Purpose
Hepatic responses have been documented in patients (pts) with unresectable hepatic metastatic colorectal cancer (UHMCRC) following the trans-hepatic arterial delivery of Yttrium-90 (Y90) microspheres with adjuvant intra-hepatic arterial FUDR or systemic 5FU/LV or after administration of systemic irinotecan & oxaliplatinum. Recently, the integration of the biologic agents cetuximab (EGFR antagonist) & bevacizumab (anti-VEGF antibody) into the therapeutic armamentarium of patients with UHMCRC, in conjunction with chemotherapy, have resulted in significant improvements in time to tumor progression and survival. However upon failure of these agents and development of chemotherapy refractoriness, the feasibility of trans-arterial liver directed therapy in patients with liver dominant disease progression is unclear. We present our ongoing experience utilizing trans-arterial Y90 microspheres in this setting.
Material and methods
9 pts (8 male,1 female) median age 61 yrs (51-70 yrs) with poor to moderately differentiated asymptomatic UHMCRC were identified as meeting study criteria. 4 patients had hepatic only disease. 1 pt had prior hepatic resection & thermal ablation. Prior to Y90 microsphere therapy the average number of chemotherapy regimens received was 6. All pts had received combinations of systemic 5FU/LV &/or capecitabine, oxaliplatinum & bevacizumab. Similarly, 7 pts had received irinotecan & cetuximab. Hepatopulmonary shunt fraction was calculated by hepatic arterial injection of 5 mCi Tc99m MAA. After vascular exclusion of the extra-hepatic arteries originating from the hepatic arteries vessels via embolization, SIR-Spheres® infusions were performed under intermittent fluoroscopy. Clinical follow up, CT/MRI scans & CEA levels were utilized to assess for tolerability & response.
Results
Abdominal visceral arteriography demonstrated vasculature conducive for Y90 microsphere delivery in all patients. Median hepatopulmonary shunt fraction was 7.9% (2.7-9.5%). Median dose delivered was 33.2 mCi (16–54 mCi). Post delivery SPECT – CT fusion Bremsstrahlung scans confirmed preferential deposition within metastases. Median follow up is 5 months. CEA levels decreased in 4/7 pts. CT/MRI follow up, available in 7 pts, demonstrated stable disease in 3. No Gr. III hepatotoxicity was noted at 90 days. No gastric ulcerations occurred. All patients experienced transient Gr. I/II fatigue.
Conclusion
Liver directed therapy with Y90 microspheres, SIR-Spheres® , represents a potential therapy in pts with UHMCRC following administration of multiple systemic chemotherapy regimens including cetuximab and bevacizumab.