Toxicity prediction in radiotherapy for pelvic cancers, assessing the added value of biological parameters to RT treatment planning variables

Radiotherapy is a cornerstone of treatment of pelvic tumors, especially in
patients with prostate cancer, cervical cancer, cancer of the bladder and
rectal cancer. Most patients can be cured due to radiotherapy, but
unfortunately, irradiation of the pelvic area is accompanied by several side
effects. Technological advances in the past and present have demonstrated to
reduce the occurrence of side effects by reducing the amount of unwanted
irradiated volume. Radiation dose and irradiated volume have been identified as
the most important risk factors for late radiation toxicity.
Nevertheless, about 10% of patients still get serious side effects, even after
a relatively low dose and a small volume of healthy tissue.
In a previous project (MEC 08/098 ; KWF-project UVA 2008-4019) with 200 men who
received radiotherapy for prostate cancer, our PhD student Dr Bregje van
Oorschot examined whether there might be a genetic predisposition for radiation
side effects in some patients.
Through microarray analysis she investigated gene expression in white blood
cells of patients. She found indeed that the severity of the irradiation side
effects was associated with the activity of genes needed for repairing
irradiation induced DNA damage. She constructed a genetic profile for late
radiation damage at a group level, however the test is not sensitive enough yet
for risk estimation in individual patients.
That is why we propose to investigate whether we can improve the prediction of
the genetic test by combining it with individual dose-volume data of the
irradiated healthy organs, and with a number of clinical risk factors (age,
diabetes, high blood pressure etc.).

Improvement of late radiation toxicity prediction comes with three practical
advantages for patients with a tumor in the pelvic area:
(1) patients with a high risk of developing late radiation toxicity may not
need to be treated with radiation, but with surgery, hormones or chemo for
example.
(2) patients at low risk we can safely give a higher dose, thereby increasing
cure rates, and
(3) because of a better understanding of the coherence of genetic profile,
dose-volume and risk factors, we can
also adjust the irradiation technique

After signed informed consent, 200 patients that will receive radiotherapy or
already received radiotherapy due to cancer in de pelvic area will be included
in the study. A blood sample of 50 ml will be drawn, preferably prior to
radiotherapy treatment. Late radiation toxicity will be evaluated through a
standardized questionnaire before, after and then half yearly up to 2 years
after radiotherapy. Toxicity is also monitored by physician judgement every
follow-up visit (standard follow-up). Gene expression and y-H2AX foci will be
determined in irradiated lymphocytes and will be correlated through a
multivariate analysis to late toxicity and clinical risk factors (age, tumor
stage, medication, prescribed dosis to the target organ, fractioning,
dose-volume distributions of organs at risk).

Inclusion in this study will have no influence on the course of standard
treatment and the patient burden of this study will be very low to low.
The patient burden comprises one venous puncture (50 ml) and 6 questionnaires
(1 before, 1 directly after and then at each follow-up visit until 24 months
after completion of radiotherapy).