There Is No "Nutshell" Version

I was asked to write an article about my cancer riot. It was to be shared with fellow patients on a cancer forum. Here is what I wrote:

In September 2013, I was a 47-year-old engineer-turned-programmer, wife, and homeschooling mom. My life was full and happy. I had no concern about cancer, so when I heard the doctor say, “I think you have cancer,” I could hardly believe that he was talking to me.

Just two short days later, I woke up from surgery with a sharp pain in my abdomen that brought the reality of my diagnosis screaming into focus. Eight inches of cancer-containing colon was cut out, along with a tumor-laden artery, part of my bladder, and twenty-one lymph nodes (pathology would later find seventeen of them to be cancerous). Though I hurt, I was thankful that 1) I woke up at all, and 2) the tumor was gone. I thought that the surgeon’s scalpel had brought my cancer history to an end that very day. Silly me.

FOLFOX chemotherapy was next as soon as I recovered from surgery, “Just to be sure,” they said, “that it’s all gone.”  Slowly, sickeningly, I slogged my way through six months of nauseating treatments, bone-crushingly painful supportive measures, and countless needle punctures. Though I grew sicker and wearier as the weeks progressed, after each treatment I told myself that I was one step closer to restored health. I would endure whatever it took to be able to continue raising my family with my husband.

One year after diagnosis my oncologist ordered routine scans to determine whether the treatments had been successful. Though a few small nodules in my lungs were noted, the PET scan was inconclusive. So, I underwent a needle biopsy. It was also inconclusive. Next, I had a lung wedge procedure which finally, sadly, proved unequivocally that colon cancer had metastasized to my lungs. My case was considered terminal.

FOLFIRI was offered as the next step, but I declined. I told my doctor that I wanted to look into clinical trials before doing any more chemotherapy. I had read about a patient who underwent immunotherapy at the NIH in 2014, and I was curious to know whether it would work for me.

Two days later, on my 49^th birthday, I was on the phone with a research nurse at the NIH asking about Dr. Rosenberg’s TIL trial. I filled out paperwork and requested medical records and scans to be sent to the NIH.

Exercising due diligence, I visited one of my state’s university oncology research clinics to find out what trials were offered there. Shockingly, not only did the clinic director inform me that he had no trials for which I qualified, he went further to actually discourage me from applying for a trial at the NIH! It seemed that bedside manner, if he ever had any, was not to be wasted on a terminal patient. At least, not this one.

Though my request to be screened for the TIL trial was twice denied, in February of 2015 they accepted me. On April 1, I underwent tumor harvest surgery at the NIH. The goal was for the surgeon to extract a large enough sample of tumor tissue to obtain a sufficient number of tumor-infiltrating lymphocytes (TIL) from it. I was sent home to recover while the scientists began to work on my cells. Weeks crawled by as I waited for word about whether or not a treatment could be developed from my cells.

In mid-June I got the long-awaited call. The immunotherapy fellow said they did indeed find enough cells, and they were excited to discover that some of the cells targeted a driver mutation. I had no idea what these words meant, but it sounded like extra-good news.

Back to the NIH I went. I underwent grueling “conditioning chemo” for seven days to quiet my immune system. Then, exactly three months after the lung harvest surgery, on July 1, 2015, 148 billion of my own mutation-targeting cells were infused into my body. Immediately after that, I was given the first of what would be five doses of IL-2. Two weeks later, my immune system recovered enough so that I could return home. My total stay was twenty-four days.

Each follow-up in the weeks to come showed more and more shrinkage to seven lung tumors. However, by nine months post-treatment it was clear that one of the seven tumors had changed. It was growing again.

Several options were discussed, but ultimately the decision was made to surgically remove the recalcitrant tumor. Due to its threatening location, the doctor opted to perform a lobectomy rather than attempt to remove just the tumor.

On April 7, 2016, I became the first person to undergo surgery post-TIL therapy. Remarkably, the scientists’ study of the tumors they examined post-surgery uncovered one of the mechanisms that is used by cancer cells to evade the immune system. Those results were published in the New England Journal of Medicine eight months later.

From the day of that surgery, I was declared NED—no evaluable disease. I maintain that status today. Trial NCT01174121 worked to eliminate six tumors from my lungs using my own cells, and the team at NIH saw me through to NED by performing surgery to eradicate the final one. I could not be more grateful!

Follow Up 17

I'm happy to report that my scans were clear!

This visit was a little different, due to COVID-19 restrictions. First off, my longsuffering husband was not allowed in the building with me.

The building seemed quite empty with no visitors. COVID screening and mask-donning happened just inside the entrance. I imagine these precautions will continue for quite some time.

You might think that after six years of visits to Building 10 that I'd know the place like the back of my hand. Well. That is not at all the case. I am a person who could get lost on her own doorstep. Thankfully, I did make it everywhere I had to be. Most people will be able to use NIH's "Take Me There" app (found here) to navigate inside Building 10. However, I am not most people. My ancient Tracfone cannot accommodate such new-fangled wizardry.

Another change from standard protocol is that I was not required to drink oral contrast prior to my CT scan. Oh frabjous day! It was music to my ears. Instead of drinking a liter of iohexol, I was treated to four cups of refreshingly cool, clear water. I was instructed to drink it with a straw, leaving my mask in place as much as possible.

I will return in one year's time, God-willing.

The Five Year NED mark was reached on Wednesday.
Five years of good health. Five Christmases. Five Birthdays. Twenty-Five kid-years--so much happens in a year. I am so thankful to still be here, and a part of it all.

To God be the glory!

Follow-Up #16

I am still NED, and still very, very grateful to be cancer-free and healthy.

We brought our three sons with us on the drive this time, and had a fun time touring the Smithsonian and other D.C. spots. As it was very early in March, the pandemic had not yet compelled us to stay in our homes.

My visits are officially going to be only annually from now on. I am glad for that.

I ran across some interesting reading in the book "Darwin's Black Box" this week. It sheds new light on what could be the reason that a fourth cell showed up in my post-treatment bloodwork shortly after I had TIL therapy.

Some background:  When I returned to NIH for the lobectomy in April 2016--almost a year subsequent to treatment with TIL, the Lab Guru visited me in my room to talk about what he was learning about my case. The scientists had known about three types of T-Cells that were included in the treatment bag on July 1, 2015. Around 70% of those TIL were known to be of a particular variety. What they found in subsequent blood-draws (post-TIL therapy) was a different population of cells, also reactive to the KRAS G12D mutation. "What does it mean?" I asked at the time. "We are not sure..." he had said.

Here's what biochemist Michael Behe wrote in his 1996 book that popped out at me yesterday while I was reading: "When a cell binds to foreign material, it receives a signal to replicate; during many rounds of replication the cell 'intentionally' allows a very high level of mutation in just the variable regions... This produces variations on a winning theme. Because the parent cell coded for an antibody that already was known to bind pretty well, mutating the sequence might produce a stronger binder. In fact, studies have shown that antibodies produced by cells late in an infection bind much more tightly to foreign molecules than antibodies produced early in an infection."

Could mutation be the reason the Lab Guru found that my circulating T-cells--post-treatment--had a much higher percentage of a new, and unexpected fourth cell? He said that the initial population had diminished to "almost nothing" but that my circulating blood still retained a "crazy high" amount of these new cells.

I remember him saying of this cell at the time, "It's very particular about what it binds to. It will only bind to chains that are ten mers long--no others fit."

The Lab Guru has moved on, so I've got no one to ask my questions anymore. EDIT: My medical student daughter tells me that this property of immune cells is well-known--just not to me, until now.
: )

I have this verse on endless loop:
I praise you because I am fearfully and wonderfully made;
your works are wonderful,
I know that full well.Psalm 139:14

Follow-Up #15

Follow-up #15 happened at the end of February.
Still NED!

Earlier this month was the anniversary of the first-ever time I was clinically recognized to have "No Evaluable Disease". Three years ago, a thoracic surgeon at NIH removed the only remaining living cancer from my body. I remember waking up in the ICU disoriented, weak, and heavily-drugged, but more-importantly, cancer-free.

Cancer-free! I remain so today. To God be the glory, now and forever. Lord, never let me forget what good was done to me. I reiterate my deepest thanks to every person who worked on my case at the National Institutes of Health--what an outstanding facility--and to those who still follow up with me. I pray that many more lives will be saved by the work of those dedicated to solving cancer's mysteries.

To celebrate the anniversary, my former immunotherapy fellow--though separated by miles--and I each raised a glass "to NED." I toasted every NIH doctor and nurse that I could remember, starting with him. My glass emptied before I could name them all (even with small sips, haha).

New this week: Dr. Yang requested some blood. They now know how to build (for other patients) the particular HLA that successfully attacked the cancer that was threatening my life. Now they want to study the other five HLAs in my blood to see if any of them also recognize cancer mutations, particularly G12D. If so, they'll sequence those genes in order to add another "recipe" to their cancer-killing agents catalog. "We want to build a library of sorts," he said. To that end, a local phlebotomist drew some blood and then FedEx transported it to the NIH in Bethesda, Maryland. Go, Science!

I didn't want to post a picture of blood (gahh!), so here you go instead.

Three Year Celebratory cocktail

FIVE YEARS and follow-up 14

At the end of August Patrick and I drove to Bethesda for follow-up #14. All of my scans came back NED. WooHOO!!!

This time, to my great delight, I was joined in the CT waiting area by my dear former fellow, who happened to be at NIH for a visit that day. To be polite I offered him some of my oral contrast, but he wisely declined.

Pro Tip: Crystal Light On the Go packets make iohexol (oral contrast) much, MUCH more palatable. I highly recommend the wild strawberry flavor.

Also this visit:  I finally got to meet the person whose news story led me to the NIH. She was the first patient with solid tumors who responded to TIL therapy back in 2014. We had been in contact many times before, but had never met in person--until this visit!

We even took a photo with The Guy, himself.
Here we see Responder 2 (me), The Guy, and Responder 1 together for the first time.

OP3 at NIH--August 21, 2018

But wait, there's more! Here's a link to an article that mentions my case:
 

Moderna thinks the immune system can be recruited to help fight KRas where small-molecule drugs have failed. In 2016, researchers at the National Cancer Institute reported on discovering a person whose immune system developed a T-cell response to cancers with KRas... “That was really the watershed moment for the field,” says Tal Zaks, Moderna’s chief medical officer.

 

Follow-Up #13

My scans were all clear--no trace of cancer anywhere. Yes! Thank God.

Just for fun, I asked the attending when it would be OK to use the word, "cure." He laughed and asked if I had any other questions. ha ha

This visit, I was asked for my consent for NIH to do further research on my cells. They'll use cells that they already have for this, plus blood from the routine draws they do at each visit. I was relieved to know that apheresis was not required!

The attending physician explained that the scientists will be attempting to turn back the genetic clock on my cells, to see whether they can revert them to their earlier stem-cell "selves." I can't even imagine how this could happen, but according to my doctor, another researcher (outside of NIH) has already had some success with this. Exciting stuff!

Of course I gave my consent. I signed the papers, and my husband signed also, as a witness. It was an honor to do so. To God be the glory, now and forever!

Cruel November

My dear friend Tom Marsilje died this week. I spent the wee hours of the morning today re-reading some of the many texts, emails, and facebook messages we shared since 2015 when we "met" online.

In January of 2015, Tom went public with his Terminally Optimistic blog. He, my husband, and I met at an online support group called The Colon Club. That same month, I started a thread on The Colon Club pertaining to the clinical trial that I was hoping to (and eventually did) get into. Tom was one of the first to reply to the thread. He was excited about the trial, and stated that he had been considering it a possibility for himself, if needed.

Our community on The Colon Club celebrated when Tom was filmed for part of Ken Burns' documentary, Emperor of All Maladies, because of his work on the cancer drug, LDK-378 (ceritinib). Fellow Colon Clubbers flung good-natured jabs at him after the show aired. He always responded with humor and grace. He took fighting cancer completely seriously, but he could always laugh at himself. It was one of his most endearing qualities.

We found common ground beyond our stage IV cancer diagnoses. We both found sleep elusive, which made the time zone difference between us irrelevant; he had two young daughters (I had two young sons...plus three more); we both married engineers; and Tom had lived in Michigan until he left for grad school. We kept close tabs on each other. We joked about arranging a marriage (or two!) between his kids and mine. We previewed each other's blogs, and we prayed for each other often. More times than I can count, he was the first one I'd message whenever I had urgent (good or bad) news to share. He was always there.

After reading his first blog posts, I encouraged him to share his blog with another online community where I hung out, colontown. Initially, he told me he was "spread too thin to join another group". He asked if I would post his blog link there so that he wouldn't have to divide his attention with yet another outlet. I encouraged him (again) to join so that he could post it himself. He finally relented with one caveat: 
"I'll join as long as it's OK if I don't post too frequently."

Funny, Tom.

Tom not only joined the group, he transformed it. That spin-off page started with just three members, myself included, who had participated in a clinical trial. We patients were there to spread awareness and answer questions from other colontown members about the clinical trials we had joined. When Tom came onboard, he turbo-charged that space with unending links to more and more clinical trials almost daily. With the help of a mutual friend and advocate, Maia, plus a couple of research scientists--another dear friend and fellow patient, Danielle Maatouk, among them--who he recruited to help, even more patients would be reached. This Facebook page has become a resource unlike any other in the world. Other trial pages spun off from this first one; each bears Tom's name in tribute to him for his zeal for educating patients about clinical trials.

I had the honor of meeting Tom in person for the first time in July, 2016. He was enjoying what he called a cannonball life that summer, but also investigating potential treatment options in Michigan. My house was a short car trip from his destination, so my husband threw some steaks on the grill in anticipation of his visit. We discussed science, and cancer, and life. We laughed like we had known each other all our lives.

Too often Tom and I grieved when one after another of our mutual friends would die. Several died last November, including Danielle. We both agreed that November was the cruelest month. And now it has taken Tom, too.

Rest in Peace, dear Tom. I hope that the friends we knew were there to greet you. I hope that in the other world, you have found the knowledge you sought so fervently your entire adult life. I wish that you could whisper what you've learned to those you left behind.

I will think of you often, tears streaming at times, but always with your words, "To Life" at the forefront of my mind. You gave so much, and worked so hard. Be at rest now, and live forever with God, the Author of life.

Friends forever.