Cardiac Magnetic Resonance Imaging and Blood Biomarkers for Evaluation of Radiation-Induced Cardiotoxicity in Patients With Breast Cancer: Results of a Phase 2 Clinical Trial

Speers, Corey; Murthy, Venkatesh L.; Walker, Eleanor M.; Glide-Hurst, Carri K; Marsh, Richard L.; Tang, Ming; Morris, Emily; Schipper, Matthew J.; Weinberg, Richard L.; Gits, Hunter C.; Hayman, James A.; Feng, Mary; Balter, James M.; Moran, Jean M.; Jagsi, Reshma; Pierce, Lori J.

doi:10.1016/j.ijrobp.2021.08.039

Cited by 15 publications

(24 citation statements)

References 48 publications

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“…Similar ndings were noted for 5 HL survivors who underwent chemotherapy and proton RT with LVEF of 60% at 5 years post treatment [49]. Over shorter follow-ups, LVEF did not change at 3 months post-RT in 51 breast cancer patients who were exposed to a low dose of radiation to the heart (2 Gy) [44], at 2-or 6-months in 21 lung cancer patients following 3DCRT (69-70%) [50], at 6 months in 11 chest tumor patients who underwent chemoradiotherapy [51], at either therapy completion or 13 months post-therapy in 66 breast cancer patients who were treated by chemoradiotherapy (60%) or only RT (62-64%) [52], and nally at 6-or 18months in 19 and 24 survivors of esophageal cancer, respectively, who received chemoradiotherapy (60-65%) [53], [54]. Additionally, no change in LVEF was noted for 81 pediatric cancer patients with different malignancies who were treated by chemotherapy with/without irradiation at 1-year and 2-year follow up (range: 60-62%) [55].…”

Section: Iia2 Lvef Unchangedsupporting

confidence: 68%

“…At 24 years follow up of 80 HL and NHL survivors who were treated with mediastinal RT with/without chemotherapy, T2 values did not differ from healthy controls (both 50 ms, p=0.13) [47]. In shorter follow-ups, T2 signal in 51 breast cancer patients did not change at therapy completion or 3 months post-RT [44]. Similar ndings were noted in highly or minimally irradiated patients with chest tumors at 6 months post chemoradiotherapy [51].…”

Section: Iic21 T2 Unchangedsupporting

confidence: 55%

“…Finally, in 49 left-sided breast cancer patients who were treated by intensitymodulated radiation therapy (IMRT), 3DCRT, with/without chemotherapy, LVEF was measured over a 24month follow-up. No signi cant reduction of LVEF was noted at 6 months in the whole cohort ( Recent RT-induced MCT studies showed no signi cant changes of LVEF and/or relations between LVEF and dose mostly due to short follow-ups [51], [52], low dose of radiation to the heart [44], small sample size [49], and uncertainty in the exact cumulative dose for longer follow-up studies. However, studies with longer follow-up (20 years and more) showed a decrease in LVEF [46], [47].…”

Section: Iia2 Lvef Unchangedmentioning

confidence: 92%

“…Bene ts of this metric and de ned cutoffs for cardiotoxicity are that LVEF is a widely accepted and clinically utilized metric of cardiac function assessable by multiple imaging modalities (though these modalities may result in slightly different values for the same person [43]). A primary drawback is that declines in LVEF may not be observed in early MCT [44], [45] since global cardiac function may be able to compensate for mild early or focal cardiac damage. Thus, reliance on LVEF alone may delay the diagnosis and early treatment of MCT.…”

Section: Iia Left Ventricular Ejection Fraction (Lvef)mentioning

confidence: 99%

“…Even with concurrent treatments, the changes were resolved in a few months. These ndings can demonstrate the low likelihood of myocardial edema development following RT [44], [47], [52]. Regional analysis of T2 mapping in longitudinal studies of patients with higher dose to the heart over both short and long-term follow ups are required for further evaluation.…”

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confidence: 96%

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Quantitative assessment of radiotherapy-induced myocardial damage using MRI: A systematic review

Omidi

Weiss

Trankle

et al. 2022

Preprint

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Purpose: To determine the role of magnetic resonance imaging (MRI)-based metrics to quantify myocardial toxicity following radiotherapy (RT) in human subjects through review of current literature. Methods: 21 MRI studies published between 2011-2022 were identified from available databases. Patients received chest irradiation with/without other treatments for various malignancies including breast, lung, esophageal cancer, Hodgkin’s, and non-Hodgkin’s lymphoma. In 11 longitudinal studies, the sample size, mean heart dose, and follow-up times ranged from 10-81 patients, 2.0-13.9 Gy, and 0-24 months after RT (in addition to a pre-RT assessment), respectively. In 10 cross-sectional studies, the sample size, mean heart dose, and follow-up times ranged from 5-80 patients, 2.1-22.9 Gy, and 2-24 years from RT completion, respectively. Global metrics of left ventricle ejection fraction (LVEF) and mass/dimensions of cardiac chambers were recorded, along with global/regional values of T1/T2 signal, extracellular volume (ECV), late gadolinium enhancement (LGE), and circumferential/radial/longitudinal strain. Results: LVEF tended to decline at >20 years follow-up and in patients treated with older RT techniques. Changes in global strain were observed after shorter follow-up (13±2 months) for concurrent chemoradiotherapy. In concurrent treatments with longer follow-up (8.3 years), increases in left ventricle (LV) mass index were correlated with LV mean dose. In pediatric patients, increases in LV diastolic volume were correlated with heart/LV dose at 2 years post-RT. Regional changes were observed earlier post-RT. Dose-dependent responses were reported for several parameters, including: increased T1 signal in high-dose regions, a 0.136% increase of ECV per Gy, progressive increase of LGE with increasing dose at regions receiving >30 Gy, and correlation between increases in LV scarring volume and LV mean/V10/V25 Gy dose. Conclusion: Global metrics only detected changes over longer follow-up, in older RT techniques, in concurrent treatments, and in pediatric patients. In contrast, regional measurements detected myocardial damage at shorter follow-up and in RT treatments without concurrent treatment and had greater potential for dose-dependent response. The early detection of regional changes suggests the importance of regional quantification of RT-induced myocardial toxicity at early stages, before damage becomes irreversible. Further works with homogeneous cohorts are required to examine this matter.

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Section: Iia2 Lvef Unchangedsupporting

confidence: 68%

Section: Iic21 T2 Unchangedsupporting

confidence: 55%

Section: Iia2 Lvef Unchangedmentioning

confidence: 92%

Section: Iia Left Ventricular Ejection Fraction (Lvef)mentioning

confidence: 99%

mentioning

confidence: 96%

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Quantitative assessment of radiotherapy-induced myocardial damage using MRI: A systematic review

Omidi

Weiss

Trankle

et al. 2022

Preprint

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Quantitative assessment of intra‐ and inter‐modality deformable image registration of the heart, left ventricle, and thoracic aorta on longitudinal 4D‐CT and MR images

Omidi

Weiss

Wilson

et al. 2021

J Applied Clin Med Phys

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Purpose Magnetic resonance imaging (MRI)‐based investigations into radiotherapy (RT)‐induced cardiotoxicity require reliable registrations of magnetic resonance (MR) imaging to planning computed tomography (CT) for correlation to regional dose. In this study, the accuracy of intra‐ and inter‐modality deformable image registration (DIR) of longitudinal four‐dimensional CT (4D‐CT) and MR images were evaluated for heart, left ventricle (LV), and thoracic aorta (TA). Methods and materials Non‐cardiac‐gated 4D‐CT and T1 volumetric interpolated breath‐hold examination (T1‐VIBE) MRI datasets from five lung cancer patients were obtained at two breathing phases (inspiration/expiration) and two time points (before treatment and 5 weeks after initiating RT). Heart, LV, and TA were manually contoured. Each organ underwent three intramodal DIRs ((A) CT modality over time, (B) MR modality over time, and (C) MR contrast effect at the same time) and two intermodal DIRs ((D) CT/MR multimodality at same time and (E) CT/MR multimodality over time). Hausdorff distance (HD), mean distance to agreement (MDA), and Dice were evaluated and assessed for compliance with American Association of Physicists in Medicine (AAPM) Task Group (TG)‐132 recommendations. Results Mean values of HD, MDA, and Dice under all registration scenarios for each region of interest ranged between 8.7 and 16.8 mm, 1.0 and 2.6 mm, and 0.85 and 0.95, respectively, and were within the TG‐132 recommended range (MDA < 3 mm, Dice > 0.8). Intramodal DIR showed slightly better results compared to intermodal DIR. Heart and TA demonstrated higher registration accuracy compared to LV for all scenarios except for HD and Dice values in Group A. Significant differences for each metric and tissue of interest were noted between Groups B and D and between Groups B and E. MDA and Dice significantly differed between LV and heart in all registrations except for MDA in Group E. Conclusions DIR of the heart, LV, and TA between non‐cardiac‐gated longitudinal 4D‐CT and MRI across two modalities, breathing phases, and pre/post‐contrast is acceptably accurate per AAPM TG‐132 guidelines. This study paves the way for future evaluation of RT‐induced cardiotoxicity and its related factors using multimodality DIR.

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The right heart in patients with cancer. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio‐Oncology

Keramida,

Farmakis,

Rakisheva

et al. 2024

European J of Heart Fail

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Right ventricular dysfunction induced by radiation therapyThe effects of RT on the RH chambers have been insufficiently investigated. 3,44,45 It is well known that the anatomical position © 2024 European Society of Cardiology. 142 (100-184) 136 (94-178) 130 (87-172) ESV (ml) 68 (38-98) 64 (34-94) 59 (29-89) 55 (29-82) 51 (25,77) 46 (20-72) SV (ml) 108 (74-143) 108 (74-142) 107 (73-141) 8 7( 6 1-112) 85 (59-111) 8 4( 5 8-109) EF (%) 61 (48-74) 63 (50-76) 65 (52-77) 61 (49-73) 63 (51-75) 65 (53-77) Mass (g) 70 (42-99) 69 (40-97) 67 (39-95) 54 (33-74) 51 (31-72) 49 (28-70) Indexed to BSA EDV/BSA (ml/m 2 ) 91 (68-114) 88 (65-111) 8 5( 6 2 -108) 84 (65-102) 80 (61-98) 76 (57-94) ESV/BSA (ml/m 2 ) 3 5( 2 1-50) 33 (18-47) 30 (16-45) 32 (20-45) 30 (17-43) 27 (14-40) SV/BSA (ml/m 2 ) 56 (40-72) 55 (39-71) 5 5( 3 9 -7 1) 5 1 (39-63) 50 (38-62) 49 (37-61) Mass/BSA (g/m 2 ) 36 (23-50) 35 (22-49) 34 (21-48) 32 (22-42) 30 (20-40) 29 (19-39)

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Cardiac Magnetic Resonance Imaging and Blood Biomarkers for Evaluation of Radiation-Induced Cardiotoxicity in Patients With Breast Cancer: Results of a Phase 2 Clinical Trial

Cited by 15 publications

References 48 publications

Quantitative assessment of radiotherapy-induced myocardial damage using MRI: A systematic review

Quantitative assessment of radiotherapy-induced myocardial damage using MRI: A systematic review

Quantitative assessment of intra‐ and inter‐modality deformable image registration of the heart, left ventricle, and thoracic aorta on longitudinal 4D‐CT and MR images

The right heart in patients with cancer. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio‐Oncology

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