Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer

Atkins, Katelyn M.; Rawal, Bhupendra; Chaunzwa, Tafadzwa L.; Lamba, Nayan; Bitterman, Danielle S.; Williams, Christopher; Kozono, David; Baldini, Elizabeth H.; Chen, Aileen B.; Nguyen, Paul L.; D’Amico, Anthony V.; Nohria, Anju; Hoffmann, Udo; Aerts, Hugo J.W.L.; Mak, Raymond H.

doi:10.1016/j.jacc.2019.03.500

Cited by 189 publications

(196 citation statements)

References 33 publications

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“…Contemporary and more sophisticated administration of thoracic radiotherapy and systemic immunotherapy have been effective in reducing cancer-related mortality and limiting exposure to the heart. However, radiotherapy to the chest increases the risk for cancer-unrelated morbidity and mortality, especially cardiovascular mortality, in a dose-dependent manner [1,[5][6][7][8]. Furthermore, recent studies have shown that major adverse cardiovascular events, like acute myocardial infarction and stroke, are likely occurring earlier post-treatment than previously thought [1,5].…”

Section: Introductionmentioning

confidence: 99%

“…Radiotherapy remains a cornerstone of treatment for many cancers. Lung, esophageal, breast, and proximal gastric cancers still receive incidental radiation to the heart as part of curative intent or palliative care [1][2][3][4]. Contemporary and more sophisticated administration of thoracic radiotherapy and systemic immunotherapy have been effective in reducing cancer-related mortality and limiting exposure to the heart.…”

Section: Introductionmentioning

confidence: 99%

“…However, radiotherapy to the chest increases the risk for cancer-unrelated morbidity and mortality, especially cardiovascular mortality, in a dose-dependent manner [1,[5][6][7][8]. Furthermore, recent studies have shown that major adverse cardiovascular events, like acute myocardial infarction and stroke, are likely occurring earlier post-treatment than previously thought [1,5]. In a well-characterized cohort of 945 women with breast cancer who had received a mean radiation dose to the heart of 2.5 Gray (Gy), Saiki et al showed that 60 patients (6%) developed new-onset heart failure (HF) 5.8 ± 3.4 years following radiotherapy [9].…”

Section: Introductionmentioning

confidence: 99%

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Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

et al. 2020

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Background: Irradiation of the heart during cancer radiotherapy is associated with a dose-dependent risk of heart failure. Animal studies have demonstrated that irradiation leads to an inflammatory response within the heart as well as a reduction in cardiac reserve. In the current study we aimed to evaluate whether inflammatory biomarkers correlated with changes in cardiac function and reserve after radiotherapy for breast or lung cancer. Methods and results: We studied 25 subjects with a history of breast or lung cancer without a prior diagnosis of cardiovascular disease or heart failure, 1.8 years [0.4-3.6] post-radiotherapy involving at least 5 Gray (Gy) to at least 10% of the heart. High-sensitivity C-reactive protein (CRP) was abnormal (≥2 mg/L) in 16 (64%) subjects. Cardiac function and reserve was measured with Doppler echocardiography before and after exercise and defined as leftventricular ejection fraction (LVEF), early diastolic mitral annulus velocity (e'), and increase in LV outflow tract velocity time integral cardiac output (cardiac reserve) with exercise. Subjects with abnormal CRP had significantly lower LVEF (51 [44-59] % vs 61 [52-64] %, P = 0.039), lower e' (7.4 [6.6-7.9] cm/sec vs 9.9 [8.3-12.0] cm/sec, P = 0.010), and smaller cardiac reserve (+ 1.5 [1.2-1.7] L/min vs + 1.9 [1.7-2.2] L/min, P = 0.024). Conclusion: Elevated systemic inflammation is associated with impaired left-ventricular systolic and diastolic function both at rest and during exercise in subjects who have received radiotherapy with significant incidental heart dose for the treatment of cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

et al. 2020

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“…[10,11] Delivering radiation dose to the heart can increase the risk for a late competing toxicity precipitating non-cancer morbidity and mortality. [12] More recently, cardiac radiation dose has been shown in numerous series to be associated with lower overall survival and early cardiac event rates. [13][14][15][16] In spite of decades of research, fundamental questions about the etiology of radiation-induced heart disease (RIHD) remain.…”

Section: Introductionmentioning

confidence: 99%

Cardiac MRI utilizing late gadolinium enhancement (LGE) and T1 mapping in the detection of radiation induced heart disease

Ricco

Slade

Canada

et al. 2020

Preprint

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Abstract Background and Purpose: Radiotherapy has been associated with late dose-dependent cardiovascular toxicity. In this cross-sectional pilot study, radiation dose distributions were correlated with areas of localized and diffuse myocardial fibrosis as measured by novel cardiac MRI (CMR) sequences including late gadolinium enhancement (LGE) and T1 mapping with the goal to identify early markers of myocardial damage.Materials and Methods: Twenty-eight patients with chest tumors including lung, breast, esophagus, and lymphoma underwent CMR per study protocol on average 46.4 months (range 1.7-344.5) after radiotherapy. Patients without pretreatment cardiac history were included if the volume of heart receiving 5 Gy or more was at least 10% (V5Gy≥10%). The association of LGE with cardiac dosimetric factors, clinical factors (e.g., tumor type, smoking history, BMI), , and T1 values was analyzed. Results: Cardiac maximum (Dmax) and mean dose (Dmean) equivalent to doses delivered in 2 Gy fractions (EQD2) were on average 50.9 Gy (range 6.2-108.0) and 8.2 Gy (range 1.0-35.7), respectively, compared to 60.8 Gy (40.8-108.0) and 6.8 Gy (1.8-21.8) among the 9 patients with LGE. Doses were not different between patients with and without LGE (p=0.16 and 0.56, respectively). The average T1 value of the left ventricle myocardium was 1009 ms (range 933-1117). No significant correlation was seen for heart Dmax and Dmean and T1 values (p=0.14 and 0.58, respectively). In addition, no significant association between clinical factors and the development of LGE was identified.Conclusions: No relation between cardiac doses, the presence of LGE or T1 values was observed. Further study is needed to determine the benefit of CMR for detecting radiotherapy-related myocardial fibrosis.

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“…Importantly, recent studies have shown that short-term cardiac events in NSCLC are common. [12][13][14][15] Within 24 months after treatment, the reported incidence of serious cardiac adverse events was 11%-23% in a pooled analysis of prospective dose-escalated radiotherapy trials, where the given radiation dose was higher compared with standard care to improve treatment tolerability or maximise treatment effects. [12][13][14] This high incidence of cardiac events was confirmed in a cohort of stage II and III NSCLC (n=748) treated in daily clinical practice showing a cumulative incidence of cardiac events of 23%.…”

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Are patients with stage III non-small cell lung cancer treated with chemoradiotherapy at risk for cardiac events? Results from a retrospective cohort study

et al. 2020

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ObjectivesDyspnoea is one of the symptoms frequently encountered after treatment with chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC). Long-term data on mild to moderately severe cardiac events as underlying cause of dyspnoea in patients with stage III NSCLC are lacking. Therefore, the incidence of new cardiac events, with a common terminology criteria for adverse events (CTCAE) score of ≥2 within 5 years after diagnosis, were analysed.DesignRetrospective multicentre cohort study of patients with stage III NSCLC treated with CRT from 2006 to 2013. The medical files of the treated patients were reviewed.Outcome measuresThe primary endpoint of the study was the incidence of new cardiac events with a CTCAE score of ≥2 within 5 years after diagnosis. Secondary endpoint was to identify risk factors associated with the development of a cardiac event.ResultsFour hundred and sixty patients were included in the study. Of all patients, 150 (32.6%) developed a new cardiac event. In patients with a known cardiac history (n=138), 44.2% developed an event. The most common cardiac events were arrhythmia (14.6%), heart failure (7.6%) and symptomatic coronary artery disease (6.8%). Pre-existent cardiac comorbidity (HR 1.96; p<0.01) and WHO-performance score ≥2 (HR 2.71; p<0.01) were significantly associated with developing a cardiac event. The majority of patients did not have pre-existent cardiac comorbidity (n=322). Elevated WHO/International Society of Hypertension score was not identified as a significant predictor for cardiac events.ConclusionOne-third of patients with stage III NSCLC treated in daily clinical practice develop a new cardiac event within 5 years after CRT. All physicians confronted with patients with NSCLC should take cardiac comorbidity as a serious possible explanation for dyspnoea after treatment with CRT.

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Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer

Cited by 189 publications

References 33 publications

Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

Cardiac MRI utilizing late gadolinium enhancement (LGE) and T1 mapping in the detection of radiation induced heart disease

Are patients with stage III non-small cell lung cancer treated with chemoradiotherapy at risk for cardiac events? Results from a retrospective cohort study

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