Quality of life and symptom intensity over time in people with cancer receiving palliative care : results from the international European Palliative Care Cancer Symptom study

Background People with advanced cancer experience multiple symptoms during their illness trajectory, which can fluctuate in intensity. Aim To describe the course of self-reported quality of life, emotional functioning, physical functioning and symptom intensity over time in cancer patients receiving palliative care. Design Longitudinal study with monthly assessments, using the EORTC QLQ-C15-PAL. Data were analysed (1) prospectively, from baseline to >= 8-month follow-up; and (2) retrospectively, by taking death as index date and comparing results from three cross-sectional subsamples at different stages of illness (time to death >= 6, 5-3 and 2-0 months). Linear mixed models were calculated. Setting/participants A total of 1739 patients (mean age 66, 50% male) from 30 palliative care centers in 12 countries were included. Results In prospective analyses, quality of life, functioning and symptoms-except nausea/vomiting-remained generally stable over time. In retrospective analyses, patients 2-0 months before death reported significantly lower quality of life and physical functioning scores than those 5-3 months before death, who in turn scored lower than those >= 6 months before death, suggesting progressive decline. Emotional functioning remained initially unchanged, but decreased in the last months. Pain, fatigue and appetite loss showed a stable increase in intensity towards death. Dyspnea, insomnia and constipation increased from 5-3 to 2-0 months before death. Nausea/vomiting only increased when comparing those >= 6 months before death with those 2-0 months before death. Conclusion While the prospective approach showed predominantly stable patterns for quality of life, functioning and symptom severity throughout study duration, retrospective analyses indicated that deterioration was already apparent before the terminal phase and accelerated close to death. Our findings support the importance of early symptom identification and treatment in this population, and highlight the need for further studies to explore what characterizes those with either lower or higher symptom burden at different time points towards death

Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?

© 2015, BMJ Publishing Group. All rights reserved. Objectives: Opioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness. Setting: 17 hospice/palliative care services (tertiary services) in 11 European countries. Participants: 2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. Primary outcome measures: The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). Secondary outcome measures: The same measures for people on oxycodone (n=402) or fentanyl (n=429). Results: SNPs not in Hardy-Weinberg equilibrium or with allele frequencies ( < 5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with oxycodone. Conclusions: This large, exploratory study identified 1 biologically plausible SNP that warrants further study in the response of breathlessness to morphine therapy

Home death for children dying in six European countries

Aim: Guidelines on pediatric palliative care underline that care at the end of life of chronically ill children should preferably be provided in the child’s home situation. Till present, no European data at population level are available for place of death of children. The aim of this study was to compare proportions of home death for children in six European countries and investigate relation between place of death and sociodemographic and clinical factors. Method: Data were collected from death certificates of all deceased children aged 1-17 in Belgium (BE), the Netherlands (NL), Norway (NO), England (E), Wales (W) (2003) and Italy (IT) (2002). Gender, cause (cancer, natural non-cancer and external) and place of death (home vs. outside home) and sociodemographic factors (socio-economic status (SES), degree of urbanization and number of hospital beds in the area) were included in the analyses. Data were analyzed using frequencies and multivariate logistic regression. Results: A total of 3.187 deaths were included in the analyses, 534 (16,8%) died from cancer. The proportion of home deaths was 19,6% (IT), 20,5% (E), 20,6% (W), 21,0% (NO), 23,8% (BE) and 28,6% (NL). Home death was more likely for children dying from cancer in BE, NL, E and W, for children with high SES in BE, in areas with low number of hospital beds in IT, and for boys in NL. Conclusion: The proportion of home deaths for children differs between studied countries. In most, but not all, countries children dying from cancer had better odds of dying at home than those not dying from cancer. Although acknowledging the influence of culture in the differences, studying care provisions in countries with higher proportions of home deaths, particularly in chronically ill children, can be helpful to identify factors facilitating terminally ill children to die at home. Early involvement of palliative care and equal access to these services can be important in this context. Funding: IWT-Flanders

Genetic variation and cognitive dysfunction in opioid-treated patients with cancer

Background and purpose The effects of single‐nucleotide polymorphisms (SNP s) on the cognitive function of opioid‐treated patients with cancer until now have not been explored, but they could potentially be related to poor functioning. This study aimed at identifying associations between SNP s of candidate genes, high opioid dose, and cognitive dysfunction. Methods Cross‐sectional multicenter study (European Pharmacogenetic Opioid Study, 2005–2008); 1586 patients; 113 SNP s from 41 genes. Inclusion criteria: cancer, age ≥18 year, opioid treatment, and available genetic data. Cognitive assessment by Mini‐Mental State Examination (MMSE ). Analyses: SNP s were rejected if violation of Hardy–Weinberg equilibrium (P < 0.0005), or minor allele frequency <5%; patients were randomly divided into discovery sample (2/3 for screening) and validation sample (1/3 for confirmatory test); false discovery rate of 10% for determining associations (Benjamini–Hochberg method). Co‐dominant, dominant, and recessive models were analyzed by Kruskal–Wallis and Mann–Whitney tests. Results In the co‐dominant model significant associations (P < 0.05) between MMSE scores and SNP s in the HTR 3E , TACR 1 , and IL 6 were observed in the discovery sample, but the replication in the validation sample did not confirm it. Associations between MMSE scores among patients receiving ≥400 mg morphine equivalent dose/day and SNP s in TNFRSF 1B , TLR 5 , HTR 2A , and ADRA 2A were observed, but they could not be confirmed in the validation sample. After correction for multiple testing, no SNP s were significant in the discovery sample. Dominant and recessive models also did not confirm significant associations. Conclusions The findings did not support influence of those SNP s analyzed to explain cognitive dysfunction in opioid‐treated patients with cancer

Health care providers underestimate symptom intensities of cancer patients: A multicenter European study

<p>Abstract</p> <p>Background</p> <p>Many patients with advanced cancer depend upon health care providers for symptom assessment. The extent of agreement between patient and provider symptom assessments and the association of agreement with demographic- and disease-related factors was examined.</p> <p>Methods</p> <p>This cross-sectional study included 1933 patient-health care provider dyads, from 11 European countries. Patients reported symptoms by using the four-point scales of the European Organization of Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) version 3, and providers used corresponding four-point categorical scales. Level of agreement was addressed at the group level (Wilcoxon Signed-Rank test), by difference scores (provider score minus patient score), at the individual level (Intraclass Correlation Coefficients, ICCs) and visually by Bland-Altman plots. Absolute numbers and chi-square tests were used to investigate the relationship between agreement and demographic-, as well as disease-related factors.</p> <p>Results</p> <p>The prevalence of symptoms assessed as moderate or severe by patients and providers, respectively, were for pain (67 vs.47%), fatigue (71 vs. 54%), generalized weakness (65 vs. 47%), anorexia (47 vs. 25%), depression (31 vs. 17%), constipation (45 vs. 30%), poor sleep (32 vs. 21%), dyspnea (30 vs. 16%), nausea (27 vs. 14%), vomiting (14 vs. 6%) and diarrhea (14 vs. 6%). Symptom scores were identical or differed by only one response category in the majority of patient-provider assessment pairs (79-93%). Providers underestimated the symptom in approximately one of ten patients and overestimated in 1% of patients. Agreement at the individual level was moderate (ICC 0.38 to 0.59). Patients with low Karnofsky Performance Status, high Mini Mental State-score, hospitalized, recently diagnosed or undergoing opioid titration were at increased risk of symptom underestimation by providers (all p < 0.001). Also, the agreement was significantly associated with drug abuse (p = 0.024), provider profession (p < 0.001), cancer diagnosis (p < 0.001) and country (p < 0.001).</p> <p>Conclusions</p> <p>Considerable numbers of health care providers underestimated symptom intensities. Clinicians in cancer care should be aware of the factors characterizing patients at risk of symptom underestimation.</p

Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain

<p>Abstract</p> <p>Background</p> <p>Genetic variation contributes to differences in pain sensitivity and response to different analgesics. Catecholamines are involved in the modulation of pain and are partly metabolized by the catechol-O-methyltransferase (COMT) enzyme. Genetic variability in the <it>COMT </it>gene may therefore contribute to differences in pain sensitivity and response to analgesics. It is shown that a polymorphism in the <it>COMT </it>gene, Rs4680 (Val158Met), influence pain sensitivity in human experimental pain and the efficacy for morphine in cancer pain treatment. In this study we wanted to investigate if variability in other regions in the <it>COMT </it>gene also contributes to interindividual variability in morphine efficacy.</p> <p>Results</p> <p>We genotyped 11 single nucleotide polymorphisms (SNPs) throughout the <it>COMT </it>gene, and constructed haplotypes from these 11 SNPs, which were in Hardy-Weinberg equilibrium. We compared both genotypes and haplotypes against pharmacological, demographical and patient symptoms measurements in a Caucasian cancer patient cohort (n = 197) receiving oral morphine treatment for cancer pain. There were two frequent haplotypes (34.5% and 17.8%) in our cohort. Multivariate analyses showed that patients carrying the most frequent haplotype (34.5%) needed lower morphine doses than patients not carrying the haplotype, with a reduction factor of 0.71 (p = 0.005). On the allele level, carriers of alleles for six of the SNPs show weak associations in respect to morphine dose and the alleles associated with the lowest morphine doses constitute part of the most frequent haplotype.</p> <p>Conclusion</p> <p>This study suggests that genetic variability in the <it>COMT </it>gene influence the efficacy of morphine in cancer patients with pain, and that increased understanding of this variability is reached by expanding from analyses of single SNPs to haplotype construction and analyses.</p

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids

Acknowledgments. We are grateful to all the researchers involved in The European Pharmacogenetic Opioid Study (EPOS) and to Gunnhild Jakobsen who organized the collection of data.Peer reviewedPublisher PD

An exploratory study examining the relationship between performance status and systemic inflammation frameworks and cytokine profiles in patients with advanced cancer

The role of cytokines in the systemic inflammatory response (SIR) is now well established. This is in keeping with the role of the SIR in tumorigenesis, malignant spread, and the development of cachexia. However, the relationship between performance status/systemic inflammation frameworks and cytokine profiles is not clear. The aim of the present study was to examine the relationship between the Eastern cooperative oncology group performance status/modified Glasgow prognostic score (ECOG-PS/mGPS) and cooperative oncology group performance status/neutrophil platelet score (ECOG-PS/NPS) frameworks and their cytokine profile in patients with advanced cancer.This was a retrospective interrogation of data already collected as part of a recent clinical trial (NCT00676936). The relationship between the independent variables (ECOG-PS/mGPS and ECOG-PS/NPS frameworks), and dependent variables (cytokine levels) was examined using independent Mann-Whitney U and Kruskal Wallis tests where appropriate.Of the 40 patients included in final analysis the majority had evidence of an SIR assessed by mGPS (78%) or NPS (53%). All patients died on follow-up and the median survival was 91 days (4-933 days). With increasing ECOG-PS there was a higher median value of Interleukin 6 (IL-6, P = .016) and C-reactive protein (CRP, P &lt; .01) and lower albumin (P &lt; .01) and poorer survival (P &lt; .001). With increasing mGPS there was a higher median value of IL-6 (P = .016), Macrophage migration inhibitory factor (MIF, P = .010), erythrocyte sedimentation rate (ESR, P &lt; .01) and poorer survival (P &lt; .01). With increasing NPS there was a higher median value of TGF-β (P &lt; .001) and C-reactive protein (P = .020) and poor survival (P = .001). When those patients with an ECOG-PS 0/1 and mGPS0 were compared with those patients with an ECOG-PS 2 and mGPS2 there was a higher median value of IL-6 (P = .017) and poorer survival (P &lt; .001). When those patients with an ECOG-PS 0/1 and NPS0 were compared with those patients with an ECOG-PS 2 and NPS1/2 there was a higher median value of IL-6 (P = .002), TGF-β (P &lt; .001) and poorer survival (P &lt; .01).In patients with advanced cancer IL-6 was associated with the ECOG-PS/mGPS and ECOG-PS/NPS frameworks and survival in patients with advanced cancer. Therefore, the present work provides supporting evidence that agents targeting IL-6 are worthy of further exploration

Sleep quality with WHO Step III opioid use for cancer pain

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Calling for advocacy, education and public policy actions on pain control for patients with cancer in Africa

It is of serious concern that there is a lack of focus on pain management in patients with cancer in Africa. Most patients with cancer present with advanced disease on diagnosis, experiencing moderate to severe pain and in need of palliative care. Integration of palli-ative and oncology care is recommended by European Society of Medical Oncology (ESMO) and by the World Health Assembly resolution WHA67.19.At the recent ESMO Summit Africa 2020, a Pain Workshop was attended by representatives from across Africa. A consensus was reached to escalate concerns about lack of pain management in patients with cancer in Africa and to call on ESMO to make universal cancer pain control, and integrated oncology and palliative care as an immediate priority area