Brain Metastases: The Latest Answers To Your Questions

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.

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9 responses to “Brain Metastases: The Latest Answers To Your Questions”

  1. Avatar Rick Fleming says:

    Just wondering, what is the largest size brain met that can be treated with gamma, if there are 2.

  2. Avatar Mr Ziggy Bis says:

    Hi Veronica

    How important are steroids after initial diagnosis of secondary brain tumours and primary melanoma. ?

    Kind regards

    • Catherine Poole Catherine Poole says:

      Steroids can be very helpful in mitigating your side effects. They do not block the effectiveness of the therapy.

  3. Avatar Patricia Wood says:

    KEYTRUDA: My sister has Stage 111B melanoma and is being treated with Keytruda. She has an infusion once every 21 days. She recently had her third infusion. How many infusions are generally needed before there is a response?

    • Catherine Poole Catherine Poole says:

      Response to the immunotherapy treatment can be very individual. It can be slow or fast. Your doctor will know if it is working by scans and how she feels.

  4. Avatar Jane Millard says:

    My husband has Stage IV Metastatic Melanoma. Had lobectomy for lung tumor 2016, then craniotomy 2016 followed by radiation in surgery site plus additional lesion. Keytruda for five months, didn’t work, tumors in lungs, liver, cecum and brain, same site as previous surgery. October 2016 second craniotomy to remove regrown tumor. Began Opdivo/Yervoy combo, near fatal side effects, mega colon, diarrhea. He had ileostomy and removal of cecum tumor. Opdivo and reduced Yervoy tried as lung tumors were resolved and only one liver tumor remains. Time off immunotherapy to allow kidneys to recover. April 2017 Third craniotomy done to remove regrown tumor. Opdivo alone started and tolerated well. Recent MRI went before tumor board as they believe there is another lesion in same place now inoperable. They recommend researching clinical trials and BRAF gene testing. They didn’t know he already tested negative for it. Are you aware of any other treatments available. My husband has no new symptoms as yet. Neurosurgeon saw black dots and couldn’t dig anymore and suspected tumor would grow back. Any suggestions would be extremely appreciated.

  5. Avatar Olivia says:

    My husband has mesothelioma and is going to do proton therapy. He is currently enrolled in a clinical trial with a hospital. Is this type of technology better than proton?

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