When noncompliance is your best option

Last week Lungevity hosted the Scientific and Clinical Research Roundtable in DC and I was invited to be the keynote speaker. Really. I could be wrong but I have a sneaking suspicion that most of my invitations to speak will not be followed up with a second invitation. I have transitioned unequivocally from advocate to activist and I’m not sure everyone is ready to hear what I now feel the strong need to say. In a nutshell, I feel that clinical trial participants are the graduate students/sherpas/indentured servants of the cancer world. We do the heavy lifting–it’s all guts and no glory but we can’t say no because we’ve got nowhere else to turn.

I’ve shared the entire transcript of my talk here. It’s a long haul and for those of you familiar with my story, there will be some repetition in the first half. But then I get down to nuts and bolts (or screws and nails, the way I describe my neuropathy).

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Good afternoon. I am happy to be here today. In fact, I am happy to be here every day.

It’s not something I take for granted, ever. The first thing I do when I wake in the morning is to say ‘I’m alive.’

The wonder never lessens. And that is because a little over eight years ago, I heard the words ‘there is nothing else we can do.’ Never one to turn away from the truth I wanted to know more, I wanted to know how much time remained. The answer was three to five months.

And so I began to let go of my life—and to help my family do the same. Both I and my youngest, then eleven, started individual counseling. I travelled to Colorado, for a hastily organized and tearful family reunion. I said my goodbyes.

But then at my next oncology appointment something totally unexpected happened. A recent biopsy had been submitted for genetic testing and had come back positive for a newly identified target in non small cell lung cancer, an ALK translocation. A phase I clinical trial for an experimental agent targeting ALK mutations had begun recruiting at my hospital. So far there had been only one other participant and he had died within weeks of starting the trial, in part because of side effects of the experimental agent.

It was not a lot of information to go on but I liked the sound of targeted and my oncologist, though cautious, seemed enthusiastic as well. I hoped the drug wouldn’t hasten my death, but I knew that if I did nothing, my cancer would surely kill me. I was between a rock and a hard place but the way I saw it, this clinical trial offered at least a sliver of hope where now I had none. And I said yes.

On October 1st of 2008 I became the fourth person in the world with non small cell lung cancer to take crizotinib. Seven weeks later, as we went over my scans, my oncologist characterized my response as flipping amazing. And all those goodbyes became hello, I’m back.

I got lucky, really lucky. I was at the right place, in the right time, and with the right oncologist. And I’ve been lucky ever since, having now been an early participant in three phase I clinical trials. Innovative medical research has extended my life far beyond what I ever thought possible.

This has meant the world to me and my family. In June, almost eight years to the day after I was told I had three to five months left to live, I watched my youngest graduate cum laude from Phillips Exeter Academy. Four weeks ago he began his freshman year at MIT.

And me? I’m loving life, all of it. 45 when diagnosed, I will turn 57 in November. Between my three kids, art, writing, advocacy and my plethora of friends, I couldn’t be busier.

Of course, I do still have lung cancer. Although I have enjoyed two years of stability on my current therapy, my most recent scan showed progression. I have scans again in two days, and by next week, I should know if it is time to switch things up again.

I hope that medical research will stay one step ahead of me. I also hope my body will hold out.

It has been my privilege to participate in clinical research. But it has also been my burden. I have shared my joy, my gratitude. Now I would like to share my concerns and I feel I have rather a unique perspective for doing so.

There was an old paradigm for clinical trials, and that was that they were usually a one off.

When I enrolled in the trial for crizotinib in 2008, it was with the hope that it might extend my life for several months, nothing more than that. Because honestly, there was no precedence.

Even once it became clear that I’d in fact responded to the experimental therapy, my joy was tempered with the knowledge that I would eventually develop resistance to the drug and that when I did, I was once again out of options. Because that is where things stood in 2008.

I never imagined that I would go from trial to trial, and, at that time, I’m not sure anyone else could have imagined such a scenario either.

But I have and my participation has kept me alive. However, it has come at a price.

Enrollment in a clinical trial requires a greater commitment of time, resources, blood and tissue. And often, additional scans as well.

The clinical trial that I am now enrolled in initially had a protocol that required not only a Chest CT scan, but an abdominal scan, brain MRI, and echocardiogram every six weeks. I might point out that a schedule more akin to every three months is the standard of care when it comes to scans for a metastatic patient. I might also point out that my histology, invasive mucinous adenocarcinoma, almost always stays confined to the chest when it metastasizes, and that I have never had brain, bone or abdominal mets.

Initially my trial also required a bone scan, every three months. I had the first one, and afterward was handed the the same little card that you carry around for three days after every PET scan, just in case someone in law enforcement or at an airport picks up remaining background radiation. This struck me as ludicrous, and also an unacceptable risk with neither scientific justification nor personal gain. I told my oncologist that I wasn’t going to get any more bone scans even if it meant dropping out of the trial. Fortunately she is as invested in my future as I am and as a PI in the trial, was able to contact the sponsor and had the protocol changed.

Fast forward to July of 2015 when I happened to see a report in the Stanford Medicine newsletter regarding DNA damage seen in patients undergoing CT scanning. This line in particular jumped out at me ‘“We now know that even exposure to small amounts of radiation from computed tomagraphy scanning is associated with cellular damage.” I started to think about all the scans I’d had and would continue to get and wondered if anyone was keeping track. With access to my electronic medical records, I decided to tabulate the results myself and what I found shocked me. Now keep in mind that this only reflects care and clinical trial participation at my current hospital, and does not take into account previous imaging, such as the scans that led up to my diagnosis. Or workups for other health issues, or routine imaging such as mammograms or dental work.

When I sat down and counted I found that I’d had 19 chest x-rays but also close to 70 CT scans of my chest. For those of you who don’t know, each chest CT scan, even those that are low dose, has the equivalent radiation of 4-500 chest x-rays. Now multiply 400 times 70 and tell me if that is a number you are comfortable with. I was really surprised when I counted the number of abdominal scans I’d been given; 44. Given the complexity of the tissue in the abdomen, scans of that area of the body expose cells to an even greater amount of radiation. And keep in mind that I have no cancer in that part of my body. Yet. But I do have highly mutable cells.

The first CT scan of my chest saved my life. But is my scan schedule eventually going to lead to a secondary cancer?

I don’t know, but I can’t let that happen. And so I did what any reasonable person would do. I spoke not only to my oncologist, a PI in the trial, I contacted the sponsor personally. However, I really made no headway until I talked to the right person in a bar. That’s right. I have been a peer reviewer for the CDMRP for a number of years and after a session last fall I chatted up a fellow reviewer in the bar—told them my tale of woe. When I concluded he let me know that his wife worked for the sponsor and he was going to share my story with her.

Well sometimes the back door is the right one and this time the sponsor contacted me. I had a private phone conference where I spoke not only about my scans but about what I view as a rather prevalent disregard of the sacrifices clinical trial participants make. And I asked that they not only change the scan schedule, but that they pay for parking.

When I got my response it was from my scheduler. My scan schedule would not be changed. I told her to tell my oncologist that I now had no choice but to become noncompliant—that I would continue to get CT scans of my chest but there would be no more abdominal scans.

I am fortunate that my oncologist truly is as invested in my future as I am. She called me almost immediately and we discussed the situation. To my surprise, she was fully supportive, although she did explain what noncompliance put at risk for me personally as well as for the trial and my institution. I told her that if she asked me to go to Mars the next day I would do it, I trust her so implicitly, but that I simply could not keep getting scans every six weeks for the rest of my life.

The bottom line is this—currently clinical trials are monitored as discreet events, a residual of the old one-off paradigm. No one seems to be keeping track of patients such as myself, who are traveling from trial to trial. I am an outlier, an exceptional responder, and I am also a bit of an anomaly amongst the ALK positive population with my invasive mucinous adenocarcinoma histology.

But that is the point—I am first and foremost an individual, a human being. Participation in clinical trials does not cede my humanity, although it certainly does result in a certain loss of autonomy. And words like compliant and noncompliant only underscore that fact.

Per my scans—I really like to do things the right way. Also, as an advocate, this was never just about me but rather about everyone who participates in clinical trials. And so I would periodically contact the sponsor. What I didn’t realize is that my oncologist was also in continuing dialogue with them about the scanning schedule. Several months ago I got word that the protocol would be changed and that after a year on trial, participant’s scans would move out to every three months, the standard of care. When I spoke to my oncologist, I realized that it was her input, not mine, that made the real difference. But the important thing is, she respected my concerns which motivated her to request a change in protocol.

As for me, I moved to the every three month schedule as soon as I heard the news, even though it is not yet official. Jumping the gun a little, but then again, I remain noncompliant as to my abdominal scans, so what’s a skipped chest CT scan or two. And don’t think I am simply being cheeky—I donated my body to science a long time ago and I feel no guilt when it comes to a skipped scan or two.

I still wish I didn’t have to get brain MRI’s every six weeks—I’ve now had almost thirty and nothing causes me more anxiety than the loud clanking, claustrophobia of a brain MRI. Also, I am convinced that we don’t yet understand the risks—again, there is very little precedence for such a frequent MRI schedule in someone with healthy brain tissue. After reading that the contrast agent, gadolinium, is not readily cleared from the body I did request that we forgo contrast so that is one small victory.

The irony is, were this anything other than a clinical trial, say, a war or a sporting event, I and my fellow participants would not be fighting for our basic human rights. We would be decorated for our valor, celebrated, maybe even highly compensated. And we can’t even get our parking comped.

And yet, I am alive. It is a wondrous thing, and something most people take for granted.

I would do almost anything to stay alive. I already have. But I am also not willing to throw away this second chance at life by submitting to ridiculous requirements simply to satisfy the science and to speed drugs to market. As Richard Pazdur has said, ‘People are not for clinical trials. Clinical trials are for people.’ It’s imperative that we not lose sight of why trials exist in the first place. It is not to advance the careers of researchers. It is not to keep oncologists and hospitals in business. It is not to enrich sponsors and their shareholders.

Rather, it is to provide patients such as myself with an opportunity to hang onto our very dear lives.

*for a dose of happy/hopeful Linnea, check out this video interview about Clinical Trials from the Lungevity site.

Where the heart and science intersect

Way back in 2008, when I enrolled in a clinical trial for crizotinib (Xalkori), it was the only ALK inhibitor in the world. That meant that once it stopped working (and my oncologist stressed from the get-go that this was not a cure, but rather a respite from cancer) it was the end of the road.

One year in I began to develop resistance to crizotinib but without further options, I stayed on trial and eked out almost two more years. Then, just in the nick of time, a phase I trial opened for a second ALK inhibitor–ceritinib (Zykadia).

Of course, in my universe the individuals who develop the therapies that have extended my life are absolute superstars and I the ultimate groupie. I was given the opportunity to meet Dr. Jean Cui, who formulated crizotinib, at the Xalkori Launch in 2011 and I became her number one fangirl.

I couldn’t tell you the exact moment in which Dr. Tom Marsilje and I entered the same orbit (and nor could he, as we both have chemo brain), but he codeveloped ceritinib (Zykadia). By the time I was introduced to Tom, he was battling his own cancer and suddenly our connection became a whole lot more personal.

My friend Tom is an absolute rockstar in every sense of the word and you’d be remiss not to read this profile of him in STAT–Cancer researcher races to find a cure–for his own incurable cancer. This article hits all the high points so I’ll just provide a few more personal details.

About six weeks ago Tom was in Boston and we got together for dinner (along with our mutual friend, John Novack, of INSPIRE) at the appropriately named Miracle of Science. Obviously we should have taken a selfie but neither of us thought of it (blame it on the chemo brain). We’ll just have to do a redux at a later date.

However, the first time Tom and I met in the flesh (like so many of my friendships, ours existed in the email/social media sphere), it was entirely by accident. We were both in DC this past spring, lobbying for our individual cancers (lung and colon). I was waiting for an elevator in the basement of the Russell Senate Building and noticed a man standing with his back to me and thought ‘he sort of looks like Tom Marsilje’. Well, that man turned around, saw me, started to shake a little (we were both gobsmacked), and then I rushed over to give him a big ol hug. The serendipity of our encounter was just sort of perfect.

Anyway, count me a huge fan. Even if he if wasn’t one of the reasons I’m still here, I’d be impressed by and with Dr. Tom Marsilje.

When you can’t remember shit

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Perhaps the best greeting card ever.

First, a blanket apology to anyone whose birthday I have forgotten this year. Same goes for all those unanswered emails, texts, phone calls, missed appointments and other no-shows.

Once upon a time I and my ability to recollect were reliable. As a child, I possessed an eidetic memory and when I wished to retrieve an event it was almost as if I were watching a movie of the past in my brain. According to literature the ability to remember things in an almost photographic sense disappears in adulthood, but I am a highly visual person and always utilized a sort of Hansel and Gretel bread crumb approach; when trying to remember something I would visually retrace footsteps in my mind until I came back to the thing I was searching for.

That is, until I started my current therapy, lorlatinib. A small molecule designed specifically to cross the blood brain barrier, lorlatinib is able to deliver drug to tumors within the central nervous system. This is great news for individuals with brain mets but it also means that there may be accordant cognitive side effects. I started early in the trial during dose escalation and at a previously higher dose than I am now taking, and those cognitive side effects were so pronounced that a few weeks into the trial I felt as if I could no longer process or reason. Fortunately lowering my dose improved that scenario but I still felt as if my memory had been completely wiped and that I had suffered something akin to a brain injury.

Because I was also in the midst of a nasty divorce it was hard to parse the stress from the effects of therapy, but suffice it to say that life was challenging.

Two years out I am not only still alive, I feel almost as smart as I used to be. However, my memory is still completely shot. Add advancing age into the mix, and I think it’s fair to assume that I will continue to do things like purchase airline tickets to the wrong city (last summer) or for the wrong day (upcoming trip). It’s a little unnerving and yet you know I like to look on the bright side (cue Life of Brian). Historically I was a mental ruminator, and often made myself miserable by reviewing unpleasant situations over and over. Well guess what! Not being able to remember shit sometimes comes in handy, and I no longer dwell on much of anything.

Although my memory challenges make life less predictable, I am learning a lot about flexibility, personal forgiveness, and a whole lot of scrappy. In the case of the flight to the wrong city, I rented a car (first time ever, alone) and drove the additional 400 miles to my intended destination.

So even if I miss the boat entirely (wink wink–see above), I know I’ll still get there. I just might not remember how.

Because magic can be in a moment

I’ve gotten an adventure or two under my belt since my last post (with more to come) and I plan on divulging in detail. But before I get to all that I’d like to share a truly magical moment. On Sunday I accompanied my friends/neighbors Machiko and Koichiro Kurita and their dog Momo to Mill No. 5; an enchanted space if there ever was one. The four of us were wandering about and came across this most perfect of props. I whipped out my handy iPhone for an impromptu portrait of two of my favorite photographers and their little peach Momo. Serendipity.

Koichiro, Machiko & Momo.

Koichiro, Machiko & Momo.

It’s all Fun

Two years ago I was going through a tough patch, as I had recently separated from my husband and my health and financial situation were both a bit grim.

I spent a fair amount of time on the phone talking to my mother Evalynn and I’m awfully glad I did, as she passed away unexpectedly that June. During what would be one of our last conversations, my mother asked me what I did for fun. ‘Everything’ I said. ‘Everything I do is for fun’.

And I really meant it.

Approximately 2975 days have passed since I was told that I had three to five months left to live. Each and every one of these days has been a glorious bonus; an unexpected gift; an amazing treasure.

Recently I heard about someone who had ‘made the best’ of a similar situation where they’d received an extended reprieve from death. This individual was traveling the globe. Sounds like fun.

However, bucket lists are not an option for me–out of reach financially but also not what I really desire so much as to go on with life.

And so I have. Living each day as if it weren’t my last. Yet doing so with utmost awareness of how unexpected but also special each and every moment is.

I choose to love life unconditionally and so without judgement. It’s all good. And 99% of it–also fun. Simple stuff like waking up in the morning. Having that first cup of coffee. And then the second. Texting my kids. Hanging out with friends. Going to a thrift store. Smiling at a baby. Striking up a conversation with a stranger. Taking long walks.

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But also paying bills, sitting in a waiting room, getting blood drawn. Doing laundry, languishing in traffic, buying groceries. Watering the garden, scrubbing the tub, unloading the dishwasher. All fun fun fun. Because each and every one of these tasks is a privilege I never thought I’d have.

Sometimes it is incredibly poignant and I am reminded of certain moments from childhood: playing outside as dusk approached but knowing that a grownup would soon call us all indoors. The slight anxiety and anticipation would lend a tingling excitement and new intensity to our games. Perhaps we ran a little faster; shouted with a little more bravado, became a bit bolder than before.

That which is fading is often held all the more dear. And I am hanging onto dear life with all the joy I can muster.

xo

 

Me and my hero

 

Linnea (me!) and Dr. Alice Shaw

Linnea (me!) and Dr. Alice Shaw

Just thought this was as good a time as any to post a recent photo of me with my personal goddess/oncologist Dr. Alice Shaw. She is a rock star and with Alice by my side I feel as safe as a person with stage IV lung cancer can possibly feel. Better than that, actually. I know my doctor will do everything within her power to achieve the best possible outcome in regard to my future. That when she says we are a team, she really means it.

Her role is to watch my cancer like a hawk and to stay abreast of any developing treatment options. She’s got that. My task is to work on being as strong as I am able–emotionally and physically–so as to better bear up under both changing health conditions and new treatment regimens. To hang onto optimism and to keep the faith. And, perhaps the most challenging of all, to continue to sit with uncertainty.

It takes commitment and an incredible amount of confidence; on the part of my doctor but also myself. Alone, I don’t believe I could manage. Together, we’re a formidable team. Cancer better watch its back.

It was good while it lasted.

Stability, that is.

As any metastatic cancer patient understands only too well, what doesn’t kill you often just keeps trying.

I’ve been in this battle for so long now–more than eleven years–and most of that time has involved active combat with an ever advancing foe. But thanks to lorlatinib, my disease has been stable since June of 2014; my most sustained period of response yet. As a bonus, I’ve felt so damn good it’s been easy to imagine myself cancer free.

However, my scans have always told a slightly different story, with remaining nodules and opacities scattered here and there.

Lungs and Airways: The patient is status post left lower lobectomy for lung
cancer. There is a left lower lobe solid nodule on image 41 series 201 measuring
5 mm unchanged dating back to 5/14/2015. There is also subpleural patchy opacity in the left lower lobe image 63 series 201 that remains stable compared to 5/14/2015. There are small centrilobular groundglass nodules in the left lower lobe image 51 series 201 also stable compared to 5/14/2015 the largest of which measures 9 mm. There is a stable 2 mm right upper lobe nodule image 32 series 201. There is a stable subpleural groundglass nodule in the right upper lobe image 48 series 201 measuring 5 mm. A second groundglass right upper lobe nodule measuring 5 mm but is essentially unchanged from 12/10/2015 and 4/14/2016. A 4 mm solid nodule along the right minor fissure is stable. There are no new nodulesPleura: There is a small left basilar postoperative pleural effusion that remains essentially stable.

The words unchanged and stable are absolutely key here.

However, on my scan report today it was noted that one nodule had in fact changed size: There is a 5mm nodule on image 52 that appears to have grown since 5/14/2015 when it measured 3 mm but is unchanged compared to 3/6/2016.

Obviously it had escaped the notice of previous radiologists. However, upon reading today’s report, my oncologist Dr. Shaw reviewed the scans and agreed that this particular nodule had in fact enlarged and likely represented progression.

Nothing to panic about but a potent reminder that shit is still real.

Dr. Shaw is already talking game plan. We will scan again in three months. If the nodule continues to grow, we might biopsy in an effort to determine what the mechanism of resistance is. If it can be identified, I might be a candidate for a combination therapy of ALK inhibitors. As this is a solitary nodule and in my right lung this time, surgery is a possibility. So is radiation.

Stability may have been rattled but I’ve still got options.

And honestly, that’s the most important thing.