Cancer of EsophagusHeartcheckNCT03619317
Impact of Cancer Therapy on Myocardial Function in Patients With Esophagus Cancer
An observational study of Cancer of Esophagus, run by Aarhus University Hospital Skejby at 1 site in Denmark.
Trial summary
Introduction: Patients with cancer in esophagus and gastroesophageal junction (EGEJ) treated with chemoradiotherapy (chemoRT) have increased risk of cardiovascular disease. EGEJ patients often have frailty and pre-existing cardiovascular disease. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Cancer of Esophagus
- How many people
- 56 participants
- Where
- 1 siteDenmark
- Study dates
- 25 Jun 2018to Mar 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * Age < 18 years * Patients not being able to give informed consent (decided by the investigator). * Patients not being able to understand Danish language. * Acute myocardial infarct within the last 6 months. * Present clinical severe heart valve disease and/or congestive heart failure with left ejection fraction < 25 %. * Patients with prior thoracic radiation and overlapping RT fields.
Who may be able to join
- Biopsy verified EGEJ cancer verified by gastroscopy, biopsy and PET/CT scan.
- The final diagnosis must be locally advanced, non-metastatic as determined at a multidisciplinary team conference.
- Patients referred to curative treatment with preoperative or definitive chemo- and radiotherapy.
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
University Hospital of Aarhus, Department of Cardiology
Aarhus N, 8200
Mette Søndergaard, 30130565, metast@rm.dk
Steen Poulsen, steen.hvitfeldt@rm.dk
About this study
Official title: Identification of Chemo and Radiation Induced Systolic and Diastolic Myocardial Dysfunction in Patients With Cancer in Oesophagus and Gastroesophagael Junction - a Prospective Study
Introduction: Patients with cancer in esophagus and gastroesophageal junction (EGEJ) treated with chemoradiotherapy (chemoRT) have increased risk of cardiovascular disease. EGEJ patients often have frailty and pre-existing cardiovascular disease. This may disqualify them for standard trimodal curative treatment and offer surgery alone, chemoRT alone or palliative treatment only. The current understanding of radiation induced heart disease (RIHD) in EGEJ patients is limited. Hence, there is a need for additional studies. Especially on myocardial function during and after chemoRT as congestive heart failure is a serious complication associated with increased morbidity and mortality. Proton-based radiation therapy (RT) is a new alternative to standard photon-based radiation therapy, that is likely to reduce the risk of cardiovascular complications.
Hypothesis: Treatment with chemoRT might induce myocardial dysfunction, symptoms of heart failure and decreased physical performance in patients with EGEJ Cancer.
Read more
The aim: Is to investigate the influence on chemoRT on myocardial function in EGEJ patients and evaluate the cardiac prognosis and eventually identify potential high-risk patients who might benefit from proton-based RT instead of the current photon-based RT.
Method: From power calculation the investigators plan to include 56 patients with EGEJ cancer during a period of two years. Inclusions criteria: biopsy verified EGEJ cancer supported by findings from gastroscopy, PET CT scan and with the final diagnosis locally advanced, non-metastatic. The patients will be examined with serial cardiac investigations to evaluate if they develop impairment of the heart function during or after chemoRT. The investigations include; electrocardiogram, cardiac biomarkers, echocardiography and cardio pulmonary exercise test. The examinations will be performed at study entry (baseline) and after six weeks and again after six months.
Read the detailed description
Background:
Patients with cancer in the esophagus and gastroesophageal junction (EGEJ) treated with chemoradiotherapy (chemoRT) have increased risk of cardiovascular disease. Both chemotherapy and radiotherapy have been reported to be associated with increased cardiovascular morbidity. Still, there is a survival benefit due to multimodal treatment and a careful patient selection. Radiation induced heart disease (RIHD) may include pericarditis, systolic and diastolic myocardial dysfunction, coronary heart disease, valvular heart disease and conduction abnormalities. Standard treatment of locally advanced EGEJ cancer today consists of neoadjuvant chemoRT followed by surgery or chemoRT alone. Elderly patients with frailty and pre-existing cardiovascular disease are in general not offered surgery but might be candidates for treatment with chemoRT alone, still with curative intent. However, the current understanding of RIHD in EGEJ patients is limited as data are sparse. In Sweden a single study has shown that chemoRT might potentially induce acute impairment of both systolic and especially diastolic left ventricular function. The lack of more substantial evidence leaves room for variation in clinical practice. Hence, there is a need for additional studies to provide more insights into the risk of RIHD, in particular on myocardial function during and after chemoRT as congestive heart failure is a serious complication associated with increased morbidity and mortality. Proton-based radiation therapy (RT) is a new alternative to standard photon-based radiation therapy, which reduces the radiation dose to the heart and subsequent risks of cardiovascular complications. However, the availability of proton therapy is still relatively limited for the general EGEJ population, and the indication for proton based RT is not yet evidence based. It is crucial to evaluate risk of heart failure during and after standard chemoRT and to identify potential high-risk patients who might benefit from proton therapy instead of the current standard therapy.
Hypothesis:
Treatment with chemoRT might induce myocardial dysfunction, symptoms of heart failure and decreased physical performance in patients with EGEJ Cancer.
The aim is:
- to identify systolic and diastolic myocardial dysfunction at rest and during peak exercise with advanced non-invasive imaging (echocardiography) following chemoRT.
- to evaluate if baseline myocardial biomarkers (Troponin T (TNT) and N-terminal pro b-type natriuretic peptide (NT-pro-BNP)) and risk factors (diabetes, smoking, hypertension, dyslipidemia) can predict development of myocardial dysfunction.
- to detect whether exercise echocardiography compared to resting echocardiography can identify additional patients with myocardial dysfunction following chemoRT.
- to examine whether development of myocardial dysfunction in EGEJ patients will be reflected in impairment of psychical capacity evaluated by cardiac pulmonary exercise test with assessment of maximal oxygen consumption.
- to evaluate if baseline symptoms classification with clinical frailty score and New York Heart Association (NYHA) and can predict development of myocardial dysfunction.
Method:
Design:
A prospective observational study of patients with EGEJ cancer. Fifty-six patients will be enrolled during a period of 18 months. For the individual patient the heart check investigations will be performed within six months and follow up in general is until 5 years.
After informed consent in the Department of Oncology, the patients will be examined with heart investigations (ECG, Echocardiography rest/exercise and CPX test) in the Department of Cardiology before they start oncologic treatment (baseline) after 6 weeks and again after 6 months.
Clinical frailty, risk factors and cardiac symptoms will be evaluated from structured interview at follow-ups. The investigators will use validated models for graduating risk factors, clinical frailty and shortness of breath (NYHA classification). The patients will serve as own controls comparing the baseline findings with the findings thereafter.
The heart investigations:
Electrocardiogram (ECG): Is made to detect ST-segment depression, elevation or negative T-waves, LV strain or arrhythmias.
Blood samples (Cardiac biomarkers): TNT to detect myocyte necrosis and NT-pro-BNP to detect myocardial dysfunction and lipids to be used in risk evaluation.
3D echocardiography at rest and during exercise: Two-and three-dimensional Doppler echocardiography is used to evaluate Left ventricular (LV) systolic and diastolic function.
LV systolic function is evaluated by 3D echocardiography estimated ejection fraction (LVEF) and by 2D global longitudinal strain (GLS), which is a sensitive marker of myocardial function beyond LVEF. The test will be performed at rest and at peak exercise using a semi-supine ergometer bicycle. Determination of LV contractile reserve capacity is evaluated by the difference in GLS and LVEF at rest and at peak exercise. Myocardial systolic reserve capacity in other cardiac diseases has demonstrated to be a significant marker of functional capacity.
LV diastolic function is evaluated by left atrial volume and pulsed and tissue-Doppler parameters according to current guidelines by the European Society of Cardiology.
Cardio pulmonary exercise (CPX) test:
Maximum oxygen uptake (VO2 max) from a cardio pulmonary test is gold standard to measure the physically capacity of patients and is known to add prognostic information in patients with heart failure independently of etiology. The patient will be placed on a semi-supine special designed bicycle with simultaneous determination of VO2 during increasing watts. Hemodynamic parameters as pulse, blood pressure and ECG will be measured continuously. Echocardiography will be performed at rest and during peak exercise
- Conditions
- Cancer of Esophagus
- Keywords
- Heartdisease, Radiation, Chemoradiotherapy, cardiovascular disease
- Medical subject headings
- Esophageal Neoplasms, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cancer esophagus and gastroesophageal junction | EGEJ cancer patients referred to combined therapy of chemoRT and surgery can be included. |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Left ventricular systolic function estimated by 2D longitudinal strain (GLS) and ejection fraction (EF) at rest and peak exercise
where a decrease of peak GLS of 10 % is considered clinical significant.
Measured: From Baseline till 6 weeks after.
Secondary outcomes (9)
• Change of NT-pro-BNP
with a double increase provided that serum level is above >300 pmol/L after ChemoRT provided e-GFR >30 ml/min.
Measured: From Baseline till 6 weeks after.
• Change in TNT
2 x upper normal value = >28 ng/l provided that Estimated glomerular filtration rate >50 ml/min.
Measured: From Baseline till 6 weeks after.
• Change of peak VO2
of 10% ml/kg/min after chemoRT compared to baseline.
Measured: From Baseline till 6 weeks after.
• Change in diastolic function
defined as an increase of at least one diastolic grade
Measured: From Baseline till 6 weeks after.
• Admission to hospital with clinical heart failure.
To investigate if the have had heart related admission to hospital
Measured: Baseline, after 4 weeks and 6 months.
• Dead - not cancer related.
Dead that is not related to the cancer diagnosis
Measured: From Baseline till 6 weeks after.
• Increased use of diuretics compared to baseline
accumulated use of thiazide, loop or aldosterone antagonists
Measured: Baseline, after 4 weeks and 6 months.
• Change in use of ace-inhibitors, betablockers, digoxin and hydralazine compared to baseline.
Increased use of the drugs mentioned
Measured: From Baseline till 6 weeks after.
Left ventricular systolic function estimated by 2D longitudinal strain (GLS) and ejection fraction (EF) at rest and peak exercise
where a decrease of EF 5 % (absolute) is considered clinical significant.
Measured: From Baseline till 6 weeks after.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2018
- Study start25 Jun 2018
- Primary completionAug 2021 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Cancer of EsophagusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital Skejby
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Cancer Society
- Responsible party
- Principal investigator, Steen Hvitfeldt Poulsen, Aarhus University Hospital Skejby
- Investigators
- Steen H Poulsen, MD phd DMSci, Principal investigator, Aarhus University Hopital, Skejby, Department of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03619317
- Sponsor's protocol ID
- 1-16-02-189-18
- Acronym
- Heartcheck
- Status last verified
- Mar 2021
- First submitted
- 3 Jun 2018
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Nielsen KM, Offersen BV, Nielsen HM, Vaage-Nilsen M, Yusuf SW. Short and long term radiation induced cardiovascular disease in patients with cancer. Clin Cardiol. 2017 Apr;40(4):255-261. doi: 10.1002/clc.22634. Epub 2017 Jan 31.
PubMed 28139844Madan R, Matalon S, Vivero M. Spectrum of Smoking-related Lung Diseases: Imaging Review and Update. J Thorac Imaging. 2016 Mar;31(2):78-91. doi: 10.1097/RTI.0000000000000185.
PubMed 26479130Beukema JC, van Luijk P, Widder J, Langendijk JA, Muijs CT. Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer? Radiother Oncol. 2015 Jan;114(1):85-90. doi: 10.1016/j.radonc.2014.11.037. Epub 2014 Dec 30.
PubMed 25554226Lund M, Alexandersson von Dobeln G, Nilsson M, Winter R, Lundell L, Tsai JA, Kalman S. Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial. Radiat Oncol. 2015 Jan 13;10:16. doi: 10.1186/s13014-014-0310-7.
PubMed 25582305Clemmensen TS, Eiskjaer H, Molgaard H, Larsen AH, Soerensen J, Andersen NF, Tolbod LP, Harms HJ, Poulsen SH. Abnormal Coronary Flow Velocity Reserve and Decreased Myocardial Contractile Reserve Are Main Factors in Relation to Physical Exercise Capacity in Cardiac Amyloidosis. J Am Soc Echocardiogr. 2018 Jan;31(1):71-78. doi: 10.1016/j.echo.2017.09.007. Epub 2017 Oct 27.
PubMed 29111120Chuong MD, Hallemeier CL, Jabbour SK, Yu J, Badiyan S, Merrell KW, Mishra MV, Li H, Verma V, Lin SH. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):488-497. doi: 10.1016/j.ijrobp.2015.11.043. Epub 2015 Dec 14.
PubMed 27084662Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011 Jul;12(7):681-92. doi: 10.1016/S1470-2045(11)70142-5. Epub 2011 Jun 16.
PubMed 21684205Xi M, Xu C, Liao Z, Chang JY, Gomez DR, Jeter M, Cox JD, Komaki R, Mehran R, Blum MA, Hofstetter WL, Maru DM, Bhutani MS, Lee JH, Weston B, Ajani JA, Lin SH. Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. Int J Radiat Oncol Biol Phys. 2017 Nov 1;99(3):667-676. doi: 10.1016/j.ijrobp.2017.06.2450. Epub 2017 Jun 27.
PubMed 29280461Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Alexandru Popescu B, Waggoner AD; Houston, Texas; Oslo, Norway; Phoenix, Arizona; Nashville, Tennessee; Hamilton, Ontario, Canada; Uppsala, Sweden; Ghent and Liege, Belgium; Cleveland, Ohio; Novara, Italy; Rochester, Minnesota; Bucharest, Romania; and St. Louis, Missouri. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016 Dec;17(12):1321-1360. doi: 10.1093/ehjci/jew082. Epub 2016 Jul 15. No abstract available.
PubMed 27422899van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.
PubMed 22646630Astrup Sondergaard MM, Nordsmark M, Sloth Moller D, Melgaard Nielsen K, Poulsen SH. Reduction in myocardial function and oxygen consumption after chemoradiotherapy in patients with esophageal cancer. Acta Oncol. 2022 May;61(5):566-574. doi: 10.1080/0284186X.2022.2048068. Epub 2022 Mar 15.
PubMed 35289694Sondergaard MMA, Nordsmark M, Nielsen KM, Poulsen SH. Cardiovascular Burden and Adverse Events in Patients With Esophageal Cancer Treated With Chemoradiation for Curative Intent. JACC CardioOncol. 2021 Dec 21;3(5):711-721. doi: 10.1016/j.jaccao.2021.10.002. eCollection 2021 Dec.
PubMed 34988480
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Chemo and Radiation Induced Systolic and Diastolic Myocardial Dysfunction in Patients With Cancer in Oesophagus and Gastroesophagael Junction - a Prospective Study
- ClinicalTrials.gov ID
- NCT03619317
- Acronym / sponsor ID
- Heartcheck / 1-16-02-189-18
- Conditions
- Cancer of Esophagus
- Keywords
- Heartdisease, Radiation, Chemoradiotherapy, cardiovascular disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Aarhus University Hospital SkejbyUniversity, hospital or other
- Collaborators
- Danish Cancer Society
- Study start
- 25 Jun 2018 (actual)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 7 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Introduction: Patients with cancer in esophagus and gastroesophageal junction (EGEJ) treated with chemoradiotherapy (chemoRT) have increased risk of cardiovascular disease. EGEJ patients often have frailty and pre-existing cardiovascular disease. This may disqualify them for standard trimodal curative treatment and offer surgery alone, chemoRT alone or palliative treatment only. The current understanding of radiation induced heart disease (RIHD) in EGEJ patients is limited. Hence, there is a need for additional studies. Especially on myocardial function during and after chemoRT as congestive heart failure is a serious complication associated with increased morbidity and mortality. Proton-based radiation therapy (RT) is a new alternative to standard photon-based radiation therapy, that is likely to reduce the risk of cardiovascular complications.
Hypothesis: Treatment with chemoRT might induce myocardial dysfunction, symptoms of heart failure and decreased physical performance in patients with EGEJ Cancer.
The aim: Is to investigate the influence on chemoRT on myocardial function in EGEJ patients and evaluate the cardiac prognosis and eventually identify potential high-risk patients who might benefit from proton-based RT instead of the current photon-based RT.
Method: From power calculation the investigators plan to include 56 patients with EGEJ cancer during a period of two years. Inclusions criteria: biopsy verified EGEJ cancer supported by findings from gastroscopy, PET CT scan and with the final diagnosis locally advanced, non-metastatic. The patients will be examined with serial cardiac investigations to evaluate if they develop impairment of the heart function during or after chemoRT. The investigations include; electrocardiogram, cardiac biomarkers, echocardiography and cardio pulmonary exercise test. The examinations will be performed at study entry (baseline) and after six weeks and again after six months.
Detailed description
Background:
Patients with cancer in the esophagus and gastroesophageal junction (EGEJ) treated with chemoradiotherapy (chemoRT) have increased risk of cardiovascular disease. Both chemotherapy and radiotherapy have been reported to be associated with increased cardiovascular morbidity. Still, there is a survival benefit due to multimodal treatment and a careful patient selection. Radiation induced heart disease (RIHD) may include pericarditis, systolic and diastolic myocardial dysfunction, coronary heart disease, valvular heart disease and conduction abnormalities. Standard treatment of locally advanced EGEJ cancer today consists of neoadjuvant chemoRT followed by surgery or chemoRT alone. Elderly patients with frailty and pre-existing cardiovascular disease are in general not offered surgery but might be candidates for treatment with chemoRT alone, still with curative intent. However, the current understanding of RIHD in EGEJ patients is limited as data are sparse. In Sweden a single study has shown that chemoRT might potentially induce acute impairment of both systolic and especially diastolic left ventricular function. The lack of more substantial evidence leaves room for variation in clinical practice. Hence, there is a need for additional studies to provide more insights into the risk of RIHD, in particular on myocardial function during and after chemoRT as congestive heart failure is a serious complication associated with increased morbidity and mortality. Proton-based radiation therapy (RT) is a new alternative to standard photon-based radiation therapy, which reduces the radiation dose to the heart and subsequent risks of cardiovascular complications. However, the availability of proton therapy is still relatively limited for the general EGEJ population, and the indication for proton based RT is not yet evidence based. It is crucial to evaluate risk of heart failure during and after standard chemoRT and to identify potential high-risk patients who might benefit from proton therapy instead of the current standard therapy.
Hypothesis:
Treatment with chemoRT might induce myocardial dysfunction, symptoms of heart failure and decreased physical performance in patients with EGEJ Cancer.
The aim is:
- to identify systolic and diastolic myocardial dysfunction at rest and during peak exercise with advanced non-invasive imaging (echocardiography) following chemoRT.
- to evaluate if baseline myocardial biomarkers (Troponin T (TNT) and N-terminal pro b-type natriuretic peptide (NT-pro-BNP)) and risk factors (diabetes, smoking, hypertension, dyslipidemia) can predict development of myocardial dysfunction.
- to detect whether exercise echocardiography compared to resting echocardiography can identify additional patients with myocardial dysfunction following chemoRT.
- to examine whether development of myocardial dysfunction in EGEJ patients will be reflected in impairment of psychical capacity evaluated by cardiac pulmonary exercise test with assessment of maximal oxygen consumption.
- to evaluate if baseline symptoms classification with clinical frailty score and New York Heart Association (NYHA) and can predict development of myocardial dysfunction.
Method:
Design:
A prospective observational study of patients with EGEJ cancer. Fifty-six patients will be enrolled during a period of 18 months. For the individual patient the heart check investigations will be performed within six months and follow up in general is until 5 years.
After informed consent in the Department of Oncology, the patients will be examined with heart investigations (ECG, Echocardiography rest/exercise and CPX test) in the Department of Cardiology before they start oncologic treatment (baseline) after 6 weeks and again after 6 months.
Clinical frailty, risk factors and cardiac symptoms will be evaluated from structured interview at follow-ups. The investigators will use validated models for graduating risk factors, clinical frailty and shortness of breath (NYHA classification). The patients will serve as own controls comparing the baseline findings with the findings thereafter.
The heart investigations:
Electrocardiogram (ECG): Is made to detect ST-segment depression, elevation or negative T-waves, LV strain or arrhythmias.
Blood samples (Cardiac biomarkers): TNT to detect myocyte necrosis and NT-pro-BNP to detect myocardial dysfunction and lipids to be used in risk evaluation.
3D echocardiography at rest and during exercise: Two-and three-dimensional Doppler echocardiography is used to evaluate Left ventricular (LV) systolic and diastolic function.
LV systolic function is evaluated by 3D echocardiography estimated ejection fraction (LVEF) and by 2D global longitudinal strain (GLS), which is a sensitive marker of myocardial function beyond LVEF. The test will be performed at rest and at peak exercise using a semi-supine ergometer bicycle. Determination of LV contractile reserve capacity is evaluated by the difference in GLS and LVEF at rest and at peak exercise. Myocardial systolic reserve capacity in other cardiac diseases has demonstrated to be a significant marker of functional capacity.
LV diastolic function is evaluated by left atrial volume and pulsed and tissue-Doppler parameters according to current guidelines by the European Society of Cardiology.
Cardio pulmonary exercise (CPX) test:
Maximum oxygen uptake (VO2 max) from a cardio pulmonary test is gold standard to measure the physically capacity of patients and is known to add prognostic information in patients with heart failure independently of etiology. The patient will be placed on a semi-supine special designed bicycle with simultaneous determination of VO2 during increasing watts. Hemodynamic parameters as pulse, blood pressure and ECG will be measured continuously. Echocardiography will be performed at rest and during peak exercise
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cancer esophagus and gastroesophageal junction | – | –EGEJ cancer patients referred to combined therapy of chemoRT and surgery can be included. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Age < 18 years * Patients not being able to give informed consent (decided by the investigator). * Patients not being able to understand Danish language. * Acute myocardial infarct within the last 6 months. * Present clinical severe heart valve disease and/or congestive heart failure with left ejection fraction < 25 %. * Patients with prior thoracic radiation and overlapping RT fields.
Key inclusion criteria (3 listed)
- Biopsy verified EGEJ cancer verified by gastroscopy, biopsy and PET/CT scan.
- The final diagnosis must be locally advanced, non-metastatic as determined at a multidisciplinary team conference.
- Patients referred to curative treatment with preoperative or definitive chemo- and radiotherapy.
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
• Left ventricular systolic function estimated by 2D longitudinal strain (GLS) and ejection fraction (EF) at rest and peak exercise
Time frame: From Baseline till 6 weeks after.
where a decrease of peak GLS of 10 % is considered clinical significant.
9 secondary outcomes
• Change of NT-pro-BNP
Time frame: From Baseline till 6 weeks after.
• Change in TNT
Time frame: From Baseline till 6 weeks after.
• Change of peak VO2
Time frame: From Baseline till 6 weeks after.
• Change in diastolic function
Time frame: From Baseline till 6 weeks after.
• Admission to hospital with clinical heart failure.
Time frame: Baseline, after 4 weeks and 6 months.
• Dead - not cancer related.
Time frame: From Baseline till 6 weeks after.
• Increased use of diuretics compared to baseline
Time frame: Baseline, after 4 weeks and 6 months.
• Change in use of ace-inhibitors, betablockers, digoxin and hydralazine compared to baseline.
Time frame: From Baseline till 6 weeks after.
Left ventricular systolic function estimated by 2D longitudinal strain (GLS) and ejection fraction (EF) at rest and peak exercise
Time frame: From Baseline till 6 weeks after.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Background: PubMed 28139844Nielsen KM, Offersen BV, Nielsen HM, Vaage-Nilsen M, Yusuf SW. Short and long term radiation induced cardiovascular disease in patients with cancer. Clin Cardiol. 2017 Apr;40(4):255-261. doi: 10.1002/clc.22634. Epub 2017 Jan 31.
- Background: PubMed 26479130Madan R, Matalon S, Vivero M. Spectrum of Smoking-related Lung Diseases: Imaging Review and Update. J Thorac Imaging. 2016 Mar;31(2):78-91. doi: 10.1097/RTI.0000000000000185.
- Background: PubMed 25554226Beukema JC, van Luijk P, Widder J, Langendijk JA, Muijs CT. Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer? Radiother Oncol. 2015 Jan;114(1):85-90. doi: 10.1016/j.radonc.2014.11.037. Epub 2014 Dec 30.
- Background: PubMed 25582305Lund M, Alexandersson von Dobeln G, Nilsson M, Winter R, Lundell L, Tsai JA, Kalman S. Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial. Radiat Oncol. 2015 Jan 13;10:16. doi: 10.1186/s13014-014-0310-7.
- Background: PubMed 29111120Clemmensen TS, Eiskjaer H, Molgaard H, Larsen AH, Soerensen J, Andersen NF, Tolbod LP, Harms HJ, Poulsen SH. Abnormal Coronary Flow Velocity Reserve and Decreased Myocardial Contractile Reserve Are Main Factors in Relation to Physical Exercise Capacity in Cardiac Amyloidosis. J Am Soc Echocardiogr. 2018 Jan;31(1):71-78. doi: 10.1016/j.echo.2017.09.007. Epub 2017 Oct 27.
- Background: PubMed 27084662Chuong MD, Hallemeier CL, Jabbour SK, Yu J, Badiyan S, Merrell KW, Mishra MV, Li H, Verma V, Lin SH. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):488-497. doi: 10.1016/j.ijrobp.2015.11.043. Epub 2015 Dec 14.
- Background: PubMed 21684205Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011 Jul;12(7):681-92. doi: 10.1016/S1470-2045(11)70142-5. Epub 2011 Jun 16.
- Background: PubMed 29280461Xi M, Xu C, Liao Z, Chang JY, Gomez DR, Jeter M, Cox JD, Komaki R, Mehran R, Blum MA, Hofstetter WL, Maru DM, Bhutani MS, Lee JH, Weston B, Ajani JA, Lin SH. Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. Int J Radiat Oncol Biol Phys. 2017 Nov 1;99(3):667-676. doi: 10.1016/j.ijrobp.2017.06.2450. Epub 2017 Jun 27.
- Background: PubMed 27422899Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Alexandru Popescu B, Waggoner AD; Houston, Texas; Oslo, Norway; Phoenix, Arizona; Nashville, Tennessee; Hamilton, Ontario, Canada; Uppsala, Sweden; Ghent and Liege, Belgium; Cleveland, Ohio; Novara, Italy; Rochester, Minnesota; Bucharest, Romania; and St. Louis, Missouri. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016 Dec;17(12):1321-1360. doi: 10.1093/ehjci/jew082. Epub 2016 Jul 15. No abstract available.
- Background: PubMed 22646630van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.
- Derived from this study: PubMed 35289694Astrup Sondergaard MM, Nordsmark M, Sloth Moller D, Melgaard Nielsen K, Poulsen SH. Reduction in myocardial function and oxygen consumption after chemoradiotherapy in patients with esophageal cancer. Acta Oncol. 2022 May;61(5):566-574. doi: 10.1080/0284186X.2022.2048068. Epub 2022 Mar 15.
- Derived from this study: PubMed 34988480Sondergaard MMA, Nordsmark M, Nielsen KM, Poulsen SH. Cardiovascular Burden and Adverse Events in Patients With Esophageal Cancer Treated With Chemoradiation for Curative Intent. JACC CardioOncol. 2021 Dec 21;3(5):711-721. doi: 10.1016/j.jaccao.2021.10.002. eCollection 2021 Dec.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steen H Poulsen, MD phd DMSci principal investigator
Aarhus University Hopital, Skejby, Department of Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer of Esophagus, run by Aarhus University Hospital Skejby at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mette MA Søndergaard, Cand.Med (004530130565, metast@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• Left ventricular systolic function estimated by 2D longitudinal strain (GLS) and ejection fraction (EF) at rest and peak exercise (time frame: From Baseline till 6 weeks after.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03619317, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2021.