Echocardiography for RILI Prediction

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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NSCLC

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, echocardiography, radiation-induced lung injury, prognostic, chemo radiotherapy, non-small cell lung cancer