New Year Resolutions in this post truth world

In this post-truth world public figures have a tendency to talking solutions rather than rationally discussing the nature of a problem and reviewing the evidence which identifies it. The temptation to lie to support their case is emphasised. Just as important is their ability to deny expert evidence and call someone who is taking them to task a liar.

Extremist thinking leads to extreme expressions and extreme behaviour, well evidenced by the EU referendum campaign and the Trump presidential campaign in 2016. British politics is culturally unable to call a blatant lie a lie, partly because of a parliamentary convention aimed at avoiding extreme behaviour. There are no such constraints in the USA and their recent election campaign was the worse for it. Neither situation is desirable.

The Leave campaigners offered a simplistic solution to a complex problem, turned it into a populist mantra, and lied to achieve their objective. They had no plans on how to deliver a practical solution. Donald Trump identifies problems and talks solutions, but when he chooses a problem he fails to consider contexts and dismisses any evidence which either supports or denies the solution he has chosen.

The UK is the worse off for Brexit, the USA will be the worse off for Trumpism. It appears that Theresa May is being very level-headed, aiming to mitigate the damage caused by lies. We must hope that level-headed Americans will surround Trump and deliver rational policies.

In politics of course no-one ever makes a mistake. This extreme solutionism supported by self-justification based on level of volume, is a ‘movement’ or a ‘style’. Sadly it is being reflected in other areas of public life too.

In religion simplistic extreme approaches affect both Islam and Christianity. The jihadist view is based on selective literalism, they shout loud, put down co-religionists who disagree, and are violent. There are Christians who are just as selective and as literal, though not with the same violent intent. They can however use violent language to attempt to diminish other Christians who have a more considered faith.

Fortunately we do not often see this kind of behaviour in medicine, the denial of the MMR vaccine was perhaps the biggest example. There are some unsettling undertones in US based email lists where patients get advice, sometimes quite extraordinary, and viewpoints can get very vocal support. The hyping of drugs, manipulating media ‘experts’ and patient interest groups, and setting exploitative drug prices is all slowly being brought under control. However generally it is a area where evidence rules, and good science is appreciated.

The lessons of the medical world should be carried into political life. I would suggest for our politicians some New Year Resolutions, built on the medical research world.

Construct your argument rationally, without emotion, seek and recognise good quality evidence.

When you use evidence pay proper regard to the conclusions the researchers arrived at.

Don’t assume that someone with a view which opposes yours is stupid or telling a lie.

Don’t assume that an expert has an interest in denying a cause just because his evidence does not support it.

If there is a lie, and the evidence shows it to be one, say so.


Another conference season is over and sarcoma researchers have reported on their activities in laboratories and clinics across the world. I am no longer able to attend all these events like I used to. After a couple of years watching from afar you begin to get a slight sense of detachment and start to look at the entire field of activity in a different way.

Sarcoma research is focused on delivering a cure. It is an admirable aim but the search for a cure gets increasingly complex as tumours are better understood. Most of the different histological types of sarcoma now have a list of primary mutations but few have an affordable targeted therapy able to inhibit or correct these mutations in a real patient.

We have a good understanding of the way cancers respond to targeted therapies. GIST has been treated by imatinib for more than 15 years now. As early as 2003 there was work going on to discover why new metastatic tumours showed resistance and this uncovered new mutations, some of which are treatable and some are not. More than 10 years on this work continues but GIST patients with advancing disease eventually run out of treatment options. Can we anticipate that every sarcoma is going to head in this direction?

The recent study of oloratumab with/without doxorubicin in first-line chemotherapy resulted in EMA approval for the drug. Many doctors have reservations about the design of the study and the interpretation of the results. From a patient viewpoint the side effects of the additional drug were worse than doxorubicin on its own and there was no quality of life survey undertaken. Patient numbers were very small and there is the real possibility that some of the statistics reported were open to error. A Phase 3 study is now underway. Immunotherapy is showing great promise with a number of cancers and is being used in clinical trials in sarcoma. We must hope that it will do better than other much hyped ‘breakthroughs’.

Research must start to deliver higher degrees of patient benefit than has previously been possible, otherwise why should patients continue to support research. It is time for the research emphasis to shift. We need to look at better treatment in a more holistic manner while we keep our eye on finding a cure.

We must get patients to initial treatment more quickly, we know it can be curative. We need maintenance therapies which prevent recurrence following initial treatment, based on the better understanding of genetics across the range of sarcoma sub-types. Some patients will still develop metastasis so we need to explore better surgical and ablation therapies and make these more readily available. Chemotherapy must become the last resort in a menu of options for patients at this stage, not a sole choice as it is today for so many. On top of this we must build a better understanding of quality-of-life and develop systems which route patients to supportive care when they need it.

It’s a package of ideas which takes patient benefit forward, reduces the demand for toxic drugs and by researching what best helps patients, sets the tone for whatever the scientific community may offer next on the route to a cure.

Neo-adjuvant chemo – study identifies benefits

Every so often, and not often enough in the case of sarcoma, a research study is published which throws up an unexpected answer. Studies like this are a lifeblood in research. Innovative thinking and preparedness to use new approaches to resolving a key question are one thing, but when such a study opens up potential practice-changing ideas we must take notice.

Alessandro Gronchi published the results of the Italian Sarcoma Group study of neo-adjuvant chemotherapy at ESMO on Monday as a late-breaking abstract. I won’t go into the details of the study, those are readily available online. The surprise from the study is that the comparator regime of epirubicin+ifosfamide was superior to all the tailored regimes which formed the experimental arms of the study. The drugs were given to patients with high risk limb and trunk tumours as  three cycles of neoadjuvant treatment prior to surgery and the primary outcome measure was relapse free survival with overall survival also recorded.

Neoadjuvant treatment is not usual practice in soft tissue sarcoma. The epirubicin+ifosfamide combination had been previously trialled by the Italian Sarcoma Group and they had concluded that 3 cycles had a similar effect to 5 cycles. The tailored arms used drugs which are well known in sarcoma treatment and only one of them managed to compare favourably with the epirubicin+ifosfamide combination. That was the newest drug in the study,  trabectedin, which was paired with myxoid liposarcoma.

High grade soft tissue sarcoma frequently recurs after surgery, despite the best efforts of experienced surgeons. Recurrence most frequently involves metastasis which is difficult to treat. Taking every possible step to reduce that risk is welcome. Adjuvant (post operative) chemotherapy has little or no benefit, trials of that treatment go back a long way, all with similar conclusions.

Widespread use of neoadjuvant chemo is not likely to result from this study but it opens the way to further clinical trials with neoadjuvant epirubicin+ifosfamide. There is now justification for its use with high risk patients based on this study alone and I would anticipate that the investigators in the study, which includes some of Europe’s leading sarcoma oncologists, will be looking very hard at the results and thinking seriously of its impact on their practice.

Congratulations to Alessandro Gronchi and Paolo Casali, the innovators who drove this study. It is opening up a new route to deliver patient benefit. Also congratulations to EuroSarc, the collaborative project supported by the European Commission, led by Jean-Yves Blay, which funded the study.

Goodbye to the Rarer Cancers Foundation

It is with great regret that I heard of the decision by the Trustees of the Rarer Cancers Foundation to close the charity down. The founder of the charity, Penny Wilson-Webb died in 2009 and her husband, Andrew, took it on. Sadly Andrew died, from a rare cancer, in June this year. Clearly the Trustees have found it too challenging to find a new CEO, or to drive a new direction for the charity. It will leave a gap.

I worked with both Penny and Andrew over the years. Penny’s drive and charisma opened doors and forced change. Andrew’s approach was quieter but no less effective. Perhaps his greatest achievement was the quiet lobbying of David Cameron when Leader of the Opposition which resulted in the Cancer Drugs Fund (CDF) soon after he became Prime Minister. Others contributed but Andrew opened the door.

Whatever the faults and failings of the CDF it saved lives. The new structure for the CDF within NICE is still too new to comment on. We have certainly seen accelerated access to new therapies recently and that is most welcome.

The Rarer Cancers Foundation evolved from a support and advocacy body into a support and information organisation, with Andrew continuing the advocacy. He worked on the steering groups of both the Cancer Campaigning Group and Cancer52, the two organisations which represent cancer charities. His insights also informed European initiatives on rarer cancers, often with information coming from patients which the professionals did not know. I worked with him on a number of ‘think tank’ events and he was a valued colleague, sharing many of my views.

He rang me some time ago to tell me about his cancer. Unidentified, despite the efforts of some of the best UK cancer brains and treatment from some of the best oncologists in the world, it was clearly a threat to his life. And so it proved, a bitter irony.

Now the RCF itself is to disappear.

Behold, a toe

Well now it’s out. Sarcoma is a natural cancer, caused by life, not by any environmental or human factors. Not by diet, smoking, poor exercise, pesticides, volcanoes, or even old age. Well, that’s pushing it a bit far I admit but the discovery from Johannesburg that a 1.7m old fIMG_0511ossilised toe, from a hominid we cannot even guess what he or she looked like, showed evidence of osteosarcoma, opens the way for some speculation.

The majority of cancers are carcinomas and arise in visceral sites. A proportion are blood and lymph related – non-solid tumours. Another proportion are brain tumours. Then there are the mesenchymal tumours, cancers of connective tissue, sarcomas – about 1% of the total cancer incidence. We rehearse these differences frequently but we never speculate which of these cancers came first, doesn’t seem much point. Now we have some evidence. It’s far from conclusive but it leads to some more interesting thoughts.

Sarcomas can appear at any age and in just about any part of the body. The youngest patient I have known was 3 months old. He is now a healthy teenager. The oldest was 95, a delightful retired GP who quietly confided in me that he had done a ‘whoops’ surgery on a sarcoma back in the late 1940s. I have met patients with a primary tumour in the heart, having had a forequarter amputation, a facial rebuild from a skull tumour, and many like me who have lost a leg. None of these are regarded as typical of cancer.

Sarcomas can be difficult to treat. Getting good surgery is a priority but some sarcoma sub-types have a nasty habit of recurring even when all the post-surgical indications are good. Most are incurable at that stage although the pathway from incurable to terminal can be an exceedingly long one, as evidenced by me and many others. If we define cure as ‘dying from something else’ the cure rate improves significantly.

Sarcomas are relatively common in animals too. It is the most frequently diagnosed cancer in dogs and some of the tumour types which appear have strong similarities to human sarcomas. There are also variants of sarcoma which do not appear in humans, including transmissible tumours.

Tellingly sarcomas are more common in younger people that other solid tumours. At the time the Johannesburg toe was attached to a living being life expectancy would not have been great. Even if aggressive causes (human or animal) are ruled out what we would call natural causes would ensure that few, if any, lived much beyond two decades. Sarcoma could well have been the only solid tumour they faced. If that is true, other cancers are diseases of sophistication while sarcomas are diseases of life.

So where are we with treating sarcoma if surgery has not worked? We are far behind the game with targeted therapies. Immunotherapy is being worked on and first indications are uncertain. If diagnosed with unresectable sarcoma metastases a patient is still most likely to be offered doxorubicin as chemotherapy, a treatment that is in its fifth decade of use. With unpleasant side effects, about a 30% response rate and rapid relapse by the majority of responders it is a questionable treatment for many. Novel agents like trabectedin, derived from a sea squirt toxin, have value in extending life for some but not for all. Sarcoma is not seen as a priority for drug development even though great work is going on to define genetic characteristics which could open the way for new treatments.

The owner of the Johannesburg toe may well have died from lung metastases associated with the tumour on the toe. It could happen just like that today.

That kind of commentary applied to a more common tumour would be a widely heard clarion call for urgent action. However this is sarcoma, the ignored cancer, the boring 1.7m year old story.

Publishing All Trial results: a Covenant with Patients

A recent study from the USA published in BMJ highlights an issue which has been lurking under the carpet, despite the work of the All Trials campaign.

The study looked at the publication record of academically led clinical trials in the USA. It was led by Yale University. Over 5000 trials were identified as starting between October 2007 and September 2010. A number of these were excluded leaving 4347 across 51 academic institutions to be analysed. Overall 2892 (66.5%) had been published by July 2014. The study has a comprehensive analysis by type of trial and intervention, institution etc and certainly satisfied me it had considered all the issues. It came to the sad conclusion that publication rates are very variable and there is “poor performance across leading academic medical centers in the dissemination of clinical trial results.”

The focus for All Trials has been on industry studies and great steps have been achieved. However this BMJ study shows that the academic world needs closer examination and needs to be provoked into action too. In Europe it may be less of a problem but we don’t know, we certainly cannot be sure. We have clear commitments about publishing from EORTC and from many leading academic collaborative groups, national and multi-national. Individual institutions have made commitments too but what is the real story? We don’t know. Is the positive action from the prominent few allowing others to hide away, ignoring the issue in the hope it will go away?

We don’t actually need a study like the one from the USA. We could just start to take action.

The best way of finding out would be through the registration authorities. Each sponsor should provide a simple table of studies sponsored, completion information and planned publication dates, regularly updated and made publicly available. This table could be entitled The Patient Covenant. Any sponsor (quite often these are academic bodies) which has outstanding trial publications should be unable to register any new trial until their obligations are met.

In addition any principal investigator taking a study to ethics for approval should have his study placed on hold if trial publications are outstanding. This would give a two-tier coverage and will stop institutions breaching their covenant with patients.

As patients we should be quite uncompromising about trial publication. There are no excuses for not publishing. Failure to do so violates the explicit promise made to patients entering the trial that it aims to provide clinical evidence, even failure to achieve a trial objective can still provide evidence. Not publishing impairs understanding and threatens the integrity of clinical evidence, squandering resources in doing so.

I was very taken by four verbs used in the conclusion of the study published by BMJ. Think about them. I use them above and I list them out of context below because I think it adds to their impact:

  • impairs
  • violates
  • squanders
  • threatens

If you are reading this you know the context; avoid these blistering criticisms.


This blog first published by the 26th February 2016

In praise of independence of thought

The National Archives continually releases items of interest which the press keep an eye on. This week the Times has reported on the 1982/84 correspondence which reveals that Margaret Thatcher’s government put pressure on the University of Lancaster not to award an honorary degree to Nelson Mandela. The Independent repeated the story and I have linked to them because you don’t need a subscription to read it

Mrs Thatcher had previously dismissed the African National Congress (ANC) as “a typical terrorist organisation” and refused to back sanctions against the South African government which operated the brutal separatist policy of apartheid. Everything changed of course in 1990 when apartheid fell apart and Mandela was released from prison.  No-one as far as we know ever accused Mrs Thatcher in person of being two-faced but the lady who famously said “you turn if you want to, this lady is not for turning” (another issue at another time it is true) delivered a beaming smile for the No10 doorstep handshakes when Mandela came to the UK.

However the University of Lancaster stuck to its guns. Government pressure had no effect. Although he could not be present Princess Alexandra, the University Chancellor, awarded an honorary LLD to Nelson Mandela in 1984. At that time it must have been like a small light in the dark, a symbol of hope that honesty and justice would eventually prevail.

This where I declare an interest. The University of Lancaster awarded me an honorary LLD in 2012. When I saw the list of those who had preceded me I was blown away by one name above all others, Nelson Mandela. I was privileged to be awarded the honour of the degree but to be in his company made it extra special.  When Sir Chris Bonnington, the University Chancellor, shook my hand I was thinking of my inspirational predecessor who did not have to face this grand (and slightly ludicrous) ceremony because he was behind bars.

Let us give thanks for independence of thought. It is one of our treasured freedoms and we should never be scared of using it.


More and more the Christian underpinning of our society seems under attack. Britain was renowned for its liberal Christian faith. People mattered. Social welfare, the NHS, state education, a paternal approach to those in need globally, all have been a matter of pride for a country which valued people. Now we have greedy bankers, politicians we don’t trust or believe, and a society where every change or development is measured in £s.

The Christian ethic seems to be fast withering away. People like us are merely there to make up the numbers. There seems to be no alternative. Leaders in public life all look and sound alike. Where is faith?

At another time and in another place in a famous incident a young preacher disrupted a money market. He sent the tables flying and released the animals and birds captured for sacrifice. Somewhere else he told a story about a widow and her valued farthing, highlighting a bleak outlook for unscrupulous moneychangers and rapacious tax gatherers. At other times he talked about ordinary people and how their generosity of spirit was a different kind of wealth, even if they were Samaritans.

In his day there was a confusion of religious and secular authorities all of which had to be respected. Above all there was the law, religious rules which governed daily life and which were to be seen as sacrosanct. The keepers of those laws allowed the moneychangers’ tables and were immune from criticism. Woe betide he who challenged them.

We tell ourselves we have to learn from these stories but how often do we surround the real message with dogma and tradition? Our approach should be inclusive, open and questioning, looking for what we can learn, putting no barriers around it and looking at how we can use it in our daily life.

It is our remit to take Christian faith to challenge the philosophies of modern life in practical and pragmatic ways. Little things count, sometimes more than big ones. We may not be able to copy Jesus by turning over the tables of the moneychangers but we can learn from his example and take small incremental steps, driven by our faith.

First published as URC Voice in Stretton Focus, June 2015


As a patient working in cancer research for over ten years now, one thing has slowly become more and more apparent.

The greatest patient benefit accrues from studies which are academically led. A bold statement which needs a bit of unpicking.

Pharmaceutically led studies dominate our attention because of the scale of investment and the power of the public relations team. They may well be led by talented academic clinicians but the protocol has been driven by commercial requirements even if it is an early phase study. The reality is that larger and larger amounts of money are being committed to studies which benefit fewer and fewer patients.

I am not decrying all that effort. My personal view is that if a new drug can benefit just one patient let us have that drug. However I don’t have deep pockets, any more than any healthcare system does, so that principle has some weaknesses – as does the current pharmaceutical business model.

Academically led studies, which draw funding from government, charities or philanthropic sources, may have a component from pharma providing free access to drugs. These studies can also draw on treatments more widely available in the market such as generic versions of previously patented drugs. Academic studies will be seeking to find better ways of treating patients using more clinically relevant outcomes and taking fuller account of the whole patient. They are not seeking solely to identify the numeric significance of a treatment.

This sets academic studies apart from highly publicised drug studies with registration objectives.

The EORTC (a charity) is an important provider of academic studies. The European Commission is funding studies through its R&D programme. Governments support studies, often providing funding to a university hospital. An important source for such studies is the UK, where local funding from Cancer Research UK is a critical component. Occasionally one trial will stand out.

STAMPEDE is a ‘basket’ study looking at a range of drugs in treating advanced prostate cancer. It is a 7,000 patient multi-arm study. It could not be run by pharma. Its first results published at ASCO 2015 looked at docetaxel, which is now off patent. The drug was given earlier than it is in current practice. An OS (overall survival) improvement of 24% and ‘failure free’ survival of 38% translates into significant clinical benefit, improving patient longevity by a median of just under two years.

The Chief Investigator, Professor Nick James from University of Warwick, said “Our headline conclusion would be that docetaxel should be considered as routine practice in men with newly diagnosed metastatic disease. With non-metastatic disease, there remains uncertainty as to whether there’s a survival benefit or not but it certainly improves failure-free survival by a substantial amount.”

Pharma company researchers would give their right arms for results like that in a cohort of patients as large as this. It will change clinical practice without truckloads of expensive documentation being required by EMA.

So lets pay more attention to academic studies. They can change things in big ways and have the potential to provide patient benefit far beyond the seemingly eternal procession of pharma company registration studies targeting smaller and smaller cohorts of patients.

First published on the Cancer Blog at

Further reading on STAMPEDE