Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

Pharmacological treatments for fatigue associated with palliative care: executive summary of a Cochrane Collaboration systematic review.

BACKGROUND: In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The review aimed to evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases. METHODS: We considered randomized controlled trials concerning adult palliative care with a focus on pharmacological treatment of fatigue compared with placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We searched the CENTRAL, MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. Two review authors independently assessed trial quality and extracted the data. RESULTS: We screened 1645 publications of which 45 met the inclusion criteria. In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials. Meta-analysis of data was possible for modafinil, pemoline, and methylphenidate. CONCLUSIONS: Due to the limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Some drugs, which may be beneficial for the treatment of fatigue associated with palliative care such as amantadine, methylphenidate, and modafinil, should be further researched

Extension for Community Healthcare Outcomes-Palliative Care in Africa Program: Improving Access to Quality Palliative Care

Purpose: There is limited access to quality palliative care (PC) for patients with advanced cancer in sub-Saharan Africa. Our aim was to describe the development of the Project Extension for Community Healthcare Outcomes- Palliative Care in Africa (ECHO-PACA) program and describe a preliminary evaluation of attitudes and knowledge of participants regarding the ability of the program to deliver quality PC. Methods: An interdisciplinary team at the MD Anderson Cancer Center, guided by experts in PC in sub-Saharan Africa, adapted a standardized curriculum based on PC needs in the region. Participants were then recruited, and monthly telementoring sessions were held for 16 months. The monthly telementoring sessions consisted of case presentations, discussions, and didactic lectures. Program participants came from 14 clinics and teaching hospitals in Ghana, Kenya, Nigeria, South Africa, and Zambia. Participants were surveyed at the beginning, midpoint, and end of the 16-month program to evaluate changes in attitudes and knowledge of PC. Results: The median number of participants per session was 30. Thirty-three (83%) of 40 initial participants completed the feedback survey. Health care providers’ self-reported confidence in providing PC increased with participation in the Project ECHO-PACA clinic. There was significant improvement in the participants’ attitudes and knowledge, especially in titrating opioids for pain control (P = .042), appropriate use of non-opioid analgesics (P = .012), and identifying and addressing communication issues related to end-of-life care (P = .014). Conclusion: Project ECHO-PACA was a successful approach for disseminating knowledge about PC. The participants were adherent to ECHO PACA clinics and the completion of feedback surveys. Future studies should evaluate the impact of Project ECHO-PACA on changes in provider practice as well as patient outcomes

Distinct trajectories of fatigue in chronic heart failure and their association with prognosis

Aims To identify distinct trajectories of fatigue over a 12-month period and to examine their impact on mortality in chronic heart failure (CHF). Methods and results Consecutive CHF patients (n = 310) were assessed at baseline and at 2- and 12-month follow-up for symptoms of exertion and general fatigue. Latent growth mixture modelling was used to examine the course of fatigue over time. The endpoint was mortality following the 12-month assessment of fatigue. Over the initial 12-month follow-up, six distinct trajectories for exertion fatigue and four distinct trajectories for general fatigue were identified. Beyond the 12-month follow-up (mean follow-up period, 693 days), 50 patients (17%) had died. After controlling for standard risk factors and disease severity, both severe exertion fatigue [hazards ratio (HR) = 2.59, 95% confidence interval (CI): 1.09-6.16, P = 0.03] and severe general fatigue (HR = 3.20, 95% CI: 1.62-6.31, P = 0.001) trajectories predicted an increased mortality rate (29 vs. 19% and 28 vs. 14%, respectively). The low exertion fatigue trajectory was associated with a decreased mortality risk (3 vs. 19%, HR = 0.12, 95% CI: 0.02-0.93, P = 0.04). Conclusion Fatigue trajectories varied across CHF patients and had a differential effect on mortality. Persistent severe fatigue was a predictor of poor prognosis. These results may help identify distinct groups of CHF patients with potentially differential risks of adverse health outcomes

Cytokines as mediators of chemotherapy-associated cognitive changes: Current evidence, limitations and directions for future research

10.1371/journal.pone.0081234PLoS ONE812-POLN

Integration of oncology and palliative care : a Lancet Oncology Commission

Full integration of oncology and palliative care relies on the specific knowledge and skills of two modes of care: the tumour-directed approach, the main focus of which is on treating the disease; and the host-directed approach, which focuses on the patient with the disease. This Commission addresses how to combine these two paradigms to achieve the best outcome of patient care. Randomised clinical trials on integration of oncology and palliative care point to health gains: improved survival and symptom control, less anxiety and depression, reduced use of futile chemotherapy at the end of life, improved family satisfaction and quality of life, and improved use of health-care resources. Early delivery of patient-directed care by specialist palliative care teams alongside tumour-directed treatment promotes patient-centred care. Systematic assessment and use of patient-reported outcomes and active patient involvement in the decisions about cancer care result in better symptom control, improved physical and mental health, and better use of health-care resources. The absence of international agreements on the content and standards of the organisation, education, and research of palliative care in oncology are major barriers to successful integration. Other barriers include the common misconception that palliative care is end-of-life care only, stigmatisation of death and dying, and insufficient infrastructure and funding. The absence of established priorities might also hinder integration more widely. This Commission proposes the use of standardised care pathways and multidisciplinary teams to promote integration of oncology and palliative care, and calls for changes at the system level to coordinate the activities of professionals, and for the development and implementation of new and improved education programmes, with the overall goal of improving patient care. Integration raises new research questions, all of which contribute to improved clinical care. When and how should palliative care be delivered? What is the optimal model for integrated care? What is the biological and clinical effect of living with advanced cancer for years after diagnosis? Successful integration must challenge the dualistic perspective of either the tumour or the host, and instead focus on a merged approach that places the patient's perspective at the centre. To succeed, integration must be anchored by management and policy makers at all levels of health care, followed by adequate resource allocation, a willingness to prioritise goals and needs, and sustained enthusiasm to help generate support for better integration. This integrated model must be reflected in international and national cancer plans, and be followed by developments of new care models, education and research programmes, all of which should be adapted to the specific cultural contexts within which they are situated. Patient-centred care should be an integrated part of oncology care independent of patient prognosis and treatment intention. To achieve this goal it must be based on changes in professional cultures and priorities in health care