Transcatheter Embolization of Liver Metastases

Radioembolization

When ⁹⁰ Y, a pure beta-emitting radioisotope, is combined with an embolic material and is injected into the tumor via the tumor hepatic arterial supply, the limited tissue penetration of beta particles leads to the deposition of energy in the tumor while relatively sparing the surrounding liver parenchyma. 90Y has a short half-life of approximately 64 hours, with a maximum energy of the beta particles of 2.27 MeV and a mean energy of 0.93 MeV. The deposition of ⁹⁰ Y particles within liver metastases has been shown to result in tumor necrosis, which is radiation-mediated rather than a result of microarterial embolization.

When considering radioembolization as a therapy for liver metastases, there are some general considerations to be made regarding patient suitability, in addition to the disease-specific factors, which are discussed later in this chapter.

• 1.

  The patient should be medically fit for the procedure, and this is often quantified using the Eastern Cooperative Oncology Group (ECOG) performance status scale ( Table 35.1 ). Typically a patient is considered with an ECOG score of 0–2, and an ECOG score of 2 or greater is taken to be a relative contraindication to treatment.

  TABLE 35.1

  Eastern Cooperative Oncology Group (ECOG) Scoring System

  ECOG Scale	Characteristics
  0	Fully active, able to carry on all predisease performance without restriction
  1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  2	Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
  3	Capable of only limited self-care; confined to bed or chair more than 50% of waking hours
  4	Completely disabled; cannot carry on any self-care; totally confined to bed or chair
  5	Dead

• 2.

  The patient should have liver-dominant or liver-only disease, and the pathology should be unresectable.

• 3.

  Liver function should be adequate given the potential complication of radiation hepatitis and liver failure. Prothrombin time, albumin, and total bilirubin give the best assessment of overall liver function. A bilirubin <34 μmol/L has been used as a cutoff, although, again, clinical judgment should be exercised.

• 4.

  A life expectancy of more than 3 months is sometimes taken as a criteria for treatment.

• 5.

  Iodinated contrast allergy and impaired renal function may preclude treatment.

Patients without an intact sphincter of Oddi, whether due to previous surgery or endoscopic sphincterotomy, are at increased risk of biliary sepsis after radioembolization due to bacterial colonization of the biliary tree, and these patients should receive antibiotic prophylaxis before and after the procedure. Patients with biliary obstruction should undergo endoscopic or percutaneous drainage before radioembolization, due to the risk of biliary necrosis. Attention should be paid to the chemotherapy the patient is receiving. Capecitabine increases the radiation sensitivity of tissues.

Any decision to proceed with radioembolization should be made by a multidisciplinary team made up of interventional radiology, medical oncology, radiation oncology, surgical oncology, nuclear medicine, and hepatology. All risks and benefits should be reviewed in detail with the patient. Once a patient is considered to be a candidate for radioembolization, planning begins with review of a multiphase computed tomography (CT) scan. Arterial phase images are reviewed to define the arterial supply to the liver and to identify any anatomical variants. The gastroduodenal artery, right hepatic artery, and any other hepatic artery branches supplying nontarget organs are identified. The portal venous phase images are assessed to ensure that the disease remains liver-confined or liver-dominant, and also to assess portal vein patency. Although portal vein thrombosis was previously considered a contraindication to radioembolization, radioembolization has been performed safely in this setting. Glass microspheres may be preferred over resin microspheres in these cases because of their reduced embolic potential.

The next stage is a planning procedure involving hepatic angiography and low-dose radionuclide injection. With knowledge of the patient’s anatomy already gained from the CT, digital subtraction angiograms are performed from multiple locations, with the primary aim of identifying any anastomoses to the enteric circulation. Nontarget radioembolization of the stomach and bowel can result in severe and insidious injury, and should be avoided. Acute pancreatitis has also been described as a complication of nontarget radioembolization.

Traditional teaching was that all potential sites of vascular communication needed to be identified and occluded with endovascular coils. The vessels that were targeted for embolization included the gastroduodenal artery, right gastric artery, supraduodenal artery, retroduodenal artery, and falciform artery, among others. However, as experience has evolved, aggressive coil embolization is increasingly being considered unnecessary as a routine practice, although coiling of vessels is still undertaken where it is felt likely to be of benefit. In the absence of coil embolization, clear identification of these collaterals is key and necessitates good-quality angiography. High flow rates are required to ensure visualization of potentially small collaterals that may only be seen with relatively forceful contrast injection. When identified, accessing a falciform artery with a microcatheter to perform coil embolization can be technically challenging, and it has been shown that using an ice pack on the abdominal wall to vasoconstrict the cutaneous vasculature is effective for avoiding skin complications.

Before technetium99m macroaggregated albumin ( ^99m TcMAA) injection, a decision must be made regarding how the radioembolization procedure will be performed in light of the angiographic findings. In cases where a whole liver treatment is planned for treatment of metastases in both lobes, this is typically done in a staged lobar fashion because of the lower risks of complications when compared with delivery of the entire radiation dose to the whole liver in one procedure. In this scenario, the microcatheter is positioned in the right and left hepatic arteries in turn, and the ^99m Tc MAA dose is divided between the two injection points. Alternatively, in cases where the disease is more localized, the treatment can be administered in a more selective fashion to two or fewer segments, in a technique termed radiation segmentectomy.

After vessel mapping and coiling of any potentially problem vessels, and once the treatment plan has been decided, the microcatheter is positioned at the planned point or points of radioembolization. A cone-beam CT scan can be performed from each of these positions to assess the volume of liver that will be treated and to ensure adequate coverage of the target liver lesions. After this, the ^99m Tc MAA is injected.

^99m Tc MAA has a similar diameter to ⁹⁰ Y microspheres and acts as a useful surrogate for distribution of the particles after treatment. After the ^99m Tc MAA has been injected from the proposed treatment sites, the patient is transferred to nuclear medicine for a single-photon emission computed tomography (SPECT) CT scan. In hypervascular lesions predominantly supplied by the hepatic artery, ^99m Tc MAA uptake in the lesions will be high relative to background liver, and this relatively high uptake within the lesions has been shown to correlate with an improved response to treatment.

In addition to the pattern of ^99m Tc MAA uptake, assessment is made of two key criteria that will further decide whether a patient is suitable for radioembolization.

• 1.

  The deposition of any tracer in the stomach, bowel, pancreas, or other unintended organ is identified, which might lead to complications in the event of proceeding to radioembolization.

• 2.

  The degree of lung shunting is calculated. In all patients a degree of atriovenous shunting will take place in the liver, leading to deposition of radioembolic material in the lungs. The lung shunt fraction is calculated using the formula (total lung counts)/(total lung counts + total liver counts). The acceptable dose to the lungs is taken to be 30 Gy in one treatment and 50 Gy cumulatively over multiple treatments. Exceeding this dose can lead to the severe complication of radiation pneumonitis. In cases where this lung threshold could be reached or exceeded, it may be necessary to reduce the planned treatment dose. Patients with underlying lung conditions such as chronic obstructive pulmonary disease or interstitial lung disease may have a lower tolerance for shunted radiation to the lungs, and the treatment dose may need to be tailored accordingly.

After the ^99m Tc MAA planning studying and assuming the patient is suitable for treatment, the radioembolization procedure is arranged. A single-session planning study and radioembolization has been described, but this is not commonplace and requires significant institutional experience. There are currently two commercially available systems for the delivery of ⁹⁰ Y to the liver: SIR-Spheres and TheraSpheres.