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

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.

Follow Up 12

Once again, I traveled to NIH in Bethesda for blood work and scans. All is well--I am still NED. What's more, the attending physician (at long last) has extended my next visit to six months out instead of three. Hurray!

Life is GOOD and health is a tremendous gift that I pray I will never again take for granted.

Eleventh Follow-Up

Follow-up eleven (what?!) happened earlier this week. No cancer was found on any scan. On the seventh of this month I passed the one year NED mark. This amazes me!


BEST PART of the visit was eating ice cream with friends.

WORST PART was saying good-bye to my dear former fellow. The gravity of the event hasn't sunk in yet. I don't think it will until the next time I go back and he isn't there.

Today I got to experience one of the milestones that cancer often steals from families. I witnessed my oldest child receive an award from the Honors College at her university. I remember well the day she started her college career--it was the same day that I was told, "You have cancer." I wondered then if I'd see her graduate. I wondered if my disease would interrupt her education. I so did not want that to happen. I thank God that she did such excellent work, and that I am here (!!!) to write about it.

Easter Sunday is only a few hours away. I cannot wait to celebrate!
He is risen, just as He said. Alleluia! Alleluia!

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.

Follow-up #9

My scans were good! The radiology report included the word, "unremarkable" a total of five times. That is a record number of times for me.

When a radiologist deems an organ "unremarkable" it means that no evidence of injury or disease is seen on the scan. It is one of those DoctorSpeak words that mean something completely different to the uninitiated.

Question: Who wants to be "unremarkable"

Answer: Cancer patients

Overshadowing this visit, sadly, was news that my friend and fellow cancer patient, D., had passed away suddenly. We had made plans to meet at NIH this week. Our visits overlapped, just as they had last winter. We were in contact weekly--often daily--for over a year. It didn't make sense. She was supposed to be visiting NIH for harvest surgery and scans...

Incomprehensible.

Consistent with the roller-coaster theme of this visit (the highs were as extreme as the lows) The Guy met with me at my clinic appointment. He confirmed that the New England Journal of Medicine will be publishing my case. He also told me that I am "an historic figure in medicine".

Incomprehensible.

Also this trip, I said good-bye to my dear Lab Guru. He has exhausted every extension that The Guy could arrange. I am confident that he will continue to do great things in his very own lab, just as he did during his time at NIH. I look forward to the opportunity to visit his new digs one day (and hopefully not for the purpose of apheresis).

Finally, a story of hope. Tonight, a friend on 3NW at NIH awaits her TIL with sheer joy (and maybe some fatigue after the conditioning chemo). It will happen soon! I pray she sees success. I believe that she will!

Follow-Up #8

We are home from another follow-up at NIH. It was all good news! The clinic meeting, for the first time, was boring. My scans showed nothing new, and nothing growing. I won't be scanned again for four months. Woo! I can live (literally, ha!) with boring follow-ups.

A highlight of this visit:  I got to meet a fellow patient who became a fast friend. I have high hopes for her, for great success with this trial. She's as curious (maybe moreso!) as I am about all things TIL, and our visit slipped away too quickly. We will meet again!

News:  The Lab Guru has submitted an article about my case to a journal. I hope to have more news on that later.

Another highlight: Visiting with my Top 3. Two docs, and a nurse. So happy they were all available!

If you're interested in enrolling in the TIL trial, the link is here.
A recent post on how cell therapy works is here.

Under "Highlights" on the right side bar, you'll find a link labeled "Key Posts" which can serve as a short-cut to navigating the blog for particular steps in my cancer Riot.

Sneaky Tumor

Breaking News!
The Lab Guru shared some stunning information about the non-responding, sneaky tumor that was surgically removed three months ago. After analyzing it, he now knows how that tumor progressed in spite of TIL therapy! His work was published in the NEJM (see link below).

It may be helpful to understand how immunotherapy did work to kill many tumors.
Disclaimer 1: I am neither a doctor nor a scientist.
Disclaimer 2: What follows is my understanding of the details of my own case.

Many Thanks to the brilliant doctors and scientists at the NIH who answered loads of questions at virtually every visit (and between times, too!) with patience and competence.

What worked:
Six tumors in my lungs are now dead, dead, all the way dead. (Update 6 years later: my scans show no remnant of any tumor.) They were killed by my immune system! Killer T-cells infiltrated the tumors to seek and destroy cells that harbored the baddest bad guy. This was possible in part because I inherited a hero HLA allele. It makes a particular protein molecule that worked in concert with killer T-cells to eliminate almost every tumor. HLA has the ability to mark cells that are "broken." Its job is to grab stuff from inside cells, bind it, and then present that stuff outside, on the cell surface.

More on the good guys, later! The villain in my case is a mutation to a gene called KRAS (KAY rass). Pieces (called "peptides") of mutated KRAS proteins are the stuff that my HLA binded with to mark my tumor cells for destruction. KRAS is vital to our cells, but mutations in this gene can lead to cancer.

Killer T-cells can't peer inside a cancer cell (or any other kind) to see what's going on there, but the HLA lives there. If a cell becomes deranged, as happens in cancer, HLA will grab its evidence (the mutated peptide) that something is way wrong, and thrust it outside the cell while still holding it in its grasp. This is the only way that a killer T-cell can sense its target; it must be bound to an HLA molecule on the surface of a cell.

Hundreds of types of HLA alleles exist, but each person inherits only a few. Each type creates a molecule that has a unique binding surface. Think of molecule-sized Lego bricks--if the peptide can snap together with the HLA molecule, the two form a complex. When this happens, the peptide gets swiftly escorted to the surface, and the courier (HLA) announces to the world outside the cell, "Look what I found!"

Unlike Lego bricks, not all peptides will fit with an HLA molecule. But, happily, it was found that for the mutation that I had, and the HLA type that I inherited, the two did fit together and HLA was able to bind the criminal and set it up for possible detection (and execution!) by my immune system.

Another layer of complexity:
Note the use of the term "possible detection" above. Just because the tumor cell, thanks to HLA, had the ability to present the mutation to my immune system, it was no guarantee that my immune system could recognize that mutation. Killer T-cells are the immune system's soldiers, but they are highly specific in what they "see." Most types, it seems, are blind and deaf to cancer cells, even when HLA is doing its best to let the T-cells know there is a problem. Why?

Each T-cell type is capable of recognizing only one particular antigen (bad guy), which is often referred to as its "target." T-cells sense their target with receptors (TCRs). These receptors are the embodiment of programmed randomness. Our bone marrow churns out millions of T-cells in our lifetimes, each equipped with unique TCRs that are constructed (as far as we know) at random in order to comprise a host of potential future armies against an equally stunning array of potential onslaughts. Each TCR is highly specific to its target and to no other. Because TCRs are so hyper-focused, we need lots and lots of varieties of them if we are to remain safe from the constant threat of incalculable numbers of viruses, bacteria, and even cancer cells. Lucky for me (understatement!) my body produces a few different types of  T-cells whose target is the baddest bad guy (KRAS G12D), and I inherited an HLA type (C*08:02) that has the ability to show that bad guy to the killer T-cell.  

When the killer T-cell connects with its target, the HLA-bound mutant peptide, it sends a signal to the tumor cell to self-destruct! Also, when a T-cell finds its target, it replicates itself and can go on to find and kill more tumor cells. Thanks to the Lab Guru's expertise, he was able to expand 30 million of my mutation-specific T-cells to 148 billion. These are the cells that comprised my TIL therapy. These are the cells that killed six known tumors in my lungs. Perhaps even more astounding: These are the cells that are still circulating in my system, keeping the KRAS G12D mutation from causing any more tumors for (I pray) the rest of my life.

Tumors are a collection of cells that have lost at least one important capacity that normal cells have--the ability to die. As tumors change over time, mutations accumulate. Tumors can evolve in ways that give them an advantage over the immune system. That is exactly what happened in the case of the one tumor that progressed even after TIL therapy. That tumor's cells developed an advantage that allowed them to escape detection.

What the Lab Guru discovered about the recalcitrant tumor is that it was missing one copy--healthy cells have a pair--of Chromosome 6. Chromosome 6 is where the HLA genes live! Since one copy of the chromosome was still present, it must mean that the hero HLA allele resided on the copy of the chromosome that went missing from the progressing tumor's cells. The other chromosome of the pair was a different allele; one that doesn't recognize the mutation, and so the sneaky tumor left it alone.

The Sneaky Tumor's Game:
Any tumor cell that was absent the hero HLA was essentially cloaked from my immune system. The killer T-cells could no longer sense their target (even though it was still present) because the hero HLA--the thing with the ability to display the bad guy--was gone! Any cells that were missing that particular Chromosome 6 (either the one from Mom, or the one from Dad) now had an advantage that would help them survive. When they multiplied, those new cancer cells, too, were missing a copy of Chromosome 6. Killer T-cells wouldn't kill those cells, because without the HLA complex to shout, "Look here!" the T-cells passed on by as if those tumor cells were normal, healthy cells.

I can only echo the Psalmist who wrote:

I will give thanks to You, for I am fearfully and wonderfully made; Wonderful are Your works, and my soul knows it very well.
Psalm 139:14 NASB

The End, A Surgeon's Knife:
Similar to the way cancer didn't eliminate just the single version of the HLA gene that threatened it (C*08:02) but the entire copy of chromosome 6 the gene resided on, my surgeon didn't just excise the sneaky tumor—he removed the entire lung lobe it resided in. It was a medical necessity to remove the entire lobe, but also something more: Poetic Justice.

Links to media:
Read the Lab Guru's article for the NEJM
Three newspaper reporters interviewed me for articles:
New York Times
Wall Street Journal
Philadelphia Inquirer
Joan Lunden interviewed The Guy and me for the Today Show.
Sneak peak for that story on FaceBook here.
Tom Marsilje's blog about my case.

Milestone

Last Friday was the anniversary of "Cell Day". I sent my husband out for a Pepperidge Farm Chocolate Cake just like the one they gave me on the day of the transfusion.

On Sunday we packed up the kids and headed for Frankenmuth, where I was registered to participate in a 5K Walk. That evening, I raised a glass to toast my esteemed immunotherapy fellow, who soon would be turning over my case to someone else. I chose a drink that he likes best. (This was less of a sacrifice than I was expecting!)

We watched fireworks with our kids, and some dear friends. Our youngest was enthralled by the spectacular explosions and declared his appreciation (loudly) after almost every round. As the smoke from the finale cleared, he announced in the darkness of the night that it had been "the best day of (his) life".

The 5K took place the following morning. I was nervous! It seemed to me that all of my health problems began after I ran a 5K in 2011.

Maybe 5K races are bad luck!

My oldest daughter and my husband accompanied me. They kept me to a challenging-enough pace for me, but one slow enough for them to chat effortlessly with each other. Neuropathy in my feet (from stupid FOLFOX) caused some pain, and my lungs...well, they did OK. I wasn't breathing like I felt I needed (wanted) to, but I was breathing adequately, apparently. I could not chat! My lungs would let me walk, or talk, but not both. We walked at about 3.5 mi/h and I finished in 51 minutes.

In movies sometimes a dramatic moment is depicted as happening in slow-motion. That is what happened to me at the finish line. In slow-motion, I saw my foot hit the mark, and it felt like a literal weight had lifted. I could almost hear the woosh as it flew off my shoulders. I've never experienced anything like it before.

When I crossed over the finish line, it felt like a new beginning.

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.

Follow-Up #7

No real news this time, for once!  It's been ten months since I received TIL therapy.  I was back at the hospital for follow-up number seven last week.

First thing on Monday, as usual, I went directly to phlebotomy for a blood draw (only six vials this time).  Later in the day, I had a CT scan.

On Tuesday, I had apheresis. To my immense relief (understatement!) the procedure turned out to be the shorter one. Even better, my research fellow spent some time with me, talking about his work in the lab. The conversation helped to get my mind off of the blood circulating out of and back into...me (gack) and I was very thankful for that.

When the requisite amount of white cells had been collected, my husband and I bolted over to Medical Records to pick up the disk of CT images from the previous day's scan.  I set up the laptop at one of the teensy tables in the atrium.  I was taken aback at how different the scan looks now that I have one fewer lung lobes! I wasn't able to study the images for very long; it was almost time to go to "OP3", where my follow-up would happen.

Even though I expected to hear good news, I had dreaded this appointment for weeks.  It was the last one I would have with my current immunotherapy fellow. It makes me sad to think of someone else as my doctor, but I'm happy that he had (what I hope was!) an interesting and fulfilling year on the service. I consider myself most fortunate to have been in his care over the past year, and I am confident that his future patients will feel the same way.

We stepped into the hallway to review the scans, and I stood there thinking how bizarre they look now.  My right lung lobes have sneaked their way over to where the now-missing left lower lobe had been. My heart is literally in a new place! "Mother Nature will not tolerate empty space," is what I was told. It's so strange-looking to me. Regarding cancer, my fellow saw nothing of concern.  Thank God!

The next morning I met with the thoracic surgeon for follow-up.  He wanted to see how the incisions were healing, first thing.  Little did I know that he would find something that needed attention.  He said that my body was "spitting out a couple of stitches" (gack! again!), and so he removed them.  Actually, his assistant removed them but Ow! OW! QUIT IT!!! After that unpleasantness, he had only good things to tell me, so we left the NIH on a high note.

My follow-ups will get stretched out from now on. I'll go back quarterly for a time, and after that, even less-frequently if all continues to go well.  I am praying that it will!