Table 3 Overview of the literature on the association between cardiac biomarkers and cardiac radiation exposure. (Note: The criteria for inclusion were: (a) patients with breast cancer had to be treated with radiotherapy, and; (b) any cardiac biomarker was tested to determine its association with radiotherapy. Studies which measured biomarker change in relation to chemotherapy alone or were performed in animals, were excluded.)
Author, year [Ref] | Design | n | Population | RT dosea | Techniquea | Anthracycline/ Anti-Her2 therapy | Mean (SD) Heart Dmean | Biomarkers measured | Biomarker measurement timepoints | Reported findings on the association of biomarkers with cardiac dosimetry | Commentsc |
|---|---|---|---|---|---|---|---|---|---|---|---|
Studies without reported Heart Dmean | |||||||||||
Hughes-Davies et al., 1995 [13] | Prospective | 50 | Left Breast cancer | 45-46 Gy/23-25Fx + boost | Conventional Photon | Not Available | NR | TnT | Pre-RT and immediately post-RT | No association of TnT with estimated cardiac irradiation (< 10%) | Indirect estimation of irradiated cardiac volume |
Wondergem et al., 2001 [14] | Case–control; retrospective case selection | 188 | Breast cancer (48; L/R = NR), Hodgkin’s lymphoma (73) vs Healthy Controls (67) | 50-60 Gy/20-30Fx | Conventional Photon | Not Available | NRb | ANP | 9.5 years (mean; SD = 0.9) post-RT | ANP elevated with estimated cardiac irradiation (20–30%) compared to control group. Elevated ANP associated with CVD | Multi-variable analysis of predictors for ANP not performed. Indirect estimation of irradiated cardiac volume |
D’Errico et al., 2015 [18] | Prospective | 59 | Left breast cancer | 40-50 Gy/15-25Fx | 3DCRT | Permitted | NRd | TnI, BNP | Pre-RT, during RT, immediately post-RT and 1, 3, 6, 9, 12 months post-RT | Heart V50% was associated with normalised BNP at 1 year. e No association with TnI | Logistic regression performed after dosimetric variables and BNP at 1 year were categorised (full model NR). Analysis of absolute measurements not performed. No correction for multiple comparisons |
Chalubinska-Fendler et al., 2019 [23] | Case–control; Prospective | 51 | Left breast cancer | 50-66 Gy/25-33Fx | 3DCRT | Permitted | NR | LBP, TnT, NT-proBNP, FABP, CRP | Pre-RT, immediately after RT and 1 month after RT | LBP levels were associated with cardiac dosimetry on multivariable linear regression. No association of other biomarkers with cardiac dosimetry | - |
Aula et al., 2020 [25] | Prospective | 63 | Breast cancer (L/R = 50/13) | 50 Gy/25Fx ± boost or 42.6 Gy/16Fx | 3DCRT | Not Permitted | NRb | sST2, | Pre-RT, immediately after RT and 3 months after RT | Patients with > 15% worsening in global longitudinal strain (GLS)(14/63) on echocardiography showed a significant increase in ST2 levels. No association of biomarkers with cardiac dosimetry | Logistic regression performed after patients were categorised based on GLS cut-off of 15%. Analysis of absolute measurements with dosimetric variables not performed |
Studies with reported Heart Dmean | |||||||||||
Erven et al., 2012 [15] | Prospective | 75 | Breast cancer (L/R = 51/24) | 50 Gy/25Fx ± boost | 3DCRT, mixed photon-electron or electrons | Permitted | 9.0 (4.0)b | TnI | Pre-RT and immediately post-RT | TnI levels were significantly elevated post-RT in left-sided patients | Multi-variable analysis of predictors for TnI not performed |
D’Errico et al., 2012 [16] | Case–control; retrospective case selection | 60 | Left breast cancer (30, Pre-RT vs 30, Post RT) | 40-50 Gy/15-25Fx + boost | 3DCRT | Permitted | 2.5 (1.2) | TnI, NT-proBNP | 11.2 months (mean; SD = 4.2) post-RT | No correlation of cardiac dosimetry with overall post-RT NT-proBNP or TnI | Small sample size. Association of post-RT NT-proBNP with cardiac dosimetry was established on a small subgroup (8/30) of patients |
Skyttä et al., 2015 [17] | Prospective | 58 | Left breast cancer or DCIS | 50 Gy/25Fx ± boost or 42.6 Gy/16Fx | 3DCRT | Not Permitted | 3.0 (1.4) | hsTnT, BNP | Pre-RT, during RT and immediately post-RT | Patients with hsTnT rise > 30% (12/58) had higher heart Dmean. No association with BNP | Exclusion of chemotherapy limits generalisability |
Palumbo et al., 2015 [19] | Prospective | 43 | Left breast cancer | 50–50.4 Gy/25-28Fx ± boost | 3DCRT | Not Permitted | 2.4 (0.8) | BNP | Pre-RT and 1, 6, 12 months post-RT | Normalised BNP at 1 month,, 6 months and 1 year post-RT were associated with cardiac dosimetry. e No association with absolute BNP levels | Small sample size. Exclusion of chemotherapy limits generalisability |
Skyttä et al., 2019 [20] | Prospective | 80 | Breast cancer or DCIS (L/R = 60/20) | 50 Gy/25Fx ± boost or 42.6 Gy/16Fx | 3DCRT | Not Permitted | 3.1 (1.5)b | hsTnT, NT-proBNP | Pre-RT, immediately after RT and 3 years after RT | No association of biomarkers with cardiac dosimetry | Exclusion of chemotherapy limits generalisability |
Demissei et al., 2019 [21] | Prospective | 87 | Breast cancer (60; L/R = NR), Lung Cancer (13), Mediastinal lymphoma (14) | Conventional fractionation) | Photon (technique NR) or Protons | Permitted | 1.5 (1.1)b | hsTnT, NT-proBNP, PIGF, GDF-15 | Pre-RT and a median of 20 days post-RT (IQR 1–35) | No association of biomarkers with cardiac dosimetry in breast cancer patients | PIGF and GDF-15 associated with cardiac dosimetry in lung and lymphoma group, though sample size was small. Analysis for left breast not performed |
Yu et al., 2019 [22] | Retrospective | 47 | Her2 + breast cancer (L/R = 26/21) | 50 Gy/25Fx or 42.4 Gy/16Fx ± boost | 3DCRT or IMRT | Permitted | 1.8 (1.5)b | hsTnI | Baseline (Pre-Chemotherapy), Pre-RT, immediately post-RT and 6 months post-RT | Statistical analysis not performed due to incomplete data on paired samples | - |
De Sanctis et al., 2020 [24] | Prospective | 44 | Breast cancer (L/R = 27/17) | 42.4 Gy/16Fx ± boost | 3DCRT | Permitted | 1.3 (NR)b | hsTnI, NT-proBNP | Pre-RT, during RT, immediately post-RT and 12 months post-RT | No association of biomarkers with cardiac dosimetry | Heart Dmean not used for linear mixed modelling. Small sample size |
Speers et al., 2021 [26] | Prospective | 51 | Left breast cancer | 50 Gy/25Fx ± boost | 3DCRT or IMRT | Permitted | 2.0 (NR) | hsTnI, NT-proBNP, hsCRP, ET-1, IL-6, Lipid Profile f | Pre-RT, immediately after RT and 3 months after RT | IL-6 immediately after completing RT, associated with heart Dmean. No association of other biomarkers with cardiac dosimetry | Multi-variable analyses of predictors for biomarkers not performed |