Radioembolization of Hepatic

Malignancies Using Yttrium-90

Microsphere Brachytherapy

April 12, 2014

Lawrence Lou, MD, FRCPC

Objectives

• To understand transarterial radioembolization(TARE)

• To understand its indications in hepatic malignancies

• To learn the steps in performing TARE, focusing on the nuclear medicine aspects

TARE

• A procedure in which intra-arterially injected radioactive microspheres are used for internal radiation purposes

• To selectively deliver a high radiation dose to targeted tumors within the liver, while limiting radiation to normal liver to tolerable levels

Radiation from “inside out”

External Beam TARE

Liver blood supply

• TARE takes advantage of blood supply of normal liver vs tumor:

▫ Normal liver gets ~ 75-80% from portal vein

▫ Tumor gets >= 80% from hepatic artery with increased microvascularity around them

TARE vs. TACE

• TACE = transarterial chemoembolization

▫ occlusion of medium and large size arteries (with the use of particles 3–10 times larger than those used in radioembolization) -> tumor ischemia, with drug delivery potentially enhancing tumor cell killing

• TARE = transarterial radioembolization

▫ deliver tumoricidal doses of radiation, not by ischemia due to vessel occlusion

• TARE appears to provide better disease control with less toxicity than TACE with equivalent survival

• safe in more advanced disease including portal vein invasion and larger tumors

• Meta-analysis (425 pt with HCC) - median survival from 9.4 to 24 months. Response rates were complete response 0–9%, partial response 16–72%, and stable disease 29–65%.

Yttrium-90 (90Y) • Production: 89Y (neutron) → 90Y

• Decay: 90Y (b-, 64.2 hr/2.67 days) 90Zr; a pure β emitter

• β energy: 0.937 MeV (mean) & 2.28 MeV (max)

90Y deposits >90% energy in 5 mm of tissue & in 11 days; 2.5 mm (mean) & 11 mm (max)

90Y can deliver radiation absorbed doses of 50Gy/kg of tissue with 1 GBq activity

Sarfaraz et al., Med Phys 31, 2449-53, 2004

Indications

• for radiation treatment or as a neoadjuvant to surgery or transplantation in patients with unresectable HCC who can have placement of appropriately positioned hepatic arterial catheters

Contraindications

• whose Tc-99m MAA hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract which cannot be corrected by angiographic techniques

• who show shunting of blood to the lungs which could result in delivery of > 16.5 mCi of Y-90 to the lungs. Radiation pneumonitis has been seen in patients receiving doses to the lungs > 30 Gy in a single treatment

• in whom hepatic artery catheterization is contraindicated; such as patients with vascular abnormalities or bleeding diathesis

• who have severe liver dysfunction or pulmonary insufficiency

Barcelona Clinic Liver Cancer staging system

Alberta Hepatocellular Carcinoma algorithmBurak KW, Kneteman NM. Can J Gastroenterol 2010; 24(11):643-650

Indications

• Patient with confirmed HCC

• Not suitable for surgery, RFA/PEI or TACE

• Failed TACE with progressive disease by mRECIST/ EASL

• Liver transplant candidate qualifying for down-staging

• *TARE may be alternative to TACE, especially in patients with portal vein thrombosis*

Steps in TARE

• Procedure Day 1 (mapping +/- embolization)

• 1st angiogram

▫ To map arterial vascular anatomy and possibly embolize arteries that may lead to inadvertent delivery of radiation to other areas (GI tract)

▫ to calculate the lung shunt fraction, and

▫ the safe and effective dose of radiation

Y90 outside

the liver =

BAD!

• Procedure Day 2

▫ Deliver the Y-90 particles

How is the NM part done?

• Following hepatic arterial catheterization

• 75-150 MBq (2-4 mCi) of Tc-99m MAA administered

• determine the extent of A-V shunting to the lungs (pulmonary shunt fraction) and

• Look for extrahepatic activity to confirm the absence of gastric/duodenal flow

Planar and SPECT/CT

• use geometric means calculation,

• correct for background activity,

• % lung shunt =

▫ Total lung counts / (Total lung counts + Total liver counts) x 100

TheraSphere - Calculation of “total counts” is not explicitly described

SIR-Spheres - Calculate ROI counts for liver and lung regions from geometric-mean images

Example Calculation: % lung shunt

Lung

Liver

Why do we care?

• Radiation pneumonitis can been seen in patients receiving doses to the lungs > 30 Gy in a single treatment

• Limit lung absorbed dose < 30 Gy/Rx (50 Gycumulative)

SPECT/CT

• Evaluation of extrahepatic tracer deposition

▫ Planar - Difficult to differentiate radiotracer accumulation in the liver from that in an adjacent organ

▫ SPECT/CT – increase the sensitivity in the diagnosis of abdominal extrahepatic shunting, leading to a change in approach and therapy

SPECT/CT

• Evaluation of intrahepatic tracer distribution

▫ The aim of RE is to treat the total hepatic tumour load while avoiding delivery of particles to healthy liver tissue.

SPECT/CT

• Pretherapeutic dose estimation and dosimetry

▫ more accurate dose estimation for well delineatedtumours such as HCC but is of limited value in multiple/disseminated lesions.

Dezarn et al: AAPM recommendations Y-90 microsphere brachytherapy. Med. Phys. 38(8), August 2011

Therapy Planning Calculations

CLINICAL VALIDATION – Ph III IA FUDR +/- SIR-Spheres Gray BN et al Annals of Oncology 2002.

Package inserts

Device Method Equation

SIR-Spheres

3GBq

Non-Unit Activity

BSA*GBq = [BSA - 0.2] +

(Tumor Vol) / (Tumor+Liver Vol)

Empiric

Liver Involvement by Tumor<25% ►2.0 GBq25-50% ►2.5 GBq>50% ►3.0 GBq

Partition Liver RT Tolerance 40Gy

TheraSphere

3, 5, 7, 10, 15, 20 GBq

Individualized Activity

Recommended dose 80-150 Gy

Activity (GBq) = [D (Gy) x M (kg)] / 50

Lung Shunt Reduction

For SIR-Spheres

<10% ► 0

10-15%► 20

15-20%► 40

>20% ► 100

Bremsstrahlung (BS) SPECT/CT after

radioembolization• BS means “braking radiation”, produced by the

deceleration of emitted beta particles when they lose energy in the tissue

• Performed within 24 hrs of radioembolization

• to confirm satisfactory microsphere delivery to the target arterial territory

▫ absence of Y-90 accumulation in a considerable lesion correlates well with an unfavourable response.

• to confirm the safe distribution of 90Y microspheres and for the prediction of GI side effects, , for an appropriate and timely management strategy if extrahepatic tracer deposition occurs.

ComplicationsRadiation cholecystitis

Radiation induced biliary complications

Gastroduodenal ulceration

Radiation induced liver disease

Radiation pneumonitis

QUESTIONS?