Detection of (Sub)Clinical Toxicity in Irradiated vs. Non-irradiated Surgically Treated Esophageal Cancer Patients: a Pilot Study (CROSS SECT)
Condition: Thoracic Tumor
MeSH terms: Esophageal Neoplasms; Thoracic Neoplasms
Study type: Observational

Summary: 
      Rationale: Radiation-induced cardiac and pulmonary toxicity after treatment for
      intra-thoracic 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..

      Objective: 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.

      Study design: Cross-sectional pilot study

      Study population: 40 EC patients who were treated with curative intent by esophageal
      resection with or without neo-CRT

      Intervention (if applicable): Not applicable.

      Main study parameters/endpoints: As this is an exploratory pilot study to determine the most
      suitable diagnostic tests for future studies, there will be several endpoints related to
      (sub)clinical cardiopulmonary dysfunction.

      Signs of myocardial ischemia, systolic or diastolic dysfunction, rhythm and valve disorders,
      pericardial effusion and fibrosis, myocardial fibrosis, focal wall motion disorders and
      coronary calcifications will be analyzed. The cardiopulmonary (dys)function in EC survivors
      treated with neo-CRT followed by surgical resection will be compared to cardiopulmonary
      (dys)function in EC survivors treated with surgical resection alone.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: 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 (feeling sick)
      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.
    


Intervention name(s): CTTC scan, cardiac MRI, ECG, 6 minute walking test, echocardiogram
Intervention type(s): Diagnostic Test
Intervention description(s): CTTC scan, cardiac MRI, ECG, 6 minute walking test, echocardiogram
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with EC treated with or without neo-CRT, alive without evidence of disease,
        treated between 2000 and 2012 at the University Medical Centre Groningen will be eligible.
        Twenty patients will be included in both treatment groups. Length of follow up after
        treatment does not seem to be an important confounding factor as surgery is not considered
        to be an important risk factor for late toxicity.