Dataset Information

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

ABSTRACT:

Background

Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured.

Method

In five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method.

Results

MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories.

Conclusion

In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

SUBMITTER: Chau OW

PROVIDER: S-EPMC10538714 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

Chau Oi-Wai OW El-Sherif Omar O Mouawad Matthew M Sykes Jane M JM Butler John J Biernaski Heather H deKemp Robert R Renaud Jennifer J Wisenberg Gerald G Prato Frank S FS Gaede Stewart S

PloS one 20230928 9

<h4>Background</h4>Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quant ...[more]

PMID: 37768966

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Project description:BackgroundThe cardiotoxicity caused by radiotherapy is a critical problem in the treatment of patients with breast cancer. The appropriate radiotherapy modality sparing for cardiac valves in left-sided breast cancer has not been well defined. The aim of this study was thus to compare the dosimetric differences in heart and cardiac valves of 3-dimensional conformal radiotherapy (3D-CRT), fixed-field intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) to find the optimal radiotherapy modality sparing for cardiac valves in patients with left breast cancer.MethodsFrom January 5, 2021, to March 15, 2021, 21 patients with left-sided breast cancer postmastectomy were included in this study, and 3 different plans for adjuvant radiation were created using 3D-CRT, IMRT, and VMAT for each patient. All patients received 50 Gy in 25 fractions. The mean dose (Dmean) of the heart; percentage volume of the heart receiving ≥5 Gy (V5), ≥30 Gy (V30), and ≥40 Gy (V40); and the Dmean and the near-maximum dose (D0.03cc) of cardiac valves were extracted from dose-volume histograms (DVHs) and compared. The correlations in dosimetric factors between cardiac valves and the whole heart were analyzed.ResultsIMRT significantly decreased the values of V5, V30, V40, and Dmean in the whole heart compared to 3D-CRT and VMAT (P<0.001). Among the 3 different plans, IMRT had the lowest radiation dose to the Dmean and the D0.03cc of the aortic valve (1.27 Gy/1.75 Gy), pulmonary valve (3.44 Gy/6.89 Gy), tricuspid valve (1.02 Gy/1.14 Gy), and mitral valve (0.93 Gy/1.00 Gy). Pearson correlation analysis found that local parameters (Dmean and D0.03cc) within valves were strongly correlated to the global parameters (V5, V30, V40, and Dmean) of the heart.ConclusionsThis study revealed that IMRT showed the lowest cardiac valves dose compared with 3D-CRT and VMAT in left-sided breast cancer radiotherapy. IMRT might be the optimal modality sparing for cardiac valves in this group of patients. Further studies need to be carried out in order to validate the protective role of IMRT on the cardiac valves.

Project description:BackgroundThis study investigated the feasibility and potential clinical benefit of utilizing a new proton treatment technique: Spot-scanning proton arc (SPArc) therapy for left-sided whole breast radiotherapy (WBRT) to further reduce radiation dose to healthy tissue and mitigate the probability of normal tissue complications compared to conventional intensity modulated proton therapy (IMPT).MethodsEight patients diagnosed with left-sided breast cancer and treated with breast-preserving surgery followed by whole breast irradiation without regional nodal irradiation were included in this retrospective planning. Two proton treatment plans were generated for each patient: vertical intensity-modulated proton therapy used for clinical treatment (vIMPT, gantry angle 10°-30°) and SPArc for comparison purpose. Both SPArc and vIMPT plans were optimized using the robust optimization of ± 3.5% range and 5 mm setup uncertainties. Root-mean-square deviation dose (RMSD) volume histograms were used for plan robustness evaluation. All dosimetric results were evaluated based on dose-volume histograms (DVH), and the interplay effect was evaluated based on the accumulation of single-fraction 4D dynamic dose on CT50. The treatment beam delivery time was simulated based on a gantry rotation with energy-layer-switching-time (ELST) from 0.2 to 5 s.ResultsThe average D1 to the heart and LAD were reduced to 53.63 cGy and 82.25 cGy compared with vIMPT 110.38 cGy (p = 0.001) and 170.38 cGy (p = 0.001), respectively. The average V5Gy and V20Gy of ipsilateral lung was reduced to 16.77% and 3.07% compared to vIMPT 25.56% (p = 0.001) and 4.68% (p = 0.003). Skin3mm mean and maximum dose were reduced to 3999.38 cGy and 4395.63 cGy compared to vIMPT 4104.25 cGy (p = 0.039) and 4411.63 cGy (p = 0.043), respectively. A significant relative risk reduction (RNTCP = NTCPSPArc/NTCPvIMPT) for organs at risk (OARs) was obtained with SPArc ranging from 0.61 to 0.86 depending on the clinical endpoint. The RMSD volume histogram (RVH) analysis shows SPArc provided better plan robustness in OARs sparing, including the heart, LAD, ipsilateral lung, and skin. The average estimated treatment beam delivery times were comparable to vIMPT plans when the ELST is about 0.5 s.ConclusionSPArc technique can further reduce dose delivered to OARs and the probability of normal tissue complications in patients treated for left-sided WBRT.

Project description:BackgroundRadiotherapy for breast cancer (BC) and its resulting cardiac exposure are associated with subclinical left ventricular dysfunction characterized by early decrease of global longitudinal strain (LS) measurement based on 2D speckle-tracking echocardiography. Recent software allows multi-layer and segmental analysis of strain, which may be of interest to quantify and locate the impact of cardiac exposure on myocardial function and potentially increase the early detection of radiation-induced cardiotoxicity. The aim of the study was to evaluate whether decrease in LS 6 months after radiotherapy is layer-specific and if it varies according to the left ventricular regional level and the coronary arterial territories.MethodsLS was measured at baseline before radiotherapy and 6 months post-radiotherapy. The LS was obtained for each myocardial layer (endocardial, mid-myocardial, epicardial), left ventricular regional level (basal, mid, apical) and coronary artery territory (left anterior descending artery (LAD), circumflex artery, right coronary artery).ResultsThe study included 64 left-sided BC patients. Mean age was 58 years, mean doses to the heart, the left ventricle and the LAD were respectively 3.0, 6.7 and 16.4 Gy. The absolute decrease of LS was significant for the three layers (endocardial: - 20.0 ± 3.2% to - 18.8 ± 3.8%; mid-myocardial: - 16.0 ± 2.7% to - 15.0 ± 3.1%; epicardial: - 12.3 ± 2.5% to - 11.4 ± 2.8%, all p = 0.02), but only the relative decrease of LS in the endocardial layer was close to be significant (- 4.7%, p = 0.05). More precisely, the LS of the endocardial layer was significantly decreased for the most exposed parts of the left ventricle corresponding to the apical level (- 26.3 ± 6.0% vs. -24.2 ± 7.1%, p = 0.03) and LAD territory (- 22.8 ± 4.0% vs. -21.4 ± 4.8%, p = 0.03).ConclusionSix months post-radiotherapy, LS decreased predominantly in the endocardial layer of the most exposed part of the left ventricle. For precise evaluation of radiotherapy-induced cardiotoxicity and early left ventricular dysfunction, the endocardial layer-based LS might be the most sensitive parameter.Trial registrationClinicalTrials.gov: NCT02605512 , Registered 6 November 2015 - Retrospectively registered.

Project description:BackgroundDeep inspiration breath hold (DIBH) is an effective technique for reducing heart exposure during radiotherapy for left-sided breast cancer. Despite its benefits, cost considerations and its impact on workflow remain significant barriers to widespread adoption.ObjectivesThis study aimed to assess the cost-effectiveness of DIBH and compare its operational, financial, and clinical outcomes with free breathing (FB) in breast cancer treatment.MethodsTreatment plans for 100 patients with left-sided breast cancer were generated using both DIBH and FB techniques. Dosimetric data, including the average mean heart dose, were calculated for each technique and used to estimate the cardiotoxicity of radiotherapy. A state-transition microsimulation model based on SCORE2 (Systematic Coronary Risk Evaluation) algorithms projected the effects of DIBH on cardiovascular outcomes and quality-adjusted life-years (QALYs). Costs were calculated from a provider perspective using time-driven activity-based costing, applying a willingness-to-pay threshold of €40,000 for cost-effectiveness assessment. A discrete event simulation model assessed the impacts of DIBH vs FB on throughput and waiting times in the radiotherapy workflow.ResultsIn the base case scenario, DIBH was associated with an absolute risk reduction of 1.72% (95% CI: 1.67%-1.76%) in total cardiovascular events and 0.69% (95% CI: 0.67%-0.72%) in fatal cardiovascular events over 20 years. Additionally, DIBH was estimated to provide an incremental 0.04 QALYs (95% CI: 0.05-0.05) per left-sided breast cancer patient over the same time period. However, DIBH increased treatment times, reducing maximum achievable throughput by 12.48% (95% CI: 12.36%-12.75%) and increasing costs by €617 per left-sided breast cancer patient (95% CI: €615-€619). The incremental cost-effectiveness ratio was €14,023 per QALY.ConclusionsDespite time investments, DIBH is cost-effective in the Belgian population. The growing adoption of DIBH may benefit long-term cardiovascular health in breast cancer survivors.

Project description:BackgroundMyocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment.MethodsForty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups.ResultsLV KEiEDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P < 0.05). In logistic-regression analysis, systolic KEiEDV (Beta = - 0.24, P < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE (r = 0.5, Beta = 1.1, P < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEiEDV were reduced (P < 0.05) and time difference to peak E-wave KE propagation during diastole increased (P < 0.05) when compared to controls with normal EF.ConclusionsReduction in LV systolic function results in reduction in systolic flow KEiEDV. Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEiEDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population.

Dataset Information

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

Background

Method

Results

Conclusion

Publications

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

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