Clinical trial NCT02501707: Echocardiography for RILI Prediction
Official title: 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.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: NSCLC
Keywords: echocardiography
radiation-induced lung injury
prognostic
chemo radiotherapy
non-small cell lung cancer
NSCLC
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Academisch Ziekenhuis Maastricht
First posted: 2015-07-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Dyspnea score at three months after (chemo)radiotherapy, assessed by the patient version of the CTCv4.0
timeFrame: up to 3 months
Secondary outcomes:
measure: Dyspnea score at six months after (chemo)radiotherapy, assessed by the patient version of CTCv4.0
timeFrame: up to 6 months
measure: Changes in dyspnea score after radiotherapy, compared to baseline
timeFrame: up to 12 months
measure: Change in Left Ventricle Ejection Fraction (LVEF) (baseline versus 3-month after chemo radiation)
timeFrame: up to 3 months
measure: Change in left atrial volume (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)
timeFrame: up to 3 months
measure: Radiation pneumonitis at 3-months after start of radio(chemo)therapy, assessed on a follow-up 3D CT scan image.
timeFrame: up to 3 months
measure: Lung fibrosis score at 6-months after start of chemo radiation, assessed on a follow-up CT scan image
timeFrame: up to 6 months
measure: Prevalence-based dyspnea measure, reflecting severity as well as duration of dyspnea
timeFrame: up to 12 months
measure: Changes in physical activity levels and sedentary behavior, assessed by accelerometry
timeFrame: up to 12 months
measure: Pulmonary function based on spirometry
timeFrame: up to 3 months
measure: Change in left atrial ejection fraction (from pts in SR)(2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)
timeFrame: up to 3 months
measure: Change in mitral inflow (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)
timeFrame: up to 3 months
measure: Change in pulmonary vein inflow patterns (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)
timeFrame: up to 3 months
measure: Change in tissue doppler patterns of the mitral annulus (2009 AHA/ESC guidelines)(baseline versus 3-month after chemo radiation)
timeFrame: up to 3 months
measure: Cardiac blood biomarkers at baseline and during treatment, Brain natriuretic peptide(BNP), troponin I (TnI) and troponin T(TnT)
timeFrame: up to 3 months
measure: Haemoglobin parameters in the blood at baseline and during treatment
timeFrame: up to 3 months
measure: Inflammatory parameters (CRP, IL-6 and TNFa) in the blood at baseline and during treatment
timeFrame: up to 3 months
measure: Time trends in physical activity and sedentary time from baseline till 12 months after radiotherapy, measured by accelerometers in four weekly periods
timeFrame: up to 12 months
Other outcomes:
measure: Cardiac Comorbidity according to ICD v10
timeFrame: up to 12 months
measure: Radiomics (the evolving field of texture analysis) of normal tissue(heart and lung)
timeFrame: up to 3 months
measure: Mitochondrial DNA (prognostic value of mtDNA for development of RILI)
timeFrame: up to 12 months
measure: Body composition, analysed by evaluation of muscle mass and fat mass on computed tomography (CT) scans at a standardized vertebral landmark (third lumbar vertebra)
timeFrame: up to 12 months
measure: Muscle strength, measured by respiratory mouth pressure measurement, maximum inspiratoire mouthpressure, (Pimax)
timeFrame: up to 12 months
measure: 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
timeFrame: up to 12 months
measure: 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
timeFrame: up to 3 months
Locations:
city: Maastricht
country: Netherlands
facility: MAASTRO clinic
state: Limburg
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: MAASTRO-clinic (senior researcher)
name: Dirk De Ruysscher, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: AzM/MUMC (cardiologist)
name: Bas Kietselaer, MD,Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: MAASTRO-clinic (radiation oncologist)
name: Judith van Loon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MAASTRO-clinic (radiation oncologist)
name: Philippe Lambin, Prof,MD,Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: MAASTRO-clinic (pulmonogist)
name: Anne-Marie Dingemans, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: