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

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

doi:10.1016/j.jacc.2019.03.500

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

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

Research output: Contribution to journal › Article › peer-review

169 Scopus citations

Abstract

Background: Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints. Objectives: The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM). Methods: This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD). Results: After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028). Conclusions: Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.

Original language	English (US)
Pages (from-to)	2976-2987
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	73
Issue number	23
DOIs	https://doi.org/10.1016/j.jacc.2019.03.500
State	Published - Jun 18 2019
Externally published	Yes

Keywords

NSCLC
cardiac toxicity
cardiotoxicity
non–small cell lung cancer
radiotherapy

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2019.03.500

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Atkins, K. M., Rawal, B., Chaunzwa, T. L., Lamba, N., Bitterman, D. S., Williams, C. L., Kozono, D. E., Baldini, E. H., Chen, A. B., Nguyen, P. L., D'Amico, A. V., Nohria, A., Hoffmann, U., Aerts, H. J. W. L., & Mak, R. H. (2019). Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer. Journal of the American College of Cardiology, 73(23), 2976-2987. https://doi.org/10.1016/j.jacc.2019.03.500

Atkins, KM, Rawal, B, Chaunzwa, TL, Lamba, N, Bitterman, DS, Williams, CL, Kozono, DE, Baldini, EH, Chen, AB, Nguyen, PL, D'Amico, AV, Nohria, A, Hoffmann, U, Aerts, HJWL & Mak, RH 2019, 'Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer', Journal of the American College of Cardiology, vol. 73, no. 23, pp. 2976-2987. https://doi.org/10.1016/j.jacc.2019.03.500

@article{30e2cdffc4ae4225ba6ab22253eef4f9,

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

abstract = "Background: Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints. Objectives: The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM). Methods: This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD). Results: After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028). Conclusions: Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.",

keywords = "NSCLC, cardiac toxicity, cardiotoxicity, non–small cell lung cancer, radiotherapy",

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

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = jun,

day = "18",

doi = "10.1016/j.jacc.2019.03.500",

language = "English (US)",

volume = "73",

pages = "2976--2987",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "23",

}

TY - JOUR

T1 - Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer

AU - Atkins, Katelyn M.

AU - Rawal, Bhupendra

AU - Chaunzwa, Tafadzwa L.

AU - Lamba, Nayan

AU - Bitterman, Danielle S.

AU - Williams, Christopher L.

AU - Kozono, David E.

AU - Baldini, Elizabeth H.

AU - Chen, Aileen B.

AU - Nguyen, Paul L.

AU - D'Amico, Anthony V.

AU - Nohria, Anju

AU - Hoffmann, Udo

AU - Aerts, Hugo J.W.L.

AU - Mak, Raymond H.

PY - 2019/6/18

Y1 - 2019/6/18

N2 - Background: Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints. Objectives: The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM). Methods: This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD). Results: After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028). Conclusions: Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.

AB - Background: Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints. Objectives: The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM). Methods: This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD). Results: After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028). Conclusions: Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.

KW - NSCLC

KW - cardiac toxicity

KW - cardiotoxicity

KW - non–small cell lung cancer

KW - radiotherapy

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U2 - 10.1016/j.jacc.2019.03.500

DO - 10.1016/j.jacc.2019.03.500

M3 - Article

C2 - 31196455

AN - SCOPUS:85066407354

SN - 0735-1097

VL - 73

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EP - 2987

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 23

ER -

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

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ASJC Scopus subject areas

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