Radioembolization for liver tumors

Biological effects of radiation

Radiation is known to damage cellular DNA and ultimately lead to cell death. The energetic electrons that damage cellular DNA may arise from either internal radionuclide decay or from interactions in tissue from external photons/protons. The indirect action is caused by the production of hydroxyl radicals (OH ⁻ ) when the secondary electron interacts with a water molecule, which is responsible for two thirds of the x-ray damage to DNA. The main mechanisms of cell death include mitotic death, apoptosis, and the bystander effect.

The basic principle of radiation therapy is to maximize radiation absorbed dose within diseased tissue while sparing dose where disease is absent (see Chapter 95 ). Among other considerations, external beam radiation dose plans are ultimately limited by radiation to normal tissue at both entry and exit. A benefit to brachytherapy is its ability to emit energy internally, which enables limiting of the normal tissue absorbed doses. Transarterial radioembolization with yttrium-90 is a form of brachytherapy and has often also been referred to as selective internal radiation therapy (SIRT). In conventional radiotherapy, the probability of tumor response is known to be related to the radiation absorbed dose. SIRT has been for many years primarily a palliative treatment, so careful dosimetric treatment planning was not routinely performed and large uncertainties in absorbed dose calculations have been clinically acceptable. However, the potential of SIRT goes well beyond palliation, as demonstrated by recently published correlations between dosimetry and tumor response and survival. ^, With recent evidence for tumor and parenchymal dose response thresholds with ⁹⁰ Y radioembolization, ^, SIRT has expanded from a whole-liver salvage agent to a precise instrument for definitive, high-dose, conformal radiotherapy.

Transarterial radiation delivery

The preferential delivery of SIRT to liver tumors via the transarterial approach is based on two anatomic and pathologic factors: the normal liver parenchyma receives ≥75% of its blood from the portal vein, whereas liver tumors derive 80% to 100% of their blood supply from the hepatic artery (see Chapter 2 ); and the neovascularization around tumors leads to increased microvascular density in liver lesions compared with normal liver parenchyma. These features mean that when ⁹⁰ Y-microspheres are released into the hepatic artery, they will preferentially accumulate in the periphery of tumors in at least a 3:1 to 20:1 ratio compared with a normal liver.

⁹⁰ Y-microspheres must be deposited in the network of tumor vessels within the tumors. Any particles situated within the afferent tumor vessels, more than 3 mm from the tumor, will not have a direct antitumor effect. For this reason, the particles that are used for SIRT need to be small enough (~20 to 40 mm) to allow optimal penetration and deposition within the tumor plexus, but large enough to prevent the passage of microspheres through the capillary bed into the venous circulation that escapes the liver. The principles and mode of action of SIRT are fundamentally different from transarterial chemoembolization (TACE) (see Chapter 94A ); in TACE, the vessels that feed the tumor are filled with chemotherapeutic agents and subsequently embolized with particles to ensure a static, ischemic environment to maximize exposure to those agents and to promote ischemic necrosis. In contrast, optimal perfusion and blood flow are required during SIRT to allow the generation of free radicals by ionization of water molecules near the tumor cell’s DNA.

Patient selection

All patients should undergo a multidisciplinary clinical evaluation including professionals from interventional radiology; hepatology; medical, surgical, and radiation oncology; and nuclear medicine. Clinical history, physical examination, and laboratory liver function profiling should be examined carefully. In addition, detailed radiologic imaging is needed, showing unequivocal and measurable evidence of hepatic lesions that cannot be surgically resected or ablated with curative intent, and arterial anatomy conducive for hepatic arteriography. The best candidates for SIRT are patients with unresectable liver-only or liver-dominant tumors.

Dosimetry methods