Coping Strategies and Associated Symptom Burden Among Patients With Advanced Cancer.

BACKGROUND: Few studies examine how patients with advanced cancer cope with stress. The objective of our study was to evaluate coping strategies adopted by patients with cancer and their relationship with symptom burden. METHODS: A secondary data analysis of a prospective cross-sectional survey of patients with cancer and tobacco use was conducted, which examined demographics, symptom burden (Edmonton Symptom Assessment System), and coping strategies (the Brief COPE Questionnaire). Demographic characteristics were summarized by standard summary statistics; we also examined associations between patient characteristics and coping strategies using t-test, rank-sum test, chi-squared test, or Fisher's exact test depending on the distribution of data. RESULTS: Among 399 patients, the majority were female (60%), Caucasian (70%), the mean age was 56.5 (±12.0) years, and the most common malignancies were gastrointestinal (21%) and breast (19%). Patients with cancer adopted multiple adaptive coping strategies, most frequently acceptance (86.7%) and emotional support (79.9%), with humor (18.5%) being the least. Common maladaptive strategies included venting (14.5%) and self-distraction (36.6%), while substance use (1.0%) was infrequently reported. Of the adaptive strategies, female gender was significantly associated with higher engagement with emotional and instrumental support, positive reframing, religious coping, and acceptance (P < .05 for all). College educated patients reported significantly higher implementation of humor, planning, and acceptance. Maladaptive coping strategies such as denial were associated with increased pain and depression, while patients adopting emotional-focused strategies rated decreased emotional distress. CONCLUSIONS: The majority of patients with advanced cancer reported adopting multiple, adaptive coping strategies, and a minority utilized maladaptive or avoidant strategies, rarely substance use, and may need additional psychological support.

Anamorelin for the Treatment of Cancer Anorexia-Cachexia Syndrome.

PURPOSE OF REVIEW: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. RECENT FINDINGS: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence.

Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): a parallel-group, double-blind, randomised, controlled trial.

BACKGROUND: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea. METHODS: The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4-6 vs 7-10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed. FINDINGS: Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was -1·6 (95% CI -2·0 to -1·2) in the dexamethasone group and -1·6 (-2·3 to -0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI -0·8 to 0·7]; p=0·48). The most common all-cause grade 3-4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group. INTERPRETATION: High-dose dexamethasone did not improve dyspnoea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnoea. FUNDING: US National Cancer Institute.

Supportive care for the prevention of nausea, vomiting and anorexia in a phase 1B study of selinexor in advanced cancer patients: an exploratory study.

INTRODUCTION: Clinical observations of cancer patients treated with selinexor have reported high incidence of nausea and anorexia. The study objective was to investigate the adoption of prophylactic olanzapine for the prevention of nausea, vomiting and anorexia in cancer patients receiving selinexor and standard chemotherapy. METHODS: We retrospectively reviewed supportive care interventions in patients receiving selinexor and recorded frequency of adverse events (NCI-CTAE). Association between categorical variables were analyzed using Fisher's exact tests; repeated measures analysis was performed to assess weight changes over time. RESULTS: Of 124 evaluable patients, 83 (66.9%) were female, 93 were white (75.0%), and the most common cancer was ovarian (N = 30, 24.2%). One hundred and four patients (83.9%) received olanzapine, of which 93 (89.4%) were prophylactically treated, the majority (86.5%) receiving low 2.5 mg daily dose. Other anti-emetics included ondansetron in 90 patients (72.6%), dexamethasone prescribed in 50 patients (40.3%) and metoclopramide in 49 patients (39.5%), while aprepitant/fosaprepitant (N = 2, 1.6%) were prescribed infrequently. Cancer patients receiving prophylactic olanzapine (N = 93) compared to patients who never received olanzapine (N = 20) had more Grade 1 + anorexia (31.2% vs 20.0%), less nausea (53.8% vs 70.0%), less vomiting (33.3% vs 40.0%), and increased hyperglycemia (29.0% vs 10.0%), but differences were non-statistically significant. In addition, there was minimal weight loss over time in both groups and no statistically significant differences in weight loss between groups. CONCLUSION: Prophylactic olanzapine decreased nausea, vomiting and maintained weight over 3 months but did not prevent anorexia in patients receiving selinexor and chemotherapy. Low dose olanzapine was well tolerated but associated with hyperglycemia.

Anamorelin combined with physical activity, and nutritional counseling for cancer-related fatigue: a preliminary study.

PURPOSE: Cancer-related fatigue (CRF) is the most frequent and debilitating symptom in patients with advanced cancer. There are limited effective treatments for CRF. The objective of this prospective longitudinal study was to evaluate the change in CRF at Day 43 after treatment with combination therapy of oral Anamorelin 100 mg daily with physical activity and nutrition counseling. METHODS: In this study, patients with CRF [≤ 34 Functional Assessment of Chronic Illness Therapy-Fatigue subscales(FACIT-F)] received Anamorelin 100 mg orally daily with standardized physical activity and nutrition counseling for 43 days. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Anorexia Cachexia(FAACT-ACS), Multidimensional Fatigue Symptom Inventory-Short Form(MFSI-SF), Patient-Reported Outcomes Measurement Information System(PROMIS-Fatigue), body composition, and physical performance tests were assessed at baseline, Day 15, 29, and 43. Frequency and type of side effects were determined by NCI CTAE 4.0.(NCT03035409). RESULTS: 28/45 (62%) of patients dosed were evaluable at Day 43. The mean, SD for FACIT-F subscale improvement from baseline was 4.89 (± 13.07), P = .058, MFSI-SF (G) - 3.46 (± 6.86), P = 0.013, PROMIS-fatigue - 4.14 (± 7.88), P = 0.010, FAACT ACS 3.48 (± 8.13), P = 0.035. Godin Liesure-Time physical activity questionnaire 7.41 (± 16.50), P = 0.038. Weight (kg) 1.81 (± 2.63), P = 0.005, and Lean Body Mass 1.54 (± 1.85), P = 0.001, IGF-1 36.50 (± 48.76), P = 0.015. There was no significant improvement in physical performance outcomes. No adverse events > grade 3 related to the study drug were reported. CONCLUSION: The use of the combination therapy was associated with improvement of CRF (FACIT-F fatigue, PROMIS-fatigue, MFSI-SF-general), activity (Godin-leisure time), anorexia (FAACT), body composition, and IGF-1 levels. Further studies using combination therapy for CRF are justified.

Oncology patients' perception of physicians who use an integrated electronic health record (EHR) during clinic visits: PRIME-EHR double-blind, randomized controlled trial.

BACKGROUND: Patients with cancer prefer and positively perceive physicians who communicate face-to-face without the use of a computer. However, the use of electronic health records (EHRs) in the examination room remains a practical necessity. On the basis of existing literature, the authors developed and tested an integration model, PRIME-EHR, that focuses on the best-practice guidelines. To their knowledge, no randomized controlled trials (RCTs) have been conducted to test the effectiveness of such models. METHODS: In this double-blind, crossover RCT, 120 eligible patients with cancer were enrolled between April 1, 2019 and February 15, 2020 at The University of Texas MD Anderson Cancer Center. The objectives were to compare patients' perceptions of physicians' skills and their overall preference after they watched 2 standardized, scripted video vignettes of physicians: 1 portraying the use of a standard EHR and the other portraying the use of a PRIME-EHR. Actors and patients were blinded to the purpose of the study. Investigators were blinded to the sequence of videos watched by the patients. Validated questionnaires to rate physicians' compassion (0 = best, 50 = worst), communication skills (14 = poor, 70 = excellent), and professionalism (4 = poor, 20 = very good) were used. RESULTS: PRIME-EHR, compared with the standard EHR, resulted in better scores for physician compassion (median score, 5 [interquartile range, 0-10] vs 12 [interquartile range, 4-25]; P = .0009), communication skills (median score, 69 [interquartile range, 63-70] vs 61 [interquartile range, 50-69]; P = .0026), and professionalism (median score, 20 [interquartile range, 18-20] vs 18 [interquartile range, 14-20]; P = .0058). The majority of patients preferred physicians who used PRIME-EHR (n = 70 [77%] vs n = 21 [23%]; P < .0001). CONCLUSIONS: The PRIME-EHR approach significantly improved patients' perceptions of and preference for the physicians. This integrated model of health care delivery has the potential to improve communication and compassion in cancer care.

Random urine drug testing among patients receiving opioid therapy for cancer pain.

BACKGROUND: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics. METHODS: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU. RESULTS: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01). CONCLUSIONS: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.

Acupuncture for Cancer-Related Anorexia: a Review of the Current Evidence.

PURPOSE OF REVIEW: Loss of appetite/anorexia is extremely common among cancer patients, affecting as many as half of newly diagnosed patients and 70% of patients with advanced disease. Effective management of this disabling symptom of cancer remains a major challenge in the field of oncology. We conducted a systematic review of the current evidence on acupuncture and/or moxibustion as an intervention for cancer-related anorexia. RECENT FINDINGS: Acupuncture, as a part of traditional Chinese medicine practice, has demonstrated effectiveness in managing many cancer- and treatment-related symptoms, especially chemotherapy-induced or postoperative nausea. However, the efficacy of acupuncture in treating cancer-related anorexia/loss of appetite is not clear. The current level of evidence is insufficient to make a definitive conclusion on the benefit of acupuncture/moxibustion for treating chronic cancer-related anorexia/appetite problems. Future large randomized controlled trials of high methodological quality are needed.

Predicting survival in patients with advanced cancer in the last weeks of life: How accurate are prognostic models compared to clinicians' estimates?

BACKGROUND: It is unclear if validated prognostic scores such as the Palliative Performance Scale, Palliative Prognostic Index, and Palliative Prognostic Score are more accurate than clinician prediction of survival in patients admitted to an acute palliative care unit with only days of survival. AIM: We compared the prognostic accuracy of Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival in this setting. DESIGN: This is a pre-planned secondary analysis of a prospective study. SETTING/PARTICIPANTS: We assessed Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival at baseline. We computed their prognostic accuracy using the Concordance index and area under the receiver operating characteristics curve for 7-, 14-, and 30-day survival. RESULTS: A total of 204 patients were included with a median overall survival of 10 days (95% confidence interval: 8-11 days). The Concordance index for Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival were 0.74, 0.71, 0.70, and 0.75, respectively. The areas under the curve for these approaches were 0.82-0.87 for 30-day survival, 0.75-0.80 for 14-day survival, and 0.74-0.81 for 7-day survival. The four prognostic approaches had similar accuracies, with the exception of 7-day survival in which clinician prediction of survival was significantly more accurate than Palliative Prognostic Score (difference: 7%) and Palliative Prognostic Index (difference: 8%). CONCLUSION: In patients with advanced cancer with days of survival, clinician prediction of survival and Palliative Performance Scale alone were as accurate as Palliative Prognostic Score and Palliative Prognostic Index. These four approaches may be useful for prognostication in acute palliative care units. Our findings highlight how patient population may impact the accuracy of prognostic scores.

Association between tobacco use, pain expression, and coping strategies among patients with advanced cancer.

BACKGROUND: The objective of the current study was to evaluate the association between tobacco use, symptom expression, and coping strategies in patients with advanced cancer. METHODS: The authors prospectively enrolled patients with advanced cancer and collected data regarding patient demographics, cancer diagnosis, morphine equivalent daily dose, cigarette smoking status using the Behavioral Risk Factor Surveillance System, symptom expression as measured by the Edmonton Symptom Assessment System, the Cut down/Annoyed/Guilty/Eye opener alcoholism questionnaire, the Screener and Opioid Assessment for Patients with Pain-short form survey, and the Brief COPE Questionnaire. RESULTS: Among 399 patients, 195 (49%) were never-smokers, 158 (40%) were former smokers, and 46 (11%) were current smokers. The most common malignancies were gastrointestinal (21%) and breast (19%). Current smokers demonstrated significantly higher pain scores at the time of consultation compared with former or never-smokers (mean 6.4 vs 5.9 vs 5.1, respectively; P = .015), demonstrated increased morphine equivalent daily dose (median 90 mg/day vs 60 mg/day vs 50 mg/day, respectively; P = .002), were more likely to screen as positive on the Cut down/Annoyed/Guilty/Eye opener questionnaire (33% vs 24% vs 8.7%, respectively; P < .0001) and were more likely to screen as positive (≥4) on the Screener and Opioid Assessment for Patients with Pain-short form survey (74% vs 13% vs 9.3%, respectively; P < .0001). Compared with former and never-smokers, current smokers were significantly more likely to cope maladaptively with substance use (P = .02), denial (P = .007), and self-blame (P < .0001). CONCLUSIONS: Among patients with advanced cancer, current and former smokers appear to be significantly more likely to have higher pain expression and thus require higher opioid doses, and to have more risk factors for using opioids in a nonprescribed manner. The results of the current study highlight the need to provide closer monitoring and increased psychosocial support for patients with cancer who smoke while receiving chronic opioid therapy.

Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic.

BACKGROUND: The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer. METHODS: Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group. RESULTS: In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well-being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5 mg/day [interquartile range (IQR), 30-135 mg/day] vs 60 mg/day [IQR, 30-105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use. CONCLUSIONS: The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.

The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium.

BACKGROUND: The Richmond Agitation-Sedation Scale (RASS) is commonly used to assess psychomotor activity; however, to the authors' knowledge, its minimal clinically important difference (MCID) has not been determined to date. The objective of the current study was to identify the MCID for RASS using 2 anchor-based approaches. METHODS: The current study was a secondary analysis of a randomized controlled trial to compare the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium. The primary outcome was change in RASS (10-point numeric rating scale ranging from -5 [unarousable] to +4 [combative]) from baseline to 8 hours after treatment administration. The sensitivity-specificity and within-patient change methods were used to identify the MCID, with the anchor being patient comfort after the study intervention as perceived by caregivers and nurses. RESULTS: A total of 90 patients were randomized and 58 (64%) received the study medication for restlessness/agitation (mean baseline RASS, 1.6). A total of 23 caregivers (61%) and 23 nurses (55%) perceived that the patient was more comfortable after treatment. Using the sensitivity-specificity method, the optimal RASS reduction was ≥4 points according to both caregivers (sensitivity of 61% and specificity of 80%; area under the curve, 0.71) and nurses (sensitivity of 73% and specificity of 84%; area under the curve, 0.78). The RASS cutoff value based on the within-patient change method was similar (-4.2 for caregivers and -4.0 for nurses). CONCLUSIONS: For patients with persistent restlessness/agitation, a reduction of ≥4 points in RASS was considered to be the MCID for both nurses and caregivers. These preliminary findings may have implications for sample size calculation and the interpretation of treatment effect in future delirium trials. Cancer 2018;124:2246-52. © 2018 American Cancer Society.

The Evolving Approach to Management of Cancer Cachexia.

Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not reversible by increasing caloric intake. The pathophysiology of cancer cachexia is complex and includes symptoms that impact caloric intake, as well as chronic inflammation, hypermetabolism, and hormonal alterations. Cancer patients require routine screening for cachexia and, ideally, interventions should be initiated in the early stages of weight loss. No guidelines exist for the treatment of cancer cachexia. Appetite stimulants, such as megestrol acetate and glucocorticoids, have been shown to increase appetite and weight; however, single pharmaceutical interventions alone for cachexia do not result in meaningful functional outcomes. In the future, clinicians should consider multimodality treatment that is personalized for each patient. These interventions would include nutritional counseling, assessing and treating symptoms that have an impact on caloric intake, and a rational combination of pharmacologic approaches directed at underlying pathophysiology. Use of an appetite stimulant could be considered for patients who exhibit decreased appetite. Treatment with an anti-inflammatory agent should be considered for patients with elevated C-reactive protein, and hormonal alterations resulting from anti-cachexia therapy should be thoughtfully addressed.

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients.

BACKGROUND: Transdermal fentanyl (TDF) is 1 of the most common opioids prescribed to patients with cancer. However, the accurate opioid rotation ratio (ORR) from other opioids to TDF is unknown, and various currently used methods result in wide variation of the ORR. The objective of this study was to determine the ORR of the oral morphine equivalent daily dose (MEDD) to the TDF dose when correcting for the MEDD of breakthrough opioids (the net MEDD) in cancer outpatients. METHODS: The records of 6790 consecutive patients were reviewed at the authors' supportive care center from 2010 to 2013 to identify those who underwent rotation from other opioids to TDF. Data regarding Edmonton Symptom Assessment Scale scores and MEDDs were collected for patients who returned for a follow-up visit within 5 weeks. Linear regression analysis was used to estimate the ORR between the TDF dose and the net MEDD (the MEDD before opioid rotation [OR] minus the MEDD of the breakthrough opioid used along with TDF after OR). RESULTS: In total, 129 patients underwent OR from other opioids to TDF. The mean patient age was 56 years, 59% were men, and 88% had advanced cancer. Uncontrolled pain (80%) was the most frequent reason for OR. In 101 patients who underwent OR and had no worsening of pain at follow-up, the median ORR from net MEDD to TDF (in mg per day) was 0.01 (range, -0.02 to 0.04), and the correlation coefficient of the TDF dose to the net MEDD was 0.77 (P < .0001). The ORR was not significantly impacted by body mass index or serum albumin. The ORR of 0.01 suggests that an MEDD of 100 mg is equivalent to 1 mg TDF daily or approximately 40 micrograms per hour of TDF (1000 micrograms/24 hours). CONCLUSIONS: The median ORR from MEDD to TDF in mg per day was 0.01. These results warrant further studies.

Use of Palliative Care Services in a Tertiary Cancer Center.

BACKGROUND: Despite increasing prevalence of palliative care (PC) services in cancer centers, most referrals to the service occur exceedingly late in the illness trajectory. Over the years, we have made several attempts to promote earlier patient access to our PC program, such as changing the name of our service from PC to supportive care (SC). This study was conducted to determine the use of PC/SC service over the past 8 years. METHODS: We reviewed billing data for all PC/SC encounters. We examined five metrics for use: inpatient consultations as a percentage of hospital admissions, ratio of inpatient consultations to average number of operational beds, time from hospital registration to outpatient consultation, time from advanced cancer diagnosis to consultation, and time from first outpatient consultation to death/last follow-up. RESULTS: Over the years, we found a consistent increase in patient referrals to the PC/SC program. In the inpatient setting, we found approximate doubling of the inpatient consultations as a percentage of hospital admissions and the ratio of inpatient consultations to hospital beds (from 10% to 19% and from 2.4 to 4.9, respectively; p < .001). In the outpatient setting, we observed variations in referral pattern between oncology services, but, overall, the time from consultation to death/last follow-up increased from 4.8 months to 7.9 months (p = .001), which was accompanied by a significant decrease in the interval to consultation from hospital registration and advanced cancer diagnosis (p < .001). CONCLUSION: We have observed a consistent annual increase in new patient referrals as well as earlier access for outpatient referrals to our SC service, supporting increased use of palliative care at our cancer center. IMPLICATIONS FOR PRACTICE: In response to accumulating evidence on the benefits of palliative care (PC) referral to oncology patients, efforts are being made to increase PC use. This study, conducted at MD Anderson Cancer Center, demonstrates consistent annual growth in PC referrals, which was accompanied by a significant increase in the outpatient referral of patients with nonadvanced cancer and earlier referral of those with advanced cancer. However, significant variations in the referral patterns between oncology services were observed. These results have implications for other cancer centers looking to enhance use of PC services by having a business model that allows for appropriate space and staff expansion.

Acute symptomatic complications among patients with advanced cancer admitted to acute palliative care units: A prospective observational study.

BACKGROUND: Limited information is available on the symptomatic complications that occur in the last days of life. AIM: We documented the frequency, clinical course, and survival for 25 symptomatic complications among patients admitted to acute palliative care units. DESIGN: Prospective longitudinal observational study. MEASUREMENTS: Their attending physician completed a daily structured assessment of symptomatic complications from admission to discharge or death. SETTING/PARTICIPANTS: We enrolled consecutive advanced cancer patients admitted to acute palliative care units at MD Anderson Cancer Center, USA, and Barretos Cancer Hospital, Brazil. RESULTS: A total of 352 patients were enrolled (MD Anderson Cancer Center = 151, Barretos Cancer Hospital = 201). Delirium, pneumonia, and bowel obstruction were the most common complications, occurring in 43%, 20%, and 16% of patients on admission, and 70%, 46%, and 35% during the entire acute palliative care unit stay, respectively. Symptomatic improvement for delirium (36/246, 15%), pneumonia (52/161, 32%), and bowel obstruction (41/124, 33%) was low. Survival analysis revealed that delirium (p < 0.001), pneumonia (p = 0.003), peritonitis (p = 0.03), metabolic acidosis (p < 0.001), and upper gastrointestinal bleed (p = 0.03) were associated with worse survival. Greater number of symptomatic complications on admission was also associated with poorer survival (p < 0.001). CONCLUSION: Symptomatic complications were common in cancer patients admitted to acute palliative care units, often do not resolve completely, and were associated with a poor prognosis despite active medical management.

Impact of timing and setting of palliative care referral on quality of end-of-life care in cancer patients.

BACKGROUND: Limited data are available on how the timing and setting of palliative care (PC) referral can affect end-of-life care. In this retrospective cohort study, the authors examined how the timing and setting of PC referral were associated with the quality of end-of-life care. METHODS: All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had a PC consultation were included. Data were retrieved on PC referral and quality of end-of-life care indicators. RESULTS: Among 366 decedents, 120 (33%) had an early PC referral (>3 months before death), and 169 (46%) were first seen as outpatients. Earlier PC referral was associated with fewer emergency room visits (39% vs 68%; P<.001), fewer hospitalizations (48% vs 81%; P<.003), and fewer hospital deaths (17% vs 31%; P5.004) in the last 30 days of life. Similarly, outpatient PC referral was associated with fewer emergency room visits (48% vs 68%; P<.001), fewer hospital admissions (52% vs 86%; P<.001), fewer hospital deaths (18% vs 34%; P5.001), and fewer intensive care unit admissions (4% vs 14%; P5.001). In multivariate analysis, outpatient PC referral (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.28-0.66; P<.001) was independently associated with less aggressive end-of-life care. Men (OR, 1.63; 95% CI, 1.06-2.50; P5.03) and hematologic malignancies (OR, 2.57; 95% CI, 1.18-5.59; P5.02) were associated with more aggressive end-of-life care. CONCLUSIONS: Patients who were referred to outpatient PC had improved end-of-life care compared with those who received inpatient PC. The current findings support the need to increase the availability of PC clinics and to streamline the process of early referral.

Phase angle for prognostication of survival in patients with advanced cancer: preliminary findings.

BACKGROUND: Accurate survival prediction is essential for decision-making in cancer therapies and care planning. Objective physiologic measures may improve the accuracy of prognostication. In this prospective study, the authors determined the association of phase angle, handgrip strength, and maximal inspiratory pressure with overall survival in patients with advanced cancer. METHODS: Hospitalized patients with advanced cancer who were seen by palliative care specialists for consultation were enrolled. Information regarding phase angle, handgrip strength, maximal inspiratory pressure, and known prognostic factors including the Palliative Prognostic Score, Palliative Prognostic Index, serum albumin, and body composition was collected. Univariate and multivariate survival analysis were performed, and the correlation between phase angle and other prognostic variables was examined. RESULTS: A total of 222 patients were enrolled. The average age of the patients was 55 years (range, 22 years-79 years); 59% of the patients were female, with a mean Karnofsky performance status of 55 and a median overall survival of 106 days (95% confidence interval [95% CI], 71 days-128 days). The median survival for patients with phase angle 2 to 2.9°, 3 to 3.9°, 4 to 4.9°, 5 to 5.9° and ≥ 6° was 35 days, 54 days, 112 days, 134 days, and 220 days, respectively (P = .001). On multivariate analysis, phase angle (hazards ratio [HR], 0.86-per degree increase; 95% CI, 0.74-0.99 increase [P = .04]), Palliative Prognostic Score (HR, 1.07; 95% CI, 1.02-1.13 [P = .008]), serum albumin (HR, 0.67; 95% CI, 0.50-0.91 [P = .009]), and fat-free mass (HR, 0.98; 95% CI, 0.96-0.99 [P = .02]) were found to be significantly associated with survival. Phase angle was found to be only weakly (γ < 0.4) associated with other prognostic variables. CONCLUSIONS: Phase angle was found to be a novel predictor of poor survival, independent of established prognostic factors, in the advanced cancer setting. This objective and noninvasive tool may be useful for bedside prognostication.

Association between hypogonadism, symptom burden, and survival in male patients with advanced cancer.

BACKGROUND: A high frequency of hypogonadism has been reported in male patients with advanced cancer. The current study was performed to evaluate the association between low testosterone levels, symptom burden, and survival in male patients with cancer. METHODS: Of 131 consecutive male patients with cancer, 119 (91%) had an endocrine evaluation of total (TT), free (FT), and bioavailable testosterone (BT); high-sensitivity C-reactive protein (CRP); vitamin B12; thyroid-stimulating hormone; 25-hydroxy vitamin D; and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. The authors examined the correlation using the Spearman test and survival with the log-rank test and Cox regression analysis. RESULTS: The median age of the patients was 64 years; the majority of patients were white (85 patients; 71%). The median TT level was 209 ng/dL (normal: ≥ 200 ng/dL), the median FT was 4.4 ng/dL (normal: ≥ 9 ng/dL), and the median BT was 22.0 ng/dL (normal: ≥ 61 ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (P ≤ .04), poor Eastern Cooperative Oncology Group performance status (P ≤ .05), weight loss (P ≤ .01), and opioid use (P ≤ .005). Low TT and FT were associated with increased anxiety (P ≤ .04), a decreased feeling of well-being (P ≤ .04), and increased dyspnea (P ≤ .05), whereas low BT was only found to be associated with anorexia (P = .05). Decreased TT, FT, and BT values were all found to be significantly associated with elevated CRP and low albumin and hemoglobin. On multivariate analysis, decreased survival was associated with low TT (hazards ratio [HR], 1.66; P = .034), declining Eastern Cooperative Oncology Group performance status (HR, 1.55; P = .004), high CRP (HR, 3.28; P < .001), and decreased albumin (HR, 2.52; P < .001). CONCLUSIONS: In male patients with cancer, low testosterone levels were associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival. A high frequency of hypogonadism has been reported in male patients with advanced cancer. In the current study, an increased symptom burden, systemic inflammation, weight loss, opioid use, and poor survival were found to be associated with decreased testosterone levels in male patients with cancer. Cancer 2014;120:1586-1593. © 2014 American Cancer Society.

Clinical signs of impending death in cancer patients.

BACKGROUND: The physical signs of impending death have not been well characterized in cancer patients. A better understanding of these signs may improve the ability of clinicians to diagnose impending death. We examined the frequency and onset of 10 bedside physical signs and their diagnostic performance for impending death. METHODS: We systematically documented 10 physical signs every 12 hours from admission to death or discharge in 357 consecutive patients with advanced cancer admitted to two acute palliative care units. We examined the frequency and median onset of each sign from death backward and calculated their likelihood ratios (LRs) associated with death within 3 days. RESULTS: In total, 203 of 357 patients (52 of 151 in the U.S., 151 of 206 in Brazil) died. Decreased level of consciousness, Palliative Performance Scale ≤20%, and dysphagia of liquids appeared at high frequency and >3 days before death and had low specificity (<90%) and positive LR (<5) for impending death. In contrast, apnea periods, Cheyne-Stokes breathing, death rattle, peripheral cyanosis, pulselessness of radial artery, respiration with mandibular movement, and decreased urine output occurred mostly in the last 3 days of life and at lower frequency. Five of these signs had high specificity (>95%) and positive LRs for death within 3 days, including pulselessness of radial artery (positive LR: 15.6; 95% confidence interval [CI]: 13.7-17.4), respiration with mandibular movement (positive LR: 10; 95% CI: 9.1-10.9), decreased urine output (positive LR: 15.2; 95% CI: 13.4-17.1), Cheyne-Stokes breathing (positive LR: 12.4; 95% CI: 10.8-13.9), and death rattle (positive LR: 9; 95% CI: 8.1-9.8). CONCLUSION: We identified highly specific physical signs associated with death within 3 days among cancer patients.