Hyponatremia as a prognostic factor in non-small cell lung cancer: a systematic review and meta-analysis

Background: Hyponatremia is a common electrolyte disorder in cancer patients and has been evaluated as a negative prognostic factor in several cancer types, especially in small cell lung cancer (SCLC). However, the prognostic value of hyponatremia is less studied in non-small cell lung cancer (NSCLC) patients. Therefore, we conducted a systematic review and meta-analysis to investigate the prognostic value of pretreatment hyponatremia in NSCLC patients. Methods: The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting checklist. The databases PubMed, Embase, Scopus, and Web of Science were searched on March 26th 2020 without time restrictions. The protocol was submitted to the PROSPERO database (ID 184612). Studies were included if they evaluated sodium level as a prognostic factor in NSCLC patients and contained original data published in English. Hazard ratios (HRs) for overall survival (OS) were pooled in a random-effects model. Results: Of 10,888 identified titles, 14 articles were included in the review including a total of 4,364 NSCLC patients. In 13 of the 14 articles, hyponatremia was found to be significantly correlated to a shorter OS. Ten articles were included in the meta-analysis. Here, patients with hyponatremia had a significantly shorter OS compared with patients with normal sodium level {pooled HR =2.02 [95% confidence interval (CI): 1.65-2.47]}. Two out of four studies found hyponatremia to be associated with a reduced progression free survival (PFS). Normalization of the sodium level during treatment was found to be associated with a prolonged PFS and OS in one study. Conclusions: This meta-analysis indicates that hyponatremia is a relative common condition in NSCLC patients associated with an increased mortality. Hence, sodium level could be a useful biomarker for stratifying NSCLC patients and thereby for preparing individual treatment plans.