Association of Sinoatrial Node Radiation Dose with Atrial Fibrillation and Mortality in Patients with Lung Cancer

Kyung Hwan Kim; Jaewon Oh; Gowoon Yang; Joongyo Lee; Jihun Kim; Seo Yeon Gwak; Iksung Cho; Seung Hyun Lee; Hwa Kyung Byun; Hyo Kyoung Choi; Jinsung Kim; Jee Suk Chang; Seok Min Kang; Hong In Yoon

doi:10.1001/jamaoncol.2022.4202

Association of Sinoatrial Node Radiation Dose with Atrial Fibrillation and Mortality in Patients with Lung Cancer

Kyung Hwan Kim, Jaewon Oh, Gowoon Yang, Joongyo Lee, Jihun Kim, Seo Yeon Gwak, Iksung Cho, Seung Hyun Lee, Hwa Kyung Byun, Hyo Kyoung Choi, Jinsung Kim, Jee Suk Chang, Seok Min Kang, Hong In Yoon

Department of Internal Medicine

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

4 Citations (Scopus)

Abstract

Importance: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. Objective: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. Design, Setting, and Participants: This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. Exposures: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. Main Outcomes and Measures: Main outcomes were AF and overall survival. Results: Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN D_max) exhibited the highest predictive value for prediction of AF. A higher SAN D_maxsignificantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P <.001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P =.008). However, SAN D_maxwas not associated with non-AF cardiac events. Increased SAN D_maxwas significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P <.001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P <.001). Conclusions and Relevance: In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.

Original language	English
Pages (from-to)	1624-1634
Number of pages	11
Journal	JAMA Oncology
Volume	8
Issue number	11
DOIs	https://doi.org/10.1001/jamaoncol.2022.4202
Publication status	Published - 2022 Nov 17

Bibliographical note

Funding Information:
Funding/Support: This work was supported by the Severance Hospital Research fund for Clinical excellence (SHRC) (grant number C-2020-0040) to Dr Yoon); National Research Foundation of Korea (NRF) (grant numbers NRF-2021R1I1A1A01060135 [to Dr Oh] and NRF-2019R1C1C1009359 [to Dr Chang]); and Korea Food Research Institute funded by the Ministry of Science, ICT & Future Planning (grant number E0210400-01 [to Dr Choi]).

Publisher Copyright:
© 2022 American Medical Association. All rights reserved.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1001/jamaoncol.2022.4202

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@article{bf7728c03e48452c85c92d4e6fc4ca4f,

title = "Association of Sinoatrial Node Radiation Dose with Atrial Fibrillation and Mortality in Patients with Lung Cancer",

abstract = "Importance: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. Objective: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. Design, Setting, and Participants: This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. Exposures: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. Main Outcomes and Measures: Main outcomes were AF and overall survival. Results: Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmaxsignificantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P <.001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P =.008). However, SAN Dmaxwas not associated with non-AF cardiac events. Increased SAN Dmaxwas significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P <.001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P <.001). Conclusions and Relevance: In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.",

author = "Kim, {Kyung Hwan} and Jaewon Oh and Gowoon Yang and Joongyo Lee and Jihun Kim and Gwak, {Seo Yeon} and Iksung Cho and Lee, {Seung Hyun} and Byun, {Hwa Kyung} and Choi, {Hyo Kyoung} and Jinsung Kim and Chang, {Jee Suk} and Kang, {Seok Min} and Yoon, {Hong In}",

note = "Funding Information: Funding/Support: This work was supported by the Severance Hospital Research fund for Clinical excellence (SHRC) (grant number C-2020-0040) to Dr Yoon); National Research Foundation of Korea (NRF) (grant numbers NRF-2021R1I1A1A01060135 [to Dr Oh] and NRF-2019R1C1C1009359 [to Dr Chang]); and Korea Food Research Institute funded by the Ministry of Science, ICT & Future Planning (grant number E0210400-01 [to Dr Choi]). Publisher Copyright: {\textcopyright} 2022 American Medical Association. All rights reserved.",

year = "2022",

month = nov,

day = "17",

doi = "10.1001/jamaoncol.2022.4202",

language = "English",

volume = "8",

pages = "1624--1634",

journal = "JAMA oncology",

issn = "2374-2437",

publisher = "American Medical Association",

number = "11",

}

TY - JOUR

T1 - Association of Sinoatrial Node Radiation Dose with Atrial Fibrillation and Mortality in Patients with Lung Cancer

AU - Kim, Kyung Hwan

AU - Oh, Jaewon

AU - Yang, Gowoon

AU - Lee, Joongyo

AU - Kim, Jihun

AU - Gwak, Seo Yeon

AU - Cho, Iksung

AU - Lee, Seung Hyun

AU - Byun, Hwa Kyung

AU - Choi, Hyo Kyoung

AU - Kim, Jinsung

AU - Chang, Jee Suk

AU - Kang, Seok Min

AU - Yoon, Hong In

N1 - Funding Information: Funding/Support: This work was supported by the Severance Hospital Research fund for Clinical excellence (SHRC) (grant number C-2020-0040) to Dr Yoon); National Research Foundation of Korea (NRF) (grant numbers NRF-2021R1I1A1A01060135 [to Dr Oh] and NRF-2019R1C1C1009359 [to Dr Chang]); and Korea Food Research Institute funded by the Ministry of Science, ICT & Future Planning (grant number E0210400-01 [to Dr Choi]). Publisher Copyright: © 2022 American Medical Association. All rights reserved.

PY - 2022/11/17

Y1 - 2022/11/17

N2 - Importance: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. Objective: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. Design, Setting, and Participants: This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. Exposures: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. Main Outcomes and Measures: Main outcomes were AF and overall survival. Results: Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmaxsignificantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P <.001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P =.008). However, SAN Dmaxwas not associated with non-AF cardiac events. Increased SAN Dmaxwas significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P <.001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P <.001). Conclusions and Relevance: In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.

AB - Importance: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. Objective: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. Design, Setting, and Participants: This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. Exposures: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. Main Outcomes and Measures: Main outcomes were AF and overall survival. Results: Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmaxsignificantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P <.001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P =.008). However, SAN Dmaxwas not associated with non-AF cardiac events. Increased SAN Dmaxwas significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P <.001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P <.001). Conclusions and Relevance: In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.

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Association of Sinoatrial Node Radiation Dose with Atrial Fibrillation and Mortality in Patients with Lung Cancer

Abstract

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UN SDGs

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