Ablation of bone tumours

For patients with advanced cancer bone tumours, (whether from primary bone cancers like osteosarcoma or metastases from other types of cancer, such as breast or prostate), can be a cause of persistent and hard to treat pain. A standard treatment in many such situations is radiotherapy, which can have unpleasant side-effects, and, in the case of Li Fraumeni Syndrome patients, might also have long-term implications regarding further cancers. Additionally, treating cancer pain with opiate-based pain-killers, such as morphine, can also be problematic given the evidence that opioids can cause further cancer progression (though this can be reversed with the use of naltrexone).

In which case there’s some encouraging news being reported at the 29th Annual Meeting of the American Academy of Pain Medicine. A group of French clinicians have reported on treating patients with tumour pain, including bone tumours, with micro-wave ablation (MWA).

One of the doctors, Adrian Kastler of the Centre Hospitalier Universitaire, in Besançon, France, is reported as saying:

"This technique may be applied to any patient suffering from bone tumour pain, mainly in patients suffering from bone metastases, refractory to conventional therapies. The main advantage of ablation techniques is the fast pain relief obtained - immediately after the procedure - as opposed to delayed pain relief obtained with radiation therapy… Our research showed that the use of MWA in bone and soft-tissue tumours is feasible and effective concerning pain palliation. However, MWA needs to be studied in order to apply the same procedure in a curative intention." 

The last point is certainly one that needs urgent attention. Bone tumours are notoriously hard to treat, so any new treatment that shows signs of being effective needs to be researched as a matter of priority. And, given that primary bone cancers are often unresponsive to chemotherapy, any physical treatments that can be used alongside surgery are urgently needed.

Milk, cancer and hype

The headlines were striking enough, for example the Daily Mail declared that 'Breast cancer patients who eat cheese, yogurts or ice cream could HALVE their chances of survival', while the Daily Mirror ran the headline 'High-fat dairy food increases risk of death in breast cancer patients'. The question is are these scary headlines warranted?

The source of the headlines is a study that looked at dairy intake in women after they had been diagnosed with early-stage invasive breast cancer between 1997 and 2000. These women were asked to fill in questionnaires about their diet, and these were followed up five or six years later. The researchers then looked at the associations with dairy intake and outcomes. The reported outcome was that intake of high-fat dairy was associated with a great risk of death, both from cancer and other causes.

The first thing to say is that this paper is not open access. It's published in the Journal of the National Cancer Institute (JNCI), which is a tax-payer funded body, and it's outrageous that scientific research like this is kept away from the public. When there's a story as potentially important as this then there's no excuse for keeping the data behind a pay-wall. US tax-payers should be demanding that the JNCI switch to open access publishing immediately.

That said, and without access to the full paper, there are some comments to make on what's reported in the abstract of the paper. Firstly this is a study that depends on questionnaires. This is one of the most unreliable sources of information on long term diet that there is. It depends on people being able to accurately remember what they eat and drink, and that they're not lying to themselves or trying to impress the people running the survey. In a long time frame, it also means the researchers have to make assumptions about the long periods between questionnaires. Remember, the researchers are trying to establish the cumulative intake of dairy.

Itraconazole - Anti-fungal and anti-cancer

One of the common themes of this site is the use of existing drugs as anti-cancer agents. Given the many years and millions of dollars it takes to get new drugs from the lab and into early phase human trials, it makes a lot of sense to re-look at existing, approved drugs to see if they can be re-purposed as anti-cancer therapies. Prominent examples of such drugs include metformin (used in diabetes), aspirin (pain killer), beta blockers (used for treating hypertension) and mebendazole (used as an anti-parasitic agent).

The latest example is the anti-fungal drug Itraconazole. A Phase II trial has just been reported in a paper in the Oncologist - freely accessible to all here: http://theoncologist.alphamedpress.org/content/18/2/163.full. The drug was used to treat advanced prostate cancer (metastatic castration-resistant prostate cancer to be exact). Two dosing schedules were used, low-dose (200 mg/day) or high-dose (600 mg/day), and the men were treated for 24 weeks and then assessed for a reduction in PSA and, more importantly, for progression free survival.

The low dose arm of the trial was abandoned early because of the low levels of response, however the higher dose arm continued to completion. The results were fairly impressive. The primary end-point of the study was stopping the increase in PSA levels, and this was acheived in 48% of men on the high dose (12 of 25 men). The main secondary end point was freedom from disease progression (which is the more important measure overall), and here the result was that 24-week PFS rate was estimated to be 61.6%.

The 2-Day Diet

It may seem odd to find a review of a diet book on a web site devoted to cancer, but there are good reasons for looking at this book. Firstly, it's an accepted fact that there is a strong link between obesity, metabolism and cancer. Secondly, there is an increasing view among some researchers that cancer is a metabolic syndrome, and that cancers are associated with a whole set of metabolic changes, both in the tumour and the surrounding tissues. Cancer and metabolism, and therefore diet, are inextricably linked. And, as discussed on this site in the past, there is evidence that altering diet can impact cancer treatments as in the work that looked at chemo response and fasting. There is another reason for looking at this book - the authors (Professor Tony Howell and Dr Michelle Harvie) are both working in breast cancer research, and are involved specifically in helping patients reduce their chances of getting the disease or reducing the risk of recurrence. One of the authors, Tony Howell, is well known to regular readers of this site for his work on the reverse Warburg effect and his association with Michael Lisanti and the development of new theories that link cancer with metabolism.

That said, this is primarily a book about diets and losing weight rather than a book specifically about cancer. Although the links to cancer are there in the text, and many of the patient stories include mention of cancer, the main aim is to help readers lose weight and keep it off. And, in doing so, to reap the overall health benefits across the board.

So, what is the 2-day Diet, and how does it differ from the thousands of other diet books on the market? A key point to make up front is that this is a diet that's been backed up by clinical data. There are no celebrity endorsements, no one selling expensive supplements or foods, no hand waving or bold claims unsupported by evidence. This is a diet that has been shown to work, it's that simple. Simple too is the basic idea behind the diet - it's simpler to stick to a strict diet for two days per week than it is for seven. And, importantly, the changes induced by a strict two day a week diet are significant enough to cause changes in body weight, glucose tolerance, mood and so on.

PDT Norfolk

The mainstays of cancer treatment remain chemotherapy, surgery and radiotherapy. These are the big three treatment modalities and have, largely, remained in place as the core weapons in the arsenal of oncologists despite the advent of a number of newer treatments. However, there is a class of treatments called ablative therapies that really need to become the fourth big weapon in the anti-cancer arsenal. Ablative therapies include photodynamic therapy (PDT), cryoablation, radio-frequency or microwave ablation and the new kid on the block, irreversible electroporation (which I have previously written about here).

Of these treatments, which all take the approach of directly and physically attacking tumours rather indirectly using drugs or radiation, it is PDT which is the most mature and most widely used. PDT works by injecting a light sensitive drug (called a photosensitiser) into a patient and then letting the drug accumulate in tumour cells – normal cells do not take up the drug to the same extent. Once the drug has been absorbed by the tumour light is applied to it – usually by a surgeon operating to gain access to the tumour and then shining a laser or LED directly on to the tumour. The photosensitive drug in the tumour cells reacts to the light and in the process kills the cell. In this way PDT can be used to destroy solid tumours directly.

While PDT is the most mature of the ablative treatments, it’s still not used widely enough in the UK, and even many oncologists remain unaware that it is available and that it’s a viable treatment option for their patients. This is a treatment that works, can be used against a wide variety of tumour types and does not produce the long-term side-effects of radiotherapy or chemotherapy. If ever there was a treatment that needed to become more widely known and available to more patients it’s this one. And, luckily, there are people around who are actively campaigning to raise awareness of PDT amongst the medical profession, amongst patients and the general public.

One such group is PDT Norfolk (take a visit to their site here: http://www.pdtnorfolk.co.uk/). Recently I travelled up from London to meet with the team at PDT Norfolk to discuss some of the science, some strategy and ways that we could work together. It was a good meeting and I think some very positive ideas came out of it. I think this is a campaign that has the potential to advance research in PDT as well as to raise the profile of the treatment, provide resources for patients and help to bring this treatment to a wider range of patients.

Of Mice and Men

I’ve written about the state of cancer research on a number of occasions in the past, in particular focusing on the use of different models of cancer – for example here: http://www.anticancer.org.uk/2012/05/wrong-models-of-cancer-part-2.html and here: http://www.anticancer.org.uk/2012/04/standards-in-cancer-research.html and here: http://www.anticancer.org.uk/2011/11/test-tube-cancer-cells-and-people.html. So I hope it’s not getting repetitive to raise the subject again in the light of an important new paper in the Proceedings of the National Academy of Sciences (PNAS). The paper, Genomic responses in mouse models poorly mimic human inflammatory diseases is not about cancer as such, but it’s as important and relevant as any paper on cancer.

The opening line of the paper makes plain why these results are important:

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials.

And it’s true enough in most areas of medicine, but none more so than in cancer research, where the mouse model is king. But the only problem is that mouse models don’t always match human disease profiles at all well. In the specific case that this paper outlines, it turns out that mouse models of massive inflammatory responses in critically ill patients are miles apart. To quote from the paper again:

The success rate is even worse for those trials in the field of inflammation, a condition present in many human diseases. To date, there have been nearly 150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed.

The reason for this divergence turns out to be because the relationship between genes changed in human patients bears little relationship to the genes expressed in the mouse models of the diseases – the relationship is pretty much random. However, for years scientists who have been studying these diseases have focused on drugs that work for mice and then these drugs have subsequently failed in humans. Not only has this cost millions, it also means that much research effort has been wasted in targeting genes that have nothing to do with human diseases. It also means that potentially useful drugs have been abandoned precisely because they failed to do anything in mice.
And it’s not just inflammatory diseases at stake – the same is true in cancer research. We can only speculate on how much money, effort and intellectual energy has been wasted on research that doesn’t apply to people. The reliance on test tubes and mouse models means that much time and effort has been for nothing.

Something needs to change.

LFS SIGNIFY Trial Looking for Volunteers

This just in from the people running the SIGNIFY trial for Li Fraumeni Syndrome:

We are conducting a small scale pilot study to investigate the use of whole body magnetic resonance imaging (MRI) in families with Li Fraumeni Syndrome.

We would like to enrol individuals in the trial who are between 18 and 60 years old and are known to have a genetic mutation (alteration) in the P53 gene as well as unrelated people who do not carry the gene mutation whose scan results can be used as controls.

All study participants will undergo a whole body MRI scan at the Royal Marsden Hospital, Sutton, Surrey.

If you are interested please contact SIGNIFY study coordinator Dr Emma Killick or another member of the SIGNIFY team at the Institute of Cancer Research on 0208 661 3375.