Cardiovascular disease-specific mortality in 270,618 patients with non-small cell lung cancer
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.
References (34)
- et al.
US Food and Drug Administration review of statistical analysis of patient-reported outcomes in lung cancer clinical trials approved between January, 2008, and December, 2017
Lancet Oncol.
(2019) - et al.
Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial
Lancet.
(2019) - et al.
Cardiac radiation dose, cardiac disease, and mortality in patients with lung Cancer
J. Am. Coll. Cardiol.
(2019) - et al.
Cardiac toxicity in association with chemotherapy and radiation therapy in a large cohort of older patients with non-small-cell lung cancer
Ann. Oncol.
(2010) - et al.
Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries
Lancet Oncol.
(2005) - et al.
Cancer immunotherapy: current applications and challenges
Cancer Lett.
(2020) - et al.
Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012
Eur. J. Cancer
(2013) - et al.
Impact of pneumonia and lung cancer on mortality of women with hypertension
Sci. Rep.
(2016) - et al.
Prevalence of preexisting cardiovascular disease in patients with different types of cancer: the unmet need for onco-cardiology
Mayo Clin. Proc.
(2016) - et al.
Cardiovascular comorbidities and survival of lung cancer patients: Medicare data based analysis
Lung Cancer
(2015)
Reduced lung-Cancer mortality with volume CT screening in a randomized trial
N. Engl. J. Med.
A population-based study of cardiovascular disease mortality risk in US cancer patients
Eur. Heart J.
Lung cancer radiation may increase the risk of major adverse cardiac events
CA Cancer J. Clin.
Synergistic opportunities in the interplay between Cancer screening and cardiovascular disease risk assessment: together we are stronger
Circulation.
Evaluation of cardiovascular risk in a lung cancer screening cohort
Thorax.
Long-term heart-specific mortality among 347 476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort study
Eur. Heart J.
New-onset cardiovascular morbidity in older adults with stage I to III colorectal Cancer
J. Clin. Oncol.
Cited by (18)
Toxicities and Deaths From Intercurrent Disease Following Contemporary Postoperative Radiotherapy in Resected Non-Small-Cell Lung Cancer
2023, Clinical Lung CancerCitation Excerpt :To ensure safe delivery of PORT, optimal RT techniques should be considered. Cardiopulmonary toxicity is thought to be the leading non-cancer driver of deaths among survivors of NSCLC.22 Studies have shown that higher radiation doses to the heart and lungs are associated with an increased risk of adverse outcomes.2,6-9
Cardio- oncology: A view from the cardiologist's window
2021, International Journal of CardiologyNon cancer causes of death after gallbladder cancer diagnosis: a population-based analysis
2023, Scientific ReportsAssociation between radiotherapy and risk of death from cardiovascular diseases in lung and bronchus cancer
2023, Frontiers in Cardiovascular Medicine
- 1
The first three authors contributed equally to this work.