Cardiac Changes After Stereotactic Radiotherapy for Early Stage NSCLC Cancer or Lung Metastasis (HALO)

The investigators aim to optimize the radiation treatment of early stage lung cancer patients. Therefore, detailed understanding is needed of the type of toxicity and the location of these toxicities for patients who receive high fraction doses. These have not been measured in these patients before, therefore our primary research question is: is it possible to measure changes in cardiac condition after radiotherapy, with respect to cardiac arrhythmias, fibrosis, hemodynamic function change and pericarditis?

Study Overview

• Status: Terminated
• Conditions: Lung Metastases; Lung Cancer Stage I; Lung Cancer Stage II
• Intervention / Treatment: Diagnostic test: Cardiac condition measurements

Detailed Description

Rationale: For lung cancer patients that receive thoracic irradiation, cardiac toxicity was not considered to play a role, because it was expected to occur many years after treatment. However, recently several studies have shown higher death rates for lung cancer patients receiving higher cardiac doses, possibly due to cardiac toxicity. Most knowledge on cardiac toxicity that is available, is based on patients that receive conventionally fractionated radiation treatment, where the heart receives a relatively low dose of radiation. For patients that receive stereotactic body radiation therapy (SBRT), which gives high fraction doses, the heart may receive peak doses of radiation, especially for centrally located lung tumours. This type of therapy is standard of care for early stage lung cancer patients, with very high local control that is similar to surgically treated patients. In order to improve the radiation treatment for these early stage lung cancer patients, detailed knowledge on cardiac toxicity in these patients is necessary.

Objective: the investigators aim to optimize the radiation treatment of early stage lung cancer patients. To reach that goal, detailed understanding is needed of the type of toxicity and the location on the heart of these toxicities for patients who receive high fraction doses. These have not been measured in this category of patients before, therefore our primary research question is: is it possible to measure changes in cardiac condition 3 or 12 months after radiotherapy, with respect to cardiac arrhythmias, tissue fibrosis, hemodynamic function change and pericarditis? Our secondary research question is: is it possible to measure local fibrosis and correlate this to local dose? The third research question is: is it possible to measure early cardiac morphology changes during the course of the irradiation? Study design: Twenty five patients with early stage lung cancer or a solitary lung metastasis of a solid tumour, who are treated with SBRT will be enrolled in an observational prospective cohort study and treated following standard clinical practice on a cone-beam or MR guided linear accelerator (Linac). Condition of the heart will be examined before treatment using ECG, cardiac MRI with added T1- and T2-mapping, echocardiography and blood biomarkers. These tests will be repeated 3 and 12 months after treatment.

Study population: 25 patients with a lung tumour in close proximity to the heart (edge of tumour <3cm from the heart) will be included. All patients receive SBRT for a primary lung tumour (stage IA-IIB), or for a solitary lung metastasis of a solid tumour.

Intervention (if applicable): not applicable Main study parameters/endpoints: It will be investigated 1) if changes in cardiac condition (cardiac arrhythmias, fibrosis, hemodynamic function change and pericarditis) can be visualised and quantified. A negative change of more than 5% between pre-and post-treatment measurements is considered toxicity. 2) If local fibrosis is associated to local dose, 3) if morphology changes are visible during treatment.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The patient will have 3 sessions with several diagnostic tests: ECGs, cardiac MRIs, echocardiography and blood sampling, and will fill out 3 questionnaires. Limited side effects of these tests are expected. Cardiac tests will be evaluated by a cardiologist and dedicated radiologist and reported to the radiation oncologist who will inform the patient and refer to the cardiologist if needed. The burden for these patients will be, next to the time spent for the diagnostic tests and travel time; an intravenous blood sampling and administration of MRI contrast agent. The additional time spent for diagnostic tests per session are: echo (30 min), ECG (5 min), vena puncture (5 min) and MRI (45 min) + time in the waiting room. Filling out the 3 questionnaires will take 15 min each. The possible benefit for the patient is the extensive cardiac screening. Should a problem come to light, the patient will be referred to the cardiologist.

Results from this patient cohort are directly relatable to all early stage NSCLC who are treated with SBRT, and possibly oesophageal cancer patients as well. Should this study show that cardiac dose causes cardiac toxicity in this time frame, the aim should be to improve treatment for all patients who are comparable. Ergo, patients who receive cardiac dose because of their tumour location, and who are generally unfit for surgery because of their physical condition (early stage NSCLC patients and oesophageal cancer patients).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jose Belderbos, MD, PhD; Phone Number: +31 20 512 9111; Email: j.belderbos@nki.nl
• Study Contact Backup: Name: Barbara Stam, PhD; Phone Number: +31 20 512 9111; Email: b.stam@nki.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Netherlands Cancer Institute
  • Amsterdam, Netherlands, 1105AZ
    • Amsterdam UMC, location AMC
  • Leiden, Netherlands, 2333ZA
    • Leids Universitair Medisch Centrum (LUMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Receive SBRT treatment for stage 1A-2B NSCLC or for a solitary lung metastasis of a solid tumour
• Closest distance between edge of tumor and heart < 3 cm

Exclusion Criteria:

• Pacemaker/ICD
• Renal function below GFR <30 ml/min/1.7m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: A; Radiotherapy; SBRT Additional cardiac diagnostics	Diagnostic test: Cardiac condition measurements; Cardiac MRI, ECG, echocardiography, cardiac blood markers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with a change in cardiac condition	Percentage of patients with at least 5% change in cardiac arrhythmia (outcome 2) and/or at least 5% change in fibrosis (outcome 3) and/or at least 5% change in hemodynamic function (outcome 4) and/or development of pericarditis post-treatment (outcome 5)	1 year
Percentage of change in cardiac arrhythmia	Percentage of change in ECG-derived QRS duration (s) between Pre- and Post-treatment values	1 year
Percentage of change in fibrosis	Percentage of change in MRI-derived Extra Cellular Volume (cc) between Pre- and Post-treatment values	1 year
Percentage of change in hemodynamic function	Percentage of change in MRI- and echocardiography-derived ejection fraction (%) between Pre- and Post-treatment values	1 year
Binary change in pericarditis status	Presence of pericarditis signs on MRI post-treatment while absence of pericarditis signs pre-treatment: yes/no	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local fibrosis	Is there a correlation between the presence of local fibrosis and dose to this region	1 year
Morphology changes	Are changes in morphology visible on the MRI scans made during treatment, compared to the pre treatment MRIs	1 year

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Dutch Cancer Society
• Investigators: Principal Investigator: Jose Belderbos, MD, PhD, The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2021
• Primary Completion (Actual): April 1, 2023
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: May 21, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: M19CCR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No