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Background: The interdependence of cytokines and appetite-modifying hormones implicated in cancer anorexia-cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non-inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes., Methods: Clinical characteristics of 133 patients [61.7% male; mean age = 63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex-standardized skeletal muscle index (z-SMI) and fat mass index (z-FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite-modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two-step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan-Meier analysis., Results: Patients had low z-SMI (mean = -3.78 cm 2 /m 2 ; SD: 8.88) and z-FMI (mean = 0.08 kg 2 /m 2 ; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F-1) IFN-γ, IL-1β, Il-4, IL-6, IL-10, IL-12, TGFβ1 (positive contribution), and IL-18 (negative); (F-2) IL-8, IL-18, MCP-1, TGFβ1, TNF-α (positive), and ghrelin (negative); and (F-3) TRAIL and leptin (positive), and TGFβ1 and adiponectin (negative). RFS-1 was associated with cachexia (P = 0.002); RFS-2, with higher CRP (P < 0.0001) and decreased physical function (P = 0.01); and RFS-3 with better appetite (P = 0.04), lower CRP (P = 0.002), higher z-SMI (P = 0.04) and z-FMI (P < 0.0001), and less cachexia characteristics (all P < 0.001). Four patient groups were identified with specific RFS clusters aligning with the CACS continuum from no cachexia to pre-cachexia, cachexia, and terminal cachexia. Compared to the other two groups, groups 1 and 2 had higher plasma levels of IL-18 and TRAIL. Group 1 also had lower inflammatory cytokines, adiponectin, and CRP compared to the other three groups. Group 3 had inflammatory cytokine levels similar to group 2, except for TNF-α and leptin which were lower. Group 4 had very high inflammatory cytokines, adiponectin, and CRP compared to the other 3 groups (all P < 0.0001). Groups 3 and 4 had worse cachexia characteristics (P < 0.05) and shorter survival (log rank: P = 0.0009) than the other two groups., Conclusions: This exploratory study identified three distinct pathways of inflammation, or lack thereof, characterizing different CACS phenotypes., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Cancer-related cognitive impairment (CRCI) is one of the most concerning conditions experienced by patients living with cancer and has a major impact on their quality of life. Available cognitive assessment tools are too time consuming for day-to-day clinical setting assessments. Importantly, although shorter, screening tools such as the Montreal Cognitive Assessment or the Mini-Mental State Evaluation have demonstrated a ceiling effect in persons with cancer, and thus fail to detect subtle cognitive changes expected in patients with CRCI. This study addresses this lack of cognitive screening tools by developing a novel tool, the Fast Cognitive Evaluation (FaCE).A population of 245 patients with 11 types of cancer at different illness and treatment time-points was enrolled for the analysis. FaCE was developed using Rasch Measurement Theory, a model that establishes the conditions for a measurement tool to be considered a rating scale.FaCE shows excellent psychometric properties. The population size was large enough to test the set of items (item-reliability-index=0.96). Person-reliability (0.65) and person-separation (1.37) indexes indicate excellent internal consistency. FaCE's scale is accurate (reliable) with high discriminant ability between cognitive levels. Within the average testing time of five minutes, FaCE assesses the main cognitive domains affected in CRCI.FaCE is a rapid, reliable, and sensitive tool for detecting even minimal cognitive changes over time. This can contribute to early and appropriate interventions for better quality of life in patients with CRCI. In addition, FaCE could be used as a measurement tool in research exploring cognitive disorders in cancer survivors., (© 2023. The Author(s).)

Introduction: Methylphenidate is a psychostimulant drug used to treat fatigue in patients with advanced cancer, for which there is no gold standard of treatment., Objective: To explore the efficacy of methylphenidate in the relief of fatigue in patients with advanced cancer., Materials and Methods: A randomised double-blind placebo-controlled multicentre clinical trial, stratified according to the intensity of fatigue. The treatment was considered effective if the improvement in mean fatigue intensity between baseline values and day 6 was significantly higher in the methylphenidate group than in the placebo group. The responses were measured using the Edmonton Symptoms Assessment System (ESAS) and the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scales., Results: 35 patients received placebo and 42 patients received methylphenidate. The populations of both groups were homogeneous. Patients receiving methylphenidate did not exhibit statistically significant improvement of fatigue in comparison to patients receiving placebo (p=0.52). The mean improvement of fatigue (ESAS) on day 6 was -1.9 (±2.5) in the placebo group, and -2.3 (±2.6) in the methylphenidate group (p=0.52). The results obtained with the FACT-F were congruent with those obtained by the ESAS. The responses in patients with severe fatigue were -2.4 (±2.9) in the placebo group and -3.4 (±2.5) in the methylphenidate group; the difference was not statistically significant (p=0.3)., Conclusion: Methylphenidate was not more efficient than placebo to treat cancer-related fatigue. Fatigue improved significantly after 3 days of treatment and was stabilised on day 6, both with placebo and methylphenidate. The side effects of methylphenidate were mild and infrequent., Trial Registration Number: EudraCT Registry (2008-002171-27)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cancer-associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C-reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer-associated WL (primary endpoint) and overall survival (OS, secondary endpoint)., Methods: The data set included a total of 12,253 patients at risk for cancer-associated WL. Patient-reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively., Results: Patients had a mean weight change of -7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5-5.9% (19.7%), 6.0-10.0% (23.2%), 11.0-14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P < 0.0001) if food intake was moderately [OR 6.28, 95% confidence interval (CI 5.28-7.47)] or severely reduced [OR 18.98 (95% CI 15.30-23.56)]. In subset analysis, adjusted for food intake, CRP was independently associated (P < 0.0001) with ≥15% WL [CRP 10-100 mg/L: OR 2.00, (95% CI 1.58-2.53)] and [CRP > 100 mg/L: OR 2.30 (95% CI 1.62-3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5-10.3), with median follow-up of 39.7 months (95% CI 38.8-40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001)., Conclusions: Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer-associated cachexia., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objective: Palliative care providers may face questions from patients and relatives regarding the heritability of cancers. Implications of such discussions for providers have been little explored. This study aimed to gather palliative care providers' views on their main needs, roles, and ethical concerns regarding cancer family history discussions., Method: The palliative care providers who participated in the 2015 and 2017 annual meetings of the Quebec Palliative Care Association were approached to complete a web-based questionnaire. Study participants answered the questionnaire between November 2016 and July 2017. They were asked to identify the most facilitating factor for cancer family history discussions, as well as their most important knowledge needs, potential role, and ethical concerns. Descriptive analyses were conducted., Results: Ninety-four palliative care providers answered the questionnaire. Access to specialized resources to obtain information and protocols or guidelines were considered the most facilitating factors for cancer family history discussions by 32% and 20% of providers, respectively. Knowledge of hereditary cancers was the most relevant educational need for 53%. Thirty-eight per cent considered essential to be informed about their rights and duties regarding cancer family history discussions. Being attentive to patients' concerns and referring families to appropriate resources were identified as the most relevant roles for palliative care providers by 47% and 34% of respondents, respectively. Fifty-eight per cent agreed that cancer family history discussions should be initiated only if beneficial to family members., Significance of Results: Education on hereditary cancers made consensus among palliative care providers as the most important knowledge need regarding discussing cancer family history at the end of life. Nonetheless, other less commonly expressed needs, including access to genetics specialists, protocols, or guidelines, and awareness of provider rights and duties concerning such discussions, deserve attention. Answering providers' needs might help optimize cancer predisposition management in palliative care.

Palliative care may be an opportunity to discuss cancer family history and familial cancer risks with patients' relatives. It may also represent the last opportunity to collect, from dying patients, clinical data and biospecimens that will inform cancer risk assessment and prevention in their surviving relatives. This study aims to explore the perspectives of cancer patients' relatives about cancer heritability, addressing cancer family history, and performing genetic testing in palliative care settings. Thirteen first-degree relatives of cancer patients who died in palliative care participated in the study. Two focus groups were conducted and transcribed verbatim. Two independent coders conducted a thematic content analysis. The themes included: (1) Knowledge of cancer heritability; (2) Experiences and expectations regarding cancer family history discussions, and (3) Views on genetic testing in palliative care patients and DNA biobanking. Participants seemed aware that cancer family history is a potential risk factor for developing the disease. They considered the palliative care period an inappropriate moment to discuss cancer heritability. They also did not consider palliative care providers as appropriate resources to consult for such matters as they are not specialized in this field. Participants welcomed DNA biobanking and genetic testing conducted at the palliative care patients' request. Cancer occurrence within families raises concerns among relatives about cancer heritability, but the palliative care period is not considered the most appropriate moment to address this issue. However, discussions about the risk to cancer patients' relatives might need to be considered on a case-by-case basis.

Objective: With increasing evidence from controlled trials on benefits of early palliative care, there is a need for studies examining implementation in real-world settings. The INTEGRATE Project was a 3-year real-world project that promoted early identification and support of patients with cancer who may benefit from palliative care. This study assesses feasibility, stakeholder experiences, and early impact of the INTEGRATE Project METHODS: The INTEGRATE Project was implemented in four cancer centers in Ontario, Canada, and consisted of interdisciplinary provider education and an integrated care model. Providers used the Surprise Question to identify patients for inclusion. A mixed methods evaluation of INTEGRATE was conducted using descriptive data, interviews with providers and managers, and provider surveys., Results: A total of 760 patients with cancer (lung, glioblastoma, head and neck, gastrointestinal) were included. Results suggest improvement in provider confidence to deliver palliative care and to initiate the Advanced Care Planning (ACP) conversation. The majority of patients (85%) had an ACP or goals of care (GOC) conversation initiated within a mean time to conversation of 5-46 days (SD 20-93) across centers. A primary care report was transmitted to family doctors 48-100% of the time within a mean time to transmission of 7-54 days (SD 9-27) across centers. Enablers and barriers influencing success of the model were also identified., Conclusions: A standardized model for the early introduction of palliative care for patients with cancer can be integrated into the routine practice of oncology providers, with appropriate education, integration into existing clinical workflows, and administrative support., (© 2019 John Wiley & Sons, Ltd.)

Background: People with cancer may experience change in what constitutes quality of life (QOL) over time as a result of the cancer progression (true change) or adaptation to the experience, considered as a response shift phenomenon. As individualized measures are ideally suited to explore response shift, this study aimed to estimate the extent to which reconceptualization response shift occurred over time in a cancer population and the impact of this response shift on estimates of change on QOL measures., Methods: Ninety-seven people with advanced cancer completed the study measures including the Patient-Generated Index (PGI) at diagnosis (T0) and 1 year later (T1). The response shift indicator was the change in the number of areas nominated (range - 4 to + 3). Multivariate linear regression was used to estimate the effect of changing areas on change in the PGI score, single indicators of global QOL, and the EQ-5D index adjusted for age and sex., Results: Approximately 72% of people in this sample either added or dropped areas over time. People who dropped more than two areas had higher PGI scores at T1 than T0 while people who added areas showed low PGI score., Conclusion: The results are consistent with the PGI framework as areas nominated tend to focus on negative aspects of QOL.

Addressing the concerns of end-of-life patients or their relatives about their family history of cancer could benefit patients and family members. Little is known about how palliative care providers respond to these concerns. The purpose of this pilot study was to assess palliative care providers' knowledge about familial and hereditary cancers and explore their exposure to patients' and relatives' concerns about their family history of cancer, and their self-perceived ability to deal with such concerns. A cross-sectional survey was conducted in the Quebec City (Canada) catchment area among palliative care professionals. Fifty-eight palliative care professionals working in hospice, home care and hospital-based palliative care units completed the questionnaire. All physicians and 63% of nurses occasionally addressed concerns of patients and relatives about their family history of cancer, but they reported a low confidence level in responding to such concerns. They also showed knowledge gaps in defining features of a significant family history of cancer, and most (78%) would welcome specific training on the matter. Our findings highlight the relevance of offering education and training opportunities about familial cancers and associated risks to palliative care providers. The needs and concerns of end-of-life patients and their families need to be explored to ensure palliative care providers can adequately assist patients and their relatives about their family history of cancer. Ethical implications should be considered.

Background: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/- computerized tomography-defined LSMI. We also explored whether the transcription in muscle of identified genes was altered according to such cachexia phenotype METHODS: A retrospective cohort study design was used. Analysis explored associations of candidate SNPs with WL (n = 1276) and WL + LSMI (n = 943). Human muscle transcriptome (n = 134) was analysed using an Agilent platform., Results: Single nucleotide polymorphisms in the following genes showed association with WL alone: GCKR, LEPR, SELP, ACVR2B, TLR4, FOXO3, IGF1, CPN1, APOE, FOXO1, and GHRL. SNPs in LEPR, ACVR2B, TNF, and ACE were associated with concurrent WL + LSMI. There was concordance between muscle-specific expression for ACVR2B, FOXO1 and 3, LEPR, GCKR, and TLR4 genes and LSMI and/or WL (P < 0.05)., Conclusions: The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI. These findings focus attention on pro-inflammatory cytokines and the renin-angiotensin system as biomarkers/mediators of muscle wasting in cachexia., (© 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: People with advanced cancer experience different sequelae which have unique effects on quality of life (QOL). The patient-generated index (PGI) is a personalized measure that allows patients to nominate, rate, and value areas that have the most impact on QOL. Fatigue, pain, and aspects of physical function are among the top 10 areas with QOL impact. An area of validation that is lacking for the PGI is the extent to which spontaneously nominated areas of QOL that patients are concerned with, agree with ratings obtained from standard patient reported outcomes (PROs)., Methods: Data from 192 patients were used to compare ratings on fatigue, pain, and physical function obtained from PGI to those from standard outcome measures., Results: Within one severity rating, agreement ranged from 32.1 to 76.9 % within the fatigue domain, 34.2 to 95.24 % for pain, and between 84.2 and 94.7 % for physical function. Of the 10 items where the PGI had the highest agreement, 7 came from the RAND-36. At the domain level, people nominating an area scored in the more impaired range on standard measures than people who did not., Conclusion: PGI gives comparable information as do standard measures., Implications for Cancer: PGI provides important information to guide clinical care of the patient and also produces a legitimate total score suitable for research.

Background: Cachexia is a metabolic disorder characterised by muscle wasting, diminished response to anti-cancer treatments and poor quality of life. Our objective was to identify blood-based biomarkers of cachexia in advanced cancer patients. Hence, we characterised the plasma cytokine and blood cell mRNA profiles of patients grouped in three cohorts: patients with cachexia, pre-cachexia (no cachexia but high CRP levels: ⩾ 5 mg l⁻¹) and no cachexia (no cachexia and CRP: < 5 mg l⁻¹)., Methods: A total of 122 newly diagnosed cancer patients with seven cancer types were studied prior to their initial therapy. Plasma levels of 22 cytokines were quantified using the bio-plex technology. mRNAs isolated from whole blood and expression profiles were determined by the chip array technology and Ingenuity Pathway Analysis (IPA) software., Results: In comparison with non-cachectic individuals, both pre-cachectic and cachectic patients showed an increase (⩾ 1.5-folds) in mRNA expression of neutrophil-derived proteases (NDPs) and significantly elevated angiotensin II (Ang II) (P = 0.005 and P = 0.02, respectively), TGFβ1 (P = 0.042 and P < 0.0001, respectively) and CRP (both P < 0.0001) in the plasma. Moreover, cachectic patients displayed a significant increase in IL-6 (P = 0.005), IL-8 (P = 0.001) and absolute neutrophil counts (P = 0.007)., Conclusions: Ang II, TGFβ1, CRP and NDP are blood biomarkers for cancer cachexia. These findings contribute to early diagnosis and prevention of cachexia.

Purposes: Patient Generated Index (PGI) is designed to both ask and document quality of life (QOL) concerns. Its validity with respect to standard QOL measures has not been fully established for advanced cancer when QOL concerns predominate. The specific objective of this study is to identify, for people with advanced cancer, similarities and differences in ratings of global QOL between personalized and standard measures., Methods: A total of 192 patients completed five QOL measures at study entry: PGI, generic measures (SF-6D, EQ-5D), and cancer-specific measures of QOL (McGill Quality of Life Questionnaire and Edmonton Symptoms Assessment Scale). Comparisons among total scores were compared using Generalized Estimating Equations (GEE)., Results: Patients voiced 114 areas of QOL concerns by the PGI with the top three being fatigue, sleep, and pain (39.2, 22.6, and 21.6%, respectively). PGI total QOL score was 25 to 30 percentage points lower than those documented by the other measures, particularly when QOL was poor. Correlations between PGI and other measures were low., Conclusion: PGI allowed patients to express a wide range of QOL concerns, many that were not assessed by other QOL measures. If only one QOL measure is to be included, either in a clinical setting or for research, the PGI would satisfy many of the criteria for "best choice." PGI could be considered a cancer-specific QOL measure., Implications for Cancer: This study provides evidence that the PGI would be a good measure for patients and clinicians to use together to identify areas of concern that require attention and monitor changing needs.

Background: Cancer and cancer-related treatments are associated with a constellation of physical and psychological changes. Treatments associated with noncentral nervous system neoplasms can have short- and long-term effects on cognition, affecting quality of life in people with cancer. Clinical measurement tools specific to cancer-related mild cognitive impairment (MCI) are lacking. The Montreal Cognitive Assessment (MoCA) has been validated in a geriatric population and used in studies assessing MCI in persons with cancer, but no studies have yet shown its psychometric properties when used with this population., Purpose: The purpose of this study is to explore the psychometric properties of the MoCA within a population of persons with noncentral nervous system cancer., Methods: A total of 74 participants were included from persons attending a Cancer Nutrition-Rehabilitation Program at the McGill University Health Centre. Rasch analyses were conducted., Results: The MoCA data fit all the properties of the Rasch model with a person separation index of 1.04 and person reliability of 0.52. The MoCA items were found to measure a unidimensional construct and spanned 6.57 logits, with item difficulty levels between 2.49 and -4.08 logits. However, the MoCA presented a lack of items of higher difficulty, as person cognitive ability levels ranged from -0.51 to 5.17 logits., Conclusion: Within the limits of a small sample size, the results of this exploratory study suggest the possibility that the MoCA, when used within a population of persons with cancer, may meet criteria for unidimensionality and adequate item fit but may present weaknesses when used with participants of higher cognitive abilities.

Context: In Canada, governments have increased spending on home care to promote better end-of-life care. In the province of Québec, Canada, home palliative care (PC) services (HPCS) are provided by Public Local Community-Based Health Care Service providers (Centres Locaux de Services Communautaires [CLSC]) with universal coverage. Accordingly, there should be no regional variations of these services and their effect on quality of end-of-life PC (QEoLPC) indicators., Objectives: To test if all the CLSCs provided the same level of HPCS to cancer patients in the province of Québec, Canada, and the association between level of HPCS and QEoLPC indicators., Methods: Characteristics of 52,316 decedents with cancer were extracted from administrative databases between 2003 and 2006. Two gender-specific "adjusted performance of CLSCs in delivering HPCS" models were created using gender-specific hierarchical regression adjusted for patient and CLSC neighborhood characteristics. Using the same approach, the strength of the association between the adjusted performance of CLSCs in delivering HPCS and the QEoLPC indicators was estimated., Results: Overall, 27,255 (52.1%) decedents had at least one HPCS. Significant variations in the adjusted performance of CLSC in delivering HPCS were found. Higher performance led to a lower proportion of men having more than one emergency room visit during the last month of life (risk ratio [RR] 0.924; 95% CI 0.867-0.985), and for women, a higher proportion dying at home (RR 2.255; 95% CI 1.703-2.984) and spending less time in hospital (RR 0.765; 95% CI 0.692-0.845)., Conclusion: Provision of HPCS remained limited in Québec, but when present, they were associated with improved QEoLPC indicators., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Studies of opioid use in cancer patients have been cross-sectional or have focused on mean consumption over a specific time interval., Objectives: This study aimed to determine the temporal pattern of prescribed opioids at a population level., Methods: Using Quebec administrative databases, we ascertained details of cancer-related deaths and filled community-based opioid prescriptions (COPs) in 48,420 decedents from 2003 to 2006., Results: Using group-based trajectory modeling, based on when people started to fill COPs, our population-based study demonstrated patterns of filled COPs with six distinct trajectories. An earlier start in opioid consumption resulted in a higher group average morphine daily dose; those who were already filling COPs at study entry (5.2%) had a final dose of more than 300mg by the time of death. Remarkably, 58.8% of people had not filled COPs with a biweekly average greater than 1mg earlier than two weeks before death, marking the end of follow-up. Breast cancer in women, prostate or colorectal cancer in men, and younger age and multiple myeloma in both sexes were positively associated with earlier filling of COPs., Conclusion: Patients dying of cancer require increasing doses of opioids over time; although we cannot distinguish the relative contributions of disease progression and opioid tolerance, age and certain cancers seem related to this phenomenon. Given the potentially prohibitive cost of prospective epidemiological studies, more elaborate clinical administrative databases that include regular pain assessment are necessary to determine optimal opioid use and factors associated with dose increases over time at a population level., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The definition of health for people with cancer is not focused solely on the physiology of illness and the length of life remaining, but is also concerned with improving the well-being and the quality of the life (QOL) remaining to be lived. This study aimed to identify the constructs most associated with QOL in people with advanced cancer., Methods: Two hundred three persons with recent diagnoses of different advanced cancers were evaluated with 65 variables representing individual and environmental factors, biological factors, symptoms, function, general health perceptions and overall QOL at diagnosis. Three independent stepwise multiple linear regressions identified the most important contributors to overall QOL. R(2) ranking and effect sizes were estimated and averaged by construct., Results: The most important contributor of overall QOL for people recently diagnosed with advanced cancer was social support. It was followed by general health perceptions, energy, social function, psychological function and physical function., Conclusions: We used effect sizes to summarise multiple multivariate linear regressions for a more manageable and clinically interpretable picture. The findings emphasise the importance of incorporating the assessment and treatment of relevant symptoms, functions and social support in people recently diagnosed with advanced cancer as part of their clinical care.

Context: Low circulating testosterone concentrations are commonly observed in male patients with cancer and have been shown to be associated with weight loss and increased severity of many symptoms, including fatigue and weakness., Objectives: The aim of the present study was to determine the extent to which testosterone deficiency is associated with poor physical function in male patients with nonhormonal cancers., Methods: We measured serum free testosterone concentration in 101 male patients with cancer evaluated at a nutrition-rehabilitation clinic and performed univariate and multivariate linear regression analyses to assess the effect of a free testosterone concentration in the lowest quartile on six-minute walk distance (6-MWD) (n=100) and maximal gait speed (n=49)., Results: In the univariate analyses, patients in the lowest free testosterone quartile had a 6-MWD that was 96 m (95% CI 51, 141) less and a maximal gait speed that was 0.26 m/second (95% CI 0.06, 0.47) slower on average than patients in the upper three free testosterone quartiles. When controlling for other demographic, clinical, and biological factors, a free testosterone concentration in the lowest quartile was associated, on average, with a 51 m (95% CI 44, 97) lower 6-MWD but did not affect maximal gait speed., Conclusion: The present study shows that in male patients with cancer, an extremely low serum free testosterone concentration is independently associated with 6-MWD but not maximal gait speed. Hence, a severe testosterone deficiency may impair their ability to perform sustained activity, but to a lesser degree, short bursts of activity., (Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Objective: Delirium is a highly prevalent and deleterious disorder in terminally ill cancer patients. We assessed whether a multicomponent preventive intervention was effective in decreasing delirium incidence and severity among cancer patients receiving end-of-life care., Methods: A cohort of 1516 patients was followed from admission to death at seven Canadian palliative care centers. In two of these centers, routine care included a delirium preventive intervention targeting physicians (written notice on selective delirium risk factors and inquest on intended medication changes), patients, and their family (orientation to time and place, information about early delirium symptoms). Delirium frequency and severity were compared between patients at the intervention (N = 674) and usual-care (N = 842) centers based on thrice-daily symptom assessments with the Confusion Rating Scale., Results: The overall rate of adherence to the intervention was 89.7%. The incidence of delirium was 49.1% in the intervention group, compared with 43.9% in the usual-care group (odds ratio [OR] 1.23, P = 0.045). When confounding variables were controlled for, no difference was observed between the intervention and the usual-care groups in delirium incidence (OR 0.94, P = 0.66), delirium severity (1.83 vs. 1.92; P = 0.07), total days in delirium (4.57 vs. 3.57 days; P = 0.63), or duration of first delirium episode (2.9 vs. 2.1 days; P = 0.96). Delirium-free survival was similar in the two groups., Conclusion: A simple multicomponent preventive intervention was ineffective in reducing delirium incidence or severity among cancer patients receiving end-of-life care. Delirium prevention remains a difficult challenge in terminally ill cancer patients., (Copyright © 2010 John Wiley & Sons, Ltd.)

Purpose of Review: Delirium is the most frequent neuropsychiatric disorder that affects the advanced cancer population who are receiving palliative care. There is limited evidence and much debate about the role of hydration in delirium management at the end of life. The purpose of this article is to review the literature on delirium management with regards to pharmacological management and hydration., Recent Findings: Pharmacological management is the first line of treatment for delirium, whereby antipsychotics are the medication of choice. However, they have not been approved by the United States Food and Drug Administration for delirium management as there is insufficient evidence supporting their use. Hydration is a believed to be a key component of delirium reversibility; yet there are conflicting results on its efficacy as an intervention for delirium management. As there are few studies of good methodological quality on the topic and large variations in practice, the effectiveness of hydration as an alternative management option for delirium is unclear., Summary: More work is required to assess the role of hydration in delirium at the end of life. Given the lack of evidence-based research on hydration, more randomized clinical trials are needed to elucidate the effects of hydration as a delirium intervention.

This multicenter trial examined the efficacy and safety of dextromethorphan (DM) as an enhancer of analgesia and modulator of opioid tolerance in cancer patients with pain. Eligible patients were randomized to slow-release morphine plus DM or slow-release morphine plus placebo. The initial DM dose was 60 mg four times daily for seven days, with an increase to 120 mg four times daily, if tolerated, for another seven days. During the study, patients recorded medications and scores for pain, nausea, drowsiness, and insomnia. Sixty-five patients were randomized. Although average pain scores (12.6 vs. 15.8), number of breakthrough doses (9 vs. 11.3), and change in total morphine consumption (550.9 mg vs. 597.1mg) were less in the DM group than placebo group, the differences were not statistically significant (P=0.31-0.33). Side-effect scores were not statistically significantly different. Dizziness was greater in the DM (58%) than placebo (36%) group. This study showed a statistically nonsignificant enhancement of analgesia or modulation of opioid tolerance in cancer patients with pain when DM was added to morphine. Participants receiving the DM also had more toxicity, particularly dizziness. This toxicity and the limited evidence of effect do not support the use of DM to enhance opioid analgesia or to modulate opioid tolerance in cancer patients.

Objective: To investigate the clinical improvement observed in patients with advanced cancer and hypoactive delirium after the administration of methylphenidate hydrochloride., Methods: Fourteen patients with advanced cancer and hypoactive delirium were seen between March 1999 and August 2000 at the Palliative Care Day Hospital and the inpatient Tertiary Palliative Care Unit of Montreal General Hospital, Montreal. They were chosen for inclusion in a prospective clinical study on the basis of (1) cognitive failure documented by the Mini-Mental State Examination (MMSE), (2) sleep-wake pattern disturbances, (3) psychomotor retardation, (4) absence of delusions or hallucinations, and (5) absence of an underlying cause to explain the delirium. All patients were treated with methylphenidate, and changes in their cognitive function were measured using the MMSE., Results: All 14 patients showed improvement in their cognitive function as documented by the MMSE. The median pretreatment MMSE score (maximum score 30) was 21 (mean 20.9, standard deviation [SD] 4.9), which improved to a median of 27 (mean 24.9, SD 4.7) after the first dose of methylphenidate (p < 0.001, matched, paired Wilcoxon signed rank test). One patient died before reaching a stable dose of methylphenidate. In the other 13 patients, the median MMSE score further improved to 28 (mean 27.8, SD 2.4) (p = 0.02 compared with the median MMSE score documented 1 hour after the first dose of methylphenidate). All patients showed an improvement in psychomotor activities., Conclusions: Hypoactive delirium that cannot be explained by an underlying cause (metabolic or drug-induced) in patients with advanced cancer appears to be a specific syndrome that could be improved by the administration of methylphenidate.

Purpose: Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA., Patients and Methods: Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d., Results: A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable., Conclusion: This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.

Most cancer patients will experience pain requiring opioid therapy during their illness. Standard opioid therapy includes fixed scheduled doses and so-called "rescue" doses for breakthrough pain. Circadian rhythms seem to influence the expression of pain and the responsiveness to analgesic medication. Delirium is a common complication in advanced cancer patients and it also may modify the expression of pain and the use of analgesic medication. We reviewed the circadian distribution of breakthrough analgesia (BTA) doses in 104 advanced cancer patients who were part of a prospective study of the occurrence of delirium. We found that the circadian distribution of BTA is significantly different from a random distribution in the case of patients with and without delirium. Patients without delirium tended to use more BTA (P < 0.001) in the morning, whereas patients with delirium tended to use more BTA in the evening and at night (P = 0.02). We conclude that delirium is associated with changes in the circadian distribution of BTA, which is possibly related to reversal of the normal circadian rhythm.

Background: Delirium is a common neuropsychiatric complication in patients with advanced cancer. The Memorial Delirium Assessment Scale (MDAS) is a recently developed 10-item severity rating instrument. The purpose of the current prospective study was to further assess the clinical utility, factor structure, and validity of the MDAS in a relatively homogeneous population of patients with advanced cancer., Methods: Study entry of 104 patients occurred on their consecutive admission to a tertiary-level, acute palliative care unit in a university-affiliated teaching hospital. Patients underwent regular cognitive screening using the Mini-Mental State Examination, and serial monitoring of delirium using standardized semistructured interviews and MDAS ratings, up to the study endpoints of either patient discharge or death., Results: Seventy-one patients met Diagnostic and Statistical Manual (of Mental Disorders)-IV criteria for a first episode of delirium. In 15 of 71 (21%) patients with a first episode of delirium, the first MDAS ratings were prorated because of dyspnea, fatigue, or profound delirium. In the remaining 56 patients (79%), the first MDAS ratings were rated fully and therefore evaluable. Correlations among the scale items ranged from moderate to low (correlation coefficient [r] = 0.68-0.02). Analysis of the pattern of factor loadings identified two primary correlated factors: global cognitive (Factor I) and neurobehavioral (Factor II) (r = 0.33). Cronbach alpha coefficients for Factors I and II were 0.8 and 0.66, respectively, indicating a relatively high level of correlation for items within each. The Cronbach alpha coefficient for all 10 items was 0.78, suggesting a general underlying factor. In a larger sample of complete MDAS ratings (n = 330) a cutoff total MDAS score of 7 of 30 yielded the highest sensitivity (98%) and specificity (96%) for delirium diagnosis. The MDAS was correlated moderately with the Mini-Mental State Examination (r = 0.55)., Conclusions: The authors concluded that the MDAS structure is representative of the many features of delirium, broadly grouped as global cognitive and neurobehavioral dimensions. Prorating item scores is necessary in approximately 20% of advanced cancer patients with delirium. This poses potential limitations on the applicability of the MDAS in research. Conversely, the ability to prorate item scores confers a clinical advantage to the instrument when assessing delirium in a patient population with advanced cancer., (Copyright 2000 American Cancer Society.)

Context: Delirium impedes communication and contributes to symptom distress in patients with advanced cancer. There are few prospective data on the reversal of delirium in this population., Objectives: To evaluate the occurrence, precipitating factors, and reversibility of delirium in patients with advanced cancer., Design: Prospective serial assessment in a consecutive cohort of 113 patients with advanced cancer. Precipitating factors were examined using standardized criteria; 104 patients met eligibility criteria., Setting: Acute palliative care unit in a university-affiliated teaching hospital., Main Outcome Measures: Delirium occurrence and reversal rates, duration, and patient survival. Strengths of association of various precipitating factors with reversal were expressed as hazard ratios (HRs) in univariate and multivariate analyses., Results: On admission, delirium was diagnosed in 44 patients (42%), and of the remaining 60, delirium developed in 27 (45%). Reversal of delirium occurred in 46 (49%) of 94 episodes in 71 patients. Terminal delirium occurred in 46 (88%) of the 52 deaths. In univariate analysis, psychoactive medications, predominantly opioids (HR, 8.85; 95% confidence interval [CI], 2.13-36.74), and dehydration (HR, 2.35; 95% CI, 1.20-4.62) were associated with reversibility. Hypoxic encephalopathy (HR, 0.39; 95% CI, 0.19-0.80) and metabolic factors (HR, 0.44; 95% CI, 0.21-0.91) were associated with nonreversibility. In mulitivariate analysis, psychoactive medications (HR, 6.65; 95% CI, 1.49-29.62), hypoxic encephalopathy (HR, 0.32; 95% CI, 0.15-0.70), and nonrespiratory infection (HR, 0.23; 95% CI, 0.08-0.64) had independent associations. Patients with delirium had poorer survival rates than controls (P<.001)., Conclusions: Delirium is a frequent, multifactorial complication in advanced cancer. Despite its terminal presentation in most patients, delirium is reversible in approximately 50% of episodes. Delirium precipitated by opioids and other psychoactive medications and dehydration is frequently reversible with change of opioid or dose reduction, discontinuation of unnecessary psychoactive medication, or hydration, respectively.

In the past 20 years, cachexia in cancer patients has attracted increasing interest from both clinicians and basic researchers. It is now clear that the cachexia is secondary to major metabolic abnormalities due to tumour by-products and cytokine release. These metabolic abnormalities produce numerous symptoms such as cachexia, anorexia and asthenia. There are now effective drugs such as corticosteroids and progestational drugs that have been shown to improve appetite, food intake and sensation of well-being, and which elicit bodyweight gain. While hydrazine (hydrazine sulfate) has received much attention, unfortunately it has been shown to be ineffective in improving the symptoms of the patient with cancer cachexia. A new group of drugs, such as thalidomide and melatonin because of their effects on tumour necrosis factor-alpha, and beta 2-adrenoceptor agonists because of their effects on muscle metabolism, and other agents, is presently reaching the clinical trial stage. There is now the possibility of addressing this fascinating syndrome at a different level and an opportunity for combined therapy to try to improve the quality of life of these patients.