Cardiovascular disease-specific mortality in 270,618 patients with non-small cell lung cancer

https://doi.org/10.1016/j.ijcard.2021.02.025Get rights and content

Highlights

  • Investigate the trend of CVD-specific mortality in patients with NSCLC.

  • Evaluate prognostic factors for CVD-specific death in stage I, II, and III patients.

  • Highlight the importance of cardio-oncology.

Abstract

Background

This study aimed to investigate the trend of cardiovascular disease (CVD)-specific mortality in patients with non-small cell lung cancer (NSCLC) and identify prognostic factors for CVD-specific death in stage NSCLC patients.

Methods

In this study, 270,618 NSCLC patients were collected from the Surveillance, Epidemiology, and End Results database. CVD- and NSCLC-specific cumulative mortality and proportion of death were calculated and graphically displayed to describe the probability of specific endpoints. Prognostic factors for CVD-specific mortality were evaluated by cause-specific hazard ratios (HR) with 95% confidence intervals (CI) using the competing risk model with non-cardiovascular death as competing risks.

Results

Among all competing causes of death, lung cancer resulted in the highest cumulative mortality, followed by CVDs and other causes. In the proportion of cause-specific death, heart diseases accounted for approximately 5.3% of the total death, only secondary to primary cancer. In all three stages, higher age, squamous cell carcinoma, and no-or-unknown chemotherapy and/or radiotherapy were associated with a higher risk of CVD-specific death, while surgery treatment seemed to be a protective factor. Female gender was statistically related to CVD-specific death in stage I and III patients with HRs of 0.84 (0.78–0.91) and 0.84 (0.77–0.93), respectively. Interestingly, right-sided laterality was correlated with lower CVD-specific mortality with HR of 0.82 (0.74–0.90) in stage III.

Conclusions

This study illustrated the historical trend of CVD-specific death in NSCLC patients and assesses potential prognostic risk factors, highlighting the involvement of cardio-oncology teams in cancer treatment to provide optimal comprehensive care and long-term surveillance for cancer patients.

Introduction

Lung cancer is a major cause of cancer-related death, which poses a substantial financial and health burden worldwide [1]. Owing to the advances in cancer screening, diagnosis and treatment, the life expectancy of patients with non-small cell lung cancer (NSCLC) has been appreciably extended in the last three decades [2,3]. Accordingly, it has become increasingly significant to provide long-term care to improve the quality of life, considering the growing population of lung cancer survivors [[4], [5], [6]].

Several studies on the causes of death among patients with NSCLC have revealed that cardiovascular diseases (CVDs) present a formidable health problem and are important elements entailing death among lung cancer patients [4,5]. Moreover, previous studies have demonstrated the close association between cancer treatment (radiotherapy and chemotherapy) and increased cardiovascular risk in NSCLC patients [7,8]. However, it remains unknown what prognostic factors can be used to predict CVD-specific mortality in NSCLC patients, and adequate practice guidelines are lacking [4].

The Surveillance, Epidemiology, and End Results (SEER) database, covering data from 18 regional US cancer registries, has been substantially used to assess risk factors predicting cancer prognosis and CVD-specific mortality in breast cancer [9], colorectal cancer [10], esophageal cancer [11], as well as lung cancer [12].

The purpose of this study was to investigate the historical trend of CVD-specific mortality in patients with NSCLC and evaluate prognostic factors for CVD-specific death in NSCLC patients.

Section snippets

Data sources

The SEER database is a population-based cancer registry network, covering approximately 28% of the US population [13]. Demographic, tumor incidence, survival status, and treatment strategies (e.g., radiation therapy, surgery, chemotherapy) of cancer patients were collected. To perform the registry-based retrospective cohort study, the SEER database (SEER 18 Regs Custom Data with additional treatment fields, Nov 2018 Sub) was queried by SEER*Stat software (version 8.3.6). Institutional Ethics

Clinical characteristics

From the 635,981 lung cancer patients registered in the SEER program, 365,363 cases were excluded due to unknown grade, clinical stage, surgery status, laterality, or radiation sequence. Finally, a total of 270,618 NSCLC patients were eligible for this study (Fig. 1), with a median follow-up time of 14 months (IQR, 4–44 months). The baseline clinical characteristics are presented in Table 1. Among these patients, cases in stage I, stage II, stage III, and stage IV were 89,013, 19,187, 73,666,

Discussion

In this registry-based cohort study, we described the historical trend of CVD-specific mortality in patients with NSCLC and identified prognostic factors for CVD-specific death in stage I-III patients. Our results corroborated that CVD-specific death remains a challenge in NSCLC patients. Moreover, the competing risk model identified several risk factors for CVD-specific death, including age, gender, ethnicity, laterality, primary site, histology type, chemotherapy and/or radiotherapy, surgery,

Study limitations

Despite the novel insights into CVD-specific mortality of NSCLC patients, several limitations should be highlighted. First, the SEER database does not provide information on pre-existing comorbidities, margin status, surgical pathology, systemic therapy, cardiac radiation dose, smoking status, or many other vital parameters, which holds considerable importance for the prognosis of cancer patients. Second, patients with CVDs were naturally associated with a higher risk of CVD-specific death and

Conclusion

In conclusion, this study illustrates the historical trend of CVD-specific mortality in NSCLC patients and identifies potential prognostic factors for CVD-specific death. Further studies are strongly desirable and required to validate these results, and more detailed clinical data should be examined as potential prognostic risk factors. This study highlights the importance of cardio-oncology teams in providing optimal comprehensive care and long-term surveillance for cancer patients, especially

Funding

This study was supported by grants from the National Natural Science Foundation of China (81770331), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_1305).

Authors contribution

Jin-Yu Sun, Zhen-Ye Zhang, Chang-Ying Zhang, and Ru-Xing Wang developed the concept of the study; Jin-Yu Sun, Zhen-Ye Zhang, and Qiang Qu designed this study and carried out the data analysis; Jin-Yu Sun wrote the manuscript with the help from Qiang Qu, Ning Wang, Yu-Min Zhang, Li-Da Wu, and Ying Liu; Ling-Feng Miao and Ji Wang provided critical reviews of the paper. All authors have read and approved the final manuscript.

Data availability statement

All the data were acquired from the Surveillance, Epidemiology, and End Results (SEER) database.

Ethics approval

Not applicable.

Declaration of Competing Interest

The authors declared that no conflicts of interests exist.

Acknowledgements

Jin-Yu Sun sincerely acknowledged Prof. Wen-Yi Shen, Dr. Jia-Zhu Wu, Dr. Chen Peng, and Dr. Zheng-Xu Sun for their generous help and gelivable support during his resident training. We sincerely acknowledged Dr. Chen Peng from Nanjing Medical University for her valuable advice on managing cancer treatment cardiotoxicity. Finally, Jin-Yu Sun was grateful for the guidance from Mr. Hui Shen, who was a kind friend, an encouraging elder brother, and a hard-working clinical scientist.

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