Treatment of skeletal metastases

Clinical problem

In many advanced-stage malignant diseases, tumors spread to the skeletal system, which are referred to as skeletal metastases. The most important tumor diseases that can be accompanied by skeletal metastasis are prostate carcinomas, breast carcinomas, bronchial carcinomas, kidney carcinomas and thyroid carcinomas. Skeletal involvement by malignant tumor cells leads to an increased risk of bone fracture as well as pain due to detachment or infiltration of the surrounding periosteum, which can also be exacerbated by mechanical or muscular causes such as nerve compression, muscle spasms, compression of the bone marrow, etc.

Basis and principle of treatment of bone metastases with radionuclides

In palliative nuclear medicine therapy of bone metastases, the aim is to deliver the highest possible radiation dose to the bone metastases while at the same time sparing the bone marrow. To this end, radionuclides with α- or ß-radiation are administered, which predominantly accumulate on the skeleton, especially where bone metabolism is greatly increased. This is mainly the case with so-called osteoblastic metastases, which, in contrast to osteolytic metastases, stimulate osteoblast activity and thus the formation of new bone. Osteoblastic metastases are mainly observed in prostate carcinomas, but also in breast carcinomas and other tumor diseases.

Treatment of skeletal metastases with Xofigo® (Ra-223)

Treatment with Xofigo® (Ra-223) can prolong survival in patients with bone metastases who show progression of the disease during hormone therapy. The therapy is generally approved and is covered by health insurance companies. Patients must not have organ or very large lymph node metastases.

Mode of action of therapy with Xofigo® (Ra-223)

Skelettszintigraphie ventral — Skeletal scintigraphy from ventral (front) and dorsal (back) before the 1st cycle and after completion of therapy with Ra-223 dichloride. The images show a clear decrease in the metabolic activity of the bone metastases. The PSA value fell from 239 ng/ml to 10 ng/ml. The patient reported a decrease in pain symptoms.

Radium-223 is a so-called calcium analog and, like calcium, is incorporated into the hydroxyapatite of newly formed bones. This incorporation occurs to a greater extent within bone-forming (osteosclerotic or osteoblastic) metastases, which are predominantly present in prostate carcinoma. Xofigo® (Ra-223) specifically irradiates neighboring tumor cells with high-energy α-radiation and thus has a localized cytotoxic effect. Due to the low penetration depth of the α-particles, the surrounding bone marrow is spared and there are fewer side effects in the area of the hematopoietic system than with comparable bone-penetrating radiotherapeutic agents. This means that after several cycles, slower growth or even a reduction in bone involvement in prostate cancer can be achieved without affecting the patient's quality of life or the possibility of other therapies due to additional side effects.

Implementation and procedure of the therapy

After clarification of the indication and feasibility of therapy with radium-223, the patient is informed in a detailed consultation and informed about important complications. The therapy is carried out on an outpatient basis. Six doses of Xofigo® (Ra-223) are administered at intervals of one month. Before the first and after the sixth cycle, a skeletal scintigraphy is carried out to determine storage behavior and tumor infestation before the start of therapy as well as the response to the administration of radium-223.

What documents and examination results must be available before treatment with Xofigo® (Ra-223) therapy?

Current doctor's letter with a detailed description of the previous course and therapies of the prostate carcinoma
History of PSA values; the last PSA value should not be older than 4 weeks.
Overview of all medication taken by the patient
Current laboratory results (can be obtained at the Clinic and Polyclinic for Nuclear Medicine)
CT or MRI findings of the thorax/abdomen/pelvis (not older than 8 weeks)
No evidence of organ metastases or larger lymph node metastases (>3 cm).
Current skeletal scintigraphy (can be performed at the Clinic for Nuclear Medicine at LMU Munich)

If treatment with Ra-223 is not possible, e.g. due to visceral metastases, treatment with radiolabeled peptides (e.g. Lu-177 PSMA) can be carried out on an individual basis.

Palliative nuclear medicine pain therapy
for bone metastases with samarium-153

Requirements, indications, side effects

This therapy is suitable for all patients with osteoblastic skeletal metastases who exhibit pain symptoms. This nuclear medicine therapy offers patients an effective and relatively low-risk way of alleviating bone pain and thereby improving their quality of life. However, the therapy must be seen from a palliative point of view, i.e. it cannot cure the condition.

Radionuclide therapy with samarium-153 requires a significant accumulation of the radionuclide in the metastases. This must be checked before each radionuclide therapy by means of a bone scintigraphy, which should preferably not be older than 4 weeks. Therapy should be considered if the patient has a very painful, multilocular to disseminated skeletal metastasis, if the primary treatment options have been exhausted and if the patient's blood count does not indicate that the therapy should not be carried out. Radionuclide therapy must not be carried out if the patient is pregnant or breastfeeding. A pathological fracture of the vertebral body as the cause of the pain symptoms and significant compression of the spinal cord should be ruled out.

Carrying out the therapy

Szintigraphie Aufnahmen ventral dorsal — Scintigraphy images of ventral (front) and dorsal (back) following treatment with Sm-153, which was carried out at 3-month intervals. The PSA value dropped significantly over the course of the treatment (1st cycle: PSA 25.6 ng/ml, 2nd cycle: PSA 4.05 ng/ml, 3rd cycle: PSA 5.9 ng/ml). In the scintigram, the bone metastases accumulate significantly less or some bone metastases no longer show metastasis-typical accumulation. The patient reported a decrease in pain.

After clarification of the indication and feasibility of palliative pain therapy, the patient is informed in a detailed consultation and informed about important complications and rules of conduct, after which a written declaration of consent is obtained. The therapy can be carried out on an outpatient basis at the Polyclinic for Nuclear Medicine if the appropriate conditions are met. Of course, pre- and post-diagnostics as well as the therapy can also be carried out as part of a 2-day inpatient stay on our K0 ward if necessary. The therapy consists of a single intravenous administration of the radionuclide. After the injection of Sm-153-EDTMP, a whole-body scintigram must be taken to document the tracer distribution.

The therapy can be applied repeatedly. According to the so-called "Vienna protocol", the therapies are repeated at 3-month intervals in the first year. From the 2nd year onwards, the intervals are extended to 6 months

Treatment of skeletal metastases

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