Indications, safety and warnings for TheraSphere™ Yttrium-90 Glass Microsphere System

CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician.

Prior to use, please refer to all applicable “Instructions for Use” for more information on Intended Use/Indications for Use, Contraindications, Warnings, Precautions, Potential Adverse Events, and Operator’s Instructions.

Intended use/Indications for use

TheraSphere Microspheres are indicated for use as selective internal radiation therapy (SIRT) for local tumor control of solitary tumors (1 cm to 8 cm in diameter), in patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh Score A cirrhosis, well-compensated liver function, no macrovascular invasion, and good performance status.

Contraindications

TheraSphere Microspheres are contraindicated in patients:

• whose Tc-99m macroaggregated albumin (MAA) hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques.
• who show shunting of blood to the lungs that could result in delivery of greater than 16.5 mCi (0.61 GBq) of Y-90 to the lungs. Radiation pneumonitis has been seen rarely in patients receiving doses to the lungs greater than 30 Gy in a single treatment.
• in whom hepatic artery catheterization is contraindicated, such as patients with vascular abnormalities or bleeding diathesis.
• who have pulmonary insufficiency (conventionally defined by an arterial oxygen pressure (Pa,O2) of < 60mmHg, or oxygen saturation (Sa,O2) of < 90 %).
• with portal vein thrombosis (PVT) Type 4 involvement and lack of Tc-99m MAA deposition on the PVT seen on the Tc-99m MAA imaging.
• with > 70 % tumor replacement in the liver.
• who have severe liver dysfunction, including hepatic encephalopathy, clinically evident ascites, or treatment with diuretics for ascites.
• with comorbidities or poor overall health (e.g., Eastern Cooperative Oncology Group (ECOG) performance status rating > 2) which may make the patient a poor candidate for locoregional radiation treatment.
• who are pregnant.

Warnings

The following pre-treatment, high-risk factors (disease characteristics) have been associated with serious adverse events deemed possibly related to use of the device:

• infiltrative tumor type
• tumor nodules too numerous to count
• AST or ALT > 5 times ULN
• bilirubin > 2 mg/dL
• tumor volume > 50 % combined with albumin < 3 g/dL

Procedural

• It is important to avoid any aggressive arterial procedure that may lead to arterial spasm that impairs TheraSphere Microspheres distribution in the perfused liver target volume and may lead to underdosing or non-target deposition of TheraSphere Microspheres.

Radiation Safety

• Keep the TheraSphere Microspheres dose vial upright and stored in its lead pot before and during patient treatment, except as required for radiation measurement. Failure to do so could cause radiation exposure or damage to the product. Do not open the dose vial acrylic shield prior to patient treatment.
• Beta radiation from the tubing and exposed microcatheter is highest during microsphere transfer. Stand behind shielding and/or maintain distance.
• Post-treatment, waste materials require caution to prevent contamination and beta shielding due to residual glass microspheres. See Cleanup of Administration System.
• As in the use of any radioactive material, ensure minimum radiation exposure to the patient unrelated to the therapeutic objective, and to minimize radiation exposure to workers and others in contact with the patient.

Precautions

Patients with Impaired Liver Function

• No efficacy or safety data from the LEGACY study are available to support the use of the device in patients with Child-Pugh score B or C cirrhosis.

Procedural

• Two needles are located inside injector assembly. When removing the cap from the needle injector assembly, follow standard sharps procedure.

Release and Post-Treatment

• Use universal precautions for body fluid contact. Trace Y-90 may be detectable in blood and urine; handle with gloves and dispose as normal body fluids. The radiation field is expected to be less than 1 mrem/h (10 μSv/h) at 1 m (3 ft) from the patient’s abdomen. Supplemental shielding and segregation of the patient are not required to maintain exposure to others below regulated limits.
• The patient should follow good hygiene (e.g., proper hand washing). Caregivers, family, and others do not require restrictions on patient contact; however, they can minimize their radiation exposure by avoiding prolonged time (> 12 hours per day) within 0.3 m (1 ft) of the patient’s abdomen for the first week post therapy. Patients should be advised that radiation emitted from the patient may be detectable at security screening.
• If the patient requires hospitalization, surgery, medical assessment or treatment regarding any part of their thorax or abdomen within first 2 weeks of treatment, the patient should advise the hospital and treating physician of the TheraSphere Microspheres implant. The physician should consult their radiation safety staff for handling and disposal of liver tissue.
• Special liver tissue handling may be required for post-treatment surgery, explant, or transplant since the glass microspheres remain permanently implanted in the liver tissue. Disclosure of the treatment will be required if cremation is considered.
• See Release and Post-Procedure for more information.

Vulnerable Patients

• No effectiveness or safety data are available to support the use of the device in children or breast-feeding women.

 

Adverse events

The use of this product leads to irradiation of both tumorous and normal liver tissue. As a result, patients with compromised liver function may be at greater risk of liver function impairment and hence could experience complications. See Warnings for more information.

Potential adverse events which may be associated with the use of TheraSphere Microspheres in the treatment of hepatocellular carcinoma usually occur within the first 4 to 6 weeks after treatment.

Based on clinical trial data, literature reviews and post market surveillance, adverse events potentially associated with treatment using Y-90 microspheres, including TheraSphere Microspheres, may include the following:

• Allergic reaction (contrast or other)
• Anorexia
• Arrhythmia (e.g. supraventricular arrhythmia)
• Ascites
• Aspiration pneumonia (procedure related)
• Bile duct injury
• Bleeding/hemorrhage
• Chills/rigors
• Cholangitis
• Cholecystitis
• Cognitive changes (i.e. mood alteration, anxiety)
• Colitis
• Death
• Dehydration
• Dizziness
• Edema including pulmonary edema
• Electrolyte abnormalities
• Fall
• Fatigue/muscle weakness
• Fever
• Flushing (procedure related)
• Gastrointestinal bleeding
• Gastrointestinal symptoms (e.g. abdominal distention, constipation, diarrhea, nausea, vomiting)
• Gastrointestinal ulcer or ulceration
• Hematological cytopenia (e.g. anemia, lymphopenia, neutropenia, thrombocytopenia)
• Hematoma
• Hepatic dysfunction
• Hepatic encephalopathy
• Hepatic failure
• Hiccups
• Hypertension
• Hypotension
• Infection/abscess/sepsis
• Malaise
• Need for additional intervention or surgery
• Nerve damage (procedure related)
• Pain/discomfort
• Pleural effusion
• Portal hypertension
• Post-Embolization syndrome (PES)
• Pulmonary Fibrosis
• Radiation exposure (unintended)
• Radiation induced disease (i.e. fibrosis, esophagitis, pneumonitis, pancreatitis, ulceration)
• Radio Embolization Induced Liver Disease (REILD)
• Renal insufficiency/failure (elevated BUN/creatinine)
• Respiratory distress/ insufficiency/failure/dyspnea
• Thrombosis/thrombus
• Tumor inflammation including tumor edema
• Tumor lysis syndrome
• Vessel trauma (e.g. dissection, injury, pseudoaneurysm, perforation, rupture)
• Weight loss