Cutting cancer rates: Data, models and a happy ending?

In theory, the definitive treatment for early stage cancer patients should be surgical resection. Just get in there and cut the tumour out. If the lump is small and well-constrained, then surgical removal is all that should be needed. Unfortunately, this isn’t usually what happens. Even when the tumour is nice and small and …

[Khaptain]

Data and its problems

Data is just that "data". One of the problems, as this article shows, is that we never know if the data is complete, or even how to complete it if it is not and of the importance that the completeness requires.

The intial dataset was incomplete and had the potential to become "unhelpfull" but after the inclusion of the aneasthetists data is suddenly became usefull again, almost like the bimodality of the cancer itself.

Data is whatever we want it to be depending upon what is or is not included and of how that information is interpreted.

I tried to defend a colleague this week who complained that she as overworked. Upon pulling out the data it appeared that she was doing less than half the work of previous colleagues, everyone was amazed and ready to start disciplinary proceeding.. I went further and interviewed her, what was not apparent in the data was the fact that contract procedures had changed and she was now in fact doing more work that her previous colleagues.... Our intial dataset did not include the contract changes, it would have been very difficult to model and I doubt that anyone would have realised the importance and yet it was fundamental to obtaining a usefull conclusion.

Data is just that, "data". It is the understanding of the data that is important not the data itself.

I found this to be a very interesting article, kudos El Reg.

[Matt 21]

Re: Data and its problems

Yes, and have an up vote.

I was a bit confused by the data for breast cancer. If operating on pre-menopausal women tends to lead to the cancer coming back is that not still better than not operating at all? Not screening because it only buys some women an extra few years is not an argument to stop screening. On the other hand if it only buys an extra few weeks, fair does.

I was also surprised about the ant-inflammatory. I thought it was well known that steroids reduced the effectiveness of the immune system. I've got a friend who's had more than 25 operations and they've never been treated with this kind of ant-inflammatory, is it specific to cancer operations? Or is it given before the patient comes back to the ward so they may not know they've had it?

[Frankee Llonnygog]

Thank you

I think that's all I need to say here

[DrBobK]

Excellent

Another thank you for a genuinely interesting article.

[gregthecanuck]

Well-written. Thanks!

[Anonymous Coward]

+1

Just wanted to say that if this is the sort of article we can regularly expect in the Weekend Edition then I'm all for it.

More please.

[SecretSonOfHG]

Informative and useful

No tech angle but who cares. Thanks

[Splodger]

Also popped into the comments to add my thanks for a genuinely interesting article.

[David Pollard]

An NHS Style Guide

Though I wouldn't wish to hinder important work, if the author could find time to write a style guide for NHS choices and other areas where there is an interface with the general public this might do a lot of good.

[silent_count]

"Statistics are one thing, but actually having a randomised controlled trial is still the gold standard in medicine."

And it can not be stated too emphatically - this is the difference between medicine and homeopathy (and similar bunkum).

[Britt Johnston]

the randomised controlled trial is still the gold standard in medicine?

The logical idea is to disentangle the effects of each of one or more interesting parameters.

Medics, on the one hand, are less scientific and more use-oriented. Doctors will switch regimes if the first one is unsatisfactory or, on occasion, try unproven drugs on an anecdotal report.

The trials are more scientific, more costly, and leave many parameters uninvestigated. That is why, for instance, cancer studies don't want to test for multiple co-medication, or relevant patient populations like children, women or over 65s.

'Gold' is the price of being scientific about evaluating new medicines. It has done well this last half century in checking for effiacy or reducing expected side-effects, and less well on quick access for serious diseases, cost reduction or finding underlying mechanisms.

[phil dude]

genetics and...

The problem is the medical profession is conservative, and only recently using "evidence based" techniques. Ask Ben Goldacre...

It should be clear with the DNA sequencing dropping in price (funny it stopped recently at $5k... not enough profit? have a peek here ), every single person who gets a tumour should have their DNA sequenced (methylation if possible...). This "guess" work with medications, surgery and all ignore the problem that is "how does a cell's DNA determinate differentiation?". Having the DNA of all tumours would be a start...

Does that mean no surgery? Of course not. But biology is very complex and it pays to have all the tools available when we understand the problem. Sequencing has already been done for some prolific cancers (google studies of melanoma, stomach cancer, childhood leukemia, for examples, sequencing both somatic and tumours).

Due to a political storm last year, the publication of the DNA sequence of the long studied HeLa cells, is not in the public domain. The most teasing thing from the "special deal done", can be read here , though I must be honest I have not tried to get access to the data yet, although I will.

One question I want answered (as do most) is "how broken can a cells metabolism get and keep living?". It is the cell refusing to die on cue that is a problem, and the HeLa line are pretty much immortal.

My thesis central topic is personalised medicine and how to design, target and administer pharmaceuticals based upon a patients genotype (each of us have unique DNA). A very small step, I should add, but one that is targeted at the molecular level, and at the moment just one protein.

Anything that improves our understanding and treatment of disease is to be welcomed. It is still shocking that women in the 21st century need to have prophylactic surgery....

P.

[Anonymous Coward]

randomised controlled trial is still the gold standard in medicine

If theory were practice it would be but as it is currently, it is emphatically not. I used to work in clinical trialling, at the randomisation and data collection end, and it was totally broken. What happened there was unforgivable.

This was reviewed by the very large well-known drugs companies (the ones who used us) and they would regularly inspect it and sign the process off because they just didn't have a clue (they sent executives rather than statisticians or IT people).

Finally, after I left someone sent a slightly competent team and they laid down the law, but it took too long.

I also worked with a guy who knew what happened earlier in the process and he said it was typically crap even before it reached us.

Maybe everything's changed in the 15 years since. Maybe.

(good article though, more please)

[IWVC]

Chemo and radiotherapy before surgery

A very interesting article. I had a run in with bowel cancer 7 years ago. The treatment at the time recommended Chemo and radiotherapy BEFORE the surgery. Fortunately for me it worked! The thinking was that cancer is an uncontrolled multiplication of cells and that the healing process is itself cell growth as it repairs the cuts. Some mechanism may cause the healing process to rum amok. Using chemo and radiotherapy after surgery slows the healing process and this may have some effect on the possibility of uncontrolled cell division happening. However the consultant surgeon warned me that if possible never to have surgery in that area again. Quoting him, "cancer loves an open wound" which fits in with the more detailed explanation in the article.

[david 12]

False history, artificial conflict

Everything in research gets re-invented every 30 years, due to the natural turn-over of staff. And, due to the exponenctial increase in medical knowledge and research technique, research avenues that were dead-ends 30 years ago often reveal new insites when revisited.

But having said that, you don't need to pretend that anyone in the last 50 years ever thought that surgery didn't trigger metatisation in some cases. The article would still have been interesting and informative without the faux conflct between 'old ideas' and 'new ideas'

[Anonymous Coward]

Interesting, if slightly concerning.

My sister has recently been through breast cancer surgery at 38. I really hope it was the right thing.

[xenny]

Reading this article - which I found fascinating, I'm left wondering how many of the health issues associated with breast implants are actually due to the silicon implants, and how many due to the surgery disturbing near sleeping dogs. :-(

[Benjol]

I read recently that there is a similar debate concerning screening for prostate cancer, can't remember where.

[HMinney]

Cancer - we're looking at the wrong mechanism

I think we're looking in the wrong direction here.

I'm with a charity that focuses on Vitamin B12, so I'll talk about cancer from the B12 point of view, although there are other causes. The mechanism will be much the same.

Vitamin B12 is the primary methylation agent for DNA. Methylated DNA can switch genes off, if DNA is short of methylation then it can't switch genes off. The metaphor I use is that the cell is like a kitchen, and the DNA like a cook book - if the pages blow freely, then every time the cook comes up to the cookbook to check what to make next, it reads a different recipe and makes a different protein. And 99% of genes in the DNA are supposed to be switched off at any one time, because they are all for building new cells. Result, lots of energy used up making random components (the weight loss of cancer sufferers), and lots of growth of new cells (because the materials are there) leading to tumours, active ones.

Add lots of Vitamin B12, and it sticks the pages of the cookbook down so the cookbook functions correctly. Cell stops making random components. Cancer stops. So much so, that cells naturally disappear and the tumour goes too.

So on to the model for the spread of cancer. Well it isn't due to cells migrating from the site of the surgery or from the site of the original tumour - it's simply that the next batch of cells have too low Vitamin B12 to be able to methylate their DNA. Just like draining the swamp (as the water level goes down, you find all the stumps and tangles).

Any evidence? when you give mice with cancer high doses of B12, they stop getting worse and in many cases the tumour actually disappears eventually. Any risk? none (obviously you need to keep an eye out for co-morbidities that need treating, but high B12 has no risk).

So what about the connection with surgery and chemotherapy? The first thing that B12 does (DNA methylation is probably the longest term) is to get rid of toxins from the body, and it does this by escorting them out. Blood full of tobacco? You've probably used up all of your B12 taking the tobacco out. Lead, arsenic, cyanide, organic poisons, etc - all take B12 out. Radicals from surgery? Yup. Chemotherapy? Yup. Less B12 = more cancer.

I know this is a very biassed view, and I expect lots of flames to follow, but have a look at it. It explains the mechanism and it has been shown in experiments, however it is low cost and there's no profit to be made so it's generally opposed.

[Anonymous Coward]

Re: Cancer - we're looking at the wrong mechanism

I signed up specifically to make this comment because your comment made me so angry. I sent your comment to a cancer researcher (specifically a molecular biologist and geneticist) who has worked in the field for many years. This is his response. I specifically am not going to address how upset your comment made me. I know I will resort to all kinds of furious rants about people who spout pseudo scientific jargon with zero citations to support nut job theories that give people with cancer false hope and stop them from getting proper treatment. I can barely contain my rage so i shall merely post the comments my learned friend had to make.

He said he wasn't going to bother with citations to prove your nonsense is NOT TRUE; as any reasonable commenter here knows, the onus is on you to provide credible research that backs up your garbage. (Let me make a shocking prediction: there isn't any! ) It took him all of 10 minutes to make these notes; that's how easy it was for someone with scientific training to dismantle your comment.

My biologist friend's comment is below:

It is most unfortunate to all of us, but vitamin B12 does NOT cure cancer.

I don't have time for a full literature search to prove that these things are NOT true - he should provide references that they are. What I've written below is scientifically correct - my comments in []:

Vitamin B12 is the primary methylation agent for DNA [True]. Methylated DNA can switch genes off [True], if DNA is short of methylation then it can't switch genes off [Doesn't work like that - check textbooks, do some reading, etc]. .... And 99% of genes in the DNA are supposed to be switched off at any one time [In some cells, not in others, and this is regulated by many mechanisms, DNA methylation only being one of them – they safeguard each other], because they are all for building new cells [Nonsense. Most of the cells in our body do NOT divide.]. Result, lots of energy used up making random components (the weight loss of cancer sufferers) [Absolutely not true. This is text book], and lots of growth of new cells (because the materials are there) leading to tumours, active ones.

Add lots of Vitamin B12, and it sticks the pages of the cookbook down so the cookbook functions correctly [This is the most important comment: There is no evidence for this whatsoever. All we know is that dietary intake of methyl-donor micronutrients is associated with measures of DNA methylation and gene expression, and epidemiologically to cancer risk in a very small subset of cancers - HPV-induced cancers. These cancers have a very direct and relatively simplistic cause – the virus; shut down viral gene expression, cancer won’t happen. Even then however, we have no idea what is the mechanistic link, if there is any at all, between B12 and the aetiology of these cancers; and we certainly have NO evidence that lack of vitamin B12 causes these or any cancers!!]. Cell stops making random components [Hilarious; nonsensical. -basic cell biology]. Cancer stops. So much so, that cells naturally disappear and the tumour goes too [Ridiculous, new age crap. I will NOT look for references to dispute that – homeopaths and people like him should be those to provide references of their fairy tales].

So on to the model for the spread of cancer. Well it isn't due to cells migrating from the site of the surgery or from the site of the original tumour - it's simply that the next batch of cells have too low Vitamin B12 to be able to methylate their DNA [???? ]. Just like draining the swamp (as the water level goes down, you find all the stumps and tangles).

Any evidence? when you give mice with cancer high doses of B12, they stop getting worse and in many cases the tumour actually disappears eventually. Any risk? none (obviously you need to keep an eye out for co-morbidities that need treating, but high B12 has no risk). [References or it never happened.]

So what about the connection with surgery and chemotherapy? The first thing that B12 does (DNA methylation is probably the longest term) is to get rid of toxins from the body, and it does this by escorting them out. Blood full of tobacco? You've probably used up all of your B12 taking the tobacco out. Lead, arsenic, cyanide, organic poisons, etc - all take B12 out. Radicals from surgery? Yup. Chemotherapy? Yup. Less B12 = more cancer [See my comment above.].

I know this is a very biassed view [I can fart a view that will be scientifically more sound than that.], and I expect lots of flames to follow [Because you have no idea what you’re talking about; remind me not to give money to your charity], but have a look at it. It explains the mechanism and it has been shown in experiments, however it is low cost and there's no profit to be made so it's generally opposed." [Ah, a conspiracy of course! All doctors want is to make money on the backs of their dying patients. What a doosh.]

[Speltier]

Inflammation

So basically the argument is made that inflammation facilitates cancer (there are secondary effects like the mechanical spreading, an excellent if gruesome example being the use of morcellation for reducing fibroids).

In the distant past inflammation reduced mortality by facilitating defense against infectious organisms. Now that is not so necessary, but it seems like medical practice hasn't quite caught up to modulating inflammation but more typically suppresses pain (opioid use then causing addictions and adding to morbidity... but that is another thread. Survive the injury and end up ruined on drugs).

The link to inflammation might be more direct than just the insult of surgery, since it is well known that low dose NSAID (Aspirin or aspirin) reduces the incidence of several cancers.