Grey’s Anatomy and Li-Fraumeni

I was doing some work on my computer on Thursday evening when the notification on Facebook got my attention.  I checked in, and saw some LFS chatter.  “Anyone watching Greys Anatomy?”  Apparently there was a storyline about LFS.  I took a break from what I was doing and went to watch.

I do not generally watch the show, but DVR it for when I need some brain candy.  On a day where I need distraction from my worries, I might watch several episodes back to back, fast forwarding through the commercials.  This makes my son laugh, as though we do not have enough doctors and hospitals in our lives.  I am not at all caught up on who is seeing who…  they are Sleepless in Seattle, because everyone is sleeping with each other.

At any rate, one of the medical storylines centered on a family who had a strong cancer history (breast, lung, pancreatic, testicular, brain and bone) One of their teenage daughters, Rory, who had a previous history of brain tumor, presented with likely osteosarcoma. There were questions about whether this was metastatic brain tumor or a novel cancer diagnosis.  It was soon discovered that she also had pulmonary involvement. It was decided that she would have a CT with contrast as part of the staging process.

A large mass was found in her chest, complicating matters because it was vascular and would be a challenge to either remove or biopsy.  It was unclear to the surgeons if this was a third primary cancer or metastatic osteosarcoma.  Given that the patient was 16, and this was at least her second cancer diagnosis, her genetics were considered suspect.

The family was asked to submit saliva samples for genetic testing. They declare that they are “the family that beats cancer…that is what we do!”

A P53 mutation and discovery of Li-Fraumeni Syndrome was established for Rory the same evening that the chest CT and bone biopsy were done.  No one had heard of LFS, and Bailey declared that it was really rare, only perhaps a hundred families in the literature.  The residents were ordered to research on the web, and find case studies at the library in order to help this patient. (If they had only come here–I happen to know some mutants!

The sisters were both 16. (Which begs the question, are they twins?  If not Irish twins, than they must have been fraternal, given the discussion that follows.)  They talked about the problems with knowing your genetic status, Rory indicating that she wished that she didn’t know.  The healthy sister asks Karev if she must know, if she might make her own decision.  Given her age, she was told that she could decide for herself. With encouragement from her sister, she decided not to find out if she carries the mutation.

Rory became unresponsive and was rushed to surgery where the tumor appeared to have ruptured.  The residents worked together and it was suggested that they came up with a solution that they excitedly rush to share with the surgeons, but not in time, as the patient had died. 

The healthy daughter, learning of her sister’s death, impulsively asked for her genetic results and was told in a word, that she has Li-Fraumeni.  She declared that she always wanted to be like her sister and now, she was.

The doctors, regretting the loss of their patient, speculate that they might be able to use this to help the remaining sister.  The residents all go out for a drink.

I turned off the television. I returned to my work and saw many comments from folks who were discouraged with the ending.  We really hate losing mutants, even fictional ones.

I was actually waiting for pathology results on some lymph nodes on my son, who incidentally completed treatment for osteosarcoma less than two years ago.  He has recently been diagnosed with melanoma, stage IIIA…contingent on the status of these nodes.  My daughter had adrenal cancer and a brain tumor.  So, this story, while fiction, really isn’t completely foreign to our experience with regard to the pediatric cancers involved.  We just split them up between two kids…sigh…

I was personally uncomfortable watching them kill off 16 year old with osteosarcoma, likely with massive lung mets. On principle, it was not something I needed to see, given our current position.  However, I am hopeful that by exposing the public to the genetic realities of LFS, that there might be more money directed in the research.

I am hopeful that doctors will become more aware and thoughtful, rather than calling a strong cancer history “bad luck,” and failing to refer patients to genetic counselors.  We have all faced some variation of this response at some time, I believe.  While, no one would deny that repeated cancer diagnosis falls under the “Bad Luck” umbrella, there are things that can be done to change your luck if anyone bothers to find a genetic link. 

We follow the Toronto protocol, and have discovered two cancers in our children that I absolutely know we would not have found in the earlier and more treatable stages, without being proactive.  This recent melanoma is one.  And while I am not happy with my son’s current staging, which calls for a year of interferon, I know that he would have far more advanced disease if we did not know about his LFS status, and had him screened. We would be on a much, much harder road.

Looking at this episode from a fact checking perspective, there were some striking differences between the drama, and how things work in a real hospital.

1. Time warp

In order to make this work in a one hour show, leaving plenty of time for the hook-ups in the on call room (which, lets face it, keeps the ratings up) there is a compression of time.  Biopsy results for osteosarcoma take a week, at least.  They discuss your case at tumor board, and come up with a plan before you learn the results.  Ours took nearly two weeks because they were sent out to another hospital for a second opinion. 

Genetics results take even longer …a month.  And it is a staged process to test a family, generally speaking, with the proband being tested first, and if a mutation is found, then a second round of testing is done with parents and siblings of the proband (and sometimes this part is done in two stages), looking for the identical mutation.  Even when you know what you are looking for, it takes weeks, not hours.  I would love to have the genetic sequencer that Bailey had, because waiting is really hard.

2.  I am pretty sure that LFS is tested with blood samples and not spit. I could be wrong, but everyone I have talked to rolls up a sleeve, rather than ‘thinking about pickles,’ in order to produce ample saliva.  Might just be an easier devise for TV…they certainly have no problem showing lots of blood on this show…and open ghastly wounds.  I am not really sure what that was about.

3.  Genetics, both the decision to test and the manner in which those results are shared, is more controlled and much more thoughtful. A surgeon will not blurt out the results, particularly on the heels of revealing a poor outcome… in a public hallway.  It is just not how it works.

4. Given that genetics results take a month to come in, treatment is generally well underway before that information is available.  Further, when available, it is only one consideration among many.  Sometimes radiation is used, even on mutants.  The giant lung tumor would be what we call ‘the shark closest to the boat’ in this case. Real doctors would recognize that while radiation should be avoided, sometimes it is necessary.  You want to be thoughtful in selecting your weapons, but ultimately you must battle the shark with whatever you have. The genetics would take a back seat.

There were some things that I thought were thoughtfully done.

1.  Putting all of the “faults” aside, which I simply consider creative license, I am glad that they featured Li-Fraumeni. I think that the discussion between the sisters about the burden of “knowing” was the dramatic construct used to condense what happens in genetic counseling sessions.  Knowing does not come without consequences, and you cannot un-ring the bell.  Everyone does not want to know.  You have to be ready.  You have to be sure.

2. The remaining sister upon learning her status, declared that she was glad to be ‘just like her” as she had always wanted. This may seem crazy, because no one wants this horrible predisposition to cancer. There can be survivors guilt, in a way, for someone with a negative status in a family of mutants.  I have a mixed status family.  I have not seen this in my kids, but am on the alert for it.  It is common for people to struggle with being negative.

3.  The part where none of the surgeons had ever heard of Li-Fraumeni, well, that is not just possible, but probable.  We have all had to explain it to doctors at some time…sometimes google searching it for them in the office, or bringing in papers that explain the syndrome.  It is very rare, as Bailey said.  perhaps a hundred of families in the literature.  But with testing becoming more common, and less expensive, more people are being diagnosed all the time.  Unfortunately.

4.  The creative energy of the residents in figuring out a solution…well, I am hopeful about this.  There are physicians who are intellectually curious and passionately determined to help.  It will not happen in an afternoon of brainstorming as the writers of this episode portrayed it.  But, in that same representative fashion, I am hopeful that there will be greater attention brought to Li-Fraumeni, and to the considerations of our genetics.  The residents represent the positive collaborative effect that is currently happening with researchers from institutions all over the world…who study and work together to find solutions for us.

I hope to meet these researchers in the bar at the end of the day.  The first round will be on me.


Pediatric Cancer: LFS style

It is difficult for most people to imagine what it is like when your child has cancer.  I have tried to explain what my son Brent’s journey was like on our caringbridge site, because I know that my friends could not understand nor relate to how brutal the chemotherapy beat down was for him, nor understand the giant surgeries that he has endured over the past two years.  Thankfully, it would appear that he is finally done with surgery at this point.  I have tried, but have failed, to express the fear, the despair, and the complete helplessness that we have felt at times as parents.  I cannot describe the bone weary exhaustion that comes with pediatric cancer, and I do recognize that neither Dan nor I actually did the treatment.  It was exhausting just bearing witness to it.  I cannot even begin to fathom what Brent was feeling.

Some parents on the oncology floor could relate to these things. The general approach to cancer is three pronged: “Cut, Poison and Burn.”  The osteosarcoma protocol calls for ‘just’ cut and poison. Brent would have quite a bit of both.

But, our pediatric cancer story was complicated by the fact that when Brent was shockingly diagnosed just over two years ago with a huge osteogenic tumor on his right pelvis at age 11, he had a brother aged 13, and two sisters, aged 9 and 3.  And our oldest daughter, Lauren, had already had an adrenal cortical cancer at 17 months.  We knew immediately that we had a genetic problem.  The question for that fall of 2011, was who else had this problem. How far did this cancer risk go?

For anyone who has gone through this process, you know that genetic testing takes time.  Like a month.  I was well aware of this, because we had tested Lauren before.  Her adrenal cancer was so rare, that back in 2004 when she had this adrenal mass removed, we had genetic testing done, looking for Li-Fraumeni Syndrome.  It took a month for those results to come back. This, for the record, is a very long time to have your future, and that of your family, hang in the balance. Somehow, she was found to be negative.

So, as Brent began chemotherapy, we waited again, this time for a more refined test to be done on his DNA.  I worried about all of our children, as did my husband, Dan. One day as Brent was sleeping off some chemo, our geneticist stopped in for a consult.  She and I sat in a private room and talked about Brent’s results.  She revealed that he had tested positive for LFS. 

This, I would point out, was one of the few days that I completely and utterly lost it in the hospital, an activity that I usually tried to relegate to a more private locale.  I interrupted rounds that day, and hauled the attending oncologist into our meeting…and I was crying, kind of a lot, because I knew that each of my other children had a 50/50 chance of having the mutation.  And, I should point out, I wasn’t feeling so lucky those days.  Lauren, because of the adrenal cancer, I was certain, (with no one really arguing the point) would be positive.  We had to draw labs on the rest of the Ramers, and wait again.

It was about at this point in Brent’s treatment that we learned about the surgical options for him.  He was likely to lose his leg.  We sought second opinions…from the Mayo Clinic, from St. Jude’s, from the Cleveland Clinic…all in favor of amputation.  We finally heard back from a surgeon at MSKCC in NYC…who invited us out for a consult.  I know that sounds like a dinner invitation, rather than a doctor’s appointment, but it was the first indication that we might have some better options for Brent, in terms of his mobility. I really hoped we wouldn’t drive 9 hours, only to be advised, once again, to amputate.

When the genetics results finally came back, just before Thanksgiving, Lauren was indeed positive for LFS with an identical mutation as Brent’s.  Our other two children, most thankfully, were negative.  And, oddly enough, Dan and I were also both negative for a germ line mutation.  Once I answered the very awkward questions about how certain I was with regard to Dan’s paternity of Brent and Lauren (that was awesome, btw, like my life wasn’t already in full throes of the crap-o-matic 3,000…) one of us was presumed to be a mosaic, possibly with mutated cells scattered throughout our body, possibly isolated to certain organs…but most certainly present in either sperm or eggs.  Oh, welcome to research.

We tabled our own issues for the moment, though; because Brent was due to have his big surgery at Memorial Sloan Kettering, in New York City, one that would allow him to walk.  But as he prepared for that, finishing his last few weeks of pre-op chemo, oncology arranged for Lauren to have her initial surveillance scans, following the recently released Toronto Protocol, out of the Hospital for Sick Kids.  The premise behind the tests (labs and ultrasounds every 3 months, full body and brain MRI annually) was to detect cancer in the early stages when it was more manageable and more easily treated.  Small cancer is better than big cancer.  One look at Brent’s MRI, and you would have to agree.

Knowing that Brent had a giant surgery planned for mid-January, they managed at Rainbow Babies and Children’s Hospital in Cleveland, to schedule Lauren’s scans before we went.  She had her workup on December 22, 2011 to get a baseline read of what would become her routine scans.  I explained this all to her, and assured her that we would do something special afterward.  She was an amazing trooper. 

We came home after a long day at the hospital, and had a late dinner together as a family.  Then, the phone rang, on our land line.  I knew instantly when the doctor asked me if I was sitting down, that something was amiss.  He said that there was a mass the size of a golf ball, in the frontal lobe of Lauren’s brain, discovered by MRI.  They had no idea what it was, and wouldn’t learn what it was until they took it out, which they would do right after Christmas.  We needed to meet with the neuro surgeon the next morning.  He would call back to firm up the time. I was stunned, and completely blindsided. 

She had no symptoms.

We were supposed to celebrate our Christmas early, starting with our nuclear family in the morning, spreading out the understandably emotional and tiring celebrations with extended family over several days for Brent’s sake, because he had been so beat up by chemo and had been plagued with neutropenia.  So, as Dan and I wrapped gifts that night, Dan leading the charge to make our Christmas one the kids would think on and remember with joy, we had very heavy hearts. 

I mostly wept.  I doubted that I would ever forget this Christmas.  I wondered, at one point, how many stockings we would hang the following year.  The fear and the despair that we felt were immeasurable.  Without my husband, I swear that I would have simply remained in the fetal position, Christmas be damned.  He truly carried me, and act for which I am very, very grateful.

In the morning, the kids were thrilled.  Mostly, I recall how excited they were to give their gifts to each other. Lauren, who loves zebras, got a zebra print bandana from Alex.  Dan and I looked at each other, taken aback with emotion.  We had come across clips and such that we had purchased for Lauren, which contributed to my incessant crying the night before…knowing that chemo or radiation, could take her long beautiful hair.  This bandana turned head cover could be a more practical gift than Alex might have anticipated. 

As hard as the hair loss was to think about, it was much easier than entertaining thoughts about how bad this brain tumor could be.

The phone rang in the middle of our gift exchange, with a doctor telling me that we needed to head to the hospital to meet the surgeon.  I replied that it was our Christmas.  We needed some more time.  We would leave in an hour.  I have no idea what sort of scheduling problems that I might have caused with this executive decision, made in that moment.  But we did need another hour of relative normal (We had begun to set the bar pretty low, if we were using this term to refer to ‘only’ having Brent with a very serious case of high-grade osteosarcoma, rather than two of our children in the oncological crosshairs)
We needed more time as a family, in our home, before we changed Lauren’s world and that of her siblings.  Again.  The doctors could wait, for once.  I felt that we might not have this situation again, with all of us together, and I needed to have a bit more time.  We all want more time, I realize, but this seemed to be a particularly fragile moment to me.

Things moved pretty fast for Lauren.  Within 5 days, she had a PET scan to establish that the tumor originated in the brain, rather than metastasized from somewhere else.  There was a different scan of her spinal column, to gather further information, reassuring the surgeon with the fact that there was no evidence of other CNS tumors.   

We had a little Christmas here, a bit of Christmas there.  But in truth, it was all kind of a blur. 

Dan and I refused to think beyond the brain surgery on 12/28.  Brent had 2 more weeks of chemo after the New Year, at which point we were supposed to head to NYC.  We were repeatedly asked how we would manage it if Lauren needed post surgical treatment, in the form of chemotherapy or radiation.  I refused to go there in my own mind, because you cannot possibly choose…do you stay with your daughter with the brain tumor, or attend the removal of your son’s hip and the possible amputation of his leg in another state?

This is pediatric cancer, LFS style. 
This, was also the point that I stopped being able to relate easily with other “normal pediatric cancer moms,” as if kids getting cancer should ever be considered normal.  As Ramers, we were officially off in the oncological wilderness, and it has taken us nearly two years to find our way back.  There have been bumps, and detours, but I am happy to report that as a family, we are finally taking a break from hospitals. 

Both kids are currently cancer free.  Brent has his leg, and Lauren, most thankfully, was found to have a Pleomorphic Xantho Astrocytoma (PXA) that did not require further treatment.  Like when she was a baby with the adrenal tumor, Lauren was again surgery and out. 

Dan and I went together with Brent to NYC a few weeks later, and were able to support one another during Brent’s initial surgery, one lasting 18 hours.  I am very grateful for this…and have found that with LFS, I am grateful for so many things of this ilk, things that others find odd, or take for granted altogether. 

September is pediatric cancer awareness month.  As all of our cancer has been pediatric, for me, it is very hard to distinguish between LFS and pediatric cancer, which somehow seem to be one in the same.  However, many children with LFS do not get cancer.  Some adults with LFS never get cancer.  Without wishing their childhood away, I do look forward to when my kids can graduate to the adult oncology side of things…strictly for quarterly surveillance scans, of course.  

And I also look forward to when there is a cure for it all.