No abstract

Depsipeptide, FR901228, has demonstrated potent in vitro and in vivo cytotoxic activity against murine and human tumor cell lines. In the laboratory, it has been shown to be a histone deacetylase (HDAC) inhibitor. In a phase I trial of depsipeptide conducted at the National Cancer Institute, 3 patients with cutaneous T-cell lymphoma had a partial response, and 1 patient with peripheral T-cell lymphoma, unspecified, had a complete response. Sé zary cells isolated from patients after treatment had increased histone acetylation. These results suggest that inhibition of HDAC is a novel and potentially effective therapy for patients with T-cell lymphoma. (Blood. 2001; 98:2865-2868)

A B S T R A C T PurposePrevious research has demonstrated relationships of social support with disease-related biomarkers in patients with ovarian cancer. However, the clinical relevance of these findings to patient outcomes has not been established. This prospective study examined how social support relates to long-term survival among consecutive patients with ovarian cancer. We focused on two types of social support: social attachment, a type of emotional social support reflecting connections with others, and instrumental social support reflecting the availability of tangible assistance. Patients and MethodsPatients were prospectively recruited during a presurgical clinic visit and completed surveys before surgery. One hundred sixty-eight patients with histologically confirmed epithelial ovarian cancer were observed from the date of surgery until death or December 2010. Clinical information was obtained from medical records. ResultsIn a Cox regression model, adjusting for disease stage, grade, histology, residual disease, and age, greater social attachment was associated with a lower likelihood of death (hazard ratio [HR], 0.87; 95% CI, 0.77 to 0.98; P ϭ .018). The median survival time for patients with low social attachment categorized on a median split of 15 was 3.35 years (95% CI, 2.56 to 4.15 years). In contrast, by study completion, 59% of patients with high social attachment were still alive after 4.70 years. No significant association was found between instrumental social support and survival, even after adjustment for covariates. ConclusionSocial attachment is associated with a survival advantage for patients with ovarian cancer. Clinical implications include the importance of screening for deficits in the social environment and consideration of support activities during adjuvant treatment.

Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epinephrine [E]) levels among 68 ovarian cancer patients. We also examined whether associations observed between biobehavioral measures and tumor catecholamines extended to other compartments. Higher NE levels were found in advanced stage (p=0.006) and higher grade (p=0.001) tumors. Adjusting for stage, grade, and peri-surgical beta blockers, patients with a perceived lack of social support had significantly higher tumor NE (β = −0.29, p=0.012). A similar trend was seen for social support and ascites NE (adjusting for stage, peri-surgical beta blockers and caffeine: β=−0.50, p=0.075), but not for plasma NE. Other biobehavioral factors were not related to tumor, ascites, or plasma NE (p values > 0.21). Tumor E was undetectable in the majority of tumors and thus E was not further analyzed. In summary, these results suggest that tumor NE provides distinct information from circulating plasma concentrations. Tumor NE levels were elevated in relationship to tumor grade and stage. Low subjective social support was associated with elevated intratumoral NE. As beta-adrenergic signaling is related to key biological pathways involved in tumor growth, these findings may have implications for patient outcomes in ovarian cancer.

Elevations in the pro-inflammatory cytokine interleukin-6 (IL-6) and alterations in the anti-inflammatory hormone cortisol have been reported in a variety of cancers. IL-6 has prognostic significance in ovarian cancer and cortisol has been associated with fatigue, disability, and vegetative depression in ovarian cancer patients prior to surgery. Ovarian cancer patients undergoing primary treatment completed psychological self-report measures and collected salivary cortisol and plasma IL-6 prior to surgery, at six months, and at one year. Patients included in this study had completed chemotherapy and had no evidence of disease recurrence. At six months, patients showed significant reductions in nocturnal cortisol secretion, plasma IL-6, and a more normalized diurnal cortisol rhythm, changes that were maintained at one year. The reductions in IL-6 and nocturnal cortisol were associated with declines in self-reported fatigue, vegetative depression, and disability. These findings suggest that primary treatment for ovarian cancer reduces the inflammatory response. Moreover, patients who have not developed recurrent disease by one year appear to maintain more normalized levels of cortisol and IL-6. Improvement in fatigue and vegetative depression is associated with the normalization of IL-6 and cortisol, a pattern which may be relevant for improvements in overall quality of life for ovarian cancer patients.

IntroductionHypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment.Materials and MethodsParticipants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables.ResultsEach cortisol measure was associated with decreased survival time, adjusting for covariates (all p<.041). A one standard deviation increase in night cortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r >.36, all p<.017).DiscussionAbnormal cortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity.

BACKGROUND Sleep disturbance is a common clinical complaint of oncology patients and contributes to substantial morbidity. However, because most sleep studies have been cross-sectional, associations between sleep quality and distress in ovarian cancer patients over time remain unclear. This prospective longitudinal study examined rates of sleep disturbance; contributions of depression, anxiety, and medication use in sleep disturbance; and associations between sleep quality and quality of life (QOL) during the first year post-diagnosis among women with ovarian cancer. METHODS Women with a pelvic mass completed measures of sleep quality, depression, anxiety, and QOL before surgery. Those diagnosed with primary epithelial ovarian, fallopian tube, or peritoneal cancer repeated surveys at six months and one-year post-diagnosis. Mixed modeling was used to examine trajectories of psychosocial measures over time, as well as associations between changes in distress and sleep quality. Relationships between changes in sleep and QOL were also examined. RESULTS The majority of patients reported disturbed global sleep (PSQI > 5) at all three time-points. Medications for sleep and pain were associated with worse sleep at all time-points. Greater increases in depression were associated with increased disturbances in sleep quality over time (p < .04). Worsening sleep was also associated with declines in QOL over time (p <.001). CONCLUSION Sleep disturbance is common and persistent in women with ovarian cancer, and is linked to depressive symptoms and QOL. Pharmacologic treatment does not appear to adequately address this problem. Results highlight the need for ongoing screening and intervention for sleep disturbance in this population.

Autopsy rates are decreasing at our institution. With the more widespread use of screening, the prevalence of latent prostate cancer has decreased 3-fold. The decrease in the prevalence of latent prostate cancer is especially dramatic in men older than 70 years. Further study will determine the significance of many of the tumors currently detected clinically, which may have been latent and found at autopsy if not for screening.