Follow-Up #20

Hello again!

I'm back with another report of NED--no evaluable disease. Huzzah!

On clinic rotation this time I met with Dr. Yang, who was the first-ever attending physician that I met at NIH. It was Dr. Yang who screened me for the TIL trial back in 2015. I often recollect his parting words of that day, "Mrs. Ryan, the stars really seem to be aligned for you." He was referring to the slow-growth of the tumors thus far, the fact that I had declined more chemotherapy after the first line failed, and that I had found the TIL trial at all.

At that time, I did not consider that my path to NIH was "aligned" in any way (they rejected me twice after all), but Dr. Yang's use of the word "stars" that day did make me remember the miracle of Our Lady of Guadalupe (the stars on her cloak match the constellations as they were when she appeared to Juan Diego). It was a comfort to me.

This clinic visit was a happy one! Though Dr. Yang wore a surgical mask* his smile was evident nonetheless. He decided that my next scans should happen in two years' time rather than annually. "After that," he said, "we'll discuss whether any more scans are necessary."

Imagine that!

Today marks the 8th anniversary of being declared NED. This is the day, eight years ago, that I woke up with one fewer lung lobes and zero cancerous tumors. I shall toast with a celebratory G&T this evening!

*NIH still requires masks in all "patient areas." Mask stations were in place at all reception areas, and we were expected to change to a fresh mask each time we entered a different patient area.

Follow-Up #19

Greetings, readers. I am late to update.

In October last year, I suffered a compression fracture to my spine. When I could bear the thought of riding in a car, I saw my G.P., who Rx prednisone, which was a problem. After undergoing TIL treatment, we patients are to avoid steroids in perpetuity (and I have the Medic-Alert bracelet to prove it...I'm not actually wearing it anymore, however. Shhh...).

Me: I can't take steroids.

G.P.: You can't? Why not?

Me: Because of the clinical trial. They told me "no steroids, forever because they are bad for lymphocytes."

G.P.: I am more concerned with your spine right now than with your immune system. Here's the Rx. Have a nice day.

What to do? Usually, I trust this G.P., but I wasn't keen to contradict the instruction given by The Guy at NIH. I sent my immunotherapy fellow an email. His response:

Steroids are an immunosuppressant and could therefore interfere with the key mediator behind your amazing response. For that reason we kindly ask that you continue to avoid steroids...

And so I didn't take the steroids. Instead, I lived with an ice pack pressed to my spine almost constantly for weeks. I swallowed lots of Advil and Tylenol and it was no fun! No fun at all. To date, this pain was worse than even the accidental spleen biopsy of 2014. Thank God for the numbing effect of ice, or I may have lost my mind. 

In the spring I was feeling much, much better and took the annual trip to NIH for follow-up nineteen. I met the new attending doc, and had a little chat about the news regarding my former Lab Guru and the success he had when using my T-Cell receptors to treat a patient with pancreatic cancer. 

Me: It seems they're being very careful not to tie this case to mine, or even to the NIH. Why do you suppose that is the case?

Doc: Well, there are a lot of rules about what they can and can't say. I mean, it's not like you're Melinda Bacchini. Her case was written up in the New York Times! Anyone can talk about her! 

Me: << confused silence because, hello: NYT Article >>

That conversation ended right there. The doctor went on to say, "Maybe it's time we stopped your follow-ups. You're doing so well. I will look into that."

A week or so later, after not hearing from the attending doc on this point, I reached out again to my fellow. As I suspected, NIH is not stopping my follow-ups yet. I will return in the spring for another one. I have to say, I'm feeling invisible to this new attending doc!

The good news is: I am still NED! and still very, very thankful to be. This month marks ten years since my initial diagnosis. All glory to God, and thanks to the NIH and the amazing people who worked on my cells, and who took care of me so well.

Follow-Up #18 and NEWS from Portland, OR

I had a very early CT scan appointment on a Monday in late April at NIH. Similar to the way it was one year ago when I visited, all who enter Bldg. 10 were to wear masks at all times, but unlike last time, my husband was able to accompany me. A COVID screening station just inside the door was our first stop. We were given fresh masks--replacing those we were wearing--and asked the now-familiar litany of health questions before we were allowed to make our way to Phlebotomy.

Once again instead of the yucky iohexal oral contrast, I was asked to drink "three paper cupsful of water, using a straw placed under (my) mask." Can do.

Later that day, we met my new (#8, if you're counting) immunotherapy fellow, K.H., in the clinic. The attending physician joined us shortly afterwards. They found nothing especially worrying on the scans or bloodwork, but do want me to have an MRI of my liver within the next 3 to 4 months. The attending doc downplayed the findings as, "Stuff we've seen before, that will probably go away like it has before." The radiology report notes: Stable subcentimeter low density lesions in the liver that are too small to be accurately characterized. I've seen notes like this on past reports, so I am choosing to not freak out. I still am officially NED and optimistic that I will remain that way.

UPDATE: I was scanned at my local hospital several months after this follow-up as instructed. My liver showed no abnormalities. WooHOO!

Exciting News! My beloved lab guru, who now works at Providence Cancer Institute in Oregon, has taken the "recipe" for my receptors with him and has tested them in a patient who is now no longer dying of pancreatic cancer! This is the kind of result that NIH has been hoping for! This patient has a matching HLA to mine, and evidently her tumors included the KRAS G12D mutation. Dr. Tran was able to engineer T-Cells to express the receptors that are native to my cells and infuse them into the patient.

Here's one article, but there are lots more if you're inclined to search.

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