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!

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 gene that threatened it but the entire chromosome 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.

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.

Radiation?

Patrick and I visited the clinic soon after the PET scan to get the oncologist's take on it.  I was hoping to hear more happy words from her like, "You're done with this place, go home and live your life."  But no, that wasn't what I heard.

My doctor told me that she wanted me to consult with a radiation oncologist.  I couldn't believe my ears--she wanted me to pursue further treatment?  Was chemotherapy not enough?  When would it end?  I left disheartened, clutching a scrap of paper with yet another doctor's contact information scrawled across it.

From the first radiation oncologist, I learned that there were no studies done in cases like mine.  His opinion was that I would receive an anti-cancer benefit of maybe 15%, if chemo was given concurrently with radiation targeted specifically at the top of the bladder, where the original tumor had infiltrated.

A second opinion at a different hospital suggested the same potential benefit, but with a much more horrific list of side-effects owing to this new doc's more aggressive approach.  She would target not only the suture site, but the entire "surgical bed".  Side effects included night sweats and hot flashes due to the ovaries' destruction, chronic diarrhea, and a constant feeling that a urinary tract infection was pending.  Top all of that off with fatigue and nausea from the chemo this doctor would also recommend.

Two words:  No Way.

I called my oncologist to ask about the chemo-part of the equation.  Throughout the five weeks of radiation, I would receive fluorouracil via the harpoon + pump for six out of seven days.  I thought I mis-heard her--six out of seven?!  Who could do that?  I couldn't fathom lugging around that chattering thing, attached by a harpoon in my chest for six days every week!  Sure, the drug would be at a lower dose than I had taken previously, but the equipment itself, and the skin-blistering Tegaderm dressing that I'd have to use six out of seven days was the bigger concern at that moment.  I asked about taking chemo pills (xeloda) instead, but she maintained her stance that the pump would be a more effective delivery method.

In a this-can't-be-happening sort of stupor, I hung up the phone.  Again, all I could think was:  No Way!