Effects of irradiation on hypoxia and proliferation in cervical cancer and their potential predictive value; a pilot study

Tumour hypoxia is an important variable in the treatment outcome (i.e.
radiotherapie or systemic treatment) of cervical cancer. Hypoxia is related to
al less favourable prognosis. Proliferation is a second important variable.
Both variables are known prognostic factors in cervical cancer. Both
radiotherapy and chemotherapy can influence the hypoxic en proliferative status
of a tumour. Experimental studies have shown a reduction in expression of
hypoxic markers (pimonidazole as exogeneous marker) and proliferation markers
with a single fraction dose of 20 Gy. Next to the reduction in proliferation
was an increase in apoptosis visible. An alterered expression pattern of
hypoxia and proliferation may lead to a better predictive value than the
expression pattern prior to treatment. To our knowledge this is the first
clinical study to investigat this in cervical cancer.

The objective is to determine if, and if so to what extend, there is a change
in expressionpattern for hypoxic en proliferative markers.

Patients who are treated with radiotherapy or radiotherapy combined with
chemotherapy or hyperthermia will have a biopsy after pimonidazole
administation after the fifth and tenth radiotherapyfraction. The biopsy will
take place at the outpatient gynaecology department.

Pimonidazole will be administered intravenously to patients after te fifth and
tenth radiotherapy fraction. Pimonidazole is a validates marker for hypoxia and
widely used in clinical research. No serious side effects are known with the
administered dosage of maximal 1000 mg. Possible side effects during infusion
are a slight flush or unwellbeing. After the administration of pimonadazole a
biopsy will be taken of the tumour. This will take place at the outpatient
gyaecology department if needed with the use of a local anesthetic.