Indecision point

The latest suggested immunotherapy is called ``nivolumab'', or ``nivo'' for short. Both nivo and atezo are known as ``immune checkpoint inhibitors'', the difference being that nivo tries to block PD-1 (``death cells'') whereas atezo tries to block PDL-1 (``death cell ligands''). I originally thought the PD-1's were the good guys and the PDL-1's the bad guys, but apparently the game is just to prevent by whatever means necessary the linking of the PDL-1's (which are on the cancer cells) to the PD-1's (which are on the good cells). This frees the cavalry to charge out to the rescue and attack the cancer cells. Well, obviously I don't yet understand the biology here, but in any case such understanding only serves to satisfy intellectual curiosity---it doesn't help make the decision.

The one major study of nivo involved 275 patients. It had a somewhat higher ``objective response rate'' than the atezo study, although with such small sample sizes I doubt this is statistically significant. The side-effects are the same, with fatigue and colitis (diarrhea) being the most common. The colitis sounds like it can be bad enough to prevent you from doing much of anything. Supposedly it can be treated with steroids, which of course have their own nasty side-effects. Moreover the colitis doesn't necessarily go away when the treatment is stopped. Without meaning to be overly cynical, I will also mention that the nivo study was funded by Bristol-Squibb, the company that makes and sells the drug. All things considered, then, I am much less enthusiastic than the authors of the study about the prospects of nivo (or atezo).

I wish it were possible to get case studies. Was the typical patient a 98-year old chain-smoking alchoholic with a bad heart and a wooden leg? Or was it a robust young man in the prime of health like myself? I wish I could obtain individual reports or accounts written by the patients themselves. It's very hard to know what to make of the statistics, since the definitions of partial response, complete response and so on are so vague.

The oncologist favors atezo over nivo, because (a) the infusions are once every three weeks for the former and every two weeks for the latter, and (b) atezo is cheaper and therefore a better choice for the common good. Well, I certainly want to do my part for the common good, although I confess item (a) would be the deciding factor for me---assuming I go this route at all. Once again I asked him what he thought would be the likely outcome if I choose no therapy at all. After stressing that there is no such thing as a ``median patient'', he said the median survival would be six months. I knew this from the literature already, but wanted to hear it from him. Of course, as I've said before, I would be mortified to only reach the median; the sheer embarassment of croaking that quickly would motivate me to beat the odds.

The oncologist seemed okay with the idea that I wait for the next scan before deciding, although I think this is because he's given up on convincing me to play a conservative game. The fact is that I still don't know what I will do. No one can help me with this decision (and I must say I'm very grateful that no one---doctors, family, friends---has pressured me to do anything). It's all on me, as it should be. Despite that dire ``six months'' figure, one side of me wants to say screw it, I'm going to put off therapy indefinitely and keep focusing on enjoying life now. The colitis (says the doc) can mean ten or more diarrhea attacks a day, which would put a bit of a damper on enjoyment, or even functioning. I wouldn't mind risking this if I knew it could be stopped by stopping the therapy, but the thought of a permanent such condition is pretty repulsive. And how bad is the fatigue? This is the kind of information that's impossible to get. There are other side-effects too.

I take much inspiration from Tiziano Terzani. He eventually reached a point where he said enough is enough; I'm done with treatments, I'll enjoy life now and accept death when it comes. Now admittedly, Terzani pursued treatment options much more extensively than I have. He spent a lot of time at Sloan-Kettering in New York undergoing chemo and radio (ironically, our cab from JFK went right past Sloan-Kettering on the way to meet Abby), and then travelled the world experimenting with various ``Eastern'' and even New Age-y approaches. He didn't really believe in most of these; the trip was motivated also by journalistic curiosity and led to his book ``Another spin on the merry-go-round''. Terzani also had a much more highly developed personal philosophy than I do, based in part on his extensive studies of Hindu and Buddhist ideas. Nevertheless, in my own way, I feel a strong connection to his point of view.

Would I have been better off not interrupting my chemo to go to Italy? From the conservative point of view, i.e. of maximizing life-span at all costs, maybe yes. But I'm not going to do that. Would I have been better off starting immunotherapy last month, even if it rendered our New York trip impossible? Conservatively, maybe yes. But I am very, very glad that I didn't jeopardize the trip. We had a fantastic time visiting Abby and Oliver. I'm not going to forego living for the sake of living longer.

Maybe I should decide just how long I'm going to procrastinate. But not today. The sun is out, and life is wonderful!

Of bladders and bobcats

The purpose of this follow-up post is to report on the actual scan results, which I've just received. However, I have to also report an unusual wildlife sighting on the Pipeline Trail (which goes up from the Sammamish river valley along the Pipeline right-of-way): a very large bobcat. By "large" I mean that when you first spot it out of the corner of your eye, you think it's a dog on the order of a German shepherd. It is then a bit disconcerting to realize that it is clearly a member of the cat family. A mountain lion? But the coloring is all wrong, with the spotted fur pattern. As soon as it saw me it lay down in the low bushes, so I couldn't see if it had a tail; indeed it was so well camouflaged that I hadn't already known it was there, I wouldn't have noticed it at all. Finally I decided to lob a couple of small rocks its way, just to be absolutely sure it wasn't a mountain lion (in which case a 911 call would be in order, with all the houses around). It jumped up and ran off, clearly a bobcat. But a HUGE one. I had no idea they got that big (up to 65 pounds or so, as I later checked).

Now, as to the scan. This one illustrates why I want to see it myself, as what the oncologist tells me over the phone is not necessarily the complete story. If you're interested in such things, here are some actual excerpts:


Liver: Significant interval increase in size of segment 7 hepatic metastatic
lesion (3/120), measuring 4.4 x 4.0 cm, previously 2.7 x 2.0 cm. Previously
noted small left satellite nodules is no longer identifiable on today's CT.
There is a new 1.6 x 1.1 cm lesion in the segment 6 (3/154).

An then in the summary:

1. Significant interval worsening of hepatic metastatic disease with new
lesion in the segment 6 and significantly enlarging known segment 7 lesion.
2. Unchanged thickening of the inferior urinary bladder walls, consistent with
primary bladder cancer.
3. Unchanged retroperitoneal and pelvic lymph nodes.
4. No evidence of new disease.

The doc didn't mention the "new lesion", but maybe it's another mirage. In any case, as I already knew, it's not exactly good news. But hardly surprising. Also, I think he's stretching it a bit to say that my bladder is "pristine". I can see the ad now at Al's Used Bladder Emporium: "Almost like new! Top quality bladder in pristine condition, used only on Sundays by a little old mathematician!"

The radiologist looks at everything in the abdomen/pelvic area, and had this to say about my hip replacement: "No evidence of hardware failure." Well, that's good to know!

Another scan, and a very happy Wendy birthday

Last Monday's scan showed that the original lesion in my liver has again increased in size, but ``not dramatically'', to quote the oncologist. On the other hand, the second apparent lesion now appears to have been a mirage. So that's good news, although I myself have not yet seen the radiologist's report. It really irks me that they're so slow to forward it to me. The doc also said that my bladder looked ``pristine''. It's not often you hear those two words used in the same sentence.

He also told me about a new treatment as a possible alternative to atezo. I'll report on that later, when I've had a chance to investigate. For now I'm just looking forward to our New York City trip, coming up on Wednesday! We're going to see Abby in the chorus of Fidelio at the Met, and we're all going to see Aida as well. It will be great to see Abby and Oliver in their native habitat.

Not to mention I'll finally meet the legendary Earl Grey (the cat).

Meanwhile, we had a wonderful celebration of Wendy's xx-th birthday, where the number has been censored because I can't believe a young man like myself is married to a woman that old. On the Saturday we went out for dinner and then saw the movie ``A United Kingdom'', which is fabulous. Very highly recommended. On Sunday, her actual birthday, we had birthday dinner at the Brown's house. Now, it is well-known that Kaia and Finley are the cutest grandkids on the planet, as has been verified by an independent research firm. But they really outdid themselves this time:

They met Wendy at the door and sang Happy Birthday to her. Kaia made a colorful Happy Birthday poster. They each made a present for her out of cardboard etc.: Kaia made a Boeing airplane, and Finley made a doll house (``Be careful! It's fragile!'' he warned). Kaia helped her mother make a strawberry birthday cake, in the shape of a strawberry (according to Kaia, ``I told mommy how to make it''). My favorite image of the evening, which makes me smile just to think about it, is Kaia serving cake and icecream while wearing a cute little apron and a white chef's hat. Would you like one strawberry or two? she asked each of us. Later she announced that she was going to go around the table and give each of us a hug, which she did. Finley decided to make a present for his daddy. ``Don't look over here!'' he exclaimed about once a minute. ``Guys, don't look at the art table!'' It turned out to be a Star Wars vehicle---the name of which I forget, not being a connoisseur of the form as Finley is. Meanwhile, Kaia was whispering to me about her plans for Daddy's birthday cake (his being the next family birthday coming up).

It doesn't get any cuter than that! Life is beautiful, indeed.

Still holding

The oncologist only sent me information on one research study. Regular eye exams are frequently mentioned, as this treatment can apparently cause eye problems. That's a deal-breaker for me. The other point about the research studies is that both the benefits and the side-effects are for the most part unknown. I don't think I'll be joining any research studies.

That leaves the atezo immunotherapy. I'm really struggling with this one. Its unimpressive results and serious side-effects make it difficult to muster up much enthusiasm. So I've been coming up with reasons to procrastinate. First I decided to wait until after the opera, coming up this evening (more on that below). Then I thought, well, the next CT-scan is in mid-March, so I might as well just wait for that and see what happens. If the lesion in the liver is stable, I'll wait until after our NYC trip to do anything. Then again, I really don't want to risk my spring class, which I'm very excited about. Maybe I should wait until summer. But of course I don't want to do it in the summer either. The fall isn't good either...well, you get the idea. The reality is that I can't wait too long before making a decision. But for now, I'm waiting.

Meanwhile, life goes on as though cancer didn't exist. Tonight Wendy and I are going with Jessie and Kevin to the opera! We've found a nice Mediterranean restaurant as a change from the traditional Thai place, so it's going to be a real evening out with adult conversation; imagine that! The opera is Katya Kabanova, by the Czech composer Janacek (written around 1920). Lately Janacek has become one of my favorite composers (I've listened to the CD of Katya four times), so I'm looking forward to it even if S.O. does weird things with the production.

My classes have been keep me incredibly busy. I'm no longer willing to say that my Mathematical Reasoning class is going well. It is without a doubt the weakest class of its kind I've ever had. These kids are supposedly math majors, but the reasoning ability of most of them is very poor, sometimes beyond belief. Most readers of this blog, with a summer to prepare, could not only take this course but even teach most of it. It's not rocket science, as they say. Here are some examples of what I'm dealing with:

One student proved that an integer cannot be divisible by two different primes. Thus the number 6 does not exist, a most surprising result.

Another student, when confronted with the question ``when does ca=cb imply a=b'' said that was true only when c=0. This leads to two striking conclusions: First, all numbers are equal, since 0 times anything is zero. Second, since it's true ONLY for c=0, in particular it is not true for c=1, and therefore a=b does not imply a=b.

On yesterday's quiz they had to prove a certain formula involving a number n. More than half the class produced an answer which for n=1 implied 2=4, and for n=2 implied 4=16. As for as I know, these equations are not correct, and if it were me I would begin to suspect there was something wrong with my solution. Furthermore, by their own argument they were effectively saying they had positive numbers a,b,c such that b=a+b+c. In most cases the source of the error was a claim amounting to saying that a+b squared = a squared + b squared. If you try to carpet a square room whose sides have length a+b with this formula, the result will be unsatisfactory. But who cares? If it makes the problem easier, just assume it's true.

It's unbelievable. I'm tearing my hair out, which is problematic since I don't have that much left. They're nice kids, and most of them work hard. I don't get it.

In my differential geometry class too some students are struggling, but in this case it's completely understandable. Einstein had a terrible time with differential geometry, which he needed for his General Theory of Relativity. On the one hand the subject has much beautiful imagery and vivid intuition, but on the other hand, it has a morass of very confusing notation. We'll get there; I give constant encouragement and remind them that Einstein struggled with it too. It's a beautiful subject and a lot of fun. I have some excellent students too, although not quite at the level of previous editions of this course.

Well, it's time to start thinking about what tie to choose from my vast selection; J and K are picking us up at five. I'll leave you with a Kaia story:

We're all sitting around the dinner table. I'd been venting a bit about the mathematical reasoning class, and Kevin got going on a similar theme involving programming and job applicants at Microsoft. At one point Kaia abruptly cut in:

``This is funny; Daddy is a better math teacher than Grandpa!''

``Why do you say that?'' someone asked.

``Because Daddy is talking about math, and Grandpa has a confused look on his face.''

Clearly she confused my ``confused look'' with my ``penetrating insight'' look. I get that a lot.

Holding pattern

I joke that ``the suspense is killing me'', but it's not all a joke. If the cancer is going to kill me, I almost wish it would just get on with it. Well not really, but it's a thought that occurs to me in darker moments. This continual state of limbo, experiencing no symptoms and yet being told a time-bomb is ticking away within, is starting to wear on me.

I had a phone consultation with the oncologist on Tuesday. It was singularly uninformative. He is very reluctant to make any recommendation; he just lays out the options, such as they are, and leaves it to me to choose. None of the options are appealing. My interpretation of his reluctance is that he himself is not enthusiastic about any of the treatments. Nor should he be. The atezo immunotherapy, as he pointed out once again, has only a 15 percent track record of so-called complete response---and even this term increasingly seems meaningless to me. After my first round of chemo, the result was considered a ``complete response''. So it doesn't mean much.

The atezo can have some very bad side-effects. His patients in particular have had bad luck with colitis, and by the way these toxicities don't necessarily go away after the treatment stops; they can continue indefinitely. The fact that Atezo is FDA approved is of little or no significance; even the doc seems to think it is overrated.

The ``research studies'' are a complete shot in the dark. No one knows if they work; it's research after all. Nor does anyone know what the side-effects will be. He is sending some information on the research studies, so that I can ``look them over at my leisure''. That surprised me, because I thought there was supposed to be some urgency about getting started. That's fine, though, because frankly I welcome any excuse to postpone a decision that I do not want to make.

So I'm in a holding pattern. When it is a beautiful day, and I feel fine, I cannot bring myself to deliberately destroy my health with treatments that probably won't work anyway. For today, I won't. Tomorrow, we'll see.

Well, enough of that. Just had dinner with the Brown family at the ``Little Mexican restaurant''. The name of the place is actually ``Plaza Garcia'', but decades ago we started calling it ``the little Mexican'' and the name stuck. Kaia and Finley were in fine form, and told us all about their latest skiing adventures. What a trip down nostalgia lane to hear of those two zooming down Brooks, Hogsback, Skyline and other runs at Stevens Pass. For some reason I have a particular nostalgia for Brooks, which was always a fun family run. Jessie thinks Kaia is almost ready to try a black diamond run.

Classes going great, apart from a horrible case of the flu that really set me back last week (Wendy had it too). Differential geometry is in a slow period, where we have to do some important but not very exciting background work. Soon, however, we are on to Gaussian curvature, and it doesn't get any more fun than that!

I've been at my wits' end with my Mathematical Reasoning students, many of whom seem incapable of thinking for themselves---and they are beginning math majors, no less. I wonder if it has something to do with the internet generation. It's the weakest class I've had. Yet they are so earnest and hard-working, and I really do want them to succeed. I just gave the easiest midterm in the history of midterms, fearing that they still might blow it. They did okay though; what a relief!

I belatedly tried to learn some Chinese pronunciation, just for the names. The Roman alphabet transliteration system is called Pinyin; its creator died just recently at the age of 105 or so. No wonder I've been confused all these years: Many of the letter combinations in Pinyin are pronounced in completely unintuitive (to an English speaker) ways. Moreover they come with five different ``accents'' that are actually tone markers, and these tone markers don't show up on my printed class list. It's incredibly difficult. Even my pathetic attempts, however, seem to be appreciated by the Chinese students. It's really too late for this year, but next September I'm even going to take a few lessons before Fall classes start. It's a challenge, and so different from any other language I've studied.

I keep moving forward, one day at a time.

Addendum

At my last meeting with the doc, we had not yet received the radiologist's report; the doc evaluated the scan himself. A few days ago said report finally arrived, and unfortunately the news is slightly worse: in addition to the doubled lesion, there is a new lesion in the liver that the radiologist marked as "suspicious for further metastasis".

I have a phone appointment with the doc next week to discuss next steps. We would have done it earlier this week, but I was hit with the worst case of the flu I've had in decades. Wendy got it too.
Not fun!

Latest news...more bumps in the road

Sorry, I can't get this thing to move the text up. Scroll down for blog!

I had another CT-scan on Wednesday. The good news is that my bladder seems fine, even ``better than it was before'' according to the doc, and nothing new is going on with the lymph nodes. The bad news is that the ``lesion'' in the liver, although still small, has doubled in size. We will need to decide soon, although not immediately, on a new course of treatment. In what follows I'll discuss the situation openly, without mincing any words. If you're squeamish about discussing death (or even just about discussing gross side-effects of possible treatments), read no further. For me it's a form of self-therapy; avoiding the subject would be much worse. But it's not a pretty picture.

I still have no symptoms whatsoever of the metastatic part of the disease, in particular the liver. What would the symptoms be? I finally got an answer to this: pain in the liver itself, nausea caused by the failure of the liver to eliminate toxins, and fatigue. The doc was at pains to emphasize, however, that if you get to the point of experiencing liver symptoms, ``it will be a short trip''. He doesn't like to use the word ``death'', but you get the drift. It's also true, statistically speaking, that regardless of treatment the cancer is likely to get me sooner or later. Yet I feel fine. It's surreal, to say the least. The suspense is killing me!

I come back to the basic philosophy, discussed elsewhere in this blog, that keeps me on an even keel:

1. I've had a wonderful, lucky life, and I'm still having it today. If I were to die soon, even tomorrow, I would have no cause for complaint. Well, okay, if I actually died tomorrow I'd be pretty pissed. But in the big scheme of things, to feel self-pity would be absurd.

2. There is no point whatever in worrying about it. I think of it this way: Suppose I was told I had x years to live; say x=1 just to illustrate. If I worry for a year, then turn out to be fine, I've wasted a year worrying. If I worry for a year, then die, I've wasted my last year worrying. It's a waste of time, and life, either way.

3. Death is a part of life, to be accepted and not feared. Expanding further on this point leads to mysticism/spirituality/philosophy of a personal nature. In previous posts I attempted to explain my views, to the extent

that they can be expressed in words at all. I'll leave it at that.

As to the new course of treatment, further ``platinum-based therapy'' (i.e. cisplatin) is not considered an option. As the oncologist (=''the doc'') explains it, there are three options, only the first of which is FDA approved: the atezolizumab immunotherapy (``atezo'', for short) discussed in an earlier post, the one involving the lovely term ``programmed death-cell ligands''. The other course is to join a research study, of which there are two ongoing. Research studies involve treatments that are not yet FDA approved, but this doesn't mean they can't be tried on volunteers. One of the research studies involves another form of chemotherapy; the other is a different immunotherapy. All treatments involve side-effects, ranging from the annoying to the very serious. Some immunotherapies inadvertently attack the pancreas and lead to diabetes, although apparently this hasn't happened with atezo. In the doc's personal experience with his patients, by far the most common side-effect of atezo is colitis, or to be more graphic, severe diarrhea---as in going ten times a day. There are further medications to counter it, but I can't imagine teaching, for example, under those conditions. It's also true that being dead would significantly impact my teaching. The image comes to mind of our hero as he ascends the scaffold to his execution, raising a clenched fist with the defiant cry: ``Death before diarrhea!'' A little gallows humor there.

This brings me to a digression. Contrary to what many of my nurses seem to think (the doc too, I suspect), all this joking around, flippant talk, and putting up a happy front, is not ``denial''. This really annoys me; I've never been in denial.

Maintaining a positive attitude is not denial. I'm well aware that the prognosis is grim. How grim? Well, let me quote a few points from the article on which the doc's current atezo protocol is based. If you want to see it yourself, it's in v. 386 of The Lancet, May 7, 2016, intitled ``Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy'', by the usual mob of authors found in medical journals.

Here ``progressed'' means ``gotten worse'' (the cancer has progressed, not the patient). So I'm exactly in the category of patients described.

In the introduction the authors remark: ``Platinum-based chemotherapy is the standard of care...[in bladder cancer]...and is associated with an overall survival of around 9-15 months. The prognosis for patients who relapse after platinum-based chemotherapy is poor, with median survival ranging from 5 to 7 months and no known life-prolonging treatments available. New approaches are needed to break this therapeutic stalemate.''

Atezo is such an approach, but it's not a miracle cure by a long shot. There were 315 subjects in this study, which took place in 2014, and by September 2015, 193 had died despite the atezo treatment. The percentages of ``complete response'' and ``partial response'' are low; moreover, it has to be born in mind that even ``complete response'' does not imply a cure. The statistics given for ``duration of response'' are not easy to decipher, but they aren't promising.The authors also note that ``...the presence of liver metastasis in patients resulted in a lower objective response rate than in patients with no liver metastases (5% vs. 19%)''.

So no, I'm not in denial. When I ask them about something like the time commitment required for a research study (it's fairly high), or whether the side-effects will impact my ability to work, maybe they think this is an odd question for someone whose life is at stake. But as the literature makes abundantly clear, there is a high probability that the cancer will get me anyway, with or without any given therapy, so why shouldn't I maximize the quality of whatever time remains?

On the other hand, I'm certainly not throwing in the towel! I need to do some more research; then I'll choose one of the treatment options. At the moment I'm leaning heavily toward trying the atezo, just because it's FDA approved and I know more about it. In any case, once I start treatment, I'll assume it will work and start planning a trip to Sardinia. But I swear, the next person to imply I'm ``in denial'' is going to be beaten to death with a used catheter.

Meanwhile, the surreal dream continues. I feel perfectly fine. I'm doing all the usual stuff I love to do. My two courses are especially fun this quarter. (If you see the movie ``Hidden Figures'', which I recommend, listen for an early mention by one of the stars of the ``Frenet frame''. I just lectured on this in differential geometry last week. It will be featured on one of my topology-geometry theme park rides, the Torsion Tube of Terror.) Our little grand-munchkins are as cute an interesting as ever. In my next post maybe I'll talk more about all the fun stuff. Life is beautiful!