Increased Hemorrhage During Excision of Bevacizumab-Treated NF2-Related Vestibular Schwannomas.

OBJECTIVES

To determine if the chronic use of bevacizumab, prior to withholding for elective surgery in the preoperative period, increases the risk of hemorrhage during vestibular schwannoma (VS) resections.

METHODS

Retrospective reviews of estimated intraoperative blood loss volume during surgical resection of 50 bevacizumab-treated and 56 bevacizumab-untreated VS from patients with NF2-related schwannomatosis (NF2-SWN). Two index cases are included. Additionally, masked histopathologic examination of tissues from bevacizumab-treated and untreated VS was evaluated.

RESULTS

The mean blood loss during VS resection was statistically increased in patients with prior bevacizumab treatment (421 mL) compared to untreated patients (285 mL) (p = 0.015). When accounting for both tumor size and the amount of tumor resected, blood loss per percent of tumor resected was also elevated in the bevacizumab treated group (15.78 mL/%resection) when compared to the untreated group (12.97 mL/%resection) (p = 0.024). Intraoperative hemostasis using standard techniques was difficult, and some cases resulted in early termination of the surgical procedure prior to total resection. Eighteen percent of bevacizumab-treated patients had gross total or near total tumor resection, while untreated tumors had 52% gross total or near total resections (p-value = 0.001). The length of time on bevacizumab preoperatively correlated with intraoperative blood loss (p = 0.049). The median time patients were treated with bevacizumab prior to surgery was 23.5 months and ranged from 3 to 121 months. The median time off bevacizumab prior to surgery was 11.5 months and ranged from 0.75 to 87 months. Histopathologic examination revealed no readily apparent difference in blood vessel density, integrity, or growth patterns.

CONCLUSIONS

Bevacizumab treatment prior to excision of NF2-SWN VS in this retrospective case series is associated with increased intraoperative hemorrhage. Bleeding was difficult to control using standard techniques, thus warranting preoperative surgical awareness. Underlying pathologic mechanisms are not yet understood and are under further investigation.