Hyponatremia develops frequently and predicts an increased risk of death among patients with some common cancer types, according to a new study.

Findings also suggest that hyponatremia may adversely impact progression-free survival.

Among patients with lymphoma and breast, colorectal, and lung cancer, development of hyponatremia is associated with a 4.5, 3.7, 2.4, and 2.4 times increased risk of death, respectively, investigators reported in BMC Cancer (2016;16:564).

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The study, by Jorge J. Castillo, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues, included 1758 patients with lymphoma or breast, colorectal, or lung cancer. Of these, 943 had 1 or more hyponatremia episodes during follow-up and 815 did not. Overall, the incidence of euvolemic or hypervolemic hyponatremia was 54%. The hyponatremia incidence was highest (76%) among patients with small-cell and non-small cell lung cancer; 37% for patients with breast cancer; 64% among those with colorectal cancer; and 60% among those with lymphoma. The incidence observed in the lung cancer group was considerably higher than the 20% to 50% incidence previously reported, Dr Castillo’s group stated.

Hyponatremia was not statistically associated with progression-free survival, but patients with stage 3 or 4 cancer diagnosis had a significantly increased likelihood of disease progression.

The investigators defined hyponatremia as a serum sodium value of 135 mEq/L or less, and classified hyponatremia as mild, moderate, or severe (131–135, 125–130, and less than 125 mEq/L, respectively), based on the lowest observed serum sodium value during the episode. Hyponatremia was mild in 84% of cases. The median time to first hyponatremia episode was 59 days (ranging from 10 days in small-cell lung cancer to 194 days in breast cancer) and the median duration was 16 days.

For the study, Dr. Castillo’s group excluded patients with hypovolemic hyponatremia because this type of hyponatremia generally responds to treatment with intravenous fluids, whereas euvolemic and hypervolemic hyponatremia tend be more difficult to manage.

The investigators noted that questions remain as to whether hyponatremia is a marker of disease severity or if correcting the condition can result in improved outcomes. They cited a study (BMC Cancer 2015;15:163) suggesting correction of sodium levels in cancer patients with severe hyponatremia leads to additional treatment and significantly greater overall survival, although the researchers who conducted the study acknowledged it was not possible to determine if this is related to a specific hyponatremia therapy or the resolving hyponatremia reflected an improvement in clinical condition.

“Little is known about the actual mechanism by which hyponatremia influences a poorer prognosis,” Dr Castillo and his colleagues pointed out. “Underlying renal and/or endocrine dysfunction, more aggressive biologic behavior of cancer cells that produce antidiuretic hormone (ADH), and the effects of higher than normal levels of ADH overall are all plausible potential explanations.”

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