Minimally Invasive Tumor Therapy (MITT)

Department of Radiology, Charité – Universitätsmedizin Berlin

DE | EN | RU

References

  1. Inarrairaegui M, Pardo F, Bilbao JI, Rotellar F, Benito A, D'Avola D, et al. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2012;38(7):594-601.
  2. Kennedy A, Coldwell D, Sangro B, Wasan H, Salem R. Radioembolization for the treatment of liver tumors general principles. Am J Clin Oncol. 2012;35(1):91-9.
  3. Hendlisz A, Van den Eynde M, Peeters M, Maleux G, Lambert B, Vannoote J, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. 2010;28(23):3687-94.
  4. Sharma RA, Wasan HS, Love SB, Dutton S, Stokes JC, Smith JL. FOXFIRE: a phase III clinical trial of chemo-radio-embolisation as first-line treatment of liver metastases in patients with colorectal cancer. Clin Oncol (R Coll Radiol). 2008;20(3):261-3.
  5. Van Hazel G, Blackwell A, Anderson J, Price D, Moroz P, Bower G, et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol. 2004;88(2):78-85.
  6. van Hazel GA, Pavlakis N, Goldstein D, Olver IN, Tapner MJ, Price D, et al. Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. J Clin Oncol. 2009;27(25):4089-95.
  7. Gil-Alzugaray B, Chopitea A, Inarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J, et al. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology. 2013;57(3):1078-87.
  8. Golfieri R, Bilbao JI, Carpanese L, Cianni R, Gasparini D, Ezziddin S, et al. Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma. J Hepatol. 2013;59(4):753-61.
  9. Salem R, Gilbertsen M, Butt Z, Memon K, Vouche M, Hickey R, et al. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2013;11(10):1358-65 e1.
  10. Salem R, Lewandowski RJ, Gates VL, Nutting CW, Murthy R, Rose SC, et al. Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol. 2011;22(3):265-78.
  11. Bester L, Meteling B, Pocock N, Pavlakis N, Chua TC, Saxena A, et al. Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients. J Vasc Interv Radiol. 2012;23(1):96-105.

Video

Radioembolization or Selective Internal Radiation Therapy (SIRT) of Malignant Liver Tumors

 

Radioembolization or selective internal radiation therapy (SIRT) is a new treatment option for patients with primary or secondary liver tumors (hepatocellular carcinoma or metastases) that cannot be removed by surgery or that do not/no longer respond to chemotherapy.

 

How Does Radioembolization Work?

 

Radioembolization uses tiny radioactive beads or particles, which are injected into the hepatic artery (the main blood vessel that supplies blood to the liver). The beads are made of glass or resin (microspheres with a diameter of 20 - 40 µm) and contain a radioactive substance (yttrium-90, a high-energy beta emitter) which gives off radiation that only penetrates a few millimeters. The radioactive particles tend to concentrate in the tumor, with only a small amount reaching healthy liver tissue. The reason is that liver tumors receive most of their blood supply from the hepatic artery, while normal liver tissue gets most of its blood from the portal vein (the large vein that carries blood from the gut and spleen to the liver). This dual blood supply of the liver allows SIRT to deliver a high radiation dose to the tumor area, while minimizing the dose to surrounding healthy tissue.

 

Figure 1: Diagram of the liver and its arterial blood supply. The hepatic artery arises from the aorta and gives off other smaller branches that do not enter the liver. These branches must be occluded with tiny spirals (coil embolization) before SIRT is performed.

 

Yttrium-90 has a half-life of 64 hours. This means that, after injection, the radioactive SIRT microspheres deliver radiation to a liver tumor from within the tumor for several days, causing the tissue to die over time. Radiation destroys a tumor by directly damaging the tumor cells (DNA damage) or by damaging the cells while they are dividing.

 

Figures 2 to 5 illustrate how the microspheres for radioembolization are delivered and how they work inside the liver.

 

Figure 2: Diagram of the aorta with a catheter in the liver artery (common hepatic artery) and arterial blood supply of liver tumors.

 

Figure 3: Radioactive particles (white) and red blood cells (erythrocytes) in the artery. The particles are much larger than red blood cells, so they will get stuck in the small blood vessels (capillaries) around liver tumors.

 

Figure 4: Liver tumors with feeding arteries. The white radioactive particles are retained in the dense capillary network of the tumors.

 

Figure 5: Diagram illustrating the emission of radiation from the small radioactive particles in the capillary bed of a liver tumor.

 

SIRT is a local treatment intended to stop disease progression in the liver. It is considered successful if the tumor size remains stable. The primary aim of SIRT is not to cure cancer but to improve quality of life and help patients live longer. Sometimes, however, SIRT may lead to shrinkage of liver cancer or liver metastases and an improvement in tumor markers. In an occasional patient with primary liver cancer, the resulting shrinkage may reduce the tumor volume in the liver to such an extent that the remaining cancer tissue can then be removed by surgery (1, 2).

 

Because the treatment effect is local, radioembolization is an option for patients whose cancer is predominantly located in the liver. It has no effect on cancer cells outside the liver. Metastatic liver cancer, or cancer that has spread to other parts of the body (like the lungs or lymph nodes), requires a treatment that involves the whole body. In some cases, it is possible to combine radioembolization with other treatments such as chemotherapy. Whether this is possible depends on a number of factors, including the amount of cancer outside the liver, and the decision must be made for each patient individually.

 

Radioembolization of the liver can only be performed in patients who meet several criteria. Therefore, it is very important that candidates are given a thorough diagnostic workup and preparation before treatment. Radioembolization is usually offered to cancer patients who have run out of other treatment options. These are patients in whom established local or systemic treatments (surgery, chemotherapy, local tumor ablation (brachytherapy, radiofrequency ablation (RFA)), or laser-induced thermotherapy (LITT)) are not or no longer expected to provide any benefit.

 

How is Radioembolization Performed?

 

Before accepting a patient for SIRT treatment, we thoroughly review the medical history and imaging studies such as computed tomography (CT) or magnetic resonance imagining (MRI) and, where available, positron emission tomography (PET). We therefore ask interested patients to send us recent images and a detailed history of their disease including all prior treatments to decide whether the most important criteria for having SIRT treatment are met. Candidates must have enough remaining liver function (as indicated by laboratory tests of bilirubin and liver enzymes in blood) and, as a rule, there should be no excess free fluid in the abdominal cavity (ascites). If this initial review indicates that a patient may indeed be a candidate for SIRT, an appointment will be set for further discussion and preparation in our minimally invasive tumor treatment unit.

 

Radioembolization is performed in two sessions.

In the first session, an angiography (an X-ray examination of the blood vessels) is performed to assess the individual vascular anatomy and make sure that it is suitable for SIRT treatment. If this is the case, the interventional radiologist will then proceed to occlude side branches of the hepatic artery that supply other organs. This is important to ensure that the radioactive microspheres enter the liver and no other organs, where they might cause serious problems like stomach ulcers or inflammation of the pancreas.

 

The side branches are permanently blocked with small metal coils (coil embolization). Next, some weakly radioactive test material (Tc-99m MAA, a technetium radiopharmaceutical) is injected into the hepatic artery for a nuclear scan. This scan shows the distribution of the material and is performed to rule out abnormal short circuits (shunts) to the lung. Most patients will be hospitalized for 2 days for this first session. During this hospital stay, we will perform an MRI examination with a special liver contrast agent and, if deemed necessary for planning, a CT scan.

 

If at this point there are still no reasons against radioembolization treatment (contraindications), patients can proceed to have the procedure 1 – 2 weeks later. During the second session, another angiography of the liver blood vessels will be done, and any new branches of the hepatic artery not entering the liver will be occluded first before the yttrium-90 microspheres are given. The microspheres are injected slowly over 30 – 60 minutes. Depending on the liver’s tumor burden, the microspheres can be delivered to the tumor only, to one liver lobe, or to the entire liver.

 

Patients scheduled for radioembolization will be admitted to a specialized ward equipped for nuclear medicine treatment. Depending on their clinical condition, patients can usually be discharged from the hospital 2 or 3 days after the SIRT procedure.

 

Other Simultaneous Treatment

 

Most medications can be continued as usual before and around the time of the radioembolization procedure. Medicines that prevent clot formation in the blood (anticoagulants or blood thinners) may have to be stopped or changed to minimize the risk of bleeding during angiography. Details will be discussed with the patient before hospital admission.

 

We prefer not to perform radioembolization during or shortly after chemotherapy. Some studies have investigated this issue (3-6).

 

There are several reasons for this. First, many chemotherapy regimens include agents that make the liver tissue more sensitive to radiation, so that we cannot reliably predict the effect of SIRT on the tumor or possible damage to healthy liver tissue. Second, chemotherapy prevents tumor cells from dividing, rendering them less sensitive to the destructive effects of radiation. Third, many modern chemotherapies attack the arterial blood supply of a tumor. This makes radioembolization less effective because it reduces the amount of microspheres that can reach the tumor with the blood.

 

Possible Side Effects and Complications

 

Several side effects can occur. In many patients, the body’s reaction to the rapid decay of the tumor immediately after the radioembolization procedure (1 – 5 days) causes flu-like symptoms including nausea, vomiting, body aches, fever, chills, and upper abdominal pain. This constellation of symptoms is known as the postembolization syndrome. The radiation emitted by the SIRT microspheres can cause inflammation of the stomach (gastritis) or stomach ulcers. Some other possible complications are related to angiography, such as bleeding, hematoma (bruise), infection, allergic reactions, shock, injury of the vessel wall, thrombosis, and nontarget embolization (undesired effects of the particles outside the liver). In very rare cases, a patient may develop lung fibrosis or radiation damage of the liver (radioembolization-induced liver disease (REILD)) (7). To minimize these risks, we pay great attention to careful planning and use of a meticulous technique. The most common side effects are effectively suppressed by medications given before, during and after injection of the radioembolization particles. Therefore, overall, radioembolization is tolerated well by most patients (8-10).

 

Aftercare

 

Follow-up after radioembolization includes blood work and MRI examinations. We ask our patients to return for follow-up MRI scans first after 6 and 12 weeks and then every 3 months. If, over time, the tumor starts to grow again, some patients can have a second radioembolization procedure. Alternatively, local progression in the liver may be treated using another minimally invasive approach. In such cases, we will discuss treatment options with you and your doctor to identify the best strategy for your case.

 

Results of Radioembolization

 

Radioembolization or SIRT is a palliative treatment, which means that it is intended to help you live longer and relieve your symptoms. Many patients treated with SIRT cannot expect complete cure. However, we had a few patients with initially inoperable tumors in whom SIRT reduced the tumor to such an extent that it was then possible to remove it surgically.

 

The prognosis after SIRT depends on many factors, in particular the type of primary tumor, the tumor cell division rate, the extent of disease, and the remaining liver function. Therefore, it is very difficult to give a general estimate of the survival benefit from radioembolization treatment.

 

Three studies investigating chemotherapy and radioembolization treatment in patients with liver metastases from colorectal cancer found survival benefits of 17, 3, and 5 months for patients with additional SIRT compared to patients treated by chemotherapy alone (5, 6, 11).

 

  • Contact:

Minimally Invasive Tumor Therapy (MITT)

Charité, Campus Virchow-Klinikum

Department of Radiology

Augustenburger Platz 1

13353 Berlin, Germany

Phone: +49 (0)30/450-557309

Fax: +49 (0)30/450-557947

minimal-invasive-ambulanz@charite.de oder mia@charite.de

 

Case Example

 

The case presented here illustrates how radioembolization treatment is performed in a 65-year-old patient with liver metastases from colon cancer.

 

Figure 6:  Before a patient can undergo SIRT, the arterial blood supply of the liver is assessed. This is done by an angiography - a special X-ray examination that uses a contrast medium injected through a catheter to define the outlines of the blood vessels. In this patient, the angiogram shows arterial branches supplying the stomach and other abdominal organs. These branches are blocked (coil embolization) before SIRT can be performed.

 

Figure 7: This angiogram was obtained after embolization of 3 arterial branches supplying the stomach, the pancreas, and the small bowel. The arrows indicate the coils used for embolization. Blocking of these arteries before SIRT is necessary to prevent radioactive particles from traveling through these branches and damaging the organs they supply.

 

Figure 8:  The patient had an MRI examination before treatment. The T1-weighted image obtained after contrast medium administration shows multiple liver metastases in the right hepatic lobe (arrow) and some metastases in the left lobe.

 

Figure 9:  This image is from the MRI examination performed at follow-up 6 months after SIRT. The contrast-enhanced T1-weighted image shows marked regression of metastatic disease in the liver. The arrows indicate remaining metastases in the right liver lobe.