A Gastro-Intestinal Stromal Tumour is rare, but you are not alone!

May 9TH 2008

We held another very interesting and supportive meeting with 55 patients and carers at the Hilton Hotel in Sheffield on 9th May. Our two speakers were Dr David Hughes and Professor Penella Woll, both from the Sheffield GIST team. Both talks provoked interest, laughter and a number of questions.



Dr David Hughes talked about the role of pathology in the diagnosis and management of GIST. He is a consultant histopathologist and one of the small number of sarcoma specialists in the country.

He said that it was an area of medicine where advances are moving apace, but that the rate of gaining knowledge about GIST is limited by its rarity.

Essentially, in order to decide on the most appropriate treatment, a specimen from a resection or biopsy is cut up, pickled in formalin and embedded in paraffin wax. This is a 19th century procedure. Preserving in wax allows the cutting of very thin sections (usually 40 microns or 1/250 mm) which can be stained in beautiful and revealing colours.

Certain things are important, and the most important of all is to ensure that the specimen is properly identified with the correct donor! The worst mistake is to issue a report on the wrong person. His lab processes requests for over 50,000 cases per year and unfortunately mistakes can happen..

The report on each sample must include:

  • Is it from a biopsy or a resection?
  • Where it is from, stomach, jejunum etc?
  • What is the size of the tumour and its relationship to other anatomical structures?
  • If it is a surgical resection, how clear are the margins?
  • What type is it, is it GIST or something else?
  • What risk category does it fit into? (worked out from location, size and mitotic activity).

He then went on to say how cancer care today really was, or should be, delivered by multi-disciplinary teams. These include: a surgeon, a radiologist, a pathologist, an oncologist and a nurse specialist. Nowadays, pathologists spend less time attending events involving their speciality and more time attending multi-disciplinary conferences. There is a lot of value placed on dialogue between professionals and patients.


Recently the labs are becoming more involved in mutational analyses. This is used to detect mutations of exons, introns of defined genes. The quantity of DNA is increased using PCR ("Polymerase Chain Reaction") techniques, and then alterations in the sequence of the largest genes or parts of genes can be detected. Although increasingly common, this analysis is not done routinely, owing to its cost. However, to put it in perspective, each test costs no more than 2 or 3 days of Glivec treatment. In the future Dr Hughes sees more up front mutational analyses being done to identify the genotypes of individual tumours, and to see how they change.


He then mentioned a technique known as micro array analysis, which although costly can evaluate many variables at once and could yield valuable information.


He thanked us for our attention and responded to questions.


QUESTION: Does Glivec cause tissue mutation?

ANSWER: It could do. Glivec only puts the tumour to sleep, so it lives longer and this could allow time for mutation to occur. However, since it has defective DNA and is constantly having to repair pathways, it is likely to mutate anyway. Why we get mutations is not well understood.


QUESTION: Have you ever had to analyse cystic tumours of someone on Glivec after death?

ANSWER: Only one. In this case the tumour was not completely wiped out. It consisted of a blood filled, mostly fibrous cavity.


From such analysis we may gain information on how effective the treatment was, and this could give indictors on dosage/switching to different agents.


QUESTION: How reliable are the pathologists? Could some results lead to different treatments being given?

ANSWER: The systems now in place for ongoing development and peer review have made the reliability of the results better. It is now more of a science than an art, and some practitioners have chosen to drop out. There is now less proliferation, and a concentration of expertise in centres of excellence.


QUESTION: Is mutational analyses being done now on tumours which were removed some time ago?

ANSWER: Yes this can be done, and it is being done to help decide next course of treatment. All tumours are kept for 25 years so there are no missed opportunities. Dr Hughes then went on to discuss the ethics of using tissue for research, compared with using it for the benefit of the particular patient. We have massive archives of material that just sits there. There is a potential dilemma if a stock of tissue gets exhausted by research, and is then needed for the treatment of the patient. So the guideline is, if the sample small, then it can't be used for research. If the sample big, then perhaps it can. The tissue can only be accessed for ethically approved studies and the tissue remains anonymous.


QUESTION: How many centres are doing genetic analyses?

ANSWER: It is still a bit of a minority hobby. Several centres are developing, and a few are doing very well, but there is no national driver.


QUESTION: "GISTs have a lifetime of their own". What exactly did you mean?

ANSWER: If it is not operable or has metastasised, then its behaviour will change. We will learn more as people live longer.


QUESTION: If a person has two resections would the mutational analyses reveal that they were the same?

ANSWER: Yes, they are likely to be the same.


QUESTION: For those with rare genotypes, i.e. not kit and not PGFRA, where are the mutations likely to occur?

ANSWER: I can't answer that. Maybe micro array analyses will reveal this.


Doctor Hughes was thanked for his presentation, which was both quite humorous and very interesting, and with many amusing pictures..




Professor Woll is a sarcoma specialist medical oncologist and leader of the Experimental Cancer Medicine Centre at Sheffield.



Professor Woll introduced her presentation on adjuvant treatment for GIST by running over the basics of what is currently known about GIST and the use of imatinib (Glivec) in patients with advanced disease. (For an explanation on this please refer to the excellent publication "Patient Guide-GIST" by the Global GIST - NETWORK available from Sarcoma UK.)


In describing survival rates, she showed the results of a trial where survival for patients on imatinib (Glivec) was similar whether on 800 or 400mg dose. In contrast, survival for patients treated with doxorubin (traditional chemotherapy) was very poor, with 50% dead within 9 months (this was based on historical data, pre-dating the availability of imatinib). People on Glivec often still relapse and die eventually. (50% within 5 years , but 10 years or more for some).


In many tumour types, combinations of treatments give better results than a single treatment type. Radiotherapy can be useful in other tumour types but is not suitable for GIST because it harms other organs in the abdomen. Various drug treatments, including hormones and chemotherapy drugs, have been combined with surgery in other tumour types, resulting in better survival. This approach is now being tested with imatinib (Glivec) before or after surgery for GIST:

  • Adjuvant therapy is given after surgery
  • Neoadjuvant therapy is given before surgery.

Professor Woll then told us about the EORTC Adjuvant Imatinib Trial for GIST patients. Patients can be included if they have had a GIST surgically removed but are at high risk of tumour recurrence. The risk can be estimated from the size of the tumour and its growth rate (as judged under the microscope).


A prerequisite to get onto this trial is to have had a complete resection within three months of starting the trial. (This sounds a long time but can be quite demanding). However, Professor Woll showed us a graph of the recruitment for the trial from 9/12/04 to 4/12/08, showing that at the time the list was closed there were 772 patients signed up. Recently, permission has been given to increase the number to 900, so the trial is recruiting again, but probably not for long. This very rapid recruitment in such a rare condition is testament to the enthusiasm of all the doctors and patients involved.


Other criteria for eligibility:

  • Both surgeon and pathologist must agree that all the tumour has been removed (an R0/R1 resection).
  • The patient must be over eighteen years old
  • The tumour must have been localised GIST, with no metastases.
  • It must have been kit +ve
  • It must be in the high or fairly high risk category (ie large tumour, with a high mitotic count per 50 HPF)
  • The patient must be up and about, and reasonably fit.

The patients are randomised, so 50% will receive no post operative treatment while 50% will take 400mg Imatinib per day for two years.


End Points:

  • Primary: Survival time
  • Secondary: Time to relapse

There will be translational studies to see if patients with some kit mutations benefit more than others. Safety will be a primary consideration.


There will be close monitoring of patients in both arms of the study:

  • 3 monthly CT scans, in the first two years
  • 4 monthly in year 3-5
  • Thereafter: annually.

The benefits to patients come from the close monitoring and the ability to give Glivec promptly to those in the control group in the event of a relapse. For those taking Glivec, this may delay or prevent relapse.


The risks to patients come from the level of CT radiation exposure, the side effects of the Glivec that they may not need, and the possibility of an early development of resistance to Glivec (thus lessening its effect if it is needed later).


There are no results to discuss yet, but there have been no serious unexpected adverse effects reported.


Professor Woll compared this study to a completed American study where the selection criteria were much simpler: just a GIST at least 3cm in diameter. 644 patients were recruited and given either imatinib or a placebo for 1 year.

End points:

  • Primary: Relapse free survival
  • Secondary: Overall survival

The study found that patients receiving placebo relapsed sooner than those receiving Glivec (17% vs 3% after 1 year). It is easy to conclude that everyone should be on Glivec post-operatively, but no survival results are available, so it is not certain whether there is a long term benefit to taking adjuvant Glivec. Also, the relapses were almost all in patients with larger tumours, so Glivec might be unnecessary in patients with smaller tumours. Because everyone on the trial was put on Glivec after one year, the secondary endpoint of overall survival will never be known.


Professor Woll then went on to list a number of other studies in Sweden, USA, Scandinavia and Quebec that were in progress where results are still not known. For example, the Scandinavian study is comparing 1 year and 3 years adjuvant Glivec. The point being to show that there was a lot of activity and interest around the world.


There followed a Question and Answer session:


Question: For patients taking Glivec for advanced disease, if we are clear can we stop taking the pills?

Answer: No, stay with it, because tumours can re-grow when the Glivec is stopped. Side effects get more tolerable with time and any risk to the heart is low. We do not know of any other long-term effects of taking Glivec. Those on Sunitinib are more at risk because it acts on blood vessel growth factors and is more likely to lead to heart problems.


Question: With no more metastases, and responding to Glivec, is there any evidence that people are ever cured?

Answer: Probably not. We think that it is a safe assumption that the disease has not gone. However, some patients die with GIST and not of GIST. An interesting question is whether surgical removal of the residual disease would be helpful - a new EORTC study addressing this question will be opening at the end of this year.


Question: Please define cystic disease. Is it static or active? They can be mis-reported as getting worse.

Answer: We don't know if the metastases which develop cystic changes are active or not. It would be good to do a study of removed cystic tumour tissue which may give this information.


Question: Why was there no placebo in the adjuvant trial described? And what exactly is meant by being "Up and about"? Is this age related?

Answer: Three questions !

Question 1: Why no placebo?

Answer: Placebo trials are scientifically cleaner, but more expensive to run. Also the fact is that patients are less enthusiastic about joining trials which include placebos. In this trial it is usually obvious if you are not on the treatment.

Question 2: What is meant by being "up and about"

Answer: This is defined by a robust performance scale which predicts well how people will do. Performance status 0 (PS 0) means able to do all normal activities including work and leisure activities. PS 1 means able to do light work or housework, but not the most strenuous activities. PS 2 means able to wash, dress and feed onself, restricted to a chair or bed for less than 50% of waking hours. Patients with these activity levels are eligible for this study. The scale is remarkably good at picking out patients who can benefit from cancer treatments.

Question3: Is it adjusted for age? Who scores it, the patient or the Doctor? (Much laughter!)

Answer: Age is not used to discriminate patients for the studies. The "normal activities" described may differ with age, but the same principles apply. Of course, the patient, their carer and the doctor may disagree about how active a patient is - and patients may claim to be more active than they really are. In most research studies, the doctor fills out the score after talking to the patient.



Question: How many of us have no side effects from Glivec?
(From the show of hands it appeared that there were not many. This implies that we would have known if we were on the placebo.)


Question: What do people with GIST do when on placebo?

Answer: There are no studies which involve putting people with active GIST tumours on placebo. Studies with people who have had curative surgery are different. In this trial, the care they get will be preferable to a "pat on the back and a hope it doesn't come back."


Question: If an operation removes a primary tumour and then another GIST arises in the same site, is this another primary?

Answer: The decision as to whether this is a primary or a metatastic GIST is difficult and it would probably be treated as a second primary. PET scans can be helpful in picking up other tumours.


Question: Oesophageal tumours, any comments?

Answer: They are not common but they do occur. GIST does not always occur in the abdominal area. In my experience, they respond to Glivec like GISTs in other sites.


Question: Is there any evidence that people with allergies are more likely to be adversely affected by side effects?

Answer: Because of the way Imatinib and Sunitinib work, this is not likely and I am not aware of any studies about this. It does not seem to be an issue.


Question: How do you get onto the trial?

Answer: Patients must be referred to a specialist oncologist by their surgeon. It can take some time to confirm the diagnosis and so this may be difficult to achieve within the 3 month window. We don't want to extend the window to 6 months because progression could already have taken place.


Question: Is it a good idea to have a liver tumour, which has not increased in size, removed after 6 years on Glivec?

Answer: We don't know. There is a trial planned to explore this, which should open at the end of this year.


Question: Since being on Glivec, my eyes stream and the tears burn my skin, what can I do?

Answer: Suggested from the floor - "Wear tinted specs. This may help, it helped me."


Questions then ended and Judith thanked Professor Woll for an interesting and informative talk.


At the business meeting of GSUK at the end of the afternoon, it was agreed that GSUK should set up its own bank account, and then set in motion the process of becoming a Charitable Trust. We now have volunteers for the roles of Treasurer, Secretary, and Chair, as well as four others willing to be Trustees.

It was also decided that we would expand the use of the special telephone number 0300-400-0000, now given on this web site, so that new contacts can phone us as well using the existing email address. Several people said they would be willing to help with this service, and they will be added to the list in due course.

Roger Wilson then told us about the Team Sarcoma event to be held during the second week-end in July in Derbyshire, and invited us to go and join in. He also explained about the situation with regard to the possibility of NICE looking at sunitinib.

We all felt that it had been a good day. Not only were the speakers very interesting and easy to listen to, but the chocolate gateau was wonderful! The chance to meet new members, and renew friendships with those we have met before was as valuable as ever.





Clinical Trial - 3 v 5 years adjuvant imatinib recruitment extended until 31st March 2020- trial centre list update here

The next PAWS-GIST clinic is happening on Friday 12th April 2019. Registration is via PAWSGISTCLINIC.ORG.UK 

Our next Patient Meetings are in Leeds on Friday 4th October 2019 and London - 6th March 2020. If you would like to join us please email  to register. We look forward to seeing you...

Rare Cancer Patient Survey - collecting feedback on rare cancer patient experience with clinical trials...

On the 10th October the Scottish Sarcoma network are holding a day called RISE at the Western Park Hotel in Falkirk. The day is dedicated to people with a sarcoma diagnosis and their families to focus on "what matters to me". This poster contains the registration details if you would like to attend. GIST Support UK will be represented at this meeting and we look forward to seeing you. 

A big thank you to Scotmid Co-operative for choosing to support GIST Support UK and the development of our national tissue bank. Read more here


If you missed any of our previous meetings, you can view the speakers' presentations here

Clinical Trial - 3 v 5 years adjuvant imatinib - trial centre list update here

19th August 2017 - Page 19 of the Times GIST report - READ HERE

New UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST) published by British Sarcoma Group - NEWS >>>

GSUK's Chair Nic Puntis discusses the BBC's report on the Cancer Drugs Fund on BBC Wiltshire Radio - NEWS>>>.  

Update on GIST clinical trials that are recruiting and in the pipeline....

We have launched our first GIST patient survey and hope to gather a better understanding of the landscape for GIST patient treatment in the UK. The survey closes on 10th September 2016 so if you would like to participate please complete the survey by clicking this link

'ALT' GIST Trial to open in the UK soon! We have been alerted to a new trial that will be opening in the UK in the near future for metastatic GIST patients. Read more on our Trials & Research page 

PAWS-GIST Clinic 7 - Newsletter June 2016

GSUK attends Cancer52 parliamentary reception to raise awareness of rare and less common cancers.

GSUK Research Update 2016 - Read all about it here

NHS England's Sarcoma Service Specification consultation is open until Weds 20th April 2016.       Please register your views by responding directly via this link.                             GSUK's response can be viewed here

Cycle for GSUK! We have four allocated charity places on the RideLondon event for this year and also for 2017 and 2018. Go to our News page to find out more!

The Masitinib Trial is now open.  For further details of this trial, and to find out which centres and clinicians are involved, please go to our Research & Trials page. 

Regorafenib has remained on the NHS England Cancer Drug Fund List for GIST patients! Read more!

Can you help Professor Eamonn Maher with his research Study? If you have had, or have, two or more primary GISTs, or a GIST and another tumour, find out more at the bottom of our research page

PRESS RELEASE - UKTV announces GIST Support UK as its Charity of the Year 2015

TUMOUR BANK UPDATE: "We have been granted approval from the NHS ethics committee for our National GIST Tissue Bank which will store these valuable GIST tumour samples for research. If you are about to have an operation and would like to donate your tissue for research please email  with your contact details. Visit our Retention of tissue page for regular updates.

Scottish Sarcoma Network: Interested in attending their Sarcoma education days or finding out about the services on offer ? Read our News page

Use of human tissue
Do go to our new "Retention of Tissue" page and please sign a consent form!

GSUK funds research!
GSUK provides £20,000 from donated funds to help start a research project at the Royal Marsden. Visit our News page for further information and picture.

Funds being raised for UK PAWS GIST clinic
See our News Page for more information.

NICE approves improved treatment for ascites
The PleurX system allows the patient to drain fluid from the abdominal cavity without having to pay repeated visits to hospital. More information on our News Page.

European Commission approves three years' adjuvant use of Glivec
Visit our News page for more details.

A press release in February claiming the effectiveness of this drug as a replacement for Sunitinib appeared to be premature at the time. However subsequent news may be more encouraging! See our News page for more details.