Pseudo Progression
Treatment of Melanoma Brain Metastases with immunotherapy has produced a new Magnetic Resonance Image (MRI) construct named “Pseudo Progression”. The hallmarks of pseudo progression are sudden, dramatic growth in size and number of brain tumors following one or more infusions of an immunotherapy such as Keytruda (aka pembro), Opdivo, and/or Yervoy.
My experience with pseudo progression started with an MRI of June 20, 2017 after my third infusion of pembro. In the preceding week, I had developed neurological symptoms including five local seizures, (tongue, mouth, left eye, and the left side of my face) and a loss of motor control over my left leg. Suddenly, I needed hiking poles to safely walk around the house or on city streets.
My oncologist agreed to my request of a new MRI, because these symptoms were very concerning and the next routine MRI wasn’t due until July 18th. The new MRI was more startling than the neurological symptoms, because it was dotted with numerous new tumors, some already more than a centimeter in diameter in addition to my resected tumor pocket, which doubled in size. At first glance, this MRI looked like dramatic disease progression.
Oncologists believe that pseudo progression appears in the MRI because Immunotherapy creates inflammation in the area surrounding tumors of all sizes. This inflammation is caused when Killer T-Cells attack and destroy melanoma tumor cells. On the MRI screen, inflammation lights up; microscopic tumors look like small white dots; visible tumors appear as larger white lights, larger than they actually are. It’s like shining a flashlight at the dark woods and suddenly seeing many dangerous wild creatures looking back at you.
Pseudo progression is difficult to distinguish from actual rapid cancer progression because MRIs are low resolution images that don’t distinguish and differentiate individual cells.
Pseudo progression is both a blessing and a curse. On the plus side pseudo progression suggests that my immune system, empowered by infusions, is mounting an attack on active melanoma metastases. But in the brain, resulting inflammation can cause dangerous immune-related-adverse-events (IRAEs), including malfunctioning nerves that can disable a patient. Oncologists must balance treating the cancer with avoiding and providing relief from the IRAEs. Fortunately steroids, are effective at reducing inflammation and side-effects, at a cost of slowing down the treatment effects, so it’s best to minimize the use of steroids.
My care team agreed to delay pembro infusion #4 by several days, while doubling my daily dosing with anti seizure compound (levetiracetam) together with adding a low dose of steroid (dexamethasone), a strategy to reduce seizures and reduce inflammation in hopes of relieving my left leg impairment. With these precautions in place the new plan is to administer pembro infusion #4 on Monday June 23.
After discussing this matter of pseudo progression, and in parting, my radiation oncologist said, “There is an International Gamma Knife Society Meeting in March of 2018. If you prove to be a positive case for my studies of pseudo progression, I will use your MRI for my talk. You will make me famous.”
I replied, “Count on me, I’ll do my best to help make you famous!”