Journal of Neuro-Oncology

, Volume 123, Issue 1, pp 103–111 | Cite as

Hypofractionated radiosurgery has a better safety profile than single fraction radiosurgery for large resected brain metastases

  • Bree R. EatonEmail author
  • Michael J. La Riviere
  • Sungjin Kim
  • Roshan S. Prabhu
  • Kirtesh Patel
  • Shravan Kandula
  • Nelson Oyesiku
  • Jeffrey Olson
  • Walter Curran
  • Hui-Kuo Shu
  • Ian Crocker
Clinical Study


The purpose of this study is to compare the safety and efficacy of single fraction radiosurgery (SFR) with hypofractionated radiosurgery (HR) for the adjuvant treatment of large, surgically resected brain metastases. Seventy-five patients with 76 resection cavities ≥ 3 cm received 15 Gray (Gy) × 1 SFR (n = 40) or 5–8 Gy × 3–5 HR (n = 36). Cumulative incidence of local failure (LF) and radiation necrosis (RN) was estimated accounting for death as a competing risk and compared with Gray’s test. The effect of multiple covariates was evaluated with the Fine-Gray proportional hazards model. The most common HR dose-fractionation schedules were 6 Gy × 5 (44 %), 7–8 Gy × 3 (36 %), and 6 Gy × 4 (8 %). The median follow-up was 11 months (range 2–71). HR patients had larger median resection cavity volumes (24.0 vs. 13.3 cc, p < 0.001), planning target volumes (PTV) (37.7 vs. 20.5 cc, p < 0.001), and cavity to PTV expansion margins (2 vs. 1.5 mm, p = 0.002) than SFR patients. Cumulative incidence of LF (95 % CI) at 6 and 12-months for HR versus SFR was 18.9 % (0.07–0.34) versus 15.9 % (0.06–0.29), and 25.6 % (0.12–0.42) versus 27.2 % (0.14–0.42), p = 0.80. Cumulative incidence of RN (95 % CI) at 6 and 12 months for HR vs. SFR was 3.3 % (0.00–0.15) versus 10.7 % (0.03–0.23), and 10.3 % (0.02–0.25) versus 19.2 % (0.08–0.34), p = 0.28. On multivariable analysis, SFR was significantly associated with an increased risk of RN, with a HR of 3.81 (95 % CI 1.04–13.93, p = 0.043). Hypofractionated radiosurgery may be the more favorable treatment approach for radiosurgery of cavities 3–4 cm in size and greater.


Hypofractionated Radiosurgery Brain Central nervous system Metastases 


Conflict of interest

Ian Crocker serves as a consultant for Varian Medical Systems (Varian, Palo Alto, CA).


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Bree R. Eaton
    • 1
    • 4
    Email author
  • Michael J. La Riviere
    • 1
  • Sungjin Kim
    • 2
    • 5
  • Roshan S. Prabhu
    • 1
    • 6
  • Kirtesh Patel
    • 1
  • Shravan Kandula
    • 1
  • Nelson Oyesiku
    • 3
  • Jeffrey Olson
    • 3
  • Walter Curran
    • 1
  • Hui-Kuo Shu
    • 1
  • Ian Crocker
    • 1
  1. 1.Department of Radiation OncologyWinship Cancer Institute of Emory UniversityAtlantaUSA
  2. 2.Department of Biostatistics and BioinformaticsWinship Cancer Institute of Emory UniversityAtlantaUSA
  3. 3.Department of NeurosurgeryWinship Cancer Institute of Emory UniversityAtlantaUSA
  4. 4.Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  5. 5.Biostatistics and Bioinformatics Research CenterCedars-Sinai Medical CenterLos AngelesUSA
  6. 6.Southeastern Radiation Oncology GroupLevine Cancer InstituteCharlotteUSA

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