Brain metastases: Single-dose radiosurgery versus hypofractionated stereotactic radiotherapy: A retrospective study
Background: Radiosurgery is employed for the treatment of brain metastases. The aim of this study is to evaluate the efficacy and tolerability of single-dose radiosurgery (SRS) compared to hypofractionated stereotactic radiotherapy (hFSRT).
Material and methods: Between 2004-2018 we analyzed treatments of 97 patients with 135 brain metastases. 56 patients were treated with SRS, and 41 patients were treated with hFSRT. Median dose was 16 Gy (12-20 Gy) for the SRS group and 30 Gy in 5-6 fractions for the hFSRT group. hFSRT was used for larger lesions and lesions located near critical structures. Kaplan-Meier curves were constructed for overall survival and local control.
Results: Median age was 64 years (range, 32–89 years). Median survival was 10 months (1-68 months). With a median follow up of 10 months, no significant differences in overall survival between groups were found (p = 0.21). Local control for all patients was 67%. Local progression-free survival (LPFS) at 6 months and 1 year were 71% and 60% for the SRS group, respectively, and 80% and 69% for the hFSRT group, respectively (p = 0.93). Although hFSRT was used for larger lesions and lesions in adverse locations, LPFS was not inferior compared to lesions treated with SRS. We observed acute toxicity grade 1-2 in 25 patients (25.8%). Late complications were observed in 11 patients (11.3%). Acute and late toxicity were similar in the SRS- and hFSRT-treated patients (p = 0.63 and p = 0.11, respectively). Brain recurrence occurred in 37.5% and 14.6% in the hFSRT and SRS group, respectively (p = 0.06).
Conclusions: Because patients treated with hFSRT exhibited similar survival and LPFS rates without differences in toxicity compared to those treated with SRS, hFSRT can be beneficial particularly for patients with brain metastases.
Relevance for Patients: Hypofractionated schemes in stereotactic radiosurgery offers treatment alternatives to patients with large lesions or lesions near critical structures.
- Kim YJ, Cho KH, Kim JY, Lim YK, Min HS, Lee SH, et al. Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases. Int J Radiat Oncol Biol Phys 2011;81:483-9.
- Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, 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;29:134-41.
- Weiss SE, Kelly PJ. Neurocognitive Function after WBRT Plus SRS or SRS Alone. Lancet Oncol 2010;11:220-1.
- Mahmood U, Kwok Y, Regine WF, Patchell RA. Whole Brain Irradiation Forpatients with Brain Metastases: Still the Standard of Care. Lancet Oncol 2010;11:221-2.
- Aoyama H, Shirato H, Onimaru R, Kagei K, Ikeda J, Ishii N, et al. Hypofractionated Stereotactic Radiotherapy Alone without Whole-Brain Irradiation for Patients with Solitary and Oligo Brain Metastasis using Noninvasive Fixation of the Skull. Int J Radiat Oncol Biol Phys 2003;56:793-800.
- Khan M, Lin J, Liao G, Li R, Wang B, Xie G, et al. Comparison of WBRT Alone, SRS Alone, and their Combination in the Treatment of One or More Brain Metastases: Review and Meta-Analysis. Tumour Biol 2017;39:1010428317702903.
- Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic Radiosurgery for Patients with Multiple Brain Metastases (JLGK0901): A MultiInstitutional Prospective Observational Study. Lancet Oncol 2014;15:387-95.
- Minniti G, Scaringi C, Paolini S, Lanzetta G, Romano A, Cicone F, et al. Single-Fraction Versus Multifraction (3×9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis. Int J Radiat Oncol Biol Phys 2016;95:1142-8.
- Minniti G, Clarke E, Lanzetta G, Osti MF, Trasimeni G, Bozzao A, et al. Stereotactic Radiosurgery for Brain Metastases: Analysis of Outcome and Risk of Brain Radionecrosis. Radiat Oncol 2011;6:48.
- Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Brenema JC. Irradiated Volume as a Predictor of Brain Radionecrosis after Linear Accelerator Stereotactic Radiosurgery. Int J Radiat Oncol Biol Phys 2010,77:996- 1001.
- Lippitz B, Lindquist C, Paddick I, Peterson D, O’Neill K, Beaney R, et al. Stereotactic Radiosurgery in the Treatment of Brain Metastases: The Current Evidence. Cancer Treat Rev 2014;40:48-59.
- Lesueur P, Lequesne J, Barraux V, Kao W, Geffrelot J, Grellard JM, et al. Radiosurgery or Hypofractionated Stereotactic Radiotherapy for Brain Metastases from Radioresistant Primaries (Melanoma and Renal Cancer). Radiat Oncol 2018;13:138.
- Marcrom SR, McDonald AM, Thompson JW, Popple RA, Riley KO, Markert JM, et al. Fractionated Stereotactic Radiation Therapy for Intact Brain Metastases. Adv Radiat Oncol 2017;2:564-71.
- Murai T, Ogino H, Manabe Y, Iwabuchi M, Okumura T, Matsushita Y, et al. Fractionated Stereotactic Radiotherapy using Cyber Knife for the Treatment of Large Brain Metastases: A Dose Escalation Study. Clin Oncol 2014;26:151-8.
- Feuvret L, Vinchon S, Martin V, Lamproglou I, Halley A, Calugaru V, et al. Stereotactic Radiotherapy for Large Solitary Brain Metastases. Cancer Radiother 2014;18:97-106.
- Ernst-Stecken A, Ganslandt O, Lambrecht U, Sauer R, Grabenbauer G. Phase II Trial of Hypofractionated Stereotactic Radiotherapy for Brain Metastases: Results and Toxicity. Radiother Oncol 2006;81:18-24.
- Narayana A, Chang J, Yenice K, Chan K, Lymberis S, Brennan C, et al. Hypofractionated Stereotactic Radiotherapy Using Intensity-Modulated Radiotherapy in Patients with One or Two Brain Metastases. Stereotact Funct Neurosurg 2007;85:82-7.
- Kwon AK, Dibiase SJ, Wang B, Hughes SL, Milcarek B, Zhu Y. Hypofractionated Stereotactic Radiotherapy for the Treatment of Brain Metastases. Cancer 2009;115:890-8.
- Wiggenraad R, Kanter AV, Kal HB, Taphoorn M, Vissers T, Struikmans H. Dose-Effect Relation in Stereotactic Radiotherapy for Brain Metastases. A Systematic Review. Radiother Oncol 2011;98:292-7.
- 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;70:510-4.
- Cho KH, Hall WA, Gerbi BJ, Higgins D, Bohen M, Clark HB. Patient Selection Criteria for the Treatment of Brain Metastases with Stereotactic Radiosurgery. J Neurooncol 1998;40:73-86.
- Kim SH, Weil RJ, Chao ST, Toms SA, Angelov L, Vogelbaum MA, et al. Stereotactic Radiosurgical Treatment of Brain Metastases in Older Patients. Cancer 2008;113:834-40.
- Inoue HK, Sato H, Suzuki Y, Saitoh JI, Noda SE, Seto KI, et al. Optimal Hypofractionated Conformal Radiotherapy for Large Brain Metastases in Patients with High Risk Factors: A Single-Institutional Prospective Study. Radiat Oncol 2014;9:231.
- Peng L, Grimm J, Gui C, Shen CJ, Redmond KJ, Sloan L, et al. Updated Risk Models Demonstrate Low Risk of Symptomatic Radionecrosis Following Stereotactic Radiosurgery for Brain Metastases. Surg Neurol Int 2019;10:32.
- Fahrig A, Ganslandt O, Lambrecht U, Grabenbauer G, Kleinert G, Sauer R, et al. Hypofractionated Stereotactic Radiotherapy for Brain Metastases-Results from Three Different Dose Concepts. Strahlenther Onkol 2007;183:625-30.
- Kohutek ZA, Yamada Y, Chan TA, Brennan CW, Tabar V, Gutin PH, et al. Long-Term Risk of Radionecrosis and Imaging Changes after Stereotactic Radiosurgery for Brain Metastases. J Neurooncol 2015;125:149-56.
- Donovan EK, Parpia S, Greenspoon JN. Incidence of Radionecrosis in Single-Fraction Radiosurgery Compared with Fractionated Radiotherapy in the Treatment of Brain Metastasis. Curr Oncol 2019;26:e328-33.
- Zhuang H, Zheng Y, Wang J, Chang JY, Wang X, Yuan Z, et al. Analysis of Risk and Predictors of Brain Radiation Necrosis after Radiosurgery. Oncotarget 2016;7:7773-9.