The main objective is to test if PH occurs in patients treated with thoracic radiotherapy and identify dose metrics and other risk factors for the development of PH after thoracic radiotherapy. In addition, changes in systolic and diastolic…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Pulmonary vascular disorders
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following primary endpoints will be assessed:
Primary aim is to confirm that PH occurs in patients receiving thoracic
radiotherapy and assess incidence and time course. Therefore we decided to use
high-risk pulmonary hypertension as assessed by echocardiography at one year
after radiotherapy as primary endpoint. Following the ECS/ERS guidelines (25),
a patient is classified as high risk of PH when meeting one of the following
criteria:
- tricuspid valve Doppler velocity 2.9-3.4m/s with other signs of PH (see below)
- tricuspid valve Doppler velocity >3.4m/s
Other signs of PH are:
- Pulmonary artery acceleration time (<105 ms)
- Early pulmonary valve diastolic velocity (>2.2 m/s)
- Doppler notching of right ventricular outflow tract signal (y)
- Inferior Caval Vein collapsibility (>21 mm and <50% collapse)
- Left ventricle eccentricity index (>1.1 in systole)
- RV dilatation (RVEDV>45mm)
Secondary outcome
The following secondary endpoints will be assessed:
- Intermediate risk of PH:
o tricuspid valve Doppler velocity <2.8m/s in combination with other signs of PH
o tricuspid valve Doppler velocity 2.9-3.4m/s without *other signs of PH*
- Right ventricle systolic dysfunction
- Right ventricle diastolic dysfunction
- Left ventricle systolic dysfunction
- Left ventricle diastolic dysfunction
- Change in NT pro BNP
- Acute and late cardiac and pulmonary toxicity: Common Toxicity Criteria for
Adverse Events version 4.0.
- Patient-rated outcome is assessed using the EORTC quality of life core
questionnaire (EORTC QLQ-C30) and additionally the shortened version of EORTC
QoL -LC13.
Background summary
Radiotherapy improves locoregional control and survival of thoracic tumour
patients. However, the associated exposure of normal tissues, often leads to
side effects and possibly even reduces survival. Indeed, there is growing
evidence that overall survival after radiotherapy for lung and oesophageal
cancer is related to the radiation dose to heart and lungs. This suggests that
thoracic radiotherapy causes mortality, which is currently not recognized as
radiation-induced toxicity. So the question arises how to explain this
treatment-related mortality.
Interestingly, we demonstrated in rats that thoracic irradiation can lead to
pulmonary hypertension (PH). Histopathological analysis showed that
radiation-induced PH closely resembles the pulmonary arterial hypertension
(PAH) subtype. Moreover, in a clinical pilot study we confirmed early signs of
PH including dose-dependent reductions in blood flow towards the lungs in
radiotherapy patients.
In general PH significantly affects survival. Moreover, the PAH subtype is the
most-rapidly progressive and lethal subtype. However, medical treatment can
significantly slow down PAH progression, providing opportunities for secondary
prevention. Yet, hard evidence that radiation-induced PH is a clinically
relevant phenomenon in patients treated for thoracic tumours, is lacking.
Study objective
The main objective is to test if PH occurs in patients treated with thoracic
radiotherapy and identify dose metrics and other risk factors for the
development of PH after thoracic radiotherapy. In addition, changes in systolic
and diastolic myocardial function of the systemic and pulmonary circulation
after radiotherapy will be investigated.
Study design
Prospective multicenter cohort study.
Study burden and risks
We will perform a prospective cohort study in 320 patients with lung and
oesophageal cancer treated with standard (chemo-)radiotherapy. In these
patients we will assess parameters of cardiovascular function using
echocardiography and serum biomarkers prior to radiotherapy and at 6, 13, 26
and 52 weeks after radiotherapy. All patients will also be invited for further
characterization of vascular and cardiac damage with cardiac MR prior to
treatment and at 13 and 52 weeks after treatment and in case of cardiovascular
abnormalities are observed during echocardiography. Also physician-rated
toxicities and patient-rated outcome measures will be assessed as part of our
prospective standardized follow up programs (METC nr 2014.379 and METc nr
2013.101)
To establish treatment-dependence, signs of PH will be related to lung dose. To
estimate the impact on health, signs of pulmonary hypertension will be related
to survival, toxicity and QoL.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
• Patients with oesophageal cancer in the mid or distal oesophagus and patients
with NSCLC stage IIA-III or NSCLC stage IV with limited brain metastases
(treatable with surgery or stereotactic radiosurgery) or SCLC limited disease
(stage I-IIIB)
• Scheduled for external-beam radiotherapy with curative intention.
• WHO 0-2.
• Age >= 18 years
• Written informed consent.
Exclusion criteria
• Heart failure in the last 2 months
• Pulmonary embolism in the last 2 months
• COPD gold IV
• BMI >35
• History of thoracic radiotherapy
• Noncompliance with any of the inclusion criteria
- For MRI part: Contra indications for MRIFor MRI part:
• contra-indications for MRI
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 |
|---|---|
| CCMO | NL62680.042.17 |
| Other | volgt |