Safety and feasibility of the ketogenic diet in therapy resistand paediatric recurrent or progressive pontine glioma, a pilot study

In the Netherlands each year approximately 150 children are newly diagnosed
with a tumour of the central nervous system. 5% of these children are diagnosed
with pontine glioma. Prognosis of children with malignant pontine glioma is
extremely poor. With the present treatment protocol which consists of
radiotherapy followed in case of tumour recurrence by oral Temozolomide the
reported 2 year survival rate is only 5%.
Until now, no further treatment options remain after tumour recurrence or
progressieve tumour growth during Temozolomide treatment. In a recent nation
wide Dutch study on the effect of Temozolomide treatment of 40 children with
recurrent ponsglioma after radiotherapy, survival after stop oral Temozolomide
varied from 3-9 months.
New therapies to ameliorate survivalof this tumour with grim prognosis are
urgently needed.
A high grade glioblastoma like pontine glioma is known for its high glucose
consumption. Glucose is also the preffered energy stubstrate of normal neurons
and glia but under fasting induced reductions of blood glucose these cells are
also able to meet their energy requirement by metabolizing ketone bodies. In
contrast, malignant brain tumour cells lack metabolic flexibility and for
energy supply depend on glucose. When the patient is treated with a ketogenic
diet (a high fat 70-90en% and low carbohydrate 5-19 en% diet) the glucose
supply (read; energy supply) of the brain tumour in fact is beiing sabotaged.
The ketogenic diet as treatment for refractory childhood epilepsy has proven
its safety and efficacy and is widely acceptated as treatment modality in this
patient group. There are two versions of the ketogenic diet widely used; the
classical form ( mainly in USA) and the MCT version of the diet (in Europe and
Netherlands). There is no difference in effect of the two diets.
The work of the group of Prof Seyfridt USA has shown a 35-65 % reduction of
braintumors on ketogenic diet in mousemodels with human braintumors A high
grade glioblastoma.

To establish the safety, feasibility and quality of life in children with
recurrent of progressive pontine glioma who receive a ketogenic diet during a
study period of 3 months

open label prospective pilot study (phase II)

Ketogenic diet (first Classical version of the diet with shakes , soups and
smoothies) after that the MCT version of the diet

The child has to use a stadaridized Ketocal formula for max of 2 weeks or until
adequate level of ketosis (3-4+ blood ketones) is achieved. The ketocal formula
consist of exchanges of shakes, soups and smoothies matching the individually
calculated energy need of the child based on the results of a Indirect calorie
measurement and a 3-days pre-diet food diary. At time of adequate and stable
ketosis the child is allowed to substitute the shakes of soups into
individually calculated meals based on the MCT version of the ketogenic diet.
Growth curve will be monitored closely.
Bloodglucose and bloodketones will be measured daily by parents until adequate
and stable ketosis (3-4+) is reached and after that once a month.
Questionnair quality of life and Vineland behaviour scale will be noted at
start of the study in outpatient clinic and at end of the study at home.
Adverse effects related to the diet will be noted on a questionnaire and
communicated by mail or telephone by parents. In case of problems and worries
parents can contact the nurse practioner by mobile phone. When necessary the
nursepractioner will contact the dietitian or paediatric neurologist.
The child follows the diet as long as the child and parents want until the end
of the study periode of 3 months which adequate ketosis (3-4+ bloodketones) is
maintained.
Based on the results of this study the search for treatment therapies in
malignant and progressive brain tumours hopefully will set up new ways.