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

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!

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.

Queen of X-Rays and of Pain

I am four days post lung surgery.  The chest tube is still doing its thing.  Sort of.  Seems that some air is not making its way to the tube, but instead leaking into other tissues.  I am "spongy", they say.  Who knew that was a thing?  Not me.  The thoracic surgeon says this is not a big deal, so I will believe him.

I've had quite a few x-rays since surgery...par for the course, I'm told.  I've had two per day for the past few days. I'm becoming a familiar face to the techs.

During grand rounds this morning, I asked the Lab Guru for "the scoop," so he stayed after the others had left and told us all about what's happened in the lab so far, and what will happen next. I got to see photos of the two tumors that were in my lung!  ick! ick! ick!

When I saw "Junipero" (who-KNEE-pair-oh), my first reaction was, "So there's the bastard!" My second thought was, "Wow...how many patients have this opportunity? This is amazing."  Shortly after that, the ick-factor kicked in and my brain shut off.  ha.

Each tumor will be tested in ways that I can't even imagine. It is the first time they've had both a necrotic tumor and a live tumor to study from the same post-TIL patient.

During our conversation, I believe that I solidified my standing of "weirdest patient ever", by accidentally letting the very dear Lab Guru in on the naming convention I have been using all along.  I usually hesitate to reveal this to the medical types, but it just came tumbling out.  "José is dead!  Woo Hoo!"  That little outburst led him to ask, "What's the other one called?"  Yeah, so.

Stop staring at me.

Backing up to yesterday:
It was a horrible, awful day. I woke at 6 AM in excruciating pain. The chest tube was causing back spasms, the insertion wound felt stabby, my shoulder throbbed, and I could not inhale except for what seemed a woefully inadequate amount. I cried. I sat up in my bed and cried and cried...no sobbing though--that takes too much air. All I could do was wipe away--over and over--the unstoppable stream of tears that slid down my face.

Misery.

During this episode, the surgical fellow walked in. She assessed my situation, checked my suction box thingy, and offered some sincere words of condolence. I hate crying, and I especially hate crying while being watched...watched by a stranger. It was humiliating. So there I was, in pain and humiliated. Not a great way to start the day. The doctor left, formulating a plan as she went, I'm sure. Shortly thereafter, meds arrived and things eventually got better. I don't tolerate narcotics well, but a type and dose was found that works without turning my brain to mush. Thank goodness.

According to the thoracic surgeon, as of this morning I still may have an air leak. He's going to try clamping off the chest tube this evening to see how I do. In the morning I'll get another x-ray, and he will maybe remove the tube.

Today, my job is to walk around as much as possible, and to use the incentive spirometer ten times each hour. Patrick is being helpfully (?) anal about this, and has set a timer on his iPhone to remind me when it's time to use the thing again. Six minutes go by quicker than I thought...it's a lot of work.

I cannot breathe as deeply as I'd like to, yet. I walk slower than I'd like, but when I speed up, I can't pull in enough air to keep me going. I get light-headed and have to stop. I need to figure out the best pace.

I see the Wandering Priest everywhere I go. I accused him of following me, today. "I follow all my patients," was his reply. I wonder if he bi-locates?  ha ha

From ICU to Regular Room and NED!

After surgery, I spent some time in the ICU, a place I had never been before.  It reminds me of a refrigerator, in a way.  It was chilly, and there were a lot of stainless steel surfaces... My memories are a bit jumbled, so I'm not sure if these events happened in the order I've recorded them here.

My first memory upon waking up after surgery is of a male nurse talking about "the pain". "She doesn't have that excruciating shoulder pain they always have.  That's a real blessing."  I wondered how he knew about my level of pain.  Maybe I had heard him wrong? Did he say, "scar"...I was confused. He could have said, "She doesn't have that huge scar that people sometimes do..." My left shoulder hurt, and it hurt a lot to breathe due to the chest tube that was (and still is) wedged into my side.  Someone took a chest x-ray while I sat up in the bed.  I only remember that it was a herculean effort to sit upright to facilitate the process.

Breathing hurt. The thoracic surgeon stopped at my bedside and said that the surgery had gone well. He had removed the entire lower left lobe of my lung. The lung was taken directly to the Lab Guru. Pathology would have to wait, because "those immunotherapy guys", as he called my doctors, were adamant that the specimen go to them first. I was beyond thankful to have the tumor gone. ...glad to be awake and alive.

The bed had a balloon-like mattress. I struggled to think. I hurt. I remember opening my eyes--and wishing I had my glasses. Some fuzzy, tall somebody was at the front of the room--a man, washing his hands. Was it a doctor? There was no lab coat. When he turned around I recognized that it was my fellow. Relief. Only then did I realize how scrunched up my face had become from the pain, because as recognition dawned, the tension eased away.

My doctor said something like, "Those meds really take a lot out of you..." to which I muttered, "It's temporary?" "Yes," he said, "It's temporary." I drifted off again.

The next thing I knew, the male nurse was explaining the controller for the PCA (patient-controlled analgesia).  I think it was delivering dilaudid.  I could push the button as often as once every ten minutes, he had said.  The machine would beep twice if it was dosing, or once if I had pushed the button too soon.

The sliding "refrigerator" doors opened again, and in walked an attending physician. This was the doctor who, along with my fellow, had cared for me while I underwent the protocol in July. I hadn't seen him in many months, and was a little alarmed at his presence now. Bedside manner had not been his strong suit, but he did have my respect for other reasons. I couldn't figure out why he would be visiting me. We stumbled through a brief exchange of some sort, then he very deliberately picked up the PCA and clicked the button. "Be sure you use that," he said as he returned the clicker to its former resting spot. Then he left without another word.

The ICU was sterile in appearance and in fact. It was very, very quiet. I had trouble thinking but didn't know whether it was from the pain or the pain meds.

I slept in a half-sitting position. I faced a wall clock, and I woke up almost every hour. Blood pressure measurements were being taken automatically, and the noise the machine made as it sprung into action woke me time and again. I checked the clock each time I woke to see that an hour had passed in what felt like only seconds to me. The clock might as well have been a toy; time had no meaning. I wasn't sure if it was day or night.

Later, a male nurse offered me a bath. I could imagine nothing more absurd at that moment. I wanted to snark, "Are you freaking kidding me right now?" but didn't. I only said in a surprisingly feeble voice, "No. I don't want that." There was no mention of it again. My ears were ringing, and my vision was jumpy. I decided to hit the PCA button less frequently. The nurse helped me get to a chair--this was his idea; not mine. I was content to stay in the bed, but I hobbled very gingerly to the recliner. I was given a welcome cup of ice chips, and later a lemon ice. I noticed that I had two I.V.s, and several new bruises and needle marks on my arms.

Next, they wanted me to have a "proper" x-ray.  This meant traveling to the radiology department.  I was connected to all manner of tubes and wires that seemed to be just everywhere. The nurse somehow got me into a wheelchair amidst the tangles of equipment, and we began the seemingly long journey to x-ray. I could barely stand, so they did the imaging with me sitting on a stool. Two views: side, and front. Then back to ICU.

I tried very hard to make the incentive spirometer move. I could only pull the bare minimum (250 ml) at first, incredibly slowly, and not without a great deal of pain. I kept at it. I knew there were some who were dubious about my refusal of an epidural, but I did not regret my choice. Had I consented to the epidural, they now said, recovery would go faster and with less pain. "It's too late now," I said. The idea of a catheter in my spine was too invasive, too dangerous, too nauseating to me. I remember being relieved that the anesthesiologist had not questioned my choice, but had instead said, "We have other options..."

Each time a new person entered the ICU, they'd tell me that I was going to be moved "to a regular floor" later that day. I'd ask, "Which floor? 3NW?" Always the reply came, "We don't know yet." I really, really did not want to go back to the lymphoma wing.

Then a nurse loaded me, with all of my tubes and wires, into a wheelchair.  As we slowly moved out of the ICU, and down the hall she triumphantly announced, "We're going to 3NW!"

"Hurrayyyyyyyyyyyyyy! That is The.Best.News!!!" I (feebly) fist-pumped the air, and thought that I couldn't be any happier. She wheeled me down a passage where my fellow and some others were eating lunch. The Lab Guru saw us first. He stood as my wheelchair approached, and broke into a huge grin. My fellow turned to see what had got the Guru's attention. "They're taking me 'home' to 3NW!" I babbled, "I'm so happy!" My fellow joked about sending me to a room in the basement instead. ha ha...

This was one of the best days of my life, on par with the days that I heard, "Will you marry me?", and "Meet your new baby." This is the day that my doctor had said would render me--for the first time, ever--NED, no evaluable disease. I was floating.

Exiled

Greetings from my hospital room at NIH.  I've been placed (temporarily, I hope) at the lymphoma wing, due to lack of available beds on the immunotherapy ward.

It's lonely over here.

Today, I am scheduled for surgery.  I met the thoracic surgeon yesterday, and we discussed the very real possibility that he will remove the entire lower left lobe of my lung.  Regardless of  how much he ends up taking, I'm guaranteed to wake up with a chest tube.  I am sort of dreading that (not the waking up part, haha).

I'm "in my head" this visit, and not adequately equipped to articulate my thoughts.  I am relying on the knowledge and belief that Grace is given in time and measure according to my need of it.  I am working on re-framing this episode as one of restoring health, rather than focusing on what needs to happen to get there.

I had a visit from the Lab Guru on my first night here.  That was a most-welcome surprise.  He told me that he found four different T cell receptors (TCRs) in my blood that all react to KRAS G12D.  I had heard previously that it was three types, which was pretty stunning.  Four seems even better.  He explained how the fourth one is "very particular" about what it recognizes, and I just sat there listening in utter wonder at how cleverly our immune systems were designed.  He also said that the cells are persisting at a relatively high level, even seven months out, which he thinks is a good sign.  That was the good news.

The bad news is that, since I do have a tumor that is now growing, my case can no longer be described as "Partial Response".  Instead, I've moved to the ultra-depressing category of "Progressive Disease".  It does not change the fact that six of seven tumors have responded (and continue to do so), however, so I need to "get over" the whole labeling thing.  I was never a fan of RECIST criteria, but it's the tool the oncology world uses, so I'm stuck with it.

Today I will have surgery.

I hear, outside my door, the sounds of the Medical Oncology ward waking up:  voices, wheeled carts bumping through the hallway, and doors opening and closing.

I hope that when I awake from surgery, I'll be greeted with the news that I won't be returning to this room, or this wing. My fellow assured me that "they" are doing what they can. He joked that it is "far too long a walk" for him to make in order to do his rounds. "Yeah, we've gotta get you back where you belong," he said.

I couldn't agree more.

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 #6: A Bump in the Road

I am now almost nine months out from "cell day", July 1, 2015.  This week, I met with the docs at NIH for my sixth follow-up.

While the results were mostly good, the one tumor that showed up "hot" on PET in October is now very obviously growing.  Of seven tumors scattered across my lungs, only this one seems to have not gotten the message that it's time to bounce!

Why did this one tumor not respond to therapy?  That's what we hope to discover.  My next visit to NIH will (we think) include a procedure by an interventionist radiologist.  Though a needle biopsy is theoretically the least invasive means to obtain a tissue sample, my last experience with an I.R. was less than pleasant. By a lot.  I have some mental hurdles to overcome before my return to the operating room.

Once the scientists have a sample of the rogue tumor, they'll test it for mutations.  If a couple of parameters are met concerning the properties of the tissue sample, a cell therapy may already be available for me.  I would undergo the preparatory seven days of chemo, like last time, and then have a different population of cells returned to me.  This population of cells was "Set B" from my prior lung wedge surgery.  "Set A" were the cells they ended up returning to me in July, but these other cells also reacted to the KRAS G12D mutation.  They could potentially be just the ticket for getting this final tumor to start shrinking away.

It is possible that the tumor does not have the two properties we're looking for.  In that case, we will have to discuss what the next steps should be.  Way-smart medical types are already contemplating all of this, and though I have some inkling of what could be next, I can't address that yet.

It was an emotionally draining day in the clinic (!), but it was encouraging, too.  It was far from the worst news I could've heard.  My over-arching thought is: There must be More to Learn from my case, and that is a pretty great thing.

Other results:  The rest of the tumors remain stable.  By RECIST, I'm still at 46% reduction from baseline.  No new tumors were seen.  TIL therapy is working, at least partially.  For that I am excited, and grateful, and ever-more hopeful that it will work for me a second time.

If you pray, please pray especially for the team of doctors and scientists connected to my case.  Pray for revelation to complement the determination they already possess.  Pray that they do their best work. Pray that I, and they will cooperate with Divine Grace for the outcome that God wills.

Whew.  That's a lot of prayers.  THANK YOU!

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

The Shoe Drops. Forgiveness Prayer

Patrick accompanied me to the oncology clinic to follow-up on the pathology report from the lung wedge surgery I had done only five days prior.  We were taken to an exam room where the doctor sat across from us as she delivered the news.  "I'm so sorry," she said, which is all she needed to say.  She then began to read from the pathology report itself.  I've reproduced a portion of it below:

DIAGNOSIS:

***ALERT***ALERT***ALERT***
A. LUNG, RIGHT MIDDLE LOBE, WEDGE BIOPSY
--- BENIGN LUNG PARENCHYMA WITH SMALL INTRAPARENCHYMAL LYMPH NODE
--- NO MALIGNANCY IDENTIFIED

B. LUNG, RIGHT LOWER LOBE, WEDGE BIOPSY
--- METASTATIC ADENOCARCINOMA CONSISTENT WITH COLORECTAL PRIMARY, SEE COMMENT
--- MAXIMUM LINEAR DIMENSION OF CARCINOMA: 1.5 CM
--- INKED STAPLED SURGICAL MARGIN IS POSITIVE FOR ADENOCARCINOMA

COMMENT:
The sections reveal a lung parenchyma infiltrated by adenocarcinoma.
Neoplastic cell are positive for CK20 and CDX2 while negative for CK7 and TTF-1. Overall, the clinical history, morphologic features and immunohistochemical findings are consistent with metastatic adenocarcinoma from colorectal primary.

My birthday would be two days later. Christmas was less than a week away. What a rotten time to get news like this. I had a burning question after reading the report. It stated that "positive margins" remained after the wedge was taken. This meant that cancer cells near where the node had been cut off were still present. My question was:  Why? Why when current theories of cancer promote the idea that a single cancer cell can eventually lead to death, why wasn't care taken to obtain clean margins? When the surgeon stated that the intent of the surgery was "not therapeutic" (see this post), I never imagined that the procedure itself, by its very nature could be instrumental in spreading the disease it sought to diagnose. That was naive on my part. I had assumed that a large enough wedge could be taken and would be taken such that the sought-for nodule would be completely removed, and all trace of nearby cancer cells with it. Why didn't the surgeon check for clean margins before closing? This question haunted me for weeks. I became angry.

If physical harm had been done to me, it was too late to mitigate, but it wasn't too late to repair the spiritual damage that I could do to myself by despairing or becoming bitter. I needed to forgive the surgeon. Some weeks later, with the help of a holy priest, and the Sacrament of Confession, I started the process. The priest explained that though I might not be ready to offer my own forgiveness, I could ask God to do the forgiving in my place. He shared with me this most-helpful prayer, carefully pronouncing each word with reverence, "Lord, forgive those bums for what they did to me." (Emphasis his.) The priest encouraged me to repeat this prayer multiple times a day, whenever I thought about what happened. "After enough time," he promised, "you'll forget what you're asking to be forgiven."

Since the surgery, I've been informed that I received the standard of care. Because the intent of a biopsy is never curative, maintaining clear margins is not part of the equation. The situation makes me wonder if I will ever know the right questions to ask before a procedure. Meanwhile, I haven't yet forgotten what I'm asking to be forgiven. Until then I keep repeating:
Lord, forgive those bums for what they did to me.