Purpose
Background information and definitions
Definitions
Radionuclides
Radioactive microspheres (Table 1)
Characteristics | SIR-Spheres® | TheraSphere® | QuiremSpheres® |
---|---|---|---|
Material | Resin | Glass | Poly-L-lactic acid |
Particle size and range (μm) | 30 (20–60) | 25 (20–30) | 30 (15–60) |
Embolic effect | Moderate | Mild | Moderate |
Activity per sphere (Bq) | 40–70 | 4534 * | 200–400 |
Specific gravity (g/dL) | 1.6 | 3.7 | 1.4 |
Activity available (GBq) | 3# | 3–20^ “ | “ |
Handling for dispensing | Required | Not required | Not required |
Multiple dosing from one vial | Possible | Not possible | Not possible |
Background
Indication
Contraindications
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Pregnancy, breastfeeding
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Life expectancy of less than 3 months
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Clinical liver failure (i.e. ascites, icterus, encephalopathy)
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Disseminated extrahepatic malignant disease (see section Diagnostic work-up for reference)
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In case the pre-treatment intra-arterial scout dose scintigraphy (or peri-procedural C-arm CT) shows any extrahepatic activity (or contrast enhancement) in the gastrointestinal tract that cannot be corrected by angiographic techniques (exceptions include the gallbladder, lymph nodes, falciform ligament)
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Child-Pugh score higher than B7. A liver decompensation rate as high as 89% after glass administration with standard dosage (i.e. single compartment modelling) has been reported in patients with B7 liver cirrhosis [68]. Caution is warranted in any treatment that is not (bi-)segmental.
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High intrahepatic tumour burden. Depending on tumour type, more (e.g. neuroendocrine, more indolent, hypervascular, symptomatic disease in need of palliation) or less (hepatocellular carcinoma, underlying liver disease, more aggressive) tumour burden is acceptable. A cut-off of 50–70% is often reported.
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High extrahepatic tumour burden. Depending on tumour type, more (e.g. neuroendocrine, prognosis depends on liver disease, more indolent) or less (e.g. intrahepatic cholangiocarcinoma (ICC), more aggressive) extrahepatic disease is acceptable. Hilar lymph nodes (up to 2 cm short axis) and lung nodules (up to 1 cm; up to 5) are often accepted.
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Main portal vein thrombosis (PVT) with poor targeting evidenced by scintigraphy. These patients will have a very poor outcome with little benefit from treatment.
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Poor targeting of portal vein thrombosis in the main trunk.
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Acute or severe chronic renal failure (i.e. creatinine clearance <30 ml/min).
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Contraindications to hepatic artery catheterization (e.g. unmanageable coagulation disorder, renal failure, severe allergy to contrast media, vascular abnormalities).
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Lung shunting that would lead to a lung dose >30 Gy per session or > 50 Gy cumulatively (determined by pre-treatment planar 99mTc-MAA scintigraphy). Not an absolute contraindication, because lung shunting by planar 99mTc-MAA is overestimated and a reliable safety limit has not been established yet.
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Inadvertent delivery of microspheres to the gastrointestinal tract or pancreas may cause acute abdominal pain, acute pancreatitis or peptic ulceration.
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Prior external beam radiation therapy (EBRT) of the liver. Radioembolization appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT, with the strongest predictor for hepatotoxicity being the liver fraction exposed to ≥30 Gy [25]. While liver regeneration might allow combined treatments, little is known about the cumulative thresholds. Absorbed dose values cannot be simply summed, since a reliable method to combine such values is still lacking.
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Repeated radioembolization treatments seem less critical than radioembolization after EBRT. Young et al. [26] repeated lobar radioembolization an average of 2.6 times in HCC patients with 17% toxicity incidence. No data is available to strictly demonstrate whether the dose tolerance in a second treatment can be considered the same as for the first treatment. However, liver regeneration might allow this strategy, provided that a sufficient interval between treatments is kept (3 months or longer).
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Markedly abnormal liver function tests (e.g. aspartate aminotransferase or alanine aminotransferase >5 times upper limit of normal or elevated bilirubin). Caution is advised when bilirubin exceeds normal levels, especially in bilobar metastatic disease, in case whole liver treatment is warranted.
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Excessive radiation to the normal liver parenchyma may result in radiation hepatitis or radioembolization-induced liver disease [29], characterized by the combination of increased bilirubin, low albumin and ascites. The usual onset is 2–6 months after radioembolization [79]. It may co-exist with progressive disease (complicating the clinical presentation), but the diagnosis is definite in the absence of progressive disease.
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The risk of cholangitis or abscess may be elevated in patients with a history of biliary intervention. Although a direct relation has not been established (in contrast to TACE), caution is advised, and prophylactic antibiotics may be considered.
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Excessive hepatotoxic systemic therapy prior to radioembolization may increase the risk of post-treatment liver failure. However, in mCRC, it was evidenced in randomized controlled trials that the combination of first- and second-line systemic therapy with radioembolization is safe [30‐32]. In HCC, the combination of first-line sorafenib and radioembolization proved to be safe [33], but an unacceptable risk of liver failure was identified for ICC patients with underlying cirrhosis treated as first-line with concomitant radioembolization and standard chemotherapy in a multicentre phase II study [34].
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Non-dosimetric activity calculation methods (single compartment modelling; BSA-method) may lead to under- or overtreatment. Please note that under- and overtreatment may be equally harmful to the patient.
Diagnostic work-up
Clinical and laboratory evaluation
Pre-treatment imaging
Peri-procedural imaging
Treatment planning
Radiation segmentectomy
Radiation lobectomy
Lobar disease with/without PVT
Bilobar disease
Dosimetry
Single versus multi-compartment versus voxel-based dosimetry
Activity calculation and treatment planning
Single compartment | Multi-compartment | ||||
---|---|---|---|---|---|
Clinical scenario | Perfused volume dose | LOE | Normal liver dose | Tumour dose | LOE |
HCC | |||||
Segmentectomy | > 400 [83] | 3 | Not applicable | ||
Lobectomy | > 150 if whole liver dose <150 [67] 140–150 [84] | 1* 3 | ≥ 88** [85] < 75 (range: 50/90***) [86] | ≥ 205 [67] ≥ 250–300**** | 3 |
Unilobar | > 150 if whole liver dose <150 [67] | 1* 3 | < 120** if HR < 30% [67] < 75 (range: 50/90***) [86] | ≥ 205 [67] ≥ 250–300**** | 1* 3 |
Bilobar | 1, 4 | < 50/90*** [86] | ≥ 205 [62] | 3 | |
ICC | |||||
Segmentectomy | > 400 [60] | 4 | Not applicable | ||
Lobectomy | 140–150 | 4 | < 75 (range: 50/90***) | ≥ 260 [88] | 3 |
Unilobar | 80–150 [89] | 3 | < 75 (range: 50/90***) | ≥ 260 [88] | 3 |
Bilobar | 80–150 [89] | 3 | < 75 (range: 50/90***) | ≥ 260 [88] | 3 |
mCRC | |||||
Segmentectomy | > 400 [90] | 3 | Not applicable | ||
Lobectomy | 140–150 | 4 | < 75 (range: 50/90***) | ≥ 189 [91] | 3 |
Unilobar | 80–150 [92] | 3 | < 75 (range: 50/90***) | ≥ 189 [91] | 3 |
Bilobar | 80–150 [92] | 3 | < 75 (range: 50/90***) | ≥ 189 [91] | 3 |
Single compartment | Multi-compartment | ||||
---|---|---|---|---|---|
Clinical scenario | Perfused volume dose | LOE | Normal perfused liver dose | Tumour dose | LOE |
HCC | |||||
Segmentectomy | > 150 [93] | 4 | Not applicable | ||
Lobectomy | Not recommended | > 70 [93]* | ≥ 100–120 [93] | 4 | |
Unilobar | < 40 [93] | ≥ 100–120 [65] | 3 4 | ||
Bilobar | < 30**/40 [93] | ≥ 100–120 [65] | 3 4 | ||
ICC | |||||
Segmentectomy | > 150 [93] | 4 | Not applicable | ||
Lobectomy | Not recommended | > 70 [93] | ≥ 100–120 [94] | 3 4 | |
Unilobar | < 40 [93] | ≥ 100–120 *** [94] | 3 4 | ||
Bilobar | < 30**/40 [93] | ≥ 100–120 *** [94] | 3 4 | ||
mCRC | |||||
Segmentectomy | > 150 [93] | 4 | Not applicable | ||
Lobectomy | Not recommended | > 70 [93] | > 100 **** [93] | 4 | |
Unilobar | < 40 [93] | > 100 **** [95] | 3 4 | ||
Bilobar | < 30**/40 [93] | > 100 **** [95] | 3 4 |
One-compartment | Multi-compartment | ||||
---|---|---|---|---|---|
Clinical scenario | Perfused volume dose | LOE | Whole normal liver dose | Tumour dose | LOE |
HCC | |||||
Segmentectomy | 60 | 3 | Not applicable | ||
Lobectomy | 60 | 3 | < 60 | Not available | 4 |
Unilobar | 60 | 3 | < 60 | Not available | 4 |
Bilobar | 60 | 3 | < 40*** | Not available | 4 |
ICC | |||||
Segmentectomy | 60 | 3 | Not applicable | ||
Lobectomy | 60 | 3 | < 60 | > 150* | 3–4 |
Unilobar | 60 | 3 | < 60 | > 150* | 3–4 |
Bilobar | 60 | 3 | < 40*** [96] | > 150* [96] | 3–4 |
mCRC | |||||
Segmentectomy | 60 | 3 | Not applicable | ||
Lobectomy | 60 | 3 | < 60 | > 90** [97] | 3 |
Unilobar | 60 | 3 | < 60 | > 90** [97] | 3 |
Bilobar | 60 | 3 | < 40*** | > 90** [97] | 3 |
Resin 90Y-microspheres
Glass 90Y-microspheres
166Ho-microspheres
Administration
Post-treatment imaging
Facility and personnel
Staff exposure
Patient information and instruction
Radiation protection
Side effects
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Fatigue
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Abdominal pain
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Nausea
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Fever/cold chills
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Transitory elevation of liver enzymes
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Transitory decline in lymphocytes
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Radioembolization-induced liver disease (i.e. hyperbilirubinemia, hypoalbuminemia, ascites, typically occurring 2–6 months after treatment, without evidence of disease progression)
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Non-target irradiation: radiation gastritis, gastrointestinal ulceration, upper gastrointestinal bleeding, pancreatitis, (radiation pneumonitis)