Prognostic impact of hyponatremia in patients affected by advanced non-small cell lung cancer (NSCLC) with bone metastases (BMs)

Background: In recent years, due to the development of new treatment options, the outcome of patients with metastatic non-small cell lung cancer (NSCLC) has improved. However, hyponatremia and bone metastasis still correlate with poor prognosis. Some studies suggest that hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. Aim of this study is to investigate the prognostic role of hyponatremia in patients with bone metastases (BMs) due to NSCLC. Material and methods: NSCLC patients’ data were retrospectively collected. Survival curves were estimated using Kaplan-Meier method, and comparisons were made using chi-square test. Age, gender, tumor stage, histology, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS), smoking history and presence of hyponatremia were included in the Cox analysis to investigate their prognostic relevance. Results: 647 patients with advanced NSCLC were enrolled; of them 440 (68%) were male. Median age was 72y (range 32-93y). A total of 264 patients (41%) presented with BMs, which were synchronous in 170 patients (26%) and metachronous in 94 (15%). At diagnosis, hyponatremia was described in 105 (16%) patients, a total of 237 (37%) patients developed hyponatremia during the first line. Median overall survival (OS) was 15,9 (95% CI 14,1-17,9) months for patients without BMs, 11.4 (95% CI 9,4-13,4) months for patients with BMs, while mOS was 16,3 (95% CI 14,6-18,0) months for eunatremic patients and 10.3 (95% CI 7,6-12,8) months for patients with hyponatremia. Considering the two variables, mOS was 10.1 (95% CI 4,3-15,9) months for patients with BMs and hyponatremia, 11.9 (95% CI 11,4-12,4) for patients with hyponatremia without BMs, 13.1 (95% CI 12,0-14,2) for eunatremic patients with BMs, 17.1 (95% CI 15,2-19,1) months in eunatremic patients without BMs (p: 0.0020). Metachronous BMs appeared earlier in hyponatremic patients (3.73 vs. 5.76 months, p: 0.0187). At multivariate analysis in the whole population, ECOG-PS≥2, IV tumor stage, male sex, hyponatremia and BMs were independent prognostic factors for worst OS. In patients with BMs, smoking history, IV tumor stage were independent prognostic factors for worst OS. Conclusions: Our study suggests that hyponatremia represent an important prognostic factor and it should be necessary considered in order to optimize the management of NSCLC patients with BMs.