Therapy

SIRT

Selective Internal Radiotherapy (SIRT) is a locally applied method to treat inoperable liver metastases or primary liver tumors. The liver as a vital organ is frequently an early site of metastatic spread and a life-limiting organ in late metastatic disease. The liver is a site, where multiple localized therapeutic interventions can be applied, and multiple possibilities offered by several medical disciplines are available for local therapy.

SIRT using resinous microspheres, is a reimbursable procedure in Switzerland. The text in the Swiss catalogue (KLV) listing such procedures states: in cases of inoperable liver tumors not amenable to chemotherapy, in which other locally ablative therapies are not possible or have not shown any effect”. This holds for all liver metastases or primary liver tumors at Zurich University Hospital mainly patients in late inoperable states and after multiple lines of chemotherapy are presented to the interdisciplinary tumor board. In such cases, first an all encompassing internal medical / oncological assessment of the patient is necessary. This assessment hinges on the performance status of the patient, the identification of the primary dominant localization of the tumor in the liver, the identification of the most recently applied chemotherapy and its potential interference with a SIR-Therapy. Important prerequisites to treat the patient with a SIR-Therapy are mainly a intact liver function, i. e. the absence of ascites as a sign of an advanced liver insufficiency, elevated bilirubin (1.5x above normal values), deranged coagulation status, elevated transaminases as well as thrombocytopenia. The indication for SIRT is summarized below.

After a discussion of the procedure with the patient, the preparatory procedures for a SIR-Therapy are done. This out-patient preparation concerns mainly the angiographic planning of the therapy. Only after this angiographic preparation is the patient ready for a SIR-Therapy, and the out-patient Y-90 based therapy itself can be planned and executed. Usually, the time lag between planning and therapy is around 2 weeks. After a 5 hour observation period at the hospital, the patient can normally be sent home. The follow-up occurs in close collaboration with the referring physician and mostly under his auspices.

A SIR-Therapy done by experienced physicians generally shows very few untoward reactions. Frequently, low grade fever is observed, capsular pain is noted,and the patient complains of some nausea and fatigue for a few days. Serious complications which have to be discussed with the patient prior to the procedure, concern the migration of the injected microspheres through gastric and duodenal artieries into the corresponding organs. This is very annoying for the patient and leads to local ulcerations. These rare but possible side effects have to be discussed with the patient in the first contact with the responsible physician.

The entire process from treatment request to the end of the therapy lasts around 1 month. The treatment is done in close collaboration between Nuclear Medicine, Medical Oncology and Interventional Radiology.

Additional literature
Nonsurgical precedures at regional metastases of colorectal carcinoma (PDF) / only in German

Responsible physicians Nuclear Medicine/Oncology
Ivette Engel-Bicik MD
University Hospital Zurich
Nuclear Medicine
Rämistrasse 100
8091 Zurich
ivette.engel-bicik@usz.ch

Alexander Siebenhüner MD
University Hospital Zurich
Medical Oncology
Rämistrasse 100
8091 Zürich
Alexander.Siebenhüner@usz.ch

Responsible physician, Radiology
Prof. Thomas Pfammatter MD
University Hospital Zurich
Diagnostic and Interventional Radiology
Rämistrasse 100
8091 Zürich
Thomas.Pfammatter@usz.ch

Expiry of Therapy

Indication for a SIR-Therapy

Indication	Contra-Indication
Inoperable liver tumors, which are refractory to chemo-therapy and in which other locally ablative procedures are not possible or have not shown any benefits	Patient has already received an external radiation therapy oft h liver (not applicable for stereotactic RT)
	Ascites of clinical liver failure
	Abnormal synthetic or excretory liver function tests (ASAT, ALAT 5x above norm, Bilirubin > 35 mumol/l)
	Hepato-pulmonic shunt of more than 20% as per Tc-99m MAA scintigraphy
	gastric refulux, pancreas or gut in Tc-99m-MAA scintigraphy
	Dominant extrahepatic disease

Neuroendocrine Tumors

Zurich University Hospital (USZ) is a certified center for t he treatment of Neuroendocrine tumors. The European Society for Neuroendocringe Tumors (ENETS) has designed USZ as the only Swiss center with the “excellency status”. All patiens who are presente to us for diagnosis or therapy, are discussed at our ENETS tumor board. All referring physicians are cordially invited to partake in that board.

In addition to many possible therapies, USZ offers the radiopeptide therapy with Lutethium-177-DOTATATE. This therapy is similar to Octreotide or Lanreatide with the compound binding to Somatostatin receptor 2 in order to irradiate the tumor cells locally. The therapy is usally applied over four cycles every 8 weeks. The patient is seen once by the oncologist between the cycles and after the end of therapy, the patient is referred back to his physician.

The risk for untoward reactions during this type of radiation therapy iss mall. Most patients do not feel any restrictions as a result. The radioactive element Lutetium-177 irradiates only tissue in within 4 mm of its presence. As it fixes in the tumor, little normal surrounding tissue is irradiated alongside.

Lutetium-177 DOTATATE is partly taken up by the kidney very much like amino acids. In order to avoid renal damage, the kidneys have to be blocked for the DOTATATE compound. This is done by intravenously applying a solution of amino acids. The infusion is usually tolerated without side effects and is not harmful to the kidneys. Nevertheless there is a small risk of kidney damage by Lutetium-177 DOTATATE. In very rare cases this can lead all the way to a dependence on renal dialysis. Studies have shown that this happens in less than half a percent of patients and most of these patients suffered from pre-existing renal disease.

While injecting DOTATATE, patients may experience some nausea and vomiting of short duration (5 min) and this occurs in approximately 5% of patients. The ensuing stay for therapy is usually tolerated without other untoward effects. During therapy 30% of patients exhibit a slight decrease in white blood cells, but the recovery occurs in just a few weeks.

Responsible physicians Nuclear Medicine/Oncology
Ivette Engel-Bicik MD
University Hospital Zurich
Medizinische Nuclear Medicine
Rämistrasse 100
8091 Zuerich
ivette.engel-bicik@usz.ch

Alexander Siebenhüner MD
University Hospital Zurich
Medical Oncology
Rämistrasse 100
8091 Zurich
Alexander.Siebenhüner@usz.ch

Additional literature
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors (PDF)

Expiry of Therapy

Indications for Lutetium-177 DOTATATE-Therapy

General indication	Contra-indications
Gemäss ENETS Guidelines (z.B. second line MIDGUT Tumore nach Sandostatin) Inoperable Erkrankung ECOG 0 – 2	Pregancy or breast feeding
	Medium to severe renal insufficiency (clearence 40 – 50ml/min)
	Severe liver disfunction (Bilirubin > 100 mg/dl)
	Severe liver disfunction
	Severe medical disease in general (e. g. COPD Gold IV)

	Therapy of bone metastases
undefined

	Patient information
Therapy with SIR-Spheres (PDF) Therapy of Neuroendocrine Tumors with Lutetium (PDF) Prostate Cancer Therapy with Radium-223 Dichloride (PDF)