Influence of extracellular volume fraction on peak exercise oxygen pulse following thoracic radiotherapy

Canada, Justin M.; Weiss, Elisabeth; Grizzard, John D.; Trankle, Cory R.; Gharai, Leila Rezai; Dana, Franklin; Buckley, Leo F.; Carbone, Salvatore; Kadariya, Dinesh; Ricco, Anthony; Jordan, Jennifer H.; Evans, Ronald K.; Garten, Ryan S.; Tassell, Benjamín W. Van; Hundley, W. Gregory; Abbate, Antonio

doi:10.1186/s40959-021-00127-6

Cited by 4 publications

(4 citation statements)

References 48 publications

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“…Included works (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were published between 2013 [22,23] and 2022 [24,25], and all but 2 [26,27] had a prospective design. Six studies were conducted in the USA [22,25,[28][29][30][31], 4 in Canada [23,[32][33][34], 4 in Germany [27,[35][36][37], 2 in the Netherlands [24,38], 1 in the UK [26], 1 in Norway [39], and 1 in Japan [40].…”

Section: Data Extractionmentioning

confidence: 99%

“…Concerning cancer therapy, 13 study parts analyzed the cardiotoxic effects of anthracyclines [22, 23, 26, 27, 29-31, 33, 37, 39], and 3 study parts focused on the combination of anthracyclines and antibodies [32,34], 3 on the combination of chest radiotherapy and anthracyclines [25,28,35], and 3 on chest radiotherapy coupled to non-cardiotoxic regimens [24,38,40], while 1 study part focused solely on the effects of chest radiotherapy [35] and 1 on the effects of antibodies [36].…”

Section: Data Extractionmentioning

confidence: 99%

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MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

Folco,

Monti,

Zanardo

et al. 2023

Eur Radiol

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Objectives MRI-derived extracellular volume (ECV) allows characterization of myocardial changes before the onset of overt pathology, which may be caused by cancer therapy cardiotoxicity. Our purpose was to review studies exploring the role of MRI-derived ECV as an early cardiotoxicity biomarker to guide timely intervention. Materials and methods In April 2022, we performed a systematic search on EMBASE and PubMed for articles on MRI-derived ECV as a biomarker of cancer therapy cardiotoxicity. Two blinded researchers screened the retrieved articles, including those reporting ECV values at least 3 months from cardiotoxic treatment. Data extraction was performed for each article, including clinical and technical data, and ECV values. Pooled ECV was calculated using the random effects model and compared among different treatment regimens and among those who did or did not experience overt cardiac dysfunction. Meta-regression analyses were conducted to appraise which clinical or technical variables yielded a significant impact on ECV. Results Overall, 19 studies were included. Study populations ranged from 9 to 236 patients, for a total of 1123 individuals, with an average age ranging from 12.5 to 74 years. Most studies included patients with breast or esophageal cancer, treated with anthracyclines and chest radiotherapy. Pooled ECV was 28.44% (95% confidence interval, CI, 26.85−30.03%) among subjects who had undergone cardiotoxic cancer therapy, versus 25.23% (95%CI 23.31−27.14%) among those who had not (p = .003). Conclusion A higher ECV in patients who underwent cardiotoxic treatment could imply subclinical changes in the myocardium, present even before overt cardiac pathology is detectable. Clinical relevance statement The ability to detect subclinical changes in the myocardium displayed by ECV suggests its use as an early biomarker of cancer therapy–related cardiotoxicity. Key Points • Cardiotoxicity is a common adverse effect of cancer therapy; therefore, its prompt detection could improve patient outcomes. • Pooled MRI-derived myocardial extracellular volume was higher in patients who underwent cardiotoxic cancer therapy than in those who did not (28.44% versus 25.23%, p = .003). • MRI-derived myocardial extracellular volume represents a potential early biomarker of cancer therapy cardiotoxicity.

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Section: Data Extractionmentioning

confidence: 99%

Section: Data Extractionmentioning

confidence: 99%

MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

Folco,

Monti,

Zanardo

et al. 2023

Eur Radiol

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“…Similarly, global ECV (i.e., in the whole myocardium) of 27% was measured in the myocardium of 20 breast cancer patients after 8.3 years of anthracycline-based chemotherapy and 3DCRT [ 48 ]. Over shorter time-points, ECV stayed unchanged at 2 years post-RT for 30 patients with various chest malignancies [ 65 ] and among 66 breast cancer patients who underwent epirubicin-based chemotherapy followed by RT (28% vs 29%) or left-sided RT treatment only (30% vs 30%) at 13±2 months follow-up [ 55 ]. A 6-months follow-up of 11 patients with various chest tumors also did not show significant ECV changes between highly or minimally irradiated patients [ 54 ].…”

Section: Mri-based Metrics Evaluationmentioning

confidence: 99%

“…Global analysis of ECV [ 50 ] and short follow-up times (less than 2 years) [ 55 , 65 ] did not show any changes post-RT. However, segmental analysis (i.e., by the American Heart Association (AHA) model) of ECV at high-dose regions over short follow-up times (0.5 year) [ 57 ] and global analysis over longer follow-ups in concurrent treatments (greater than 67.6 months) [ 63 ] demonstrated an increase of ECV signal.…”

Section: Mri-based Metrics Evaluationmentioning

confidence: 99%

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

et al. 2023

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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 Twenty-one 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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Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer

Thomas,

Weiss,

Del Buono

et al. 2024

Cardio-Oncology

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Background Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy. Methods Ten patients (69 [61–76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured. Results The VO2peak was reduced at baseline (1.245 [0.882–1.605] L·min− 1; 70 [62–86] %-predicted) and significantly declined (1.095 [0.810–1.448] L·min− 1, P = 0.047; 62 [56–76] %-predicted, P = 0.005) at 6.0 [3.0–6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27–1.88] to 1.57 [1.12–1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56–65]% to 66 [57–68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7–41.6] vs. 12.8 [3.1–35.9]). The hsCRP increased significantly from 4.4 [1.4–5.8] to 6.1 [3.7–20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49–125] to 121 [88–191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8–25] to 15.5 [11.5–20]; P = 0.021) post-radiotherapy. Conclusions Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).

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Influence of extracellular volume fraction on peak exercise oxygen pulse following thoracic radiotherapy

Cited by 4 publications

References 48 publications

MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

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

Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer

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