The association of hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer patients: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Xiaowei ¹ , CHANG Shuai ² , SONG Wenpeng ² ,  CHE Guowei ²

1. Department of Cardiothoracic Surgery, Chengdu Second People's Hospital, Chengdu, 610017, P. R. China;
2. Lung Cancer Center/Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding author：

CHE Guowei, Email: cheguoweixw@126.com

Keywords：

Hyponatremia; non-small cell lung cancer; clinicopathological characteristic; prognosis; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202109016

Video：

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Objective To explore the association of pretreatment hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer (NSCLC) patients. Methods The PubMed, EMbase, Web of Science, VIP, CNKI and WanFang databases were searched from the inception to July 12, 2021 for relevant literatures. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS) score. The relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were combined to assess the relationship between pretreatment hyponatremia and clinicopathological and prognostic characteristics. The prognostic indicators included the overall survival (OS) and progression-free survival (PFS). All statistical analysis was conducted by the STATA 15.0 software. Results A total of 10 high-quality studies (NOS score≥6 points) involving 10 045 patients were enrolled and all participants were from Asian or European regions. The pooled results demonstrated that male [RR=1.18, 95%CI (1.02, 1.36), P=0.026], non-adenocarcinoma [RR=0.86, 95%CI (0.81, 0.91), P＜0.001] and TNM Ⅲ-Ⅳ stage [RR=1.17, 95%CI (1.12, 1.21), P＜0.001] patients were more likely to experience hyponatremia. Besides, pretreatment hyponatremia was significantly related to worse OS [HR=1.83, 95%CI (1.53, 2.19), P＜0.001] and PFS [HR=1.54, 95%CI (1.02, 2.34), P=0.040]. Pretreatment hyponatremia was a risk factor for poor prognosis of NSCLC patients. Conclusion Male, non-adenocarcinoma and advance stage NSCLC patients are more likely to experience hyponatremia. Meanwhile, the pretreatment sodium level can be applied as one of the prognostic evaluation indicators in NSCLC and patients with hyponatremia are more likely to have poor survival. However, more researches are still needed to verify above findings.

Citation： WANG Xiaowei, CHANG Shuai, SONG Wenpeng, CHE Guowei. The association of hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer patients: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(3): 428-433. doi: 10.7507/1007-4848.202109016 Copy

1.	Sørensen JB, Andersen MK, Hansen HH. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. J Intern Med, 1995, 238(2): 97-110.
2.	Sandfeld-Paulsen B, Aggerholm-Pedersen N, Winther-Larsen A. Hyponatremia as a prognostic factor in non-small cell lung cancer: A systematic review and meta-analysis. Transl Lung Cancer Res, 2021, 10(2): 651-661.
3.	Castillo JJ, Glezerman IG, Boklage SH, et al. The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients. BMC Cancer, 2016, 16: 564.
4.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
5.	Wu R, Li C, Wang Z, et al. A narrative review of progress in diagnosis and treatment of small cell lung cancer patients with hyponatremia. Transl Lung Cancer Res, 2020, 9(6): 2469-2478.
6.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
7.	Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
8.	Rechnitzer S, Bulzebruck H, Ebert W, et al. Pretreatment prognostic factors for survival in non-small-cell lung cancer: A multivariate analysis of 229 patients. Onkologie, 1998, 21(3): 204-10.
9.	Jacot W, Quantin X, Boher JM, et al. Brain metastases at the time of presentation of non-small cell lung cancer: A multi-centric AERIO analysis of prognostic factors. Br J Cancer, 2001, 84(7): 903-909.
10.	Kobayashi N, Usui S, Yamaoka M, et al. The influence of serum sodium concentration on prognosis in resected non-small cell lung cancer. Thorac Cardiovasc Surg, 2014, 62(4): 338-343.
11.	Svaton M, Fiala O, Pesek M, et al. Predictive and prognostic significance of sodium levels in patients with NSCLC treated by erlotinib. Anticancer Res, 2014, 34(12): 7461-7465.
12.	Berardi R, Santoni M, Newsom-Davis T, et al. Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy. Oncotarget, 2017, 8(14): 23871-23879.
13.	Doshi KH, Shriyan B, Nookala MK, et al. Prognostic significance of pretreatment sodium levels in patients of nonsmall cell lung cancer treated with pemetrexed-platinum doublet chemotherapy. J Cancer Res Ther, 2018, 14(5): 1049-1053.
14.	Fucà G, Galli G, Poggi M, et al. Low Baseline serum sodium concentration is associated with poor clinical outcomes in metastatic non-small cell lung cancer patients treated with immunotherapy. Target Oncol, 2018, 13(6): 795-800.
15.	Lee SY, Kang EJ, Lee SY, et al. Efficacy of second-line treatment and importance of comorbidity scores and clinical parameters affecting prognosis in elderly patients with non-small cell lung cancer without epidermal growth factor receptor mutations. Oncol Lett, 2018, 15(1): 600-609.
16.	Rinaldi S, Santoni M, Leoni G, et al. The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases. Support Care Cancer, 2019, 27(4): 1255-1261.
17.	Sandfeld-Paulsen B, Aggerholm-Pedersen N, Winther-Larsen A. Hyponatremia in lung cancer: Incidence and prognostic value in a Danish population-based cohort study. Lung Cancer, 2021, 153: 42-48.
18.	Zhou XY, Chen HL, Ni SS. Hyponatremia and short-term prognosis of patients with acute pulmonary embolism: A meta-analysis. Int J Cardiol, 2017, 227: 251-256.
19.	Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med, 2008, 359(10): 1018-1026.
20.	Mohan S, Gu S, Parikh A, et al. Prevalence of hyponatremia and association with mortality: Results from NHANES. Am J Med, 2013, 126(12): 1127-1137.
21.	Mapa B, Taylor BE, Appelboom G, et al. Impact of hyponatremia on morbidity, mortality, and complications after aneurysmal subarachnoid hemorrhage: A systematic review. World Neurosurg, 2016, 85: 305-314.
22.	Sun N, Chen YQ, Sun BF, et al. Association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism. Zhonghua Xin Xue Guan Bing Za Zhi, 2018, 46(12): 976-980.
23.	Zheng Y, Zheng FP, Li H. The prevalence and causes of hyponatremia in hospitalized patients. Zhonghua Nei Ke Za Zhi, 2020, 59(1): 29-34.
24.	Kitchlu A, Rosner MH. Hyponatremia in patients with cancer. Curr Opin Nephrol Hypertens, 2019, 28(5): 433-440.
25.	Uppal NN, Wanchoo R, Barnett R, et al. Hyponatremia in a patient with cancer. Am J Kidney Dis, 2020, 75(1): A15-A18.
26.	Workeneh BT, Jhaveri KD, Rondon-Berrios H. Hyponatremia in the cancer patient. Kidney Int, 2020, 98(4): 870-882.
27.	Hermes A, Waschki B, Reck M. Hyponatremia as prognostic factor in small cell lung cancer—A retrospective single institution analysis. Respir Med, 2012, 106(6): 900-904.
28.	Sun NH, Wang SH, Liu JN, et al. The productions of atrial natriuretic peptide and arginine vasopressin in small cell lung cancer with brain metastases and their associations with hyponatremia. Eur Rev Med Pharmacol Sci, 2017, 21(18): 4104-4112.
29.	Tiseo M, Buti S, Boni L, et al. Prognostic role of hyponatremia in 564 small cell lung cancer patients treated with topotecan. Lung Cancer, 2014, 86(1): 91-95.
30.	Yang Y, Sun N, Sun P, et al. Clinical characteristics and prognosis of elderly small cell lung cancer patients complicated with hyponatremia: A retrospective analysis. Anticancer Res, 2017, 37(8): 4681-4686.
31.	Bose CK, Dey S, Mukhopadhyay A. Hyponatremia of non-small cell lung cancer: Indian experience. Indian J Med Paediatr Oncol, 2011, 32(3): 139-142.
32.	Fiordoliva I, Meletani T, Baleani MG, et al. Managing hyponatremia in lung cancer: Latest evidence and clinical implications. Ther Adv Med Oncol, 2017, 9(11): 711-719.
33.	Selmer C, Madsen JC, Torp-Pedersen C, et al. Hyponatremia, all-cause mortality, and risk of cancer diagnoses in the primary care setting: A large population study. Eur J Intern Med, 2016, 36: 36-43.
34.	Holland-Bill L, Christiansen CF, Farkas DK, et al. Diagnosis of hyponatremia and increased risk of a subsequent cancer diagnosis: Results from a nationwide population-based cohort study. Acta Oncol, 2018, 57(4): 522-527.

1. Sørensen JB, Andersen MK, Hansen HH. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. J Intern Med, 1995, 238(2): 97-110.
2. Sandfeld-Paulsen B, Aggerholm-Pedersen N, Winther-Larsen A. Hyponatremia as a prognostic factor in non-small cell lung cancer: A systematic review and meta-analysis. Transl Lung Cancer Res, 2021, 10(2): 651-661.
3. Castillo JJ, Glezerman IG, Boklage SH, et al. The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients. BMC Cancer, 2016, 16: 564.
4. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
5. Wu R, Li C, Wang Z, et al. A narrative review of progress in diagnosis and treatment of small cell lung cancer patients with hyponatremia. Transl Lung Cancer Res, 2020, 9(6): 2469-2478.
6. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
7. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
8. Rechnitzer S, Bulzebruck H, Ebert W, et al. Pretreatment prognostic factors for survival in non-small-cell lung cancer: A multivariate analysis of 229 patients. Onkologie, 1998, 21(3): 204-10.
9. Jacot W, Quantin X, Boher JM, et al. Brain metastases at the time of presentation of non-small cell lung cancer: A multi-centric AERIO analysis of prognostic factors. Br J Cancer, 2001, 84(7): 903-909.
10. Kobayashi N, Usui S, Yamaoka M, et al. The influence of serum sodium concentration on prognosis in resected non-small cell lung cancer. Thorac Cardiovasc Surg, 2014, 62(4): 338-343.
11. Svaton M, Fiala O, Pesek M, et al. Predictive and prognostic significance of sodium levels in patients with NSCLC treated by erlotinib. Anticancer Res, 2014, 34(12): 7461-7465.
12. Berardi R, Santoni M, Newsom-Davis T, et al. Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy. Oncotarget, 2017, 8(14): 23871-23879.
13. Doshi KH, Shriyan B, Nookala MK, et al. Prognostic significance of pretreatment sodium levels in patients of nonsmall cell lung cancer treated with pemetrexed-platinum doublet chemotherapy. J Cancer Res Ther, 2018, 14(5): 1049-1053.
14. Fucà G, Galli G, Poggi M, et al. Low Baseline serum sodium concentration is associated with poor clinical outcomes in metastatic non-small cell lung cancer patients treated with immunotherapy. Target Oncol, 2018, 13(6): 795-800.
15. Lee SY, Kang EJ, Lee SY, et al. Efficacy of second-line treatment and importance of comorbidity scores and clinical parameters affecting prognosis in elderly patients with non-small cell lung cancer without epidermal growth factor receptor mutations. Oncol Lett, 2018, 15(1): 600-609.
16. Rinaldi S, Santoni M, Leoni G, et al. The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases. Support Care Cancer, 2019, 27(4): 1255-1261.
17. Sandfeld-Paulsen B, Aggerholm-Pedersen N, Winther-Larsen A. Hyponatremia in lung cancer: Incidence and prognostic value in a Danish population-based cohort study. Lung Cancer, 2021, 153: 42-48.
18. Zhou XY, Chen HL, Ni SS. Hyponatremia and short-term prognosis of patients with acute pulmonary embolism: A meta-analysis. Int J Cardiol, 2017, 227: 251-256.
19. Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med, 2008, 359(10): 1018-1026.
20. Mohan S, Gu S, Parikh A, et al. Prevalence of hyponatremia and association with mortality: Results from NHANES. Am J Med, 2013, 126(12): 1127-1137.
21. Mapa B, Taylor BE, Appelboom G, et al. Impact of hyponatremia on morbidity, mortality, and complications after aneurysmal subarachnoid hemorrhage: A systematic review. World Neurosurg, 2016, 85: 305-314.
22. Sun N, Chen YQ, Sun BF, et al. Association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism. Zhonghua Xin Xue Guan Bing Za Zhi, 2018, 46(12): 976-980.
23. Zheng Y, Zheng FP, Li H. The prevalence and causes of hyponatremia in hospitalized patients. Zhonghua Nei Ke Za Zhi, 2020, 59(1): 29-34.
24. Kitchlu A, Rosner MH. Hyponatremia in patients with cancer. Curr Opin Nephrol Hypertens, 2019, 28(5): 433-440.
25. Uppal NN, Wanchoo R, Barnett R, et al. Hyponatremia in a patient with cancer. Am J Kidney Dis, 2020, 75(1): A15-A18.
26. Workeneh BT, Jhaveri KD, Rondon-Berrios H. Hyponatremia in the cancer patient. Kidney Int, 2020, 98(4): 870-882.
27. Hermes A, Waschki B, Reck M. Hyponatremia as prognostic factor in small cell lung cancer—A retrospective single institution analysis. Respir Med, 2012, 106(6): 900-904.
28. Sun NH, Wang SH, Liu JN, et al. The productions of atrial natriuretic peptide and arginine vasopressin in small cell lung cancer with brain metastases and their associations with hyponatremia. Eur Rev Med Pharmacol Sci, 2017, 21(18): 4104-4112.
29. Tiseo M, Buti S, Boni L, et al. Prognostic role of hyponatremia in 564 small cell lung cancer patients treated with topotecan. Lung Cancer, 2014, 86(1): 91-95.
30. Yang Y, Sun N, Sun P, et al. Clinical characteristics and prognosis of elderly small cell lung cancer patients complicated with hyponatremia: A retrospective analysis. Anticancer Res, 2017, 37(8): 4681-4686.
31. Bose CK, Dey S, Mukhopadhyay A. Hyponatremia of non-small cell lung cancer: Indian experience. Indian J Med Paediatr Oncol, 2011, 32(3): 139-142.
32. Fiordoliva I, Meletani T, Baleani MG, et al. Managing hyponatremia in lung cancer: Latest evidence and clinical implications. Ther Adv Med Oncol, 2017, 9(11): 711-719.
33. Selmer C, Madsen JC, Torp-Pedersen C, et al. Hyponatremia, all-cause mortality, and risk of cancer diagnoses in the primary care setting: A large population study. Eur J Intern Med, 2016, 36: 36-43.
34. Holland-Bill L, Christiansen CF, Farkas DK, et al. Diagnosis of hyponatremia and increased risk of a subsequent cancer diagnosis: Results from a nationwide population-based cohort study. Acta Oncol, 2018, 57(4): 522-527.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

The association of hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer patients: A systematic review and meta-analysis

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