Brain Metastases - Workshop Discussion
Discussion: Best Current Treatment
The best current therapy for non-disseminated metastases is surgical resection in the absence of definitive diagnosis, and generally involves stereotactic radiosurgery in patients with a known diagnosis. A significant number of metastases fail to respond to radiosurgery, or are associated with significant peritumoral edema and symptom worsening months later that might represent a mix of tumor recurrence and radionecrosis of the tumor.
Issues related to Pilot Studies
A significant number of metastases would be excluded if they were within 2 cm of the inner table of the skull, due to the effort to minimize skull heating. The initial safety study would exclude posterior fossa metastases, due to the risk of edema and sudden neurological demise due to acute hydrocephalus. It would also exclude melanoma and renal cell carcinoma due to hemorrhage risk.
Protocol option 1: FUS Feasibility in Radiosurgery Failures
The feasibility protocol would recruit 20 patients over a year who had failed stereotactic radiosurgery and had four or fewer lesions. Only one lesion would be treated, generally the most symptomatic one. The treated lesion must be at least 2 cm from the inner table of the skull, with a maximum diameter of 4 cm. Patients with a worsening radiographic picture due to either tumor re-growth or radio-necrosis due to SRS or both would be included. Study sites might include the Brigham & Women's Hospital in Boston, the University of Virginia, the University of Toronto and Sheba Medical Center.
The feasibility study protocol would involve treatment using the lower frequency (230 kHz) brain unit, which allows for slightly larger sonication volumes and target location well away from the midline. As above, patients would stop anticoagulants for two days before MRgFUS, until there is no evidence of increased risk of hemorrhage. Tumors known to have a high propensity towards hemorrhage would also be excluded (renal cell carcinoma, melanoma), as would those in eloquent regions or with significant mass effect from peritumoral edema.
Future work will involve extending the accessible treatment area closer to the skull. In addition, simulations will investigate parameters leading to cavitation in relation to the cranial vault and the skull base.
Protocol option 2: FUS Feasibility in WBXRT Failures
In Toronto, Loch MacDonald reported they are not as aggressive in treating patients with brain metastases using stereotactic radiosurgery as in the USA. This represents an opportunity to obtain de novo data in patients who have not had focused treatment. The protocol might involve MRgFUS in a head-to-head comparison, or as an adjuvant to whole brain radiation therapy (WBXRT). Brain metastases are a common disease, so a single site could generate enough data, especially for a safety study. Dr. MacDonald estimates easily recruiting 10 patients over 6 months. The protocol would involve treating patients with four or fewer brain metastases who have failed WBXRT, with treatment volume < 2.0 cm diameter, lesions in non-eloquent locations. The requirement for the lesion to be greater than 2 cm from the inner table will be a problem because most lesions occur in that range. Consensus of the group: to exclude melanomas and renal cell carcinoma due to very high hemorrhage risk. They would also exclude posterior fossa lesions until safety has been demonstrated (ie., no overwhelming edema post treatment).