Neal Andruska, MD, PhD
Central Nervous System
Purpose/Objective(s): To examine the risk factors associated with the development of symptomatic radiation necrosis (sRN) among patients with brain metastases undergoing fractionated stereotactic radiosurgery (fSRS).
Materials/Methods: Patients with brain metastases treated with 5-fraction fSRS at our institution with clinical and radiographic follow-up were retrospectively reviewed. fSRS was delivered using either a Cobalt-based or LINAC-based system. sRN was defined as grade 2 or higher per CTCAE v4.0. Biologically equivalent dose in 2 Gy fractions (EQD2) was calculated using the linear-quadratic model assuming α/β ratio of 3 for brain tissue. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. Rates of sRN were estimated using Kaplan-Meier method and compared using log-rank tests.
Results: From 2011-2018, 75 patients were treated at the following prescription dose levels: 25 (n = 12), 30 (n = 46), 35 (n = 14), and > 35 Gy (n = 3) in five fractions. 53 patients had not received intracranial radiation, while 22 patients (29%) had received prior brain radiation to the site of interest. The most common metastasis histology was non-small cell lung cancer (n = 36), followed by breast (n = 11), melanoma (n = 6), and colorectal (n = 5). At a median follow-up of 8 months (range 1.2 – 48), 14 patients (18.4%) developed sRN, with an equal number of sRN events in patients with and without prior intracranial RT. Among patients without prior radiation, 0% had sRN after 25 Gy (n = 5), 11.1% had sRN after 30 Gy (n = 34), 15.1% had sRN after 35 Gy (n = 14), and 100% had sRN after 40 Gy (n = 1). For patients without prior RT, radiation doses above 30 Gy were associated with increased risk of radiation necrosis (HR: 9.4, CI: 1.5 - 58.4, p = 0.016). After accounting for prior radiation exposure, a cumulative EQD2 > 60 Gy was associated with significantly higher rates of radiation necrosis (HR: 5.7, CI: 1.7 - 18.9, p = 0.004). At 1 year, 10.8% of patients with a cumulative EQD2 < 60 Gy and 59.5% of patients with an EQD2 > 60 Gy developed sRN (p = 0.002).
Conclusion: In the absence of prior intra-cranial radiation, fSRS of up to 30 Gy in 5 fractions for brain metastasis appear to have relatively low incidence of sRN, but the tolerability of doses ≥ 35 Gy may require further investigation. Cumulative EQD2 > 60 Gy appears to be associated with higher risk of sRN. Further detailed dosimetric data with longer follow-up data is underway to better ascertain the significance of these findings.
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