Phase II study: Radiofrequency ablation of irresectable locally advanced pancreatic cancer

Pancreatic cancer is a major cause of cancer death in the Western world and is
responsible for nearly 95.200 deaths per year in Europe and 30.300 deaths per
year in the USA . At time of diagnosis, 20% of patients present with a
resectable tumour, 40% with an irresectable locally advanced tumour and 40%
with a metastatic disease. The median survival of patients with locally
advanced pancreatic cancer and metastatic disease is 6 months.
To improve long-term survival various forms of chemotherapy have been studied.
According to the largest trial on adjuvant chemotherapy in patients with
resectable pancreatic cancer, adjuvant chemotherapy improves the survival.
Median survival of patients treated with adjuvant chemotherapy was 20.1 months
compared with 15.5 months in patients without chemotherapy.
In patients with irresectable locally advanced pancreatic cancer chemotherapy
with Gemcitabine is considered an accepted standard palliative treatment. So
far Gemcitabine did not show a statistic significant improvement in survival,
nor did other chemotherapies. However Gemcitabine showed an improvement in
disease-related symptoms.
Radiofrequency ablation (RFA) is a technique that has been demonstrated to be
effective in the treatment of several irresectable tumours Promising results
have been especially obtained in hepatic tumours. This therapy produces local
tissue destruction through high frequency alternating current flowing from an
electrode implanted directly into the tumour and causing frictional heating.
More recently, RFA has also been shown to be effective in patients with
irresectable locally advanced pancreatic cancer. In a phase II study of Girelli
R. et al., RFA resulted in tumour downstaging and improvement of progression
free survival. This therapy therefore deserves further exploration. Our group
has a special expertise and a long standing research line in the treatment of
liver tumours with a bipolar RFA. This novel RFA system could be especially
suitable to improve the RFA of irresectable locally advanced pancreatic cancer.

Primary Objective:
The proposed project involves a phase II study to investigate the feasibility
and safety of radiofrequency ablation in irresectable locally advanced
pancreatic cancer.


Secondary Objectives:
Secondary objectives of the study are tumour downstaging, VAS painscore and
hospital stay.

The proposed study is a phase II intervention study in which 15 patients will
be included. The subjects that will be included are patients with irresectable
locally advanced pancreatic cancer found at laparotomy.

The investigational treatment of this study is radiofrequency ablation.
Radiofrequency ablation of the pancreatic tumours will be produced through
application of high frequency alternating current flowing from a probe with an
electrode into the surrounding tissue. The ions in the tissue attempt to follow
the changing directions of the alternating current and cause frictional
heating. The tissue heats in the area that contacts the probe tip, and heat is
then transferred conductively to more distant tissue. This leads to denaturing
(coagulation) of the cellular proteins and subsequent necrosis of the affected
tissue volumes. The result is thermal injury of the cell structures and damage
of the cell physiology at many levels. The coagulated necrotic tissue is
recognized as such by the body and successively degraded by the body*s own
mechanisms. In this way, it is possible to completely destroy a tumour where
the indication is appropriate.

Radiofrequency ablation of the pancreas will be performed with a probe of Celon
Power System. In the preliminary animal studies the optimal settings for
ablation were determined. These settings will be used in the phase II study
(see below).



Settings:
Power: 30 Watt
Total energy: 15 KJ
Distance: 1.0 cm from duodenum or SMV/SMA
Cooling: Only for duodenum with saline of 5°C

The prognosis of patients with irresectable locally advanced pancreatic cancer
is very poor. The median survival of these patients is 6 months. The risk of
complications is 4% (see also E9). As there is a potential survival benefit of
RFA for these patients, we consider this limited burden and risks justified.