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Treatment for Hepatocellular Carcinoma (HCC) using TheraSphere

Authors: Heather Maurer BSRT(T), Nishele Lenards, M.S. CMD, R.T.(R)(T),FAAMD
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI
Abstract:
Introduction: In this paper, safety procedures are discussed for handling, calculating, and
administering Yttrium-90 in the form of a TheraSphere treatment to the liver. Proper techniques
as well as post treatment precautions are addressed.
Case Description: One of the treatment options for Hepatocellular Carcinoma (HCC) is using
Yttrium-90 (Y-90) in the form of a TheraSphere. This case study involved the procedure used to
treat HCC of the right lobe of the liver without presence of cirrhosis at a target volume of 2417.4
cc. The dose prescribed was between 100-150 Gy using a TheraSphere with an initial dose size
of 18 GBq.
Conclusion: Studies are currently being performed involving the safety of Y-90 in the form of a
TheraSphere for treatment. Previous studies have assisted with the implementation of safety
procedures to protect the patient and staff before during and after the procedure. Current
literature supports the safety of TheraSphere treatments and safe handling procedures of the Y90 source.
Key Words: TheraSphere, Yttrium-90, Hepatocellular Carcinoma, Brachytherapy, Liver cancer
Introduction
Malignant hepatoma, also known as HCC, is the most common primary liver cancer in the
world; though not as common in the United States due to the lower instances of hepatitis. A
common cause of HCC is hepatitis B or C infection or alcoholism causing cirrhosis.1 Treatments
for HCC include surgery, liver transplant, ablation, chemotherapy, radiation therapy, and
brachytherapy.2
TheraSphere is a type of intravascular brachytherapy used for the treatment of hepatocellular
carcinoma (HCC) and other liver lesions. Microspheres composed of Yttrium-90 and insoluble
glass, each with a diameter of 20-30 micrometers, are flushed through the hepatic artery to the

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designated area of the liver. Yttrium-90 has a half-life of 64.2 hours and the average energy
emitted is 0.9367 MeV. There are approximately 22,000 to 73,000 microspheres per milligram.3
The dose of the TheraSphere must be ordered for each patient and are available in dose sizes
from 3 GBq to 20 GBq in increments of 0.5 GBq. The TheraSphere comes in 0.05 mL of sterile,
pyrogen-free water contained in a 0.03 mL vee-bottom vial secured within a 12 mm clear acrylic
vial shield. The acrylic vial shield adds protection against leakage as well as the emitted
radiation. Yttrium-90 is a beta emitter and this thin acrylic will minimize the generation of
Bremsstrahlung radiation.
There are risks and benefits for patient treatments based on tumor extent and liver function.
TheraSphere treatment comes with risks of bleeding, infection, damage to bowel, stomach and
liver, and many other complications including death. Though in a study of the safety, tumor
response and survival of 43 patients who received TheraSphere treatment for HCC it was
reported that 79% of lesions indicated a response to the treatment, there were minor adverse
events mostly that coincided with disease progression. None of the events related to the
treatment were life threatening.4
Case Description
Patient Selection/ Eligibility
In order for a patient to receive TheraSphere treatment they must undergo appropriate
angiographic procedures such as a hepatic arterial catheterization using balloon catheterization to
prevent shunting outside of the liver. Using this procedure along with radiopharmaceutical
Technetium 99mTc microaggregated albumin, (Tc-99m MAA) the extent of arteriovenous
shunting to the lungs was determined as well as the volume of the liver that was treated. This
patient had a lung shunt fraction of 2.4%, the amount of liver determined to be treated was
2417.4 cc. A confirmation can be made regarding the absence of gastric and duodenal flow using
scintigraphic views of the stomach using air contrast. If there is any GI shunting, TheraSphere
treatment is no longer an option due to the risk of bowel damage. This patients gastrointestinal
shunt fraction was 0%. Once the patient was deemed eligible the calculation of dose and
ordering of the TheraSphere was completed.
Target Delineation

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The exact liver volume was determined by a Tc-99m MAA scan. After undergoing the
appropriate testing in Intravascular Radiology the patient volumes were determined as: lung
shunt fraction 2.4%, gastrointestinal shunt fraction 0%, right lobe volume 2417.4 cc, left lobe
volume 234.59 cc, total liver volume 2561.99 cc, and a target for infusion volume of 2417.4 cc to
the right lobe. The volumes were reported on an Intravascular Radiology worksheet (Figure 1).
The information must be submitted to the appropriate personnel in advance to allow adequate
time for calculations, ordering, delivery and assaying of the source before treatment may
commence.
Calculation
It is important to know the patients past medical history. Certain details must be known in order
to calculate the proper activity. Things such as previous external beam radiation, previous
brachytherapy and if the patient has cirrhosis can all change the desired dose to the designated
area of the liver. The average dose prescribed to the liver is between 80-150 Gy however, if the
patient is cirrhotic they will be prescribed a dose toward the lower end of the scale, between 80100Gy. If there is no cirrhosis the patient will likely be prescribed 100-150 Gy. Also the liver
mass and shunting values from the Tc-99m MAA scan play a role in dose limiting factors as
well. The lung can only receive a cumulative dose of up to 50 Gy in multiple treatments.5 By
using the formula in figure 2 the required activity is calculated. There were no indications of
cirrhosis or radiation therapies in this patients medical history. This patient received 7 Gy to the
lung and 112 Gy to the treatment site in the liver.
TheraSpheres are calibrated for a certain day, typically Sundays at noon. Due to the specific
calibrations the orders must be placed the week prior to the actual injection. The infusion date
and time must be specified before ordering the TheraSphere. The required activity at time of
infusion should be decay corrected.
Before ordering, the actual dose to the liver was calculated as well as the amount shunted to the
lungs. The lungs are limited to 30 Gy for a one time fraction or 50 Gy for a combination of
infusions. These doses could be limiting factors in some cases. For instance if the doctor has
prescribed the liver to receive 150 Gy the activity is calculated and put into the formula to
determine the lung shunting dose. If the lung shunting does exceed the limit, the activity will

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need to be decreased to stay within the lung dose limit which will in turn lower the maximum
amount of dose to the liver and the desired dose of 150 Gy will not be obtainable.

The formula

used to confirm the dose is found in figure 3.

This particular patient was non-cirrhotic and was to receive a dose of between 100 150 Gy.
The calculations indicated that a 18 GBq TheraSphere should be ordered and the patients lungs
would receive 7.3 Gy.
Ordering/receiving TheraSphere
Radiation Safety Services (RSS) must be contacted with the actual activity being delivered to the
patient in order to get a clearance number for shipment after the calculations were complete. A
TheraSphere order form was submitted specifying the activity required, calibration date, and date
and time of procedure.
When the TheraSphere arrives, or any time it is moved, caution must be taken and the source
must be surveyed before and after it transfers locations, including the destination where it is
arriving and where it left. Specific handling instructions are located on an insert in the
packaging explaining why lead shielding is required even though Y-90 is a high-energy beta
emitter. The attenuation of the beta particles will produce Bremsstrahlung radiation; which is
why the TheraSphere vial is located within an acrylic shield within a lead cylinder. It is advised
to leave all shielding in place and use additional shielding when possible. A TheraSphere
Administration Set and Accessory kit is provided to help with limiting exposure (Figures 4 & 5).
The kits allow the TheraSphere vial to remain sealed and stay in the clear acrylic vial shield
during injection. Only a plug is removed from the shielding to expose the septum of the
TheraSphere vial in which part of the Administration set will connect into. Also personnel
dosimeters should be worn, including finger-ring dosimeters on the dominate hand palm side, or
in the orientation most likely to receive the highest exposure.
Procedure Prep and Administration
Prior to the treatment procedure, the TheraSphere cart was prepared as noted in the treatment
checklist (Figure 6). This included treatment monitoring and survey devices, containers for
radioactive waste materials, spill kit, and proper handling devices. Since there is always a

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potential for leakage of the radioactive material, all surfaces in the room that held the
TheraSphere were covered with absorbent covers prior to introduction of the TheraSphere. This
included the cart that held the administration kit, the path for the tubing that the Y-90 passed
through to the patient, and the area of the patient and radiography equipment where the Y-90 was
introduced. These covers presented an impermeable barrier on the side away from the Y-90
path, containing any radioactivity that could spill during the procedure. All personnel present for
the procedure wore appropriate radiation protection and monitoring equipment such as lead
aprons, personal radiation dosimeters, gloves, booties, and caps. All dosimeters were operational
to survey any object or person leaving the room once the TheraSphere was present, in addition to
obtaining an initial reading of the TheraSphere delivery apparatus.
Before patient administration, the TheraSphere Written Directive was completed with a
physician signature and the plans and calculations were checked by a physicist. The TheraSphere
Administration Set and TheraSphere Administration Accessory Kit were set up following verbal
instruction of the TheraSphere checklist (Figure 7). The Administration Set contained one sterile
disposable tubing set up and one empty sterile vial. The tubing set was pre-assembled with one
way valves, a needle plunger, and an integrated 20 cc syringe. This helps ensure all pieces are
sterile, assembled correctly, and the flush will flow in the appropriate direction only (Figures 4 &
5). The TheraSphere Administration Accessory Kit contained re-usable accessories including
an acrylic box base, top shield, removable side and top shields, bag hook and a RAD-60R
radiation dosimeter. Not only does this kit provide additional shielding, it is also the best setup
for monitoring the infusion process (Figure 5).
The TheraSphere checklist (Figure 7) was read aloud with verbal confirmation of each step
throughout the procedure. The administration of the TheraSphere was completed through a
minimum of three saline flushes with the 20 cc syringe provided and an approximate flow rate of
20 cc per minute until optimal delivery has been achieved. The 20 cc per minute is the
approximate flow rate of the hepatic artery and a flow rate less than that may decrease delivery
efficiency. The infusion pressure should not exceed 30 psig (pounds per square inch guage)
during any flush. The Administration Set had a pressure relief valve to help prevent over
pressurization. Optimal delivery was determined by monitoring the Administration Set with the

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RAD-60R radiation dosimeter provided. The ratio of the dose rate readings before and after
administration provided an estimation of dose delivered to the patient.
The actual percentage of dose delivered to the patient was calculated based on ion-chamber
radiation detector measurements of the dose prior to administration, compared to measurements
of the waste after administration. Before administration the acrylic shield containing the
TheraSphere vial was measured at a distance of 30 cm from the detector (Figure 8). After
administration the waste container inside the beta shield was measured at a distance of 30 cm
from the detector (Figure 9) at 4 rotational positions. These 4 measurements were averaged. The
percentage of dose delivered to the patient was calculated using the equation seen in figure 10.
Post-Administration Procedures
All materials used in the room during the infusion were surveyed prior to removal or disposal.
Since Y-90 is a beta emitter, appropriate procedures were followed using a Geiger-Mueller (GM)
survey meter with a pancake GM probe to allow detection of such contamination. Contaminated
materials such as the dose vial, tubing, catheters, and gauze were placed in the radioactive waste
container. All personnel in the room had their hands, feet, and any apparel surveyed before they
were allowed to exit the room. Once materials involved in the procedure were surveyed and
removed, a patient survey was completed to verify that there was no surface / skin
contamination. A radiation survey was also done to verify the dose rate at 1 meter from the
patient. A room survey was also done to verify no residual activity in the treatment room.
The patient proceeded to a recovery unit as a radioactive patient although the patient did not
present a risk to others for radiation exposure. Some contamination may be present in blood or
urine following the procedure. If the patient becomes hospitalized directly after the procedure
they will require a private room with private bathroom facilities but no other shielding or visitor
limitations will be necessary. Materials that come in contact with the patients blood or urine
need to remain within the room until surveyed and cleared. For example a Foley bag would need
to remain but the urine inside the bag could be flushed.
Conclusion

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There were many precautions taken for both the patient and the personnel involved with the
TheraSphere treatment procedure. The literature supports Y-90 or TheraSphere treatments safe
and effective for HCC patients.3, 5 Currently there is an ongoing clinical trial by the Sidney
Kimmel Comprehensive Cencer Center studying the safety and overall survival of patients with
liver metastases treated with TheraSpheres at doses of 120 +/- 10%, Intra-arterial Y-90
TheraSpheres for hepatic metastases from solid tumors NCT0117707. There were 15 events
reported out of 264 TheraSphere cases between the years 2001-2007.6 The report stated that 73%
of these events were device/product defects. Though events were only reported for 5.7% of the
cases, the use of appropriate procedures and precautions helped prevent additional complications
to the events as well as prevent additional events from occurring.

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References
1. Salem R and Hunter R. Yttrium-90 microspheres for the treatment of hepatocellular
carcinoma: a review. Int. J. Radiation Oncology Biol. Phys. 2006;66(2):s83-s88.
http://dx.doi.org/10.1016/j.ijrobp.2006.02.061

2. Abdalla EK and Keith SE. Overview of treatment approaches for hepatocellular carcinoma.
UpToDate, University of Michigan Med School Web site.
http://www.uptodate.com/contents/overview-of-treatment-approaches-for-hepatocellularcarcinoma. August 05, 2013. Accessed July 10, 2014.
3. Lewandowski RJ and Salem R. Yttrium-90 radioembolization of hepatocellular carcinoma
and metastatic disease to the liver. Semin Intervent Radiol. 2006;23(1):64-72.
http://dx.doi.org/10.1055/s-2006-939842

4. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular

carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and
survival. J Vasc Interv Radiol. 2005;16(12):1627-1639.
http://dx.doi.org/10.1097/01.RVI.0000184594.01661.81

5. Ali SM. Radioembolization for hepatocellular carcinoma using TheraSphere. Saudi J

Gastroenterol. 2011;17(3):215-217. http://dx.doi.org/10.4103/1319-3767.80388
6. Schultz CC, Campbell J, Bakalyar D, Beauvais M, Feng W, and Savin M. Y-90 microsphere
therapy: prevention of adverse events. Cancer Biotherapy and Radiopharmaceuticals.
2009;24(4):427-433. http://dx.doi.org/10.1089/cbr.2008.0595

Figure 1. Worksheet showing liver volumes, lung shunt fraction and gastrointestinal shunt
fraction from Intravascular Radiology.

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Figure 2. Formula used to calculate the required activity needed to deliver the desired dose.

Figure 3. Formula used to confirm dose, where F is the fraction of injected radioactivity
localizing in the lungs, as measured by Tc-99m MAA scintigraphy. (F x A = 0.61 GBq).

Figure 4. TheraSphere Administration Set

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Figure 5. TheraSphere Administration Accessory Kit

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Figure 6. TheraSphere checklist for cart set-up/ room prep

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Figure 7. TheraSphere checklist read aloud during procedure with verbal confirmation all steps
have been completed.

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Figure 8. Acrylic shield containing the TheraSphere vial being measured at a distance of 30 cm
from the detector

Figure 9. Waste container inside the beta shield being measured at a distance of 30 cm from the
detector

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Figure 10. Formula used to calculate percentage of dose delivered to the patient