38. Reviewing my Gastric cancer – a case for Proton beam radiation therapy?

Simulation of Proton Beam Therapy specifically targeting a tumour located deep in the brain.  Accessed at http://www.proton-therapy.org/howit.htm on Wednesday, 2 February, 2016.

Next Monday morning I will sit down with Dr P to discuss the results of my CT scan carried out last Tuesday – an anxiety-invoking two week wait! What will he say? For the big picture, there’ll be a decision about whether to carry on the same treatment (EOX combo) for 6 cycles (4.5 months) or for 8 cycles (6 months).   There’s pros and cons of course, but some days I just so, so want to be free of consuming medications of one sort or another, such as “shite-tasting” pills, solutions, suspensions, revolting creamy stuff and even the marginally better but still sickly fruity stuff, that the 6 cycle option really appeals!

The alternate is to carry on to 8 courses (6 months) to “kill the buggar some more”, and then I have to bite the bullet over the current side effects. But, there’s more…! I would also have to hope that permanent damage to key areas of my body doesn’t occur. I’m thinking particularly of nerve damage to my finger-tips which do take a ‘pounding’ because of the cold-response that is induced by Oxaliplatin in my EOX Combo Chemo.

The upside of the 6 cycle option is that I’d be free of the afore-mentioned as well as other side effects a little sooner. The downside, however, is that remnants of tumour may still remain or even have developed at new sites (though not visible by CT scan) that could trigger a re-appearance of my cancer at its original site or at any new as well as old metastatic locations. Sneaky sods – these cancer cells, eh?

The only upside of the 8 cycle option is that it kills more cancer (I have already been informed that a complete eradication down to the very last tumour cell cannot be guaranteed and hence I bear my label of receiving palliative care only). When Dr P starts mentioning surgery or radiotherapy then there might be a glimmer of hope for a switch to a curative-care regime though that, it would seem, is a long way off. But hey, who knows?

So, it’s complicated! I’ve just got to have in my blog at least one Steve Martin movie – in a starring role! This is certainly not his best, but the title is just right for my “coincidental link!”.

Accessed at http://www.imdb.com/title/tt1230414/ on 2 February 2016.

Even if I was given a free choice – minus Dr P’s own advice– what would I do? What further questions should I ask this time? I’m still trying to sort this out. But of course, I am interested in any form of treatment that may give me a chance of being re-classified as a curative-care patient! As mentioned above radiotherapy could be an option if my only cancerous site could be narrowed to a single or at least easily noted location (only for certain would do).

And then suddenly, bang – there’s a BBC news item (Monday, 1 February) reporting on a recently highlighted study, published in the Lancet (Public Release: 29-Jan-2016), Yock, T. et. al., (2016). The Lancet Oncology: “Proton beam therapy offers potential to treat childhood brain cancer with fewer severe side effects than conventional radiotherapy”.

Accessed at http://www.eurekalert.org/pub_releases/2016-01/tl-tlo012816.php on 2 February 2016.

The new study involved 59 patients, aged 3 to 21, who were enrolled between 2003 and 2009, and revealed that the childhood brain cancer medulloblastoma treated via a procedure known as Proton Beam Therapy, “appears to be as safe as conventional radiotherapy with similar survival rates (83% at 3 years; 80% at 5 years)”; and additionally, compared to conventional radiotherapy, “proton radiotherapy may not be as toxic to the rest of a child’s body (hearing loss:12% at 3 years-15% at 5 years) as well as having, “no cardiac, pulmonary, or gastrointestinal toxic effects, which are common in patients treated with photon radiotherapy”. This looks interesting!

Protons can be generated and focused into beams in a controlled way using large particle accelerators. Uhm… particle accelerators.  Might I digress for a moment, or ten? CERN in Switzerland has the biggest and most powerful particle accelerator in the world – though everyone seems to own it!

CERN’s powerful particle supercollider. Accessed at http://home.cern/topics/large-hadron-collider on 2 February 2016.

This one, known as The Large Hadron Collider (LHC) comprises a 27 kilometer ring of superconducting magnets that focus and accelerate beams of particles towards one another at speeds close to that of light.  This machine though is used for things other than Proton Beam Therapy; notably, crashing sub-atomic particles into one another and creating even smaller ones! Now people in particle physics think this is great and even get Nobel prizes for their work, or share it with others who have also had a great idea or conducted an ‘elegant’ experiment. For example, Professor Peter Higgs at Edinburgh University predicted the existence of the now, so-called Higgs Boson. Its existence was only confirmed in 2012 and he got his share (with François Englert) of the Nobel prize for Physics in 2013.

Professor Peter Higgs. Accessed at https://en.wikipedia.org/wiki/Higgs_boson on 2 February 2016.

I’m not sure how great this is and if you bear with me I’ll share with you the rather different view I take. If I take my hammer and smash a large rock, I get a cluster of small rocks. If I then take one from said cluster of (smaller) rocks and smash it again with even more malice this time, lo and behold, I generate a further cluster of even smaller rocks. I think I’ll call one of these, the smallest piece as it happens, Mason’s Mason (pronounced Mayzon!).  I have so-named it because it behaves similarly to a photon which is able to appear in two places at once; and is also a particle and yet behaves like a wave at the same time.  This ‘duality‘ is a phenomenon explained by Schrodinger’s cat analogy.

Schrodinger’s thought experiment Accessed at https://en.wikipedia.org/wiki/Schr%C3%B6dinger’s_cat on 2 February 2016.

Schrodinger devised a “thought experiment” in which a cat is locked in a sealed box that contains a radioactive substance that may decay (or not). If it does this is detected and further triggers release of hydrogen cyanide which kills the cat. The “not knowing what has happened yet state” was (jokingly?) referred to by Schrodinger as the “superposition state” where the cat can be both alive and dead – until an external observer looks inside the sealed box (Schrodinger, 1935). It is then either alive or dead. And this analogy helps you understand the quantum mechanics that underpin behaviour of very small particles (but definitely not cat-sized ones) such as atoms and photons, apparently!

Anyway, the Mason obeys the same rules and thus at any one time it may be here, or it may be there, depending upon where you look for it – simple and elegant, eh? People have received Nobel prizes for less, don’t you know? And let me tell you, I predicted its existence in 1956 when I was only 4 years old, and had just learnt about hammers and how much damage they do to one and half-year-old baby sisters! Now is this rocket science? If so, I’d like my (share of) Nobel prize for “common, or is that uncommon, sense”, please!

Now to digress back to my pre-digression:

As I was saying, protons can be generated and focused into beams in a controlled way using large particle accelerators. Proton beam therapy damages cancer cells in the same way as radiotherapy. Unlike X-ray beams, however, proton beams stop once they hit their target (a tumour growth normally), rather than carrying on through the body. Thus, the proton beam more specifically targets the cancer whilst sparing more of a patient’s own nearby normal tissue. And, it is the latter that reduces side effects.

Protons are positively-charged particles found together with Neutrons in the nucleus of every atom. The movement of proton beams (like other ionising radiation sources) through ‘solids’ is governed by what is known as the Bragg peak effect, after William Henry Bragg (1903). He defined the properties of various ionising radiation sources with reference to their energy loss (Vertical axis) as they traverse matter which slows down their movement (Horizontal axis). Energy sources such as α particles, other ion rays and protons all have characteristic patterns (Fig 1).

Fig 1 Bragg curves for Photons (eg X-rays); and protons. Accessed at https://en.wikipedia.org/wiki/Bragg_peak on 2 February 2016.

What distinguishes the proton curve is the ‘peak’ of energy reached just prior to its final abrupt decay – that is also marked by an annihilation ‘explosion’, with luck and a trained operator focusing this at the 3D location of the tumour, say in the spinal cord. In contrast, X-rays continue, albeit with slower exponential decay, beyond the site of a targeted-tumour and further into normal tissue which will continue to be exposed to damaging radiation, that also affected normal tissue precisely located ahead of the tumour (double bad news there, for the radiotherapy camp!).

Proton Beam Therapy is not a new form of treatment but it is news-worthy, mainly because the UK lags behind some other countries in not having even one machine of its own capable of generating a high energy proton beam that can be used to treat patients across a sample of the total spectrum of 2000 or so cancers, and not just eye cancers (see below).

“Currently (2013) the UK has one proton beam therapy facility, at Clatterbridge Cancer Centre. But it’s a ‘low-energy’ machine, only suitable for treating people with rare eye cancers.”

Nevertheless, the UK government has recognised this glaring gap in its cancer care provision, and in 2013 it commissioned two state-of-the-art high-energy proton beam facilities to be built in the UK by 2018. These are to be located at the Christie Hospital in Manchester, and at UCL Hospital in London – at a total cost of £250 million. In addition, there are plans to build a research-focused proton beam centre in a new institute at Oxford University – a major investment being supported by the Government and Cancer Research UK, among others.

The proposed PBT facility at University College London (UCL).

Currently, cancer patients (mostly children) that require Proton Beam Therapy must be referred by the NHS to facilities in either the USA or Switzerland. From 2018, the first cancer patients treated at the new NHS facilities will be those for whom current evidence already recommends proton beam therapy:

• children with several specific types of cancer
• some adults with rare cancers, particularly where tumours have developed near the brain, base of the skull or spine.

It was in 2014 that a previous news headline propelled Proton Beam Therapy into public consciousness when a small boy, Ashya King, was snatched from a Southampton hospital by his parents, Brett and Naghmeh King, against medical advice, in order to take him to a Proton Beam Therapy treatment centre in Prague, in the Czech Republic.

His parents believed their son was not being offered the best treatment available for his condition and consequently took matters into their own hands. With hindsight, it is easy to criticise the heavy-handed approach by the hospital authorities who first tried to prevent the ‘family abduction’ and subsequently notified the police who then issued arrest warrants and ultimately withheld the parents (in Spain) from their son whist he underwent treatment in a foreign hospital in a foreign land – a scary prospect for anyone, but a small boy, come on? In defence of the local NHS hospital, it later agreed to fund this treatment, which ultimately was also successful – cancer-free for 9 months.

Should I get carried away with new possibilities such as Proton Beam Therapy for my cancer? Sadly, after reviewing even a small sample of the online literature, the answer is probably no! Leaving aside whether there is sufficient research evidence generated from properly conducted (randomised, controlled, blind etc – you get it, right?) clinical trials to claim superiority over radiotherapy, more importantly, it seems, is the type and location of the cancers best suited to Proton beam therapy. Gastric cancer (probably, especially for adults) isn’t one of these – at present.

Following completion of my 6 or 8 cycles of my current chemotherapy regime I should know whether my own primary tumour site has been declared ‘clear’ of active cancer, leaving only residual active metastatic deposits. As previously described, these are in in part of my pancreas, a few lymph nodes and one adrenal gland. If only one of these sites is active at this time (he says optimistically!), then who knows, perhaps “targeted therapies” such as Proton Beam Therapy, Cyberknife and Immunotherapy using modified viruses such as herpes and measles, will present new opportunities – even for me?

Whilst there are some benefits of Proton Beam Therapy over conventional approaches it may be premature to think that this is the ‘answer’ to cancer cure. Even leading experts remain cautious?  What follows is a range of statements made by one of the UK’s leading clinical radiotherapists and Proton Beam Therapy specialist, Dr Adrian Crellin.

“Since it delivers a lower dose of radiation to surrounding tissues, proton beam therapy’s main advantage is in reducing side-effects, rather than improving survival or cure,” he says. This helps patients whose tumours are near sensitive organs (e.g. the brain or spinal cord) by reducing damage caused to healthy tissue– especially in children, as their organs are still developing.

There are also suggestions that it can reduce the (small) risk of developing a second cancer later in life. And, for some rare cancers in adults, the reduced damage to surrounding tissue means proton beam therapy can be given at a higher dose. This, Crellin says, might be more effective at destroying cancer cells, although clear-cut evidence of survival benefit is limited. “But it’s critical to stress that for most patients right now, there’s no strong evidence that proton beam radiotherapy is ‘better’ at curing cancer, or improving a patient’s chances of survival, than conventional x-ray radiotherapy.”, says Crellin. That’s why it’s so important that more research is done on proton beam therapy (2013).

Maybe the recently published study in the Lancet Oncology at least provides further evidence that such investigations are happening and are beginning to bear fruit.  Accessed at http://scienceblog.cancerresearchuk.org/2015/07/16/proton-beam-therapy-where-are-we-now/ on 2 February 2016.

On the other hand, bloggers such as me (ie cancer patients, some with not a lot of time left) argue strongly that Proton Beam Therapy, if it was a lot cheaper (it costs about £40,000 to treat one patient!), would actually replace X-ray radiotherapy, and there would be no debate. I am not sufficiently qualified to comment, but if the recent Lancet Oncology paper is predictive of future clinical trial outcomes, then the bloggers have it, in my opinion, since Proton beam therapy is no worse on mortality data and similar or better overall on morbidity data. It boils down to money, as it always does in health matters – compare just about any aspect of the health or illness of poor people with that of wealthy folk and guess what you will find?

That’s all folks! Bye for now.

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