International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationSingle-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
Introduction
Stereotactic radiosurgery (SRS) alone has become an increasingly utilized treatment option in the initial management of patients with brain metastases. Its efficacy has been demonstrated in randomized trials that report a local control (LC) rate of approximately 75% at 1 year and a survival benefit similar to that observed with the use of SRS plus whole-brain radiation therapy (WBRT) 1, 2, 3.
The most common late-delayed radiation effect of SRS is the development of brain radionecrosis (RN), which is associated with the presence of different degrees of neurologic deficits in up to one-third of patients 4, 5, 6. Factors correlated with the development of RN are radiation dose, tumor volume, use of chemotherapy, and volume of normal brain irradiated at specific doses 5, 6, 7, 8, 9, 10. Using the normal brain volume exposed to 12 Gy (V12-Gy) during SRS to predict the risk of developing RN, a few studies have observed an occurrence of necrosis up to 60% for V12-Gy >10 cm3 4, 5, 6, 7, and this is likely to happen when treating large lesions.
Multifraction SRS (MF-SRS, 2-5 fractions) has been used as an alternative to single-fraction SRS (SF-SRS), with the aim to reduce the incidence of late radiation-induced toxicity while maintaining high LC rates. Using doses of 24 to 35 Gy given in 3 to 5 fractions, a few retrospective studies have reported an LC rate of 70% to 90% at 1 year, with a variable risk of RN in the range of 2% to 15% 11, 12, 13, 14.
In the present study we evaluated the LC and incidence of RN in patients who received SF-SRS or MF-SRS (3 × 9 Gy) for brain metastases >2 cm in size. Related factors associated with clinical outcomes and the development of RN were assessed.
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Methods and Materials
Between September 2008 and October 2014, 354 consecutive patients aged ≥18 years with cerebral metastases >2 cm on contrast-enhanced magnetic resonance imaging (MRI) derived from a histologically confirmed systemic cancer, and who received SF-SRS or MF-SRS (3 × 9 Gy), were retrospectively evaluated. All radiographic, surgical, and pathologic information was drawn from a prospectively maintained database of patients with brain tumors treated at Sant'Andrea Hospital, University of Rome Sapienza.
Patient characteristics and survivals
A total of 289 consecutive patients with 343 metastases >2 cm in size were analyzed. Patient characteristics are shown in Table 1. One hundred fifty-one patients received SF-SRS, and 138 patients received MF-SRS. Two hundred sixty-one received 1 or 2 lines of therapy before SRS. There were no statistically significant differences between groups in terms of gender, age, histology, Karnofsky performance status (KPS) scores, the diagnosis-specific graded prognostic assessment score (22), site of
Discussion
The results of this study, in which either SF-SRS or MF-SRS was delivered to patients with brain metastases >2 cm in diameter, indicate that MF-SRS is superior in terms of LC and risk of RN. The above findings are strengthened by propensity score analyses, which address potential bias when retrospective data of two nonrandomized groups are compared.
Worse LC has been seen in patients with large lesions after SF-SRS 23, 24, 25, 26. Using the RTOG recommended dose of 15 Gy for lesions >3 cm in
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Conflict of interest: none.