Timothy S. Sannes

Tai Chi Chuan: Mind-Body Practice or Exercise Intervention? Studying the Benefit for Cancer Survivors

Tai chi chuan (TCC) has been used as a mind-body practice in Asian culture for centuries to improve wellness and reduce stress and has recently received attention by researchers as an exercise intervention. A review of the English literature on research in TCC published from 1989 to 2006 identified 20 prospective, randomized, controlled clinical trials in a number of populations, including elderly participants (7 studies), patients with cardiovascular complications (3 studies), patients with chronic disease (6 studies), and patients who might gain psychological benefit from TCC practice (2 studies). However, only the studies of TCC in the elderly and 2 studies of TCC for cardiovascular disease had adequate designs and size to allow conclusions about the efficacy of TCC. Most (11 studies) were small and provided limited information on the benefit of TCC in the settings tested. There is growing awareness that cancer survivors represent a population with multiple needs related to physical deconditioning, cardiovascular disease risk, and psychological stress. TCC as an intervention may provide benefit to cancer survivors in these multiple areas of need based on its characteristics of combining aspects of meditation and aerobic exercise. However, little research has been conducted to date to determine the benefit of TCC in this population. We propose a model to study the unique characteristics of TCC compared to physical exercise that may highlight characteristic features of this mind-body intervention in cancer survivors.

NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

Cardiovascular responses to an acute psychological stressor are associated with the cortisol awakening response in individuals with chronic neck pain.

INTRODUCTION Dysregulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) is common in individuals who experience chronic psychological stress, as well as individuals with chronic pain. Changes in cortisol availability in the presence of a chronic stressor such as pain may influence the sympathetic-adrenal-medullary (SAM) system, which contributes to cardiovascular responses to stress and also exhibits altered responsiveness in the presence of pain. The purpose of this study was to investigate the relationship between HPA activity during the cortisol awakening response and cardiovascular reactivity during exposure to an acute psychological stressor in individuals with chronic neck pain. METHODS Area under the curve (AUC) of the salivary cortisol awakening response was assessed in 41 individuals with chronic neck pain aged 19-80 years (22 men, 23 women). Slopes representing the change in mean arterial pressure and heart rate during a baseline quiet sitting condition, a low stress condition with mental concentration, and a high stress condition combining mental concentration with social evaluative threat were calculated for each individual as an index of cardiovascular responsiveness to the acute stressor. Cardiovascular responses were regressed on cortisol awakening AUC and pain duration, adjusting for age and sex. RESULTS Greater mean arterial pressure (β = -0.33, p = 0.02) and heart rate responses (β = -0.41, p = 0.007) to the acute psychological stressor were associated with lower cortisol awakening responses after adjusting for age and sex. Individuals with a shorter duration of chronic pain also demonstrated a larger increase in mean arterial pressure during the laboratory stressor (β = -0.39, p = 0.01), but there was no relationship between pain duration and changes in heart rate (p = 0.25). CONCLUSIONS Individuals with a shorter duration of chronic neck pain who demonstrate heightened cardiovascular responsiveness to an acute psychological stressor also exhibit lower cortisol awakening response. These results are consistent with time-dependent adaptations across the two major stress systems in the presence of chronic pain.

Cognitive Behavioral Stress Management for Healthy Women at Risk for Breast Cancer: a Novel Application of a Proven Intervention

BackgroundWomen at risk for breast cancer report elevated psychological distress, which has been adversely associated with cancer-relevant behaviors and biology.PurposeThe present study sought to examine the effects of a 10-week cognitive behavioral stress management (CBSM) group intervention on distress among women with a family history of breast cancer.MethodsParticipants were randomly assigned to CBSM (N = 82) or a wait-list comparison group (N = 76). Baseline to postintervention effects of CBSM on depressive symptoms and perceived stress were examined using hierarchical regression.ResultsCBSM participants reported significantly lower posttreatment depressive symptoms (β = −0.17, p < 0.05) and perceived stress (β = −0.23, p < 0.05) than wait-list comparison participants. Additionally, greater relaxation practice predicted lower distress.ConclusionsGroup-based CBSM intervention is feasible and can reduce psychological distress among women with a family history of breast cancer. The present findings represent an encouraging avenue for the future application of CBSM. (Clinicaltrials.gov number NCT00121160)

Depressive symptoms and cortisol variability prior to surgery for suspected endometrial cancer.

Endometrial cancer (EC) is the most common type of gynecologic cancer affecting women; however, very little research has examined relationships between psychological factors and hypothalamic-pituitary-adrenal (HPA) axis dysregulation in this population. The current study examined relations between depressive/anxious symptoms and salivary cortisol diurnal rhythm and variability in women undergoing surgery for suspected endometrial cancer. Depressive and anxious symptoms were measured prior to surgery using the Structured Interview Guide for the Hamilton Depression Inventory (SIGH-AD). Saliva was collected four times a day for the 3 days prior to surgery and then assayed by ELISA to obtain cortisol concentrations. Cortisol slopes and intraindividual variability were then calculated across subjects. Relations between depressive/anxious symptoms and cortisol indices were examined using multilevel modeling and linear regression analyses. Participants were 82 women with nonmetastatic endometrial cancer. Anxious symptoms were not associated with either cortisol slope or intraindividual variability, and depressive symptoms were unrelated to cortisol slope. However, after controlling for presence of poorer prognosis cancer subtypes, greater depressive symptoms (excluding symptoms possibly/definitely due to health/treatment factors) in the week preceding surgery were significantly related to greater cortisol intraindividual variability (β=.214; p<.05). These results suggest that depressive symptoms prior to surgery for suspected endometrial cancer are related to greater cortisol intraindividual variability, which is suggestive of more erratic HPA axis arousal. Future research should examine whether mood symptoms may be associated with compromised health outcomes via erratic HPA axis arousal in this population.

Intraindividual Cortisol Variability and Psychological Functioning in Caregivers of Hematopoietic Stem Cell Transplant Patients.

Objective Caregiving for allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients carries a significant psychological burden, yet it remains unclear whether Allo-HSCT caregivers demonstrate disruptions to stress systems, such as the hypothalamic-pituitary-adrenal axis. Greater intraindividual cortisol variability (ICV) has been observed in psychiatric disorders; however, there is a knowledge gap evaluating ICV in caregivers. We predicted that greater ICV would be related to poorer mental health in Allo-HSCT caregivers. Methods Allo-HSCT caregivers (n = 140) collected saliva for 3 consecutive days at 4 time points/d. Psychological variables included sleep quality and a summary composite score of overall mental health. Results Regression analyses demonstrated that greater ICV was significantly related to poorer overall mental health (&bgr; = 0.25, p = .009), whereas poorer sleep did not reach significance (&bgr; = 0.16, p = .069). No significant relationships emerged for the cortisol area under the curve, diurnal decline, or awakening response. Conclusions Results extend prior work examining ICV as a unique marker that is possibly more sensitive than other widely applied measures of hypothalamic-pituitary-adrenal axis dysregulation to a distressed population of caregivers.

Distress and quality of life in patient and caregiver dyads facing stem cell transplant: identifying overlap and unique contributions

PurposeAllogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a demanding treatment requiring caregiver support. The pre-transplant period is particularly stressful. How patient and caregiver dyads respond to these stressors can impact post-transplant outcomes. The purpose of this cross-sectional study was to assess pre-transplant patient and caregiver distress, patient quality of life (pQoL), and simultaneously investigate relationship between caregiver distress, patient distress, and patient QoL.MethodsWe measured caregiver anxiety, depressive symptoms, perceived stress, sleep quality, caregiver burden, and pQoL in148 dyads compared to clinical thresholds or population norms. To reduce comparisons, we created a composite distress score from affective measures. Associations within dyads were examined via correlation and path analysis.ResultsMost dyads scored above norms for psychological measures. Patient distress was positively associated with caregiver distress. Higher caregiver distress significantly predicted poorer pQoL after accounting for the interdependence of patient and caregiver distress. Specifically, patients’ physical functioning was the primary driver of this interrelationship.ConclusionsAllo-HSCT patients and their caregivers reported elevated distress pre-transplant. Both patient and caregiver distress contributed to pQoL, with patients’ physical functioning accounting significantly for caregiver well-being. Supporting the patient-caregiver dyad before transplantation is a priority for supportive services.

Physician Bias in Prophylactic Cranial Irradiation Decision Making—An Opportunity for a Patient Decision Aid

&NA; Patients with limited‐stage small‐cell lung cancer have a complex value‐laden decision to make when weighing the potential small survival benefit of prophylactic cranial irradiation with the risks of neurocognitive toxicity. Herein, we explore the role physicians play in patient decision making and introduce a patient decision aid to potentially facilitate these discussions. Introduction: Guidelines have recommended prophylactic cranial irradiation (PCI) for patients with limited‐stage small‐cell lung cancer with at least a partial response after thoracic chemoradiation. However, the survival advantage has been small and was observed in an era before magnetic resonance imaging and surveillance. Neurotoxicity also remains a concern, especially in older adults. Thus, patients have a complex value‐laden decision to make. We sought to better understand the role physicians play in patient decision making and introduce a patient decision aid (PDA) to potentially facilitate these discussions. Materials and Methods: An e‐mail survey was sent to International Association for the Study of Lung Cancer members querying their personal perspectives and professional recommendations regarding PCI for limited‐stage small‐cell lung cancer. Results: We received 295 responses. Most were from the United States (35%) and Europe (35%) and were radiation (45%) or medical (43%) oncologists. Of those responding, 88% and 50% reported they would recommend PCI to a 50‐ and 70‐year‐old patient, respectively. Also, 79% reported that they would wish to receive PCI if faced with this decision. The physicians who would have chosen PCI if faced with the decision were 27.6 and 12.9 times more likely to recommend PCI to a 50‐ and 70‐year‐old patient, respectively, than were physicians who would not undergo PCI themselves. Most of the respondents had positive responses to the proposed PDA. Conclusion: Physician bias appears to play a role in PCI counseling, and most physicians reported that the provided PDA was better than their present method for discussing PCI and would help patients make such value‐laden choices.

Erratum: NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors (Evidence-based Complementary and Alternative Medicine)

1 The Cancer Team at Bellin Health, 1580 Commanche Avenue, Green Bay, WI 54313, USA 2National Center for Complementary and Alternative Medicine, NIH, Bethesda, MD 20892, USA 3 Samueli Institute, Alexandria, VA 22314, USA 4Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32611, USA 5University of Miami, Miami, FL 33124, USA 6Research Service (151), Veterans Affairs Medical Center and Department of Medicine, Georgetown University School of Medicine, Washington, DC 20422, USA 7University of Nebraska Medical Center, Omaha, NE 68198, USA 8Washington Cancer Institute, Washington Hospital Center, Washington, DC 20010, USA 9Department of Medicine, Hematology and Medical Oncology Division, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA