Abstract:

Purpose
Investigate the effects of angiogenesis inhibition from pretreatment with bevacizumab (Avastin) on yttrium-90 (⁹⁰Y) microsphere administration, tumor-to-normal liver vascularity ratio (TNVR) and survival in patients treated for metastatic colorectal cancer (mCRC).

Material and Methods
Retrospective review was performed of patients treated with ⁹⁰Y radioembolization for mCRC at our institution between May 2008 and March 2012. Patients were divided into those with and without pre-treatment with bevacizumab prior to radioembolization and subgroupings based on number of months (< 3, 3-9, and > 9 mo) from their last bevacizumab dose. Outcome variables included TNVR, whether the procedure was stopped due to slow flow and survival. TNVR was hypothesized to decrease with prior bevacizumab treatment and shorter intervals from last dose. Statistics were used to determine if pre-treatment with bevacizumab had a significant impact on ⁹⁰Y microsphere administration and TNVR.

Results
Thirty nine patients (22 M, 17 F) met the inclusion criteria with mean age of 64.1 years. Nine patients did not and 30 patients did have pre-treatment with bevacizumab. The interval between the last bevacizumab dose and the MAA infusion was ≤ 3 mo in 17 patients. The mean total hepatic tumor volume and mean total target tumor dose was 202.7 cubic centimeters (cc) and 308 Gray (Gy) in no bevacizumab patients and 258.3 cc and 262.3 Gy in patients with prior treatment, respectively. The number of patients with at least one infusion stopped due to slow flow was 3 of 9, 14 of 30, and 12 of 17 in the no bevacizumab, bevacizumab at any prior time, and bevacizumab within the last 3 months prior to MAA groups, respectively. Percentage of the total number of infusions stopped due to slow flow was 27.8%, 31.0%, and 39.4% for the same respective groups. TNVR was calculated for treatment planning in 26 of the subjects, 20 of these received prior bevacizumab. There was no significant difference in TNVR between the patients treated with and without bevacizumab (p=0.46).  Subgroupings of TNVR based on interval from last bevacizumab dose to MAA infusion were not significantly different from each other and the no bevacizumab group (p=0.68). Mean patient survival from mCRC diagnosis and from date of Y-90 treatment was respectively 30.8 mo and 19.8 mo for the no bevacizumab group, 31.6 mo and 12.6 mo for the prior bevacizumab group, and 27.6 mo and 13.3 mo for the bevacizumab within 3 mo of the Y-90 treatment group.

Conclusions
Treatment with bevacizumab in mCRC patients prior to radioembolization did not significantly decrease or affect TNVR in the liver. However, patients with bevacizumab dose within 3 months of MAA had an increased rate of infusions stopped due to slow flow. Prior bevacizumab did not increase survival in patients undergoing radioembolization. Compared to historical controls treated with modern chemotherapy alone, mCRC patients treated with ^90Y appear to have survival benefit.

Primary Author:

Dmitry Y. Goldin, MD
Radiology Resident - PGY4, William Beaumont Hospital, Oakland University William Beaumont School of Medicine