Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy

Abstract

The aim of the study was to assess, for the first time, the prognostic role of hyponatremia and sodium normalization in patients receiving first-line chemo-or targeted therapy for advanced non-small cell lung cancer.Four hundred thirty-three patients with advanced non small cell lung cancer were treated with first line chemo-or targeted therapy between 2006 and 2015 at our institutions. Patients were stratified in two groups, with or without hyponatremia (group A and B, respectively). Progression free survival (PFS) and overall survival (OS) were estimated using KaplanMeier method. A Cox regression model was carried out for univariate and multivariate analyses.Sixty-nine patients (16%) presented with hyponatremia at the start of first-line therapy. The median OS was 8.78 months in Group A and 15.5 months in Group B (p < 0.001), while the median PFS was 4.1 months and 6.3 months respectively (p = 0.24). In Group A, median OS was significantly higher in patients who normalized their sodium levels (11.6 vs. 4.7 months, p = 0.0435). Similarly, the median PFS was significantly higher in patients who normalized their sodium levels (6.7 vs. 3.3 months, p = 0.011). At multivariate analysis, sodium normalization was an independent prognostic factor for both OS and PFS.Sodium normalization during first-line therapy is an independent prognostic factor for OS and PFS in patients with advanced lung cancer treated with first-line therapies. Frequent clinical monitoring and prompt treatment of hyponatremia should be emphasized to optimize the outcome of these patients.

Prognostic and predictive role of hyponatremia in cancer patients

“…Recently, a study performed at two teaching hospitals in Italy and one teaching hospital in England demonstrated that serum [Na + ] normalization during first-line therapy is an independent prognostic factor for OS and PFS in patients with non-small cell lung cancer [37] . Similarly, normalization of serum [Na + ] was associated with a better prognosis in patients with metastatic RCC treated with everolimus [38] .…”

Adenoma mimicking hyponatremia of SIAD

“…In medical literature, Jessani et al described selective serotonin reuptake inhibitor-induced SIAD as another common confounder that can mask hyponatremia of hypocortisolism in patients with psychiatric history. Furthermore, lack of hyponatremia normalisation following first-line treatment should prompt physicians to pursue further workup for alternative diagnoses, as it has been described as an independent prognostic factor of survival in patients with known malignancies 6. One way to minimise the effect of anchoring bias on physicians is their cognitive awareness of such bias.…”

Recent advances in the management of hyponatremia in cancer patients

“…Treatment strategies with targeted therapies (inhibitors of angiogenesis, anti-epithelial growth factor tyrosine kinase receptor inhibitors and monoclonal antibodies) in cancer patients increases the incidence of hyponatremia (25.5%) in the treatment group. Higher incidence of hyponatremia is observed with a treatment combination of cetuximab and brivanib (63.4%) as well as with pazopanib (31.7%) [11] . Patients receiving chemotherapy generally increase their free water intake.…”

“…In cases of symptomatic hyponatremia, pharmacologic intervention may be necessary to increase serum sodium levels [8] . The management of hyponatremia is becoming increasingly important in oncology due to the negative correlation of hyponatremia with performance status and the prognosis of cancer [7,11] . Treatment of hyponatremia in small cell lung cancer patients is associated with improved survival [12] .…”