Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Breast Cancer
mdpi.com
mdpi.com
Institutional Review Board Statement
This is a case of self-experimentation. As such, it does not require ethics committee review [33,34,35]. The study was feasible only due to the unique situation in which the patient was also an expert virologist. The patient was fully aware of her illness as well as of available therapies, and as a scientist in the field of virology, she was aware of the potential of oncolytic virotherapy. After two recurrences of the same tumour, she wanted to try an innovative approach in a scientifically sound way. Her oncologists (the leading oncologists in Croatia for breast cancer) accepted to monitor the progress of the treatment, primarily with the aim of discontinuing the injections and intervening with conventional therapy if there were untoward effects or if the tumour progressed.
But she was only able to do so because of having the skill and access needed to self-administer the cure. How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?
The Last Lecture was given almost 20 years ago. Pancreatic cancer is just as deadly today.
https://www.fda.gov/patients/learn-about-expanded-access-and...
This is the heart of the difference between freedom and paternalism. If people can choose for themselves then 90% of the time it's going to be ineffective, if not an outright scam. But if people can't choose for themselves then 100% of the time they die. The paternalists say it should be the latter, because scams are bad.
This is only true for a certain set of cases, and in those cases people generally can choose for themselves.
But the same logic also works for anything non-fatal as long as the proposed treatment is also non-fatal. If you want to try something and it probably won't work but it also probably won't cause permanent damage, there is nobody who should stop you from finding out what happens for yourself.
The problem comes when these things are advertised or otherwise promoted. Ideas don't exist in a vacuum, they can become cultural parasites for all sorts of reasons, and even if they don't begin as a scam, there are always a bunch of get-rich-quickers waiting in the wings to sell, say, sheep dewormer to people with a respiratory virus.
The relevant doing stuff to yourself here is that you want to take some particular drug. Unless you're a competent chemist with the relevant equipment, that implies that somebody would have to be able to sell it to you in order for you be able to do it.
Also, what happens if the thing you want to do to yourself is to take MDMA?
Let's suppose in the base case - experimental treatments are largely suppressed and difficult to access - the odds are 10:1. That's a 10% chance of significantly prolonged survival, against 90% ineffective. And some of those "ineffective", maybe ten or twenty percent, will be actively harmful: shorter survival or a nastier death.
Unchecked, though, scammers will proliferate, and the odds get worse. Because incurable illnesses are, relatively speaking, very common compared to 10% shots at curing them. (If the reverse were true, we'd have eliminated many more of them with a shotgun approach). So now you're looking at 1% effective outcomes vs 10-20% harmful outcomes.
And that's before we even factor money - and financial harm not just to the patient but to their family and loved ones - into the picture.
Granted it's possible to imagine a much more agile approval process than the one we're lumbered with today. We may not have got the balance right between suppressing scams and approving treatments for people who otherwise have little hope. But the need to hold scammers down - and, perhaps even more so, ego-tripping quacks who have convinced themselves they're acting honestly - is real.
"First, do no harm" has been with us almost 2500 years, and with good reason.
This can't be a serious argument when the ordinary medical establishment is the thing wiping out the bank accounts of anyone who gets seriously sick, regardless of whether or not it cures them.
If people are facing death and they have money, they're going to throw the money at attempts to not die, one way or the other.
> So now you're looking at 1% effective outcomes vs 10-20% harmful outcomes.
But in this case the 10-20% harmful outcomes are in the nature of "you still died but maybe a little bit sooner" whereas the 1% effective outcomes are that you would have died and instead you didn't and lived another 50 years. If I have two months to live and there's a button I can press that has a 99% chance of making it one month and a 1% chance of making it 50 years, I'm smashing that button with no regrets.
You're also assuming we have no mechanism for detecting scams. But we do. Professionals go to school to learn science and that allows them to detect bullshit. If a substance is supposed to work against cancer by inhibiting cell growth and it's the sort of thing that could plausibly do that, it might not be a cure for cancer but it might be worth the attempt if you're going to die anyway. If a substance is supposed to work against cancer by mechanism of the astrology of Capricorn, that's a load of bullocks. So then the patient can ask a scientist they trust if the thing has any plausible mechanism of action before they waste their time or money on it.
Some of them may still be fools, but not all of them. Especially when the ones who aren't fools are the ones who are more likely to not die, which is the sort of thing otherwise-apathetic people tend to care about.
Moreover, in general "we have to kill some diligent people to keep some idiots from wasting their money" is not a sympathetic argument.
Get a PhD to try and cure their own disease?
https://www.wired.com/story/sleep-no-more-crusade-genetic-ki...
I imagine there could be other options available, and many times the issues are related to logistics, bureaucracy, and corruption. For instance, many people around the world go hungry due to logistical challenges (e.g., political interference) [1].
It seems we accept the status quo, while some companies are sending cheaper spacecraft into space.
[1] https://www.reddit.com/r/NoStupidQuestions/comments/zye4gm/w...
Then you can drill down and see locations where they are recruiting. For example,
https://clinicaltrials.gov/study/NCT05855200?locStr=New%20Yo...
I'm fine with letting people try whatever they want if there are no other options (their life, although informed consent is tricky) however i dont think we should allow marketing such things to patients or allow anyone making money off it.
The problem is, how do companies identify these patients or how do patients identify these companies without leaving room for massive abuse.
Maybe the treatments have to be zero cost? That feels like it would eliminate all bad actors?
Detect and punish scammers if they are an issue. Allow people to take risky medical treatments if they have serious incurable illnesses.
If a company or research group wants to sponsor an experimental treatment with patient approval and waiver free of charge, that's one thing.
But they almost immediately turn around and say " oh we'll need to cover costs..." and suddenly the incentive is very different.
There's no shortage of cancer patients at end-of-life stage undergoing aggressive treatments and/or experimental therapies in clinical trials for minimal to no survival benefit. For almost all of these patients, the best option for them and their loved ones will end up having been a palliative or best supportive care model.
Everyone who laughs so confidently at homeopathy, would likely do the same for a cutting edge treatment, which has yet to be widely recognized as effective. And in that case a lack of freedom would lead to a worse outcome.
Experimental treatments definitely invite skepticism, and should. Humans can generally contain more than one level of skepticism - this treatment has a certain rate of failure, this treatment is unproven, and important, this treatment has no mechanism that could work and is a scam meant to separate a fool from his money.
These same arguments get trotted out every time someone wants to defend very stupid practices and they have no teeth.
If you really want to cure cancer, and other diseases like ALS, etc, invest the money and resources necessary to do it.
If you have a disease and want to find clinical trials for unapproved drugs, they are available.
https://clinicaltrials.gov/study/NCT05855200?locStr=New%20Yo...
The trials exist. Getting patients enrolled in the trials is the biggest problem. Navigating the bureaucracy is a huge problem ("Please be dying, but not too quickly, part 1: a clinical trial story" see: https://bessstillman.substack.com/p/please-be-dying-but-not-...).
Even worse--we know the net to this stuff. It's negative and large.
We just went through this. Desperate people are stupid. Look at all the snake oil about Covid cures before the vaccines and how much damage that snake oil did.
And it's worse than that. It encourages ethical problems among the doctors themselves. You're sure your treatment will work it just needs a couple more patients. What will you do to get those patients?
Finally, if you throw the system open, the people playing by the rules will get drowned by those not. Bad money drives out good and all that.
The system as we have it certainly isn't ideal, but throwing things open would be much, much worse.
This isn't a case study about a breast cancer cure. This is a story about a single individual's cancer's response to an experimental treatment. For comparison, there are case studies of spontaneous remission in refractory cancers triggered by seasonal flu.
Virologists aren't sitting around waiting to develop cancer before they decide to roll out the miracle cancer cures. Oncolytic viruses have been researched, studied and tested on cancer patients for almost a century now.
You say that, but the article suggests otherwise. This virologist did believe that her colleagues were sitting around not rolling out something that would cure her. It is pretty easy to see how a lot of cures would be stuck in the research world, unable to get to patients; there is no reason to believe they are moving quickly to bring cures to market. You can see people arguing up and down the thread how they have higher priorities than testing stuff to see if it might work.
And because her outcome was so unexpected and unusual it got published as a case study. What you don't see are all the cases where the experimental miracle cure treatment did not work. What you also won't see in headlines are all the trials where putative miracle cures and other promising treatments failed to demonstrate survival benefits in larger cohorts than 1.
One of the counterintuitive things about cancer is how badly individual cases and responses to treatment generalize to the broader patient population. If you didn't know any better, you could easily read a story like this and think "wow, this breast cancer cure was just stuck in a lab somewhere!" But to put a story like this into context, you need to understand just how many individual miracle remission stories there are, and how varied individual cancers and responses to treatment are.
There are potential miracle cures almost everywhere, and a large number of them are being aggressively researched, tested on cancer patients at any given time - often as part of combination therapies. Some of these promising technologies do become breakthrough cancer treatments that create durable remissions, such as checkpoint inhibitors. The rest fizzle out.
There are risks, but having cancer is a risky business right from the get go.
> You're in the awkward position of arguing that an expert in a field doesn't understand what she is doing while citing evidence to support yourself that you (by construction) don't have.
No. I'm in the non-awkward position of arguing that non-experts should be careful about interpreting a single case study without context. Especially in a way that implies miracle cancer cures are sitting around in labs with no one paying any attention to them.
I don't think the average HN reader understands just how many wildly different treatments, drugs and therapies are being thrown at different cancers and how quickly medical oncology moves as a field. Cancers are an extremely complex family of diseases. Early results and case studies are correspondingly extremely difficult to interpret due to the variation in individual responses and disease course.
The existence of a "miracle" cancer treatment is almost ruled out from first principles. But if such a miracle treatment is sitting around in a lab, it would be non-trivial to tell it apart from the thousands of other promising candidate therapies that go on to pan out to nothing.
You say that as though it supports your thesis, but you obviously haven't thought thorough the implications if you don't believe there are a bunch of cures sitting around in labs.
You still can't deal with the main weakness in your argument here - this woman, who is very close to the pointy end of the stick and qualified enough, is evidence that the virology world is in fact sitting around on some fairly important techniques that could help cure her. Which is pretty much what we would expect given that taking something from the lab to the other side of the regulators involves enormous costs and demands of rigour.
And you seem a bit too focused on miracle cures. I suggest discarding that focus, miracles generally imply that something is impossible or unlikely. It is better to focus on realities and probable outcomes.
This rather famously killed ~100 men in the US and ended in 1972 long after effective treatments where available. https://en.wikipedia.org/wiki/Tuskegee_Syphilis_Study
But ethical violations are common, here’s one example where a whistleblower raised concerns in 2016 but it continued until Nov 2018 when funding ran out: https://www.kpbs.org/news/health/2021/02/12/new-details-unet...
Really smart to use the viral therapy before chemotherapy, since chemotherapy dampens the immune system, and the immune system probably promotes further tumor clearance once the tumors soften and are full of viruses.
1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system.
2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness.
3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway.
4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors.
5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival.
This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.
There are always exceptions to everything in biology, but the general mechanism of most chemotherapy drugs is that they preferentially kill or stall rapidly growing cells. That's why hair often falls out and you get skin issues. My point is that a successful immune response often involves rapid division of immune cell populations as well, which is dampened by chemo. You are also ineligible for many clinical trials if your blood cell counts get below a certain level.
Yes DNA-damaging chemotherapy drugs can induce p53, but many cancers inhibit p53 anyway. I'm not sure you would want to trade a general induction in p53 for losing a huge portion of your overall T-cell count right before injecting yourself with an oncolytic virus (depending on the tumor type).
You raise a number of good points, and there are a lot of subtleties including regulatory T-cells, which you mentioned. However, if you have the expertise and the means to design a custom treatment/regimen for yourself, I think that you can potentially do a lot better than just going through the meat-grinder of clinical oncology where the first line treatments are years behind cutting edge academic work. This paper supports this idea. I am not recommending that everyone who has cancer forgoes chemotherapy in favor of trying something risky, but as you said every individual case is different and it should be your decision whether you want to try a high-risk high-reward strategy or whether you want to go through multiple rounds of non-curative treatments which only slow down the inevitable and gradually sap away your strength and immune function. Especially if you have enough expertise in a relevant subject matter.
For example, my mother was diagnosed with stage 4 of a rare HPV+ squamous cell cancer. She was an expert on co-stimulation and immune tolerance, since she that is what she studied in the lab (https://tts.org/74-ixa/889-ixa-in-memoriam-agnes-marie-azimz... ). At times she was educating her doctor on co-stimulatory mechanisms, since he barely knew enough answer her questions and he would say the same types of things that you are saying: "it's complicated" "it might help clear cancer cells" etc..
There are a lot of customized treatments that she envisioned trying using her extensive expertise, and probably could have done so with the reagents in the lab or with her colleagues' help. Ultimately, she decided to trust the medical system but she did not respond to any chemotherapy. The one session which led to a reduction of tumor growth also led to a reduction in her blood cell counts (it was FOLFIRI), so the chemo had to be stopped. After that, she enrolled in an experimental cell therapy but it didn't work. Of course, the chances of it working are a lot less when her strength, general health, and immune function were already diminished.
It's one thing to talk about the complexities and the ethical risks of trying an experimental therapy, but when it happens to you or a loved one, the cost of failure is a lot higher and you might rethink your risk appetite. I am talking specifically about rare versions of tumors where the prognosis is poor.
In general, I don't even understand the point of making doctors go through all of the training they do, if they are forced to just follow the cookie cutter guidelines, which are influenced by the established drug companies.
In contrast, many comments here are talking about the ethics of not having this approach more broadly available, which is fairly optimistic for Hacker News.
Or maybe it’s just that a subsection of bio-ethicists on Twitter have oddly shaped moral values.
I think rational consequentialism is a common stance here on HN. e.g. I would be better off having access to this treatment (on my own terms of course), and other people having access to it would not negatively affect me, so I'm in favor.
Four Thieves Vinegar Collective – Harm Reduction for the Living - https://news.ycombinator.com/item?id=41474080 - Sep 2024 (186 comments)
"Right to Repair–for Your Body. ... enabling access to medicines and medical technologies to those who need them but don’t have them"
DEFCON talk 2 days ago: https://www.youtube.com/watch?v=5rQklSmI_F0
It sucked. Because I was doing it at home and not under observation, the dose schedule was way more conservative, so I'm not sure if it ended up saving any time at all despite the long drive to the clinic and the wait afterward. And stabbing yourself—even in the leg, as in my case—is not an easy thing to do. I thought it would get easier over time, and maybe it did a little, but there was a lot of variance and even towards the end some days it took me 10 minutes to psych myself up enough to do it. (Feeling monumentally foolish, but still not able to stick it in.)
Amusingly: after I switched to the conventional therapy of being injected by a nurse at a clinic, the nurse said she could never do it to herself. And she injects on the order of 100 patients per week!
Self-injecting into a breast... I can't even imagine. I guess the life-threatening nature, and not having an alternative, are powerful forces.
Just like from I Am Legend movie.
``` The movie opens with a scene of Dr. Alice Krippin, who created the virus to cure cancer, discussing her work. Krippin states that 10,009 clinical trials were completed and all of the participants were successfully cured. However, it is later discovered that the virus is lethal.
A genetically modified measles virus kills most humans and turns some people into mutant creatures.
```
I hope it wont end up like `I Am Legend` movie. How long those research are being there , the movie script is a coincidence?
The fascinating thing is that this has been done in a self-experiment with viruses grown in her own lab.