Cardiopulmonary Toxicity of Thoracic Radiotherapy

NCT03978377 | Recruiting DMC

• 1 other identifier: CLARIFY
• Study Type: observational
• Target: 320
• Locations: 3 countries
• Sites: 3

Brief 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, 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.

Conditions

Oesophageal Cancer; Non Small Cell Lung Cancer

Keywords

Radiotherapy; Pulmonary hypertension

Outcome Measures

Primary Outcomes (1)

• Number of patients with high risk of pulmonary hypertension

  High-risk pulmonary hypertension according to ESC/ERS classification

  1 year

Secondary Outcomes (6)

• Troponine T change

  1 year

• NTproBNP change

  1 year

• Number of patients with intermediate risk of pulmonary hypertension

  1 year

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

  1 year

• EORTC quality of life questionnaire C30

  1 year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study focuses on two patient populations: 1) Patients with oesophageal cancer in the mid or distal oesophagus, who will be treated with radiotherapy with curative intent, with or without chemotherapy, with or without surgery. 2\) 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), who will be treated with radiotherapy with curative intent, with or without chemotherapy. Patients will be included in 3 participating centers: * University Medical Center Groningen, Groningen, The Netherlands * Beatson West of Scotland Cancer Centre /NHS Greater Glasgow and Clyde, Glasgow, United Kingdom * Radboud UMC, Nijmegen, The Netherlands

You may qualify if:

• 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.

You may not qualify if:

• 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
• For MRI part:
• contra-indications for MRI

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (3)

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

TERMINATED

Radboud UMC

Nijmegen, Gelderland, 6525 GA, Netherlands

RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, United Kingdom

TERMINATED

MeSH Terms

Conditions

Esophageal Neoplasms; Carcinoma, Non-Small-Cell Lung; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

CT Muijs, MD PhD

CONTACT

00315036115179; c.t.muijs@umcg.nl

P van Luijk, DR

CONTACT

0031503611739; p.van.luijk@umcg.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: June 7, 2019
• Study Start: September 1, 2018
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); BE (1); NL (1)