Tumor Cavity Stereotactic Radiosurgery for Resected Brain Metastases

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Yasemin Bolukbasi
Ugur Selek
Duygu Sezen
Nulifer Kilic Durankus
Eyub Yasar Akdemir
Sukran Senyurek
Ahmet Kucuk
Berrin Pehlivan
Erkan Topkan


Stereotactic radiosurgery (SRS) has been utilized broadly for brain metastases not only for intact ones but as well as of late for the postoperative cavity of metastases after surgery, due to the advantages of SRS to preserve neurocognitive functions, maintain local control and prescribe the treatment in a short time frame. Randomized trials have proven the safety and efficacy of cavity SRS compared to observation. As WBRT offers no survival advantage in comparison to SRS and frequent monitorization with brain MRIs for early salvage upon failure, there has been a revolution in clinical approach for patients with limited intact brain metastases to treat with SRS only and omit WBRT. Likewise, the postoperative cavity SRS for brain metastases has gained a growing reputation. In this review, we summarize the proof for evidence-based optimization in the postoperative setting of the surgically removed brain metastases.

Brain metastases, stereotactic radiosurgery, neurosurgery, postoperative cavity radiosurgery, toxicity, efficacy, prognosis

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How to Cite
Bolukbasi, Y., Selek, U., Sezen, D., Durankus, N. K., Akdemir, E. Y., Senyurek, S., Kucuk, A., Pehlivan, B., & Topkan, E. (2020). Tumor Cavity Stereotactic Radiosurgery for Resected Brain Metastases. Journal of Cancer and Tumor International, 10(2), 15-30. https://doi.org/10.9734/jcti/2020/v10i230123
Review Article


Hardesty DA, Nakaji P. The current and future treatment of Brain metastases. Front Surg. 2016;3:30.

Delattre JY, Krol G, Thaler HT, Posner JB. Distribution of brain metastases. Arch Neurol. 1988;45(7):741-4.

Franchino F, Rudà R, Soffietti R. Mechanisms and Therapy for Cancer Metastasis to the Brain. Front Oncol. 2018; 8:161.

Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494-500.

Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al. Treatment of single brain metastasis: Radiotherapy alone or combined with neurosurgery? Ann Neurol. 1993;33(6): 583-90.

Venur VA, Ahluwalia MS. Prognostic scores for brain metastasis patients: use in clinical practice and trial design. Chin Clin Oncol. 2015;4(2):18.

Nieder C, Astner ST, Andratschke NH, Marienhagen K. Postoperative treatment and prognosis of patients with resected single brain metastasis: how useful are established prognostic scores? Clin Neurol Neurosurg. 2011;113(2):98-103.

Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70(2):510-4.

Golden DW, Lamborn KR, McDermott MW, et al. Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: Variation by primary site. J Neurosurg. 2008;109(Suppl):77-86.

Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: A randomized trial. JAMA. 1998;280 (17):1485-9.

Patel AJ, Suki D, Hatiboglu MA, et al. Factors influencing the risk of local recurrence after resection of a single brain metastasis. J Neurosurg. 2010;113(2): 181-9.

Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: A randomised controlled trial. Lancet Oncol. 2009;10(11):1037-44.

Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: A randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10): 1429-37.

Laack NN, Pugh SL, Brown PD, et al. The association of health-related quality of life and cognitive function in patients receiving memantine for the prevention of cognitive dysfunction during whole-brain radiotherapy. Neurooncol Pract. 2019;6 (4):274-82.

Brown PD, Jaeckle K, Ballman KV, et al. 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. 2016;316 (4):401-9.

McPherson CM, Suki D, Feiz-Erfan I, et al. Adjuvant whole-brain radiation therapy after surgical resection of single brain metastases. Neuro Oncol. 2010;12(7): 711-9.

Li J, Brown PD. The diminishing role of whole-brain radiation therapy in the treatment of brain metastases. JAMA Oncol. 2017;3(8):1023-4.

Ahmed Z, Balagamwala E, Murphy E, et al. Postoperative stereotactic radiosurgery for resected brain metastasis. CNS Oncol. 2014;3(3):199-207.

Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):1040-8.

Sperduto PW, Kased N, Roberge D, et al. Summary report on the graded prognostic assessment: An accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419-25.

Ellis TL, Neal MT, Chan MD. The role of surgery, radiosurgery and whole brain radiation therapy in the management of patients with metastatic brain tumors. Int J Surg Oncol. 2012; 2012:952345.

Marchan EM, Peterson J, Sio TT, et al. Postoperative cavity stereotactic radiosurgery for brain metastases. Front Oncol. 2018;8:342.

Kocher M, Soffietti R, Abacioglu U, et al. 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. 2011;29(2): 134-41.

Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: A randomized controlled trial. JAMA. 2006;295(21):2483-91.

Kocher M, Soffietti R, Abacioglu U, et al. 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. 2011;29(2): 134-41.

Churilla TM, Handorf E, Collette S, et al. Whole brain radiotherapy after stereotactic radiosurgery or surgical resection among patients with one to three brain metastases and favorable prognoses: A secondary analysis of EORTC 22952-26001. Ann Oncol. 2017;28(10):2588-94.

American Society of Radiation Oncology (ASTRO) 2014 Choosing Wisely List. Item No: 5: Don’t routinely add adjuvant whole brain radiation therapy to stereotactic radiosurgery for limited brain metastases.

Sahgal A, Aoyama H, Kocher M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91(4):710-7.

Tallet AV, Azria D, Barlesi F, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: Actual assessment. Radiat Oncol. 2012;7:77.

Brennan C, Yang TJ, Hilden P, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130-6.

Kepka L, Tyc-Szczepaniak D, Bujko K, et al. Stereotactic radiotherapy of the tumor bed compared to whole brain radiotherapy after surgery of single brain metastasis: Results from a randomized trial. Radiother Oncol. 2016;121(2):217-24.

Berger A, Strauss I, Ben Moshe S, et al. Neurocognitive evaluation of brain metastases patients treated with post-resection stereotactic radiosurgery: A prospective single arm clinical trial. J Neurooncol. 2018;140(2):307-15.

Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): A multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):1049-60.

Lamba N, Muskens IS, DiRisio AC, et al. Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: A systematic review and meta-analysis. Radiat Oncol. 2017; 12(1):106.

Hsieh J, Elson P, Otvos B, et al. Tumor progression in patients receiving adjuvant whole-brain radiotherapy vs localized radiotherapy after surgical resection of brain metastases. Neurosurgery. 2015;76 (4):411-20.

Patel KR, Prabhu RS, Kandula S, et al. Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone. J Neurooncol. 2014; 120(3):657-63.

Atalar B, Modlin LA, Choi CY, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713-8.

Ojerholm E, Lee JY, Thawani JP, et al. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014;121(Suppl):75-83.

Prabhu RS, Turner BE, Asher AL, et al. A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases. Neuro Oncol. 2019;21(8):1049-59.

Shi S, Sandhu N, Jin MC, et al. Stereotactic radiosurgery for resected brain metastases: Single-institutional experience of over 500 cavities. Int J Radiat Oncol Biol Phys. 2020;106(4):764-71.

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.

Keller A, Dore M, Antoni D, et al. Risk of radionecrosis after hypo fractionated stereotactic radiotherapy targeting the postoperative resection cavity of brain metastases. Cancer Radiother. 2017; 21(5):377-88.

Yuan M, Behrami E, Pannullo S, Schwartz TH, Wernicke AG. The relationship between tumor volume and timing of post-resection stereotactic radiosurgery to maximize local control: A critical review. Cureus. 2019;11(9):e5762.

Ahmed S, Hamilton J, Colen R, et al. Change in postsurgical cavity size within the first 30 days correlates with extent of surrounding edema: Consequences for postoperative radiosurgery. J Comput Assist Tomogr. 2014;38(3):457-60.

Wernicke AG, Hirschfeld CB, Smith AW, et al. Clinical outcomes of large brain metastases treated with neurosurgical resection and intraoperative Cesium-131 brachytherapy: Results of a prospective trial. Int J Radiat Oncol Biol Phys. 2017; 98(5):1059-68.

Iorio-Morin C, Masson-Cote L, Ezahr Youssef, et al. Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014;121 Suppl:69-74.

Alghamdi M, Hasan Y, Ruschin M, et al. Stereotactic radiosurgery for resected brain metastasis: Cavity dynamics and factors affecting its evolution. J Radiosurg SBRT. 2018;5(3):191-200.

Soliman H, Ruschin M, Angelov L, et al. Consensus Contouring Guidelines for Postoperative Completely Resected Cavity Stereotactic Radiosurgery for Brain Metastases. Int J Radiat Oncol Biol Phys. 2018;100(2):436-42.

Do L, Pezner R, Radany E, et al. Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases. Int J Radiat Oncol Biol Phys. 2009;73(2):486-91.

Bilger A, Bretzinger E, Fennell J, et al. Local control and possibility of tailored salvage after hypofractionated stereotactic radiotherapy of the cavity after brain metastases resection. Cancer Med. 2018; 7(6):2350-9.

Choi CY, Chang SD, Gibbs IC, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: Prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys. 2012;84(2):336-42.

Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291-8.

Traylor JI, Habib A, Patel R, et al. Fractionated stereotactic radiotherapy for local control of resected brain metastases. J Neurooncol. 2019;144(2):343-50.

Kumar AMS, Miller J, Hoffer SA, et al. Postoperative hypofractionated stereotactic brain radiation (HSRT) for resected brain metastases: Improved local control with higher BED10. J Neurooncol. 2018;139(2):449-54.

Garimall S, Shanker M, Johns E, et al. Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases. J Neurooncol. 2020;146(2): 357-62.

Kubler J, Wester-Ebbinghaus M, Wenz F, et al. Postoperative stereotactic radiosurgery and hypofractionated radiotherapy for brain metastases using Gamma Knife and CyberKnife: A dual-center analysis. J Neurosurg Sci; 2020.

Available:https://doi.org/10.23736/S0390-5616.20.04830-4 (Epub ahead of print).

Mousli A, Bihin B, Gustin T, et al. Surgical bed stereotactic radiotherapy of brain metastases: Clinical outcome and predictors of local and distant brain failure. Cancer Radiother; 2020.
Available:https://doi.org/10.1016/j.canrad.2019.12.002 (Epub ahead of print)

Jagannathan J, Yen CP, Ray DK, et al. Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases. J Neurosurg. 2009;111(3): 431-8.

NCCN guidelines for central nervous system cancers version; 2020.

McDermott DM, Hack JD, Cifarelli CP, Vargo JA. Tumor cavity recurrence after stereotactic radiosurgery of surgically resected brain metastases: Implication of deviations from contouring guidelines. Stereotact Funct Neurosurg. 2019;97(1):24- 30.