Should cardiac MRI or echocardiography be used for screening of fatal pulmonary hypertension after thoracic radiotherapy?

screening thoracic irradiation cardio-pulmonary toxicity

Dr. C.T. Muijs
dr P van Luijk
E Slager MSc

Nature of the research:
Clinical, prospective cohort study to investigate cardio-pulmonary complications after radiotherapy using echocardiography and cardiac MRI.

Fields of study:
radiology radiotherapy cardiology

Background / introduction
Radiotherapy plays a pivotal role in the treatment of thoracic tumours. However, the associated exposure of normal tissues often leads to severe side effects. Indeed, growing evidence even suggests that overall survival after radiotherapy for lung and oesophageal cancer is related to the radiation dose to heart and lungs. (1)
Interestingly, we showed in rats (2,3) that irradiation of lung and/or heart can damage the cardio-pulmonary circulation resulting in pulmonary hypertension (PH). With cardiac magnetic resonance imaging (cMRI) we confirmed with small group of patients that thoracic radiotherapy can indeed cause PH-like changes in the cardio-pulmonary circulation. However, currently PH is not recognized as an adverse effect of radiotherapy.
In unique multicentre prospective cohort study (CLARIFY), we are currently investigating cardio-pulmonary toxicity in patients treated for lung and oesophageal cancer. We want to test the hypothesis that PH is a clinically relevant side-effect of thoracic radiotherapy. The study might provide critical information for targets of primary prevention and for the possibility of PH screening.
Research question / problem definition
CLARIFY opened in September 2018 and will include 320 patients. Cardiopulmonary health of every patient will be investigated before and after radiotherapy using echocardiography (5x), blood sampling (5x) and optionally cardiac MRI (3x).
Aim of the present project is to investigate the correlation between heart parameters from cardiac MRI and echocardiography. Cardiac MRI is a non-invasive technique providing useful prognostic information in patients with PH. Cardiac MRI is the reference standard in assessment of RV structure and function. Echocardiography is a primary diagnostic tool of PH and is more patient- and cost-friendly, however is affected by patient observability. (4)
The question arises: if patients receiving thoracic radiotherapy will be screened for PH, will it be with cardiac MRI or echocardiography?
First you will familiarize yourself with the literature/background of the study and the study database. Subsequently you will collect and analyse the data. These data will include the heart parameters from cardiac MRI and the echocardiography results. Furthermore, the radiation dose parameters can be used in the analyses. Most echocardiographic parameters can be retrieved from the study database. Cardiac MRI parameters will be acquired using specialized software. These heart parameters will be compared using SPSS and possibly Matlab.

Daily supervision will be performed by Emmy Slager who coordinates the trial as a PhD student. In addition weekly meetings will be held with dr. Kristel Muijs (Radiation Oncologist) and dr. Peter van Luijk (Project leader).
1) Lin, S.H., Wang, L., Myles, B., Thall, P.F., Hofstetter, W.L., Swisher, S.G., Ajani, J.A., Cox, J.D., Komaki, R. and Liao, Z. (2012) Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer. International Journal of Radiation Oncology Biology Physics, 84, 1078– 1085.
2) Ghobadi, G., Bartelds, B., van der Veen, S.J., Dickinson, M.G., Brandenburg, S., Berger, R.M.F., Langendijk, J. a., Coppes, R.P. and van Luijk, P. (2012) Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension. Thorax, 67, 334–341.
3) Ghobadi, G., Van Der Veen, S., Bartelds, B., De Boer, R.A., Dickinson, M.G., De Jong, J.R., Faber, H., Niemantsverdriet, M., Brandenburg, S., Berger, R.M.F., Langendijk, J.A., Coppes, R.P. and Van Luijk, P. (2012) Physiological interaction of heart and lung in thoracic irradiation. International Journal of Radiation Oncology Biology Physics, 84, e639-46.
4) Galiè, N., Humbert, M., Vachiery, J.-L., Gibbs, S., Lang, I., Torbicki, A., Simonneau, G., Peacock, A., Vonk Noordegraaf, A., Beghetti, M., Ghofrani, A., Gomez Sanchez, M.A., Hansmann, G., Klepetko, W., Lancellotti, P., Matucci, M., McDonagh, T., Pierard, L.A., Trindade, P.T., Zompatori, M., Hoeper, M., Aboyans, V., Vaz Carneiro, A., Achenbach, S., Agewall, S., Allanore, Y., Asteggiano, R., Paolo Badano, L., Albert Barberà, J., Bouvaist, H., Bueno, H., Byrne, R.A., Carerj, S., Castro, G., Erol, Ç., Falk, V., Funck-Brentano, C., Gorenflo, M., Granton, J., Iung, B., Kiely, D.G., Kirchhof, P., Kjellstrom, B., Landmesser, U., Lekakis, J., Lionis, C., Lip, G.Y.H., Orfanos, S.E., Park, M.H., Piepoli, M.F., Ponikowski, P., Revel, M.-P., Rigau, D., Rosenkranz, S., Völler, H. and Luis Zamorano, J. (2015) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Respiratory Journal, 37, 903– 975.
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