Radioembolization of hepatic tumors

Abstract

Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 ((90)Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy is being increasingly incorporated into the standard therapy algorithms of multidisciplinary GI cancer teams worldwide. This form of radiotherapy differs significantly from daily external beam radiotherapy in many ways, particularly in dose rate, dosimetric coverage and duration of radiation delivery, side effects, and patient selection factors. A wealth of experience using RE in solid tumors exists and ongoing major prospective clinical trials will soon clarify the role of RE in the management of metastatic colorectal liver metastases.

Keywords: Brachytherapy; Yttrium-90 (90Y); liver tumors.

Figure 1

Drawing of intraarterial microcatheter (2.7F) in a hepatic artery with release of radioactive microspheres (diameter 22-40 microns) containing ⁹⁰Y. The microspheres become permanently embedded in the terminal arterioles of the tumor.

Figure 2

Illustration of microscopic view in tumor. Panel A shows microspheres at too great a distance from each other and thus they lack radiation field overlap. This can lead to insufficient radiation dose deposition and tumor regrowth in these ‘cold spots’. Panel B illustrates the desired implantation goal of uniform coverage of tumor by implanted microspheres, which are less than 2 mm apart from each other and thus can produce overlapping radiation fields. Cumulative radiation absorbed by tumor will exceed tolerance of the tumor leading to successful elimination of the tumor.

Figure 3

H&E stained section of human liver containing hepatocellular carcinoma and resin ⁹⁰Y microspheres (dark spheres upper right) in an arteriole embedded deep in the tumor (Original magnification 40×).