The Emerging Synergy between Radioembolization, Systemic Chemotherapy, and Liver Surgery in Metastatic Colorectal Cancer

The Emerging Synergy between Radioembolization, Systemic Chemotherapy, and Liver Surgery in Metastatic Colorectal Cancer

Harpreet S Wasan
US Oncological Disease 2007 - Issue I
Published: October 2008
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Table 1: Investigational First-line Treatments for Metastatic Colorectal Cancer


These important new advances in biologic and cytotoxic agents have resulted in a significant prolonging of median survival time from approximately six months with 5FU-containing chemotherapy regimens8 to an excess of 20 months in some studies.5,9,10 Yet, despite these valuable gains, metastatic colorectal cancer is almost always fatal, with up to 90% of patients dying of liver failure caused by local effects of hepatic tumors. In high-risk patients with non-resectable and chemo-refractive liver tumors, therapies should be considered palliative, with the primary aim of treatment being to achieve a maximum reduction in tumor cell burden and improvements in progressionfree survival and quality of life, as well as improving overall survival. External-beam radiation therapy (EBRT) is a cornerstone of curative and palliative therapy in nearly all malignancies, but has not been applied with much success to hepatic disease due to the low tolerance of the organ to radiation compared with tumor. Significant technological advances in radiation treatment planning and delivery—which may benefit an increasing number of patients with liver metastases—have led to improved tumordirected radiotherapy approaches, such as:

• 3-D radiotherapy;

• intensity-modulated radiotherapy; and

• stereotactic radiotherapy.

Figure 1: Kaplan-Meier Survival Curve Following First-line Treatment SIR-Spheres plus 5FU/LV or 5FU/LV Alone in 21 Patients with Metastatic Colorectal Cancer12
Figure 2: Kaplan-Meier Survival Curve from Day of Treatment to Censure or Death in 208 Patients with Chemotherapy-refractory Disease Treated with SIR-Spheres

However, the key limitation of this treatment is the tolerance of normal liver parenchyma to radiation. The maximum acceptable dose to the whole liver is 35Gy, which is far below the required dose to destroy adenocarcinoma metastases, estimated at 70Gy or above (for monotherapy) or at 50Gy or above when concurrent chemotherapy is given. An alternative approach is the implantation of radiation sources into the tumor (brachytherapy).

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