Cardiotoxicity of mediastinal radiotherapy

Abstract

Aim: To explore available recent literature related to cardiotoxicity following mediastinal radiation.

Background: Radiotherapy-related heart injury is well documented, with no apparent safety threshold dose. The number of long-term cancer survivors exposed to mediastinal radiotherapy at some point of their treatment is increasing. Heart dosimetric parameters are of great importance in developing a treatment plan, but few data are available regarding radiosensitivity and dose-volume constraints for specific heart structures.

Materials and methods: In October 2018, we identified articles published after 1990 through a PubMed/MEDLINE database search. The authors examined rough search results and manuscripts not relevant for the topic were excluded. We extracted clinical outcomes following mediastinal radiotherapy of childhood cancers, lymphoma, medulloblastoma, thymic cancers and hematopoietic cell transplantation survivors and evaluated treatment planning data, whenever available.

Results: A total of 1311 manuscripts were identified in our first-round search. Of these manuscripts, only 115 articles, matching our selection criteria, were included.

Conclusions: Studies uniformly show a linear radiation dose-response relationship between mean absorbed dose to the heart (heart-D_mean) and the risk of dying as a result of cardiac disease, particularly when heart-D_mean exceeds 5 Gy. Limited data are available regarding dose-volume predictors for heart substructures and the risk of subsequent cardiac toxicity. An individual patient's cardiotoxicity risk can be modified with advanced treatment planning techniques, including deep inspiration breath hold. Proton therapy is currently showing advantages in improving treatment planning parameters when compared to advanced photon techniques in lymphoma, thymic malignancies, malignant mesothelioma and craniospinal irradiation.

Keywords: 2D-RT, two-dimensional radiotherapy; 3D-CRT, three-dimensional conformal radiation therapy; CI, confidence interval; CSI, craniospinal irradiation; CVD, Cardiovascular disease; Cardiotoxicity; Dmax, maximum absorbed dose in a specified volume; Dmean, mean absorbed radiation dose in a specified volume; Dose-volume predictors; EQD2, equivalent dose in 2 Gy fractions; G, grade; Gy, Gray; HR, hazard ratio; HT, Helical tomotherapy; IFRT, involved field radiotherapy; IMRT, intensity modulated radiation therapy; INRT, involved node radiotherapy; ISRT, involved site radiotherapy; LAD, left anterior descending artery; Mediastinal radiotherapy; Mediastinal tumours; Mv, megavoltage; NTCP, normal tissue complication probability; Normal tissue complication probability; OAR, organs at risk; OR, odds ratio; PTV, planning target volume; RR, relative risks; TBI, total body irradiation; VMAT, volumetric modulated arc therapy; Vx, receiving at last x Gy.

Fig. 1

Cumulative risks of coronary artery disease (CAD) as the first cardiac event among 5-year survivors of Hodgkin Lymphoma by time since initial Hodgkin Lymphoma treatment by categories of Heart-D_mean. The estimated 25-year cumulative CAD incidence was 4.1%, 9.4% and 12.6% for patients with a Heart-D_mean of 0 Gy, 15 Gy and ≥25 Gy, respectively. Reprinted with permission. © (2016) American Society of Clinical Oncology. All rights reserved. Van Nimwegen et al.: J Clin Oncol Vol. 34 (3), Year: 2016, 235–43.

Fig. 2

Free breathing (FB) VMAT plan and dose-volume histogram taking into account internal target motion based on 4D-CT scan versus deep inspiration breath hold (DIBH) VMAT plan in a 50-year old patient after R1 resection of thymoma.