Primary hypothesisCardiac function measured by echocardiography is a prognostic factor for developing radiation-induced dyspnea after (chemo) radiotherapy.Primary objectiveAssess the prognostic value of cardiac function, assessed by clinical…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter/endpoint:
* Dyspnea score at three months after (chemo)radiotherapy, assessed by the
patient version of the CTCv4.
Secondary outcome
Secondary study parameters/endpoints (if applicable)
* Dyspnea score at six months after (chemo)radiotherapy, assessed by the
patient version of CTCv4.
* Changes in dyspnea score after radiotherapy, compared to baseline.
* Change in Left Ventricle Ejection Fraction (LVEF) (baseline versus 3-month
after chemo radiation)
* Change in diastolic function (baseline versus 3-month after chemo radiation)
* Radiation pneumonitis at 3-months after start of radio(chemo)therapy,
assessed on a follow-up 3D CT scan image.
* Cardiac blood biomarkers at baseline and during treatment.
* Haemoglobin and inflammatory parameters (CRP, IL-6 and TNFa) at baseline and
during treatment
* Lung fibrosis score at 6-months after start of chemo radiation, assessed on a
follow-up CT scan image.
* Prevalence-based dyspnea measure, reflecting severity as well as duration of
dyspnea.
* Changes in physical activity levels and sedentary behavior, assessed by
accelerometry.(additional research: stage III NSCLC)
* Time trends in physical activity and sedentary time from baseline till 12
months after radiotherapy. (additional research: stage III NSCLC patients)
* (Change in) pulmonary function based on lung function tests (additional
research: stage III NSCLC patients)
Other study parameters (if applicable)
* Patient characteristics: age, gender, baseline FEV1, smoking, WHO-PS, weight
change past 6 months, weight change during treatment, weight, height, histology
and/or cytology
* Radiotherapy volumes: GTV, CTV, PTV
* Cardiac comorbidity according to ICD v10
* Classification of cardiac comorbidity into dyspnea-prone and dyspnea
non-prone comorbidities
* Treatment characteristics: chemotherapy, dosimetric parameters lung,
dosimetric parameters heart, radiotherapy technique
* Echocardiography variables
* Calcification score of the coronary artery and thoracic aorta
* Cardiac blood biomarkers at baseline and during treatment
* Arterial inflammation as revealed by 18F-FDG PET. Standardized quantification
parameters will be applied: 1. Standardized uptake value (SUV), 2.
target-to-background ratio (TBR), 3. Most diseased segment analysis
* Mitochondrial DNA
* Blood biomarkers related to heart damage and repair
* Radiomics of normal tissue (heart and lung)
* Body composition, muscle strength (both limb and respiratory muscles), muscle
function, exercise tolerance
Background summary
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. [6] 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 we hypothesize that biomarkers based on
echocardiography, which reflects cardiac function, are prognostic for
development of radiation induced lung injury after chemoradiotherapy. In
addition, we will validate our previous finding that presence of cardiac
comorbidity is associated with RILI.
Main study parameters/endpoints: Severe RILI, defined as dyspnea * grade 2
(according to CTCv4.0)
Study objective
Primary hypothesis
Cardiac function measured by echocardiography is a prognostic factor for
developing radiation-induced dyspnea after (chemo) radiotherapy.
Primary objective
Assess the prognostic value of cardiac function, assessed by clinical
examination and echocardiography, for radiation-induced dyspnea.
Secondary objectives
Investigate the prognostic value of mitochondrial DNA for radiation-induced
dyspnea.
Investigate the prognostic value of blood biomarkers for radiation-induced
dyspnea.
Investigate the association between heart damage/repair and tumour
growth/response.
Investigate the value of radiomics for prediction of normal tissue toxicity.
Investigate the association between mustle wasting and dyspnea.
Investigate the association between physical activity measured by accelerometry
and patient reported dyspnea.
Investigate time trends in physical activity, sedentary behavior and
radiation-induced dyspnea.
Investigate the association between changes in lung function tests, patient
reported dyspnea and CT-based scoring of radiation-induced lung toxicity.
(additional research: stage III NSCLC patients).
Study design
Study design:
A prospective cohort study.
Duration
The expected duration of the study is 26 months.
The expected start date is 06-2016.
The enrolment finished date is expected to be 12-2018.
The treatment period end date is expected to occur in 12-2018.
The follow-up period end date is expected to occur in 12-2019.
The statistical analysis of the primary endpoint will be in 06-2019.
Based on the decision of either the principal treating physician or the patient
himself, treatment for this patient within the study can be discontinued at any
time. Reasons for this decision (medical reasons, personal decision) should be
documented. The patient is not obliged to give a reason for stopping treatment.
Study burden and risks
Patients will receive standard (chemo-) radiation treatment and standard
follow-up according to the protocol of Maastro-clinic.
The following procedures are required for the study:
* Echocardiography and electrocardiography, at baseline and 3 months after
(chemo) radiation
* Cardiac examination, including assessment of muscle wasting, at baseline and
3 months after (chemo) radiation
* PET-CT scan 3 months after (chemo) radiation
* Saliva sample for genetic research that will be stored in the MAASTRO biobank
* A blood sample that will be stored in the biobank, at three time points
* Accelerometry to assess physical activity during four periods
Patients with stage III NSCLC will participate in an additional part which
consists of:
* A lung function test
* Extra assessment of muscle wasting at two time points
The questionnaires to assess patient reported outcome are already being used in
standard clinical practice for all lung cancer patients treated at MAASTRO
clinic. There are no risks associated with participation. All procedures are
carried out with non-investigational products.
Patients will not receive direct benefit for themselves.
The baseline PET-CT is according to standard clinical practice and the PET-CT*s
required for the study will give an extra dose of 13-16 mSv per scan. This
dose is negligible compared to standard radiotherapy treatment. The contrast
materials used in PET-CT (used in standard clinical practice) are safe drugs;
adverse reactions ranging from mild to severe do occur but severe reactions are
very uncommon. The standard safety protocols will be used according to standard
clinical practice.
Dr. Tanslaan 12
Maastricht 6229 ET
NL
Dr. Tanslaan 12
Maastricht 6229 ET
NL
Listed location countries
Age
Inclusion criteria
* Clinical stage I-III non-small cell lung cancer
* 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
* 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
* WHO performance status >2
* History of prior chest radiotherapy
* Uncontrolled infectious disease
* Other active malignancy
* Prior lung surgery
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02501707 |
| CCMO | NL53276.068.15 |