Minocycline Therapy for Management of Adverse Radiation Effects

Although stereotactic radiosurgery (SRS) has proven to be highly effective in the management of brain metastases, it is not without risk. Despite selective targeting of lesions and the sharp dose fall-off associated with radiosurgical treatments, adverse radiation effects (AREs) can occur in 10-15% of patients. Adverse radiation effects (AREs) can be defined as unexpected or undesirable post-radiosurgery imaging change regardless of whether it is clinically symptomatic. Patients showing ARE have limited therapeutic options with corticosteroids being the main treatment modality. This single arm clinical trial, will evaluate the safety and feasibility of minocycline in improving AREs. Brain metastases patients with documented AREs will be treated with minocycline (100 mg twice a day) for 3 months in addition to the standard treatment with oral corticosteroids. The investigators anticipate recruiting a total of 15 patients over 12 months. Primary aim: The primary aim is of this study to evaluate safety and feasibility of minocycline therapy in patients with ARE after radiosurgery. The investigators' hypothesis is that minocycline will be safe in this patient population. Safety will be assessed by monitoring blood levels of drug, liver enzymes, renal function tests, and monitoring for major and minor side-effects. Research Strategy The investigators plan to conduct a single arm observational study to evaluate safety and feasibility of minocycline in patients diagnosed with radiosurgery associated adverse radiation effects. In addition to clinical and biochemical monitoring for safety, the investigators will also employ neuroimaging techniques to investigate whether minocycline reduces enhancement at lesion in post contrast T1 weighted MRI and reduces hyper intensity surrounding the tumor as detected by T2 MRI radiosurgery. Primary Outcomes: 1) The primary clinical outcome will be safety of minocycline use in this patient population. Secondary outcomes: 1) The investigators will also review brain images in detail to find any evidence of benefit from Minocycline therapy such as reduction or resolution of volume of T2 hyper intensity and contrast enhancement at the lesion (radiation necrosis) at 4-6 weeks and 3 month follow-up. 2) Overall neurological status 3) Change in neurocognitive status, 4) Reduction in the number of patients needing resection 5) Changes in plasma biomarkers, and plasma drug levels. Target Population: Recruitment will take place at Center of Image-guided Neurosurgery of UPMC. All patients with AREs after brain metastases radiosurgery will be potentially eligible for the study. The investigators anticipate enrolling 15 patients. Patients will be diagnosed based on MRI findings. The investigators will evaluate T1 pre and post contrast, T2, FLAIR and Perfusion MR in order to diagnose ARE. MR spectroscopy or CT Pet will be obtained when clinically indicated. The investigators will use T1/T2 matching and proportion of edema versus lesion volume as a guide for diagnosing ARE.