Selective Internal Radiation Therapy (SIRT)
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.
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How does SIRT work?
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.
Figures 2 to 5 further clarify how SIRT works to irradiate liver tumours from within.
What are the goals of SIRT?
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).
For which patients do we recommend SIRT?
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.
How is SIRT carried out?
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.
SIRT is carried out in two sessions:
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.
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.
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.
What complications should patients be aware of?
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.
The following side effects can occur due to radioembolisation:
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.