Cancer is not a moral failure

Back during the Cold War, cancer was often compared to communism, and vice versa. Seriously. It was during the height of those hostilities, in the early 1950s, that the British epidemiologists Richard Doll and Austin Bradford Hill published two papers that clearly established the relationship of smoking to lung cancer. Although the idea had been around for some time, many eminent scientists, most notably R. A. Fisher, were convinced that Doll and Hill had it all wrong.

Of course they were right. Sadly, Epidemiology, my chosen profession, has not had a similarly important contribution to public health since, and likely never will.

Another unfortunate downstream effect of the smoking - lung cancer story is that cancer has become associated in many minds with risky behavior. If you have cancer, you must not have lived right. This is bullshit, and a moment's thought will tell you so. The majority of smokers do not get cancer (although smoking certainly causes cancer), so even among lifetime heavy smokers only the unlucky end up with lung cancer, or bladder cancer, pancreatic cancer, or one of the several other cancers caused by smoking. Even among smokers who get lung cancer, a (very) small fraction have cancer for some other reason (genetic susceptibility, radon exposure, unknown causes, . . .), and among ex-smokers and non-smokers this fraction is much larger (100% of non-smokers, of course). 

Sometimes risky behavior is mistaken for immoral or shameful behavior. Smoking is risky, in the sense that it increases your risk of many diseases and death. Mountain climbing is risky, too, but is rarely viewed as bad behavior. So maybe the distinction has to do with how these behaviors affect other people, but that doesn't work out either: secondhand smoke does affect the health of those exposed, but bad mountain climbing decisions often lead to multiple deaths, and essentially victimless behavior such as overeating gets put in the "bad behavior" category a lot more often than it gets put in the "heroic but crazy" category.

The public health community would like you to know that avoiding risky behavior of all kinds is better for everyone, which is true enough, all else being equal. But strangely enough we all get sick and die, even epidemiologists, and how and when we die is only affected in part by how we have lived. How big a part our behavior plays is impossible to say given what we know now. The sum of our ignorance about the full set of events that lead to cancer or any other way of dying has to be counted on the "bad luck" side of the ledger, since we can hardly know to avoid something that we don't know can hurt us. 

There's a lot of bad luck out there. If you come up with an algorithm for avoiding it, you will have made the greatest contribution to epidemiology since Doll and Hill, at least. Also, you should buy a lottery ticket.

How to die, and when

Don't get all excited about the title -- that's just click bait. But in the absence of anything new to report as a patient, I'd like to step back a little and think about some life-threatening events in my past, how I slipped past them, and how those events compare to my current circumstances.

First, though, a little more justification of the title. I've had some memorable conversations with people over the years that start (in my version) with the other person saying something along the lines of: "that's the way I want to go -- all of a sudden, no warning [optionally: in my sleep]." My revulsion for this formula goes back to when I was very small and the prescribed bedtime prayer was 

Now I lay me down to sleep

I pray to God my soul to keep.

If I should die before I wake

I pray to God my soul to take.

That third line got me, and I renounced bedtime prayer just as soon as I was given enough privacy. Thankfully that was pretty young, maybe 4 or 5. I have never really reconsidered my position, so it may be the oldest continuously-held opinion I have: that I do not want to die before I have had a good long time to think about it, get my affairs in some kind of order, and say "Good-bye, I love you." to those who are still speaking to me. Thank you, multiple myeloma.

At first I thought I had three main events to recount in my past that might count as brushes with death. Then I remembered a few others, and realized that there were others, more numerous, with lower probability, some totally ambiguous, maybe some I never even knew about, etc. For example, there were a couple of spin-outs during my first year or so of driving (one on ice merging onto a busy highway, one in front of a dump truck coming down a long hill) that I hadn't included on my mental list. And one on a snow-covered road on the Red Mountain Pass in Colorado (look it up, if you haven't been there). Hard to evaluate how these relate to my continued existence, but I may be underrating them because they happened so quickly.

1. Those were near-accidents. One accident that did happen, and did happen quickly, was when I was a junior in college. Kenyon sits on what counts in Ohio as a Big Hill. On a beautiful Saturday afternoon in early October 1978, my friend Ethan and I were descending the north side of that hill on Wiggin Street on our bikes. Mine was an "English racer," with the classic trimmings: Sturmey-Archer 3-speed shifter, lugged alloy steel frame, caliper brakes, skinny tires. Ethan (a proud product of Ann Arbor-East Lansing-Detroit with loyalties to the glory days of American manufacturing) had a Schwinn (or maybe a Huffy?) with a curvilicious frame, a Bendix two-speed hub, and a highly suspicious paint job. My bike (no lightweight by modern standards) weighed maybe 30 pounds, and his weighed something like twice that. No matter, we were going downhill (see Gallileo). We were both smart enough to know that playing chicken wasn't a good idea, but subsequent events would show that he was smarter, or at least less dumb, than I was.

The events in question involved his left pedal being inserted between the spokes of my front wheel and my fork. This is a very effective way to stop a bike (mine). His bike remained quite stable. Meanwhile, I did not stop -- I flew over the handlebars (would have made a great photo or video if there had been anyone around to record it). What record there was, was written on my body, mostly in minor abrasions, except for my left hand, which was trashed. Bicycle helmets in 1978 were something you might have heard of but no one had seen one, let alone worn one. My head was doing about 30 MPH and heading straight for the pavement, when forces not directly under my control forced me to stick my left hand (the good one) out in front, and stiff-arm the pavement. I don't remember any of that, but there was a beautifully clear pattern of road rash from the hand up my left arm, across my shoulder blades, and down my right side that was easy to read. Meanwhile my head had not a mark. 

Ethan and I walked up the hill, about a mile, to the volunteer fire station. My left hand was bloody pulp, but I had just walked a mile up the hill, and the Ohio State - Penn State football game was on TV, so the firemen triaged me to campus security, who drove me to the local hospital ER, where all the appropriate things were done, most memorably removing embedded gravel with a wire brush. Ouch.

Villain: my own damn self. Hero: reflexes, Ethan, campus security (Reed, for those who were there). Long-term consequence: can't hold change in my left hand.

2. A slow-moving accident. Utah was a great place for accidental death. We avoided that, although not all of our friends did. Liz and a few friends had an ill-fated river trip, about which more some other time. I had enough sense/fear not to participate, and I was right for all the wrong reasons. One time that I failed to avoid danger -- indeed I was the prime instigator -- involved a desert backpacking trip in what is now (but might not be for much longer) the Grand Staircase - Escalante National Monument. I recruited Liz's brother Tim for a long weekend in Paria and Hackberry Canyons in early May. I had planned a loop hike up Hackberry and a side canyon, down into Paria and out. We came in late in the day, missed the mouth of Hackberry, and found ourselves hiking up what we deduced must be Paria. It was a beautiful hike, and rather than retrace our steps and go back to the car, we decided to reverse the route. The guidebook was written by a highly productive Canadian who had written dozens of trail guides to southern Utah but must have hiked so fast he wasn't great with details. The first night was great: camping in a side canyon of the Paria that was easy to find, gorgeous, and had almost no sign of human activity. In the morning, I was awakened by a VERY loud buzzing in my ear, and leapt up (reflexes again) thinking ground hornet, snake, or something terrible. It turned out to be a hummingbird checking out my ear as a possible flower. Day two we followed that canyon uphill, trying to find a "beehive-shaped rock" that would lead us across the high country. Turns out that every rock in the high country looks like a beehive (also there are a lot of bees). So we kept going up the canyon until it was clear that we had a problem. Water was getting a bit low. At this point, to my undying gratitude, Tim took over, and climbed (with full pack) to the top of the highest beehive and made me come up and see what he saw (I dropped my pack, however). Finally we could see our problem -- we had gone way north of the route we had selected, and had to figure out which of several deep side canyons to aim for (all but one of which were said to be "box canyons" without a survivable way in). It was a little after noon, hot, and there was no source of water in the high country. My cheery pictures of cactus flowers were becoming pictures of bones dried in the sun. Cue Ennio Morricone.

We chose a route that put us back in the general direction of where we thought we wanted to go. The closer we got to the canyon, the steeper the approach became, but we could see there was water down there. We tried several approaches, to no avail. Finally, Tim found a nearly circular wash head that looked passable, and we tossed our packs down and slid down the sandstone into a spectacularly beautiful side canyon, with a cute little stream and a healthy population of desert pupfish. We still weren't sure where we were. Eventually we worked out that it was Stone Donkey Canyon, one of the supposedly inaccessible box canyons, well north of our objective. From there, it was a nice long wet hike in the narrows down to where the car was parked, and, in one of those improbable (in Utah!) juxtapositions of need and fulfillment, a Navajo family pulled into the turnout as we exited Hackberry Canyon, and offered us cold beer.

Villain: my own damn self, speedy Canadian guy, geology. Hero: Tim, guy with beer. Long-term consequence: GPS?

3. Unintended consequences. I found I had MM in the Fall of 2015. By then, I had a lot of issues with my department Chair, and enjoyed telling him that I would not be available to teach in the next semester, without telling him why. I also told him that if he wanted to find the source of the low morale in the department, he should look in the mirror, and walked out of his office. He has not spoken to me since. The day after that meeting, I was scheduled for a session of chemo, with the attendant blood work. As it happened, my white cell count was basically zero, meaning that I had no useful immune system whatsoever. The hematologist thought that most likely I was having a reaction to one of the ancillary drugs (Bactrim), and that I should stop what I was doing and report immediately to the ER if I had signs of fever. Sure enough, a few hours later I started shaking like a leaf with a fever of 102. I was quickly admitted (not without a lot of questioning looks from everybody else in the ER who had probably been there for hours, nor without learning that my hematologist did not have admitting privileges to the hospital he had told me to report to). The next few nights I had continuous infusions of IV antibiotics and antivirals, fever dreams, and my general feeling that this might be the end. Daytime was better -- Liz and I were working on a grant proposal, and the isolation of that room was an unexpected bonus to the writing process, although I tired easily [the grant got good scores, but was not funded]. Another important plus was that Rosie introduced me to Words with Friends, a game we have been playing more or less continuously ever since (by the way, it's your turn). Dropping Bactrim has been effective in preventing and recurrences of the immune system crash, so it's all good (sort of) now.

Villain: Bactrim, RNB and KBB. Hero: Liz, Keith Carter (my primary care doc -- with admitting privileges), Rosie. Long-term consequence: new grant deadline strategy, new hematology practice.

In each of these cases, my destiny was completely out of my control, once I got to the point of near-, or near-near-, death. I am still confident that it's better facing an inevitable, but slow, path to death from cancer, even if I haven't yet accomplished much in terms of getting my affairs in order and telling all of those who need to know that I love them. But of course you're reading this -- I love you! -- Goodbye, if not just yet. More to come.

Cosmetics

The chemotherapy has settled into a regular routine now, 21 days of Ninlaro, Revlimid, and dexamethasone, followed by one week with just dexamethasone. So far, this seems to be working in the sense that the kappa (that's the protein produced by the tumor cells) levels in my blood continue to decline. There's still about 7 times as much kappa as lambda (produced by properly working plasma cells), though, so there's plenty of work left to do. While all this is happening, I feel good most of the time, and I've been able to get out on my bike quite a lot during this weirdly mild winter.

When I don't feel great, it mostly seems to be something related to the drugs. Besides the chemo trio, there is a set of old-lady-who-swallowed-the-fly companion drugs, to prevent or treat possible consequences of chemotherapy: an antibiotic (doxycycline), an antiviral (acyclovir), aspirin (to prevent blood clots), prilosec (to prevent heartburn induced by dexamethasone). And stool softeners and laxatives for the usual reason (also a consequence of dexamethasone). All this is just now a part of the daily cycle.

There are a couple of things that are puzzling, and we're trying to figure them out, if only out of curiosity. I've already mentioned the rash, which I blamed on shrimp. It turns out that even now that I am avoiding shrimp, the rash still occurs, then fades after a week or so, seemingly in relation to the chemotherapy cycle. Another cyclical feature is an obnoxious rosacea or acne-like condition that will overtake my nose and surrounding skin very quickly and disappears just as quickly. The rash is still mysterious, but the acne seems to be following a predictable pattern at this point, peaking during the last 7 days of the 28 day cycle, when I am taking only the dexamethasone. On the first day of the next cycle, I take the Ninlaro and Revlimid, and the sores disappear rapidly. Of course, I'd like to know which is doing the job, but what I'd really like is to find something I could use during that week to control the nastiness.

Less annoying, though peculiar, is the fact that my hair has become curly. I'm happy to have it back, and the novelty of having curly hair is fun, although I have no idea how to deal with it. Liz has helpful advice, of course--in fact, my hair looks a lot like hers now. We've been speculating about how this happens at the cellular level. It doesn't seem possible for it to be a genetic effect, because that would be confined to one or a few follicles. Instead, it seems that all the hairs on my head decided to become curly in unison--so the follicles must be talking to one another. Maybe there's some literature on this out there somewhere.

Full disclosure: I've had curly hair before, sort of--a mid-70's perm, which explains why I didn't get many dates in college. I blame Mike Schmidt for this epic lapse in judgement. Never mind.

The return of the shrimp

So I'm most of the way through the first cycle of post-transplant chemo, have my hair back (I promise to post a new photo soon), even had a haircut the other day. All the lab numbers are looking good enough--I could wish for a little more hemoglobin, and the kappa could go down further, but I am not complaining and feel pretty good. Almost all my current complaints are related to my old friend dexamethasone, and even those are greatly reduced by the lower dosage.

So it was a little alarming to find my torso, neck, and arms covered with hives a couple of days ago. It didn't feel like much, but it sure looked like something was going on. Fortunately, I had my monthly oncologist visit scheduled for the next day, and we figured we could discuss whether this was some kind of adverse reaction when we came in the next day. So we reported for duty at 7:50 AM, barely caffeinated, and went through the prelim paces (draw blood, insert IV tube, wait for labs, check vitals, check the med list, are you in any pain), and then I mentioned to the nurse that I had hives, just like I used to get when I ate shrimp . . . and Liz and I looked at each other and I don't know whose draw dropped lower.

I had been allergic to shrimp and other crustaceans since I'd had an arthrogram (involving a largish injection of radioiodine) at age 16, but the allergy had faded over the years and I had enthusiastically welcomed shrimp back into my diet, especially in the last couple of years. A great sustainable, highly nutritious source of protein, really easy to cook and mighty tasty to boot. Two nights before the visit, we'd made a (gluten-free, for those of you keeping score) pasta with a cilantro-jalapeno-lime-cream-shrimp sauce. It was very good, and I'd eaten leftovers for lunch the following day. What's more, the last night we were in Maryland after Dad died, I'd had shrimp and grits at a great restaurant in Frederick.

I will probably have no more. I'm guessing here, but I'm pretty sure that the stem cell transplants have reset enough of my immune system to have restored the old shrimp allergy. It's a minor thing, in context. I will remember those shrimp fondly.

postscript

We have been sifting through the memorabilia since my father died, and it's hard to keep straight what has been posted where. Just for the record, I want to put this photo here. It must have been taken when Dad was in high school (1944 or 1945, I guess). I think it has that mythic quality of old photos: all the thousands of images we can generate now, cropped, shopped, auto-tuned ad infinitum can't hold a candle to it.

In Memoriam

My father died last night. He had been declining for a long time, heart, kidneys, and brain more or less in sync, and while at the end the turn for the worse seemed sudden, I think it was really just the result of a long slow descent, like an airplane landing (safely) in the fog.

I have the impression that stoicism is having a moment, appropriate for confusing and difficult times, and coincidentally Dad was the paramount example of stoicism among all the people I've ever known. He was famously self-contained. He grew up poor on tenant farms during the Depression, the family abandoned by his father at an early age, finding an escape route by working as a stable hand for posh families on the Main Line.

In spite of circumstances, and his legendary unwillingness to speak, he managed to become Class President and Salutatorian of his high school class (1945). According to legend, he enlisted in the Navy to avoid having to give a speech at graduation. As it happened, the war ended while he was still in training at Pearl Harbor, so he did a brief stint in postwar Manchuria, then a few months in Japan. He was discharged in 1946, but still owed Uncle Sam the best part of a year, and was called up for service in Korea in 1951. There he was attached to a logistics unit, set up to distribute pay to soldiers and sailors invading the North--which service was abruptly interrupted when the Chinese army routed the UN troops and the entire enterprise was abandoned in a mad scramble for the ships. When his term of service was over, he was offered a chance to take Navy pilot training, but was not enamored of the prospect of landing planes on ships, and decided to come back home instead. Not long after, he met and married my mother (BTW, the second most stoic person I know). They were married for 64 years.

His love for and ability with horses was something I didn't really know about until Karen and I were old enough to be introduced to riding lessons when I was 10 or so. I was a sad disappointment to him, lacking both ability and confidence, but Karen took to it. It was only a few years later we moved to a small farm with pastures and surrounding open country, and horses re-entered his life in a major way.

From that point on, I watched the most interesting developments in his life from a distance, although he had considerable (I won't say endless) patience for my insistence on fishing, tennis, ping-pong, horseshoes, and other recreations more compelling to me. Until age became a major factor, he was consistently better at all that stuff than I was, and my adolescent frustration fueled some pretty serious, seriously one-dimensional, competition. It might be that the whole drama was contained within me--an outside observer might have had trouble finding any drama--but I thought it was real at the time.

Dad's competence (and his confidence) was such that he rarely hesitated to quit a job when he had had enough. Mostly he had a new job within a few weeks, and he generally he seemed to feel better off for having made the change. Not always, however: he did a stint as "Mr. Goodwrench" at a local Chevy dealer, and hated the association with a lame but well-known advertising campaign. He quit that job too.

I think his glory days came in the decade or so after he retired (maybe a trifle early, truth to tell). He became a full-time horseman. Between fox hunts, horse shows, and the daily cycle of feeding/watering/grooming/exercising/mucking out, he was fully engaged and extremely good at his work. This was a job he didn't want to quit, and he didn't. He was still working at horses last year, in spite of age, infirmity, and people finding him an easy mark. If that could have been sustained, I think he might have lived forever.

Overdue update

Lots of changes in the last few weeks. I've started the next round of chemotherapy, with a new oncologist, gone on long-term disability, and finally managed to arrange a quick visit to Maryland to see Mom, Dad, and Karen. 

Dad's cognitive slippage has continued, and he needs pretty constant help. While he has trouble remembering lots of things, he is still pretty certain that he does not need to take instruction from his wife or daughter, so professional assistance is the only thing that works (my own feeble efforts are no better rewarded than Karen's or Mom's, and in any case are too infrequent to do much good). So he will be moving into assisted living soon. Mom will stay in their current apartment, which is right across the "street" (really it's a parking lot). I was happy to find a decent last-minute airfare and squeeze in a quick pre-Holiday visit, complete with a mini-Christmas dinner (glorified finger food). It wouldn't have impressed an outside observer, but our little gathering will rank right up near the top of my Christmas memories.

As for me, I am feeling good, and the new chemo routine seems a bit easier to take than previous rounds, partly because the new proteasome inhibitor (Ninlaro or ixazomib) is delivered orally rather than by injection, and especially because the dexamethasone dose is only 1/4 of the pre-transplant dose. I still go in for weekly blood draws, but am responsible for managing all the meds myself. Everything is on it's own schedule, so it's not quite trivial. Quoting from the Clinical Note: 

He will start with Ixazomib 4 mg/week (days 1, 8, 15 every 28 days), lenalidomide 25 mg daily days 1-21 every 28 days, and dexamethasone 20 mg days 1, 8, 15, and 22. Supportive care would include acyclovir 400 bid, aspirin 325 mg daily. 

The Ninlaro is something to behold. A 28-day supply consists of 3 capsules, and according to Express Scripts, they pay a little over $12,000 for those (I think this includes the negotiated discount!). Each $4000 cap comes in its own fancy (cardboard) box, although you might hope for a little gold leaf or at least some decent inlay at those prices. Of course, its true value lies in the unobservable things it does, and I don't want to sound ungrateful--I am depending on this stuff to keep me alive--but still.

Rosie is here for the week, and we have somewhat belatedly got our holiday situation together. The tree is a little on the short side. I swear we weren't (much) slower than usual in our tree shopping, but all the usual sources were mysteriously tapped out. I blame my fellow consumers for being over-eager. It's a cute tree, anyway, and Rosie was able to put the angel on top without benefit of a stool or ladder. 

2016 has been a strange year in so many ways. I guess I'm ready to take my chances on the next one. What could possibly go wrong?