Detection of (sub) clinical toxicity in irradiated vs. non-irradiated surgically treated esophageal cancer patients: a pilot study.

Radiation-induced cardiac and pulmonary toxicity after treatment for
intrathoracic tumors is a clinically relevant problem, which may jeopardize the
benefit of (neo-adjuvant) (chemo) radiotherapy. Although cure rates are rising
since the introduction of neo-adjuvant chemoradiation (neo-CRT) as current
standard treatment for esophageal cancer (EC), recent studies showed that there
is a substantial risk of non-cancer treatment-related death in these patients.
Furthermore, this risk is underestimated as the cause of death of many patients
remains unknown, since the distinction between tumor related and non-cancer
related death can be difficult.
Cardiac and pulmonary toxicity and its interaction as seen in pre-clinical
studies might explain for these unknown deaths as suggested in several
clinical studies.Clinical imaging studies performed shortly after treatment
showed changes in different cardiac function parameters, all related to
radiation dose parameters. Systematic imaging studies analysing subclinical
toxicities at longer follow up have never been performed, most probably because
of poor survival rates. However, identification of the magnitude of
(subclinical) cardiopulmonary toxicity, by performing several cardiopulmonary
function tests, is essential in this patient group as this toxicity is most
likely the cause of the increased mortality after thoracic radiotherapy. For
future perspectives, these results can be used to select the best diagnostic
methods for a prospective cohort study to develop prediction tools for
cardiopulmonary toxicity. Finally, this might lead to optimization of
radiotherapy dose-distributions (including patient selection for proton
therapy) and hopefully reduce radiation induced cardiopulmonary toxicity and
improve overall survival.

The main objective of this study is to determine the most suitable diagnostic
test to identify cardiopulmonary (dys)function in EC survivors treated with
neo-CRT followed by surgical resection. Furthermore, we want to estimate the
difference in cardiopulmonary (dys)function in EC survivors treated with
neo-CRT followed by surgical resection compared to EC survivors who were
treated with surgical resection alone.

Cross-sectional pilot study

Several tests will be performed at one time point, 5-10 years after given
treatment. If the findings of the test indicate cardiovascular complications,
the patient will be referred to the cardiologist for further analysis and/or
preventive measures. As one of the tests, cardiac MRI, including gadolinium
(Dotarem 0.2 mmol/kg) enhancement will be performed. Potential side effects of
gadolinium include brief headache, nausea and dizziness for a brief time
following the injection. Allergic reactions are rare. Furthermore, a cardiac CT
scan will be performed . With a total radiation exposure of 0.6 mSv (less than
a third of the annual background radiation dose), the risks will be minimal.