Total Symptom Distress Score Research Articles

A randomized, double-blind controlled trial of medicinal cannabis vs placebo for symptom management in patients with advanced cancer receiving palliative care.

12020 Background: Medicinal cannabis remains very popular amongst cancer patients. In our previous study (JCO 2023; 41(7):1444-1452), cannabidiol (CBD) did not improve symptom management above that provided by standard palliative care alone. This study utilized the same design to test whether the addition of tetrahydrocannabinol(THC) to CBD resulted in improved symptom control. Methods: Patients with advanced cancer and a total symptom distress score (TSDS) of ≥10/90 as measured by the Edmonton Symptom Assessment Scale (ESAS) who were receiving palliative care were randomised to a 10mg/ml THC:10mg/ml CBD combination oil (MC) or matched placebo. The dose was escalated according to tolerance and perceived efficacy from 2.5 to 30mg/day over 14 days and continued at that dose to day 28. The primary outcome was the change in TSDS from baseline at day 14. Secondary outcomes included change in individual symptoms, patient-selected dose, global impression of change, anxiety/depression, opioid use, quality of life and toxicity. Results: Of the 144 randomized from Sept 2019 to July 2023 (72 to MC, 72 to placebo), 56 and 65 participants reached the primary analysis point at 14 days, and 33 and 50 to day 28. The most common cancers were breast, lung and gynecological. Most participants were of reasonable performance status (AKPS 70%) and were taking opioids at baseline. Mean baseline TSDS scores were 37.6/90 (MC) and 36.5/90 (placebo). Mean TSDS scores fell over time with no difference between arms at day 14 (-6.3 (SD 12.3) MC and -6.98 (SD 12.6), p = 0.76) or day 28 (-9.24 (SD 15.3) and 8.42 (SD 13.6), p = 0.8). Adjusted for baseline, there was a significant improvement in pain score from baseline in favor of MC (-1.41 (2.15) vs -0.46 (2.82), p = 0.04) and in overall wellbeing in favor of placebo (-0.48 (2.78) and -1.29 (2.74), p = 0.02) at day 14. The median (range) patient selected dose of oil at day 14 was 1.5ml (0.5-3.0) (equivalent to a dose of 15mgTHC/15mg CBD) and 3.0ml (0.5-3.0) for placebo. Side-effects were generally mild. More participants on MC reported confusion (26/69 and 12/72, p = 0.005), feeling high (21/69 and 10/72, p = 0.02) and an exaggerated sense of well-being (10/69 and 2/72, p = 0.01) as worse than baseline. Those on MC reported an improved global impression of change over time but this lost significance when considering those who exited early. Conclusions: Although showing no advantage over placebo with respect to improving total symptom distress, a 1:1 THC:CBD medicinal cannabis oil resulted in a statistically significant improvement in cancer-related pain at the expense of increased psychomimetic toxicity. Trial registration: ACTRN 12619000037101. Sponsor: Australian Government Medical Research Future Fund. Clinical trial information: ACTRN12619000037101.

Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer—a study protocol for a randomised controlled trial

BackgroundDistressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care.Methods and designOne hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose.The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep.DiscussionMedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis’ role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally.Trial registrationANZCTR ACTRN12622000083796. Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

Abstract P6-05-43: Validity of EQ-5D-5L for women with breast cancer

Abstract Background: The EuroQol- 5 Dimension (EQ-5D) is a generic patient-reported outcome measure widely used to capture meaningful change in health-related quality of life between treatments to inform drug and health technology reimbursement decision making. We investigated the construct validity of EQ-5D-5L in women with breast cancer. Methods: This study included adult women diagnosed with stage I to IV breast cancer, who completed the EQ-5D-5L and the Edmonton Symptom Assessment System (ESAS) during outpatient clinic visits at two academic cancer centres in Toronto. We evaluated construct validity through assessing known-group validity and convergent/divergent validity. For known-group validity, the primary analysis tested the hypothesis that EQ-5D-5L could adequately discriminate between patients with metastatic disease and early-stage disease; secondary analyses addressed utility values between women in breast-cancer associated health states. A suggested minimally important difference (MID) for the Canadian scoring of the EQ-5D-5L is 0.037; we evaluated whether the lower bound of the 95% confidence interval (95%CI) exceeded this value. In terms of convergent/divergent validity, the primary analysis tested the hypothesis that EQ-5D-5L mean utility values for each health state (HS) would be at least moderately correlated with ESAS total symptom distress score (SDS) (|r|>0.30) using Wilcoxon rank-sum tests and Spearman’s correlation tests. Construct validity was considered as acceptable if the hypotheses of the primary analysis are satisfied. Results: We recruited 549 women, 406 (74%) with early-stage disease and 143 (26%) with metastatic disease (HS5), with a mean age of 57 (SD 12); 412 (75%) had been diagnosed with breast cancer in the 7 years prior to recruitment and were receiving active treatment for their cancer. The mean utility value for early-stage breast cancer was 0.84 (95% CI 0.83-0.86) and for metastatic breast cancer (0.78, 95% CI 0.76-0.81). This difference was 0.060 (95% CI 0.036 to 0.085, p< 0.001) with the lower bound of the confidence interval slightly less than the prespecified MID (0.037). There was no significant difference between the mean utility value for women in the first year after primary breast cancer diagnosis (HS1), and women in their second to fifth year after a primary breast cancer treated with curative intent (HS3) or between women in HS1 and women in their sixth and following years after a primary breast cancer treated with curative intent (HS4). EQ-5D-5L also did not discriminate between women in HS3 and HS4. For convergent/divergent validity, there was a negative correlation between utility values and ESAS physical, emotional and total SDSs. EQ-5D-5L and ESAS total SDSs correlation coefficients were higher than 0.30 for all health states. Conclusion: EQ-5D-5L met criteria for convergent/divergent validity in women with breast cancer. The tests for discriminant validity were equivocal, suggesting more research is needed for assessing construct validity with a larger sample size. Table 1. EQ-5D-5L Utility Values. N= number; Std Dev= standard deviation; IQR= interquartile range; CI= confidence interval Citation Format: Sofia Torres, Maureen Trudeau, Geoffrey Liu, Nicholas Mitsakakis, Ahmed Bayoumi. Validity of EQ-5D-5L for women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-43.

Symptom Burden of Patients with Advanced Pancreas Cancer (APC): A Provincial Cancer Institute Observational Study.

Patients with advanced pancreatic cancer (APC) experience many disease-related symptoms. ESAS-r measures the severity of 9 symptom domains and has been validated for use in the ambulatory oncology setting. We aimed to describe symptom burden at baseline for patients with APC treated with modern chemotherapy (CT), and to determine whether symptom burden at baseline is prognostic. Patients diagnosed with APC between 2012–2016, treated with ≥1 cycle of CT, who completed ≥1 ESAS-r were identified. Descriptive statistics were used to report symptom burden and common moderate-to-severe symptoms. A joint model was used to describe the trajectory of ESAS-r during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Of 123 patients identified, the median age was 65 and 61% had metastatic disease. The median baseline ESAS-r total symptom distress score (TSDS) was 24. A total of 86% of patients had at least one symptom score of ≥4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Median overall survival was 10.2 months. Baseline TSDS was not predictive for worse survival in the era of modern CT. Patients with APC have a high burden of cancer-associated symptoms and a high prevalence of moderate-to-severe symptoms. Early intervention has the potential to improve quality of life in this group of patients and should be investigated.

Longitudinal Symptom Burden Trajectories in a Population-Based Cohort of Women with Metastatic Breast Cancer: A Group-Based Trajectory Modeling Analysis.

Understanding the symptom burden trajectory for metastatic breast cancer patients can enable the provision of appropriate supportive care for symptom management. The aim of this study was to describe the longitudinal trajectories of symptom burden for metastatic breast cancer patients at the population-level. A cohort of 995 metastatic breast cancer patients with 16,146 Edmonton Symptom Assessment System (ESAS) assessments was constructed using linked population-level health administrative databases. The patient-reported ESAS total symptom distress score (TSDS) was studied over time using group-based trajectory modeling, and covariate influences on trajectory patterns were examined. Cohort patients experienced symptom burden that could be divided into six distinct trajectories. Patients experiencing a higher baseline TSDS were likely to be classified into trajectory groups with high, uncontrolled TSDS within the study follow-up period (χ2 (1, N = 995) = 136.25, p < 0.001). Compared to patients classified in the group trajectory with the highest relative TSDS (Group 6), patients classified in the lowest relative TSDS trajectory group (Group 1) were more likely to not have comorbidities (97.34% (for Groups 1–3) vs. 91.82% (for Group 6); p < 0.05), more likely to receive chemotherapy (86.52% vs. 80.50%; p < 0.05), and less likely to receive palliative care (52.81% vs. 79.25%; p < 0.0001). Receiving radiotherapy was a significant predictor of how symptom burden was experienced in all identified groups. Overall, metastatic breast cancer patients follow heterogeneous symptom burden trajectories over time, with some experiencing a higher, uncontrolled symptom burden. Understanding trajectories can assist in establishing risk-stratified care pathways for patients.

Follow-up study on symptom distress in esophageal cancer patients undergoing repeated dilation.

BACKGROUNDRepeated endoscopic probe dilatation is the most preferred treatment for esophageal stenosis which may cause high levels of symptom distress in the patient's home rehabilitation stage.AIMTo explore the changes in the symptom distress level and its correlation with the dilation effect in patients with esophageal carcinoma undergoing repeated dilations for lumen stenosis.METHODSThe difference (R2-R1) between the diameter of the esophageal stenosis opening (R1) of the patients before dilation (R1) and after dilation (R2) was calculated to describe the extent and expansion of the esophageal stenosis before and after dilation. The M.D. Anderson Symptom Inventory was used to describe the symptom distress level of patients with dilation intermittence during their stay at home and to explore the correlation between the dilation effect and symptom distress level.RESULTSThe diameter of the esophagus (R1) increased before each dilation in patients undergoing esophageal dilation (P < 0.05). The diameter (R2) increased after dilation (P < 0.05); the dilation effect (R2-R1) decreased with the number of dilations (P < 0.05). The total symptom distress score significantly increased with the number of dilations (P < 0.05). The symptom distress scores of the patients were negatively correlated (P < 0.05) with the previous dilation effect (R2-R1) and the esophageal diameter (R2) after the previous dilation. After the 1st to 4th dilations, the patient's symptom distress score was negatively correlated with the esophageal diameter (R12) before the next dilation, while there was no significant correlation (P > 0.05) with the other dilations.CONCLUSIONIn patients who have undergone repeated dilations, better effect stands for lower symptom distress level and the increase in symptom distress has a prompt effect on the severity of the next occurrence of restenosis.

Symptom burden and characteristics of patients who die in the acute palliative care unit of a tertiary cancer center.

Acute palliative care unit (APCU) is a novel inpatient program in a tertiary cancer center that provides aggressive symptom management and assists with the transition to hospice. However, patients often die in the APCU before successfully transferring to hospice. The aim of this study was to evaluate the symptom burden and characteristics of advanced cancer patients who died in the APCU. We retrospectively reviewed the medical records of all advanced cancer patients admitted to the APCU between April 2015 and March 2016 at a tertiary cancer center in Korea. Basic characteristics and symptom burden assessed by the Edmonton Symptom Assessment System (ESAS) were retrieved. Statistical analyses were conducted to compare patients who died in the APCU with those who were discharged alive. Of the 267 patients, 87 patients (33%) died in the APCU. The median age of the patients was 66 years (range, 23-97 years). The most common primary cancer types were lung (21%), stomach (17%), and colorectal cancer (15%). Patients who died in the APCU had higher ESAS scores for drowsiness (6 vs. 5, P=0.002), dyspnea (4 vs. 2, P=0.001), anorexia (8 vs. 6, P=0.014) and insomnia (6 vs. 4, P=0.002) compared to patients who were discharged alive. The total symptom distress score (SDS) was also significantly higher (47 vs. 40, P=0.001) in patients who died in the APCU. In the multivariate analysis, patients who died in the APCU were more likely to be male [odds ratio (OR) 2.63, 95% confidence interval (CI): 1.49-4.64, P=0.001] and have higher ESAS scores for drowsiness (OR 2.08, 95% CI: 1.08-3.99, P=0.029) and dyspnea (OR 2.19, 95% CI: 1.26-3.80, P=0.005). Patients who died in the APCU showed significantly shorter survival after APCU admission (7 vs. 31 days, P<0.001). Advanced cancer patients who die in the APCU were more likely to be male and have significantly higher symptom burden including drowsiness and dyspnea. These patients showed rapid clinical deterioration after APCU admission. More proactive and timely end-of-life care is needed for these patients.

Do Longitudinally Collected Symptom Scores Predict Time to Death in Advanced Breast Cancer: A Joint Modeling Analysis

ContextPatients with advanced breast cancer have low rates of survival that can be associated with symptom burden. ObjectivesThis study seeks to characterize the effect of longitudinally collected symptom scores on predicting time to death for patients with advanced breast cancer. MethodsA cohort of 993 Stage IV breast cancer patients was constructed using linked population-level health administrative databases that captured longitudinally collected symptom data using the Edmonton Symptom Assessment System. Data were captured on individual symptom scores (20,371 assessments) for pain, tiredness, drowsiness, nausea, appetite, dyspnea, depression, anxiety, and wellbeing, as well as three summative scores of total symptom distress score, physical subscore, and psychological subscore. A joint modeling approach was undertaken to simultaneously model repeated-measures longitudinal data and time-to-event data. ResultsOf patients who died in the study, 56.11% survived for a mean time of less than three years and had lower mean symptom scores for all symptoms except shortness of breath, in comparison with patients who lived for more than three years. Symptom burden was predictive of patient time to death for all symptoms, with risk of death increasing with worsening symptom scores. For total symptom distress score, age at diagnosis (0.009; P < 0.05), chemotherapy (−0.63; P < 0.001), and palliative care (3.15; P < 0.001) were significant predictors of patient time to death. ConclusionPatients with advanced breast cancer experience chronic ongoing low symptom burden, which predicts patient time to death. Future research should examine the mechanisms by which patient characteristics, treatment, and supportive and palliative care can have an impact on patient survival.

Are population-based patient-reported outcomes associated with overall survival in patients with advanced pancreatic cancer?

BackgroundAdvanced pancreatic cancer (APC) patients often have substantial symptom burden. In Ontario, patients routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for nine symptoms (scale: 0‐10), in cancer clinics. We explored the association between baseline patient‐reported outcomes, via ESAS, and overall survival (OS).MethodsAdvanced pancreatic cancer patients with ESAS records prior to receiving publicly funded drugs from November 2008 to March 2016 were retrospectively identified from Cancer Care Ontario's administrative databases. We examined three composite ESAS scores: total symptom distress score (TSDS: 9 symptoms), physical symptom score (PHS: 6/9 symptoms), and psychological symptom score (PSS: 2/9 symptoms); Composite scores greater than defined thresholds (TSDS ≥36, PHS ≥24, PSS ≥8) were considered as high symptom burden. Crude OS was assessed using Kaplan‐Meier method. Hazard ratios (HRs) were assessed using multivariable Cox models. Analysis was repeated in a sub‐cohort with Eastern Cooperative Oncology Group (ECOG) status and metastasis.ResultsWe identified 2199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving chemotherapy. Crude median survival was 4.5 and 7.3 months for high and low TSDS, respectively. High TSDS was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). In the sub‐cohort (n = 393) with ECOG status and metastasis, high TSDS was also associated with lower OS (HR = 1.34, 95% CI: 1.04, 1.73). Similar trends were observed for PHS and PSS.ConclusionsHigher burden of patient‐reported outcome was associated with reduced OS among APC patients. The effect was prominent after adjusting for ECOG status.

Comparison and Clinical Implementation of Quality of Life Tools in Patients with Small Bowel Neuroendocrine Tumors Treated with Lu-DOTA-TATE PRRT

Aim: This study assesses if clinically developed quality of life (QoL) tools are as effective in small bowel neuroendocrine tumors (NETs) as NET-specific research questionnaires. Methods: QoL in patients with small bowel NETs treated with Lu-DOTA-TATE was assessed with The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-GI.NET21 and Edmonton Symptom Assessment System Revised (ESAS-r) at baseline and after four treatments. Repeated measures ANOVA was performed. Results: Both EORTC and ESAS-r demonstrated maintained overall QoL. EORTC demonstrated statistically and clinically significant improvement in insomnia, diarrhea, gastrointestinal, endocrine symptoms and social function. ESAS-r demonstrated statistically and clinically significant improvement in overall total symptom distress score. Conclusion: ESAS-r is quick and easy to interpret. It is not as sensitive to individual symptoms but does track overall function. EORTC assessment is more complex, but better reflects QoL for NET specific symptoms.

Symptom burden of patients with advanced pancreas cancer (APC): A provincial cancer institute observational study.

384 Background: Patients (pts) with advanced pancreatic cancer (APC) experience many disease-related symptoms. The Edmonton Symptom Assessment System (ESAS) measures the severity of 9 separate domains, and is completed by pts at each visit at our provincial cancer institute. The aim of this study was to describe symptom burden at baseline and over time for chemotherapy (CT) treated pts with APC, using ESAS. Methods: Pts diagnosed with APC between 2012-2016 and treated with at least 1 cycle of CT were identified. ESAS scores were extracted from the electronic medical record. Descriptive statistics were used to report the most common symptoms of pts with APC. A joint model was used to describe the trajectory of ESAS during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Results: Of 123 pts identified, 61% had metastatic disease, 82.1% had a baseline ECOG of 0-1, with an average age of 64.8. 1608 clinic visits had an ESAS score documented and 87% of pts completed ≥ 2 ESAS assessments. Median overall survival was 10.2 months. Median progression free survival was 6.7 months. At baseline, the 10th percentile, median and 90th percentile for total symptom distress (TSD) score were 6.2, 24 and 53 respectively. 86% of pts had at least one ESAS score of ≥ 4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Using a joint model, average TSD scores for the cohort improved for the first 4 to 5 months after starting CT and started to rise after 6 months. Average TSD scores at 15 to 18 months were similar to scores at baseline. Controlling for metastatic disease and CT type, for every increase of 10 in baseline TSD score, there was a 5% increased risk of death. Conclusions: The ESAS tool reflects the heavy burden of cancer-associated symptoms in APC. Symptoms improve months after starting CT and eventually worsen. The impact of early intervention to address symptom management is an important area of investigation in APC.

Are real-world patient-reported outcomes associated with survival in patients with advanced pancreatic cancer?

205 Background: Advanced pancreatic cancer (APC) patients often have a substantial symptom burden. In Ontario, patients visiting cancer clinics routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for 9 symptoms (scale: 0-10). Using ESAS, we explored the association between baseline patient-reported outcomes and overall survival (OS). Methods: APC Patients with ESAS records prior to receiving publicly-funded drugs from November 2008 to March 2016 were identified from Cancer Care Ontario’s New Drug Funding Program and Symptom Management databases. We examined 3 baseline composite ESAS scores: Total Symptom Distress Score (TSDS: all 9 symptoms), Physical Symptom Score (PHS: 6/9 symptoms), and Psychological Symptom Score (PSS: 2/9 symptoms); Composite scores greater than a threshold (defined as number of symptoms in composite score multiplied by clinically relevant score (≥4)) were categorized as High Symptom Burden (TSDS ≥ 36, PHS ≥ 24, PSS ≥ 8). The primary endpoint, OS, was assessed using Kaplan-Meier. Multivariable Cox models were used to adjust for age, gender, income, prior therapies (surgery, adjuvant gemcitabine, radiation), and Charlson's comorbidity. Analysis was repeated in a sub-cohort with identifiable ECOG status and stage. Results: We identified 2,199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving gemcitabine (54%), FOLFIRINOX (40%) or gemcitabine/nab-paclitaxel (6%). Crude median survival was 4.5 and 7.3 months for patients with high and low TSDS burden, respectively (HR = 1.50, 95% CI: 1.36, 1.66). After adjustment with multivariable Cox model, high TSDS burden was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). Similar trends were observed for PHS and PSS. When adjusting for both PHS and PSS in a Cox model, only the effect of PHS remained significant. In the sub-cohort (n = 393), high TSDS burden (HR = 1.34, 95% CI: 1.04, 1.73) was associated with lower OS, after adjusting for ECOG and stage. Conclusions: Among APC patients, a higher burden of patient-reported symptoms, via ESAS, at baseline was associated with reduced OS. The effect was prominent for physical symptoms, even after adjusting for treatment, stage and ECOG.

Assessing the prognostic features of a pain classification system in advanced cancer patients.

The Edmonton Classification System for Cancer Pain (ECS-CP) has been shown to predict pain management complexity based on five features: pain mechanism, incident pain, psychological distress, addictive behavior, and cognitive function. The main objective of our study was to explore the association between ECS-CP features and pain treatment outcomes among outpatients managed by a palliative care specialist-led interdisciplinary team. Initial and follow-up clinical information of 386 eligible supportive care outpatients were retrospectively reviewed and analyzed. Between the initial consultation and the first follow-up visit, the median ESAS pain intensity improved from 6 to 4.5 (p<0.0001) and the median total symptom distress score (0-100) improved from 38 to 31 (p<0.0001). At baseline, patients with neuropathic pain (p<0.001) and those with at least one ECS-CP feature (p=0.006) used a higher number of adjuvant medications. At follow-up, patients with neuropathic pain were less likely to achieve their personalized pain goal (PPG) (29 vs 72%, p=0.015). No statistically significant association was found between increasing sum of ECS-CP features and any of the pain treatment outcomes at follow-up. Neuropathy was found to be a poor prognostic feature in advanced cancer pain management. Increasing sum of ECS-CP features was not predictive of pain management complexity at the follow-up visit when pain was managed by a palliative medicine specialist. Further research is needed to further explore these observations.

The Frailty Phenotype and Palliative Care Needs of Older Survivors of Critical Illness.

To assess symptoms in older intensive care unit (ICU) survivors and determine whether post-ICU frailty identifies those with the greatest palliative care needs. A prospective cohort study. Urban tertiary care hospital and community hospital. Medical ICU survivors of mechanical ventilation aged 65 and older (N = 125). Baseline measurements of the Edmonton Symptom Assessment Scale (ESAS), categorized as mild (0-3), moderate (4-6), and severe (7-10), and the frailty phenotype were made during the week before hospital discharge. Functional recovery was defined as a return to a Katz activity of daily living dependency count less than or equal to the prehospitalization dependency count within 3 months. In the last 29 participants recruited, we made additional assessments of fatigue and ESAS both at baseline and 1 month after discharge. Fatigue was the most-prevalent moderate to severe symptom (74%), followed by dyspnea (53%), drowsiness (50%), poor appetite (47%), pain (45%), depression (42%), anxiety (36%), and nausea (17%). At 1-month follow-up, there were no significant differences in the proportions of participants with moderate to severe symptoms. Each increase in baseline ESAS fatigue severity category was associated with 55% lower odds of functional recovery (odds ratio = 0.45, 95% confidence interval = 0.24-0.84), independent of age, sex, comorbidities, and critical illness severity. Frail participants had a higher median baseline total ESAS symptom distress score (34, interquartile range (IQR) 23-44) than nonfrail participants (13, IQR 9-22) (P < .001). Older ICU survivors have a high burden of palliative care needs that persist 1 month after discharge. Fatigue is the most-prevalent symptom and may interfere with recovery. Post-ICU frailty may be a useful trigger for palliative care consultation and a treatment target.

Minimal Clinically Important Difference in the Physical, Emotional, and Total Symptom Distress Scores of the Edmonton Symptom Assessment System

ContextThe Edmonton Symptom Assessment System (ESAS) is one of the most commonly used symptom batteries in clinical practice and research. ObjectivesWe used the anchor-based approach to identify the minimal clinically important difference (MCID) for improvement and deterioration for ESAS physical, emotional, and total symptom distress scores. MethodsIn this multicenter prospective study, we asked patients with advanced cancer to complete their ESAS at the first clinic visit and at a second visit three weeks later. The anchor for MCID determination was Patient's Global Impression regarding their physical, emotional, and overall symptom burden (“better,” “about the same,” or “worse”). We identified the optimal sensitivity/specificity cutoffs for both improvement and deterioration for the three ESAS scores and also determined the within-patient changes. ResultsA total of 796 patients were enrolled from six centers. The ESAS scores had moderate responsiveness, with area under the receiver operating characteristic curve between 0.69 and 0.76. Using the sensitivity-specificity approach, the optimal cutoffs for ESAS physical, emotional, and total symptom distress scores were ≥3/60, ≥2/20, and ≥3/90 for improvement, and ≤−4/60, ≤−1/20, and ≤−4/90 for deterioration, respectively. These cutoffs had moderate sensitivities (59%–68%) and specificities (62%–80%). The within-patient change approach revealed the MCID cutoffs for improvement/deterioration to be 3/−4.3 for the physical score, 2.4/−1.8 for the emotional score, and 5.7/−2.9 for the total symptom distress score. ConclusionWe identified the MCIDs for physical, emotional, and total symptom distress scores, which have implications for interpretation of symptom response in clinical trials.

Screening for body image dissatisfaction in patients with advanced cancer: a pilot study.

Cancer and its treatment can significantly affect appearance and body integrity. A number of studies have explored the impact of cancer and its treatment on body image, primarily in head and neck and breast cancer. The aim of this pilot study was to examine the construct of body image dissatisfaction and its measurement using a single question in patients with advanced cancer. Outpatients with advanced cancer were recruited (n=81). Assessments included Body Image Scale (BIS), Appearance Schema Inventory (ASI-R), Edmonton Symptom Assessment System (ESAS) with a total symptom distress score (TSDS) and two subscales scores (physical distress [PHS] and psychological distress [PSS]), Hospital Anxiety Depression Scale (HADS), and one question assessing the overall appearance satisfaction from the Multidimensional Body-Self Relations Questionnaire (MBSRQ). We also asked patients to rate the body image changes importance compared with five symptoms (pain, fatigue, depression, insomnia, lack of appetite). Forty-seven (58%) patients had a BIS score >10 (body image dissatisfaction) with a median of 11 (first-third quartiles, Q1-Q3; 5-16) and a median ASI-R of 3.1 (Q1-Q3; 2.8-3.5). Sensitivity and specificity of ≤3 for body image dissatisfaction in the single overall appearance question using the BIS as a standard was 0.70 and 0.71, respectively. BIS score was significantly correlated with ASI-R (r=0.248; p=0.025), age (r=-0.225; p=0.043), HADS-A (r=0.522, p<0.001), HADS-D (r=0.422, p<0.001), PSS score (r=0.371, p=0.001), PHS score (r=0.356, p=0.001), TSDS score (r=0.416, p<0.001), and the overall appearance question (MBSRQ; r=-0.449, p<0.001). Body image dissatisfaction was frequent and associated with symptom burden. A single item ≤3 has a sensitivity of 70% for body image satisfaction screening.

Association between supportive care interventions and patient self-reported depression among advanced cancer outpatients.

Advanced cancer patients often experience moderate to severe physical and emotional distress. One of the main components of emotional distress is depression. The objective of this study was to examine the association between supportive care interventions and patient self-reported depression (PSRD) among advanced cancer outpatients. We included consecutive patients seen in the outpatient Supportive Care Center between February 2008 and February 2010 with at least one follow-up visit. We used the Edmonton Symptom Assessment Scale (ESAS) to assess their symptom intensity. Clinical improvement of PSRD was defined as an improvement of at least 30% between the initial visit and the first follow-up. We used logistic regression models to assess possible predictors of improvement in PSRD. We included 444 patients with a median age of 59 years (Q1-Q3; 51-65). The most common type of cancer was gastrointestinal (98, 22%). Out of the 444 patients, 160 (36%) reported moderate/severe depression at baseline (ESAS item score ≥ 4/10). Higher baseline depression intensity was significantly associated to anxiety (r = 0.568, p = 0.046), total symptom distress score (TSDS; r = 0.550, p < 0.001) and personal history of depression (r = 0.242, p = 0.001). Of the 160 patients, 90 (56%) with moderate/severe PSRD at baseline showed a significant improvement at the follow-up visit (p = 0.038). Improvement in anxiety, sedation, and feeling of well-being were associated with higher depression improvement (OR 7.93, CI 3.74-16.80 and OR 2.44, CI 1.09-5.46, respectively). More than 50% patients with moderate/severe PSRD significantly improved after one single supportive/palliative care consultation. Improvements of anxiety and sedation were independently associated with PSRD improvement.

Symptom Clusters in Men and Women With Heart Failure and Their Impact on Cardiac Event-Free Survival

Because patients with heart failure (HF) experience multiple symptoms simultaneously, it is necessary to explore symptom clusters rather than individual symptoms to determine their impact on outcomes. Given gender differences in symptom experience, examination of potential gender differences in clusters is reasonable. The objective of the study was to compare symptom clusters between men and women with HF, differences in patient characteristics among symptom clusters, and the impact of symptom clusters on cardiac event-free survival. A total of 331 patients with HF recruited from HF clinics were included (35% were female and 62% were of New York Heart Association classes III/IV). Cluster analysis was used to identify symptom clusters between men and women based on ratings of distress related to 7 symptoms. Analysis of variance or chi test was used to compare characteristics of patient groups that were divided by the median split of total distress scores of each cluster. Cox proportional hazards regression was used to determine whether total scores of symptom distress in symptom clusters predicted time to first cardiac event. Two identical symptom clusters were identified in men and women: a physical symptom cluster composed of dyspnea, fatigue/increased need to rest, fatigue/low energy, and sleep disturbances and an emotional/cognitive symptom cluster composed of worrying, feeling depressed, and cognitive problems. Patients with higher distress from the physical symptom cluster were primarily females and of New York Heart Association classes III and IV (P < .05). Patients with higher distress from the emotional/cognitive symptom cluster were younger than those with lower distress (P < .05). The total symptom distress score in the emotional/cognitive cluster, but not the physical cluster, was an independent predictor of cardiac event-free survival (hazard ratio, 1.18; 95% confidence interval, 1.03-1.37). Although distress for individual symptoms may differ between men and women, they both experienced identical symptom clusters. Only the emotional/cognitive cluster predicted a higher risk for a cardiac event. These results suggested that interventions should be developed that consider symptom clusters. Targeting patients who have high distress from emotional/cognitive symptoms may be particularly important as they may be most vulnerable for adverse outcomes.

Diabetes-Related Symptom Distress in Association With Glucose Metabolism and Comorbidity

OBJECTIVE—The purpose of this study was to determine the associations between diabetes-related symptom distress, glucose metabolism status, and comorbidities of type 2 diabetes.RESEARCH DESIGN AND METHODS—This was a cross-sectional sample of 281 individuals with normal glucose metabolism (NGM), 181 individuals with impaired glucose metabolism (IGM), and 107 subjects with type 2 diabetes. We used the revised type 2 Diabetes Symptom Checklist (DSC-R) to assess diabetes-related symptom distress.RESULTS—The total symptom distress score (range 0–100) was relatively low for diabetic subjects (mean ± SD 8.4 ± 9.4), although it was significantly different from that for subjects with IGM (6.5 ± 7.1) and NGM (6.1 ± 7.9) (F = 3.1, 2 d.f., P = 0.046). Ischemic heart disease was associated with elevated DSC-R scores on three subscales, whereas depression showed higher symptom distress levels across all DSC-R domains.CONCLUSIONS—Worsening glucose metabolism is associated with increasing diabetes-related symptom distress. This relationship is attenuated by ischemic heart disease and particularly by depression.

The Association of Physical and Psychological Symptom Burden with Time to Death Among Palliative Cancer Outpatients

Previous studies have reported on the symptom burden of cancer inpatients, but outpatient studies have been few and have not examined the association of symptoms with time to death (TTD). Cancer patients seen in an oncology palliative care clinic from January 2005 to June 2006 and who subsequently died were identified from a palliative care database. Data from the last outpatient Edmonton Symptom Assessment Scale (ESAS) score completed in clinic were analyzed among patients who were followed during the last four months of life. Multiple linear regression analyses with Bonferroni adjustment were used to determine the association of ESAS total symptom distress score (TSDS), physical subscore (PHS), psychological subscore (PSS), and individual symptom scores with demographic parameters, disease characteristics, and TTD. Data from 198 patients were analyzed. All had stage IV cancer, the median age was 65, and 55% were men. There was no significant association between symptom burden and age, gender, or cancer site. TTD was significantly associated with TSDS ( P = 0.001) and PHS ( P = 0.001) but not with PSS ( P = 1.0). Individual symptoms most strongly associated with TTD were lack of appetite ( P = 0.001), drowsiness ( P = 0.006), dyspnea ( P = 0.009), and fatigue ( P = 0.01). There was no significant association between TTD and anxiety ( P = 1.0) or depression ( P = 1.0). Lack of appetite, drowsiness, dyspnea and fatigue represent a cluster of symptoms that tend to intensify at the end of life. The lack of intensification of psychological symptoms in relation to time to death is striking and needs to be further investigated using specific validated measures for depression and anxiety.