Echocardiography for RILI Prediction

The Value of Echocardiography for Prediction of Radiation-induced Lung Injury in Non-small Cell Lung Cancer Patients Treated With Chemoradiation: an Onco-cardiac Prospective Cohort Study.

Severe radiation-induced lung injury (RILI) occurs in approximately 20% of the lung cancer patients, who are treated with curative chemoradiation. In this study the investigators want to evaluate the prognostic value of baseline cardiac function assessed with echocardiography for prediction of RILI.

Study Overview

• Status: Terminated
• Conditions: NSCLC

Detailed Description

Severe radiation-induced lung injury (RILI) occurs in approximately 20% of the lung cancer patients, who are treated with curative chemoradiation (CRT).This side-effect can heavily impact quality of life and is a dose-limiting factor for the treatment. Identifying high risk patients before the start of the treatment would make it possible to adapt the treatment by choosing another radiation technique or proton therapy. However, despite the fact that many patient and treatment characteristics have been associated with RILI, it is not possible to accurately predict the risk of RILI for individual patients. Recently, it has been shown that the radiation dose to the heart is a risk factor for lung toxicity in both animal and clinical studies. Also, in a study, carried out jointly by CARIM and GROW, it was found that patients with a previous diagnosis of cardiac disease had a significantly higher risk to develop RILI after CRT (p-value <0.001), even with low or no radiation dose to the heart. It is unknown whether asymptomatic cardiac comorbidity is also related to development of RILI. Taking into account that approximately 30% of all lung cancer patients suffer from symptomatic cardiac comorbidity at the start of cancer treatment, there is an urgent need for research projects focusing on cardio-oncology. These projects will make it possible to unravel the complex relationship between heart, lungs, chemotherapy and radiation treatment. In the current project the investigators hypothesize that biomarkers based on echocardiography, which reflects cardiac function, are prognostic for development of radiation induced lung injury after chemoradiotherapy. In addition, the investigators will validate our previous finding that presence of cardiac comorbidity is associated with RILI.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 ET
      • Maastro Clinic
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients referred to MAASTRO Clinic with non-small cell lung cancer stage I-III disease can be included in this study (approximately 160 patients per year).

Description

Inclusion Criteria:

• Clinical stage I-III non small cell lung cancer, excluding malignant pleural/pericardial effusion
• Planned for curatively intended primary (chemo)radiotherapy, due to irresectable disease and/or medical inoperability
• WHO performance status 0-2
• No history of prior chest radiotherapy
• No uncontrolled infectious disease
• No other active malignancy
• No prior lung surgery (VATS, wedge resection, segment resection, lobectomy)
• Willing and able to comply with the study prescriptions
• 18 years or older
• Ability to give and having given written informed consent before patient registration

Exclusion Criteria:

• malignant pleural/pericardial effusion
• history of prior chest radiotherapy
• uncontrolled infectious disease
• other active malignancy
• prior lung surgery (VATS, wedge resection, segment resection, lobectomy)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dyspnea score at three months after (chemo)radiotherapy, assessed by the patient version of the CTCv4.0	up to 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Dyspnea score at six months after (chemo)radiotherapy, assessed by the patient version of CTCv4.0	up to 6 months
Changes in dyspnea score after radiotherapy, compared to baseline	up to 12 months
Change in Left Ventricle Ejection Fraction (LVEF) (baseline versus 3-month after chemo radiation)	up to 3 months
Change in left atrial volume (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)	up to 3 months
Radiation pneumonitis at 3-months after start of radio(chemo)therapy, assessed on a follow-up 3D CT scan image.	up to 3 months
Lung fibrosis score at 6-months after start of chemo radiation, assessed on a follow-up CT scan image	up to 6 months
Prevalence-based dyspnea measure, reflecting severity as well as duration of dyspnea	up to 12 months
Changes in physical activity levels and sedentary behavior, assessed by accelerometry	up to 12 months
Pulmonary function based on spirometry	up to 3 months
Change in left atrial ejection fraction (from pts in SR)(2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)	up to 3 months
Change in mitral inflow (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)	up to 3 months
Change in pulmonary vein inflow patterns (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)	up to 3 months
Change in tissue doppler patterns of the mitral annulus (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)	up to 3 months
Cardiac blood biomarkers at baseline and during treatment, Brain natriuretic peptide(BNP), troponin I (TnI) and troponin T(TnT)	up to 3 months
Haemoglobin parameters in the blood at baseline and during treatment	up to 3 months
Inflammatory parameters (CRP, IL-6 and TNFa) in the blood at baseline and during treatment	up to 3 months
Time trends in physical activity and sedentary time from baseline till 12 months after radiotherapy, measured by accelerometers in four weekly periods	up to 12 months

Other Outcome Measures

Outcome Measure	Time Frame
Cardiac Comorbidity according to ICD v10	up to 12 months
Radiomics (the evolving field of texture analysis) of normal tissue(heart and lung)	up to 3 months
Mitochondrial DNA (prognostic value of mtDNA for development of RILI)	up to 12 months
Body composition, analysed by evaluation of muscle mass and fat mass on computed tomography (CT) scans at a standardized vertebral landmark (third lumbar vertebra)	up to 12 months
Muscle strength, measured by respiratory mouth pressure measurement, maximum inspiratoire mouthpressure, (Pimax)	up to 12 months
arterial inflammation as revealed by 18F-FDG PET . Standardized quantification parameters will be applied: Standardized uptake value (SUV), target-to-background ratio (TBR), most diseased segment analysis	up to 12 months
Calcification score of the coronary artery and thoracic aorta. The calcification will be quantified by using fully automated scoring and graded according to the Agatston score method	up to 3 months

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Collaborators: Academisch Ziekenhuis Maastricht
• Investigators: Principal Investigator: Dirk De Ruysscher, PhD., MAASTRO-clinic (senior researcher); Principal Investigator: Bas Kietselaer, MD,Phd, AzM/MUMC (cardiologist); Principal Investigator: Judith van Loon, MD,PhD, MAASTRO-clinic (radiation oncologist); Principal Investigator: Philippe Lambin, Prof,MD,Phd, MAASTRO-clinic (radiation oncologist); Principal Investigator: Anne-Marie Dingemans, MD, PhD, MAASTRO-clinic (pulmonogist)

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2017
• Primary Completion (Actual): September 12, 2019
• Study Completion (Actual): September 12, 2019

Study Registration Dates

• First Submitted: July 13, 2015
• First Submitted That Met QC Criteria: July 16, 2015
• First Posted (Estimate): July 17, 2015

Study Record Updates

• Last Update Posted (Actual): December 4, 2019
• Last Update Submitted That Met QC Criteria: December 2, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; echocardiography; prognostic; radiation-induced lung injury; chemo radiotherapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Lung Injury
• Other Study ID Numbers: echocardiographyRILI