What is DSRCT?

DSRCT is a malignancy first described in the literature by Dr. Rosai of Memorial Sloan-Kettering Cancer Centre in New York in 1991. There are distinctive clinical and histological characteristics that differentiate DSRCT from other small cell tumours. The malignancy most commonly occurs in young males of adolescent age and is characterized as a large intra-abdominal mass with no apparent origin first spreading to the peritoneal surfaces, then to the liver, lymph nodes and/or lungs. Since this lesion is normally not attached to an organ, it usually grows to a very large size and spreads to other parts of the body before the person experiences any ill effects of the disease. Typical symptoms include intestinal blockage, swelling and pain in the abdomen and/or fever. Since DSRCT is so rare, probably less than 200 cases reported, statistics are unreliable. It appears that approximately 3/4 of cases are male with an average age in the late teens or early twenties and that over 95% of the cases had tumours located in the abdomen/pelvic area. However, cases have been reported in all age groups of both males and females and with tumours present in other parts of the body. It would be unrealistic to guess at statistics on prognosis and survival rates at this time. Early reports describe a dismal prognosis for DSRCT due to its aggressive behaviour and general non-responsiveness to known treatments of similar malignancies. However, in the past several years, there have been treatments developed that show promising results with many patients experiencing complete remissions sustained for longer than two years.

 

Treatments
Treatment of DSRCT varies from patient to patient, but the most effective treatments have consisted of early resection of the tumour(s) when possible and high dose multi-agent chemotherapy followed by a stem cell transplant. Many cases include a mid-chemo surgery to remove any residual disease and make the subsequent chemo treatments more effective.
There are two main protocols reported in the literature: the P6 Protocol developed by Dr. Kushner at Memorial Sloan-Kettering Cancer Centre in New York and the Eicess EVAIA protocol used mainly in Europe. Both protocols use similar chemo drugs, use extremely high doses of chemo, and have a similar number of courses. Most successfully treated cases report the use of these, or variations of these protocols. It must be remembered though, that these protocols are not the only options. Each individual case is different and must be researched independently to determine the best approach for treatment.

 

The P6 Protocol
The P6 Protocol consists of seven courses of chemotherapy with surgery after the third course (if necessary), followed by a stem cell transplant. The courses are described below or see Abstract #68 on the Research Abstracts page for Dr. Kushner's 1996 article. Maximum tolerable doses for each course are calculated by the patient’s weight and age.

Courses 1,2,3 and 6                                                                                       Courses 4,5 and 7
cyclophosphamide                                                                                             infofamide
doxorubicin                                                                                                       etoposide
vincristine                                                                                                         (Both infofamide and etoposide are administered
(Cyclophosphamide is administered with                                                                by 1 hour infusions over 5 days)
two 6 hour infusions on the first 2 days.
Doxorubicin and vincristine are administered
by a 72 hour continuous infusion)

Suplimentary Drugs                                                                                        Additional Drugs
mesna                                                                                                              Zofran (anti-nausea)
(Mesna is administered by intravenous injection                                                   Sulfametoxazol + Trimetoprima (anti-pneumonia)
with the cyclophosphmide in courses 1,2,3 and 6,                                                 Ranitidina or Zantac (anti-ulcer)
and with each infusion of courses 4,5 and 7. It is
used to prevent bleeding in the bladder and kidneys)
filgrastima (G-CSF)
(G-CSF, a blood cell growth stimulant, is
administered by subcutaneous injection
for 10 days after the completion of each
course)

After each course, blood counts are monitored closely and transfusions of whole blood and/or platelets are given if blood counts get too low. Subsequent courses are started after blood counts rise back to normal levels, usually 18 to 20 days after the completion of the infusions.

Stem Cell Transplant
thiotepa
carboplatin

The stem cell transplant procedure consists of first harvesting stem cells from the patient, administering high doses of thiotepa and carboplatin, then re-introducing the harvested stem cells into the blood stream along with G-CSF.

 

The Eicess EVAIA Protocol:
The Eicess EVAIA Protocol has been used mainly in Europe and has been commonly used to treat Ewings Sarcoma. This protocol consists of eight courses each consisting of:

Courses 1 through 8                                                                                      Suplimentary Drugs
vincristine                                                                                                         mesna
doxorubicin                                                                                                      (Mesna is administered by intravenous injection)
infosfamide                                                                                                       filgrastima (G-CSF)

etoposide                                                                                                         (G-CSF, a blood cell growth simulate, is administered by 

                                                                                                                                                                 subcutaneous injection for 6 days after the completion of each course)
                                                                                                                                                              

Notes from Rob's Oncologists:

 

Consultants Comments 
Dr. Sheila Lane MBBS MRCP PhD
Consultant Paediatric Oncologist Children's Hospital Oxford says:

Rob was one of the patients being treated by the Children's Oncology team in Oxford.   He had a Desmoplastic small round cell tumour (DSRCT).   This is a rare tumour and was first discovered less than 20 years ago.   The tumour mainly affects young teenage males and it often presents as a large abdominal mass which is widely spread at the time of diagnosis.   Rare tumors such as DSRCT are elusive both in their nature and response to treatment.   Research is vital to help improve treatment options and survival.
Rob's wish in setting up this charity is to help other teenagers with rare tumours.   He hopes to raise sufficent money to fund a research project in the UK.   This is a challenging goal but one which the Oxford Children's Oncology Team fuly support.

Dr. Chris Mitchell 
Consultant at the John Radcliffe Childrens Hospital says:

The Desmoplastic Small Round Cell Tumor (DSRCT) was first described as a specific type of tumour in 1991.   It is usually seen in children or young adults (average age at diagnosis is 22 years) and is 5 times more common in males than in females.   It usually presents because of discomfort or pain, weight loss, and abdominal swelling.   There is usually a large mass within the abdomen, often arising out of the pelvis.   In addition there are often numerous small secondary tumours throughout the abdominal cavity.
These tumours have also been reported in a number of other sites outside the abdomen.   It is a very aggressive tumour and has often spread widely by the time of diagnosis.
However, it is a very rare tumour and so far there have probably been fewer than 100 cases described in the medical literature.   However, for a cancer biologist it is an extremely interesting tumour.   Over the past 20 years there have been a large number of genes discovered that have specific roles to play In the development of various types of tumours, both in adults and in children.   Two such genes are the EWS gene, which is associated with a bone tumour called Ewing’s sarcoma (after Dr James Ewing who first described it), and the WT1 gene, which is associated with Wilms’ tumour, a form of cancer affecting the kidney in childhood (and which is named for Dr Max Wilms).
I am sure you know, everything about us is determined by the genes that we have inherited from our mothers and fathers.   Our genes are packaged on chromosomes, of which humans have 23 pairs, half of each pair coming from the mother and the other half from the father.   In DSRCT, the chromosomes have become rearranged so that instead of having a pair of chromosomes 11 and pair of chromosome 22, there has been an incorrect repair of some random chromosome damage, so that part of chromosome 11 is "stuck onto" part of chromosome 22.   As a result of this incorrect repair, the EWS gene which normally lives on chromosome 22 finds itself next to the WT1 gene, which normally lives on chromosome 11 – this process is called a chromosomal translocation, and is described as (t11;22)(p13:q12), the first brackets describing the chromosomes and the second brackets describing the sites on each of the involved chromosomes.   These two genes then function together as a "fusion gene" to produce a new protein.   Exactly how the appearance of this protein causes the development of the DSRCT is now the focus of intense research, as it could conceivably lead to new and more effective treatments.
At the present time, the treatment of DSRCT relies heavily on chemotherapy or drug treatment.   As the tumour has often spread widely at the time of diagnosis, treatments such as surgery or radiotherapy are much less likely to be useful.   However, if it was possible to block the formation of the new protein, or to "turn off" the effects that the new protein has (while leaving the effects of the normal proteins intact), it might be possible to make tumours shrink or even disappear entirely.   There is still a very long way to go, to get from what we know now to having a useful drug – it will not happen in the nest few months, or even in the next few years.   However, it is a possibility within the next 5 to 10 years.
Unfortunately DSCRT is such a rare tumour that dug company developments are unlikely to focus on it.   Hence most of this research is going to happen in the research departments of universities and they will require large amounts of funding.   That is why Robert Holland’s appeal is so important.   It will raise the public’s knowledge about this rare but dangerous condition and also will help fund the research that might lead, ultimately to much more effective treatments than we have now


 
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