A PROspective, explorative cohort study to correlate CARdiac BIomarkers with late cardiac toxicity induced by radiotherapy alone or combined with anthracycline chemotherapy for hodgkin lymphoma (PROCARBI)

Rationale: Cardiac toxicities, mainly myocardiopathy, valvular heart disease and coronary heart disease, are unwanted delayed side effects after chemotherapy and/or mediastinum radiotherapy in Hodgkin Lymphoma patients and breast cancer patients. There are national guideline for follow-up of Hodgkin and selected non-Hodgkin lymphomas. Those guidelines include tests focusing on early detection of heart failure, including a physical examination, ECG, blood test to measure NT-proBNP and other risk factors of CHD, and a cardiac ultrasound every 5 years. The diagnosis of heart failure is generally only possible when symptoms have become manifest and the heart disease cannot be reversed. Biomarkers have the potential to screen at low cost subtle changes in the heart that may reflect or predict early adverse changes before they become clinically evident. Use of serial biomarker measurements (including NT-proBNP, ST2, GDF15, Galectin 3, and hsTn) during follow-up may provide information on individual patterns of change and may contribute to prevention, in taking early measures to prevent further deteriorating of the cardiac condition. In addition, adverse changes in the heart may also be confirmed by adding other imaging techniques to heart US such as cardiac MRI before clinical symptoms occur. Finally, using patient’s reported outcome measures (PROMs) questionnaire including the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) and the Seattle Angina Questionnaire (SAQ-7) it may be possible to correlate those objective findings and changes in these findings with the patient’s cardiac health status and with the biomarkers.
Objectives: We hypothesize that there is a combination of biomarkers that is a predictor of early development of cardiac toxicity from radiotherapy and chemotherapy in a population at risk of developing late clinically manifest cardiac toxicity after previous mediastinal radiotherapy alone or combined with chemotherapy. We also hypothesize that imaging tests including functional US and cardiac-MRI could objectively confirm those early developments, and that their clinical impact could be identified using PROMs in addition to the anamnesis and physical examinations.
Study design: This study is a prospective explorative cohort study for patients in long-term follow-up after mediastinal radiotherapy alone or combined with chemotherapy for Hodgkin and selected non-Hodgkin lymphoma to assess the correlation between a panel of blood biomarkers, cardiac US and MRI imaging, and PROMs.
Study population: All patients > 18 years, who have been treated for Hodgkin or non-Hodgkin Lymphoma with radiation of the mediastinum with or without anthracycline-containing chemotherapy with at least 5 years of disease free survival.
Intervention: There is a national prospective cohort of lymphoma patients currently followed by the BETER consortium. The current study will include patients at one of these follow-up visits and add a blood sample, PROMs, and cardiac-MRI, in addition to the scheduled measurements at the inclusion visit and the next visit two years later.

We hypothesize that the combination of biomarkers (e.g. NT-proBNP, ST2, GDF15, Galectin 3, hsTn) is an early predictor of cardiac toxicity from radiotherapy and chemotherapy in a population at risk of developing late cardiac toxicity after previous radiotherapy alone or combined with chemotherapy. We also hypothesize that imaging tests including functional US (all patients) and cardiac MRI (up to the first consecutive 80 patients) can objectively confirm those early signs of cardiac toxicities, and that the clinical impact can be assessed using PROMs.

2 points 2 years apart

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