Tyrosine kinase inhibitors (TKIs) are often used in the standard treatment for patients with metastasized renal cell carcinoma. In addition to their ability to specifically inhibit tumor growth, TKIs also interfere with the vascularisation of the tumor. Unfortunately, most patients do not obtain long-lasting clinical benefit from this treatment. The goal of the current study is to enhance the effect of TKIs by combining them with stereotactic radiotherapy treatment of one of the metastases. This type of radiotherapy allows us to precisely irradiate the tumor with minimal effect on the surrounding healthy tissue. Recently it has been demonstrated that this type of radiotherapy stimulates the immune system to attack the tumor. By combining stereotactic radiotherapy with TKIs we expect to observe a reduction of metastases in a bigger population of patients.

In the first part of our study we focus on the safety of the combination therapy. In the second part we will evaluate the combined treatment response.

Inclusion Criteria:

• signed informed consent
• diagnosis of RCC with clear-cell component histology
• at least 3 extracranial measurable metastatic lesions per RECIST
• Karnofsky Performance score >60
• patients should have undergone cytoreductive treatment of their RCC at least 6 weeks prior to inclusion
• patients should have adequate organ function for TKI treatment.

Exclusion Criteria:

• prior systemic treatment for RCC
• uncontrolled central nervous metastases
• prior radiotherapy interfering with SBRT
• any disorder precluding understanding of trial information.