Peri-SRS Administration Of Bevacizumab Offers Promising Efficacy For Large Brain Metastases With Tolerable Toxicity: A Prospective Case Series

Abstract

Brain metastases (BM) are the most common brain tumors in adults. It is estimated that around 10-30% of cancer patients would develop brain metastases during the course of their illness. Stereotactic radiosurgery (SRS) is the treatment of choice to achieve intracranial control while sparing neurocognitive function. However, the risk of radionecrosis (RN) after single-fraction SRS could be as high as 38% at 12 months if treated brain metastases were larger than 1.5 cm. Therefore, radiation dose is often compromised to avoid excessive toxicities. Herein, we propose a new combined treatment strategy to evaluate the efficacy and safety of SRS with concurrent bevacizumab for large brain metastases. Patients with the diameter of the largest BM ≥ 2 cm were enrolled for combined therapy. Bevacizumab with 5 to 10 mg/kg was given one day before the first fraction of radiosurgery and 2 weeks after the first dose. SRS was given in 1 to 5 fractions depending on tumor size. Radiographic response was assessed by RANO criteria. Intracranial (IC) metastasis progression-free survival (PFS), and overall survival (OS) were calculated by Kaplan-Meier analysis. Forty-eight patients were enrolled in this prospective case series. Nine patients (19%) had prior brain radiotherapy. The median number of BM per patient was 3 (range 1–22). The largest tumor diameter ranged from 20 to 54 mm (median 27.4 mm; 46% were ≥ 3 cm) and the median prescribed biological equivalent dose was 51.3 Gy10 (18.3 Gy single fraction equivalent). With a median follow-up of 18 months, the estimated median OS was 22.6 months (95% CI, 6.9 to 38.3 months) and the median ICPFS was 13.9 months (95% CI, 9 to 18.9 months). Only 4 patients developed local failure (LF). Significant radiographic response (complete and partial response, CR+PR) was achieved in 40 patients (83.3%). No grade 4 or 5 toxicities were observed. Eight patients (16.7%) developed ≥ grade 2 RN, and two of them required surgical intervention. After adjusting death as a competing risk, the cumulative incidence of LF, IC progression and RN at 12 months were 2.5% (95% CI, 0.3% to 17.9%), 39.4% (95% CI, 27.2% to 57.1%), and 14.4% (95% CI, 6.8% to 30.4%), respectively. Four patients (8.3%) had grade 3 hypertension. One patient experienced tumor hemorrhage without significant neurological deficit or need for intervention. Stereotactic radiosurgery with peri-radiosurgical Bevacizumab for large brain metastases is highly effective with low incidence of radionecrosis and low risk of excessive treatment-related toxicities. The combination strategy warrants further evaluation.Abstract 3723; TableMaximum relative tumor reduction and response rate observed as best response by RANO criteria among different tumor sizesLargest tumor diameterNumber of patientsMaximum relative tumor reduction (median, range)Response rate (CR+PR)2-2.5 cm1451% (7-100%)85.7%2.5-3 cm1354% (16-100%)92.3%3-3.5 cm838% (24-55%)75%>3.5 cm1335% (2-63%)76.9% Open table in a new tab