I heard this on the way back from a funeral for a dear freind who died at a very young age from breast cancer. This is a very interesting take on treatment strategy which fits a bit with the recent discussions about BAT.
I would value all your thoughts about the science of this.
Metung boy (the atheist who cringes when you mention praying)
This article/interview on game theory application to cancer treatment was very interesting. If anyone in the community has additional thought or references please post them. I can't get enough of this .... new approaches to treatment. Dr. Stankova's comment "When it comes to metastatic cancer, the success rate is really…the life expectancy is about the same as 30 years ago" is powerful and suggests a brand-new strategy to treatment is needed.
I'm all over it. Often, when I see my RO, I get a sense he feels like this is something to be "managed" and that the ending is inevitable, even if it is not immediate. I feel like a more aggressive treatment plan would be appropriate...we are facing a clear and present enemy here, why are we waiting for it to make all the moves? Maybe naive, but I have had that sense from the beginning. 4 years now, diagnosed Gleason 9 with psa reaching 28 at it's highest. No mets so far in bones or organs, maybe a false positive with a lymph node in the iliac chain that showed up on a Gallium PSA scan last year. My surgeon, who is more aggressive, went in and nipped it out but it biopsied negative. My RO seems to feel the surgeon is too aggressive and that "you can't keep cutting parts of yourself away every time you find something"...yah you can, if it gets rid of the monster. Game theory sounds to me like trying to stay a step ahead of this thing, as opposed to reacting to it's moves...like I said, all over it.
But the game theory, if also implicates eco- evolutionary factors is a question of balance, not of aggressive treatment and cutting everything!
Great find! This part sort of sums it all up when it comes to current SOC. (emphasis is added.)
Norman Swan: So in a sense, in this game, because the doctor is rational and can think and the cancer cell is dumb, the doctor has an enormous advantage to begin with.
Katerina Stankova: You would think so, right? And if this rational player, the doctor, took this into account, then from game theoretical point of view there has to be strategy, a rational strategy of the doctor which will lead to the win. But this is not really done in the current standard of care. When it comes to metastatic cancer, the success rate is really…the life expectancy is about the same as 30 years ago. So what I am claiming is that while you have this rational player, the physician which could use all these advantages of rationality, playing first, they don't do it and that's a problem.
Norman Swan: Katerina Stankova.
So with standard, repeated and inflexible courses of chemotherapy, the game flips and the winner becomes the loser. If oncologists were to accept that they could dominate this evolutionary game, how would they play it? The answer lies in the game within the tumour between drug resistant and drug sensitive cells. You want the sensitive cells to win, which means, rather uncomfortably, that the tumour actually needs to be allowed to survive.
Katerina Stankova: The standard protocol is that the physician chooses the drug at maximum tolerable dose, and this drug is kept being applied until there is an inevitable evidence of cancer progression, or until you get a very, very high toxicity and the patient cannot take it. So while the doctor could be strategic here and try to foresee what type of drug he or she could apply and what would be a possible reaction on the cancer cells, instead you choose one combination of drugs, you go for a maximum tolerable dose, which is actually the maximum level of the drug which the patient can take, and then you keep playing the same strategy until you see it does not work.
But if you now look at the game played among the cancer cells, this is like the ideal situation for them because you change their environment but you do not surprise them. Basically you do all the time something the same, while actually they keep adjusting to your drug because they keep evolving while I play still the same strategy. So basically I am training the best enemy I could have. So in the end I will end up with a tumour I cannot treat anymore.
But it might be actually better to start to be a bit strategic. If I know that there are some cancer cells which actually react to my treatment and some others which do not, then maybe it is not the best idea to actually kill all those cancer cells which actually do react to my treatment.
Definitely a different approach than I've ever heard for treating cancer! Thanks again. Be Well - cujoe
Very, very interesting article. Thank you for sharing it.
The Moffitt Cancer Centre at the University of Illinois Chicago is doing work along similar lines. However they are more inspired by the examples in agriculture than game theory. A lot of money and science has gone into battling treatment resistance for parasites in plants and livestock. In one of the studies Dr Robert Gattenby says: “The goal of using cancer drugs at maximum tolerated dose levels, is to kill as many cancer cells as possible. However, this treatment approach typically results in selection for treatment-resistant cancer cells, which eventually proliferate, repopulate the tumor, and cause disease progression.”
My take on their argument is that you treat treatable cancers only enough to keep them well under control – this allows the treatable cancers to outcompete the untreatable nasties that would otherwise evolve. The big problem for me is how do you find the right point of balance and I need good quality evidence to show the treatable tumours do outcompete the untreatables.
It seems to me that the game theory approach makes some sense. Changing the environment of the tumour drives a selection process as we all know. Eventually with the sequential treatment that we use varies resistance to each step. This to me is analogous to what happened with HIV. In the early days of HIV there was sequential monotherapy but now there is usually triple therapy although there is a move now to dual therapy only but that is because the agents have become more powerful and well tolerated.
I had patients with indwelling catheters who had recurrent symptomatic infection. They were usually treated with bursts of antibiotics and sometimes continuous low-dose antibiotics but inevitably the bacteria in their bladders became resistant to treatment. Out of desperation I suggested that they acidified their urine for three days and then Alkalinized their urine for three days and continue to rotate this strategy.
There was an enormous decrease in the rate of symptomatic infection. It is impossible to clear an infection with an indwelling catheter so this strategy was more environmentally sophisticated I think.
It makes me tempted to have a go at BAT as a way of maintaining a population of tumour cells that is able to be controlled again by androgen deprivation. We need some trials! All this theorising is fun and interesting but we need evidence otherwise we sound like naturopaths.
I think we can get better at this once we stop trying to "win the battle". If we can get our minds around controlling the tumour and not eliminating it but making it of little consequence we might begin to do more sophisticated game theory type approaches. Some of the replies to this post reflect the fear of not winning the battle. I wouldn't mind feeling well with a moderate amount of tumour that wasn't making me sick if the treatment I was on didn't make me sick but I eventually die with a tumour load rather than from it.
I think I will try and look into game theory a bit more and will repost if I find anything.
US vs CANCER... win or lose, what a fucking game....
Good Luck, Good Health and Good Humor.
j-o-h-n Sunday 04/07/2019 1:15 PM DST
I had to laugh at that last line 
We forget how religious the yanks are compared to aussies huh?
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