Detection of (Sub)Clinical Toxicity in Irradiated vs. Non-irradiated Surgically Treated Esophageal Cancer Patients: a Pilot Study (CROSS SECT)

NCT03396614 | Completed DMC

• 1 other identifier: RT2017-06/ METc 2017/335
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Thoracic Tumor

Outcome Measures

Primary Outcomes (1)

• 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.

  cross sectional 5-10 years after treatment

Study Arms (1)

EEG, ECG, CT, MRI

Diagnostic Test: CTTC scan, cardiac MRI, ECG, 6 minute walking test, echocardiogram

Interventions

CTTC scan, cardiac MRI, ECG, 6 minute walking test, echocardiogram DIAGNOSTIC_TEST

CTTC scan, cardiac MRI, ECG, 6 minute walking test, echocardiogram

EEG, ECG, CT, MRI

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Treated for EC with a curative resection between 2000 and 2012
• Age \>= 18 years
• Written informed consent
• No signs of tumor recurrence or new other malignancies.

You may not qualify if:

• Thoracic radiotherapy for indications other than EC.
• Contra indication for cardiac MRI, pacemaker, cochlear implants, metal not compliable with MRI.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

MeSH Terms

Conditions

Thoracic Neoplasms

Interventions

Electrocardiography; Echocardiography

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Cardiac Imaging Techniques; Diagnostic Imaging; Ultrasonography

Study Officials

• Jannet Beukema, Dr.

  Radiation oncologist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 11, 2018
• Study Start: October 21, 2017
• Primary Completion: October 1, 2020
• Study Completion: November 1, 2020
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)