Place-of-death preferences among patients with cancer and family caregivers in inpatient and outpatient palliative care.

OBJECTIVE: Meeting the preferences of patients is considered an important palliative care outcome. Prior studies reported that more than 80% of patients with terminally ill cancer prefer to die at home. The purpose of this study was to determine place-of-death preference among palliative care patients in the outpatient centre and the palliative care unit (PCU) of a comprehensive cancer centre. METHODS: A cross-sectional anonymous questionnaire was administered to patients with advanced cancer and caregivers (PCU and outpatient centre) between August 2012 and September 2014. PCU patients responded when there was no delirium and the primary caregiver responded when the patient was unable to respond. In the case of outpatients, dyads were assessed. The survey was repeated 1 month later. RESULTS: Overall, 65% preferred home death. There was less preference for home death among PCU patients (58%) than among outpatients (72%). Patient and caregiver agreement regarding preferred place of death for home was 86%. After 1 month, outpatients were significantly more likely than PCU patients to have the same preferred place of death as they had 1 month earlier (96% vs 83%; p=0.003). CONCLUSIONS: Although home was the preferred place of death in our group of patients with advanced cancer and their caregivers, a substantial minority preferred hospital death or had no preference. We speculate that PCU patients' higher preference for hospital death is likely related to more severe distress because they had already tried home care. Personalised assessment of place of death preference for both patient and caregiver is needed.

Edmonton Symptom Assessment Scale Time Duration of Self-Completion Versus Assisted Completion in Patients with Advanced Cancer: A Randomized Comparison.

INTRODUCTION: To compare the time duration of self-completion (SC) of the Edmonton Symptom Assessment Scale (ESAS) by patients with advanced cancer (ACPs) versus assisted completion (AC) with a health care professional. MATERIALS AND METHODS: In this randomized comparison of ACPs seen in initial consultation at the outpatient Supportive Care Center at MD Anderson, ACPs who have never completed the ESAS at MD Anderson were allocated (1:1) to either SC of the ESAS form versus AC by a nurse. Time of completion was measured by the nurse using a stopwatch. Patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) test prior to administration of the ESAS. In the SC group, the nurse reviewed the responses to verify that the reported ESAS scores were correct. RESULTS: A total of 126 ACPs were enrolled (69 patients to AC and 57 to SC). Seventy-one patients were female, median age was 60 years, and median REALM score was 65. Median (interquartile range) time (in seconds) of SC was significantly less than AC (73 [42.9-89.1] vs. 109 [79.5-136.7], p < .0001). With nurse review time included, median time of SC increased to 117 seconds, which was not significantly different from AC (p = .28). Lower literacy (REALM) score and shortness of breath were significantly associated with increased completion time (p = .007). CONCLUSION: Regular use of ESAS will have minimal impact on clinical time, as it can be completed in about 1 minute and provides a concise yet comprehensive and multidimensional perspective of symptoms that affect quality of life of patients with cancer. IMPLICATIONS FOR PRACTICE: Because the Edmonton Symptom Assessment Scale can be completed in less than 2 minutes, hopefully the routine use of this simple yet comprehensive and multidimensional symptom assessment tool will be used at all medical visits in all patients with cancer so that the timely management of symptoms affecting patients' lives and treatment courses can occur, further enhancing personalized cancer care.

Changes in the Care Setting of First Consults to Palliative and Supportive Care Over a Seven-Year Period.

CONTEXT: Optimal benefits from palliative care (PC) are achieved when first consults (PC1) occur early, in the outpatient setting. Late PC1, like those in the intensive care unit (ICU), limit these benefits. OBJECTIVES: The objective of this study was to determine the proportion of PC1 over time in the outpatient, ICU, and inpatient non-ICU settings. We also examined patients' baseline characteristics and the timing of PC access (from PC1 to death) by the setting of PC1. METHODS: We retrospectively evaluated consecutive cancer patients' records at our cancer center to ascertain the annual number of PC1 and its distribution across settings (2011-2017). ICU PC1 (n = 309) and a random sample of an equal number of outpatient and inpatient non-ICU PC1 were reviewed to retrieve patients' characteristics and death date. RESULTS: PC1 total annual number increased by 58% from 2011 (n = 2286) to 2017 (n = 3615). We found a significant decrease in the proportion of ICU PC1 (from 2.3% in 2011 to 1% in 2017, P < 0.001). There were no significant changes in the proportion of PC1 at outpatient versus inpatient settings (P = 0.2). Hematologic cancer patients were more likely to have an ICU PC1 (P < 0.001). Median survival (months) was 7.7 (6.3-9.7), 3.4 (2.4-4.5), and 0.1 (0.1-0.1) for outpatient, inpatient, and ICU, respectively (P < 0.01). CONCLUSION: PC1 total annual number has increased, and the proportion of PC1 at ICU, a very late clinical setting, is decreasing. Further efforts are needed to integrate PC in hematologic cancer care.

A Comparative Analysis of Academic and Nonacademic Hospitals on Outcome Measures and Patient Satisfaction.

Academic hospitals contribute to health care through patient care, research, and teaching; however, their outcomes may not be equivalent to nonacademic hospitals. Multivariate analysis of variance is used to compare publicly reported data on patient satisfaction, readmission rates, mortality rates, and hospital-acquired injury scores between 1906 academic and nonacademic hospitals, while controlling for hospital-level covariates. Results show that academic hospitals have higher levels of patient satisfaction on 7 of the 11 measures and are equivalent to nonacademic hospitals on the remaining 4 measures. Academic hospitals have lower pneumonia mortality rates than nonacademic hospitals, with no difference for other mortality or disease-specific readmissions. However, academic hospitals have a slightly higher overall readmission rate. Infection rates were equivalent between academic and nonacademic hospitals for central line-associated bloodstream infections, pressure ulcers, and wound dehiscence for abdominal and pelvic injuries, but academic hospitals have higher catheter-associated urinary tract infection rates.

Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain.

BACKGROUND: There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate-release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer. MATERIALS AND METHODS: In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self-administered survey. We assessed patients' baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7-point Likert scale ranging from "very ineffective" to "very effective." "Effective" and "very effective" were defined a priori as a good response to IR opioids for BTP. RESULTS: Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0-10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002). CONCLUSION: The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice. IMPLICATIONS FOR PRACTICE: Oral immediate-release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.

Patient Home Visits: Measuring Outcomes of a Community Model for Palliative Care Education.

BACKGROUND: Health care professionals may have limited exposure to home-based care. There is no published literature that has described the experiences and satisfaction of participation in patient home visits (PHV). OBJECTIVE: The objective of this article is to describe the characteristics of PHV, our approach, and evaluation by participants over a nine-year period. METHODS: We conducted a review of surveys completed by participants in PHV from 2005-2013. All participants anonymously completed the evaluation questionnaires at the end of PHVs. Different PHV assessment forms were used for the 2005-2010 and 2011-2013 time periods. RESULTS: A total of 34 PHVs were conducted with 106 patients and approximately 750 participants with a mean of 3 patients and 22 participants per PHV between 2005 and 2013. For 18 PHVs there are 317 surveys completed with 353 participants, making it a 90% response rate. Responding participants were physicians 125/543 (23%) and other professionals 418/543 (77%). In both time periods of 2005-2010 and 2011-2013 a survey with a 1 (completely agree) to 5 (completely disagree) scale was used. Agreeing that PHV was an effective teaching tool during 2005-2010 were 335/341 (98%); during 2011-2013, 191/202 (95%) agreed that PHV provided increased understanding and sharing of best practices in palliative care. CONCLUSIONS: PHV was perceived by participants as an effective way of providing interactive community education. A broad range of themes were addressed, and the participants reported high levels of learning in all domains of palliative care. There were no cases of patient or relative expression of distress as a result of PHV.

Symptom profiles in children with advanced cancer: Patient, family caregiver, and oncologist ratings.

BACKGROUND: Systematic symptom assessment is not routinely performed in pediatric oncology. The objectives of the current study were to characterize the symptoms of pediatric oncology outpatients and evaluate agreement between patient and proxy reports and the association between children's ratings and oncologists' treatment recommendations. METHODS: Two versions of the pediatric Memorial Symptom Assessment Scale (pMSAS) were translated into Spanish. An age-appropriate and language-appropriate pMSAS was administered independently before visits to the oncologist to patients and family caregivers (caregivers) and after visits to consenting oncologists. Statistical analysis included Spearman correlation coefficients and weighted kappa values. RESULTS: English and Spanish results were similar and were combined. A total of 60 children and their caregivers completed the pMSAS. The children had a median age of 10 years (range, 7-18 years); approximately 62% were male and 33% were Spanish-speaking. Fourteen oncologists completed the pMSAS for 25 patients. Nine patients (15%) had no symptoms and 38 patients (63%) reported ≥2 symptoms. The most common symptoms were fatigue (12 patients; 40%) and itch (9 patients; 30%) for the younger children and pain (15 patients; 50%) and lack of energy (13 patients; 45%) among the older children. Total and subscale score agreement varied by proxy type and subscale, ranging from fair to good for most comparisons. Agreement for individual symptoms between the patient and proxy ranged from a kappa of -0.30 (95% confidence interval, -0.43 to -0.01) to 0.91 (95% confidence interval, 0.75 to 1.00). Three of 51 symptomatic patients (6%) had treatment recommendations documented in the electronic health record. CONCLUSIONS: Symptoms are common and cross several functional domains. Proxy and child reports are often not congruent, possibly explaining apparent undertreatment among this group of patients.

Frequency and Outcome of Neuroleptic Rotation in the Management of Delirium in Patients with Advanced Cancer.

PURPOSE: The response to haloperidol as a first-line neuroleptic and the pattern of neuroleptic rotation after haloperidol failure have not been well defined in palliative care. The purpose of this study was to determine the efficacy of haloperidol as a first-line neuroleptic and the predictors associated with the need to rotate to a second neuroleptic. MATERIALS AND METHODS: We conducted a retrospective review of the charts of advanced cancer patients admitted to our acute palliative care unit between January 2012 and March 2013. Inclusion criteria were a diagnosis of delirium and first-line treatment with haloperidol. RESULTS: Among 167 patients with delirium, 128 (77%) received only haloperidol and 39 (23%) received a second neuroleptic. Ninety-one patients (71%) who received haloperidol alone improved and were discharged alive. The median initial haloperidol dose was 5 mg (interquartile ranges [IQR], 3 to 7 mg) and the median duration was 5 days (IQR, 3 to 7 days). The median final haloperidol dose was 6 mg (IQR, 5 to 7 mg). A lack of treatment efficacy was the most common reason for neuroleptic rotation (87%). Significant factors associated with neuroleptic rotation were inpatient mortality (59% vs. 29%, p=0.001), and being Caucasian (87% vs. 62%, p=0.014). Chlorpromazine was administered to 37 patients (95%) who were not treated successfully by haloperidol. The median initial chlorpromazine dose was 150 mg (IQR, 100 to 150 mg) and the median duration was 3 days (IQR, 2 to 6 days). Thirteen patients (33%) showed reduced symptoms after the second neuroleptic. CONCLUSION: Neuroleptic rotation from haloperidol was only required in 23% of patients with delirium and was associated with inpatient mortality and white race.

Avoidable and unavoidable visits to the emergency department among patients with advanced cancer receiving outpatient palliative care.

CONTEXT: Admissions to the emergency department (ED) can be distressing to patients with advanced cancer receiving palliative care. There is limited research about the clinical characteristics of these patients and whether these ED visits can be categorized as avoidable or unavoidable. OBJECTIVES: To determine the frequency of potentially avoidable ED visits (AvEDs) for patients with advanced cancer receiving outpatient palliative care in a large tertiary cancer center, identify the clinical characteristics of the patients receiving palliative care who visited the ED, and analyze the factors associated with AvEDs and unavoidable ED visits (UnAvEDs). METHODS: We randomly selected 200 advanced cancer patients receiving treatment in the outpatient palliative care clinic of a tertiary cancer center who visited the ED between January 2010 and December 2011. Visits were classified as AvED (if the problem could have been managed in the outpatient clinic or by telephone) or UnAvED. RESULTS: Forty-six (23%) of 200 ED visits were classified as AvED, and 154 (77%) of 200 ED visits were classified as UnAvED. Pain (71/200, 36%) was the most common chief complaint in both groups. Altered mental status, dyspnea, fever, and bleeding were present in the UnAvED group only. Infection, neurologic events, and cancer-related dyspnea were significantly more frequent in the UnAvED group, whereas constipation and running out of pain medications were significantly more frequent in the AvED group (P < 0.001). In a multivariate analysis, AvED was associated with nonwhite ethnicity (odds ratio [OR] 2.66; 95% CI 1.26, 5.59) and constipation (OR 17.08; 95% CI 3.76, 77.67), whereas UnAvED was associated with ED referral from the outpatient oncology or palliative care clinic (OR 0.24; 95% CI 0.06, 0.88) and the presence of baseline dyspnea (OR 0.46; 95% CI 0.21, 0.99). CONCLUSION: Nearly one-fourth of ED visits by patients with advanced cancer receiving palliative care were potentially avoidable. Proactive efforts to improve communication and support between scheduled appointments are needed.

Characteristics and outcomes of patients admitted to the acute palliative care unit from the emergency center.

CONTEXT: Most patients admitted to acute palliative care units (APCUs) are transferred from inpatient oncology units. We hypothesized that patients admitted to APCUs from emergency centers (ECs) have symptom burdens and outcomes that differ from those of transferred inpatients. OBJECTIVES: The purpose of this retrospective cohort study was to compare the symptom burdens and survival rate of patients admitted to an APCU from an EC with those of inpatients transferred to the APCU. METHODS: Among the 2568 patients admitted to our APCU between September 1, 2003 and August 31, 2008, 312 (12%) were EC patients. We randomly selected 300 inpatients transferred to the APCU as controls (The outcome data were unavailable for two patients). We retrieved data on patient demographics, cancer diagnosis, Edmonton Symptom Assessment System scores, discharge outcomes, and overall survival from time of admission to the APCU. RESULTS: The EC patients had higher rates of pain, fatigue, nausea, and insomnia and were less likely to be delirious. They were more than twice as likely to be discharged alive than transferred inpatients. Kaplan-Meier plot tests for product-limit survival estimate from admission to APCU for EC patients and inpatients were statistically significant (median survival 34 vs. 31 days, P<0.0001). In multivariate analysis, EC admission (odds ratio [OR]=1.8593, 95% confidence interval [CI] 1.1532-2.9961), dyspnea (OR=0.8533, 95% CI 0.7892-0.9211), well-being (OR=1.1192, 95% CI 1.0234-1.2257), and delirium (OR=0.3942, 95% CI 0.2443-0.6351) were independently associated with being discharged alive. CONCLUSION: The EC patients have a higher acute symptom burden and are more likely to be discharged alive than transferred inpatients. The APCU was successful at managing symptoms and facilitating the discharge of both inpatients and EC patients to the community although the patients had severe symptoms on admission.

Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial.

PURPOSE: Cancer-related-fatigue (CRF) is common in advanced cancer. The primary objective of the study was to compare the effects of methylphenidate (MP) with those of placebo (PL) on CRF as measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) fatigue subscale. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) was also assessed. PATIENTS AND METHODS: Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) were randomly assigned to one of the following four groups: MP+NTI, PL+NTI, MP + control telephone intervention (CTI), and PL+CTI. Methylphenidate dose was 5 mg every 2 hours as needed up to 20 mg per day. The primary end point was the median difference in FACIT-F fatigue at day 15. Secondary outcomes included anxiety, depression, and sleep. RESULTS: One hundred forty-one patients were evaluable. Median FACIT-F fatigue scores improved from baseline to day 15 in all groups: MP+NTI (median score, 4.5; P = .005), PL+NTI (median score, 8.0; P < .001), MP+CTI (median score, 7.0; P = .004), and PL+CTI (median score, 5.0; P = .03). However, there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups (5.5 v 6.0, respectively; P = .69) and among all four groups (P = .16). Fatigue (P < .001), nausea (P = .01), depression (P = .02), anxiety (P = .01), drowsiness (P < .001), appetite (P = .009), sleep (P < .001), and feeling of well-being (P < .001), as measured by the ESAS, significantly improved in patients who received NTI. Grade ≥ 3 adverse events did not differ between MP and PL (40 of 93 patients v 29 of 97 patients, respectively; P = .06). CONCLUSION: MP and NTI alone or combined were not superior to placebo in improving CRF.

Association between body image dissatisfaction and weight loss among patients with advanced cancer and their caregivers: a preliminary report.

CONTEXT: No prospective studies have dealt with the impact of cachexia-related weight loss on patients' body image as well as the impact of patients' body image changes on the level of patient and family distress. OBJECTIVES: Our aim was to examine associations between body mass index (BMI), weight loss, symptom distress, and body image for patients with advanced cancer and their caregivers. METHODS: Outpatients with advanced cancer and different levels of BMI, along with their caregivers, were recruited. Patient assessments included BMI, precancer weight, Body Image Scale (BIS; 0-30), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), and sexual interest and enjoyment as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Cancer Module 35. Caregivers were asked to assess the patient's body image, using the BIS; rate their own quality of life, using the Caregiver Quality of Life Index-Cancer; and rate their overall distress and distress regarding the patient's weight, using the Distress Thermometer (DT). RESULTS: We included 81 patients and 30 caregivers. Forty-eight patients (59%) experienced weight loss of at least 10%. The mean BIS score was 11.23 (SD = 7.24). Body image dissatisfaction was correlated with weight loss (r = 0.31, P = 0.006), anxiety (HADS-A; r = 0.39, P < 0.001), depression (HADS-D; r = 0.46, P < 0.001), decreased sexual interest (r = 0.37, P = 0.001), decreased sexual enjoyment (r = 0.33, P = 0.004), ESAS score for pain (r = 0.25, P = 0.026), fatigue (r = 0.28, P = 0.014), drowsiness (r = 0.28, P = 0.014), shortness of breath (r = 0.27, P = 0.016), sleep disorders (r = 0.24, P = 0.036), and well-being (r = 0.29, P = 0.011). We found a significant association between the caregivers' evaluation of patients' body image dissatisfaction and patients' BIS score (r = 0.37, P = 0.049) and caregivers' distress regarding the patients' weight (DT; r = 0.58; P = 0.001). CONCLUSION: Body image dissatisfaction was strongly associated with patients' weight loss and with psychosocial distress among patients and their caregivers. More research is necessary to better understand the association between the severity of body image dissatisfaction and the severity of other problems in patients with cancer.

Decisional control preferences of Hispanic patients with advanced cancer from the United States and Latin America.

CONTEXT: Understanding cancer patients' preferences in decisional roles is important in providing quality care and ensuring patient satisfaction. There is a lack of evidence on decisional control preferences (DCPs) of Hispanic Americans, the fastest growing population in the U.S. OBJECTIVES: The primary aims of this study were to describe DCPs of Hispanics with advanced cancer in the U.S. (HUSs) and compare the frequency of passive DCPs in this population with that of Hispanics with advanced cancer in Latin America (HLAs). METHODS: We conducted a prospective survey of patients with advanced cancer referred to outpatient palliative care clinics in the U.S., Chile, Argentina, and Guatemala. Information was collected on sociodemographic variables, Karnofsky Performance Scale scores, acculturation (Marin Acculturation Assessment Tool), and DCP (Control Preference Scale). Chi-square tests were used to determine the differences in DCPs between HUSs and HLAs. RESULTS: A total of 387 patients were surveyed: 91 in the U.S., 100 in Chile, 94 in Guatemala, and 99 in Argentina. The median age of HUSs was 56 years, 59% were female, and the median Karnofsky Performance Scale score was 60; the corresponding values for HLAs were 60 years, 60%, and 80. HLAs used passive DCP strategies significantly more frequently than HUSs did with regard to the involvement of the family (24% vs. 10%; P=0.009) or the physician (35% vs. 16%; P<0.001), even after age and education were controlled for. Eighty-three percent of HUSs and 82% of HLAs preferred family involvement in decision making (P=non-significant). No significant differences were found in DCPs between poorly and highly acculturated HUSs (P=0.91). CONCLUSION: HUSs had more active DCPs than HLAs did. Among HUSs, acculturation did not seem to play a role in DCP determination. Our findings confirm the importance of family participation for both HUSs and HLAs. However, HUSs were less likely to want family members to make decisions on their behalf.

Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial.

PURPOSE: The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer. PATIENTS AND METHODS: We randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups. RESULTS: The hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83). CONCLUSION: Hydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.

The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomized study.

OBJECTIVES: To determine the effects of thalidomide and placebo on anorexia-cachexia and its related symptoms, body composition, resting metabolic rate, and serum cytokines and their receptors in patients with advanced cancer. METHODS: Included in the study were patients with advanced cancer with weight loss greater than 5% in 6 months and who reported anorexia, fatigue, and one of the following: anxiety, depression, or sleep disturbances. Patients on chemotherapy within 2 weeks prior or during the study were excluded from the study. Patients were randomly assigned to either 100 mg thalidomide or placebo once a day for 14 days. The Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of Anorexia/Cachexia Therapy (FAACT), Functional Assessment of Cancer Illness Therapy (FACIT-F), Hospital Anxiety Depression Scale (HADS) Pittsburgh Sleep Quality Index (PSQI) were utilized, and in addition body composition, Resting Energy Expenditure (REE), and serum cytokine levels were assessed. RESULTS: Of the 31 patients entered in the study, 15 were assigned to the thalidomide group and 16 to the placebo group. However only 21/31 patients were able to complete the study. Compared with their baseline values, both the thalidomide and the placebo groups showed significant reduction in cytokines. Tumor necrosis factor (TNF)-α (p=0.04) and its receptors TNFR1 (p=0.04), TNFR2 (p=0.04), and interleukin (IL)-8 (p=0.04) were statistically significant in the thalidomide group. In the placebo group, TNF-α (p=0.008), TNFR1 (p=0.005), TNFR2 (p=0.005), IL-RA (p=0.005), IL-6 (p=0.005), and IL-8 (p=0.005) were statistically significant. However, improvement in these symptoms and cytokine levels were not significantly different in the thalidomide group compared with the placebo group. None of the patients withdrew from the study because of toxicity of either thalidomide or placebo. CONCLUSIONS: Based on the poor accrual rate and attrition observed in this study, it is important that future research on thalidomide as a treatment for cancer-related anorexia-cachexia symptoms (ACS) in patients with advanced cancer use less stringent entry criteria and less exhaustive outcome measures.

The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report.

CONTEXT: Autonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer. OBJECTIVES: The objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population. METHODS: We examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0-5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored. RESULTS: Forty-seven male patients were included in this study. Median age was 59 years (range: 20-79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1-5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). CONCLUSION: AD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on.