SIRT for liver tumours

Selective Internal Radiation Therapy (SIRT) or radio-embolisation is a new form of treatment for primary and secondary liver tumours (i.e. liver cell cancer and liver metastases) that are inoperable, or which cannot or can no longer be treated using chemotherapy.

With SIRT, tiny glass or synthetic resin beads (“microspheres“ with a diameter of 20 to 40 µm) are injected via a catheter into the artery supplying the liver. The flow of blood transports them further into the tumour. The spheres contain a radioactive substance (yttrium-90, a beta radiation emitter) which spreads radiation just a few millimetres into the tissue. The tumours are therefore powerfully irradiated, while the surrounding tissue barely receives any radiation.

The transport mechanism uses the fact that liver tumours are more plentifully perfused by arteries, whereas healthy tissue has a greater density of veins. The radioactive spheres injected via the artery therefore accumulate in the tumour.

The radioactive substance has a half life of 64 hours. The internal radiation in the tumour correspondingly lasts several days, during which time the DNA of the tumour cells is destroyed and the cell division process is halted. The result is that the tumour tissue dies.

Figure 1: Schematic diagram of the liver and the hepatic artery exiting the aorta. Before treatment, smaller vessels that branch off from the hepatic artery but which do not lead to the liver must be sealed off using small microspirals (coils).

Figures 2 to 5 further clarify how SIRT works to irradiate liver tumours from within.

Figure 2: Schematic diagram of the aorta with a catheter in the hepatic artery (common hepatic artery). Tumours in the liver with significant arterial perfusion.

Figure 3: Radiogenic particles (white) and red blood cells (erythrocytes) in the artery. The particles are much larger than the blood cells, in order that they become trapped in the mesh of capillaries in the liver tumours.

Figure 4: Liver tumours with supplying arteries. The white radiogenic particles remain trapped in the tumours’ dense capillary network.

Figure 5: Schematic representation of the radiation effect of the small radiogenic particles.

Video

SIRT-en

SIRT is a palliative treatment method. This means that, using this method, we wish to prolong our patients’ survival and alleviate their suffering or symptoms. Generally speaking, SIRT does not bring about a complete cure.

The treatment is deemed to be successful if the disease in the liver ceases to advance – i.e. as a rule if the tumour stops growing (size constancy). Occasionally, the dimensions of the tumour may shrink and tumour markers may recede.

In individual cases, we have even been able to convert inoperable stages of the disease into operable ones. In this instance, the surgeon was able to then remove the malignant parts of the tumour (1, 2).

Since the prognosis depends very much on the primary tumour, the tumour cell division rate, the extent of the disease, the patient’s liver function and many other parameters, it is difficult to make any general statement regarding the benefit in terms of survival. For patients with bowel cancer that has metastasised to the liver, for example, and in comparison with chemotherapy on its own, additional SIRT was able to prolong survival by 17, 3 and 5 months in 3 studies respectively (5, 6, 11).

SIRT can be used if the tumour is mainly restricted to the liver, since the treatment is ineffective outside the liver.

Secondary tumour developments (metastases) outside the liver, for example in lymph nodes or in the lungs, require treatment that covers the entire body. Occasionally, other types of therapy, for example chemotherapy, can be combined with SIRT. This depends on a number of factors, however, such as the quantity of tumour outside the liver, and must be decided on a case-by-case basis.

Another condition for the use of SIRT is that established methods of treatment have largely been exhausted, and therefore other local or systemic treatments such as surgery, chemotherapy, local tumour ablations (brachytherapy, radiofrequency ablation (RFA), laser-induced thermal therapy (LITT)) are no longer expected to be successful.

Liver function must also be adequate (measured on the basis of laboratory values such as bilirubin and liver enzymes in the blood). Furthermore, there should as a rule be no excess fluid in the abdomen.

Beforehand

SIRT requires precise diagnosis and careful preparation.

In preparation for the procedure, we evaluate the case history and any diagnostic results already available, such as CT images, MRI scans and, if available, PET-CT scans (positron emission computed tomography). To this end, we request that a detailed medical history is provided, with a list of the treatments already applied and an indication of the progression of the disease and the most up-to-date diagnostic images possible.

Based on the documentation supplied, we can check whether the most important requirements for radio-embolisation are fulfilled. If this is the case, patients will be invited for a further consultation and work-up at our outpatient clinic for minimally invasive tumour therapy.

During

SIRT is carried out in two sessions:

Preparation
First an angiogram (visualisation of the vessels) is carried out. This provides the information whether the patient’s individual vascular anatomy is suitable for SIRT in the first place.

If it is, then lateral branches from the hepatic artery which supply other organs will be closed off during this same angiography session, so that the radioactive particles cannot enter them. If this were to happen, undesirable and possibly serious side effects (gastric ulcer, pancreatitis, etc.) could be triggered. These vessels are closed permanently using tiny metal spirals (coil embolisation).

A weakly radioactive test material (technetium-labelled, macro-aggregated albumin, Tc-99m-MAA) is then injected into the hepatic artery, followed by nuclear medicine investigations to exclude any shortcuts (shunts) to the lungs or stomach and intestines.

As part of the approximately two-day inpatient stay, we also carry out a CT scan to help us ensure accurate planning of the procedure.

The procedure
Once all of the investigations have been evaluated, and if there are no contraindications to SIRT, the yttrium-90 microspheres are administered around 1 to 2 weeks after the preparatory session. On the day before the procedure, we first carry out an MRI scan using a special liver contrast agent. This is used to determine the exact dose needed in the treatment. During this procedure, the liver vessels are once again visualised, and any newly developed run-offs are sealed. The yttrium-90 microspheres are then slowly and precisely administered over a period of 30 to 60 minutes.

Patients stay on a ward specially equipped for nuclear medicine treatment. Depending on the patient’s condition, they can usually be discharged two to three days after the treatment.

Afterwards

After 6 and 12 weeks, and then every three months, we perform blood tests and an MRI scan to monitor the success of the treatment. These investigations are carried out in our outpatient clinic.

If the tumour continues to grow in size after the treatment, a further round of SIRT may be required in certain cases. In cases of locally confined growth, another minimally invasive procedure can be used. If further treatment appears to be beneficial, this decision is made on an individual basis in consultation with the patient and their doctor.

Concomitant therapy

If medications are being taken regularly to suppress blood clotting (anticoagulants), then to prevent bleeding these must be either stopped or switched before the angiography. The patient will be informed of this in an in-depth consultation before admission as an inpatient. Most medications, however, can continue to be taken as normal before and during SIRT.

For a number of reasons, we do not advise chemotherapy before or during SIRT, even though some studies advocate it (3-6):

  • Many chemotherapeutic agents sensitise the liver tissue to radiation, making it difficult to reliably predict the extent of the treatment, and therefore of any potential damage to the healthy liver tissue.
  • Chemotherapeutic agents prevent tumour cells progressing to the cell division stage. During this phase, however, they are particularly sensitive to radiation.
  • Many modern chemotherapeutic agents reduce the arterial blood supply to the tumours. This would result in fewer particles travelling to the tumour via the hepatic artery, thereby reducing the effect of radio-embolisation on the tumour.

Side effects

Durch die Radioembolisation können folgende Nebenwirkungen auftreten:

  • Often, the embolisation and rapid destruction of the tumour cause flu-like symptoms during the early period (1 to 5 days after treatment), such as nausea, vomiting, aching limbs, fever, chills, and upper abdominal pain. This constellation of symptoms is generally referred to as “post-embolisation syndrome“.
  • In addition, side effects from the radiation can also occur, such as gastritis or stomach ulcers.
  • Bleeding, bruising, infection, allergy, shock, vascular injury, thrombosis and false embolisation can also occur as a result of the angiography.
  • Very rarely, pulmonary fibroses or radiation damage to the liver (radio-embolisation-induced liver disease, REILD) are reported (7). These risks are very greatly restricted through the accurate planning and delivery of treatment.

The most common side effects are effectively prevented by means of medication before, during and after the procedure so that, overall, the treatment is well tolerated (8-10).

Illustration of treatment in a 65-year-old patient with metastases in the liver from a colorectal tumour:

Figure 6: The contrast medium visualisation of the arteries supplying the liver, carried out via a catheter before treatment, shows vessel run-offs to the stomach and other abdominal organs.

Figure 7: The same patient as in Figure 6 after the occlusion of three arteries to the stomach, the pancreas, and to the small bowel using spirals (coil embolisation; arrows). These arteries must be closed off to prevent any radioactive particles travelling to these organs.

Figure 8: The same patient as in Figure 6 and 7. The MRI image (T1-weighted using contrast medium) shows the condition of an area in the right liver lobe with evidence of multiple liver metastases (arrow), and isolated metastases in the left lobe of the liver.

Figure 9: The same patient at a later stage. The follow-up MRI scan carried out 6 months later (T1-weighted using contrast medium) shows a significant reduction in the number of liver metastases. Residual tumour elements can be seen in the right liver lobe (arrows).

Contact


Minimally Invasive Tumour Therapy (MITT)
Charité Campus Virchow-Klinikum (CVK)
Department of Radiology
Augustenburger Platz 1
13353 Berlin

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