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Peri. J Cancer Metastasis Treat 2019;5:40 I http://dx.doi.org/10.20517/2394-4722.2019.14 Page 3 of 7

Median overall survival (OS) from the day of hospitalization was 50 days. Hyponatremic patients had a
significantly reduced OS (P = 0.0255) compared to normonatremic patients. In addition, the authors reported
that the presence of metastases was associated with a reduced OS (P = 0.0418). Similar results were obtained by
[23]
Castillo et al. , who analyzed a population of patients with lymphoma, breast cancer, colorectal cancer, small
cell and non-small cell lung cancer. Hyponatremia was negatively associated with OS in all types of tumor, but
the highest HRs were found in lymphoma (HR 4.5, P < 0.01) and in breast cancer (HR 3.7, P < 0.1).

In a retrospective cohort study, performed in a single center, 204 cancer patients affected by hyponatremia
secondary to the syndrome of inappropriate anti-diuresis (SIAD), which is the most common cause of
hyponatremia in oncology, were selected. Malignancies included lymphoma, leukemia, colorectal, breast,
lung, pancreas, prostate, head and neck, bladder, esophagus, gastric cancer. About 75% of patients had
malignancy-associated SIAD, whereas in roughly 25% SIAD was due to other etiologies (e.g., medications,
pulmonary infections, pain or nausea). The authors found that patients with malignancy-associated SIAD
had a significantly shorter median survival (58 days vs. 910 days, P < 0.001). The authors hypothesized that
[24]
the cause of SIAD in cancer patients might represent a useful prognostic factor .

A correlation between hyponatremia and a negative outcome was found also in patients with terminal
cancer. A retrospective observational study conducted in a tertiary hospital palliative care unit in the
Republic of Korea reported that, in addition to serum C-reactive protein (HR 1.22; P < 0.001) and Palliative
+
Performance Scale (HR 0.69, P < 0.001), serum [Na ] ≤ 125 mmol/L was associated with a reduced survival
time (HR = 1.91; P < 0.001) among 576 terminally ill patients (pancreatic/hepatobiliary, gastric, colorectal,
[25]
lung cancer) .
In a retrospective study performed at a University Hospital in China, among patients affected by
nasopharyngeal carcinoma, glioma or oral cancer, that had been subjected to radiotherapy and developed
radiation-induced brain necrosis, the risk of progression (i.e., increase of edema area ≥ 25% on the MRI) was
three-fold higher in patients with hyponatremia compared to those with normonatremia. Thus, the authors
claimed that hyponatremia may be considered as a potential predictor for the progression of radiation-
induced brain necrosis and recommended that hyponatremia is appropriately managed also in these
[26]
patients .

Other authors addressed their attention to a different subset of cancer patients, i.e., those who develop
spontaneous tumor lysis syndrome, that induces acute uric acid nephropathy. This is a rare, yet potentially
fatal complication in cancer patients, and it is important to determine the relevance of potential prognostic
predictors. Although only 12 patients developed this condition among the 1,073 patients admitted with acute
renal failure to a single hospital during a period of four years, hyponatremia and hypoalbuminemia on the
[27]
first day of admission were the best predictors of poor prognosis .

An interesting retrospective cohort study performed in a primary care setting in Copenhagen, Denmark,
examined another issue, i.e., the predictive role of hyponatremia on the subsequent development of cancer. This
type of analysis is facilitated in countries, like Denmark, which have a National Patient Registry. The authors
showed that there is a level-dependent increased risk to develop cancer in patients with hyponatremia. The
+
cumulative incidence increased in patients with mild (serum [Na ] 130-135 mmol/L), moderate (125-129 mmol/
L) or severe hyponatremia (< 125 mmol/L) [HR 1.32 (95%CI: 1.26-1.39), 1.31 (95%CI: 1.17-1.47), 1.77 (95%CI: 1.39-
2.24), respectively] at 12 months, compared to normonatremic subjects. When different cancers types were
[28]
analyzed separately, this finding was confirmed in head and neck, pulmonary and gastrointestinal cancer .

Some studies on the role of hyponatremia in cancer have addressed specific cancer types. With regard to
renal cell carcinoma (RCC), 212 newly diagnosed patients with localized RCC undergoing nephrectomy were