Bevacizumab as a treatment for radiation necrosis following stereotactic radiosurgery for brain metastases: clinical and radiation dosimetric impacts

Background: Brain necrosis (RN) is a common radiotherapy sequela for brain metastases. Bevacizumab is identified as a therapeutic strategy for RN. This study aimed to study the clinical and radiobiological impacts on the efficacy of Bevacizumab in treating RN following stereotactic radiosurgery (SRS) for brain metastases. Methods: From April 2011 to November 2019, 40 patients diagnosed with RN after SRS for brain metastases were retrospectively analyzed. Patients were treated with Bevacizumab for RN and follow-up for 6 months using MR imaging at different timepoints. Linear regression was performed to evaluate the relationship between these variables. Results: The median time course from the end of radiotherapy to the onset of RN was 11 months (range, 7-35 months). No significant difference was found in the edema volume between the chemotherapy group and non-chemotherapy group (P>0.05). Patients received with SRS + WBRT exhibited relatively larger edema volumes post radiotherapy than those without WBRT (P<0.05). Interestingly, the ratio of BED/GTV (Gy/cm(3)) correlated positively with the severity (time for half-reduction dose of corticosteroids) (r(2)=0.13, P<0.05), and negatively with the latency period (time course for development of radiation-induced brain necrosis) (r(2)=0.21, P<0.01). A new radiation doses volume index, BED x GTV (Gy.cm(3)), was proposed to facilitate the risk stratifications of patients for radiation-induced brain necrosis. Furthermore, no significant difference was found in alleviating brain edema between different regimens of Bevacizumab, i.e., 5 vs. 10 mg/kg, 2 vs. >2 cycles (both P>0.05). Conclusions: Bevacizumab is a feasible and favorable salvage treatment of BN after SRS for patients with BM. The efficacy is mainly manifested in radiological improvement and symptoms alleviation. The development of RN was found to be largely associated with radiation dose and gross tumor volume, and thus we proposed two new indexes, i.e., BED/GTV (Gy/cm(3)) for quantitative assessment of the severity and latency time, and BED x GTV (Gy.cm(3)) for risk stratifications for BN. A low dose with two cycles of Bevacizumab is recommended.