The Doctor is in:
Veronica Chiang MD
Director, Yale Neurosurgery Radiosurgery Program
Director, Yale New Haven Hospital Gamma Knife Program
1. Should I get a brain scan when I am first diagnosed with melanoma stage III or stage IV for a baseline?
Current NCCN guidelines are for an initial MRI brain at diagnosis of stage III or IV disease and then annually after this. The biggest barrier to this seems to be getting insurance approval if the patient is asymptomatic but we would strongly advise pushing for the initial and routine annual imaging given the high rate of brain metastases in metastatic melanoma.
2. How many tumors can be zapped by gamma knife or stereotactic radiation at a session and is whole brain radiation ever a good option?
The number of tumors that can be treated at any single session is realistically determined by the radiosurgery technology available at any single institution and the patient’s ability to tolerate the head immobilization device.
With regards to radiosurgical technology : Most LINAC-based radiosurgery systems today, such as Cyberknife, have planning software that allow for the planning of up to 10 lesions. In contrast, for Gamma Knife, the limit for how many lesions can be planned and treated has not been reached medically yet – the largest number we have treated at our institution during a single day session is 51. With this many tumors, however, the more important question is whether or not radiosurgery is the best medical option.
In patients with more than 10-15 tumors seen on a standard diagnostic MRI of the brain, there is a 100% chance that there are micrometastases (bunches of tumor cells in the brain that one cannot see yet because they are too small to detect using even MRI). Because they are not visible on imaging, they will not be treated using radiosurgery alone and in this case, whole brain radiation therapy is sometimes the better option. It has been well demonstrated that uncontrolled cancer in the brain is still far worse for a patient than whole brain radiation therapy. The patient we treated for 51 tumors had unfortunately already had whole brain radiation therapy and therefore did not have that option available again.
With regards to head immobilization : Gamma Knife immobilization is obtained using a frame screwed to the skull, compared with most LINAC-based systems that use a mask. While having the frame placed for Gamma Knife seems daunting, once applied, wearing the frame is not uncomfortable and for most patients the frame can be worn for days without discomfort. The screw attachments to the skull are no different than those used for halo immobilization for neck fractures and halos are worn for 2-3 months at a time.
Masks however are rarely tolerated for more than one hour at most. Because of this difficulty with the mask, if a patient had 5 brain metastases that needed treatment, the patient undergoing Gamma Knife could have all 5 tumors treated on the one day whereas the patient undergoing LINAC-radiosurgery would likely have one tumor treated each spread out over 5 days.
3. Do any of the new melanoma therapies cross the blood brain barrier and do they work there to eliminate the cancer? Can they work alone for therapy?
The new therapies for melanoma are divided into targeted therapies and immunotherapies.
Targeted therapies include BRAF agents such as dabrafenib and MEK inhibitors such as trametinib. These agents do cross the blood brain barrier and can be very rapidly effective at reducing brain metastasis lesion size after their initiation. Unfortunately, the effect of these drugs is not long lasting (and therefore not curative). Long term durable control of brain metastases still requires the addition of radiation.
Immunotherapies alone such as pembrolizumab or nivolumab can also have effect in the brain although this is not as well studied. A recent publication in Lancet Oncology reporting the preliminary results of pembrolizumab alone for the treatment of brain metastases suggests that 20% of patients had a positive response in the brain. The difficulty with using these drugs alone in the brain is due to the fact that there are no currently known predictors of which patients will have a good response. Simply watching brain metastases while waiting to see if the drug works can result in interim bleeding or rapid growth of tumor in the brain that can cause irreversible neurological problems thus making the tumors much harder to treat with standard options. Since 80% of patients will not get a response in the brain from these drugs, using them alone for treatment of brain metastases is not the standard recommendation at this time.