Colin Loves Tractors Follow Colin's progress through treatment for a brain tumor

August 22, 2015

Colin’s Immunotherapy Treatment

Yet again, I have let too much time lapse between updates on Colin. This time, the reasons are driven externally more than internally. In the quest for an appropriate post-surgical treatment, we discovered a novel option in Augusta, GA, that provided Colin with the elusive combination of a good quality of life and the possibility of durable remission. Although there will soon be a trial open for children with relapsed high-grade brain tumors, Colin is the first child to get on this therapy and is being treated under compassionate use with the FDA.

The story of our path to this new treatment involves our dear friends, the Simkins, whose son Brennan was at St. Jude during our time there to be treated for AML (leukemia). Brennan’s story is even more remarkable than Colin’s and involves four bone marrow transplants within the course of 18 months. Ian first encountered them at the hospital as they arrived to start Brennan on treatment in Memphis and introduced them to the wonderful Montessori school on Mud Island that Aidan attended. Aidan ended up carpooling with the two other Simkins boys, Nat and Christopher, who bracket Brennan, the middle child.

The Simkins are from Augusta, and in their return to the new normal that cancer and its aftermath bring, they became very involved with local cancer research and the pediatric oncology program, which also saw them through their first phase of treatment. They have been working with the local cancer center, which is offering innovative immunotherapy that is based on long years of basic research at the labs at Georgia Regents University (GRU).

To make a long story short, Tara Simkins introduced us to Dr. Ted Johnson, a physician-scientist who was on the verge of launching a clinical trial for children with relapsed brain tumors. While Colin would be eligible for this trial, at the time estimated at that time to open in June, he felt that Colin could not afford to wait for therapy and offered to treat him under a single patient IND, an individual treatment plan to provide access to investigational therapy for a child who otherwise was outside of the realm of standard treatment.

At the time we heard of this option, we were strongly considering a surgery-only approach, removing this very simple tumor and waiting to see if our new interloper had more friends waiting in the wings/how long it would take for them to emerge. While this may seem like a cavalier strategy, it is not unheard of or entirely unreasonable, especially based on the long gap between Colin’s initial treatment and the appearance of this small lesion. There is a surgeon in Australia, Dr. Teo, who specializes in minimally invasive endoscopic brain surgery, who has gone the surgery-only route with other ependymoma patients. The primary risks are that the tumor returns in a location where surgery is much more damaging or effectively impossible to completely resect or that the cancer evolves into a metastatic state where it begins replicating like wildfire, rendering adjuvant therapy effectively impossible.

However, the original idea, monthly infusions of a drug called gemcitabine, became unappealing as we contemplated it. The chemo would affect Colin’s quality of life and Dr. Gajjar wanted to leave the tumor in place, creating an underlying anxiety for us in the risks associated with that. However, he did not want to pursue treatment without leaving a reference tumor that would give us some suggestion as to response to treatment; without that, we would be operating blind. The selection of the chemo was based on lab studies of an ependymoma model that is in the same class as Colin’s tumor, but this seemed a fairly thin thread to grasp when we had a child whose quality of life was so excellent and completely unimpeded by the new lesion. A purely surgical approach seemed to align better with our interests vis-à-vis quality of life and, based on what we could tell, didn’t introduce untenable risk.

Initially, I placed Dr. Johnson’s immunotherapy concept in the column of interesting future ideas, along with other immunotherapy and chemotherapy trials. We considered that it would be something to have on the table, under the open trial, if Colin relapsed at some time after surgery. We had already been looking at other immunotherapy options, but did not find anything that seemed worth pursuing in our first go-around and we agreed with Dr. Gajjar not to go “off the rails” in chasing Phase I trials, which are not designed for efficacy. The surgery-only approach was most attractive under the assumption that the cancer was, as asserted by Dr. Gajjar, indolent in nature and that it hadn’t reached the point of broader dissemination.

However, once we got on the phone with Dr. Johnson and he explained the science behind the new drug and the treatment, we were instantly convinced that it was in Colin’s best interests to pursue this avenue first. Given the radiological changes to the tumor between its initial discovery and the MRI before surgery in March, it was fortunate that we had this plan in place; not using some sort of treatment under the condition of apparent rapid growth was worrisome at best and despairing at worst.

After judiciously studying some articles that Dr. Johnson provided and lobbing a barrage of questions in his direction (my list of questions was so long that we had to get on the phone again; fortunately, he’s patient and willing to explain things in detail), our second conversation reinforced even more strongly our conviction of pursuing this treatment. Because of our earlier plan to have surgery, we already had a date with Dr. Boop on the books.

In order to get Colin into treatment at GRU, Dr. Johnson had to complete paperwork both for the FDA and the institutional review board (IRB), which both must approve any investigational treatment protocol. He had his work cut out for him but appears to be constitutionally undeterred by red tape, so we found ourselves headed to Augusta about three weeks after Colin’s successful surgery.

Astronaut’s First Steps on the Moon

On March 25, Colin became the first pediatric patient to receive indoximod, a checkpoint blockade inhibitor for IDO (indoleamine 2,3-dioxygenase), an enzyme that suppresses immune responses.  The drug works synergistically with other treatments, in this case the oral chemotherapy drug temozolomide (Temodar). Ideally, the immunotherapy reactives the immune system while the chemo does three things in destroying cancer cells: (1) creates antigen in order for the immune system to recognize the cancer; (2) creates inflammation to signal to the immune system to attack; and (3) destroys the existing immune cells, which have been perverted by the IDO-depleted system to not attack cancer. One advantage of the immune system over other adjuvant therapies that we typically use is that it is agnostic as to whether cells are actively dividing. By targeting proliferating cells, traditional treatments leave unharmed cells that are inactive but may eventually erupt into tumors.

Each cycle is 28 days, and he takes the chemo for the first five, while he take indoximod (oral) the entire time. The only real side effects so far have been associated with the chemo.  It has primarily sent Colin to the hospital for platelet transfusions, which he charmingly calls “confusions,” but it has not prevented Colin from going to school or playing with his friends.

We call Colin an astronaut because he is the first, stepping into unknown territory, his slow low gravity footfall billowing up plumes of moon dust. These first steps place him outside of the realm of statistics and expectations. He stands alone next to the lunar lander, the lone connection to the familiar home of Earth, its gold shielding glittering in a sun unfiltered by an atmosphere. Under the glare of that harsh light, Colin remains outside of the protection of known things, but known things weren’t going to help him and his exposure may bring his salvation as well as paving the way for others to follow.

We can examine the theory and science behind the treatment, but there is no substitute for trying it in a real patient. Furthermore, it will be impossible to say whether it worked if he is treated and no additional tumors grow. There is, we suppose, some chance that Colin never had any other errant cells waiting to erupt. Every two months, we reassess whether all systems are go; he passed the first hurdle with flying colors and we are on our way for his second border crossing.

Among other things, the first month required that we stay local to the treatment facility for a month to monitor for potential issues. This provided us with the opportunity to spend a lot of time with the Simkins and to get to know the wonderful Augusta community that they live in. We also happened to be there during the Masters golf tournament, which was an unexpected treat.

The Taste of Hope

Before I go into our Augusta trip, I need to backtrack to the harried days post-rediagnosis when we were trying to make a decision on how best to care for Colin. I had written previously that we knew radiation would be off the table for the time being, since it brought with it too great a risk of debilitation without a significant enough benefit. However, St. Jude itself had no other options, nor did the Collaborative Ependymoma Research Network (CERN), which sponsors trials. Much of the basic science for those trials originates at St. Jude, so we knew that the gemcitabine suggestion was the best we were going to get from those quarters.

As anybody who knows Colin’s story is aware, we have been around the block in order to try to give Colin the best chance of a cure. The decision making has been challenging, at times impossible seeming, and we were fortunate during his original diagnosis that we had several junctures within which we had the luxury of extra time to make the various decisions that we did – time that many families never have.

It is impossible to judge the decisions another family makes and how that process takes place because it is highly individual and it is composed of so many different factors. When I talk about this subject, I always emphasize that the parents have to make the best decision for the family. I don’t say for the child because the child does not live in a vacuum. The child is part of a family, and there are important considerations that play a role, such as the interests of siblings, work, and social support. These are not small issues, and overly straining a system in order to take care of one individual in a family in exclusion of the others wreaks its own havoc.

Something I have long understood but not grasped as clearly as I did when we started embarking on this process again is the nature of an opinion. Opinions from doctors are colored by their individual perspectives: experience; training; institutional knowledge/expertise; access to treatments; awareness of and education about new treatments; and an understanding of the needs and desires of the patient family.

For us, receiving opinions from doctors that we knew made a huge difference because we also had a sense of the inputs that were going into those opinions. We have long observed that doctors tend to recommend the treatments they are most comfortable with, so an oncologist is most likely to suggest chemo while a radiation oncologist is more deft with radiation and leans in that direction. This isn’t to say that each sticks doggedly to his own craft, but these general inclinations are the natural product of deep understanding, familiarity, and experience, and we have seen this borne out in practice.

Initially, we agreed with Dr. Gajjar not to go completely into the wilds in the pursuit of experimental treatments. This advice is strongly colored by his (and our) awareness that Phase I trials are intended to determine safety; efficacy is not their primary goal, and many such trials are, even by design, not likely to achieve a durable remission, though families are often hideously unaware of this fact. In a child with a small metastasis in an area that had not been previously irradiated, with a presumably slow-growing tumor, Dr. Gajjar’s perspective was that we had a reasonable shot at achieving the dual goals of durable remission and preserving Colin’s cognition as much as possible. The chemo was just a tool to buy us time for radiation (our best shot at durable remission after relapse) to be less devastating.

I cannot overstate how important it was that Dr. Gajjar understand Colin as a patient and us as parents in order to provide us with the treatment recommendation that he did. It was not from his standard playbook, not that there really is a standard playbook for Colin’s situation, and we greatly appreciate his thoughtfulness in offering the gemcitabine option, even though we ultimately rejected it.

The perspective of this initial recommendation was a good jumping off point for us to begin our deliberation process because we agreed with the concept of deferring radiation for as long as possible. While we were not anxious to jump into a Phase I trial, it’s not like there were other wonderful and promising options out there.

When back in the mix of things, we turned to our former fellow, Dr. Mariko DeWire, who is now an attending at Cincinnati Children’s Hospital, working under Dr. Maryam Fouladi, another St. Jude alumna. The consensus there was to offer oral etoposide (VP-16), a drug that is commonly used with ependymoma and well known to be effective in temporarily halting the disease though never curing it. Furthermore, it comes along with it a high risk of secondary cancer, particularly AML leukemia. In one clinic conversation, Dr. Gajjar joked that Colin would be the patient to get AML if he ever went on etoposide.

We explained the treatment option at GRU with Dr. Johnson, and Dr. DeWire’s response was patently negative, on the basis that it was too risky and too little known about this drug and its effects on children. It is worth noting that, while no child has ever taken it, many adults have and an adult brain tumor trial using the same drug combination had already moved beyond Phase I with no concerning side effects. The most pressing issues with immumotherapy drugs is that they can cause inflammation, when they work, which is dangerous in the restricted cavity of the skull, or that they inspire an auto-immune reaction if the immune system is encouraged to rage unchecked.

We were aware of these risks and accepted them, with the additional safety net that Colin would be required to remain in Augusta for a full four weeks after starting therapy in order to expedite the response to any negative reactions. Obviously, the question of efficacy still hung in the air, but that was not the Cincinnati group’s focus of concern.

With Dr. DeWire’s recommendation and warning in hand, I had to integrate her perspective into our overall decision. It is impossible to overstate how difficult this was, as we greatly respect her as a physician and know that she has a strong personal connection to Colin and our family. This was not a cold analysis of facts about a random child but a deeply considered opinion, and her warning about the indoximod was sincere and strong.

Even hearing her words and understanding the place they came from, we were undeterred from our decision to go to Augusta, and I struggled greatly with this dichotomy. It was not for lack of respect for Dr. DeWire or a feeling that the team at Cincinnati didn’t give the case much thought; both were clearly true, yet these facts failed to sway us as we continued to move to Augusta.

In the end, I concluded that we had more information about the drug and the mechanism. We had invested more time both in researching it and interrogating the doctor who would ultimately be responsible for Colin’s care (he has also cared for Brennan Simkins in the past, so his reputation as a physician preceded him). Furthermore, the alternatives were unpalatable. As useful a drug as etoposide is, we knew with great assurance that it had no chance of curing Colin, whereas with the indoximod, we at least had a shot.

I did ultimately let Dr. DeWire know what direction we chose, and she very graciously responded that sometimes we have to be brave. I appreciate her thoughtfulness and genuinely feel that she did not censure us for our decision. Anybody who is familiar with Colin’s course, especially in the first few months, knows that we are not worried about hurting a doctor’s feelings about our decisions related to our child. They are professionals and ought to understand their own limitations in this business in terms of what they can bring to the table within the broader scope of what a family can cull from the greater world of medicine. However, this situation was different and it mattered to me that she understood that I heard her and absorbed her opinion; our decision incorporated these thoughts rather than casting them aside, as it easily might appear we had done.

Sunrise to (Camp) Sunshine

With a small tumor lurking rather innocently in Colin’s ventricle, we opted to schedule surgery for March 6, allowing Aidan to complete his ski race season. His last race was on March 1; in two days, I was on a plane for Memphis with the boy and plans for the next phase of treatment. In the meantime, we were able to lay the groundwork for our plans for treatment in Augusta (which required considerable paperwork and preparation, mostly on the part of Dr. Johnson) and also go to Camp Sunshine in Maine.

The visit to camp was wonderful, especially so because we saw many old friends and enjoyed the communion of that diverse and wonderful company. In particular, Colin got to hang out with Jacob, his ependymoma buddy, who is similar in most ways except the relapse (let’s hope it stays that way!). We also did another parent group skit for the talent show. It wasn’t as engaging as the last one (the Police Donut Olympics), but I got to play Nancy, the psychosocial director, and we made the delightful and unexpected discovery that Jacob’s dad is a real ham on stage.

We left for camp extremely early on February 13th. Even without consulting a weather calendar, the trajectory of last winter allows me to say with great certainty that it was a cold day. I am an early riser due to my schedule at the pool, so I took the first driving shift while everybody else slept in the car. Starting family drives in the wee hours is effectively like cutting the trip short, as everybody else is able to sleep under fuzzy lap blankets and pretend they are still in bed while I enjoy the quiet contemplation of the cusp of day and the feeling of stillness, which is always accentuated by winter’s frigidity.

Setting off in the dark, we made our way through the New York countryside. The sun did not start making its presence known until  the section of the drive heading east on route 41, which cuts the corner between Routes 81 and 88, starting at Whitney Point and spilling out at Bainbridge on the long, boring stretch to Albany. This is deep farmland, quaint towns and less quaint dingy ones, and lots of well worn barns.

I remember with great clarity coming up a rise and seeing the tinges of early dawn staining the sky over the trees, a farmhouse framed prettily on the hill between the road and woods. The mood is always quiet under the snow and cold air, but those first colors of the day facing us were so warm and full of hope. I imagined a rooster crowing but I’m sure I didn’t hear it, that it was evoked by the bucolic scene.

The combined effect, the gentle beauty of that sunrise, the cock-a-doodle-doo I summoned from this picturesque landscape, and our trek eastward into a new day, summed up my feelings about embarking on a new path towards treatment. This was the visceral embodiment of hope, of knowing that we had not reached the end of the line and that there was something out there beyond the world of established science that may offer salvation and a fundamental change to how we address cancer. After all, the hope wasn’t just for our lone child but for all children in the future who may never have to experience relapse if their diseases are treated more effectively up front.

Colin’s ultimate treatment trajectory doesn’t matter. What matters is this moment and this feeling, the ability to grab onto the brass ring and live in this place, even for a time. This was the gift we received in Augusta, the combination of fortune, good friends, and the hard work of many people unknown to us in an unexpected little corner of the world. We are forever grateful and this gift endures, come what may.

5 Comments »

  1. Thank you for the update. You and Ian have done a wonderful job making these difficult decisions and caring for your family. Love to everyone! You are in my prayers.

    Comment by Diana — August 23, 2015 @ 9:05 am

  2. You guys inspire beyond words. Thank you for sharing this. Colin is amazing, you are all amazing! Thank you!!!

    Comment by Dennis — August 23, 2015 @ 11:41 am

  3. Thank you Tamiko. Your always in – depth and thoughtful posts are extremely helpful. Love you all. Hoping and praying every step of the way.

    Comment by Kirsten Stone — August 23, 2015 @ 2:04 pm

  4. You’re such a good writer, Tamiko. I love you all.

    Comment by Tracy — August 23, 2015 @ 6:11 pm

  5. I have very few words worth using after I breathlessly read your update. Know that your courage as a family is enduring and greatly admired. I feel the gravity, the heaviness of the place you guys are at, but I see it through you Tamiko as you lovingly recount in detail your decisions…the universe is designed to bring you the solution…and the gift will Pray God endure…..much much love to Colin the original Superhero!

    Comment by Sinola — August 24, 2015 @ 5:08 am

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