Cardiotoxicity and Other Late Effects After Radiotherapy and Immuno-chemoTherapy in Non-Hodgkin lYmphoma

Completed

• Conditions: Non Hodgkin Lymphoma; DLBCL; Cardiovascular Diseases; Cardiomyopathies; Cardiotoxicity; Metabolic Syndrome; Quality of Life; Late Effect; Heart Failure

• Registration Number: NCT07041827
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

Survivors of non-Hodgkin lymphoma and a control group will be screened for (sub)clinical cardiovascular disease, to assess the influence of contemporary treatments on risk and burden of (sub)clinical cardiovascular disease and their influence on survival.

Detailed Description

Rationale: Few studies have thus far addressed the burden from treatment-related cardiovascular disease in long-term survivors of non-Hodgkin's lymphoma (NHL). The life expectancy of patients with aggressive B-cell NHL has significantly increased since treatment regimens have improved. Although the addition of rituximab to CHOP chemotherapy does not appear to increase cardiotoxicity during treatment, little is known about the long-term cardiac safety of R-CHOP. Nonetheless, cardiotoxicity due to doxorubicin exposure appears to be a key problem in clinical practice, while radiation exposure of the heart may add to cardiac disease risk.

Objective: The main objective is to assess in detail risk factors for cardiovascular disease and cardiotoxicity and to compare heart function parameters, vascular parameters and biomarkers associated with cardiovascular function among five- tot fifteen-year survivors, treated for aggressive B-cell NHL, and sibling controls and to assess the effects of cumulative doses of individual immuno- and chemotherapeutic agents and radiation of the heart on cardiovascular function parameters. Secondary objectives are to assess the prevalence of other late effects (metabolic syndrome, quality of life and the predictive value of newly developed markers for cardiovascular disease).

Study design: These parameters will be assessed in a cross-sectional study, nested in a well characterized cohort of aggressive B-cell NHL survivors, with a control population consisting of siblings of these survivors.

Study population: 350 survivors will be invited who are between five and fifteen years after treatment with (R-)CHOP with/without mediastinal radiotherapy, and compare them with 175 sibling controls. Eligible participants will be approached and invited to the BETER clinic by their (former) treating physician.

Main study parameters/endpoints: The main study parameters will be echocardiographic systolic and diastolic heart parameters and global longitudinal strain measurement, arterial stiffness (by pulse wave velocity measurements), endothelial function (by peripheral arterial tonometry), electrocardiography, advanced glycation end products (by skin autofluorescence, AGE-reader), presence of (sub)clinical cardiovascular disease and biomarkers. Adverse cardiovascular events, risk factors and quality of life will be assessed through questionnaires and physical measurements. Exposure to (R-)CHOP and radiotherapy will be extracted from the medical history. Multivariable logistic and linear regression analyses will be used for analyses.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: With the results of our study, guidelines for follow up and prevention will be developed which will benefit the participants during their own follow up in the future. The burden of participating is expected to be low since the study is mainly observational and assessments required in the context of research as much as possible combined with the provided standard of care for survivors during one or two hospital visits.

Study Timeline

• Study First Submitted: 2019-02-20
• Study Start: 2020-02-01
• Primary Completion: 2022-10-01
• Study Completion: 2023-02-01
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-19
• Last Update Submitted: 2025-06-19
• Study First Posted: 2025-06-27
• Last Update Posted: 2025-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 217

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Echocardiography: systolic and diastolic heart parameters, various strain measurements such as global longitudinal strain	Once, at enrollment	LVEF (continuous), LVEF\<50%, GLS (continuous) GLS\>-18%, NT-proBNP (continuous), NT-proBNP\>=125 pg/mL

Secondary Outcome Measures

Name	Time	Method
Electrocardiography	Once, at enrollment	Presence of cardiac disease
Pulse wave velocity	Once, at enrollment	Measurement of arterial stiffness / vascular function
Association of different biomarkers	Once, at enrollment	Value of different biomarkers (Nt-proBNP, Troponin T, sST2, galectin-3, GDF-15, high sensitive CRP)
EndoPAT (peripheral arterial tonometry)	Once, at enrollment	Measurement of endothelial function / vascular function
Metabolic syndrome	Once, at enrollment	Defined if 3 out of 5 of the following criteria are present: hypertension, dyslipidemia, diabetes, obesity, increased abdominal circumference
Questionnaires	Once, at enrollment	Assessment of health related quality of life and symptoms by validated questionnaires: EORTC QLQ-C30, EORTC-NHL-HG29, EORTC-BR29/PR-25 (sexuality items)
Advanced glycation end products	Once, at enrollment	Assessment of AGEs by skin autofluorescence, as a marker for cardiovascular and metabolic disease

Trial Locations

Locations (1)

Netherlands Cancer Institute; 🇳🇱 Amsterdam, North Holland, Netherlands