New Treatment

When I last checked in, I'd just gone back home from New York. I put treatment on hold while my doctors, my family, and I investigated treatment options. There is no standard second-line therapy for Ewing's sarcoma. Rather, different doctors and hospitals have their own protocols. Sloan-Kettering used to use irinotecan and temozolomide as a second-line treatment. Now that they use these drugs as part of first-line therapy, they've switched to cyclophosphamide and topotecan. Some places, though Sloan is not one of them, if second line chemotherapy produces a response, proceed to high-dose chemotherapy. High dose chemo involves giving a dose large enough to wipe out a patient's bone marrow. To counteract this, stem cells are first harvested from the patient, that are then given back after the chemo has had its effect. High dose chemo is often a first line treatment for metastatic Ewing's in Europe.

This goes to show that there's no consensus on what to do in metastatic and recurrent Ewing's, which is difficult to treat. In my case, with the multiple lung spots and my having already had irinotecan, Dr. Meyers was concerned that combining the related drug topotecan with cyclophosphamide, another drug I've already had, wouldn't produce a satisfactory response. So we started exploring clinical trials, where a particular treatment that has not been used before is tested for safety and effectiveness. During this time, I couldn't get any treatment. Clinical trials have strict eligibility criteria that treatments can easily violate. Blood tests have to fall within certain parameters. There needs to be a gap of at least the cycle length between a chemo administration and starting treatment. Major surgery also requires a recovery period before treatment can begin.

Immunotherapy, in which the immune system is stimulated to attack tumors, was the theme. The immune system normally plays a big role in attacking cancer cells and keeping them from turning into active disease, but as these cells mutate rapidly, they can find ways to evade the immune system and establish themselves. One popular immunotherapy approach involves using vaccines to train the immune system to recognize tumors as foreign. Another involves counteracting defenses cancer cells evolve to escape destruction by the immune system. The trial we ended up focusing on uses the second method. The specific approach is called checkpoint inhibition. Cancer cells can put the brakes on the immune system by displaying what are called immune checkpoints that tell the immune system not to attack. Immune checkpoints are used by the body to prevent autoimmunity, where the immune system attacks the body itself, but cancer cells can make use of these to evade destruction.

Checkpoint inhibition is already used to treat advanced melanoma, with the FDA having approved multiple drugs that block immune checkpoints. Melanoma is not very responsive to chemotherapy or radiation, so checkpoint inhibition represented a major advance in treatment, and some patients have seen dramatic responses. Clinical trials are now underway to evaluate the effectiveness of checkpoint inhibition in many other cancers. The one I'm in uses a drug called pembrolizumab (trade name: Keytruda). It is open at multiple locations across the country. The closest to me is at the University of Southern California in Los Angeles, a 5-6 hour drive. The treatment is once every three weeks, 30 minutes by IV. There are side effects, but much less than chemo. Common ones are fatigue, diarrhea, and cough. Obviously, I'd prefer to be closer to home, but trips to LA once every three weeks is minimally disruptive compared to how things could have been if I were to get chemo or this same treatment farther away where the only option would have been air travel. I also have family there, so I won't be alone when I come in.

The preliminaries began with an initial consultation on May 5th. Then there was a CT scan of my chest, abdomen, and pelvis to establish a baseline. Thankfully, the tumors have not spread to any other organs, but I've gotten new ones since my last scan, and the existing ones have gotten quite a bit bigger, so I couldn't have waited much longer. This week, there was a needle biopsy on Wednesday to obtain a tumor sample. Another sample will be taken at week 8 to evaluate response to treatment. Then, there was more blood work. Finally, on Friday, I received my first treatment. I will be getting two more for sure. At week 8, there will be another CT scan to evaluate response. Tumor growth greater than 20% or new tumors will be counted as disease progression, at which point I'll be off the trial and will have to find another treatment option. Subsequent scans are taken every 12 weeks.

The first IV bag being hung.

I really hope this treatment works. So far, the only side effect I've felt was some fatigue yesterday. I expect to be able to live a normal life, unlike when I was getting chemo. This makes me very happy, but even so, I am quite nervous. The thing about chemo, as brutal as it is, was that I knew it was doing something to me. How couldn't I with all those nasty side effects? To be fair, that is no guarantee that the chemo is doing anything to the cancer cells, but there is something to be said for perception. With Keytruda, without those side effects, how can I tell that it's doing something? I guess the proof will be in the pudding. If I become symptomatic or start feeling extreme pain somewhere, then I know it's not working, but if I stay asymptomatic, I have reason to be encouraged. A real-life example of the saying, "No news is good news." So, outside of side effects, here's hoping I stay free of symptoms!

Well it's back...

It was all such a whirlwind. The morning after the scans, I go in for the results, and the first question I get from Dr. Meyers was, "Did you have an infection recently?" He then pointed to an enlarged lymph node in my left lung that lit up on the PET scan. There were also a few other tiny lung spots that showed up there and on my chest CT. An infection was his and my hope, given the alternative. The only thing that came to mind was a cold I'd had in late December/early January. At that time, I was given two options: wait and re-scan in 6 weeks to see if anything changed, or do a biopsy and find out now. Not in the mood to wait, I went for option 2.

The procedure was straightforward -- the general surgeon with the pediatric oncology group at Sloan, Dr. La Quaglia, took a piece of the lymph node and a small piece of my left lung as well. He was able to use a scope, which enabled a quick recovery. The alternative, if using a scope didn't work, was working through an incision, in which case I might still be in the hospital recovering instead of writing this post!

The pathology report isn't back yet, but I got the preliminary news right after I woke up. Dr. La Quaglia told me that there were small round blue cells in the biopsy sample. Given that Ewing's sarcoma is one of the small round blue cell tumors, that meant we were almost certainly looking at a recurrence. I say almost certainly, because there is some super small (something like 0.000001%) chance that this is actually another kind of small round blue cell tumor such as a lymphoma. Small enough not to be worth mentioning except that I had such small odds of having cancer back in 2012 when I was first diagnosed that I wouldn't be surprised by the unexpected.

Dr. Meyers met me as I was being wheeled into my hospital room to get moving on exploring treatment options. Chemo is one possibility, but given how much of it I received in 2013, there's the worry of resistance, so he's also looking at trials that involve vaccines or drugs that stimulate an immune response against tumors. We last spoke yesterday; he told me he was still investigating, and that I should for the moment go home, as I was sufficiently healed and capable of resuming my normal life. I'll hear from him when the pathology report is in and when he's finished looking at options. I don't know where treatment will be or how disruptive it will be to my daily routine, but here's hoping for something that is not too disruptive and also in Northern California.

I was able to find a reasonably priced flight that left New York late in the afternoon, so I headed back home and resumed work this morning. It's an eerie feeling, though, knowing what's inside me. I have no symptoms now, but if I do nothing, they'll eventually develop and intensify and, well, I don't want to go there. I'm doing my best to think happy thoughts. Hopefully whatever second-line treatment I pursue ends up working.

Another Round of Scans

I'm back in New York for more scans and tests. I had a PET scan and chest CT done today. On tap tomorrow are follow-ups with a dermatologist (another mole exam!) and the rehab doctor who oversaw my physical therapy, and more tests. There's an EKG and echocardiogram to test heart function, and a pulmonary function test to check lung function. These were ordered by the long term team, who I will be seeing Wednesday morning. Then there's a follow up with the radiation oncologist, and that evening, I fly back west.

I feel like there's a lot at stake here. If all goes well, my follow up frequency will decrease, as I'd mentioned before, but these feelings are coming elsewhere. This being the "official" one year mark has something to do with it, certainly. Emphasizing a particular date tends to increase its significance for me. There's more, though. On my last chest X-Ray, the radiologist thought, though he wasn't sure, that the lower lobe of my right lung wasn't fully inflating. I think it was nothing more than me letting some air out prematurely during the X-Ray - I'm always asked to take a deep breath and hold it while it's being taken - but I can recall letting a little bit of air out early last time. Still, he didn't rule out "early infiltrates" - i.e. something in there keeping the lung from fully inflating - so that had me wondering in the back of my mind if something could be brewing. My doctors at Sloan didn't think it was anything to worry about, though, and hopefully that's confirmed tomorrow. I'm coming in first thing in the morning to hear the results before my big battery of follow-ups and tests.

The Immune System after Chemo

Back in my post about finishing chemo, I mentioned the possibility of needing to have childhood immunizations redone. As I have mentioned on numerous occasions, chemo gives the immune system a beating. The worst of the cycles wiped it out to trace levels during the second week, which led to hospital trips upon getting sick. I only escaped this fate in the first two cycles, where I bounced back by Thursday of week 2, but the subsequent "bag" cycles (3, 6, 9, 12, 15) all ended up including hospital stays, and I didn't bounce back until the beginning of week 3.

But there are long term effects as well. One thing is that chemo carries with it an elevated risk of developing acute myeloid leukemia. Acute leukemia involves the bone marrow rapidly producing cancerous white blood cells. While this can happen to anyone, chemo ups the risk. The period of elevated risk lasts for about 10 years. Regular complete blood counts are done to catch this early if it does happen.

A lot more common is that acquired immunity to some diseases is lost. This is not just a concern during treatment itself. The cells killed by chemo include ones that produce antibodies that help fight diseases. So if enough of these cells die, the immunity given by these antibodies is lost even after treatment. But as the immune system needs time to recover for a vaccine to stimulate a proper immune response, so reimmunization cannot happen right away. In my case, the process took almost a year.

At the 6 month scan (September 2014), I was given a few blood tests to check my immune function and see what immunities I still had. The results of these tests determined whether I could stop taking the bactrim antibiotic for pneumonia prevention that I'd started back when I started chemo, what vaccines I would need again, and when I could get them. The September results had me almost at the point where I could stop taking bactrim, but not yet. More importantly, the majority of my immunizations were still in effect. The only ones missing were measles and rubella. However, I was instructed to wait before getting reimmunized. The MMR (measles, mumps, rubella) vaccine uses live but weakened viruses. A weak enough immune system, however, would not mount a sufficient response, which would lead to actual illness. I had repeat tests in December, and this time, the results were good enough for me to stop taking bactrim and get my MMR shot, which I did in January after the holidays. And just in the nick of time, as it was shortly thereafter that the California measles outbreak was all over the headlines.

I was generally able to keep any worry about catching an illness like measles in the back of my mind, but that didn't mean it wasn't there, especially when I had to travel to highly populated areas. And with a weakened immune system, the results would not have been pretty. Before my cancer experience, I didn't think all that much about the rise in parents who do not vaccinate their children beyond expressions of puzzlement every now and then, but now, the thought of future cancer patients being at heightened risks of hitting roadblocks or even losing their fights due to preventable illnesses I find very worrisome. Same goes for taking chances with having your children catch these diseases. What enabled the spread of the recent measles outbreak was a critical mass of unvaccinated individuals. Modern day residents of developed countries are privileged to be able to grow up without worrying about illnesses that used to claim many, many people in their youth. Most young parents today haven't had these illnesses, and quite possibly their parents haven't either. So with these diseases seen more and more as parts of history rather than ailments with tangible effects that caused loved ones to suffer, it becomes easier to question preventative measures such as vaccines. I'm going to say it here, as someone who's gone through a nasty illness young: if there were a vaccine for what I had, I sure would have liked to have had it.

Treatment is not the end of things

It's been almost a year since I updated this blog. I certainly did not intend it to be this way. There have been medical developments since I finished treatment, thankfully nothing that indicates a return of my cancer. But as I was so used to writing about treatment, once it stopped, my usual routine stopped with it and I found it much harder to think of topics to discuss.

A lot has happened since then. I have had scans four times (March, June, September, and December 2014). All of them have turned out clear so far; here's hoping for the rest to be the same as well. My next round of scans is at the end of March of this year. These will mark the "official" one year mark, after which my scans will decrease in frequency and I'll start being followed by Sloan-Kettering's long term team. They are internists who specialize in the effects of treatment on all the noncancerous parts of cancer patients' bodies. There are a number of long term effects that chemo and radiation can have, that varies by the drugs, treatment site, and dosage. I won't get into them here, but needless to say, I will be talking about them in future posts.

I successfully finished what remained of my Ph.D. work, defended my dissertation in early June, and deposited it a month later. Then Ashley and I at long last got married! We had a small ceremony in Champaign with a reception afterwards at a restaurant in neighboring Urbana. I was pleasantly surprised that I was able to stay out on the dance floor on just one natural leg, though I was sore for an entire week afterwards!

I also fulfilled a dream, moving back to California at the end of July to work my first "no more school" job. I'm in the Bay again, which I had featured in this much earlier post as a place I was hoping I could see again. This time I'm hoping for a longer tenure here than the four years (2003-07) that made up my prior one. The very first time I'd come back here after I left (Summer 2010) was quite the experience. I could feel memories all around me as I walked around where I used to live and then found myself missing my former times there and hoping things could have worked out differently and enabled me to stay there versus having had to come back to Illinois to finish my education. This feeling went away in subsequent summer visits (2011, 2012) as I built new memories through my internships, where I was making progress towards my Ph.D. And then in October 2012, my symptoms hit.

Nowadays, I'm reminded of my pre-cancer life on an almost everyday basis. That I simply have to put on a prosthetic leg each morning is one of them, versus the past where I could just roll in and out of bed at my own leisure without having to take any extra steps. I can't lift heavy weights anymore because of the heart toxicity associated with doxorubicin, when in the past weightlifting was one of my favorite forms of exercise. I can't help but worry that my current healthy state is going to be short-lived when in the past I had no health worries at all. This all has an effect on me. I'd like to think this will all end up working out in the end. Leaving California the first time turned out to do just that, as I wouldn't have met Ashley had I not done so. But while the feelings associated with my first return began to fade at the end of that summer, it's been just over a year since I finished treatment and the pre-cancer vs. post-cancer comparisons are still going on strong. I'm certainly hoping that the same process will happen there as it did with all the 2003-07 memories showing up in 2010, but clearly this is going to be a much longer journey.

So just as I shared the journey of treatment with you, I'm going to share this journey as well. It's easy to think that you get treated and go back to life and everything is back to normal, but as I've seen over the past year, it is unfortunately not so simple.