Basic elements of the research

The research team has specified four basic elements required to develop new treatment methods:
• Biological knowledge
• Knowledge of previous treatments
• Diagnostics
• Knowledge of tumor distribution

Ad. 1 Biological knowledge
First, in order to obtain biological knowledge, tissue is needed. In addition to gathering tissue that was previously obtained (from pathological labs, or other academic hospitals), it can also be collected through obduction or biopsy.

The research team already developed an obduction protocol, which has since been implemented nationally. There is always a member of this research team present during an obduction and a  follow up conversation (evaluation) is planned with the parents , where the results will be discussed. The type of tumor as well as the diffusion in the brain stem will be examined and subsequently, the cells will be sent to the lab for further cell culture and analysis. Furthermore, the nature of the tumor in various areas of the brain will be investigated.

Biopsy is a standard element of the new treatment protocol but is not mandatory. The aim is to use those cells in the lab to cultivate primary DIPG (Diffuse Intrinsic Pontine Glioma) cells. Currently, a couple of cell lines have been discovered. These cell lines are anonymous and are now known as VU DIPG with a number, for instance VU DIPG 001.

Ad. 2 Knowledge of previous treatments
Research was done among VUmc patients over the past five years, which resulted in the following conclusions:
• Average survival is 9 months
• 1-year survival rate is 40%, 2-years rate is 3%
• Intensive chemotherapy: 13 months survival
• Chemotherapy until progression, followed by radiotherapy: 8 months improvement, though the 2-years survival rate is still only 5%
• Cell protein therapy / monotherapy: few side-effects, no enhanced survival rate

The ‘Review’ was sent to the Neuro-oncology magazine and published in the Dutch edition; see the link for the full article in Dutch.

The same research was also carried out nationally among patients in the period 1990-2010. Objectives of the research were the following:
• Obtain an overview of symptoms at diagnosis, and duration of these symptoms before diagnosis
• Determine survival period for various treatments
• Discover long term survivors
• Revise and classify MRI scans

By far, most patients from the researched period were treated in the Erasmus Medical Center in the Netherlands. The majority was aged three to nine years. On average, twelve children were diagnosed annually. In addition, the results of treatment methods from elsewhere in the world were monitored.

Ad. 3 Diagnostics
By executing PET (Positron Emission Tomography) research, the grade of the tumor and hence the response to therapy can be predicted. However, the lack of data from a healthy pons (middle brain stem) was an issue. Though, it was discovered that for PET scans of epilepsy patients, the pons is also examined, even when healthy. Therefore, those PET scans will be compared with DIPG patients’ pons scans.

Ad.4 Knowledge of tumor distribution
A key question when treating with medicine, is whether the medicines actually reach the brain stem. The blood-brain barrier is intact and there is high pressure in the pons. Therefore, the aim is to conduct research by linking a radioactive element to a medicine. This medicine will be given to the patient and after three days, a PET scan will be made to discover whether the medicine has been absorbed into the tumor.