A study of relationship between cardiac exposure dose-volume and cardiovascular autonomic dysfunction in radiotherapy

Hongyu CHEN; Pengyu SU; Wenzi LUO; Dequan PANG; Feiran WANG

doi:10.19401/j.cnki.1007-3639.2024.11.006

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A study of relationship between cardiac exposure dose-volume and cardiovascular autonomic dysfunction in radiotherapy

Article | 更新时间：2025-12-31

- A study of relationship between cardiac exposure dose-volume and cardiovascular autonomic dysfunction in radiotherapy
- China Oncology Vol. 34, Issue 11, Pages: 1036-1044(2024)
- 作者机构：
  
  华北理工大学附属医院放疗科，河北唐山 063000
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.11.006
  CLC： R730.55
- Received：28 March 2024，
  
  Revised：2024-11-10，
  
  Published：30 November 2024
- 稿件说明：
移动端阅览
Hongyu CHEN, Pengyu SU, Wenzi LUO, et al. A study of relationship between cardiac exposure dose-volume and cardiovascular autonomic dysfunction in radiotherapy[J]. China Oncology, 2024, 34(11): 1036-1044.
DOI：

Hongyu CHEN, Pengyu SU, Wenzi LUO, et al. A study of relationship between cardiac exposure dose-volume and cardiovascular autonomic dysfunction in radiotherapy[J]. China Oncology, 2024, 34(11): 1036-1044. DOI： 10.19401/j.cnki.1007-3639.2024.11.006.

摘要

背景与目的：

晚期癌症患者心脏自主神经功能紊乱（autonomic dysfunction，AD）的发生率为65%~80%，AD导致的头晕、心悸及疲乏等神经衰弱症状，即使充分休息也难以缓解，严重影响患者的生存质量。同时，心血管自主神经系统对心率、心肌功能和心肌血流具有重要调节作用，AD会增加患者心血管疾病的发病率和死亡风险。AD不仅是一种功能状态，而且

可能是整体心肌病变的早期标志。研究显示，在调整年龄、性别和心血管危险因素后，先前的辐射暴露与静息心率增高及运动后心率恢复异常等AD表现相关，但是目前放疗对心脏自主神经功能影响的相关研究尚少，具体的损伤效应及损伤发生的剂量阈值尚不明确。本研究通过对比放疗前后的心率变异性（heart rate variability，HRV）分析参数差异，探讨胸部放疗对恶性肿瘤患者心脏自主神经功能的影响，通过对比病例组和对照组间的剂量学差异，探索发生AD的剂量学相关危险因素，为优化放疗方案的剂量分布提供理论依据，以期改善患者的预后和减少并发症的发生。

方法：

前瞻性收集2023年2月—2023年12月华北理工大学附属医院放疗科收治的行胸部放疗的恶性肿瘤患者。纳入标准：① 经病理学检查证实为恶性肿瘤（肺癌、乳腺癌或食管癌）患者；② 有放疗适应证；③ 美国东部肿瘤协作组（Eastern Cooperative Oncology Group，ECOG）评分0~1分；④ 心电图、心脏彩超等检查无明显异常；⑤ 患者知情同意并签署同意书。排除标准：① 曾接受过胸部放疗；② 治疗前自觉明显心悸、胸闷和胸痛的患者；③ 合并糖尿病、心脏病等严重基础疾病；④ 目前正在使用抗心律失常药物；⑤ 不能耐受放疗以及随访过程中失访或脱失者。采用HRV分析评估放疗后自主神经功能的变化情况，将出现AD的患者纳入病例组，其余患者纳入对照组，采用单因素和多因素logistic回归分析方法探索胸部放疗后发生AD的剂量学相关危险因素和心脏限量。本研究经华北理工大学附属医院伦理委员会批准（伦理编号：20230228020）。

结果：

本研究共收集到符合本研究条件的胸部肿瘤患者89例，其中有41例（46%）患者放疗后发生了心脏AD，病例组心脏最高受照剂量（

max

）（6 273.500 cGy

4 675.900 cGy，

0.001）、心脏平均受照剂量（

mean

）（1 513.700 cGy

452.050 cGy，

0.001）和心脏受到5 Gy以上剂量照射的体积占心脏总体积的百分比（

）（49.000%

21.250%，

0.001）、

（30.500%

7.300%，

0.001）、

（18.700%

3.600%，

0.001）、

（10.900%

1.500%，

0.001）明显高于对照组，多因素logistic回归分析结果显示，心脏

是心脏AD发生的独立危险因素[OR（95% CI）=1.583（1.093~2.291），

=0.015

]

，心脏

能预测放射性心脏损伤的发生，曲线下面积为0.788，且17.1%是心脏

预测心脏AD发生的最佳截断值。

结论：

胸部放疗后，心脏AD患者的心脏照射剂量体积明显高于对照组患者，当心脏

高于17.1%时，患者发生心脏AD的风险明显升高。

Abstract

Background and purpose:

The incidence of autonomic dysfunction (AD) in patients with advanced cancer is approximately 65%-80%. The neurasthenic symptoms such as dizziness

palpitations and fatigue caused by AD are difficult to alleviate even with sufficient rest

seriously affecting the patients’ quality of life. Meanwhile

the cardiovascular autonomic nervous system plays a significant regulatory role in heart rate

myocardial function and myocardial blood flow. AD increases the morbidity and mortality risk of cardiovascular diseases in patients. AD is not only a functional state but might also be an early sign of overall myocardial lesion. Research indicates that after adjusting for age

gender and cardiovascular risk factors

previous radiation exposure is associated with AD manifestations such as increased resting heart rate and abnormal heart rate recovery after exercise. However

there are currently few relevant studies on the effect of radiotherapy on cardiac autonomic function

and the specific injury effects and dose threshold of injury occurrence remain unclear. This study aimed to explore the impact of thoracic radiotherapy on the cardiac autonomic function of patients with malignant tumors by comparing the differences in heart rate variability (HRV) analysis parameters before and after radiotherapy

and to explore the dosimetric risk factors for the occurrence of AD by comparing the dosimetry between the case group and the control group

providing a theoretical basis for optimizing the dose distribution of radiotherapy regimens in order to improve patient prognosis and reduce the occurrence of complications.

Methods:

We prospectively collected data of patients with malignant tumors who underwent thoracic radiotherapy in the Radiotherapy Department of the Affiliated Hospital of North China University of Science and Technology from February 2023 to December 2023. Inclusion criteria: ① Patients who were pathologically confirmed to have malignant tumors (lung cancer breast cancer or esophageal cancer); ② patients with radiation therapy indications as recommended by the guidelines; ③ patients with an ECOG score of 0-1; ④ patients with no significant abnormalitie

s in electrocardiogram and echocardiography results. Exclusion criteria: ① previously received chest radiotherapy; ② patients with obvious palpitation

chest tightness and chest pain before treatment; ③ diabetes

heart disease and other serious underlying diseases; ④ anti-arrhythmic drugs are currently being used; ⑤ patients who cannot tolerate radiotherapy and who were lost or lost during follow-up. HRV analysis was used to evaluate changes in autonomic nerve function after radiotherapy. Patients with AD were included in the case group

and the remaining patients were included in the control group. Univariate and multivariate logistic regression analysis methods were used to explore the dosimetric risk factors and cardiac dose limitations for the occurrence of AD after thoracic radiotherapy. This study was approved by the ethics committee of Affiliated Hospital of North China University of Science and Technology (ethics number: 20230228020).

Results:

A total of 89 patients with thoracic tumors meeting the study criteria were enrolled in the study. Among them

41 (46%) patients experienced cardiac AD after radiotherapy. The cardiac

max

(6 273.500 cGy

4 675.900 cGy

0.001)

cardiac

mean

(1513.700 cGy

452.050 cGy

0.001)

cardiac

(49.000%

21.250%

0.001)

(30.500%

7.300%

0.001)

(18.700%

3.600%

0.001) and

(10.900%

1.500%

0.001) were significantly higher in the case group than in the control group. The results of multivariate logistic regression analysis showed that cardiac

was an independent risk factor for the occurrence of cardiac AD[OR

(95% CI)=1.583 (1.093-2.291)

=0.015

]

. Cardiac

could predict the occurrence of radiation-induced cardiac injury with an area under the curve of 0.788

and 17.1% was the optimal cut-off value of cardiac

for predicting the occurrence of cardiac AD.

Conclusion:

After thoracic radiotherapy

the cardiac irradiation dose-volume was significantly higher in patients with cardiac AD than in the control group. When cardiac

was higher than 17.1%

the risk of cardiac AD in patients significantly increased.

关键词

Keywords

references

DELANEY G , JACOB S , FEATHERSTONE C , et al. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines [J ] . Cancer , 2005 , 104 ( 6 ): 1129 - 1137 . DOI: 10.1002/cncr.21324 http://doi.org/10.1002/cncr.21324

NESS K K , ARMSTRONG G T . Screening for cardiac autonomic dysfunction among Hodgkin lymphoma survivors treated with thoracic radiation [J ] . J Am Coll Cardiol , 2015 , 65 ( 6 ): 584 - 585 . DOI: 10.1016/j.jacc.2014.11.036 http://doi.org/10.1016/j.jacc.2014.11.036

SOUZA H C D , PHILBOIS S V , VEIGA A C , et al. Heart rate variability and cardiovascular fitness: What we know so far [J ] . Vasc Health Risk Manag , 2021 , 17 : 701 - 711 . DOI: 10.2147/VHRM.S279322 http://doi.org/10.2147/VHRM.S279322

Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology [J ] . Circulation , 1996 , 93 ( 5 ): 1043 - 1065 .

葛均波 . 内科学(第9版) [M ] . 北京 : 人民卫生出版社 , 2018 : 331 - 332 .

GE J B . Internal Medicine (9th edition) [M ] . Beijing : People’s Medical Publishing House , 2018 : 331 - 332 .

KHANDELWAL E , TRIPATHI S , GUPTA A , et al. Profile of cardiovascular autonomic dysfunctions in breast cancer patients [J ] . Cureus , 2023 , 15 ( 10 ): e46773 .

BEDI R , AHMAD A , HORBAL P , et al. Radiation-associated arrhythmias: putative pathophysiological mechanisms, prevalence, screening and management strategies [J ] . Arrhythm Electrophysiol Rev , 2023 , 12 : e24 . DOI: 10.15420/aer.2022.44 http://doi.org/10.15420/aer.2022.44

GROARKE J D , TANGUTURI V K , HAINER J , et al. Abnormal exercise response in long-term survivors of Hodgkin lymphoma treated with thoracic irradiation: evidence of cardiac autonomic dysfunction and impact on outcomes [J ] . J Am Coll Cardiol , 2015 , 65 ( 6 ): 573 - 583 .

TENG A E , NOOR B , AJIJOLA O A , et al. Chemotherapy and radiation-associated cardiac autonomic dysfunction [J ] . Curr Oncol Rep , 2021 , 23 ( 2 ): 14 . DOI: 10.1007/s11912-020-01013-7 http://doi.org/10.1007/s11912-020-01013-7

郝丽荣 , 张剑白 , 解汝娟 , 等 . 心率变异性分析的检测指标及方法 [J ] . 中国地方病学杂志 , 1994 , 13 ( 2 ): 96 - 98 .

HAO L R , ZHANG J B , XIE R J , et al. Detection indicators and methods for heart rate variability analysis [J ] . Chin J Endemiol , 1994 , 13 ( 2 ): 96 - 98 .

张凤琴 , 梁保辉 , 蔡汉飞 , 等 . 胸部放疗的辐射剂量与心率变异性的相关性 [J ] . 继续医学教育 , 2021 , 35 ( 11 ): 121 - 123 .

ZHANG F Q , LIANG B H , CAI H F , et al. Correlation between radiation dose and heart rate variability in chest radiotherapy [J ] . Continuing Med Educ , 2021 , 35 ( 11 ): 121 - 123 .

GROARKE J D , MAHMOOD S S , PAYNE D , et al. Case-control study of heart rate abnormalities across the breast cancer survivorship continuum [J ] . Cancer Med , 2019 , 8 ( 1 ): 447 - 454 .

HOCA A , YILDIZ M , OZYIGIT G . Evaluation of the effects of mediastinal radiation therapy on autonomic nervous system [J ] . Med Oncol , 2012 , 29 ( 5 ): 3581 - 3586 . DOI: 10.1007/s12032-012-0237-5 http://doi.org/10.1007/s12032-012-0237-5

WU S , GUAN W Z , ZHAO H , et al. Assessment of short-term effects of thoracic radiotherapy on the cardiovascular parasympathetic and sympathetic nervous systems [J ] . Front Neurosci , 2023 , 17 : 1256067 .

HÉLISSEN O , KERMORGANT M , DÉJEAN S , et al. Autonomic nervous system adaptation and circadian rhythm disturbances of the cardiovascular system in a ground-based murine model of spaceflight [J ] . Life , 2023 , 13 ( 3 ): 844 .

MONTANO N , PORTA A , COGLIATI C , et al. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior [J ] . Neurosci Biobehav Rev , 2009 , 33 ( 2 ): 71 - 80 . DOI: 10.1016/j.neubiorev.2008.07.006 http://doi.org/10.1016/j.neubiorev.2008.07.006

THOMAS B L , CLAASSEN N , BECKER P , et al. Validity of commonly used heart rate variability markers of autonomic nervous system function [J ] . Neuropsychobiology , 2019 , 78 ( 1 ): 14 - 26 . DOI: 10.1159/000495519 http://doi.org/10.1159/000495519

BILLMAN G E . Heart rate variability-a historical perspective [J ] . Front Physiol , 2011 , 2 : 86 .

BILLMAN G E . The LF/HF ratio does not accurately measure cardiac sympatho-vagal balance [J ] . Front Physiol , 2013 , 4 : 26 . DOI: 10.3389/fphys.2013.00026 http://doi.org/10.3389/fphys.2013.00026

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