain metastases. Nat Rev Clin Oncol 2020;17:279-99.
  • Loo M, Pin Y, Thierry A, Clavier JB. Single fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: A comparative study. Clin Exp Metastasis 2020;37:425-34.
  • Lehrer EJ, Peterson JL, Zaorsky NG, et al. Single versus multifraction stereotactic radiosurgery for large brain metastases: An International meta-analysis of 24 trials. Int J Radiat Oncol Biol Phys 2019;103:618-30. doi: 10.1016/j.ijrobp.2018.10.038.
  • Marks JE, Baglan RJ, Prassad SC, Blank WF. Cerebral radionecrosis. Incidence and risk in relation to dose, time, fractionation and volume. Int J Radiat Oncol Biol Phys 1981;7:243-52. doi: 10.1016/0360-3016(81)90443-0.
  • Ruben JD, Dally M, Bailey M, Smith R, McLean CA, Fedele P. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 2006:65: 499-508.
  • Miller JA, Bennett EE, Xiao R, et al. Association between radiation necrosis and tumor biology after stereotactic radiosurgery for brain metastasis. Int J Radiat Oncol Biol Phys 2016;96:1060-9. doi: 10.1016/j.ijrobp.2016.08.039.
  • Minniti G, Clarke E, Lanzetta G, et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 2011;6:48. doi: 10.1186/1748-717X- 6-48.
  • Milano MT, Soltys SG, Marks LB, et al. The art of radiation therapy: The necessary risk of radiation necrosis for durable control of brain metastases. Int J Radiat Oncol Biol Phys 2023;115:294-6. doi: 10.1016/j.ijrobp.2022.07.036.
  • Dale R, Plataniotis G, Jones B. A generalised method for calculating repopulation-corrected tumour EQD2 values in a wide range of clinical situations, including interrupted treatments. Phys Med 2024;118:103294. doi: 10.1016/j.ejmp.2024.103294.
  • Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 2009;22:633-8. doi: 10.1097/WCO.0b013e328332363e.
  • National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health; 2017. Available from: https://ctep.cancer.gov/protocoldevelopment/ electronic_applications/ctc.htm#ctc_50 Accessed on: 03.04.2025
  • Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. doi: 10.1016/j. ejca.2008.10.026.
  • Andruska N, Kennedy WR, Bonestroo L, et al. Dosimetric predictors of symptomatic radiation necrosis after five-fraction radiosurgery for brain metastases. Radiother Oncol 2021;156:181- 7. doi: 10.1016/j.radonc.2020.12.011.
  • Balermpas P, Stera S, Müller von der Grün J, et al. Repeated in-field radiosurgery for locally recurrent brain metastases: Feasibility, results and survival in a heavily treated patient cohort. PLoS One 2018;13:e0198692. doi: 10.1371/journal.pone.0198692.
  • Terakedis BE, Jensen RL, Boucher K, Shrieve DC. Tumor control and incidence of radiation necrosis after reirradiation with stereotactic radiosurgery for brain metastases. J Radiosurg 2014;3:21-28.
  • Sayan M, Şahin B, Mustafayev TZ, et al. Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases. Neurocirugia (Astur : Engl Ed) 2021;32:261- 7. doi: 10.1016/j.neucie.2020.08.007.
  • Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2010;77:996-1001. doi: 10.1016/j. ijrobp.2009.06.006.
  • Milano MT, Grimm J, Niemierko A, et al. Single – and multifraction sereotactic radiosurgery dose/volume tolerances of the brain. Int J Radiat Oncol Biol Phys 2021;110:68-86. doi: 10.1016/j.ijrobp.2020.08.013.
  • Pham DQ, Sheehan DE, Sheehan KA, Katsos K, Fadul CE. Quality of life after stereotactic radiosurgery for brain metastasis: an assessment from a prospective national registry. J Neurooncol 2025;171:383-91. doi: 10.1007/s11060.024.04854-5.
  • Kohutek ZA, Yamada Y, Chan TA, et al. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases. J Neurooncol 2015;125:149-56. doi: 10.1007/ s11060.015.1881-3.
  • Korytko T, Radivoyevitch T, Colussi V, et al. 12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors. Int J Radiat Oncol Biol Phys 2006;64:419-24. doi: 10.1016/j.ijrobp.2005.07.980.
  • Masucci GL. Hypofractionated radiation therapy for large brain metastases. Front Oncol 2018;8:379. doi: 10.3389/fonc.2018.00379.
  • Ohguri T, Itamura H, Tani S, Shiba E, Yamamoto J. High incidence of radiation-induced brain necrosis in the periventricular deep white matter: stereotactic radiotherapy for brain metastases using volumetric modulated arc therapy. Radiat Oncol 2025; 9;20:4. doi: 10.1186/s13014.024.02579-3.
There are 27 citations in total.

Details

Primary Language English
Subjects Surgery (Other)
Journal Section Original Research
Authors

Melek Yakar 0000-0002-9042-9489

Durmuş Etiz 0000-0002-2225-0364

Publication Date October 10, 2025
Submission Date March 27, 2025
Acceptance Date June 5, 2025
Published in Issue Year 2025 Volume: 38 Issue: 3

Cite

APA Yakar, M., & Etiz, D. (2025). Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis. Marmara Medical Journal, 38(3), 235-241. https://doi.org/10.5472/marumj.1800032
AMA Yakar M, Etiz D. Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis. Marmara Med J. October 2025;38(3):235-241. doi:10.5472/marumj.1800032
Chicago Yakar, Melek, and Durmuş Etiz. “Radiation Necrosis Risk Assessment After Stereotactic Radiation Therapy for Brain Metastasis”. Marmara Medical Journal 38, no. 3 (October 2025): 235-41. https://doi.org/10.5472/marumj.1800032.
EndNote Yakar M, Etiz D (October 1, 2025) Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis. Marmara Medical Journal 38 3 235–241.
IEEE M. Yakar and D. Etiz, “Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis”, Marmara Med J, vol. 38, no. 3, pp. 235–241, 2025, doi: 10.5472/marumj.1800032.
ISNAD Yakar, Melek - Etiz, Durmuş. “Radiation Necrosis Risk Assessment After Stereotactic Radiation Therapy for Brain Metastasis”. Marmara Medical Journal 38/3 (October2025), 235-241. https://doi.org/10.5472/marumj.1800032.
JAMA Yakar M, Etiz D. Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis. Marmara Med J. 2025;38:235–241.
MLA Yakar, Melek and Durmuş Etiz. “Radiation Necrosis Risk Assessment After Stereotactic Radiation Therapy for Brain Metastasis”. Marmara Medical Journal, vol. 38, no. 3, 2025, pp. 235-41, doi:10.5472/marumj.1800032.
Vancouver Yakar M, Etiz D. Radiation necrosis risk assessment after stereotactic radiation therapy for brain metastasis. Marmara Med J. 2025;38(3):235-41.