External beam radiation therapy versus stent insertion for dysphagia relief in esophageal cancer: a multi-center randomized trial

The incidence of esophageal carcinoma is rapidly increasing, affecting 455,800
patients worldwide in 2012. At time of diagnosis more than half of patients
have incurable disease due to metastases or poor medical condition. Dysphagia
is the most common symptom of incurable obstructive esophageal cancer.
Palliative treatment aims to relieve dysphagia, maintain nutritional intake and
improve quality of life. As it has been demonstrated that brachytherapy has a
superior effect over stent insertion for long-term dysphagia relief, current
clinical guidelines advice to use brachytherapy over self-expandable metallic
stent (SEMS) insertion for dysphagia relief in patients with a life expectancy
greater than 3 months. Nevertheless, previous reports show that the use of
brachytherapy in current clinical practice is low and that initial palliative
treatment varies with hospital of diagnosis. A recent report on the use of
brachytherapy in Italian radiotherapy centers showed that in 7 out of 40
responding centers brachytherapy was used, and only 3 centers considered
brachytherapy for initial treatment. This is in accordance to an earlier remark
in the ESGE guidelines; the authors stated that the main limitations of
brachytherapy include limited availability, technical difficulty, and need for
dedicated logistics and expertise.

Alternative treatment with external beam radiation therapy (EBRT) is given for
dysphagia relief in esophageal cancer. Both EBRT and SEMS insertion have proved
to be effective in palliation of dysphagia symptoms, however, no comparative
data about these two different modalities are available. Since we can consider
both treatment modalities mainstay in the treatment of malignant dysphagia,
comparative data are warranted. Therefore, we propose a study that compares the
efficacy of EBRT versus SEMS insertion, for dysphagia relief in patients with
esophageal cancer. Results of this study could help to further tailor
palliative treatment of patients with esophageal cancer.

Primary objective
The primary objective of this study is to compare the efficacy of EBRT versus
SEMS insertion for palliation of malignant dysphagia in esophageal cancer
patients at 4 weeks after start of treatment.

Secondary objectives
Secondary objectives of this study include:
- To compare DSS-response over time of EBRT versus SEMS insertion
- To compare NRS pain score of EBRT versus SEMS insertion
- To compare major and minor complication rate of EBRT versus SEMS insertion
- To compare quality of life of EBRT versus SEMS insertion
- To compare costs of EBRT versus SEMS insertion
- To compare dysphagia free survival and overall survival of EBRT versus SEMS
insertion

We propose a multi-center randomized trial in the Netherlands. When patients
are eligible for inclusion, patients will be randomized to either treatment arm
after informed consent is acquired. The allocation is not blinded to the
patient or outcome assessor.

Patients will be randomized to either EBRT (5 fractions of 4 Gy each with
opposing fields in anterior-posterior direction) or SEMS insertion (partially
covered Niti-S S Esophageal Stent).

The proposed comparative study will provide data on treatment modalities that
we consider mainstay in current clinical practice. Hence, results of this study
could provide information to support future studies or guidelines, ultimately,
leading to an improvement of the quality of palliative care in patients with
esophageal cancer. Considering both treatment modalities are available for
standard care, the risk of injury as well as the potential benefits for
patients participating in this trial are equal to the risk in patients who are
not enrolled. A potential burden of participation could be the demand to
complete a diary and several questionnaires. This will not lead to a
significant risk of injury.
Blood samples will be obtained at baseline before onset of treatmentPermission
for the collection of additional blood samples will be obtained separately.
Hence, participants that refuse to undergo additional blood sampling can still
participate in the EXTENT trial.