Sex-based differences in the outcomes of patients with lung carcinoids
Publication: Journal of Comparative Effectiveness Research
Abstract
Objective: To assess the impact of sex on the outcomes of patients with well-differentiated lung neuroendocrine neoplasms in a real-world setting. Methods: The Surveillance, Epidemiology and End Results Research Plus database (2000–2018) was accessed, and patients with a diagnosis of typical or atypical carcinoid of the lung were reviewed. Trends in age-standardized rates (per 100,000) of the incidence of lung carcinoid tumors were reviewed among male and female patients as well as the overall population, and annual percent change (APC) was determined for the three groups. Multivariate Cox regression analysis was then used to assess the factors associated with overall and cancer-specific survival. Results: Among all patients, APC (2000–2018) for lung carcinoid diagnosis was 2.9 (95% CI: 2.4–3.5). Among male patients, APC (2000–2018) for lung carcinoid diagnosis was 1.8 (95% CI: 1.2–2.5). By contrast, among female patients, APC (2000–2018) for lung carcinoid diagnosis was 3.4 (95% CI: 2.8–4.1). Based on Kaplan–Meier survival estimates, female sex was associated with better overall survival compared with male sex (p < 0.001). Based on multivariate Cox regression analysis, the following factors were associated with worse cancer-specific survival: older age (hazard ratio [HR]: 1.036; 95% CI: 1.031–1.041), atypical carcinoid histology (HR: 3.10; 95% CI: 2.71–3.56), stage (distant vs localized stage HR: 4.05; 95% CI: 3.48–4.71), sex (male vs female sex HR: 1.76; 95% CI: 1.56–1.99) and no surgical treatment (HR: 3.77; 95% CI: 3.22–4.42). Conclusion: Female patients with lung carcinoid tumors have better overall survival compared with male patients, particularly among patients with typical carcinoid tumors.
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References
Papers of special note have been highlighted as: • of interest
1.
Fazio N, Abdel-Rahman O, Spada F et al. RAF signaling in neuroendocrine neoplasms: from bench to bedside. Cancer Treat. Rev. 40(8), 974–979 (2014).
2.
Falconi M, Eriksson B, Kaltsas G et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 103(2), 153–171 (2016).
3.
Shah S, Gosain R, Groman A et al. Incidence and survival outcomes in patients with lung neuroendocrine neoplasms in the United States. Cancers (Basel) 13(8), 1753 (2021).
4.
Iyoda A, Azuma Y, Sano A. Neuroendocrine tumors of the lung: clinicopathological and molecular features. Surg. Today 50(12), 1578–1584 (2020).
5.
Abdel-Rahman O, Fouad M. Everolimus-based combination for the treatment of advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): biological rationale and critical review of published data. Tumour Biol. 36(2), 467–478 (2015).
6.
Abdel-Rahman O, Fouad M. Bevacizumab-based combination therapy for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a systematic review of the literature. J. Cancer Res. Clin. Oncol. 141(2), 295–305 (2015).
7.
Cook MB, McGlynn KA, Devesa SS, Freedman ND, Anderson WF. Sex disparities in cancer mortality and survival. Cancer Epidemiol. Biomarkers Prev. 20(8), 1629–1637 (2011).
8.
Abdel-Rahman O. Impact of sex on chemotherapy toxicity and efficacy among patients with metastatic colorectal cancer: pooled analysis of 5 randomized trials. Clin. Colorectal Cancer 18(2), 110–115.e112 (2019).
9.
Abdel-Rahman O, Fazio N. Sex-based differences in prognosis of patients with gastroenteropancreatic neuroendocrine neoplasms: a population-based study. Pancreas 50(5), 727–731 (2021).
• Evaluated the impact of sex on the prognosis of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs).
10.
Hallet J, Law CH, Cukier M, Saskin R, Liu N, Singh S. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer 121(4), 589–597 (2015).
11.
Yao JC, Hassan M, Phan A et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J. Clin. Oncol. 26(18), 3063–3072 (2008).
12.
Travis WD, Brambilla E, Nicholson AG et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J. Thorac. Oncol. 10(9), 1243–1260 (2015).
13.
Surveillance, Epidemiology and End Results. www.seer.cancer.gov
14.
Goel MK, Khanna P, Kishore J. Understanding survival analysis: Kaplan–Meier estimate. Int. J. Ayurveda Res. 1(4), 274–278 (2010).
15.
Abdel-Rahman O. Validation of the 8th AJCC prognostic staging system for breast cancer in a population-based setting. Breast Cancer Res. Treat. 168(1), 269–275 (2018).
16.
Zahedi A, Bondaz L, Rajaraman M et al. Risk for thyroid cancer recurrence is higher in men than in women independent of disease stage at presentation. Thyroid 30(6), 871–877 (2020).
17.
Hernando-Cubero J, Grande E, Castellano DE et al. Impact of gender on multikinase inhibitors (MKIs) toxicity in patients (pts) with advanced pancreatic and gastrointestinal neuroendocrine tumors (NETs): a pooled analysis of two phase II trials with pazopanib and lenvatinib. J. Clin. Oncol. 37(Suppl. 15), 4109 (2019).
18.
Man D, Wu J, Shen Z, Zhu X. Prognosis of patients with neuroendocrine tumor: a SEER database analysis. Cancer Manag. Res. 10, 5629–5638 (2018).
19.
Singh S, Parulekar W, Murray N et al. Influence of sex on toxicity and treatment outcome in small-cell lung cancer. J. Clin. Oncol. 23(4), 850–856 (2005).
20.
Wheatley-Price P, Blackhall F, Lee SM et al. The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials. Ann. Oncol. 21(10), 2023–2028 (2010).
21.
Estrella JS, Ma LT, Milton DR et al. Expression of estrogen-induced genes and estrogen receptor β in pancreatic neuroendocrine tumors: implications for targeted therapy. Pancreas 43(7), 996–1002 (2014).
22.
Estrella JS, Broaddus RR, Mathews A et al. Progesterone receptor and PTEN expression predict survival in patients with low- and intermediate-grade pancreatic neuroendocrine tumors. Arch. Pathol. Lab. Med. 138(8), 1027–1036 (2014).
23.
Arnason T, Sapp HL, Barnes PJ, Drewniak M, Abdolell M, Rayson D. Immunohistochemical expression and prognostic value of ER, PR and HER2/neu in pancreatic and small intestinal neuroendocrine tumors. Neuroendocrinology 93(4), 249–258 (2011).
24.
Simbolo M, Barbi S, Fassan M et al. Gene expression profiling of lung atypical carcinoids and large cell neuroendocrine carcinomas identifies three transcriptomic subtypes with specific genomic alterations. J. Thorac. Oncol. 14(9), 1651–1661 (2019).
25.
Simbolo M, Mafficini A, Sikora KO et al. Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D. J. Pathol. 241(4), 488–500 (2017).
26.
Fernandez-Cuesta L, Peifer M, Lu X et al. Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat. Commun. 5, 3518 (2014).
27.
Dong S, Liang J, Zhai W, Yu Z. Development and validation of an individualized nomogram for predicting overall survival in patients with typical lung carcinoid tumors. Am. J. Clin. Oncol. 43(9), 607–614 (2020).
28.
Abdel-Rahman O, North S. Patterns of cost-related medication underuse among Canadian adults with cancer: a cross-sectional study using survey data. CMAJ Open 9(2), e474–e481 (2021).
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Pages: 523 - 531
PubMed: 35388711
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© 2022 Future Medicine Ltd.
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Received: 26 August 2021
Accepted: 17 March 2022
Published online: 7 April 2022
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Sex-based differences in the outcomes of patients with lung carcinoids. (2022) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2021-0205
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- Henning Jann, Sarah Krieg, Andreas Krieg, Johannes Eschrich, Tom Luedde, Karel Kostev, Sven Loosen, Christoph Roderburg, Analyses of sex-based clinicopathological differences among patients with gastrointestinal neuroendocrine neoplasms in Europe, Journal of Cancer Research and Clinical Oncology, 10.1007/s00432-023-04711-4, 149, 10, (7557-7563), (2023).
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