Glucocorticoids, Immunotherapy and Radiosurgery for Brain Metastases

Study Overview
=================
Brief Summary
-----------------
Background. Brain metastases are the most common intracranial tumor and occur in 20-40% of all oncological patients. The most common primary cancer in brain metastases is lung cancer, followed by melanoma, breast cancer, renal cancer and colorectal cancer. The incidence of brain metastases has been increasing but the occurrence of brain metastases is still associated with high morbidity and poor prognosis. The main treatment methods are stereotactic radiosurgery (SRS), microsurgical resection and whole brain irradiation (WBRT). The stereotactic Gamma Knife Radiosurgery (GKRS) is a non-invasive method, applying high dose radiation into an exact defined volume within the cranium, and thereby associated with significantly decreased neurotoxicity. It is the only treatment method for multiple disseminated and thereby non-resectable brain metastases. A novel treatment method of brain metastases is the combination of GKRS and systematic immunotherapy (IT), targeted therapy (TT) or chemotherapy, which showed significant improvements in survival. Furthermore, patients with brain metastases often develop cerebral edema, which is commonly treated with glucocorticoids to relieve the symptoms and decrease the fluid accumulation, but the long-term use was shown to be unfavorable due to various side effects. One of the potentially concerning side effect of glucocorticoids is the immunosuppressive properties. This raises the question of whether glucocorticoids might influence the effect of immunotherapy. Aim. The aim of the study is to evaluate if the use of glucocorticoids before, during and after treatment with gamma knife radiosurgery and immunotherapy effect the overall survival in patients with brain metastases, in contrast to patients undergoing gamma knife radiosurgery and immunotherapy alone. In addition, the effect of glucocorticoids on progression-free survival and clinical outcome will be evaluated. For the evaluation of the modern oncological treatment, patients with gamma knife radiosurgery, receiving immunotherapy, will be compared to patients not receiving immunotherapy. Patients and methods. The investigators plan to conduct a observational prospective preliminary study including about 200 radiosurgically treated patients with brain metastases. Patients will be included to our study, if they were diagnosed with one of two most common primary cancers (lung cancer or melanoma) and were treated with at least one Gamma Knife radiosurgical treatment for at least one brain metastasis. For the outcome evaluation of the different treatment options, a comprehensive database will be established. The study participations will not interfere with any clincally indicated therapeutic decisions and the study participants will not be exposed to any additional risks.

Official Title
-----------------
Effect of Glucocorticoids on the Outcome of Gamma Knife Radiosurgically Treated Patients With Brain Metastases During Immunotherapy - An Explorative Study

Conditions
-----------------
Brain Metastases

Intervention / Treatment
-----------------
* Drug: Glucocorticoids


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients, who were treated with Gamma Knife Radiosurgery for at least one or more brain metastases and diagnosed with one of two most common primary cancers (lung cancer or melanoma) Patients over 18 years and under 90 years Written, signed informed consent for study particaption after study explanation Exclusion Criteria: Patients under 18 years Patients over 90 years

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GK + IT<br>Gamma Knife and immunotherapy | |
| GK + IT + GC<br>Gamma Knife, immunotherapy and glucocorticoids | Drug: Glucocorticoids<br>* Effect of glucocorticoids (which are often prescribed for cerebral edema) on clinical outcome<br>|
| GK only<br>Gamma Knife without immunotherapy | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from first Gamma Knife Radiosurgical Treatment | Through completion of the study, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New brain metastases | Time until new brain metastases | Through completion of the study, an average of half a year | 
| Clinical outcome according to Karnofsky Performance Status Scale (KPS) | Clinical condition at last follow up according to KPS. The KPS uses steps of 10%. Patients with 100% are not affected by their disease in everday activities, whereas 0% equals death. | Through completion of the study, an average of 1 year |