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Indications / Contraindications
Indications
- HCC — unresectable, BCLC B/C, bridging to transplantation, downstaging
- Metastatic CRC to liver — SIR-Spheres FDA-approved with floxuridine (FUDR)
- Other hepatic metastases — neuroendocrine tumors (NET), breast, other primaries
- Portal vein thrombosis + HCC — TheraSphere FDA-approved (advantage over TACE, which is often contraindicated with PVT)
- Lobar, selective, or whole-liver treatment depending on tumor distribution
Contraindications
- Absolute: LSF >20% (lung dose >30 Gy) — measured on MAA scan. Never treat without MAA scan result.
- GI shunting without ability to coil-protect target vessels
- Severely compromised liver function (Child-Pugh C, bilirubin >2)
- Excessive tumor burden (>50% liver replacement)
- Life expectancy <3 months
- Uncorrectable coagulopathy (arterial access); prior external beam radiation to liver
TheraSphere (Glass — Theraspheres)
- FDA approved for HCC (HDE designation)
- ~2.5 million spheres per dose
- Higher specific activity per sphere
- FDA-approved for HCC with portal vein thrombosis — major advantage over TACE
- Dosimetry: MIRD or Partition
SIR-Spheres (Resin — Sirtex)
- FDA approved for metastatic CRC with floxuridine (FUDR)
- ~40–60 million spheres per dose
- Lower specific activity per sphere, higher sphere count
- Dosimetry: BSA or Partition (want high T:N)
- More spheres = different flow dynamics during infusion (more embolic)
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Pre-Procedure — Two-Visit Protocol
Visit 1 — Mapping Angiogram (Week 0)
Recent cross-sectional imaging (within 4 weeks). CT or MRI liver with contrast — assess tumor burden, identify dominant tumor, confirm portal vein patency, plan treatment territory (lobar vs selective).
Labs. CBC, CMP (LFTs, bilirubin, albumin, creatinine), coagulation panel, tumor markers (AFP for HCC, CEA for mCRC). Assess Child-Pugh score. Bilirubin >2 = relative to absolute contraindication.
Nuclear medicine coordination (24–48h ahead). Order Tc-99m MAA for mapping day. MAA must be prepared and ready for injection at time of angiogram — coordinate with NM department directly.
Identify vessels requiring coil protection. Right gastric artery (#1 cause of GI ulceration — must be coil-embolized if in treatment field), GDA if at risk, cystic artery (if gallbladder in field), falciform artery. In general, protective coil embolization is falling out of favor unless significant supply to treatment field.
Plan treatment territory. Lobar (right or left lobe) vs selective (single feeding vessel) vs whole liver based on tumor location, liver function, and anatomy.
Visit 2 — Treatment Session (Week 2–4)
Review MAA scan results. Confirm LSF <20%. Confirm hepatic distribution matches treatment plan. Any extrahepatic uptake (gastric, duodenal, pulmonary) must be resolved before treatment.
Dosimetry calculation completed. Activity (GBq) determined by AU using BSA method, partition model, or MIRD approach. Confirm ordered activity with radiation safety.
Radiation safety precautions. Y-90 is a pure beta emitter. Minimal external exposure hazard but institutional protocol in effect. Radiation safety officer notified. Appropriate shielding in IR suite.
Confirm coil-protected vessels still occluded. Re-angiogram at start of treatment session to confirm protected vessels remain occluded and anatomy is unchanged from mapping.
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Relevant Anatomy
Hepatic Arterial Supply
- Normal: Celiac trunk → common hepatic artery → proper hepatic artery → right + left hepatic arteries (bifurcation at porta hepatis)
- HCC vascularity: 90%+ from hepatic artery (vs. normal liver: 70% portal vein). This differential vascularity allows selective tumor delivery.
- Metastases: Variable — mCRC generally hypovascular; NET hypervascular. Y-90 works regardless (radiation effect, not embolization).
- Replaced right hepatic from SMA: ~15% of patients — very common. Must catheterize separately for right lobe treatment. Missing this = undertreated right lobe.
- Replaced left hepatic from left gastric: ~5%. Must identify and coil-protect (LGA branches can deliver spheres to stomach).
- Dome Lesions — Can recruit supply from the inferior phrenic.
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Technique
Mapping angiogram + treatment session + community cards
Visit 1 — Mapping Angiogram
Mapping Supplies
5 Fr slender sheath
RAVI MG1
180 cm Benson
150 cm 2.8 fr Progreat
Asahi Meister
Tc-99m MAA (coordinate 24–48h ahead)
Microcoils if needed (vessel protection)
Heparinized saline
Radial Cocktail (5,000u Heparin, 2.5 mg Verapamil, 500mcg Nitroglycerin)
Mapping Steps
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Left Radial arterial access
Standard radial access. Place 5fr slender sheath. RAVI MG1 and Benson to get down to SMA.
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Celiac + SMA angiogram
Celiac in AP and oblique views — identify hepatic bifurcation, variant anatomy. SMA angiogram — identify replaced right hepatic artery (present in ~15%). Document all findings.
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Selective hepatic angiogram
Microcatheter and wire to map tumor hypervascularity and feeding vessels. Identify all vessels at risk for non-target embolization. Confirm planned treatment territory corresponds to tumor location. Use cone-beam CT (CBCT) to confirm complete coverage and identify non-target supply.
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MAA injection (lung shunt scan)
Position microcatheter in planned treatment position (same location as Y-90 will be infused). Save fluoro store. Inject Tc-99m MAA (ordered dose, typically 4 mCi). Patient goes immediately to nuclear medicine for planar + SPECT imaging.
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Review MAA scan
Calculate LSF = lung counts / (liver + lung counts) × 100%. LSF <10%: proceed normally; 10–15%: reduce dose; 15–20%: consider further dose reduction; >20%: CONTRAINDICATION — cannot treat. Also check for gastric, duodenal, or other extrahepatic uptake → if present, return for additional vessel protection before treatment.
Visit 2 — Treatment Session
Treatment Steps
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Re-angiogram — confirm anatomy
Repeat hepatic angiogram to confirm anatomy.
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Position catheter in treatment vessel
Advance to identical position used for MAA injection. Confirm with DSA. Stability is critical — catheter movement changes dosimetry distribution. Use CBCT to confirm accurate position and complete tumor coverage.
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Y-90 delivery
TheraSphere: delivered via sealed infusion set connected to vial; infused under fluoroscopy per manufacturer protocol. SIR-Spheres: vial delivery with water/contrast flush. Follow radiation safety protocol strictly. Infuse slowly with continuous fluoroscopic monitoring for flow — stop if any reflux observed.
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Post-Y90 imaging
Bremsstrahlung SPECT or PET-CT can confirm hepatic distribution of Y-90 spheres. Bremsstrahlung = low-energy photon emission from Y-90 beta decay — confirms treatment territory corresponds to plan.
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Troubleshooting
Problem
High lung shunt fraction (>20%)
Likely cause: Arteriovenous shunting within tumor or via portal hypertension-related hepatopulmonary shunting.
Next step: Cannot proceed to treatment at standard dose. Reassess tumor anatomy on imaging. Some high-volume centers will treat in the 15–20% LSF zone with dramatically reduced activity. Consider TACE or ablation as alternatives. Document clearly and discuss with oncology team.
Problem
GI uptake on MAA scan
Likely cause: Non-target vessels in treatment field — right gastric, GDA, or other GI feeding vessel.
Next step: Return to angiography for coil embolization. Repeat MAA scan from same catheter position before scheduling treatment. DO NOT treat with GI uptake on scan — GI radiation injury is dose-limiting and severe.
Problem
Hypovascular tumor (mCRC) — poor enhancement
Likely cause: mCRC is inherently hypovascular compared to HCC or NET.
Next step: Still treat — Y-90 works by radiation effect, NOT embolization effect. Optimal catheter position in the tumor-feeding vessel is still essential. Do not be discouraged by lack of hypervascularity on angiogram; confirm with pre-procedure MRI/CT that the lesion is present in the planned territory.
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Complications
Radiation-Specific
- Radiation pneumonitis (<1% with LSF <20%) — cough, dyspnea 4–8 weeks post; steroids if symptomatic; prevents with MAA screening
- GI ulceration (2–4% without vessel protection; <1% with) — gastropathy, duodenopathy, cholecystitis; prevented by coil protection; PPIs post-procedure
- REILD (radioembolization-induced liver disease) — rare; elevated LFTs, jaundice, liver failure; occurs 4–8 weeks post; related to excessive dose to non-tumor liver
- Biliary injury — bile duct stenosis or biloma; uncommon with selective delivery
- Radiation-induced liver abscess — rare; usually in patients with biliary anatomy alterations (Whipple, biliary stents)
Procedure-Related & Systemic
- Post-radioembolization syndrome — fatigue, nausea, low-grade fever 1–3 weeks post; self-limited; supportive care; most common post-procedure event
- Access-site complications — hematoma, pseudoaneurysm from femoral access; standard arterial post-care
- Hepatic artery spasm/dissection — from microcatheter manipulation; nitroglycerin intra-arterial
- Tumor lysis / pain — hepatic pain from tumor infarction; manage with analgesics
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Post-Procedure Care
After Mapping Angiogram
- Radiation precautions minimal (patient minimally radioactive from MAA — no meaningful restrictions)
- Standard post-arterial access care depending on access site
- Schedule treatment visit at 2–4 weeks
- Communicate LSF result and plan to referring oncologist
After Treatment Session
- Radiation precautions per institutional protocol — Y-90 = pure beta emitter; minimal external exposure but close-contact restrictions for 7 days (sleeping alone, avoid prolonged close contact with children/pregnant women)
- Symptom management: Antiemetics, dexamethasone (if concerned about post-embolization syndrome), PPI (gastroprotection)
- Fatigue counseling: Expected for 1–4 weeks post; plan activity restrictions
Labs Follow-up
- LFTs weekly × 4 weeks — ALP and GGT commonly rise transiently post-treatment (expected)
- Significant bilirubin rise or LFT elevation beyond 8 weeks: consider REILD
- Tumor markers (AFP for HCC, CEA for mCRC) at 4–6 weeks and at imaging follow-up
Imaging Follow-up
- MRI or CT liver at 4–6 weeks: Assess treatment response using modified RECIST or LI-RADS TR criteria (enhancement-based — do not use standard RECIST size criteria alone)
- RECIST 1.1 (size) underestimates response. Use mRECIST (arterial enhancement) or LI-RADS treatment response criteria.
- Oncology coordination: Restart systemic chemotherapy typically at 4 weeks post-treatment
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Critical Pearls
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RIGHT GASTRIC ARTERY is the #1 cause of Y-90 GI complications. Identify and coil-embolize on EVERY mapping angiogram where it could be in the treatment field. It is a small vessel often arising from the proper hepatic in an oblique view — do not miss it. Use oblique angiographic views specifically to find it.
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Lung shunt fraction >20% = absolute contraindication. Always perform MAA scan. Do not rely on CT/MRI alone to estimate shunting. The scan is non-negotiable — this is the safety gate that prevents fatal radiation pneumonitis.
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Two separate visits is non-negotiable for safety. The mapping session exists specifically so you can identify and fix problems (unprotected GI vessels, high LSF, unexpected anatomy) before you are holding 3+ GBq of live Y-90 in the room. Never compress this into a single session. Some high volume centers are moving towards same day treatment but this is still not widespread.
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Replaced right hepatic from SMA in ~15% of patients. If treating the right lobe and you miss the rRHA on SMA angiogram, you will undertreate the right lobe and potentially miss protecting GI vessels in that territory. SMA angiogram is mandatory on every case.
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BCLC C (portal vein thrombosis) — TheraSphere is approved. This is a major clinical advantage over TACE, which is generally contraindicated with portal vein thrombosis. Y-90 does not rely on portal vein flow for safety, making it the preferred locoregional therapy in this setting.
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Response assessment: use mRECIST, not RECIST 1.1. Size-based criteria systematically underestimate Y-90 response. Tumors can show necrosis and decreased enhancement (true response) while maintaining or even increasing in size initially. mRECIST uses arterial enhancement; LI-RADS TR criteria also acceptable for HCC.
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Dosimetry Quick Reference
Y-90 Activity Calculation Methods
- BSA method (TheraSphere — older): A (GBq) = [0.0217 × mean absorbed dose (Gy)] × BSA. Target dose: 80–120 Gy for HCC.
- Partition model (preferred — personalized dosimetry): Uses MAA SPECT to calculate liver, tumor, and lung dose separately. Most accurate, increasingly standard of care.
- MIRD / quadrant approach (SIR-Spheres): Activity based on liver volume and tumor involvement percentage.
Lung Dose Safety Limits
- Single treatment: Lung dose <30 Gy
- Cumulative (multiple treatments): Lung dose <50 Gy
- Calculation: Lung dose (Gy) = (LSF/100) × Total activity (GBq) × 50 Gy/GBq
- LSF 10–15%: reduce planned activity; LSF 15–20%: further reduction, consider alternatives; LSF >20%: absolute contraindication
| LSF (%) | Lung Dose Implication | Action |
|---|---|---|
| <10% | Minimal lung dose | Proceed with standard planned activity |
| 10–15% | Moderate lung dose | Proceed with reduced activity; recalculate with partition model |
| 15–20% | Significant lung dose — approach limit | Further dose reduction; discuss risk/benefit with multidisciplinary team |
| >20% | Exceeds lung dose threshold | ABSOLUTE CONTRAINDICATION — do not treat |
MAA Scan Interpretation Checklist
- Hepatic distribution matches planned treatment territory (lobar vs selective)
- No gastric uptake
- No duodenal uptake
- No pulmonary uptake exceeding thresholds above
- LSF calculated and documented
- Any extrahepatic activity quantified and source identified
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References & Resources
Primary sources · Key data · Related procedures
Key Guidelines
- ASCO/ASTRO/SRS Y-90 Clinical Practice Guidelines
- SIR Standards of Practice for Y-90
- CIRSE Y-90 Radioembolization Guidelines
Primary References
- Salem R et al. Radioembolization with 90Y microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: technical and methodological considerations. J Vasc Interv Radiol. 2010;21(9):1251-1263.
- Kennedy A et al. SIRT with 90Y microspheres: treatment of patients with unresectable colorectal liver metastases. Int J Radiat Oncol Biol Phys. 2004;60(5):1552-1563.
- Lencioni R et al. SARAH trial: Sorafenib versus radioembolization. ASCO 2016 abstract 4.
- Riaz A et al. Radiological and pathological response to yttrium-90 radioembolization for liver malignancies. J Vasc Interv Radiol. 2010;21(9):1406-1413.