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Dr. Ian Judson is a medical oncologist who specializes in cancer clinical pharmacology. He has many years of experience in the conduct of phase I clinical trials of new anticancer drugs and has been involved in the development of a number of agents now licensed for cancer treatment such as carboplatin and raltitrexed. His area of particular expertise lies in the treatment and research of soft tissue sarcoma. Dr. Judson has also made a particular study of Ewing’s family tumors in adults. We asked Dr. Judson to explain what Ewing's Sarcoma is and describe the current state of diagnosis and treatment.
What is Ewing’s sarcoma, how does it affect the patient?
Ewing’s sarcoma and primitive neuroectodermal tumour or PNET are cancers that affect children and young adults. Currently we don’t know what causes them but they usually develop in one of the bones in the leg, most often just below the knee. Sometimes they arise entirely in the soft tissues, in which case they can occur anywhere in the body.
What the patient first notices is a lump or pain. Often, because the patient is young and active this is put down to bruising, muscle strain, trauma etc. and the diagnosis is delayed for many months, sometimes with fatal consequences. If the disease is not caught in time and treated effectively it will spread to the lungs, bones and the blood-forming tissue, the bone marrow. It is this tendency to spread which proves fatal without chemotherapy treatment, since the original lump can usually be removed surgically.
Who gets it, and why?
The disease is rare, occurring in less than 1 per million population per year in the susceptible age group of children and young adults. Teenagers are especially likely to be affected. We have no clues currently as to the cause.
What is the success of treatment?
Current treatment will result in a cure rate of about 60% overall. The outlook depends on things like tumour size, presence or absence of spread to other organs at the time of diagnosis, and, most importantly, the effectiveness of chemotherapy. Because the disease is essentially regarded as having already spread at diagnosis, examining the tumour when it is removed after several courses of chemotherapy tells you how likely it is to return elsewhere.
What additional research work would help?
A common feature of this and other sarcomas, i.e. connective tissue cancers, is the fact that portions of chromosomes become exchanged in a highly specific fashion. This is called a translocation and results in genes that are normally far apart on different chromosomes being brought together. One then seems to drive the other resulting in its being switched on permanently. The effect of this is to cause activation of specific genes and production of the relevant proteins that then drive the cancer cells to grow. More work is needed on the exact nature of the genes involved, why different translocations have different effects on the aggressiveness of the disease and exactly what is going on at the molecular level.
Recent work in another sarcoma type – gastro-intestinal stromal tumour (GIST), has demonstrated that if the molecular switch can be understood it may be possible to develop specific drugs to target that switch, block the signal and cause the cancer cells to die. This is much more difficult in Ewing’s than GIST because the switch is not easy to block with a small drug molecule. However, if there are to be developments along these lines they are likely to come from collaborations between academic laboratories – these tumours are too rare for drug companies to get involved.
What does the Sarcoma Unit actually need?
The Royal Marsden Hospital Sarcoma Research Fund is currently supporting work on other types of soft tissue sarcoma using a new technique called DNA micro-array. This technique allows us to examine the activity of thousands of genes at a time in individual tumours in order to find out “why do certain tumours respond to treatment while others do not?” “What makes a tumour more aggressive?” “How do we distinguish more accurately between similar but different diseases?” etc. We support both staff and equipment. The same technique could be applied to Ewing’s but first we need to establish the ability to carry out the basic molecular biology studies that we need to make an accurate diagnosis.
Currently we lack a molecular diagnostic laboratory for sarcomas in this hospital. Examination of the chromosomal changes can now be done using a variety of modern techniques, such as fluorescent in situ hybridisation (FISH) and use of the polymerase chain reaction (PCR). There is some evidence that different translocations result in a different prognosis. In addition, PCR can be used to detect small numbers of tumour cells in tissues such as bone marrow, even circulating in the bloodstream. Currently we do not know the significance of this and how to use the information.
We urgently need approximately £50k per annum to establish these molecular techniques in a diagnostic laboratory and then start to look in detail at the precise molecular events in relation to what happens to individual patients.
We believe that the experience with GI stromal tumours tells us that finding the molecular switches in Ewing’s sarcoma is now possible and likely to lead to successful new treatments. Use of micro-array techniques may lead us to which are the important switches in Ewing’s and allow us to start clinical trials using the new generation of smart anticancer drugs.
For more information about Dr. Judson's work with the Sarcoma Unit at Royal Marsden Hospital, please visit the Sarcoma Unit section of their site.
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