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Page 2 of 7 Peri. J Cancer Metastasis Treat 2019;5:40 I http://dx.doi.org/10.20517/2394-4722.2019.14

at a large University Hospital in Germany in inpatients receiving specialist palliative care, showed that
the prevalence of hyponatremia was 38.7% (e.g., 275 out of 710 patients) and that low serum sodium
[2]
+
concentration [Na ] was associated with symptom severity . Several studies have demonstrated that
hyponatremia is a negative prognostic factor in different clinical scenarios. Noteworthy, not only severe
and acute hyponatremia has been associated with an increased risk of mortality, but there is evidence that
also moderate of even mild chronic hyponatremia may increase the risk of death. This has been shown for
instance in a large cohort study, which included more than 50,000 inpatients at a teaching academic medical
+
center. This study showed that mildly reduced serum [Na ] was associated with an increased in-hospital
+
[3]
mortality. In addition, each mmol/L reduction of serum [Na ] increased the risk of death by 2.3% . Among
different clinical settings, hyponatremia has been associated with an increased risk of death in patients with
[4-6]
[12]
[7,8]
[9]
heart failure , acute myocardial infarction , pneumonia , cirrhosis [10,11] , renal failure , pulmonary
[15]
[13]
[14]
[16]
embolism , intracerebral hemorrhage , in the elderly , in intensive care patients , in patients
[18]
[17]
undergoing surgery or cardiovascular procedures . An extensive meta-analysis, including more than
850,000 patients, of whom 17.4% with hyponatremia, confirmed an increased mortality rate associated with
+ [19]
reduced serum [Na ] .
The literature addressing cancer patients indicated that hyponatremia is a negative prognostic factor also in
this subset of patients. This chapter will review the published data, so far, with the exception of patients with
lung cancer, which is the specific topic of another chapter.
HYPONATREMIA AS A PROGNOSTIC AND PREDICTIVE FACTOR IN CANCER PATIENTS
[7]
Ten years ago Waikar et al. published the results of a prospective cohort study, conducted in two teaching
+
hospitals in Boston, MS, in which the association between serum [Na ] and mortality was investigated.
The main outcome measures were in-hospital 1-year and 5-year mortality of patients with hyponatremia vs
+
those with normal serum [Na ]. Patients with hyponatremia had higher in-hospital mortality rates either
at 1 year and at 5 years, even when serum [Na ] was only slightly reduced (130-134 mmol/L). Among the
+
different clinical subgroups that were analyzed, the risk of in-hospital mortality was significantly higher in
hyponatremic patients with metastatic cancer [hazard ratio (HR) 2.05, 95% confidence interval (CI): 1.67-
2.53] compared to normonatremic patients.

Shortly after, another study addressed predictors of inpatients mortality in an acute palliative care unit at the
M. D. Anderson Cancer Center of the University of Texas. Of the 500 cancer patients admitted, 124 (25%)
[20]
died . Hyponatremia was one of the multiple predictors of a negative outcome (HR 3.02, 95%CI: 1.76-5.17, P <
0.001), together with younger age, hypernatremia, high blood urea nitrogen, high heart rate, high respiration
rate, and supplemental oxygen use.

A retrospective analysis of patients admitted at the same Cancer Center during a three months period in 2006,
[21]
+
aiming to correlate hyponatremia with 90-day mortality, was performed . Serum [Na ] was categorized
+
into four groups, e.g., normonatremia (serum [Na ] 135-147 mmol/L), mild (130-134 mmol/L), moderate
(120-129 mmol/L), and severe (< 120 mmol/L) hyponatremia. In all hyponatremic groups the risk of
mortality at 90 days was higher than in normonatremic patients (HR for mild, moderate, and severe
hyponatremia: 2.04 (95%CI: 1.42-2.91; P < 0.01); 4.74 (95%CI: 3.21-7.01; P < 0.01), and 3.46 (95%CI: 1.05-11.44;
P = 0.04), respectively. Although the authors recognized limitations to the study (observational, retrospective
study, inability to adjust for all comorbid conditions), and the fact that it has not been proven that
hyponatremia correction can reduce mortality, these data further confirmed the clear relationship between
hyponatremia and increased mortality in cancer patients.

An Italian study performed in Ancona analyzed 105 consecutive cancer patients, affected by gastrointestinal,
[22]
lung, breast, female genital tract, renal, brain tumors, and sarcoma, hospitalized during a 6 month period .