I was really starting to feel normal again, and by normal, I mean great. On 12/7/15, I started chemotherapy and radiation at Spectrum in Grand Rapids with a Pembro infusion in Chicago. Not an easy task to schedule appointments in Grand Rapids and Chicago on the same day during business hours in winter.
I was solidly running on the treadmill, lifting weights, playing with kids, taking naps and had a renewed intimacy with Staci (link is for paying ‘gray members’ only). I’m not sure how I ever had time to work. The day fills up pretty quickly. The 8 minute miles were melting to 7 and even less on the treadmill. No headaches, no gurgling sensation, just blissful fatigue. My Paxil, my Xanax.
I wasn’t worried about the actual chemotherapy and XRT, just the implication that time was passing quickly. My recovery would morph into treatment and follow-up scans and the subsequent “scanxiety.” I was over a month from the diagnosis, and soon would need to assess whether all of this treatment was effective.
The morning started as usual post surgery. I woke up around 4, tried not to wake Staci as I searched for my iPhone and earbuds, and ingested my podcasts quietly. By 5, I had my Cracklin’ Oat Bran, let Miley out, and started my routine. While jogging on the treadmill, TV 8 was reporting Jimmy Carter no longer had evidence of brain mets from melanoma. Guess what he took? This was unheard of a few years ago. This 91 year old had tolerated my Pembro therapy. That’s a good sign, I thought.
Just getting into the Pembro trial at Northwestern was a series of fits and starts. Katie made several e-mails, including to Northwestern. The Pembro trial was initially full on 10/2015, but a spot opened up after another patient had to drop out due to lab abnormalities. Even qualifying for the trial, however, was a challenge with an unexpected turn of my own liver tests. My ALT was 280, AST a bit above normal, and the rest was normal. How could that be? My liver tests were normal 10/29/15, a CT of my abdomen did not show any liver abnormalities. I stopped the only medication I was on (Keppra) and waited. Within a week, they were low enough for trial. Within a month, they were normal. Back with Pembro.
Prior to chemo, XRT, and Pembro, I thought we heard the last of the worst 10/29/15 with the MRI: almost certainly glioblastoma multiforme. We had a diagnosis. It was time to face treatment head on. But cancer has a way of giving and giving. Brace yourself. I needed to be diagnosed a few more times first.
I am young for GBM, and maybe a less malignant cancer was still possible? A CT scan a few days after the MRI of my chest / abdomen / pelvis essentially ruled out metastatic disease. That may have been the most disappointing normal CT scan ever reported, but completely expected. I guess we still had a diagnosis. I viewed my own scan. Good news: no coronary calcium. I can further classify myself from low risk to extremely low risk for a cardiac event in the next 10 years.
Figure: Left, self with a gown preparing for my CT of the chest, abdomen and pelvis. Middle, completing the tour of 2007 chief medical residents from University of Michigan with Mark Huffman (currently staff at Northwestern). Right, wearing my ‘lucky’ t-shirt.
While I was in the PACU (surgical recovery area), Dr. Jumper discussed the preliminary pathology report with my family: glioblastoma multiforme. Okay, fine, glad I was sedated for that. Finally, we could just get on with treatment. That’s what we thought, anyway. So Dr. Jumper graciously called a week after surgery and told me the final pathology report: glioblastoma multiforme. Wait, didn’t we already know that? It still could have been something else? Although the clinical presentation and every test suggested GBM, hearing it again was a blow back to reality. Maybe I still had hopes of some rare infectious disease, less aggressive tumor, or maybe just the wrong person (I’m not specifically talking about anyone else :). So it felt like I was diagnosed with GBM again and again and again.
Once the diagnosis was confirmed (again), I started reviewing prognostic factors for disease. We have all sorts of calculators in cardiology, and when possible, share results with patients. “Your risk for a stroke or an MI in the next 10 years is 15%.” So I was looking for equivalents in oncology. Despite only reading tangentially around the disease, I tried to calculate the incalculable. I tip toed through the literature. Under 40? Great, positive prognosis (never mind that I was 39, and completely aware that biology is a continuum). Frontal lobe tumor? Got that, too. I’m on a roll. Very functional at work, play and family (high performance status). I really cannot even detect a symptom in hindsight, even looking through my cancer goggles.
While I sorted through all the clinical and gross pathology prognostic factors, I was really waiting for tumor markers. I could assess the former, but needed to have the pathologist fill in a few details on tumor markers. For cancers, there are a host of tumor markers that correlate with prognosis. In fact, many argue we may stop talking about breast, lung, or colon cancer, but instead talk about the molecular fingerprint. For GBM in particular, the most important marker in 2016 is methyl guanine methyl transferase (MGMT) promotor methylation. For the healthy person, this enzyme goes about repairing your DNA.
This is a good thing. The enzyme works better when it is not methylated.
Your DNA needs to precisely replicate itself a zillion times, and withstand multiple environmental insults. Most people want a healthy, functioning (non-methylated) MGMT to make sure any errors are corrected in pairing nucleotides. We are certainly a biological marvel. Cancer develops through a series of mutations, and about 1/3 to 1/2 of patients with GBM have a mutation in this gene where the MGMT becomes methylated. This slows the whole enzyme down, and it is no longer able to repair DNA errors effectively. However, if you have this mutation, it serves you well while undergoing GBM chemotherapy. Temodar, the standard chemotherapy, is an insult to DNA. Temodar can wreak havoc on DNA, and the GBM cannot repair the damage as well with a methylated MGMT. Also, regardless of mechanism, it also just appears patients that have this mutation have a greater chance of living longer.
Every time I received an e-mail with lab results on UM patient portal or call from the 734 area code (University of Michigan), I started to have palpitations. I promised myself I would not get hung up on one lab result, one factor among many. But the MGMT status kept being delayed. In my experience, no news is no good. Doctors like to call with good news. Finally, on our first day of chemo / XRT / Pembro, I received an e-mail reply answering my 2 questions with good news and bad: “Yes, you can start swimming. Your MGMT status is not methylated.” Put that in the “Damn” category, or rhymes with bad ‘luck.’ Just felt like I was diagnosed with GBM again.
So I stopped reading about prognostic factors. I have some good, I have a few that are not so good. Mix it up, and I am the first person with this particular disease in a certain location, age, functional status, and molecular fingerprint.
But I do have a few unusual prognostic factors. My dad, a 72 year old internist in Grand Haven has a good ‘feeling’ about all of this. Call it intuition. If you know him, and there is a good chance you do if reading this, he may be the oldest person to be newly diagnosed with Attention Deficit Hyperactive Disorder (okay, diagnosis was informally made by his children). He is a load to keep focused, and his only treatment has been a mixture of coffee and naps. That said, he takes tremendous pride in his work, still studies, and has call for palliative care that rivals cardiology call for time involved. And he talks to himself quite a bit, especially when stressed. The grandkids find this funny since even George Carlin may admit some of the words from his mouth shouldn’t be said on television. But he also is frequently working through a difficult patient problem in his head. He earnestly wants to do the right thing because it is the right thing. And he is the hardest worker I know. And for that, I could have no better example in my career. He has a good doctor’s sense, and he has a good feeling about this thing I am going against. I’ll take that prognostic factor. I’ll keep my PCP.
Figure: Left, the original 3 women in my life sporting gray nail polish. Right, dad taking a power nap after coffee.
Getting back to Pembro, my mom and sisters went up for the first dose with me. We got there too early, and went for lunch at Water Tower. I am not sure what we were talking about, but my mom flatly said, “Craig is just not going to die from this. He just isn’t.” She usually gets what she wants with us — Grand Haven to Grand Rapids has been a nice buffer to avoid too many of her ‘requests’ — but this was a very special request. I laughed-cried, and then started to seriously wonder how I was going to die. If not this, then what? I started making sure traffic was very clear on the Beltline before turning, salting the front steps every time it snowed, checking dates on the milk prior to consuming (okay with 4 kids, that is never an issue). Thanks, mom. I’ll take that prognostic factor, too and stop trying to calculate.
I don’t know if Pembro works. Nobody does. That’s why I love it. I can’t read about percentage of responders because someday, someone will be reading a journal article that includes me as a subject. It is an X factor that makes my complicated prognosis even more so — too many variables to solve. Forget calculating anything now. Other patients are trying different things, and all power to them. Somebody needs to be a be a success story for others to follow. For now, I’ll just follow my mom’s advice.
Figure: Left, Staci, me, Chicago. Middle, Pembro and me. Right: Staci, me, and a Sunday on La Grande Jatte. We are just so cultured. Oh yeah, and I’m bald now.