Risk of left ventricular dysfunction after thoracic irradiation

Umut Fidan*, Arno Hessels, Robin Wijsman, Emmy Slager, Jan Bussink, Anthonie L Duijnhouwer, Tineke Willems, E S Hoendermis, J.A. Langendijk, Christina T Muijs, Peter van Luijk

*Corresponding author voor dit werk

Onderzoeksoutput: AbstractAcademic

Samenvatting

Purpose/Objective:
Despite technological improvements, thoracic radiotherapy is still associated with side-effects, such as cardiotoxicity. Indeed, various studies suggest that thoracic radiotherapy leads to cardiac damage and that dose to the heart is even associated with overall survival.
In preclinical studies, histopathological cardiac and pulmonary changes have been identified that lead to changes in both left and right-ventricle function and morphology already in the first weeks after irradiation. Therefore, the CLARIFY-study was initiated to test the hypothesis that such early changes also occur in patients, and to assess if these changes have clinical impact. In a previous interim analysis, we demonstrated that thoracic radiotherapy can cause reductions in right ventricle function in association with irradiated lung volume (1).
The aim of the present interim analysis of the CLARIFY-study was to investigate if thoracic radiotherapy can cause changes in left ventricular function in patients treated for lung or oesophageal cancer and to identify patient and treatment related risk factors for such changes.

Material/Methods:
The study population of this interim analysis was composed of 171 patients included in the prospective observational CLARIFY-study in our centre between September 2018 and September 2023 (Table 1). Left ventricular global longitudinal strain (LV-GLS) is a sensitive parameter to detect subclinical LV dysfunction. Therefore LV-GLS was assessed using echocardiography at baseline, at 6 weeks, 6 months and one year after radiotherapy. To classify LV-GLS as “subclinical LV dysfunction”, we used the commonly-used criterion of a relative reduction of at least 15% compared with baseline. Statistical significance of changes was assessed with repeated measures ANOVA. The influence of patient and treatment related factors on post-treatment LV-GLS was assessed using linear regression analysis. Differences in mean heart dose (MHD) between treatment types were tested using the t-test.

Results:
In total, LV-GLS was measured in 378 echocardiographies, with 127, 111, 77, and 63 at baseline, 6 weeks, 6 months, and one year respectively. Ninety-three patients had measurements available both at baseline and 6 weeks after radiotherapy. Thirteen of these (14.0%) developed subclinical LV dysfunction. This prevalence did not rise 6 months after radiotherapy (7 out of 66, 10.6%). On the other side, at 1 year after radiotherapy, this increased to 24.5% (13 out of 53). This is consistent with a gradual deterioration of LV-GLS over time (p=0.003, Figure 2).
At 6 weeks after treatment, patients treated with VMAT had worse LV-GLS than those treated with IMPT (β=0.198, p=0.012). A trend for worse LV-GLS was found for lung cancer patients compared to oesophageal cancer patients (β=0.153, p=0.05 at 6 weeks). Pathology, TNM classification, smoking, alcohol usage, cardiac history, hypertension, and diabetes had no effect on LV-GLS change at follow-up (p>0.05). Also, surgical resection before irradiation, induction chemotherapy and adjuvant immunotherapy had no effect on LV-GLS (p>0.05).
In the VMAT patient group, increasing MHD worsened the relative change of LV-GLS at one year after radiotherapy (β=-0.483, p=0.014). However, in the IMPT group, MHD did not influence LV-GLS (β=0.264, p=0.18). MHD was significantly higher in the VMAT group than the IMPT group (13.57 Gy vs. 7.36 Gy, p<0.001), suggesting that the impact of treatment modality on LV-GLS may be dose-related. Moreover, the lack of effect in the IMPT group suggests that the changes in LV-GLS occur beyond a certain threshold only.

Conclusion:
Thoracic radiotherapy for lung and oesophageal cancer can cause progressive subclinical deterioration of left ventricular function, with first changes visible as early as 6 weeks after treatment. Although the impact of these early changes needs to be investigated, they may be prevented by reducing the dose to the heart, for example, by using IMPT.
Originele taal-2English
Pagina's1625-1627
Aantal pagina's3
StatusPublished - 2024
EvenementESTRO 2024 - Glasgow, United Kingdom
Duur: 3-mei-20247-mei-2024
https://www.estro.org/Congresses/ESTRO-2024/2431/radiotherapyasthestandardofcareforthetreatmentofoe

Conference

ConferenceESTRO 2024
Land/RegioUnited Kingdom
StadGlasgow
Periode03/05/202407/05/2024
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