Go Ask Alice

Ten days ago I a got a call from a radiation oncologist who told me that I probably needed to have three weeks of whole brain radiation to treat lung cancer metastases that had spread to my noggin. He was very kind and meant well; I said thanks, but no thanks. I don't have lots of extra brain tissue to spare, and the thought of irradiating the good tissue along with the bad gave me serious pause. The next day, with the encouragement of the good folks I have come to know in the ROS1 cancer community, I called the clinic of Dr. Alice T.  Shaw, an internationally renowned ROS1 and ALK lung cancer expert at Massachusetts General Hospital in Boston. Dr. Shaw has been running clinical trials of targeted therapies that treat lung cancer brain mets and overcome resistance to older treatments, and I wanted to see if I could get in on one of those. To my surprise, I was able to get an appointment with her for the following week!

After meeting with Dr. Shaw and her partner Dr. Jessica Lin on Tuesday this week, we determined

that I should enter Dr. Shaw's trial for a drug called lorlatinib. It has shown some success in overcoming ROS1 crizotinib resistance caused by new mutations (mutation resistance to my old medicine, crizotinib, is probably why my disease is no longer stable), and it treats cancer metastases in the brain. The hope is that if the drug works for me, I won't need to have any radiation at all, that the brain mets will resolve, and the drug will keep the metastatic cancer in check for months or even years. So today, I got my new medicine! That's me looking ecstatic in my lucky Elvis Presley Crown Electric work shirt.

I'm gratefully and cautiously hopeful. There are a few things to keep in mind, though. This medicine is a treatment, not a cure. It works for some people, and not for others. If it does work, we don't know how effective it will be or for how long it will work. The last drug I was on, crizotinib, has worked for years for many patients, but it only worked for a few months in my case. One thing we hear over and over again in the cancer community is that "each person's cancer is different" and "each person responds differently to treatment." Cancer is a designer disease, but with new targeted and immunotherapies, researchers are developing designer treatments.

To get that designer treatment and to make sure it fits, I will have to go to Boston once a month for evaluation and to pick up the medicine. While the cost of the medication is covered by the pharmaceutical company as part of the trial, I will need to cover my own travel expenses. Thankfully, I have some resources. And if the trials are successful, the drug will become a commercially available standard of care, and eventually patients will be able to get it locally instead of having to travel to a trial site.

If it appears that the medicine is not working for me, or if it works and then stops working, or, if for some reason my body can't tolerate the drug, I will no longer be able to participate in the study and will have to seek another course of treatment.

So, those are the challenges. The hope part is more obvious. We hope the drug works. We hope I can stay on it for a very long time. We hope by the time this drug stops working, there will be another treatment, or, in the best of all possible worlds, even a cure.

And of course there's gratitude, especially for family and friends who have been sending financial resources, good wishes, and prayers my way. Also, I am grateful to have had the resources to make this trip to Boston and to meet scientists who are changing cancer treatment for the better, one genome at a time.

As a person of faith, I am also grateful for the masses offered, the novena's said, the prayer lists, the woodland rituals, the sage, and the beseechings to the saints. I believe in all of it. I believe in miracles. I also trust science. Together, they are awesome!

Steps to End Lung Cancer

This Saturday, my family and I will be participating in the American Lung Association Lung Force Walk in Nashville to raise funds in support of lung cancer research, advocacy, and education. Lung cancer is one of the deadliest forms of the disease and also one of the least funded in terms of research. Lung cancer is the number 1 cancer killer of women. We need to do more to fight this terrible disease. If you are in Nashville and would like to join us on our walk, or if you'd just like to support us from afar and help to end lung cancer, please visit my team page here:Team Leslie. Thank you for your support!

And the Hits Just Keep on Coming

I consulted with a radiation oncologist on Friday about the metastases in my brain. He showed me the MRI image, and it looked like my grey brain has acquired a bunch of white freckles. Those are the mets. At the time, the rad onc was hopeful that he could treat those freckles (my good friend Ann calls them fuckles) with stereotactic radiosurgery (SRS), a therapy that targets just the mets and leaves the rest of the brain untouched. It can have some icky side effects, including some memory loss (think Eternal Sunshine of the Spotless Mind), but generally it is much safer and less damaging than an older technique, whole brain radiation therapy (WBR). The SRS technique is sometimes referred to as cyberknife or gamma knife, and it is effective if there are not too many spots to treat. How many is too many? Hard to say exactly, but generally once we move into the double digits in terms of the number of metastases, things can start to get dicey.

So, as I said, on Friday during our first consult, the rad onc was willing to consider SRS, even though he was counting sixteen or seventeen mets. He gave me a copy of the MRI image and told me to go home and visualize the white freckles turning back to grey. But, after examining the MRI more closely and consulting with another rad onc, he called on Monday to say that, as it turns out, not only are there a lot of mets, some of them are problematically located in a cluster. As he sees it, SRS is not going to be an option because of the location and number of mets. He recommended whole brain radiation therapy instead.

Well, those who know me know I've been doing my research. And what I've learned after chatting with other ROS1+ patient-advocates and reading a fair number of medical journal articles and summaries from oncology conferences is that the benefit of whole brain radiation (namely that it stops tumor growth) does not necessarily outweigh the potentially negative effects (serious cognitive decline, language loss, and memory loss). It can wreck quality of life, and it does not really improve overall survival. WBR is considered more of a last-ditch palliative effort. The thinking about WBR in the past has been like this: Late stage lung cancer patients don't live very long anyway; if they have brain mets, at least we can treat them for the pain and edema and other effects the brain mets cause so the patients will be more comfortable. Since the patients will die pretty soon anyway, cognitive loss is no big deal, and besides, the brain mets will cause cognitive loss anyway, and, well, whatever.

So, I'm not doing that.

What I am planning to do instead is to consult with a ROS1 cancer specialist who is heading up some clinical trials of a new generation of tyrosine kinase inhibitors that overcome crizotinib resistance (possibly caused by a new mutation) and treat brain metastases. I have an appointment in Boston for next week. I may not be a candidate for the trials, or even if I am and get in, that doesn't mean the medicine will work. But it makes a whole lot more sense to me to try that than to, ya know, get my WHOLE BRAIN IRRADIATED! I think the rad onc means well and wants to help, and he was very kind, but in encouraging me to consider WBR, he's following an old protocol. Based on my research and discussions with other ROS1+ patients and patient-advocates, I think I still have some better options, so I'm going to pursue them. F**k the fuckles.

And the Scans Say

Disease progression. That's what my scans from this week show...tumor growth in the lungs and metastases to the brain. Apparently my wonder drug is no longer working wonders. Given that the typical median time for remaining progression-free on crizotinib is 18 months, and given that I am acquainted with a number of ROS1+ patients through a Facebook support group who have gotten several years without progression on the drug, I am really disappointed that crizotinib has not worked so well for me, and that I've only gotten 6 months. Still, I am grateful for those months. I've been able to live a more or less normal life, return to work, and do fun things with family and friends. So, there's that.

Why isn't crizotinib working anymore? We don't know. But, when I had my genomic profile done back in November 2017, a number of other mutations were identified along with ROS1. It's possible one of those is causing the cancer to progress. The problem is, none of those mutations has been as well-studied as ROS1, so there aren't targeted treatments available for those specific mutations. And honestly, we just don't know if one of those mutations is actually causing the problem. It is possible that a different TKI (tyrosine kinase inhibitor like crizotinib) currently in clinical studies might be effective, but we just don't know. It's also possible a combination immunotherapy/chemotherapy treatment could stabilize the disease, but again, we don't know. Researchers are studying mechanisms of resistance, but there are so many factors that can contribute, which means getting answers as to how to address resistance is taking a good long while.

My oncologist's most pressing concerns at the moment are to have the half-dozen small new brain mets treated as quickly as possible and to figure out a new treatment plan overall. So, I have a consultation scheduled with a radiation oncologist for tomorrow, and if it seems like a good option, I'll likely get the brain tumors zapped. It's not a permanent solution, as the chance of recurrence is pretty high with just radiation alone, so we'll definitely need to add another kind of treatment to address that and the progression in my lungs. Dr. Peacock is meeting with her tumor board this morning to discuss my case, and we'll start strategizing after that. I'm leaning very strongly toward getting another consultation with a ROS1 expert  as well to learn more about some clinical trials for which I might qualify.

Honestly, this is not the news I expected to get, as I've been feeling quite well. I just wrapped up grading for my spring semester and had decided, for the first time ever, not to teach over the summer so that I could take time for other things I love to do. In fact, I've been feeling so well that my husband and I had been making tentative plans to do some ambitious traveling to visit friends and family. I was envisioning a summer of road trips and even a quick jaunt across the pond to visit friends in Holland. Now all that planning seems like hubris. We still might get to do some of those trips, but it will just depend on my treatment plan at this point. Stay tuned, and I'll keep you posted.

Language Effects

Cancer does weird things to the body -- it deforms tissue with tumors, twists DNA into bizarre mutations, establishes rowdy colonies far from the original tumor site. It can shut down organ function and stop the breath. The disease is both killer pirate and imperialist parasite. But it doesn't change just the body; it alters perception, perhaps in part because it alters language. Cancer gives us a new and strange vocabulary for talking about the disease and its treatment.

Because I think mostly in words, this new Cancerland dialect is sort of fucking with my reality. I mean, I LOVE acquiring new words, truly. I hoard them in synapses and work them into conversation or poems at every opportunity.  But cancer words...hmmm...well, it feels a little like my vocabulary is growing tumors.

Linguistic signifiers in Cancerland are mostly scientific. Some originate in Greek; some just look like Greek and Klingon got together and made compounds.  For instance, the polysyllabic names for our medicine might end with "nib" (meaning they are small molecule inhibitors) or "mab"(monoclonal antibodies), and they have big-pharma-invented prefixes attached to stems derived from chemical names, so they end up looking unpronounceable. Try saying pembrolizumab or ipilimumab five times fast. For ROS1+  cancer, we take crizotinib, lorlatinib, entrectinib. Sometimes, drugs can get a cute nickname we use for shorthand, like ippy for ipilimumab. Once these nibs and mabs go on the market with FDA approval, they get new brand names, like Xalkori, the medicine formerly known as crizotinib.

In Cancerland, we use acronyms and abbreviations as words. If you have mets (metastases), your cancer is colonialist. Our doctors are our Oncs. If you need radiation, you'll see a Rad Onc. When you have Stage IV disease, you wonder how long you'll have PFS (progression-free survival) on your TKI (tyrosine kinase inhibitor like crizotinib), or if you'll ever reach NED (No Evidence of Disease). For mets in the brain, you may have WBR (whole brain radiation) or SRS (stereotactic radiosurgery).  We can have DFS (disease-free survival) or a DFI (disease-free interval). Research studies consider OS (overall survival) rates. And of course have fun reading those scan reports, laced with abbreviations and names of body parts you might not have known you had.

But probably the most common word in the parlance of Cancerland isn't medical or scientific. We all use it -- doctors, patients, researchers -- a lot. It's a four-letter word that translates well into other dialects: hope.

"Outliers" and Hope

One of the cancer survivor blogs I came across shortly after my diagnosis was Linnea Olson's Outliving Lung Cancer. I found it by googling, as I often do, "surviving stage IV lung cancer." I had seen all the terrible prognosis data, and by that point had resigned myself to believing I had maybe about 18 months, at best, left on earth and that the remaining days weren't going to be pretty. Then I found Linnea's blog. She'd been diagnosed with lung cancer in 2005 and was still kicking around the planet a dozen years later! And so much had happened in her very full life during those years -- raising kids, getting a divorce, moving into an artists' community. I clicked through her posts the way a choco-coffeeholic pops chocolate-covered espresso beans. How could this be? How could someone with Stage IV lung cancer be alive so many years after diagnosis? What magic was at work here?

As it turned out, it wasn't magic, exactly, but science. Doctors had been able to identify a genetic driver for Linnea's cancer, the ALK gene rearrangement. That was in the early days of targeted therapies, and after surgery and some failed therapy, Linnea became Patient #4 in a Phase I study of crizotinib. The new experimental drug (the one I am currently on, which is now considered standard of care) kept her cancer in check for several years. Since then, she's moved on to some chemo and other targeted therapies. Just as she was becoming resistant to one therapy, another became available. In other words, Linnea is living proof that we are truly each day on the cusp of possibility in cancer treatment.

My despondency began to lift. I started to believe that a lung cancer diagnosis did not have to be an immediate death sentence.

Now Linnea is a 13-year survivor, an "outlier" by late-stage lung cancer standards. She wrote recently about forgetting to observe her cancerversary, and what a great feeling it was to realize the day had passed like any other normal day: Thirteen Boffo Years and Counting. And here's a link to a great article about the state of research, Targeting Cancer, featuring Linnea.

We are repeatedly told that "each patient's cancer is different" and that our responses to treatment will vary due to all sorts of factors. For some of us, nothing will work. For others, something works, but not that well, or only for a little while. Others get a good long ride on one treatment before having to pursue another. Some people get cured. In Linnea's case, she's journeyed through quite a few different treatments now, including different TKI's (tyrosine kinase inhibitors like crizotinib). I for one am grateful she is telling her story of persistence, hope, and courage.

Next time someone asks me what I want to be when I grow up, I'm going to say "an outlier."

Scans and the Prosperity Gospel

"In the health-conscious mind-set that has prevailed among the world's affluent people for about four decades now, health is indistinguishable from virtue..."--Barbara Ehrenreich Natural Causes: An Epidemic of Wellness, the Certainty of Dying, and Killing Ourselves to Live Longer.

I recently read an excerpt from Barbara Ehrenreich's new book here:Why I'm Giving Up on Preventative Care. Her point in the quotation excerpted above resonated with me, especially because I have just finished reading Kate Bowler's memoir Everything Happens for a Reason and Other Lies I've Loved. In her book, Bowler examines how prosperity gospel ideology affects our thinking about illness. When a person becomes ill, especially with cancer, there is something in our Puritan-American DNA that suggests the illness is somehow the sick person's fault, that we've not worked hard enough at doing what it takes to be well. In prosperity gospel terms, we've done something that has put us out of favor with God, hence we have lost His protection against illness. In terms of new age healthism, another kind of prosperity gospel, we haven't eaten organically or exercised properly (tai chi, yoga), or have not taken the right supplements. In the world of ubiquitous medical testing, if only we'd had our regular screenings, we could have found the problem before it was a problem. The repeated message: if you are sick, you are entirely responsible for contracting the illness, and you need to do something to fix it. If it is unfixable, you just need to try harder. Sigh.

In her seventies now, and having survived breast cancer, Ehrenreich has decided to call it quits on most routine medical screenings like mammograms and dental x-rays. She rejects the medicalization of aging and death. While she's not suggesting that all of us forgo this kind of preventative maintenance, she does take issue with the medical-industrial complex that feeds on our fears of illness and death. I admire her strength in walking away from it.

At some point, I know I'm going to have to make decisions about how or even whether to move forward with medical treatments. Stage IV lung cancer patients have to face the likelihood of the cancer's eventual resistance to treatment resulting in metastasis to brain, bones, and other organs. At some point, the disease can become unmanageable; treatment yields diminishing returns with regard to quality of life. Thankfully, I'm not there yet; for now, my treatment is working, and the disease is under control. In fact, crizotinib is working so well, that some days I don't even notice my symptoms, and in the busy teaching days, there are times I even forget that I have cancer. Plus, when my current treatment reaches the end of its usefulness, there are some other options that may work for a bit to push back the disease. So, in my situation, I'm not ready to reject the testing that becomes a major part of Cancerland topography. I'll still get the routine CT scans, the occasional brain MRI, and monthly blood work to make sure I'm staying progression free, or to detect when I am no longer progression free.

The challenge here is in the temptation to live scan to scan. It seems a small way to live, and while I'm not rejecting the scans themselves, I want to reject scan-to-scan thinking. Such thinking is the thief of joy. I also want to reject the ideology that equates sickness with lack of virtue, with somehow not doing the right thing; that notion robs sick people of agency and dignity. I'll none of it.