Impact of Cancer Therapy on Myocardial Function in Patients With Esophagus Cancer

NCT03619317 | Unknown

• 1 other identifier: 1-16-02-189-18
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cancer of Esophagus

Keywords

Heartdisease; Radiation; Chemoradiotherapy; cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• • 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.

  From Baseline till 6 weeks after.

Secondary Outcomes (9)

• • Change of NT-pro-BNP

  From Baseline till 6 weeks after.

• • Change in TNT

  From Baseline till 6 weeks after.

• • Change of peak VO2

  From Baseline till 6 weeks after.

• • Change in diastolic function

  From Baseline till 6 weeks after.

• • Admission to hospital with clinical heart failure.

  Baseline, after 4 weeks and 6 months.

Study Arms (1)

Cancer esophagus and gastroesophageal junction

EGEJ cancer patients referred to combined therapy of chemoRT and surgery can be included.

Eligibility Criteria

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

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.

You may qualify if:

• 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.

Sponsors & Collaborators

• Aarhus University Hospital Skejby: lead
• Danish Cancer Society: collaborator

Study Sites (1)

University Hospital of Aarhus, Department of Cardiology

Aarhus N, 8200, Denmark

RECRUITING

Related Publications (12)

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  PMID: 28139844 BACKGROUND

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• Beukema 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.

  PMID: 25554226 BACKGROUND

• Lund 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.

  PMID: 25582305 BACKGROUND

• Clemmensen 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.

  PMID: 29111120 BACKGROUND

• Chuong 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.

  PMID: 27084662 BACKGROUND

• Sjoquist 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.

  PMID: 21684205 BACKGROUND

• Xi 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.

  PMID: 29280461 BACKGROUND

• Nagueh 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.

  PMID: 27422899 BACKGROUND

• van 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.

  PMID: 22646630 BACKGROUND

• Astrup 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.

  PMID: 35289694 DERIVED

• Sondergaard 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.

  PMID: 34988480 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Steen H Poulsen, MD phd DMSci

  Aarhus University Hopital, Skejby, Department of Cardiology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mette MA Søndergaard, Cand.Med

CONTACT

004530130565; metast@rm.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, MD, Ph.D., DMSci

Study Record Dates

• First Submitted: June 3, 2018
• First Posted: August 7, 2018
• Study Start: June 25, 2018
• Primary Completion: August 1, 2021
• Study Completion: March 1, 2022
• Last Updated: March 23, 2021

Record last verified: 2021-03

Locations

DK (1)