4. Radioembolization

MELD score greater than 15, Child C disease, portal venous thrombosis, thrombocytopenia, or the presence of ascites. While many of these criteria have excluded patients in the past, advancements in technology has led to selective and superselective chemoembolization allowing a number of these patients to be treated. Non-selective chemoembolization can damage surrounding healthy hepatic parenchyma leading patients to decompensated liver failure, especially those with poor hepatic reserve. With selective and superselective techniques, there is increased sparing of viable tissue. Many articles have exhibited TACE being safely performed in high-risk patients. One study demonstrated the rate of selective TACErelated irreversible liver failure to be 3% compared to 20% in nonselective cases [23]. Other studies showed TACE to be safe and effective in patients with portal venous thrombosis, especially in those with hepatic reserve and collateral circulation [24]. Kothary et al. analyzed 65 high-risk TACE procedures which showed a procedure-related morbidity rate of 10.8% and a 30-day mortality rate of 7.7% [25]. Yoon et al. observed a procedure-related morbidity rate of 2% and a 30-day mortality rate of 1% in 96 high-risk patients [26]. Overall, the general consensus seems to be on a case-to-case basis in which baseline hepatic function,

hepatic reserve, and overall tumor burden are commonly taken into account.

ulceration/perforation, pancreatitis, cholecystitis, pneumonitis, or skin burns.

procedurally which may lead to the misdiagnosis of a hepatic abscess.

chemotherapy-related toxicities such as alopecia, anemia, or myelosuppression.

or arteriovenous fistulas.

56 Medical Imaging and Image-Guided Interventions

3.4. Results

Non-target embolization can occur due to reflux of chemoembolic agents or failure to recognize the arterial anatomy supplying non-hepatic structures. This can lead to gastrointestinal

Hepatic abscess formation is rare in patients with unaltered anatomy. However, patients with post-surgical or disrupted anatomy of the biliary tree are at increased risk due to colonization of the biliary tree from enteric flora. One study showed 6 out of 7 patients with a prior bilioenteric anastomosis formed hepatic abscesses even after receiving standard broad spectrum prophylactic antibiotics [27]. Another study showed no formation of hepatic abscess in four patients with prior bilioenteric anastomosis when adding an aggressive bowel preparation [28]. In addition, gas formation within embolized hepatic tumors may occur post-

Vascular complications are uncommon but include access site hematomas, pseudoaneurysms,

Other rare complications include sepsis, biliary strictures, variceal bleeding, renal failure, or

Multiple studies have shown TACE to increase overall survival when compared to conservative management. A randomized control trial by Llovet et al. was terminated early as it demonstrated the one-year and two-year survival rates for chemoembolization to be 82 and 63% compared to 63 and 27% for supportive care [29]. Another randomized trial by Lo et al. showed the one-year and two-year survival rates for chemoembolization to be 57 and 31% compared to 32 and 11% for supportive care [30]. Two meta-analyses of randomized controlled trials by Camma et al. and Llovet et al. showed a significant decrease in 2 year mortality with Radioembolization, also known as selective internal radiation therapy (SIRT), consists of administering either glass or resin microspheres loaded with radioactive isotope, yttrium-90 (Y-90). Y-90 is a pure better emitter with a half-life of 64.1 h and a mean tissue penetration of 2–3 mm. Radioembolization is currently not part of the standard treatment guidelines. However, promising clinical research has driven its growing use in the management of hepatic malignancies. A multidisciplinary team consisting of surgeons, interventional radiologist, hepatologists, oncologists, and radiation oncologists determines if a patient is a candidate for Y-90 radioembolization. The Barcelona Clinic Liver Cancer (BCLC) and Eastern Cooperative Oncology Group (ECOG) scoring systems are taken into account in the decision process. The microspheres used today are either glass and resin microspheres. Glass microspheres, or TheraSpheres, is FDA approved for the treatment of unresectable HCC. Resin microspheres, or SIR-Spheres, is premarket approved by the FDA for the treatment of hepatic metastases from colorectal cancer in combination with floxuridine. Glass microspheres carry a higher activity load, thus requiring decreased volumes and number of spheres, compared to resin microspheres for the same dose [37]. Since resin microspheres require a higher volume, it would in theory produce a greater ischemic/embolic effect that would decrease the efficacy of delivering the full radiation dose. That being said, technical differences between the microspheres have not resulted in differences for overall survival in HCC [38]. Moreover computational studies comparing the resin and glass microspheres have demonstrated that particle trajectory in vessels have very little dependence on particle size. Indeed the authors concluded that the carrier fluid provides enough momentum to overcome the range of microspheres characteristics [39].

veno-occlusive disease, sinusoidal congestion, and necrosis. REILD is defined as liver failure within 90 days post-radioembolization or greater than 90 days without tumor progression. Patients with decreased baseline liver function, with whole liver treatments and polychemotherapy are at increased risk [41]. Low-dose steroids and ursodeoxycholic acid can

Liver Directed Therapies

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http://dx.doi.org/10.5772/intechopen.75163

Non-target embolization may also occur with the adverse effects similar to TACE. Gastrointestinal ulceration remains a risk though with careful administration technique and proper coil embolization during work-up, complications are decreased to less than 4% [42]. Radiation pneumonitis if very rare occurring less than 1% and is avoidable with proper work up.

Other rare complications include radiation pancreatitis, dermatitis, cholecystitis or cholangitis. In general, biliary complications occur in less than 10% of cases though patients with

Vascular complications are also similar to TACE. Patients on bevacizumab (Avastin) and other biologic agents (i.e. cetuximab, aflibercept, etc.) are at increased risk of dissection and rupture

Rarely lymphopenia may occur after glass microsphere radioembolization with greater than 25% decrease in lymphocyte count [43]. Fortunately, no opportunistic infections have been described.

For HCC, the average response rate is between 35 and 47% with median survival of 15–24 months

SARAH, an open-label, multicenter phase III trial (France), compared patients treated with SIRT versus Sorafenib alone in patients with unresectable HCC. SIRveNIB was an open label randomized controlled trial (Asia Pacific) that compared SIRT versus Sorafenib in locally advanced HCC. Both trials had a superiority design with overall survival as the primary endpoint. Both trials did not meet endpoint as there was no statistical difference in overall survival or progression-free survival. Indeed, overall survival was 8.0 months versus 9.9 months in the SARAH trial and 8.8 months versus 10 months in the SIRveNIB trial for SIRT and Sorafenib respectively [48]. However, patients treated with SIRT showed higher tumoral response rates, and increased quality of life in the intent to treat population which increased over time [49]. Moreover major criticism of these trials include inexperienced sites, a high TACE failure rate among patients, and 26.8% of the SIRT cohort in SARAH and 28.8% of the SIRT cohort in SIRveNIB did not receive

For metastatic colorectal cancer (mCRC) disease to the liver, the average response rate was between 35 and 43% with a median survival of 5–14 months [50]. TARE has demonstrated its

Three multi-center, randomized controlled phase III trials (FOXFIRE, SIRFLOX, and FOXFIRE-Global) examined the role of TARE (Y-90 resin microspheres) in combination with chemotherapy as first line therapy versus chemotherapy alone (FOLFOX or OxMdG) for liver-only or liver-dominant mCRC. Although an improvement of liver progression free survival was seen,

polychemotherapy or disrupted ampulla of Vater patients are at increased risk [43].

so careful technique and use of microcatheters should be employed.

reduce the risk of REILD.

4.4. Results

SIRT as intended.

role in second line or salvage therapy.

[44–47].

## 4.1. Indications and contraindications

Aside from the multidisciplinary approach, patients should have a life expectancy greater than 3 months with an ECOG status less than 2. Radioembolization is often used an adjuvant therapy to chemotherapy and/or salvage therapy after failure of first-line chemotherapy. This technique is also preferred in patients with portal vein thrombosis.

Absolute contraindications would include poor liver function with an elevated total bilirubin or increasing bilirubin, previous radiation to the liver, or significant hepatopulmonary lung shunting as that would lead to radiation pneumonitis. TARE should not be used as first line therapy in CRC and should be avoided in patients with extensive extra-hepatic disease burden.
