Selective Internal Radio-Therapy (SIRT) of malignant liver tumors

Why is treatment with SIR-Spheres® superior to normal radiotherapy?

Radiation can effectively destroy tumor cells. Radiation therapy is therefore a recognized method of cancer treatment. Unfortunately, however, normal human tissue is also sensitive to radiation. Radiotherapy with high doses of radiation can have a damaging effect on many organs and may even cause a loss of function. Liver tissue is particularly sensitive to radiation, which is why the options for conventional radiotherapy in the treatment of liver metastases or liver cancer are significantly limited.

SIRT, on the other hand, allows more targeted tumor treatment. Since normal liver tissue draws its nutrient-rich blood predominantly from the portal vein (hepatic vein) and, conversely, the vascular tumor tissue in the liver is heavily supplied with arterial (oxygen-rich) blood, the administration of SIR-Spheres® into the hepatic arteries leads to a preferential accumulation in the malignant tissue. The radiation emitted by the microspheres primarily damages and destroys the surrounding tumor tissue and only puts relatively little strain on normal liver tissue.

For which tumor types is SIRT particularly suitable?

Treatment with SIR-Spheres® is all the more promising the more tumor tissue in the liver is supplied with blood from the hepatic artery. Scientific studies have proven the therapeutic success of SIRT for the following types of tumors in the liver in particular:

• Hepatocellular carcinoma
• Liver metastases in colorectal carcinoma
• Liver metastases in breast cancer
• Liver metastases in neuroendocrine tumors

In addition to these standard indications, promising results are also available for a number of other tumors (e.g. liver metastases in bile duct carcinoma, pancreatic carcinoma or uveal melanoma).

What requirements must be met for SIRT to be carried out?

Treatment is generally only considered if

• other established treatment methods have been largely exhausted and the liver disease has progressed among them
• the inclusion criteria for the therapy are met
• treatment is possible without complications
• SIRT is technically feasible

It must be ensured in advance that other local and systemic treatment methods are not (or no longer) possible or do not offer sufficient treatment success. This includes, for example, surgery, radiofrequency ablation or local or systemic chemotherapy.

The most important inclusion criterion for SIRT therapy is that the tumor tissue is restricted to the liver, as the treatment can only achieve therapeutic effects within the liver due to its mode of action. Tumor tissue outside the liver is not reached by the treatment. The prerequisite for therapy is therefore that there is no extrahepatic metastasis or residual or recurrent tissue of the primary tumor. In individual cases, this can be deviated from if, for example, bone metastases show no progression over a longer period of time, as it is then assumed that the liver is the determining organ with regard to the patient's prognosis.

The therapy is only complication-free if the microspheres remain safely in the liver after administration and cannot enter the lungs via short-circuit connections or other organs (such as the stomach, gall bladder, duodenum, pancreas) via small side vessels. In addition, liver function must be largely intact; this is checked by laboratory tests (e.g. bilirubin in the normal range or at most slightly elevated, liver enzymes only slightly elevated, etc.) and the normal liver tissue must not have been damaged by previous external radiotherapy or certain forms of ongoing chemotherapy (capecitabine). As a rule, treatment is also not possible if ascites is present. These aspects are checked as part of the preliminary examinations for treatment planning.

The treatment is technically feasible if the hepatic arteries can be accessed and probed with a catheter, there is no significant anomaly in the vascular supply, branches that supply other organs can be closed without risk prior to treatment and the portal vein is free to pass through.

How is it determined whether SIRT is appropriate and possible in an individual case?

The documents sent in advance are used to check whether the most important inclusion criteria are met in the individual case. Please send us the following information:

1. Type of tumor (e.g. pathologist's report, doctor's letters)
2. Compilation of previous treatments (if possible, exact list of chemotherapies carried out, the corresponding treatment period and the success of the treatment).
3. Current computer tomography of the chest and abdomen (image data on CD-ROM or film, copy of findings).
4. Current laboratory values (tumor marker laboratory, liver values, bilirubin).
5. It is also desirable that the oncologist in charge of the patient explains why SIRT is recommended.

The family doctor or the treating oncologist can usually help you obtain these documents.

What further preliminary examinations are necessary?

If, after reviewing the documents, it turns out that SIRT treatment is indeed a promising option, further examinations are necessary, for which patients are admitted to our nuclear medicine therapy ward K0 at short notice.

During this stay, which usually lasts two to three days, in addition to a detailed determination of laboratory values, an MRI scan of the liver (and/or the whole body) and a whole-body PET/CT scan with FDG (radioactively labeled sugar) are performed. The aim of the latter two examinations is to determine the current extent and severity of the liver involvement and to rule out involvement of other organs.

In addition, the vascular supply to the liver is visualized by means of vascular imaging (angiography) under fluoroscopy. This is done by inserting a small, practically painless catheter into the groin, which is advanced into the liver region. Vessels that lead away from the liver to other organs and therefore pose a problem for SIRT can be detected at an early stage and closed if necessary. In addition, this examination simulates the actual therapy by injecting a radioactive substance with similar properties to the therapeutic microspheres. However, this substance does not contain any harmful radiation. The distribution of the actual therapeutic substance can therefore be estimated in advance and a flow (shunt) into the lungs can be ruled out.

How is the actual therapy carried out?

If the pre-diagnosis does not reveal any contraindications for carrying out the therapy, the actual treatment usually takes place during two further inpatient stays on our nuclear medicine therapy ward.

During each stay, our colleagues from interventional radiology perform a new vascular imaging of the liver in preparation for the treatment and, if necessary, close off small vascular branches in order to rule out a leakage of the therapy substance into other organs with a high degree of certainty. The nuclear medicine specialist then administers the therapeutic substance slowly and in portions (over approx. 30 to 60 minutes) separately into the right or left hepatic artery via the horizontal catheter, checking the respective flow conditions.

_{Patient with liver metastases from colon carcinoma. Extensive FDG-storing liver metastases before SIRT. 3 months later, significant improvement in findings with only isolated vital metastases.}

What happens after the treatment?

After treatment, you should continue to receive regular follow-up care from your oncology specialist. If necessary, he or she can promptly initiate further treatment measures and is the primary contact for questions about the next steps. This follow-up care is supported by regular examinations with PET/CT, liver (or whole-body) MRI and laboratory checks (usually every 3 months).

Who pays for the treatment?

SIRT is a cost-intensive treatment measure for which the costs are covered by health insurance companies in individual centers - such as the University Hospital of Munich - within the framework of special contracts (in the course of agreements on new examination and treatment methods, approvals are available for a certain number of cases/year). If patients do not have health insurance in Germany, please contact us in good time to clarify the coverage of costs by any foreign health insurance companies in advance.

This type of therapy was first carried out at our clinic in Germany in 2003. Since then, more than 1000 patients have been treated here using this method. This means that our colleagues in the interdisciplinary working group have the most extensive experience in this field in Germany.

How do I register for SIRT therapy?

The first step is to check whether the basic requirements for treatment are met (see above). If this is the case, please send the relevant documents with the enclosed referral form to the Outpatient Clinic for Microtherapy and Interventional Radiology, Clinic and Polyclinic for Radiology Campus Großhadern, Marchioninistr. 15, 81377 Munich for further assessment. You are also welcome to contact us by telephone on 089 - 4400 72752 or by email at ambulanz.radiologie@med.uni-muenchen.de.