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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.

Blog about patient involvement in research on the ABPI website

Blog about patient consent and right to know on CancerWorld ESO website

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.

http://www.esmo.org/Conferences/ESMO-2016-Congress/Press-Media/Significant-Survival-Gains-from-Neoadjuvant-Chemotherapy-for-High-risk-Soft-Tissue-Sarcoma

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.

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 fossilised 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.

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