Treatments

Radioembolization Treatment

Posted on by Prof. Dr. Özgür KILIÇKESMEZ

Radioembolization is an innovative treatment method in the fight against tumors such as liver cancer. During this procedure, the patient’s access to the liver artery is achieved via a vascular route, and the smaller vessels feeding the tumor are catheterized. Microscopic radioactive yttrium-90 particles are then directed into the tumor.

In this extremely precise procedure, radioactive substances are delivered directly to the tumor tissues. This ensures that healthy tissues receive minimal exposure during treatment. This technique is especially promising in cases that are resistant to other treatment modalities.

Clinical studies have proven that radioembolization yields effective results. With each passing day, this treatment method continues to evolve and become more widespread. It is particularly applicable in cases of very large tumors, or when tumors are widespread in both lobes and involve the liver vasculature, where chemoembolization or ablation cannot be performed, making TARE (transarterial radioembolization) a viable option.

Patients must undergo two angiographic procedures. The first is a test angiogram to determine whether the method will be beneficial and for planning/dose adjustment. The second angiogram, performed shortly after the first, is the treatment angiogram.

What Is Radioembolization Therapy?

Before and after image of TARE liver cancer treatment

Radioembolization therapy is an effective way to combat tumors in the liver. It is used in the treatment of hepatocellular carcinoma and metastatic liver cancer. This method directly targets tumor areas. Yttrium-90 loaded microspheres are injected into the tumor-feeding arteries. The success of the treatment is based on its ability to deliver a high dose of radioactive material directly to the cancerous tissue.

How Is Radioembolization Therapy Performed?

Radioembolization therapy encompasses a detailed process that is managed carefully. This treatment method is known as a minimally invasive procedure and is carried out step by step.

Pre‑Procedure Planning and Imaging:

  • Patients are carefully selected and evaluated, with liver functions and tumor characteristics examined through various blood tests and imaging techniques.
  • The first step involves mapping the vessels via angiography to identify vessels that must be preserved.
  • A test performed with technetium‑99m estimates the distribution of the microspheres and the lung shunt fraction.

Catheter Placement:

  • A catheter is advanced from the femoral artery under fluoroscopic guidance into the hepatic artery. The correct placement of the catheter is confirmed using contrast dye.

Injection of Microspheres:

  • Radioactive yttrium-90 microspheres are delivered via the catheter into the tumor’s microvasculature. These microspheres emit beta particles to target cancer cells.
  • The infusion is performed slowly and in a controlled manner to ensure effective distribution of the microspheres and to minimize the risk to healthy tissue.

Post‑Procedure Care:

  • The distribution of the microspheres is verified with SPECT or PET scans. These imaging techniques are critical in assessing the radiation dose and the treatment’s effectiveness.
  • Patients are closely monitored, with attention paid to pain, nausea, and other potential side effects.
  • Follow‑up imaging is used to evaluate the response to treatment and to plan any further interventions.

For Which Cancer Types Is Radioembolization Therapy Suitable?

Radioembolization therapy, performed using yttrium-90, is particularly effective in treating various types of liver cancers. The procedure is primarily applied to the following liver cancer types:

  • Hepatocellular Carcinoma (HCC): This method is frequently chosen for patients with advanced HCC who are not candidates for surgical intervention or who do not respond to other treatments. It slows disease progression and improves quality of life.
  • Intrahepatic Cholangiocarcinoma (iCCA): Used in cases where iCCA cannot be treated surgically and can be combined with chemotherapy for improved outcomes.
  • Colorectal Cancer Liver Metastases (CRC): In patients resistant to systemic chemotherapy, this treatment reduces the tumor burden in the liver and may render patients eligible for surgery.
  • Neuroendocrine Tumor Liver Metastases: Radioembolization plays an important role in reducing symptoms and shrinking tumors.
  • Breast Cancer Liver Metastases: In patients who do not respond to systemic treatments, reducing liver tumor burden can extend survival.
  • Other Gastrointestinal Malignancies: It is considered a palliative option for metastases from cancers such as pancreatic and gastric cancers.

What Are the Side Effects of Radioembolization Therapy?

The side effects of radioembolization therapy can range from mild symptoms to serious complications. One of the most common side effects is post‑radioembolization syndrome, where patients may experience fatigue, nausea, and abdominal pain. In most cases, these symptoms are transient and do not require special intervention. Nausea and vomiting are also common and are generally controlled with anti‑emetic medications.

Common Side Effects:

  • Post‑Radioembolization Syndrome: Characterized by fatigue, nausea, vomiting, abdominal pain, and loss of appetite.
  • Nausea and Vomiting: Typically treated with ondansetron.

Pain:

  • Discomfort in the right upper quadrant and generalized abdominal discomfort.

There are rarer, potentially serious side effects, including Radiation‑Induced Liver Disease (RILD), which manifests as impaired liver function and, in severe cases, may present with jaundice or ascites. Additionally, increases in liver function tests may be observed following treatment.

Serious Complications:

  • Radiation‑Induced Liver Disease (RILD): Impaired liver function.
  • Liver Fibrosis and Portal Hypertension: Risks specific to treatments involving both lobes.
  • Gastrointestinal Ulcers: May occur due to misplacement of the microspheres.
  • Pulmonary Complications: Rarely, microspheres may migrate to the lungs.

What Is the Post‑Procedure Recovery Process for Radioembolization Therapy?

The recovery process following radioembolization therapy involves several phases and may vary depending on the patient’s condition. Immediately after the procedure, patients are typically observed in the hospital for a few hours to monitor for any complications, with close monitoring of vital signs.

Immediate Post‑Procedure Recovery:

  • Patients may need to be observed for several hours or overnight.
  • Symptoms such as pain, nausea, and fatigue are common.
  • Pain relievers, anti‑emetics, and intravenous fluids are commonly administered.

Short‑Term Recovery:

  • Fatigue, mild fever, and flu‑like symptoms typically resolve within one week.
  • Liver function tests and imaging are usually performed within the first month.
  • Patients are advised to avoid strenuous activities.

Long‑Term Recovery:

  • Regular follow‑up visits are required.
  • Imaging studies at 1, 3, 6, and 12 months evaluate treatment response.
  • Continuous monitoring for rare long‑term complications is necessary.

When Can Patients Return to Daily Life After Radioembolization Therapy?

The recovery process after radioembolization therapy typically allows patients to return to daily activities within a few days. Most patients can resume normal activities shortly after a brief rest period. During recovery:

  • It is recommended that patients spend the first 2 to 6 hours in a recovery area.
  • The leg from which the catheter was inserted should remain immobile during this time.

Before discharge, healthcare providers perform a series of checks, including:

  • Mobility
  • Ability to eat and drink
  • Independent performance of personal needs
  • Stable vital signs
  • Control of pain and nausea

Once these assessments are favorable, patients are allowed to go home. Generally, patients adapt quickly to their normal routines after treatment.

In Which Situations Is Radioembolization Therapy Not Recommended?

Radioembolization therapy is contraindicated in certain cases. Specific health conditions may prevent the safe application of this treatment. The patient’s overall health and anatomical features determine whether the treatment can be safely performed.

Significant hepatopulmonary shunting is a serious contraindication for radioembolization, as the risk of excessive radiation dose transfer to the lungs may lead to radiation pneumonitis, adversely affecting the patient’s quality of life. Severe liver dysfunction (Child‑Pugh score > B7) is also a contraindication due to the high risk of post‑procedure hepatic decompensation.

Other contraindications include:

  • Significant Hepatopulmonary Shunt: Situations where more than 30 Gy of radiation might pass to the lungs.
  • Impaired Liver Function: Cases with a Child‑Pugh score higher than B7.
  • Extrahepatic Disease: Patients with widespread extrahepatic disease.
  • Renal Failure: Patients with a creatinine clearance of less than 30 ml/min.
  • Previous External Beam Radiation Therapy: Patients who have received extensive EBRT.
  • Pregnancy and Breastfeeding: Situations where radiation could harm the fetus or infant.
  • Life Expectancy Less Than 3 Months: Patients with very limited expected survival.
  • High Tumor Burden: When tumors occupy more than 50–70% of the liver.

What Are the Long‑Term Outcomes of Radioembolization Therapy?

The long‑term outcomes of radioembolization therapy vary based on several factors. Using yttrium-90, this treatment has proven effective particularly in liver tumors. Post‑treatment tumor shrinkage can extend patient survival and improve quality of life. The treatment’s success varies by tumor type and stage, with some patients achieving high response rates.

Long‑term outcomes include:

  • In hepatocellular carcinoma (HCC), the median overall survival ranges between 12 and 26 months.
  • Patients with neuroendocrine liver metastases (NELM) have a median overall survival of approximately 33 months.
  • 1‑year survival rate of 75 %
  • 2‑year survival rate of 62 %
  • 3‑year survival rate of 46 %
  • Similar improvements have been reported in colorectal cancer metastases and intrahepatic cholangiocarcinoma.

While the treatment is generally well tolerated, some long‑term side effects may occur:

  • Chronic Radiation‑Induced Liver Disease (REILD)
  • Radiation gastritis
  • Gastrointestinal ulcers
  • Cholecystitis
  • Radiation pneumonitis

These complications can be managed, and most patients benefit from the preservation of healthy liver tissue due to the minimally invasive nature of the treatment. Additionally, the tumor‑reducing ability may make some patients eligible for subsequent curative surgical options.

Do Patients Feel Pain During Radioembolization Therapy?

Pain is a common occurrence during radioembolization therapy. Patients often experience discomfort, particularly in the region where the catheter is inserted. As the catheter is advanced through the femoral artery to the hepatic artery, transient pain may occur. Local anesthesia is used to alleviate this pain. After the procedure, abdominal pain may develop, mainly due to the effects of radiation on the tissues.

  • The intensity and duration of the pain vary between patients.
  • Radiation-induced liver tissue reaction is the primary cause of abdominal pain.
  • Pain is usually managed with analgesics and tends to decrease within a few days.

Some patients may also experience additional symptoms after the procedure:

  • Referred pain in the shoulder due to diaphragmatic irritation.
  • General fatigue, nausea, or vomiting.

Is It Possible to Combine Radioembolization Therapy with Other Treatment Modalities?

In modern oncology, radioembolization therapy is increasingly combined with other treatment methods to enhance its efficacy. Especially yttrium‑90–based radioembolization is integrated with various cancer treatment protocols:

  • In Combination with Immunotherapy: When used with immune checkpoint inhibitors, such as pembrolizumab, radioembolization can create synergy in the treatment of liver cancer by enhancing the immune response against tumor cells.
  • In Combination with Chemotherapy: When combined with systemic chemotherapy, radioembolization provides localized tumor control while chemotherapy addresses systemic disease. This combination can improve response rates in challenging cancers such as intrahepatic cholangiocarcinoma.
  • In Combination with Stereotactic Body Radiotherapy (SBRT): The combination targets both the parenchymal and vascular components of the tumor, significantly improving tumor control and overall treatment outcomes.
  • In Combination with Targeted Therapy: Integration with targeted agents, such as tyrosine kinase inhibitors, can enhance the effectiveness of both treatments, aiming for better local and systemic disease control.

Is Radioembolization Therapy Suitable for Children?

The applicability of radioembolization therapy in children is still controversial due to limited scientific evidence. However, in recent years, treatments adjusted for children’s weight and BMI have been introduced.

The decision-making process should be managed by a multidisciplinary team comprising pediatric oncologists, hepatologists, and interventional radiologists. One major concern in pediatric radioembolization is the potential effect of high‑dose beta radiation on growing tissues. Therefore, long‑term side effects and the management of radiation‑induced liver disease must be meticulously planned and monitored.

What Are the Advantages and Disadvantages of Radioembolization Therapy?

Understanding the advantages and disadvantages of radioembolization therapy is essential to appreciate the scope and impact of this treatment. Radioembolization is a targeted approach to liver tumors that preserves healthy tissue while offering an effective solution.

Advantages:

  • Targeted treatment minimizes damage to surrounding tissues and reduces systemic side effects.
  • As a minimally invasive procedure, it offers a shorter recovery time for patients.
  • It is effective even in tumors that cannot be surgically resected, thus broadening treatment options.
  • Provides a potentially curative option in early‑stage liver cancer.
  • In advanced stages, it alleviates symptoms and improves quality of life.

Disadvantages:

  • Post‑radioembolization syndrome may affect a significant portion of patients.
  • Liver toxicity poses a risk, especially in patients with pre‑existing liver disease.
  • Misplacement of microspheres can lead to serious complications.
  • The treatment’s efficacy depends on tumor characteristics and overall liver health.
  • Cost and availability may limit access for some patients.

What Are the Latest Developments and Research in Radioembolization Therapy?

Recent advancements in radioembolization therapy are drawing attention, particularly beyond the use of yttrium‑90. Innovations include new imaging technologies and dosimetry methods that allow for more precise tumor localization and dosing adjustments.

The use of holmium‑166 as an alternative to Y‑90, with its unique physical properties, enables improved tumor mapping. Additionally, combining Y‑90 radioembolization with immunotherapy agents such as pembrolizumab has shown promising results in clinical trials, enhancing the immune system’s ability to target tumors.

Improvements in radioembolization techniques, notably radiation segmentectomy, offer potential curative results for patients with early‑stage HCC while preserving non‑tumorous liver tissue.

Recent clinical trials have demonstrated improved overall survival with Y‑90 radioembolization. The LEGACY study, for instance, reported high tumor control rates in unresectable HCC. Furthermore, safety improvements such as prophylactic antibiotic use to prevent liver abscess formation have become integral to the treatment process.

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