Skip to main content
OpenTrials
Recruiting

NCT Number: NCT03978377

Cardiopulmonary Toxicity of Thoracic Radiotherapy

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, Ghobadi et al 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.

Recruiting

Interested in participating?

Request Info

Key information

About this study

In the present study, the incidence and time course of treatment-related changes in cardio-pulmonary physiology will be assessed using standard diagnostic tools such as echocardiography, cardiac MRI (CMR) and serum biomarkers and relate them to the radiation dose distribution. Such insight in the characteristics of this possible radiation-induced PH and contributing risk factors is essential to develop primary (radiation dose optimization) prevention strategies.

The general objective of this study is to test the hypothesis that pulmonary hypertension (PH) is a clinically relevant radiation-induced side effect of thoracic irradiation. If confirmed this allows us to take appropriate measures in patient care to improve quality of life in thoracic cancer patients.

To investigate this hypothesis, the following specific aims have been defined:

  • To assess the incidence and time course of PH in a prospective cohort study in patients treated with radiotherapy for lung or oesophageal cancer.
  • To characterize other changes in myocardial function and pulmonary arteries, and their function using cardiac MR.
  • To determine treatment-related risk factors, in particular radiation dose factors to the lungs and heart that could be used for future optimization strategies to minimize the risk of inducing PH in these patients.
  • To determine the clinical impact by correlating PH to patient-rated outcome measure (PROMs) and survival. Taken together this study will determine if radiation-induced pulmonary hypertension is a clinically relevant toxicity and will provide information required for future studies on its prevention and treatment. In addition, more insight will be obtained on other forms of cardiovascular damage and complications that may occur in these patients.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

  • No heart failure in the last 2 months
  • No 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 MRI

For MRI part:

  • contra-indications for MRI

Treatment and study plan

Primary outcomes

  1. Number of patients with high risk of pulmonary hypertension

    Time frame: 1 year

    High-risk pulmonary hypertension according to ESC/ERS classification

Secondary outcomes

  1. Troponine T change

    Time frame: 1 year

    Change in Troponine T concentration, between baseline and at 1 year

  2. NTproBNP change

    Time frame: 1 year

    Change in NTproBNP concentration, between baseline and at 1 year

  3. Number of patients with intermediate risk of pulmonary hypertension

    Time frame: 1 year

    Intermediate risk of pulmonary hypertension according to ESC/ERS classification

  4. Cumulative incidence of other late cardiopulmonary toxicity, as classified by CTCAE4.0

    Time frame: 1 year

    Cumulative incidence of other late cardiopulmonary toxicity, as classified by CTCAE4.0

  5. EORTC quality of life questionnaire C30

    Time frame: 1 year

    PROMs (EORTC QoL C30), including five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting),

  6. EORTC quality of life questionnaire LC13

    Time frame: 1 year

    PROMs (EORTC QoL LC13), including lung cancer-associated symptoms (cough, haemoptysis, dyspnoea and site specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication.

Study contacts

Contact information is provided by the study sponsor or research team.

CT Muijs, MD PhD

CONTACT

[email protected]

00315036115179

P van Luijk, DR

CONTACT

[email protected]

0031503611739

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Registry information

Acronym: CLARIFY

Important dates

Study start
2018
Primary completion
2026
Study completion
2027
First posted
Jun 7, 2019
Registry last updated
Mar 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.