Pam Harrison

May 02, 2011

May 2, 2011 — Poorer psychosocial functioning is associated with greater expression of vascular endothelial growth factor (VEGF) in tumor tissue taken from patients with newly diagnosed head and neck cancer.

Greater VEGF expression, in turn, was associated with shorter disease-free survival in the same patient group.

Carolyn Fang, PhD, Fox Chase Cancer Center, Philadelphia, Pennsylvania, found that higher levels of perceived stress and lower levels of social support were associated with significantly more intense VEGF expression in tumor samples compared with patients who reported lower levels of perceived stress and higher levels of social support.

Patients who were married or who had a long-term partner also had higher levels of social support; lower levels of perceived stress, and lower levels of depressive symptoms than their unmarried counterparts. In contrast, health behaviors did not differ between married and unmarried patients.

"We saw a linear relationship between psychosocial support and VEGF such that as stress increased, there was increasing VEGF expression in tumor tissue. We also saw an inverse relationship between social support and VEGF expression such that as social support increased, people were more likely to have low levels of VEGF expression, while as social support decreased, there was more intense expression of VEGF in the tumor," Dr. Fang said.

Findings were presented at the Society of Behavioral Medicine 32nd Annual Meeting and Scientific Sessions.

Newly Diagnosed Cancer

For the study, investigators recruited 76 patients with newly diagnosed head and neck cancer. Two thirds were married or had a long-term partner, about 70% were former or current smokers, and two thirds reported moderate to heavy alcohol use. Before their surgery, patients completed a battery of questionnaires, including a perceived stress scale, a depression scale, and measures of social support. Tissue samples were taken during the surgical procedure and were analyzed for VEGF expression.

Approximately one third of the sample had early-stage disease; the remaining patients had advanced disease. As Dr. Fang explained, tissues samples are often hard to come by, so in the end, they were able to analyze only 40 tissue samples from this patient cohort. Of these samples, about half had moderate VEGF expression, about one quarter had weak expression, and the remaining quarter had very intense expression of VEGF in the tumor.

"Overall, we found patients reported fairly high levels of perceived stress, as you would expect given that they were newly diagnosed with head and neck cancer," Dr. Fang said.

However, when they assessed levels of psychosocial function, married participants had more total social support; less perceived stress, and fewer depressive symptoms than unmarried participants.

In contrast, the number of pack-years smoked or moderate to heavy alcohol use did not differ between the 2 groups.

Psychosocial Functioning

Measure Score in Married Patients Score in Unmarried Patients
Total social support 91.13 84.44
Perceived stress 20.54 25.42
Depressive symptoms 7.01 10.23

Increasing intensity of VEGF expression was also associated with greater mean scores of perceived stress and decreasing scores of social support.  "In other words, weaker VEGF expression was associated with, on average, lower levels of perceived stress, whereas higher VEGF expression was associated with higher levels of perceived stress," Dr. Fang noted.

Among patients with weak VEGF expression, for example, the mean level of self-reported stress was 17.50; among patients with moderate VEGF expression, the mean level of self-reported stress was 19.42; and among patients with intense VEGF expression, the mean level of self-reported stress was 25.75.

For social support, those reporting the highest levels of social support, at a score of 91 (of 95), had the weakest expression of VEGF; in comparison, those who reported lower levels of social support, at a score of approximately 87, had moderate VEGF expression. Those reporting the lowest levels of social support, at a score of 83, showed the most intense expression of VEGF.

"Our sample size was small so we were wavering around the significance level but given that the sample size was small, I was quite surprised to see such a robust trend, and with a larger sample, I think we will be able to show even more robust results," Dr. Fang told Medscape Medical News. As Dr. Fang also explained, data from animal models and experimental studies indicate that VEGF can be induced by several stress-related biomarkers, including interleukin-6 and norepinephrine.

"Given these findings, we hypothesized that poorer psychosocial functioning, reflected by higher levels of stress and lower levels of social support, would be associated with greater expression of VEGF in these tumor samples," she said. "And I think our preliminary evidence that psychosocial functioning is perhaps influencing outcomes is important, although we are still trying to determine the mechanisms through which this may be."

Supportive Interventions

Jamie Studts, PhD, University of Kentucky, Lexington, Kentucky, felt that if the correlation between psychosocial functioning and VEGF expression can be confirmed, it becomes a potential target for supportive interventions. "For example," he told Medscape Medical News, "we might be able to take a psychosocial intervention that has been shown to be effective in reducing stress among patients diagnosed with cancer and intervene in these patients and move that marker [ie, VEGF expression] in a positive direction. It is a challenge to put that whole piece of the equation together but it does open our eyes to the possibilities based on this preliminary data."

Pilot finding for the study was provided by the Fox Chase Cancer Center. Dr. Fang and Dr. Studts have reported no relevant financial relationships.

The Society of Behavioral Medicine 32nd Annual Meeting and Scientific Sessions. Abstract #2051. April 28, 2011.

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