Anne Kari Knudsen

Classification of pain in cancer patients – a systematic literature review

One of the aims of the European Palliative Care Research Collaborative (EPCRC) is to achieve consensus on a classification system for cancer pain. We performed a systematic literature review to identify existing classification systems and domains/items used to classify cancer patients with pain. In a systematic search in the databases Medline and Embase, covering 1986–2006, 692 hits were obtained. 92 papers were evaluated to address pain classification. Six standardised classification systems were identified; three of them systematically developed and partially validated. Both pain characteristics and patient characteristics relevant for cancer pain classification were included in the classification systems. All but one of the standardised systems aim at predicting treatment response or adequacy of treatment. Several domains and items used to describe cancer pain but not formally described as part of a classification system were also identified and systematised. The existing approaches to pain classification in cancer patients are different, mostly not thoroughly validated, and none is widely applied. An internationally accepted classification system for cancer pain could improve research and cancer pain management. This systematic review suggests a need for developing an international consensus on how to classify pain in cancer patients.

Which variables are associated with pain intensity and treatment response in advanced cancer patients?--Implications for a future classification system for cancer pain.

Background: This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain.BACKGROUND This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain. METHODS Data from an international, multicentre, cross-sectional study of cancer patients treated with opioids were investigated. Dependent variables were: average pain, worst pain, and pain relief (11-point Numerical Rating Scales). Forty-six independent variables were chosen based upon previous studies. Bivariate analyses identified independent variables associated with at least one of the dependent ones; 21 were included in multivariate linear regression analyses. RESULTS Two thousand two hundred and seventy-eight patients were investigated; 52% males, mean age 62 years, mean Karnofsky Performance Status 59%, mean daily opioid oral equivalent dose 341 mg. Fifty-eight percent had breakthrough pain. Mean pain scores were: average pain 3.5, worst pain 5.3 and pain relief 74%. Variables most strongly associated with these three dependent variables were: breakthrough pain, psychological distress, sleep, and opioid dose. CONCLUSIONS Breakthrough pain and psychological distress were confirmed as key variables of a future classification system. Candidate variables were: sleep, opioid dose, pain mechanism, use of non-opioids, pain localisation, cancer diagnosis, location of metastases, and addiction.

Which domains should be included in a cancer pain classification system? Analyses of longitudinal data

Summary Pain intensity, incident pain, pain localisation, and cancer diagnosis are important domains to include in an international cancer pain classification system. Abstract The overall aim of the present study was to further develop an evidence‐based platform for the content of an international cancer pain classification system. Data from a multicentre, observational longitudinal study of cancer patients were analysed. Analyses were carried out in 2 samples: (A) Cross‐sectional data of patients on opioids at inclusion, and (B) patients just admitted to palliative care. Outcome measures in the models we investigated were pain on average, worst pain, and pain relief at inclusion, and at day 14, respectively. Uni‐ and multivariate regression models were applied to test the explicative power on pain outcomes of a series of known pain domains, including incident pain, psychological distress, neuropathic pain, pain localisation, sleep disturbances, total morphine equivalent daily dose (MEDD), and cancer diagnosis. In the 2 analyses, 1529 (A) and 352 (B) patients were included, respectively. Incident pain, pain localisation, MEDD, use of nonsteroidal antiinflammatory drugs, and sleep were associated with one or more of the pain outcomes in analysis A, while initial pain intensity, initial pain relief, incident pain, localisation of pain, cancer diagnosis, and age were predictors in the longitudinal analysis. Identified domains explained 16% to 24% of the variability of the pain outcome. Initial pain intensity emerged as the strongest predictor of pain outcome after 2 weeks, and incident pain was confirmed to be a relevant domain. The regression models explained only a minor part of the variability of pain outcomes.

Multiple Loci Modulate Opioid Therapy Response for Cancer Pain

Purpose: Patients treated with opioid drugs for cancer pain experience different relief responses, raising the possibility that genetic factors play a role in opioid therapy outcome. In this study, we tested the hypothesis that genetic variations may control individual response to opioid drugs in cancer patients. Experimental Design: We tested 1 million single-nucleotide polymorphisms (SNP) in European cancer patients, selected in a first series, for extremely poor (pain relief ≤40%; n = 145) or good (pain relief ≥90%; n = 293) responses to opioid therapy using a DNA-pooling approach. Candidate SNPs identified by SNP-array were genotyped in individual samples constituting DNA pools as well as in a second series of 570 patients. Results: Association analysis in 1,008 cancer patients identified eight SNPs significantly associated with pain relief at a statistical threshold of P < 1.0 × 10−3, with rs12948783, upstream of the RHBDF2 gene, showing the best statistical association (P = 8.1 × 10−9). Functional annotation analysis of SNP-tagged genes suggested the involvement of genes acting on processes of the neurologic system. Conclusion: Our results indicate that the identified SNP panel can modulate the response of cancer patients to opioid therapy and may provide a new tool for personalized therapy of cancer pain. Clin Cancer Res; 17(13); 4581–7. ©2011 AACR.

The Edmonton Classification System for Cancer Pain: Comparison of Pain Classification Features and Pain Intensity Across Diverse Palliative Care Settings in Eight Countries

BACKGROUND Standardized approaches for assessing and classifying cancer pain are required to improve treatment of patients with complex pain profiles. The Edmonton Classification System for Cancer Pain (ECS-CP) offers a starting point for the evolution of a standardized international classification system for cancer pain and was introduced into multisite research initiatives of the European Palliative Care Research Collaborative (EPCRC). OBJECTIVES The primary purpose of this study was to describe the prevalence of the five ECS-CP pain classification features: pain mechanism, incident pain, psychological distress, addictive behavior, and cognition--in a diverse international sample of patients with advanced cancer. METHODS A total of 1070 adult patients with advanced cancer were recruited from 17 sites in Norway, the United Kingdom, Austria, Germany, Switzerland, Italy, Canada, and Australia; 1051 of 1070 patients were evaluable. A clinician completed the ECS-CP for each enrolled patient. Additional information, including pain intensity, were also collected through patient self-reports, using touch-sensitive computers. RESULTS Of 1051 evaluable patients, 670 (64%) were assessed by a clinician as having cancer pain: nociceptive pain (n=534; 79.7%); neuropathic pain (n=113; 16.9%); incident pain (n=408; 60.9%); psychological distress (n=212; 31.6%); addictive behavior (n=30; 4.5%); normal cognition (n=616; 91.9%). The prevalence of ECS-CP features and pain intensity scores (11-item scale; 0=none, 10=worst; rated as now) varied substantially across sites and locations of care. CONCLUSION The ECS-CP is a clinically relevant systematic framework, which is able to detect differences in salient pain classification features across diverse settings and countries. Further validation studies need to be conducted in varied advanced cancer and palliative care settings to advance the development of the ECS-CP toward an internationally recognized pain classification system.

The use of antidepressants in patients with advanced cancer—results from an international multicentre study

Depression is common in patients with advanced cancer; however, it is not often recognized and therefore not treated. The aims of this study were to examine the prevalence of the use of antidepressants (ADs) in an international cross‐sectional study sample and to identify sociodemographic and medical variables associated with their use.

Integration between oncology and palliative care: a plan for the next decade?

With the groundbreaking work of three Milan professors—Bonadonna, Veronesi, and Ventafridda—in the 1980s as the starting point, this article aims to shed light on the potential benefits of a closer and more formal integration between oncology and palliative care. More specifically, we address why integration is needed, how to do it, and the potential benefits to the patients, families, and society. The costs for cancer care are increasing rapidly. Especially during the last year of life, some treatments are futile and expensive without proven benefit for patients in terms of prolonged survival with adequate quality of life (QoL). The latest WHO definition of palliative care supports an upstream introduction of palliative care. More recent studies indicate that such an early integration has the potential to improve the patients’ QoL and reduce their symptom burden. Successful integration presupposes formal structures and explicit obligations on how and when to integrate. The Norwegian model for palliative care is presented. It covers the range of oncologic and palliative services from community health care via the local hospital to the tertiary hospital and rests on standardized care pathway as the key instrument to promote integration. Our present state of knowledge indicates that integration does not shorten life; perhaps even the opposite. Futile oncological treatment can be reduced and the QoL of patients and carers improved. We need more evidence on the potential effect upon costs, but present data indicate that integration does not increase them.

Resilience for family carers of advanced cancer patients—how can health care providers contribute? A qualitative interview study with carers:

Background: Caring for advanced cancer patients affects carers’ psychological and physical health. Resilience has been defined as “the process of adapting well in the face of adversity, trauma, tragedy, threats or even significant sources of threat.” Aim: The aim of this study was to explore factors promoting carer resilience, based on carers’ experiences with and preferences for health care provider support. Design: Qualitative, semi-structured, individual interviews with family carers of advanced cancer patients were performed until data saturation. The interviews were recorded, transcribed, and analyzed using systematic text condensation. Setting/participants: Carers (n = 14) of advanced cancer patients, not receiving curative treatment, admitted to an integrated curative and palliative care cancer outpatient clinic or to a university hospital cancer clinic, were included. Results: 14 carers of advanced cancer patients were included; 7 men, 7 women, and mean age of 59 years; 3 were bereaved; 12 were partners; 5 had young and teenage children. Four main resilience factors were identified: (1) being seen and known by health care providers—a personal relation; (2) availability of palliative care; (3) information and communication about illness, prognosis, and death; and (4) facilitating a good carer–patient relation. Conclusion: Health care providers may enhance carers’ resilience by a series of simple interventions. Education should address carers’ support needs and resilience. Systematic assessment of carers’ support needs is recommended. Further investigation is needed into how health care providers can help carers and patients communicate about death.

Depressive symptoms in the last days of life of patients with cancer: a nationwide retrospective mortality study

Objectives Depressive symptoms are common in patients with cancer and tend to increase as death approaches. The study aims were to examine the prevalence of depressive symptoms in patients with cancer in their final 24 h, and their association with other symptoms, sociodemographic and care characteristics. Methods A stratified sample of deaths was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). Adult patients with cancer with non-sudden death were included (n=1363). Symptoms during the final 24 h of life were assessed on a 1–5 scale and categorised as 1=no, 2–3=mild/moderate and 4–5=severe/very severe. Results Depressive symptoms were registered in 37.6% of the patients. Patients aged 80 years or more had a reduced risk of having mild/moderate depressive symptoms compared with those aged 17–65 years (OR 0.70; 95% CI 0.50 to 0.99). Elderly care physicians were more likely to assess patients with severe/very severe depressive symptoms than patients with no depressive symptoms (OR 4.18; 95% CI 1.48 to 11.76). Involvement of pain specialists/palliative care consultants and psychiatrists/psychologists was associated with more ratings of severe/very severe depressive symptoms. Fatigue and confusion were significantly associated with mild/moderate depressive symptoms and anxiety with severe/very severe symptoms. Conclusions More than one-third of the patients were categorised with depressive symptoms during the last 24 h of life. We recommend greater awareness of depression earlier in the disease trajectory to improve care.

Author’s reply to: Integration between oncology and palliative care: a plan for the next decade?

We appreciate the thoughtful comments on our article by Giusti et al. They portrayed integration as challenging and depending on several factors, and to us, from Northern Europe, the Italian experiences and ways of dealing with some challenges were fascinating. The authors highlight some important points. Integration presupposes something to integrate, which is not the case throughout the world. In many countries or even in regions within the same country, cancer palliative care is limited or absent, which in turn makes integration meaningless. Second, even in societies where health care services are in place, integration might be challenging locally, regionally, or even nationally. As mentioned, crucial factors seem to be the type and place of care, leadership, tradition, and culture, as well as the culture of the health care personnel providing the services. Additionally, competence in palliative care needs to be present among all involved partners in the team responsible for the integrated care pathways. In order to change Italian practice, the government has proclaimed an ad hoc law, while in Norway we have tried to use economic incentives. We are not sure whether the Norwegian way is a better strategy than the Italian. Government supervision or regulation through legislation are 2 alternative options that potentially could promote integration. Might legislation ensuring patients’ safety and evidence-based treatment have an impact on health care delivery? Or will it just increase the level of parallel play and not have a real effect on the level of interaction and thereby integration? Regardless of the method used, integration seems to challenge a core element in the medical culture: physicians’ autonomy. Why is it so difficult to change physicians’ behavior? Despite more than 30 years of efforts to improve pain treatment in cancer patients, the results do not seem to have improved (1). The stereotype of the physician as an individual promoting health and well-being to his or her patients in a one-to-one relationship is no longer valid. Health care in most cases is delivered by a team, which implies that several doctors work together as a collaborative and often with other health care providers as well. This is one of the basics of modern health care. If such an interpretation of present medical practice is correct, then medicine should borrow models from other parts of society that have solved similar challenges related to complex systems. Such models exist, and the methodology of standardized care pathways is one of them. The standardized care pathways model comes from the car industry, making health care delivery resemble assembly lines. Taking care of patients should not be compared to automobile assembly; however, a systematic approach to improve health care services is needed. Still, the effects of alternative models need to be tested with the same scientific rigorousness as other new therapies in order to find a better way to provide care for our patients and their families.