Preservation of immune function in cervical cancer patients during chemoradiation using a novel integrative approach.

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for (1) supporting cellular immunity, (2) improving mood and quality of life (QOL), and (3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4 ×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial assessments and blood sampling before chemoradiation at baseline, weeks 4 and 6. Multilevel regression analyses using orthogonal contrasts tested for differences between treatment conditions over time. HT patients had a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of RT and UC patients declined sharply during chemoradiation (group by time interaction: p = 0.018). HT patients showed greater decreases in two different indicators of depressed mood (CES-D depressed mood subscale and POMS depression scale) compared to RT and UC (group by time interactions: p<0.05). No between group differences were observed in QOL, treatment delay, or clinically-rated toxicities. HT may benefit cervical cancer patients by moderating effects of chemoradiation on depressed mood and cellular immunity. Effects of HT on toxicities, treatment delay, QOL, and fatigue were not observed. Long-term clinical implications of findings are not known.

Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients.

The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign ovarian neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon-gamma (IFN gamma), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4(+)) and T-cytotoxic (CD8(+)) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values<0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values<0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4(+) cells producing IFN gamma (TH(1) cells) vs. IL-4 (TH(2) cells) in all compartments (depressed mood: P=0.012; anxiety: P=0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8(+) cells producing IFN gamma (TC(1)) vs. IL-4 (TC(2)) (P=0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater impairment of adaptive immunity in peripheral blood and in the tumor microenvironment among ovarian cancer patients.

Quality of life and mental health in cervical and endometrial cancer survivors.

OBJECTIVES: The goal of this study was to examine quality of life and mood in long-term survivors of cervical and endometrial cancer. Relationships of quality of life and mood with demographic and disease factors were also investigated. METHODS: One-hundred fifty-two survivors of cervical or endometrial cancer diagnosed and treated 5-20 years ago at the University of Iowa Hospitals and Clinics participated. Eighty-nine healthy controls were recruited from a hospital gynecology clinic. Quality of life, mood, and demographics were assessed by questionnaires. Disease characteristics of cancer survivors were abstracted from medical records. RESULTS: There were no significant differences in quality of life or depressive symptoms between the three groups. Cervical cancer survivors reported significantly more anxiety than endometrial cancer survivors, and more dysphoria, anger, and confusion than either endometrial cancer survivors or healthy controls. Greater depression and mood disturbance were reported by unemployed and unmarried cancer survivors. Treatment modality, stage of disease, and length of time since diagnosis were not related to quality of life or mood. CONCLUSIONS: Quality of life in cervical and endometrial cancer survivors approximates that of healthy controls by 5 years post-diagnosis. However, cervical cancer survivors report more negative mood than survivors of endometrial cancer or healthy controls. Cancer survivors who are unemployed or living alone may be especially at risk for mood and mental health difficulties.

Coping and quality of life among women extensively treated for gynecologic cancer.

The current study examined the use of engagement and avoidant coping strategies among advanced-stage gynecologic cancer patients who were facing the long-term stressors of extensive chemotherapy and advanced disease. Patients were compared to a reference group of early-stage patients who had received more limited treatment. Compared to the reference group, extensively-treated women more frequently utilized both engagement and avoidant strategies including active coping, seeking social support, and mental disengagement. Use of engagement coping strategies such as active coping and seeking social support were not significantly related to quality of life or mood. However, avoidant coping strategies, including disengagement and cognitive avoidance, were strongly associated with poorer well-being and more distressed mood. Moreover, relationships between coping and quality of life differed between the extensively-treated patients and patients in the limited treatment reference group. The use of avoidance and seeking instrumental support were associated with poorer outcomes among extensively-treated patients but not among the limited treatment group. Results of the current study suggest that coping patterns and outcomes may be more pronounced among cancer patients contending with severe disease and extensive treatment and that avoidant coping strategies may be particularly detrimental with respect to these patients' mood and quality of life.

Cancer attributions, distress, and health practices among gynecologic cancer survivors.

OBJECTIVE: Personal beliefs about one's medical condition have been related to health behaviors and psychological distress among individuals with serious illness. We examined whether beliefs about cause of cancer and prevention of recurrence were associated with health practices and distress in 134 long-term endometrial and cervical cancer survivors. METHODS: Participants completed questionnaires assessing depressive symptoms, anxiety, health behavior, and beliefs about factors that may have caused their cancer and prevented recurrence. RESULTS: Genetics/heredity was rated as the most important cancer cause, followed by stress, God's will, hormones, and environmental factors. Medical screening was rated as most important in preventing recurrence, followed by positive attitude and prayer. Stronger causal attributions were generally associated with elevated depressive symptomatology and anxiety, but women citing potentially controllable causes were more likely to be practicing healthy behaviors. Similarly, women citing health behaviors as important in preventing recurrence reported greater anxiety but were more likely to practice positive health behaviors. Health behavior and lifestyle attributions interacted with health practices in predicting distress. For example, among women who had not made positive dietary changes, rating lifestyle as important in preventing recurrence was associated with greater distress, whereas among women who had made a positive change in diet, this belief was associated with less distress. CONCLUSIONS: Results suggest that stronger attributions are associated with greater distress, but engaging in behavior believed to be important in preventing cancer or recurrence may ameliorate this distress.

Social support, psychological distress, and natural killer cell activity in ovarian cancer.

PURPOSE: Psychosocial stress has been related to impaired immunity in cancer patients. However, the extent to which these relationships exist in immune cells in the tumor microenvironment in humans has not been explored. We examined relationships among distress, social support, and natural killer (NK) cell activity in ovarian cancer patients in peripheral-blood mononuclear cells (PBMC), ascitic fluid, and tumor-infiltrating lymphocytes (TIL). PATIENTS AND METHODS: Patients awaiting surgery for a pelvic mass suspected of being ovarian cancer completed psychological questionnaires and gave a presurgical sample of peripheral blood. Samples of tumor and ascites were taken during surgery, lymphocytes were then isolated, and NK cytotoxicity and percentage were determined. The final sample, which was confirmed by surgical diagnosis, included 42 patients with epithelial ovarian cancer and 23 patients with benign masses. RESULTS: Peripheral NK cell activity was significantly lower among ovarian cancer patients than in patients with benign masses. Among ovarian cancer patients, NK cytotoxicity in TIL was significantly lower than in PBMC or ascitic fluid. Social support was related to higher NK cytotoxicity in PBMC and TIL, adjusting for stage. Distress was related to lower NK cytotoxicity in TIL. A multivariate model indicated independent associations of both distress and social support with NK cell activity in TIL. CONCLUSION: Psychosocial factors, such as social support and distress, are associated with changes in the cellular immune response, not only in peripheral blood, but also at the tumor level. These relationships were more robust in TIL. These findings support the presence of stress influences in the tumor microenvironment.

Psychosocial factors and interleukin-6 among women with advanced ovarian cancer.

BACKGROUND: Relations among psychological stress, depression, social support, and interleukin-6 (IL-6, a proinflammatory cytokine) have been documented in humans and animals. Because elevated IL-6 is associated with a poorer prognosis among ovarian cancer patients and has been implicated in the metastasis of ovarian cancer, the current study examined relations between psychosocial factors and IL-6 among women with advanced-stage ovarian cancer. METHODS: Sixty-one ovarian cancer patients completed assessments of social support, distressed mood, and quality of life before surgery. Peripheral blood was drawn preoperatively, and the plasma was assayed for IL-6. Ascites samples were also assayed for IL-6 for a subset of patients. RESULTS: Both IL-6 levels and distressed mood were elevated among patients. After statistically adjusting effects of age and disease stage, social attachment was associated with lower levels of IL-6 in peripheral blood (P = 0.03), whereas poorer health-related quality of life was associated with higher IL-6 (P values ranged from 0.01 to 0.03 on different measures). This pattern of relations was also found in the ascites. Moreover, IL-6 levels in peripheral blood plasma correlated significantly with IL-6 in the ascites (P < 0.001), suggesting that peripheral IL-6 reflects IL-6 levels at the site of the tumor. CONCLUSIONS: Results suggest that social support may play a protective role with respect to IL-6 elevations, and IL-6 may be an independent marker of health-related quality of life among ovarian cancer patients. Processes involving IL-6 represent possible pathways by which behavioral factors may contribute to disease outcomes among women with ovarian cancer.

Vascular endothelial growth factor and social support in patients with ovarian carcinoma.

BACKGROUND: The modulation of immunologic activities relevant to cancer by behavioral factors, such as stress, depression, and social support, is well documented. However, associations of behavioral factors with cytokines involved in tumor angiogenesis have not been studied. Vascular endothelial growth factor (VEGF) is a key cytokine that is capable of stimulating tumor angiogenesis, and it has been associated with poorer survival in patients with ovarian carcinoma. VEGF is modulated by a variety of behaviorally sensitive factors, including sympathetic activation. This study examined relationships of social support and depressive symptoms with VEGF levels in preoperative patients with ovarian carcinoma. METHODS: Twenty-four women with ovarian carcinoma and 5 women with benign pelvic masses were recruited at the presurgical clinic visit, received psychosocial surveys, including the Functional Assessment of Cancer Therapy (Quality of Life) survey and the Profile of Mood States, and a blood draw. Serum VEGF levels were assessed by enzyme-linked immunosorbent assay. Analyses controlled for disease stage. RESULTS: Women with ovarian carcinoma who reported higher levels of social well being had lower levels of VEGF (P = 0.005). Greater support from friends and neighbors (P = 0.005) and less distance from friends (P = 0.04) were facets of social well being that were associated with lower VEGF levels. Individuals who reported greater helplessness (P = 0.03) or worthlessness (P = 0.08) had higher VEGF levels, but depression as a whole (P > 0.50) was not related to VEGF levels. CONCLUSIONS: Higher levels of social well being were correlated with lower VEGF levels in presurgical patients with ovarian carcinoma. These findings suggest a possible mechanism by which poor social support may be associated with disease progression. Further study of these relations may demonstrate novel pathways relating biobehavioral factors to tumor growth and disease progression.

Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer.

OBJECTIVE: To estimate the association of preoperative CA 125 levels with outcome in primary ovarian cancer patients. METHODS: One hundred forty-two patients with epithelial ovarian cancer, who had a serum CA 125 level drawn before surgery, were retrospectively evaluated. The relationship of preoperative CA 125 levels and various preoperative and postoperative variables was evaluated. CA 125 levels were determined using a solid-phase immunoassay. RESULTS: The median CA 125 value for all patients was 582 U/mL (range 7-52,930 U/mL). Preoperative CA 125 values did not correlate with increasing age (P =.40), but were found to be significantly associated with serous histology compared with other histology (median CA 125 of 870 versus 334 U/mL, P =.02), high-stage (III/IV) compared with low-stage (median CA 125 of 893 versus 174 U/mL, P <.001), high tumor grade (3) compared with grade 1 or 2 (median CA 125 of 928 versus 323 U/mL, P <.001), and the presence of ascites compared with absence of ascites (median CA 125 of 893 versus 220 U/mL, P <.001). Suboptimal cytoreduction (more than 1 cm residual) was associated with significantly higher CA 125 levels (1067 U/mL) compared with individuals with optimal cytoreduction (399 U/mL, P <.001). Preoperative CA 125 values less than 500 U/mL had a positive predictive value for optimal cytoreduction of 82%, but a poor negative predictive value of 48%. After adjusting for covariates, there was a significant association between CA 125 levels and disease-specific survival. As preoperative CA 125 levels increased, the risk of death increased except at the highest values of CA 125. CONCLUSION: Preoperative CA 125 is an independent risk factor for death due to disease in ovarian cancer, but not a reliable predictor of optimal cytoreduction.

Quality of life and mood in women with gynecologic cancer: a one year prospective study.

BACKGROUND: Quality of life (QOL) and mood were prospectively investigated during the first year of treatment among women with gynecologic cancers. Relationships of coping styles to QOL and mood were examined. METHODS: Ninety-eight patients with early stage or regionally advanced gynecologic cancers were recruited. Mood and QOL were assessed at initial clinic visit and at one year, and medical information was abstracted from charts at both time-points. RESULTS: Although decrements in physical, functional, and total well-being were reported at baseline by regionally advanced patients, by one year, all patients reported significant improvements in QOL and mood. There were no differences between early stage and regionally advanced patients in their improvement for these measures. Controlling for medical variables and age, patients who coped using greater acceptance and positive reframing at their initial visits reported better one year QOL; those with continued higher levels of these adaptive coping strategies at one year reported better concurrent functional and emotional well-being. Greater seeking of social support at one year was associated with better concurrent social well-being and doctor-patient relationships. In contrast, disengaged coping at study entry was associated with poorer doctor-patient relationships at one year; continued disengagement at one year was associated with poorer concurrent QOL and greater distress. CONCLUSIONS: During the first year following treatment, QOL and mood improved among both early stage and regionally advanced gynecologic oncology patients. Patients using disengaged coping are particularly at risk for poor QOL and distress.

Psychosomatic Aspects of Gynecologic Oncology: Present Status and Future Directions.

Among women genital malignancies are second in frequency only to breast cancer. Primary disease sites include the endometrium, cervix, ovary, and vulva. With early diagnosis and aggressive therapy, two-thirds of these women will survive for at least 5 years. This encouraging prognosis is in contrast to the distress that may be experienced by women during diagnosis, treatment, and recovery periods. A brief review of major avenues of current research and clinical work is provided, including; psychological responses to gynecologic cancer symptomatology; affective distress; sexual problems; and treatment-related distress. Areas for future investigation are highlighted, including difficulties occurring with disease recurrence; disruption of close relationships; and problems of the elderly woman with cancer.