Is radiosurgery in combination with other cancer therapies safe in patients with brain metastasis?

The aim of this study was to evaluate the safety of giving stereotactic radiosurgery (SRS) at the same time as other cancer treatments for patients who have brain metastasis. The study found that SRS given in combination with chemotherapy, immunotherapy, or targeted therapy was safe with low levels of side effects.

The spread of cancer from the original tumor to other parts of the body is called metastasis. Cancer types such as melanoma, lung, and breast often associate with brain metastasis (BM).

Treatment options for BM include whole-brain radiotherapy (WBRT). WBRT is associated with high levels of radiation side effects. SRS is another treatment option for BM. It delivers radiotherapy directly to the tumor rather than the whole brain area. SRS has fewer radiotherapy associated side effects than WBRT.

Treatment of BM with radiotherapy can be combined with other anti-cancer agents. Options include chemotherapy, immunotherapy, and targeted therapy (systemic therapies). However, the safety of giving SRS at the same time as systemic therapy is not yet clear.

This study evaluated results from 77 different clinical trials. Data was collected from 6384 patients with BM. Patients were given SRS at the same time as systemic therapy.

There were no trials where chemotherapy and SRS were given at the same time. However, chemotherapy given directly before or after SRS did not result in severe side effects. 

Bevacizumab (Avastin) given immediately after SRS was not associated with an increased risk of side effects. With targeted drugs that block the epidermal growth factor receptor (EGFR) such as gefitinib (Iressa), osimertinib (Tagrisso), or lapatinib (Tyverb) there was no increased risk of brain-related side effects when given together with SRS. Erlotinib (Tarceva) may be associated with an increased risk of brain-related side effects.

Trastuzumab (Herceptin) given at the same time as SRS may be associated with a higher risk of side effects related to radiation. BRAF inhibitors vemurafenib (Zelboraf) and dabrafenib (Tafinlar) were associated with an increased risk of bleeding within the tumor in the brain. Other targeted therapies such as ALK-inhibitors (crizotinib [Xalkori], alectinib [Alecensa]) or MEK-inhibitors such as trametinib (Mekinist) did not result in side effects when given at the same time as SRS. 

Immunotherapies such as ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda) given in combination with SRS also did not result in severe side effects.

The study found that giving SRS at the same time as chemotherapy, immunotherapy or targeted therapy is overall safe.

Some trials evaluated in this study did not have toxicity measurements in the absence of SRS to compare to. For use of erlotinib, there is not enough information to conclude whether SRS can be given at the same as this medication.