Programmed cell-death ligands: the trailer

I won't know until mid-November whether or not immunotherapy is recommended in my case. That makes it a little hard to get motivated to research the subject, but I don't want to be doing it at the last minute either. So I've started looking into it. The idea is that I would ``join a research study'' on atezolizumab (trade name Tecentriq, approved for bladder cancer by the FDA last May), assuming certain conditions are met as discussed below. Anyone who is interested can easily find details online, so I'm just going to give the short version.

There is a lovely term ``programmed cell death protein'' or ``''death-ligand'' PD-L1 blocking antibody. The idea seems to be
(this is all based on a cursory survey of the web, and a preliminary conversation with the onc) that PD-L1 is bad because it interferes with good guy immune cells that would like to attack the cancer.  Atezolizumab blocks or inhibits the PD-L1 so that the good guys can do their job.
In bladder cancer patients, this therapy is approved for patients who have had ``platinum-based chemotherapy'' (i.e the cisplatin), yet the disease has still progressed. That is possibly true in my case, but we will wait to see the results of the latest round of chemo.
If the cancer in the liver has been reduced or at least hasn't progressed, my understanding is that the chemo is declared a success and we don't do the immunotherapy. Of course ``success'' in this business seems to mean temporary success, apart from a few rare cases where a complete cure is obtained. One often sees the abbreviation DoR, which at first makes me think of ``dead on arrival'', but actually stands for ``duration of response''. This refers to the length of time before the bad guys start up again. By the way, a key point to be aware of when evaluating statistics is that there is a group of patients who get the immunotherapy because they are too old or in too bad of health to tolerate the platinum-based chemo. Keep this in mind if you come across gloomy death statistics; some of these people were already in bad shape for other reasons.

The second criterion for proceeding with the immunotherapy (according to the onc; the online literature is less clear on this point) is that PL-1 should be (sufficiently ``highly expressed'' on the tumor.  I think the idea is that if it isn't highly expressed, then the success rate is too low to risk the side-effects (see below) or to justify the cost. This is why they first have to send a sample of my original tumor to a lab. (Didn't know they still had it; maybe they keep it in a refrigerator in the lunchroom. Anybody ever see the movie ``The Loved One'' with Jonathan Winters? If so, you'll get the reference.)

In theory, the process of getting the immunotherapy is simpler than the chemo: one 30-60 minute infusion every three weeks (for how long, I don't know). But I assume that many more visits to the clinic are required, for check-ups and so on.

This leaves the big question: side-effects. Some people have died from atezolizumab therapy, but it's a small percentage and I suspect they're generally people who were in bad shape to begin with. On the other hand, there is the usual list of fairly common side-effects: fatigue, nausea, constipation, decreased appetite, and especially urinary tract infection. Plus a host of gruesome but less common side-effects including thyroid problems and eye problems. That last one is a potential game-changer for me. If any kind of permanent eye damage is even remotely possible, I would not do it. Even temporary problems (blurred vision, double vision and redness are all mentioned) might be enough for me to say ``no thanks''.

But it's all up in the air at this point, so I'll just wait and see. Programmed cell-death ligands, watch your step!

Date night in the infusion ward

Yesterday being a cisplatin appointment, I was in the infusion ward from 2 to 9:30. But what better place for a Friday night date?

As I had been unable to eat the dinner I ordered (explanation below), Wendy, who was already on her way, stopped at a convenience store and brought me Cheerios and milk at 7 or so. Perfect! She is a lifesaver. We could chat, or could have watched TV but there is really nothing on. Still, we had our books to read, and being in the Luxury Suite I had a bed on which I could and did fall asleep. It was almost too much excitement for one date. To sum up, with apologies to Omar Khayyam and his first English translator, Edward Fitzgerald (see the wikipedia article for a discussion of Fitzgerald's highly non-literal translation and his own interesting justification thereof):

A cup of cheerios, a touch of milk, and Thou
listening to me snore in the infusion ward,
ah, this day, this moment is paradise enow!

Now, as to why I couldn't eat: It wasn't because of the chemo; I was feeling nauseous long before that kicked in. It's the pyschosomatic reaction I've mentioned earlier. I asked Tom about it and he said oh yeah, that is a real phenomenon
they see often. Their worst case was a guy who couldn't even set foot in the medical center without throwing up; they had to move his infusions to a different hospital. Another person would react to seeing an infusion nurse in the grocery store. (Hey Tom...you don't shop at the QFC on Juanita Drive, do you?) I've noticed that even looking at the hospital menu (which actually has some good food) makes me feel queasy. In fact just typing the words gave me a twinge. It's interesting how the brain and the digestive tract are linked in that way: seasickness, for example, and as I understand it the highest concentrations of the neurotransmitter serotonin are in the brain and the digestive tract. Before your first chemo, they warn you that ``you cannot control nausea and vomiting by willpower''. Okay, but surely this reaction to simply being in the ward can be defeated? I need to get more serious
about a mental imagery/self-hypnosis approach and see if it works. Meanwhile, thank goodness my wonderful wife brings me cheerios on a Friday evening!

On the afternoon half of my stay I had Molly again, and learned something new about her. Very few people read ``classic literature''---after high school I read almost none until I got on this literature kick a few years back. At the moment I'm reading Anna Karenina, and as I had it with me, I asked her if she'd read it. ``I didn't care for it that much; too gossipy. I like Dostoevsky more, especially The Brothers Karamazov.'' Cool! I think by ``too gossipy'' she means in a soap opera-ish way. But if it's a soap opera it's a darn good one. In fact I'd like to announce this breaking news to the world: Tolstoy was a great writer!  I have the famous Karamazov brothers on my future reading list, but I think it's over a thousand pages (Anna is a mere 900) and it may be a while before I atttempt it. In any case, Molly's interest in literature was a pleasant surprise.

I have to start my infusions at 2 because my topology class gets out at 1:20. When I learned I would have to start chemo again this summer, I made up my mind I would not give up the class, and fortunately I was able to work it out with the Med people (who honestly bend over backward to accomodate my schedule; they're awesome). I am so glad it worked, because my class is just fantastic. This was unexpected because I thought with 50 students (now down to about 47)  it would be very difficult to get students engaged, speaking up etc. On the contrary, it might be the most engaged, lively class I've ever had. At last count I could
list 19 different students who've had questions or comments, and often it turns into a real dialogue. I wish I could learn more names---so far I know maybe 20---but the students seem quite impressed that I even have that many. Now I'm determined to get them all.

  My system of secret mnemonic nicknames works pretty well. It's unlikely but theoretically possible that one of my students could find this blog, so if you are such a student and recognize yourself below, please know that even when silly, the names are chosen with respect and affection. It's just a way to help me memorize. A few examples: Rasputin, Kate Winslet, Wagnerian opera guy (Tristan, as in Tristan und Isolde), Stylin', Jesse James, the fake Italian (third generation; doesn't speak the language), the Norwegian (his name isn't Norwegian, but somehow he looks Scandinavian and has the same first name as Jay's Norwegian friend), Canadian mountain man (Jasper), Punk-rocker, Compact Disc (first name Qidi, pronounced like the Italian for CD),
Mathematical Bakery woman, the Twins (two Chinese women who hang out together and thankfully use English first names here, as many of them do; they don't look at all alike), and more. Then there are the ones who don't need a nickname; there's a ``Ken'', well, two in fact, but only one ever speaks up; and a female Jordan who is the lone math grad student in the class. Also a Chinese student who has what appear to be serious burn scars on his neck and part of his face. It's unfortunate, but inevitable, that this immediately becomes the recognition clue. He's a great student.

The main problem is getting the women to speak up (there are only nine, alas). I've never come up with a good way to encourage them, because any way you do it, it risks putting even more pressure on them, as though they're obligated to speak up for the good of all. One way that sometimes works is to put encouraging notes on homeworks, but I have a grader since the course is so big. Or if any of the silent types, male or female, ask a question after class, I try to compliment them on a good question and say Hey, you should ask questions in class. Wednesday this finally worked; Kate Winslet asked a great question in class!

I was getting to the point that I thought there was only one solution: Bring in the formidable Maddie as an undergrad in disguise, to set an example. She's the lone female in my algebraic topology reading course with three males (the Italian student, an undergrad, and one other), plus me. Maddie is awesome. She immediately established herself as the leader of the pack, and pretty much runs the show. Now that I've had a chance to hear her present ideas at the board, it's clear that she really is good. Great geometric intuition combined with computational skill and precision.

By the way a high school student visited my topology class on Wednesday. Took calculus in 9th grade and moved on to other things, including topology. These prodigy types grow like weeds around here, I tell ya. I hope he comes to the UW, but if he's as good as he sounds he'll probably go to someplace like Stanford or the Stanford of the East, you know, what's that place called? Oh right, Harvard.

Well, enough dex-fueled babbling for now, but it sure helps take my mind off the chemo! Oh darn...
I made it to 7:30 pm without the hiccups (a record), but they have just started...

Revenge of the neutrophils

The rash finally went away, my neutrophils have bounced back big time (told you so!) and today's infusion went ahead as planned. 

My nurse this time was Molly, who I think I've seen before although she didn't seem to recognize me. As they always do, she emphasized that ``it's important to drink'', then felt compelled to clarify that she didn't mean alchohol. What?! You mean all this time I've been misinformed? Every infusion weekend I've been dutifully knocking off three cases of beer, five with cisplatin.

Molly is very nice, but when her shift ended at 4:30 I was happy that Dana took over. She's the one with the quirky sense of humor; we exchange movie reviews too. I recommended ``The man who knew infinity'', about self-taught Indian mathematical genius
Ramanujan and his ``discovery'' by Cambridge mathematician G.H. Hardy.  The book is fascinating, and hard to capture in a movie. But they did a pretty good job I think. Jeremy Irons is well-cast as Hardy (``I love him!'' says Dana), and Dev Patel as Ramanujan. ``Dev Patel,'' Dana sighs, ``he's so cute!'' and pretends to run off to get the movie right away. She's a nut.
She recommended ``Genius'', the movie about Thomas Wolfe (author of ``Look homeward, angel'', not to be confused with the later Tom Wolfe, author of ``Bonfire of the vanities'') and his editor Maxwell Perkins. The cast is certainly great, including Colin Firth, Jude Law, Nicole Kidman and Laura Linney. So far we've loved the movies Dana recommends, so we'll be sure to try it. 

A random oddity: While waiting a few minutes outside the infusion ward, I was surprised to find on their magazine rack a 1991 volume entitled ``What every first-grader needs to know''. Odd choice for a chemo ward, but clearly something I needed to read up on, as next Thursday I'm visiting Kaia's class during math period (don't tell my chemo team; they would be horrified). I was able to do all the math problems in the book, but was taken aback by the paragraph on the Aztecs that mentioned human sacrifice. For first-graders?

One good thing about last week's infusion postponement is that next weekend is now an off week. This means we can go to the opera: Hansel and Gretel, by Engelbert Humperdinck. Anyone of my generation tends to associate that name with the British pop singer, but that was just a stage name stolen from the real Humperdinck (1854-1921). Initially Humperdinck just wrote a few songs to be performed in a puppet show by his nieces, eventually expanding it to a full opera, with libretto written by his sister. The opening performance was conducted by Richard Strauss, who considered it a masterpiece. Wendy and I have just listened to a recording of it, and the music is indeed beautiful, with much elaborate orchestration a la Strauss. Seattle Opera is staging it in a modern setting, a practice I generally dislike, but still it should be fun.

Usually Wendy drives me to the infusions, a practice we'll probably continue for the cisplatin weekends. But it really isn't necessary on the single-dose weekends, and it requires two trips for Wendy, so yesterday I drove myself. I can't say that I felt at the top of my game on the drive home, but it isn't bad. Besides, I now have Anna Karenina to keep me company for my next 39 hours of driving.

Quarter is still off to a good start. I got the Turkish exchange student into my class, as well as a university employee who's been wanting to take topology for years. But the powers that be wouldn't budge on that sophomore Haim Grebnev. ``If we let in a student who doesn't have the prerequisites, other students will be clamoring to do the same thing''. So? The whole point is that
it should be at the discretion of the instructor. If other students come a-clamorin', I would just say great, show me that you're at Grebnev's level and I'll let you in. This guy not only was asking on day 2 ``How many distinct topologies are there on a finite set with n elements?''; when I came in yesterday he had written on the board what he claimed was a recursion formula for the number in question. A recursion formula is something weaker than an actual formula, and his formula looked too good to be true to me, but who knows? I've asked him to write up a proof, which I will then ruthlessly critique to see if it's right. It doesn't matter though if it turns out to be wrong; the point is that only a tiny handful of students would even think of the question, let  alone try to solve it. I checked around and I was right about what I said earlier: at the moment, no one knows the answer to the question.

Did a nice walk this morning (it's the day after chemo) and felt remarkably good!

The further adventures of ChemoMan

A week ago Friday, I had the pleasure of being at the med center from 8 in the morning until 7 at night. First on the agenda
was installation of the ``chest-port''. I must say that this was one of the most pleasant medical procedures I have ever experienced. Narcotics are involved, as well as a local anesthetic. The procedure is done by an ``interventional radiologist'' and takes about an
hour. I was feeling very comfortable indeed just lying there, vaguely aware that someone was fooling around with the right side
of my chest. In fact when it was over, and they announced I could go up to the infusion ward, I really didn't want to leave. Hey,
it's so nice here! Can't I just lie here for another hour?

Next up was the usual 8 hour session for the double infusion, in the luxury suite. As always, I came armed with an array of mathematics, novels and audiobooks. It's not bad really; in the luxury suite there's a bed and a sliding door you can close. The one big disappointment was missing Finley's ``kid birthday party'' at Denny Creek Park. We'd already had the ``family birthday party'', which I absolutely would not have missed for anything, and certainly not for chemo. The next day Jessie texted me that she and the kids were dropping by for a ``special delivery'' from Kaia. I've talked to Kaia and Finley about having a funny bladder problem, without using the word cancer, so they know about these hospital stays and why I wasn't at the party. Anyway, Kaia brought me a cupcake from the party, and a big apple. So cute.

But alas, it's always sumthin. For the port procedure they use the common technique of painting around the area with betadyne, if that's the right spelling, and it turns out I'm allergic to it. So that whole side of my chest, up onto the neck and shoulder, looks like a case of poison oak and periodically itches like crazy. So far, nothing has worked to reduce it (at this moment it feels better, but I've been fooled before...).

Yesterday I went in for the week 2 infusion, and further complications ensued. The infusion nurse was reluctant to even use the
port, because of my skin condition. Dammit, I went to all the trouble of getting the stupid thing and you're not going to use it?
The big concern is infection, since it's so close to the heart. Okay, let's just do it peripherally, as they say in the biz. Then my labs
come back and it turns out my neutrophil count was down to 1.2, with 1.5 being the minimum to go ahead with the chemo.
Yeah, but my neutrophils have a family motto: ``Few, but strong''. We've done it before below the minimum, with approval from the onc, with no problems whatsoever. My neutrophils can kick ass! On the other hand, the combination of skin rash + infection risk + low neutrophils led the onc to nix the infusion for the day. Two and a half hours in the ward for nothin'. Meanwhile the NP suggested dexamethosone to treat the rash (wonderful, the hiccup drug), only to be countered by the onc because, for reasons I didn't quite get, the dex can also have an adverse affect on my long-suffering neutrophils. Ultimately it was decided that I should take antibiotics prophylactically for a week, and very small doses of dex but only if ``the rash gets worse''. Otherwise I just wait and time is supposed to cure it. Then I'll do the week 2 cycle next Friday.

Further entertainment was provided by the big Husky-Stanford game. The med center is just across the street from Husky Stadium,
and game time more or less coincided with the end of my session. No way would I ask Wendy to pick me up at the hospital or anywhere near campus; it would be a nightmare. Here you have to understand that on game days, mere professors can't even park on campus; everything is reserved for the convenience of football fans. I would've ridden my bike if I had known there would be no chemo, but oh well. I considered swimming across the lake, but my pack was too heavy. So we had devised a strategy: I would start walking north on the Burke-Gilman trail, while she was driving south, and we'd meet somewhere along Sand Point Way. 
It was a beautiful fall day, like almost every day this September. Near the stadium there was much hooplah as fans were streaming in for the 6 o'clock kickoff. Fundamentalist nut-cases were marching along with them, carrying big signs and ranting mindlessly on megaphones about the wages of sin, Jesus this and Jesus that ad nauseam. Others seemed more concerned about getting tickets to the game, or scalping some, than about the afterlife. After a mile or so the noise died out, and a couple of miles later I met my lovely wife at a very nice, quiet little park: the Burke-Gilman, which oddly I'd never been to.

Meanwhile, the fall quarter has begun. My senior topology class has fifty students with more trying to get in. It's a ridiculous number, due largely to the massive influx of Chinese students the last few years. Of course students of all nationalities are very welcome in my course, as long as they really want to study topology. The problem is that there are many who do not, and I'm doing my best to weed out the non-serious ones as soon as possible. On the plus side, there are already at least half a dozen students who have been very vocal and involved in class, and that's all it takes to make teaching really fun. On the other hand, the sheer size of our bloated program (600+ math majors) brings the Bureaucratic Law of Large Numbers into play: the bigger any organization gets, the more it succumbs to bureaucracatic rules. So I have to battle my own department to enroll highly qualified, motivated students who don't technically meet the requirements. A Turkish exchange student, for example. Or a sophomore who doesn't have the prerequisites and isn't even a math major yet, but was the top student in honors calculus last year. We have amazing, world-class students in the honors program, so this kid is sure to be phenomenal. Why hold him back?
He sits in the front row, asks persistent, interesting questions, and in fact when I came into class yesterday he was at the board
holding forth on some topological problem. Great, a guest lecturer! I can take a seat. ``We have a challenge problem for you,''
he says. His question showed tremendous insight and creativity. I didn't know the answer, and I suspect no one does.
He's the ideal student! How can we not let him in? I'll continue the battle over the weekend.

Wednesday I met my two new ``preliminary advisees''. One of them is Italian! In fact Alessandro and I had already been corresponding for some time, but I hadn't met him yet. We had our entire meeting in Italian, including the mathematical part.
A very nice guy. He was assigned to me based on his interest in algebraic topology, not his language! The other is Jasmine, an African-American young lady who I may have mentioned in some earlier post. She's the granddaughter of a friend of the husband of Wendy's friend Karen (got it?), who I first heard about from the grandma at Karen's 60th birthday party. Since then
I've been encouraging Jasmine to apply to grad school at the UW, and she's been admitted to the Masters program. It is sad but true that African-American math grad students are exceedingly rare, and an African-American woman is unheard of around here.
I'm excited she was accepted and will be rooting for her to succeed. She definitely has the enthusiasm and the initiative required, and obviously her file must have looked good to the admissions committee.

Supposedly I'm cutting back on my total activity during the chemo. For instance, I've again bowed out of committee duties, by
agreement with the chair. But it's hard to resist grad students who want to do reading courses in algebraic topology. It looks like I'll have a reading course with three students (including one of those brilliant undergrads I alluded to), plus possibly Alessandro although he may be too far ahead (he has a Masters already from a top school in Switzerland). The ringleader is a young woman
named Maddie. Talk about a ``take-charge'' kind of person! Before I knew what hit me, she'd already recruited these other students, worked out a time we could all meet and reserved one of our local rooms in Padelford (not easy to do). How could I say no?

Well, enough babbling. It's therapeutic though. Thursday we had the Brown family over for dinner, and opened our bottle
of Casa Aiva wine! Enjoyed by all, although Kaia and Finley much preferred the homemade chocolate chip cookies.

Huskies are on a roll. Jury still out on the Seahawks. And will the Mariners make the playoffs? With that, I shall take my leave.