Radiation Necrosis Following Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy with High Biologically Effective Doses for Large Brain Metastases

In Radiation Therapy Oncology Group 90-05, the maximum tolerated dose of single-fraction radiosurgery (SRS) for brain metastases of 21–30 mm was 18 Gy (biologically effective dose (BED) 45 Gy₁₂). Since the patients in this study received prior brain irradiation, tolerable BED may be >45 Gy₁₂ for de novo lesions. We investigated SRS and fractionated stereotactic radiotherapy (FSRT) with a higher BED for radiotherapy-naive lesions. Patients receiving SRS (19–20 Gy) and patients treated with FSRT (30–48 Gy in 3–12 fractions) with BED > 49 Gy₁₂ for up to 4 brain metastases were compared for grade ≥ 2 radiation necrosis (RN). In the entire cohort (169 patients with 218 lesions), 1-year and 2-year RN rates were 8% after SRS vs. 2% and 13% after FSRT (p = 0.73) in per-patient analyses, and 7% after SRS vs. 7% and 10% after FSRT (p = 0.59) in per-lesion analyses. For lesions ≤ 20 mm (137 patients with 185 lesions), the RN rates were 4% (SRS) vs. 0% and 15%, respectively, (FSRT) (p = 0.60) in per-patient analyses, and 3% (SRS) vs. 0% and 11%, respectively, (FSRT) (p = 0.80) in per-lesion analyses. For lesions > 20 mm (32 patients with 33 lesions), the RN rates were 50% (SRS) vs. 9% (FSRT) (p = 0.012) in both per-patient and per-lesion analyses. In the SRS group, a lesion size > 20 mm was significantly associated with RN; in the FSRT group, lesion size had no impact on RN. Given the limitations of this study, FSRT with BED > 49 Gy₁₂ was associated with low RN risk and may be safer than SRS for brain metastases > 20 mm.