Radioembolization of Liver Metastases

Khairuddin Memon, Robert J. Lewandowski and Riad Salem

Clinical Relevance

Metastatic disease to the liver is the most common form of hepatic malignancy, the colon being the most common primary tumor location.¹ At presentation, most of these oncology patients are not candidates for operative cure, and many have failed systemic chemotherapeutic regimens. The safety and efficacy of radioembolization with yttrium-90 (⁹⁰Y) in these patients with liver-dominant disease and good performance status have been reported in the literature.^2–7 Radioembolization is performed using percutaneous transarterial techniques in the interventional radiology suite. By definition, radioembolization is injection of micron-sized embolic particles loaded with a radioisotope; an interdisciplinary team is crucial to the success of a ⁹⁰Y radioembolization program. This team should be well represented with members from interventional radiology, medical, radiation and surgical oncology, transplant surgery, nuclear medicine, radiation oncology, hepatology, and radiation safety.

Indications

⁹⁰Y can be delivered to the hepatic tumor as either a constituent of a glass microsphere, TheraSphere (Nordion Inc., Ottawa, Ontario, Canada), or as a biocompatible resin-based microsphere, SIR-Spheres (Sirtex Medical Inc., Lake Forest, Ill.).

TheraSphere was approved in 1999 by the U.S. Food and Drug Administration (FDA) under a Humanitarian Device Exemption (HDE) for treatment of unresectable hepatocellular carcinoma (HCC) in patients who can have appropriately positioned hepatic arterial catheters.⁸ Medical professionals are directed to published FDA guidance documents on HDEs for uses in diseases other than HCC.⁹ SIR-Spheres was granted full premarket approval in 2002 by the FDA for treatment of colorectal cancer (CRC) metastases in conjunction with intrahepatic floxuridine (FUDR).¹⁰ Given the FDA approval for both devices, their use in disease states other than the strict indication represents the practice of medicine. In other words, use of this therapy for indications other than HCC or colorectal liver metastases is not experimental, but rather supported by ample phase 2 data.

In general, indications for treatment of liver tumors using ⁹⁰Y include: (1) unresectability, (2) adequate hematologic and hepatic functions, (3) correctable gastrointestinal (GI) flow on technetium-99m–labeled macroaggregated albumin (^99mTc-MAA) scan, (4) cumulative lung dose for all treatments less than 50 Gy, and (5) liver-dominant disease and adequate performance status.

Contraindications

Appropriate patient selection is critical to avoid morbidity and mortality from radioembolization. Irrespective of liver tumor etiology, evaluating a patient for possible treatment with ⁹⁰Y should be driven by the patient’s Eastern Cooperative Oncology Group (ECOG) performance status (Table 67-1) rather than their clinical stage. From a practical standpoint, patients with ECOG 0, 1, or 2 status (equivalent to Karnofsky score of 60% or higher) should be considered for therapy. For patients who do not fulfill this criterion (ECOG > 2), there is a relative contraindication to radioembolization. Decision to treat these patients should be based on individual patient evaluation and clinical judgment and intent. Besides performance status, prothrombin time (PT), albumin, and total bilirubin should be scrutinized because they have been shown to be the best indicators of overall liver function.¹¹ If these values are abnormal, greater care must be taken in treating, given the relative higher risk for radiation-induced liver disease and failure. Once the patient is clinically deemed a candidate for radioembolization, angiography and ^99mTc-MAA infusion are performed. These tests may reveal further contraindications to treatment, which include uncorrectable flow to the GI system and excessive pulmonary shunting.¹²

TABLE 67-1

Performance Status Criteria

ECOG Scale	Characteristics	Equivalent Karnofsky Score
0	Asymptomatic and fully active	100%
1	Symptomatic, fully ambulatory, restricted in physically strenuous activity	80%-90%
2	Symptomatic, ambulatory, capable of self-care, more than 50% of waking hours are spent out of bed	60%-70%
3	Symptomatic, limited self-care, spends more than 50% of time in bed	40%-50%
4	Completely disabled, no self-care, bedridden	20%-30%

ECOG, Eastern Cooperative Oncology Group.

The lungs can tolerate 30 Gy per treatment session and 50 Gy cumulatively.¹³ Therefore, when treatment planning is undertaken and lung shunting is identified, the total cumulative pulmonary dose must be calculated. Patients may be treated if their cumulative pulmonary dose will not exceed 50 Gy cumulatively for all planned infusions of ⁹⁰Y. However, in patients with compromised pulmonary function, such as chronic obstructive pulmonary disease or previous lung resection, caution must be taken when approaching total cumulative doses. In these instances, the decision to treat must be individualized and based on overall clinical status.

Equipment

The TheraSphere administration set consists of one inlet set, one outlet set, one empty vial, and two interlocking units consisting of a positioning needle guide and a priming needle guide, all contained behind a Lucite shield. A MONARCH 30-mL syringe (Merit Medical, South Jordan, Utah) is used to infuse saline through the system. The saline solution containing the TheraSphere ⁹⁰Y microspheres is infused through a catheter placed in the hepatic vasculature. Once the catheter is positioned at the treatment site and the authorized user verifies the integrity of the delivery system, the catheter is connected to the outlet tubing. Delivery of TheraSphere is accomplished by pressurizing the MONARCH syringe.

The SIR-Spheres administration set consists of a Perspex shield, the dose vial, and inlet and outlet tubing with needles. Standard 10- or 20-mL injection syringes preloaded with sterile water are required to infuse the microspheres into the delivery catheter. Pressure gauges are not available when infusing SIR-Spheres.

Technique

Anatomy and Approaches

All radioembolization patients initially undergo mesenteric angiography and a ^99mTc-MAA lung shunting scan.12,14–16 The angiographic evaluation required has been described by Liu et al.¹⁴ An abdominal aortogram facilitates proper visceral catheter selection as well as assesses aortic tortuosity and mural atherosclerotic disease. The superior mesenteric artery is studied to assess any variant vessels to the liver (accessory or replaced right hepatic), as well as for visualization and identification of a patent portal vein. The celiac artery is injected to study the hepatic branch anatomy. Subsequently, selective left hepatic (flow to segments 2, 3, 4A, and 4B), right hepatic (flow to segments 1 [caudate lobe may have other blood supply], 5, 6, 7, and 8), and gastroduodenal (flow to the pancreas, stomach, small bowel, and omentum) arteriograms are performed. To visualize small vessels as well as vessels that may demonstrate reversal of flow (e.g., result of flow shunt, sumping secondary to hypervascular tumor), dedicated microcatheter injection with relatively high rates (2-3 mL/s for 8-12 mL) should be performed.¹⁴ Without adequate contrast bolus, many ancillary vessels (which have profound effect on hemodynamics and directed therapy) may go unnoticed. Although it may be argued that high injection rates may represent supraphysiologic flow dynamics, the potential changes induced as a result of regional therapy with radioembolization (spasm, ischemia, stasis, and vessel injury) may result in altered physiologic states and thus reflux into these vessels.

Aggressive prophylactic embolization of vessels prior to therapy is highly recommended, such that all hepaticoenteric arterial communications are completely eliminated. These vessels include the falciform, accessory or left phrenic, right or accessory gastric arteries (from the left hepatic artery), supraduodenal, retroduodenal, and accessory right hepatic artery feeding segment 6 (from gastroduodenal artery [GDA]). Reflux of microspheres into the GDA or gastric arterial circulation may result in grave clinical consequences that include severe ulceration, GI bleeding, or pancreatitis. Given the serious clinical risks of microsphere reflux into nontarget organs and the lack of clinical consequences of prophylactic embolization of the GDA/right gastric, the latter approach is strongly favored.7,14,16,17 Figure 67-1 demonstrates the principles of prophylactic embolization before radioembolization.