Our Cancer Journey, Part 4: Lessons from the science

March 19, 2020

Let me start our post today with some numbers, and some explanation of numbers.

First the numbers:

  • The median life expectancy of a person diagnosed with Stage IVa metastasized colon cancer is 2 ½ years. I am now more than 3 years out from my diagnosis.
  • I have had cancer most likely for somewhat more than 10% of my life
  • Marion and I have lived, loved, and sometimes cried through a bit more than 5% of my life knowing that I have cancer
  • I have now three CT scans in a row the report for each of which says, “no evidence of metastatic disease.”

We’re not sure why I am alive. A person diagnosed with the same cancer, same stage, and same month as I was passed away almost a year ago. Another such person is now receiving only palliative care. Cancer is indiscriminate, and life is fickle. There are many factors that helped keep me alive, to be sure:

  • My wife. Marion took on as her full-time job making me healthy. I did things to take care of myself that I would never have done without her.
  • The doctors, nurses, and staff of the Simon Cancer Center and IU Health. When we got to the Simon Cancer Center, their message was simple: we think we may be able to cure you; if not we can provide a good quality of life for many years; and we will always be honest with you. The Simon Cancer Center is a place where everyone acts like they always expect good outcomes.
  • My family. My family was right there with me every step of the way, supporting me emotionally and in practical ways to numerous to count.
  • My colleagues near and far. The depth and kindness of the professional communities in which I work has always been clear to me; needing to be on the receiving end this much was new for me. Learning to receive was an important but difficult lesson, one not yet completely learned.
  • Everyone who supported me, near and far, including readers of my earlier blog on Caringbridge.org. I remain overwhelmed by the support I have received.
  • My new teachers in life, including those who helped teach me about mindfulness, Qi Gong, and First Nations spirituality.
  • Whatever power it is in the universe we call God.

Perhaps some of my own behavior moved the odds a bit, but I’ll put faith in everyone and everything else first. There were times when I was definitely not in control of my own behavior at all, anyway, thanks to pain and / or pain medications, so my own behavior can’t be the cause of my current good condition.

The biggest factor in me being alive today is the incredible rate of progress of research and development of new treatments for many sorts of cancers. Immunotherapy and the feasibility of sequencing a patient’s tumor genome are two major contributing factors. Science, the journal of the American Association for the Advancement of Science, identified immunotherapy as the “breakthrough of the year” in 2013 (see https://www.cancerresearch.org/blog/december-2013/cancer-immunotherapy-named-2013-breakthrough-of-the-year). 

At a very practical level, I am alive today for the following reasons:

  • The typical, by-the-book, “standard of care” approach to cancer did pretty darn well in keeping me alive and functioning for 1 ¾ years. The importance of this cannot be overstated. There is a reason that doctors treating cancer start off with the treatment recommended by the AMA guidelines for standard of care for cancer: this standard, which is updated regularly, represents the best general approach to any particular form of cancer based on the most recent established treatment options. 
  • A particularly important point is that while I was treated by the “standard of care” approach, I moved from a local general oncologist and local “very good” quality surgeons to the Simon Cancer Center, now recognized as one of just 51 comprehensive cancer care centers in the US. There I was treated by some of the best GI cancer oncologists in the US, and operated by surgeons who are among the best in the Midwest. Finesse in implementing the standard of care is an issue. And again: thanks go here to Marion. Without her insistence, I would have just been content to be treated by the local general oncologist, and it’s clear from what I have seen of his notes that he viewed treating me as management of quality of life of a dying cancer patient. That’s NOT the approach that was taken by the Simon Cancer Center.
  • Lucky timing. A new study for an immunotherapeutic approach to metastisized colon cancer began on March 18, 2018, just over a year after I was initially diagnosed. This study is very precise in its focus: to qualify, a patient has to have refractory (recurrent) metastasized colon cancer, three specific genetic alleles, and ‘moderate’ levels of mutation in the tumor genome. Luckily enough, I have all three of these characteristics.

The science of my treatment is, I think, pretty interesting. It also demonstrates how carefully targeted newly emerging cancer treatments are.

My tumor includes two specific genes that are overexpressed, and each when overexpressed “hides” the cancer cells from being detected by my immune system. At a cartoon level what happens is that when T-cells come along – the part of the immune system that identifies foreign and abnormal cells and marks them for destruction – the cancer cells say, “nothing to see here, move along, move along.” And the T-cells simply leave the cancer alone. This is the key to why my cancer kept coming back. One of the important recent understandings about cancer treatment is that successful curing of people depends on the immune system playing a key part. When a patient is cured of cancer, what happens is that some combination of surgery, radiation treatment, and chemo knock the cancer down… but it’s the immune system that finishes it off. In my case, chemo, radiation, and surgery knocked my cancer down to the point that nothing was detectable on a CT scan twice. But because my cancer cells “protected” themselves from my immune system, each time my doctors got me to the point of no signs of cancer visible in a CT scan, the remaining – and still very many – cancer cells in my body grew to the point of creating new tumors. This also helps explain how I went from a clean CT scan in at the end of 2011 to Stage IVa metastasized cancer when I was first diagnosed at the beginning of 2017. Whenever it was that my cancer started, it was able to grow without interference from my immune system. 

The experimental drug trial I am in involves three monoclonal antibodies: Nivolumab, Ipilimumab, and Panitumumab. Nivolumab and Ipilimumab each suppress one of the two genes that, when overexpressed, “hides” my cancer from my immune system. That lets a person’s immune system “see” the cancer cells and attack them. But these two drugs, which are already approved for treatment of metastasized colon cancer, have a success rate of about 25%. That’s a great success rate if you are a major league baseball player, and plenty good if you are one of the patients who is cured by virtue of being in that 25% of patients who can be successfully treated. The “trial” aspect of the treatment I am in is adding Panitumumab to treatment with Ipilimumab and Panitumumab. Panitumumab is already approved for treatment of some types of melanoma (a form of skin cancer). It blocks the action of something called Epithelial Growth Factor – a compound that in our body enables the proliferation of epithelial cells (https://www.cancerquest.org/patients/drug-reference/panitumumab). And recall for a moment that while we are a fairly complicated torus (https://en.wikipedia.org/wiki/Torus) and the lining of our gut is basically an epithelial cell. The three-drug combination I am on basically functions like this: the Panitumumab suppressed proliferation of the cancer cells enough that my immune system, enabled by Nivolumab and Ipilimumab, can kill cancer cells faster than they grow. Or in more cartoon-ish terms, the Panitumumab holds down the cancer while the Nivolumab and Ipilimumab enable my immune system to beat it up. 

Way cool. And it is this brand-new therapy that has me free of visible signs of cancer in my CT scans, also with normal levels of Cancer Embryonic Antigen (CEA – a measure of how your body is reacting to new cancer cells, and therefore a measure of how much cancer there is in your body). Without this brand new advance we would be playing a game of “let’s see how long chemo can keep Craig alive.” I am ever so grateful for the researchers who are inventing new therapies. I’m also a bit lucky: I have a relatively common cancer – one that is actually increasing in incidence. There is a lot of money for the pharmas in finding new cures for colon cancer – as opposed to some other very rare cancers or other rare and fatal diseases. This situation also shows how silly the statement “let’s find a cure for cancer” really is. The drug combination that is keeping me in such fine fiddle is prescribed now for people with recurrent cancer, three specific drug alleles, and a specific range of DNA mutation rates. Cancer is a category of diseases, and curing all – or even many – cancers will take hundreds or thousands of different approaches. But for now, Marion and I are glad that there is a treatment that seems to help me, while cognizant that many other people are not so lucky. Thanks to all cancer researchers and health care professionals treating people with cancer. You are keeping me, and many others, alive and enjoying life.