Wednesday, April 12, 2017

Trump & Cancer, installment # 2

President Trump’s proposed budget would reduce the National Institutes of Health budget 18.3 percent, or approximately $5.8 billion, next year (and also cut $1.2 billion this year). (For the figures, see here.) How can he possibly do this? The answer seems to be that he wants to get, or appear to get, something for nothing. The something he would still get would be all the research that’s currently being done; and the nothing that he would pay for it, or more precisely the reduction of $5.8 billion that he’d pay for it, would come from reducing the “indirect overhead” payments that the NIH makes to researchers’ institutions. Those payments last year totaled $6.4 billion, or 27 % of the total of $16.9 billion that was provided in grants last year. Since $6.4 billion is even more than the $5.8 billion that Trump proposes to cut, it’s clear that in theory he could reduce the budget as he’s proposed just by cutting back very sharply, though not quite eliminating, the indirect overhead payments.

The problem with this scheme is that the indirect cost payments are needed. Essentially, they are what pays to keep the lights on in the nation’s research laboratories, so that inside those labs scientific research can proceed uninterrupted. They’re negotiated, elaborately, institution by institution, and evidently can range from 10 % to 100 % of the direct costs, though the aggregate NIH level is 27 %.

But could it be that the indirect cost payments that the federal government currently pays actually go far beyond the costs that research institutions incur in making it possible for research to go on? That seems to be the administration’s position. An article in Science reports that one Republican congressman “noted that many private foundations limit overhead payments to grantees to 10 %, whereas others, such as the American Lung Association, pay nothing.” But the same article reports that “University and research institutions … say the amount they receive doesn’t come close to covering the cost of the facilities needed to conduct federally funded research and the people needed to manage those grants.” Another Science article notes that private foundations “can get by charging a lower rate because they allow researchers to charge certain costs to their grant – such as leasing space – that can’t be charged to their NIH grant. And nonfederal grants may involve fewer regulations, lowering regulatory costs.”

It would take a detailed knowledge of grant budgeting that I don’t have to tell for sure who is subsidizing whom. But if the federal government is in effect subsidizing some of the costs of private foundations’ grants, or even subsidizing research institutions’ projects that really go beyond the indirect costs of the grants themselves, it still seems pretty safe to say that this money, or at least most of it, is actually needed. There has been an instance of a university claiming depreciation on its yacht as an indirect cost, but the school that did that (Stanford, 20 years ago), got in trouble. (This Science article touches on that story.) As a general matter, I think universities are chronically strapped for money, and research facilities don’t come cheap.

And if that’s true, then we won’t get something for nothing. When the indirect cost payments are reduced, what we’ll get is less research. That matters a lot – to research in general but also, for me now, to the research that will be done that might affect the treatment I personally receive. 

One more thing -- last month I wrote about the controversy over the Dana-Farber Cancer Institute's holding its fundraising gala at Mar-a-Lago. Many doctors and students at that hospital felt that their institution should not have been currying favor with the Administration in this way. Maybe not. But when it comes to dealing with the budget, there is no boycott option; anyone who believes this budget is wrong is going to have to deal with the President about it. One Nobel prize winner, Harold Varmus, has already written in the N.Y. Times that "In confronting the president's assault on the N.I.H., all members of Congress face a moment that will define their character and the future of the country." When they do face that moment, they'll have to face it in some sort of a negotiation with Donald Trump. 

Sunday, April 9, 2017

My mouse model

Here’s a feature of my treatment that I haven’t mentioned till now, because it hadn’t yet taken on any real substance – but now may have. This is my own mouse model.

To put that more bluntly: after my new tumor was biopsied, Sloan Kettering injected a portion of the biopsied material into a mouse. It took some time to see whether the biopsied material would actually grow in the mouse, but now it has. Even now, matters remain indefinite: the material that’s grown in mouse A now evidently must be injected into mouse B and grow there, and then many more repetitions will probably be needed.

But if it works, what they’ll have done is created a living model of my own particular cancer. If we understand it correctly, the theory, or hope, is that then they can see the likely course of my disease, and also gauge the potential impact of treatments by actually applying them to the mouse, or mice, and seeing what happens. (For a lot more information on mouse models, see here. And Teresa recalls that the Nebraska scientists we met at the Cholangiocarcinoma Foundation conference, who have been studying cancer cell death, did a poster presentation there on their work with mouse modeling.) 

It may not work. The tumors may die out instead of surviving in the mice. And what happens to the tumors in the mice may not be what happens to them in me. But it’s clearly worth a try.

I say all that, though not without some guilt. My mouse model is good for me, but not for the mice. I tell myself that a lot of our science depends on our use of animals, and that we are not being needlessly cruel. If I could say that someday what is learned may benefit mice as well as men, I would, but I don’t really believe that. All I can really say is that I need what may be learned from this work, and I am grateful to the mice who are involuntarily helping me.


Good news is more fun to report than bad!

So here is my good news: the new treatment is making progress.

Or in more detail: I’m now on a combination of irinotecan and 5FU, a combination my oncologist put me on because of the failure of the previous treatment, manifested in the sudden emergence and growth of a new tumor between November 2016 and January 2017. The scan last Wednesday found that that new tumor has grown smaller; so has another tumor that was also pretty big; and none of the tumors I have is reported as growing.

So the plan is: more of the same. My oncologist says that often, with this particular combination of drugs, they gradually lower the dosage – I think because of the side effects, which aren’t terrible but are more substantial than I usually experienced with my previous treatments. But right now, she said, she’d like to keep hitting the cancer as hard as possible, by keeping to the full dose, which sounded good to us. (It seemed a little less good as I felt nausea coming on during the treatment later that morning, but it’s still the right choice.)

And best of all: the oncologist anticipates, based on her past clinical experience, that since this combination has proved effective now, it will likely keep the tumors from growing for a substantial time down the road, even when it is no longer causing them to contract. That means that this is really what we’ve considered the most realistic hope all along: not for complete elimination of the tumors, but to get the most we can out of one treatment, then switch to another, and then to another, all the while taking advantage of everything being learned from the research that’s going on right now. And so far, so good.

Your continued best wishes, prayers, visualizations and any other forms of good will, regardless of theoretical foundation, are much appreciated!

Sunday, March 12, 2017

The Annual Meeting of the Cholangiocarcinoma Foundation

At the beginning of February, 2017 Teresa and I made our way to Salt Lake City for the fourth annual meeting of the Cholangiocarcinoma Foundation. (And we combined it with a trip to the Grand Canyon and to see relatives in Phoenix!)

The Foundation is an act of love. It was created by the survivors of a patient who died of cholangiocarcinoma, and a great deal of the organizing of the conference and of the Foundation’s activities seems to be done by those relatives and by other volunteers. It has done something that’s apparently about as rare in medicine as in other fields of human endeavor: it’s brought together people who might otherwise be competing with each other – doctors from different institutions with different perspectives on this disease and its treatment – and people who might otherwise be ignoring each other as much as possible – doctors and their patients – in a truly collegial gathering.

We met some people I’d only seen on the cholangiocarcinoma warriors facebook group – people who’ve had this disease for many years and are still fighting it hard. Several of these people told their stories in short sessions scattered through the conference. They were all the more inspirational because they weren’t simply happy stories. One of the speakers learned after the conference that she must have additional surgery. Another, a woman who seemed particularly well dressed for her presentation, had been in the emergency room just a few weeks before the conference took place.

We also met some scientists, including a very nice group of people from the University of Nebraska with whom we had lunch. They were interested in cell death. So am I, particularly in cancer cell death. It’s often said that cancer cells have escaped the various bodily controls that make ordinary cells die on schedule, but these folks said that cancer cells really want to die – they’re just blocked in various ways from doing so. I hope they’re right and that they can find ways to free cancer cells from their burdensome existence!

And we heard several presentations of pretty hard science. Hard, among other things, in the sense that it wasn’t easy to follow – especially if you, um, dozed off during some of what was said. (But for those of us in that category, the videos of the sessions are in the process of getting posted on the Foundation's page on Facebook.) It was clear that sophisticated work is being done in tracing the pathways of various processes of cell functioning. Pretty much anything that cells do is a potential weapon for cancer cells, but also a potential target for attacking them: how they get nutrition, how they avoid death, how they migrate from place to place in the body. So it was exciting to hear about the work that is underway.

And also a bit chastening, in various ways. There was the scientist who showed pictures of an autopsied liver, and commented that although scans of this patient had shown only discrete tumors, in fact on post-mortem examination it turned out that the whole liver was pervaded by cancer. Perhaps more important, even though there was obviously good work being done by good people, there weren’t a lot of these good people – all of us, patients, caregivers, and scientists, fitted in one mid-size hall – and there seem to be many disparate topics needing examination. The Foundation has generated resources and made grants, and more important sponsored a scientific community, but much more needs to be done.

Still, much is being done. The treatment I’m now getting, which is based partly on an effort to target a new mutation that has appeared in my latest tumor, is the kind of approach that has only emerged in recent years. My oncologist is part of developing this approach – and we talked with her at the conference. And meanwhile the efforts of the volunteers were truly heartwarming.

So, long live the Cholangiocarcinoma Foundation! We hope to join you in Salt Lake City for years to come!