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 #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!

NIH on NBC

Joan Lunden visted the National Institutes of Health early in January. She interviewed me and The Guy (together, because I am a big chicken) on my 10th follow-up post TIL therapy.

Here's the Today Show segment:

There I am, undergoing apheresis to supply dendritic cells (antigen presenting cells) and "feeders" for the TIL. Gahhhhhhhh!!! Five hours of lying completely still is not exactly fun.

New York Times article (this is how Today learned of the story): 1 Patient, 7 Tumors and 100 Billion Cells Equal 1 Striking Recovery

The WSJ and Philly Inquirer also ran stories.
Cancer Breakthrough Aids One Patient, Raises Hopes for Many
In a first, immune therapy tames mutation in colon and pancreatic cancers

and a follow-up by the Philly Inquirer:
Cracking the cancer code: Can immune therapy treat tumors?

To find out more about the treatment I had, this web page answers some questions about TIL therapy. It includes a link (see item 5) to start the application process too!



A post on Joan Lunden's Face Book page:

Grateful

Welcome to the 100th post.
Today is the Feast Day of Our Lady of Guadalupe! I have a special devotion to Mary under that title. The words she spoke to Juan Diego in 1531 gave me courage in 2014, when I learned that chemo had failed me. "Do not fear this sickness...," she said to Juan, referring to his uncle. I believe those words are meant for all of us.

I am humbled and honestly a bit overwhelmed by the attention that is coming my way because of the recent article in the NEJM. Other outlets have picked up the story, and it has been a little crazy for the past couple of days.

I am thrilled for the scientists and other medical staff whose work has been recognized in this public way. My greatest hope is that they will continue to see more and more successes in immunotherapy. The men and women who worked on my case are much more deserving of the kindness and attention that I am now receiving--I was just trying to stay alive, as any one of us would do. The authors of the NEJM article--and many others who were not named--have my ongoing and deep respect. In truth they had it long before the results of my case were known to anyone--even them.

I am so grateful to everyone who prayed for me, and especially those who shared the story with others and asked them to pray, too. In the Christmas letter that I wrote in 2014, just after learning that my case was considered terminal, I wrote:

I joyfully anticipate the day when we'll all "be amazed and glorifying God", saying together, just as the evangelist recounted, “We have never seen anything like this.”  Mark 2:12

Our Lady of Guadalupe, pray for us.

Remembering

Tonight, which is Father's Day in the U.S., we attended the graduation party of the son of dear friends. Last year, also on Father's Day, we attended a graduation party hosted by other dear friends. The difference is that after last year's party, Patrick and I headed straight to the airport. I would be inpatient at NIH starting that night for what would be a nearly month-long stay.

"No tears! No tears!" my friend had said as we left the party. She waved her hands in front of her eyes to keep them away. I did the same. We hugged and I almost made it out of there without crying. Then another friend joined us and I crumpled into a teary mess. We hugged as we cried. They promised me their prayers as I left the building.

My friend's husband called to me just as I reached the parking lot. "Come back! I didn't get to say good-bye!" I did, and cried some more. He promised to send me excruciatingly bad puns every day that I was away (and he did!). I told him that I loved his wife, and he said, "I do too!" and we laughed.

I got into the car then, and stared out the window, still crying. I have never felt so torn as I did that day, leaving my family and friends. Not only was I leaving the kids; I was also taking their Dad away. I felt tremendous guilt over that until I tried seeing the situation from his perspective. In his mind, being with me for as long as he could manage it was his duty, especially since the kids would have adult care-givers. "I have to take care of you," are the words he repeated so often, and always in a way that communicated, "I want to take care of you." He is a gift.

I thought about the risk involved in the clinical trial. I knew beyond a shadow of a doubt that this was my best option, but it made me sad to think that "coming back" might not be a part of this equation. I accepted the uncertainty, but I had to push thoughts of who I was leaving behind out of my mind and try to focus on what lie ahead.

A few days prior, Patrick and I had met with a lawyer to finally get a will in place. This was something we had planned on doing right after our wedding, but never did. As the years went by, one or the other of us would mention something like, "We should really make a will..." but that's as far as it went--just a suggestion. This time was different. This time the gravity of my health urgently demanded that we take action. Surprisingly, none of those preparations made me feel sad; instead I had a sense of well-being.

Driving away from that party though--that was hard.

By the time we arrived at the NIH that evening, it was pretty late. I met the night nurse, who smiled a lot and made sure every single thing was in order. She asked a bunch of questions, explained some of the mortifying practices I'd have to endure, and assured me that I would be well-cared for. Patrick left for the night. I tried to settle in. I had a big room facing the courtyard. I would have no roommate, unlike my previous visit. This was by design. Sharing a room could lead to sharing germs, and that is too big a risk for a neutropenic patient (which is what I'd be once the chemo did its thing).

It was Sunday, and the on-call immunotherapy fellow that night was the one who'd been assigned to my case from the beginning. I found this doctor to be a man of few words, but I was very happy to see a familiar face. I wished him a "Happy Father's Day", and asked how long he would remain on the service. I knew that the fellows were about to rotate out. He assured me that he'd be there on Cell Day. "What's the new guy like?" I wanted to know. He told me his name and instantly brightened. "You'll like him. He's a good guy." I knew that this was the extent of the information I'd be getting from him on that topic. I was uneasy with the knowledge that the one doctor that I was familiar with would be leaving so soon after I arrived. We discussed upcoming events briefly then said good-night.

Then--just as tonight--it was well past midnight by the time I got to bed. I was excited about finally being there, and almost couldn't believe that it was really happening. Monday morning would start early with scans and other procedures. I was on a carefully planned protocol now. I prayed that every step of the way would go as well as it possibly could.

The Girl Who Lived (apologies to J.K. Rowling)

I am now three weeks out from surgery to remove a progressing tumor and its necrotic neighbor. TIL therapy killed six other tumors, but one remained that did not fully respond to the cell therapy. Instead, it was surgically removed via lung lobectomy.

This inpatient stay lasted one week. On the day I was discharged from the hospital, I asked my doctor to "say the words." He understood exactly what I meant. He obliged by saying the happiest phrase there is for me right now:  "No Evaluable Disease." Hearing those words--from him, especially--filled me with a joy I can't begin to describe.

No
Evaluable
Disease

It is almost incredible to me. Not very many months earlier other doctors--several of them--described my diagnosis as terminal. Yet, a couple of days ago, a written discharge summary arrived via USPS from the NIH which told a better story. As I slowly read the report, my mind absorbed every word, recalling each scene as I had experienced it. My cancer riot was all there--years of uncertainty, painful treatments, and now success--distilled into a few short paragraphs on a couple of sheets of ordinary paper. It was written by the doctor who, to my great benefit,  had seen me through the rigors of the clinical trial, on-going follow-ups, and this most-recent lobectomy. It is this doctor's voice that I hear when I read the report.

COURSE IN HOSPITAL
Ms. Ryan is a 50 year-old female with a history of colon cancer who after undergoing standard therapy, self-referred to the Surgery Branch of the National Cancer Institute
.
.
.
She received 148 billion cells
.
.
.
(she underwent) a left lower lobe resection.
.
.
.
CLINICAL DIAGNOSIS:
Colon cancer metastatic to the lungs, now without evaluable disease.

I read it over and over. I marvel at all that has happened to me:  surgeries, chemotherapy, radiation, and countless needles, transfusions and bone-crushingly painful neupogen injections...the nausea, the fatigue, the waiting--waiting for acceptance onto the trial (2 no's before a yes), waiting to know whether my cells would grow, waiting to know whether they would work... All of it leading up to this one amazing report; this one phenomenal result: Restored Health. No evaluable disease. I cry tears of joy and relief, but then a wave of sorrow hits me as I think of friends who passed away in this same space of time.

I thank God for this life. Always. Always. I thank God for the men and women at the NIH, and for all of the people who prayed for me.

What's Next:
I am scheduled to undergo apheresis again early in May, to facilitate another TIL treatment (one that I may never need).  I had hoped for begged for the shorter apheresis procedure, but no. It will be the longer one, where they circulate my blood volume five times. They say they need more dendritic cells. They also need more "feeders." Bleargh!

"Feeders?!" The word conjurs unpleasant thoughts. I am too squeamish. Instead, I will dwell on the phrase, "No evaluable disease."

I am dreading the 5-1/2 hour apheresis procedure but I will try not to complain.

LIFE IS GOOD!

Will They Let Me Go?

Some drama during what did turn out to be, thankfully, my last night inpatient at NIH had me wondering. The "night thoracic fellow" came in to assess my recovery sometime after 8:00PM. The thinking had been that one more x-ray, the following morning, would be my ticket out of there. Sadly, I seemed to be too puffed up, literally, for it to go that easily.

The thoracic fellow pushed various places around my left chest and side. I could feel the sponginess. After what I thought was quite a lot of him comparing, listening to, and pushing on me, he phoned the thoracic surgeon, "the boss," as he referred to him, to find out what the next step should be.

"The boss" ordered another x-ray for that evening. Off we went. Upon our return, the night nurse offered pain meds, and took vitals. New tonight, and because of the sponginess, she told me that I'd be sleeping "with oxygen." I got to choose between humidified, or non-humidified (humidified, please). She flagged my room as "Do Not Disturb" after she left, and I fell asleep quickly. In the morning, I could tell that the puffiness was worse than it had been the night before. I was at x-ray at 7:00 AM. The tech there recognized me after so many visits, and filled out the sign-in sheet for me.

Shortly after returning to my room, the "daytime thoracic fellow" was there, assessing. She mentioned that they might have to "put in a little chest tube." This was not what I wanted to hear at all. My own fellow came in later, and did his assessment. He advised me to walk around the unit until morning rounds started. This I did, making circuit after circuit. I got light-headed at one point and crashed into my husband's shoulder, unable to move enough air. I thought, "This is it!  They're not going to let me go."

We didn't bother starting to pack up the room. We waited for the doctors to do their rounds. First to round was the immunotherapy team. It was a smallish flock this day, but it did include the principle investigator (The Guy!) The decision about whether I would stay or go was entirely up to the thoracic team. The attending said that the morning's x-ray looked "about the same" as the one from the night before. I didn't know if that was good news or bad news.

A few minutes later, the thoracic surgeon came in with his flock (of one), plus my fellow, to talk to me about how the morning walking went, how I was feeling, and how spongy he felt that I was. After listening to my lungs, and considering for a while, he told me that he was sending me home! Woo Hoo! I am to have a follow-up x-ray at my local hospital in a week, and to mail the disk to NIH.

We were strongly encouraged to include lots of stops during the drive home. The doc suggested that I get out and "do a few laps" every couple of hours. "Walking is the best thing you can do for yourself," he said, and so we did. We stopped five times on our 500+ mile trip.


It's good to be home!

What Happened to Tuesday?

So much of my stay this time is a blur. I've been mostly in my room, with two trips to x-ray (morning, and night). I'm visited by nurses throughout the day. They deliver pain meds, post-TIL treatment meds, and they take vital signs every eight hours. There is very little sleep.

With the chest tube, sleeping happened in spurts. I always woke myself when I'd try to change positions. It hurt a lot when I would move in my sleep.

Breathing was another adventure. I managed to pull 2250 ml on the spirometer (volume of air I can inhale). This was a record for me!

Last night, the thoracic surgeon clamped the chest tube closed. This meant the suction box thingy would no longer be helping me (It was pulling air from the space outside the lung, should any be leaking...pretty sure). By clamping the tube shut, the doc rendered it ineffectual. He would be able to tell by how I responded, over the course of 24 hours, whether it was safe to remove the tube itself. Even though the hose was clamped, I was still attached to the box. I eventually named it, "Beelzebub." It went everywhere I went.

More x-rays last night, and this morning. Then! Then! The thoracic doc decided that I would be O.K. to exist minus the chest tube. He pushed down (hard) around the insertion site while the fellow ripped the tube out. She was not quick at this, I am sad to say. It probably felt quick to her, but to me...notsomuch! It was not exactly painful but the longer a procedure takes, the more likely I am to get nauseous. You'd think I'd get used to this stuff, but apparently not.

I was encouraged to walk as much as possible, and to ask for pain meds. They will no longer keep me on a schedule for those (hurray!) My husband and I took a chilly walk around the hospital wing, and then I decided it was time to put on my own clothes!^†

Tomorrow, I'll have what I hope is the final x-ray during this stay. If it's good, they'll send me home! We have an eight-hour drive ahead of us, but hopefully I'll be able to tolerate it O.K.

† I have since learned that, according to the Patient Handbook, patients are expected to wear their street clothes as much as possible while inpatient. oops.

Scratch That

Needle biopsy will not be happening.  Instead, surgery is on the agenda for me.  Next week.

A thoracic surgeon is going to remove the recalcitrant tumor for the purpose of developing a new TIL treatment.  I don't have any details yet.  I'm saving my questions for when I'm back at NIH, and out of ear-shot of certain little people.

What I do know is that I've got some pre-surgical tests in store: EKG, echocardiogram, PET scan, and a lung function test.  I think, aside from cancer, that I am healthy otherwise, so these should not be a roadblock to surgery.

I'm very curious to know what the lab will find when they study this tumor!  Mostly though, I will be glad to know that it's no longer trying to kill me.

Stupid cancer.

Follow-Up #5 RESULTS

Earlier this week, by RECIST criteria, the target tumors in my lungs measured 46% smaller than they were pre-treatment. This puts me officially in the "partial responder" camp.  wooHOO!

I captured one image from the CT scan to post here, so you could get an idea of how "Target 3" is changing.  The white areas inside the blue oval are cancerous tissue--a nodule right next to my heart.  The darker areas within the tumor show that it is becoming less dense! (The white blob above the text in the image is a cross-section of a normal blood vessel.)

One tumor (not shown) still looks pretty gnarly on the CT, but it is in an area clouded by scar tissue, so it's difficult to determine what is what at that location.  All of the rest of the tumors seem to be breaking up, becoming hollow, or shrinking. No new tumors were seen, and my CEA level remained at 1.1 (same as in November).

Excitement!  Relief!  Gratitude!  HOPE!

Sleen's K-Ras Mutation

What follows is a mash-up of what I learned from the book, "The Emperor of All Maladies," from discussions with my immunotherapy fellow at NIH, and from email correspondence with my new cyber-pal, known as DK37*.

K-Ras is considered an oncogene (a gene that can cause cancer).  Colon cancer patients' DNA is typically checked in the earliest days after diagnosis to determine whether the patient is "K-Ras wild-type", or "K-Ras mutated".  I was found to be K-Ras mutated back in September, 2013 after my initial surgery.  I didn't know much about it at the time, except for the fact that certain drugs that have been found to be effective for "wild-type", would do nothing for me.

As part of the clinical trial at NIH, exomic sequencing was done, which identified my tumors' specific mutations.  The researchers found over sixty mutations, but one stood out as particularly interesting to them.  It was a mutation in the K-Ras gene.  It is referenced this way:  codon 12 G12D, and I was told that it is one of the most-common mutations in colorectal cancer (CRC). This designator is explained (ha, sort of) as: On the 12th codon, the twelfth amino acid "G" (glycine) has been replaced by "D" (aspartic acid). "D replacing G"--that is the mutation. 

Glycine, I was told, is a small, uncharged amino acid. Aspartic acid, on the other hand, is large and carries a negative charge (the charge is due to a carboxylic acid side-chain, according to my friend the medicinal chemist). Anyway, the negative charge blocks a cell's normal "stop dividing" instruction. The cell's "off switch" is effectively ignored, and so growth continues unchecked, forming tumors that grow without ceasing.

Fortunately for me, the tumors in my lungs have grown very slowly.  I would like to think that this is because I have been producing large numbers of tumor infiltrating lymphocytes (TILs) all along, but I have no way of knowing.  The aim of the clinical trial is to find TILs that are already working to remove cancerous cells in the patient, to multiply those, and to return them to the patient.  "Building up the army", is how many people think of it.

The researchers had success in the lab!  They discovered TILs in the harvested lung tumors that recognize the mutation in the K-Ras gene and are "reactive" to it.  If the 148-billion TILs they returned to me on July 1 are as effective in me as they were in the lab, we should expect to see shrinkage of my lung tumors by 12-weeks post-cells.  This is my great hope!  Alas, there are no guarantees.

* Super Genius

Science-y Things

I was sent home two days after the lung wedge surgery to recover. Ten days after that, I received an email from my immunotherapy fellow at NIH. He had good news:  my tumor infiltrating lymphocytes (TIL) were growing. He mentioned that they would continue to multiply over the next several weeks. When they reached sufficient numbers, they'd be cryogenically preserved until they were needed.

Poor, chilly lymphocytes.

DNA from the tumor had been sequenced. Healthy (non-mutated) DNA from my blood was also sequenced. Next, the two sets of DNA would be compared. Differences between them would indicate the mutations that allowed the cancer to grow. One of the attending doctors mentioned that this sequencing-and-comparing process involved terabytes (one million million bytes) of information, and would take some time to work out.

What the clinical trial (NCT01174121) seeks to achieve is to focus the body's immune system to attack precisely those mutations present in chemo-resistant tumors. It is believed that such defenses are already present in our bodies, but perhaps in numbers too small to effectively eradicate the cancer.  If researchers could identify relevant TIL; if their numbers could be increased, and if the TIL could survive the transition from lab to human circulation, then maybe they'd survive and thrive long enough to conquer every single cancer cell in the "tumor-bearing host" (that would be me, the patient).

Scientist outside of NIH would build a set of "tandem mini-genes" (TMGs) using my tumor's genetic information. The TMGs consist of mutation-containing bits of DNA strung together. Sixty-one mutations were found in my tumor, and so sixty-one mini-genes were created. In order to test more than one mutation at a time, the Scientist-slash-Wizards strung together multiple mini-genes in tandem. After the researchers constructed them, they would present these TMGs to the TIL. Any reactivity (TIL attacking) would be counted as a positive result.  If reactivity was proven in the lab, the trial could proceed.

I was told to expect a two-to-three month wait while mutations were identified and TMGs were built. After that step, if reactivity was shown, then the reacting TIL would be "expanded" (multiplied). If things moved forward to that point, my contact at NIH would give me a call to invite me back to NIH for "conditioning" (chemo to wipe out my existing immune system) and cell treatment (infusion into me of the specific TIL that attacked the cancer cells in the lab).

I settled in for the two-month wait, hoping and praying throughout every day that the trial would advance toward treatment. Beyond that, I prayed that this experimental treatment would transform my diagnosis of terminal illness into a reason to praise God for the miracle of science.

I always prayed for the doctors, scientists, and other people who were working on my case. I prayed that they would do their best work. Later, I prayed for their holiness. I believe that all people are called to be holy. Holiness, I reasoned, would promote cooperation of all those working on my case. It would facilitate Divine grace.