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The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference (p = 0.014) and HRQoL pain (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning (p = 0.007). These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.

Objectives To describe communication regarding cancer patient’s end-of-life (EoL) wishes by physicians and family caregivers. Methods An online questionnaire and telephone-based surveys were performed with physicians and family caregivers respectively in three teaching hospitals in Colombia which had been involved in the EoL care of cancer patients. Results For 138 deceased patients we obtained responses from physicians and family caregivers. In 32 % physicians reported they spoke to the caregiver and in 17 % with the patient regarding EoL decisions. In most cases lacking a conversation, physicians indicated the treatment option was “clearly the best for the patient” or that it was “not necessary to discuss treatment with the patient”. Twenty-six percent of the caregivers indicated that someone from the medical team spoke with the patient about treatment, and in 67% who had a conversation, caregivers felt that the provided information was unclear or incomplete. Physicians and family caregivers were aware if the patient had any advance care directive in 6% and 26% of cases, respectively, with low absolute agreement (34%). Conclusions There is a lack of open conversation regarding EoL in patients with advanced cancer with their physicians and family caregivers in Colombia. Communication strategies are urgently needed.

Background Men with prostate cancer experience immediate and long-term consequences of the disease and its treatment. They require both long-term monitoring for recurrence or progression and follow-up to identify and help manage psychosocial and physical impacts. Holistic Needs Assessment aims to ensure patient-centered continuing cancer care. However, paper-based generic tools have had limited uptake within cancer services, and there is little evidence of their impact. With the expansion of remote methods of care delivery and to enhance the value of generic tools, we developed a web-based Composite Holistic Needs Assessment Adaptive Tool-Prostate (CHAT-P) specifically for prostate cancer. Objective This paper described the context, conceptual underpinning, and approach to design that informed the development of CHAT-P, starting from the initial concept to readiness for deployment. Through this narrative, we sought to contribute to the expanding body of knowledge regarding the coproduction process of innovative digital systems with potential for enhanced cancer care delivery. Methods The development of CHAT-P was guided by the principles of coproduction. Men with prostate cancer and health care professionals contributed to each stage of the process. Testing was conducted iteratively over a 5-year period. An initial rapid review of patient-reported outcome measures identified candidate items for inclusion. These items were categorized and allocated to overarching domains. After the first round of user testing, further items were added, improvements were made to the adaptive branching system, and response categories were refined. A functioning version of CHAT-P was tested with 16 patients recruited from 3 outpatient clinics, with interviewers adopting the think-aloud technique. Interview transcripts were analyzed using a framework approach. Interviews and informal discussions with health care professionals informed the development of a linked care plan and clinician-facing platform, which were incorporated into a separate feasibility study of digitally enhanced integrated cancer care. Results The findings from the interview study demonstrated the usability, acceptability, and potential value of CHAT-P. Men recognized the benefits of a personalized approach and the importance of a holistic understanding of their needs. Preparation for the consultation by the completion of CHAT-P was also recognized as empowering. The possible limitations identified were related to the importance of care teams responding to the issues selected in the assessment. The subsequent feasibility study highlighted the need for attention to men’s psychological concerns and demonstrated the ability of CHAT-P to capture red flag symptoms requiring urgent investigation. Conclusions CHAT-P offers an innovative means by which men can communicate their concerns to their health care teams before a physical or remote consultation. There is now a need for a full evaluation of the implementation process and outcomes where CHAT-P is introduced into the clinical pathway. There is also scope for adapting the CHAT-P model to other cancers.

Palliative care is on the global health agenda, as only approximately 14% of people who require palliative care receive it [...]

PURPOSE Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment (P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment (P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

Healthcare aims to help older people to live well, but ultimately must also support them to die well. Most people die in old age, but predicting death in both short- and long-term is impossible for many, although not all, older people. Frail older people live with hope and pride in coping, and often anticipate recovery when ill. Key objectives of healthcare for older people are to maintain independence, minimise suffering and preserve dignity, which requires active medical, mental health and rehabilitation management, even when extending life is not the main goal. Thorough medical diagnosis and appropriate treatment and rehabilitation minimise disability, physical and mental distress and problems resulting from acute illness and crises. In these terms, ‘health gain’ can be achieved from medical intervention, even when life expectancy is short. Assumptions derived from cancer care about lack of reversibility with medical interventions are sometimes unwarranted. This has to be balanced against investigation- and treatment-burden, including that associated with hospital admission and the adverse effects of drugs and therapy interventions, and the need to respect the identity and autonomy of individuals. The resolution of these tensions requires anticipation of care options, multi-professional assessment, judicious and targeted treatment, good communication with patients and stakeholders and rigorous shared decision-making. In this commentary, we compare geriatric and palliative medicine, and describe how the geriatric medical approach can deliver appropriate healthcare towards the end of life. This is well supported by the broad knowledge, skill-set, flexibility and professional values displayed by geriatricians working in multi-professional teams.

Opioids such as oxycodone are recommended in the management of moderate-to-severe, chronic cancer pain. All opioids can potentially cause constipation, which may be a significant barrier to their use. Multiple randomised clinical trials have shown that the use of naloxone as a peripherally acting mu-opioid receptor antagonist, in combination with oxycodone can prevent or reduce opioid-induced constipation while having equivalent analgesic efficacy to oxycodone alone. However, clinical experience has shown that unexpected events may occur in some patients when unrecognized liver impairment is present. We describe the underlying biological reasons and propose simple, but effective steps to avoid this unusual but potentially serious occurrence. In healthy individuals, naloxone undergoes extensive hepatic first pass metabolism resulting in low systemic bioavailability. However, in patients with hepatic impairment, porto-systemic shunting can increase systemic bioavailability of naloxone, potentially compromising the analgesic efficacy of oral naloxone-oxycodone combinations. This reduced first pass effect can occur in a range of settings that may not always be apparent to the treating clinician, including silent cirrhosis, non-cirrhotic portal hypertension and disruption of liver internal vasculature by metastases. Hepatic function test results correlate poorly with presence and extent of liver disease, and are not indicative of porto-systemic shunting. Presence of hepatic impairment should thus be considered when medication-related outcomes with oxycodone-naloxone combination are not as expected, even if liver function test results are normal.

Purpose This study aimed to validate the Sheffield Profile for Assessment and Referral to Care (SPARC) as an effective tool for screening palliative care needs among Korean cancer patients. Materials and methods The English version of the SPARC was translated by four Korean oncologists and reconciled by a Korean language specialist and a medical oncologist fluent in English. After the first version of the Korean SPARC (K-SPARC) was developed, back-translation into English was performed by a professional translator and bilingual oncologist. The back-translated version was reviewed by the original author (S.H.A.), and modifications were made (ver. 2). The second version of the K-SPARC was tested against other questionnaires, including the Functional Assessment of Cancer Therapy-General (FACT-G) and the Edmonton Symptom Assessment System (ESAS). Results Thirty patients were enrolled in the pilot trial. Fifteen were male, and the median age was 64.5 years. Six patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. All patients except one were receiving chemotherapy. Regarding internal consistency, the Cronbach's α scores for physical symptoms, psychological issues, religious and spiritual issues, independency and activity, family and social issues, and treatment issues were 0.812, 0.804, 0.589, 0.843, 0.754, and 0.822, respectively. The correlation coefficients between the SPARC and FACT-G were 0.479 (p=0.007) for the physical domain and -0.130 (p=0.493) for the social domain. Conclusion This pilot study indicates that the K-SPARC could be a reliable tool to screen for palliative care needs among Korean cancer patients. A further study to validate our findings is ongoing.

Background The Neuberger Commission (2013) and NICE guidelines (2015, 2019) have emphasised the paucity of good quality evidence for palliative and end of life care. In the UK, hospices have a significant role in determining standard of care. We sought to quantify the extent to which hospices contribute to nationally impactful research. Methods We analysed the NIHR portfolio of clinical and service delivery research, for studies in which hospices actively recruited patients, from 2015/16 to 2018/19. All relevant clinical specialties were searched. Results The NIHR portfolio contained 172 studies in the 2015/16 to 2018/19 period which are relevant to hospice and end of life care. 65 out of 253 registered hospices were identified as participating in 42 studies. Hospices recruited 4418 patients to national portfolio studies, 3817 of these with cancer. Specialties contributing to this recruitment included: Cancer 19 studies; Health Services Research 11; Dementia & Neurodegeneration 6; Primary Care 3; Neurological Disorders 1; Respiratory 1; Children 1. These figures underestimate the true contribution of hospices because in many sites recruitment is attributed to an acute trust (an established process which sees trusts providing governance in return for recruitment accrual). Moreover, we missed studies which are locally funded, single centre or related to higher educational research. We are working with hospice organisations and local clinical research networks to rectify these data gaps. The NIHR’s expansion project, which extended recognition of research into health and social care research taking place in non-NHS settings, will support this. Conclusions We found that only a small minority of UK hospices are active in nationally impactful research. However, together they make a significant contribution to the NIHR portfolio. The NIHR & Charities Consortium for Hospice and Community Research, which funded the study, is working with the hospice sector to increase UK-wide research participation.

Introduction:\ud Do-not-attempt-cardiopulmonary-resuscitation (DNACPR) practice has been shown to be variable and sub-optimal. This paper describes the development of the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT). ReSPECT is a process which encourages shared understanding of a patient’s condition and what outcomes they value and fear, before recording clinical recommendations about cardiopulmonary-resuscitation (CPR) within a broader plan for emergency care and treatment.\ud \ud Methods:\ud ReSPECT was developed iteratively, with integral stakeholder engagement, informed by the Knowledge-to-Action cycle. Mixed methods included: synthesis of existing literature; a national online consultation exercise; cognitive interviews with users; a patient-public involvement (PPI) workshop and a usability pilot, to ensure acceptability by both patients and professionals.\ud \ud Results:\ud The majority (89%) of consultation respondents supported the concept of emergency care and treatment plans. Key features identified in the evaluation and incorporated into ReSPECT were: The importance of discussions between patient and clinician to inform realistic treatment preferences and clarity in the resulting recommendations recorded by the clinician on the form. The process is compliant with UK mental capacity laws. Documentation should be recognised across all health and care settings. There should be opportunity for timely review based on individual need.\ud \ud Conclusion:\ud ReSPECT is designed to facilitate discussions about a person’s preferences to inform emergency care and treatment plans (including CPR) for use across all health and care settings. It has been developed iteratively with a range of stakeholders. Further research will be needed to assess the influence of ReSPECT on patient-centred decisions, experience and health outcomes.

Purpose Adequate cancer pain management (CPM) is challenging in resource-limited settings, where current international guideline recommendations are difficult to implement owing to constraints such as inadequate availability and accessibility of opioids, limited awareness of appropriate opioid use among patients and clinicians, and lack of guidance on how to translate the best evidence into clinical practice. The multinational and multidisciplinary CAncer Pain managEment in Resource-limited settings (CAPER) Working Group proposes a two-step initiative to bridge clinical practice gaps in CPM in resource-limited settings. Methods A thorough review of the literature, a steering committee meeting in February 2017, and post-meeting teleconference discussions contributed to the development of this initiative. As a first step, we developed practical evidence-based CPM algorithms to support healthcare providers (HCPs) in tailoring treatment according to availability of and access to resources. The second part of the initiative proposes a framework to support an effective implementation of the CPM algorithms that includes an educational program, a pilot implementation, and an advocacy plan. Results We developed CPM algorithms for first-line use, breakthrough cancer pain, opioid rotation, and refractory cancer pain based on the National Comprehensive Cancer Network guidelines and expert consensus. Our proposed educational program emphasizes the practical elements and illustrates how HCPs can provide optimal CPM according to evidence-based guidelines despite varied resource limitations. Pilot studies are proposed to demonstrate the effectiveness of the algorithms and the educational program, as well as for providing evidence to support a draft advocacy document, to lobby policymakers to improve availability and accessibility of analgesics in resource-limited settings. Conclusions These practical evidence-informed algorithms and the implementation framework represent the first multinational step towards achieving optimal CPM in resource-limited settings. Electronic supplementary material The online version of this article (10.1007/s00520-018-4471-z) contains supplementary material, which is available to authorized users.

Pain is a major symptom of bone metastases from advanced cancer and represents a clinical challenge to treat effectively. Basic neurobiology in preclinical animal models implicates enhanced sensory processing in the central nervous system, acting through N-methyl-D-aspartate (NMDA) glutamate receptors, as an important mechanism underpinning persistent pain. The non-receptor tyrosine kinase Src is thought to act as a hub for regulating NMDA receptor activity and the orally available Src inhibitor saracatinib has shown promise as a potential analgesic in recent animal studies. Here we tested the efficacy of saracatinib as a novel analgesic in an exploratory phase II randomized controlled trial on cancer patients with painful bone metastases. Twelve patients completed the study, with 6 receiving saracatinib 125 mg/day for 28 days and 6 receiving placebo. Pharmacokinetic measurements confirmed appropriate plasma levels of drug in the saracatinib-treated group and Src inhibition was achieved clinically by a significant reduction in the bone resorption biomarker serum cross-linked C-terminal telopeptide of type I collagen. Differences between the saracatinib and placebo groups self-reported pain scores, measured using the short form of the Brief Pain Inventory, were not clinically significant after 4 weeks of treatment. There was also no change in consumption of maintenance analgesia in the saracatinib-treated group and no improvement in Quality-of-Life scores. The data were insufficient to demonstrate saracatinib has efficacy as analgesic, although it may have a role as an anti-bone resorptive agent. Keywords: Cancer pain, Src inhibitor, Metastasis, Clinical trial, Saracatinib

Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient’s morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone provided effective analgesia with improved bowel function in patients suffering from severe cancer-related and noncancer-related pain. The combination has the potential to improve the quality of pain management significantly in these patients.

As people are living longer after a diagnosis and primary treatment for cancer, or indeed living with cancer as a chronic disease, new problems are emerging in this growing population of so-called 'survivors'. Persistent or chronic pain is one of the commonest complaints, arising from the tissue damage caused by the original neoplasm, consequences of surgery and other therapies, and - especially in older people - multimorbidity. This review explores some of the principle causes and mechanisms of this phenomenon and reviews the evidence for their management.We review recent findings regarding persistent pain in adults after surgery, chemotherapy (including targeted biological therapies), hormone manipulation and radiation therapy; and osteonecrosis from corticosteroid treatment in children with cancer. Recent research has revealed some of the molecular, genetic, phenotypic and psychological factors that predispose some people to developing more persistent pain after cancer, and their long-term outcomes.Although persistent pain in cancer patients surviving after primary treatment has been recognized for decades, only recently has research shown how this arises and some possible ways to intervene by prevention and interventions. New holistic models for management of persistent cancer-related pain are needed.

Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid–opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N -methyl-d-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation.

The National Institute for Health Research (NIHR) and Marie Curie are the two largest funders of end of life care research in the UK. NIHR and Marie Curie enable and support research at different times of the translational pathway, or by co-funding research. Undertaking a research impact assessment (RIA) on our combined investment is important to make the case for continued investment research and to be accountable to our stakeholders (Morgan Jones and Grant, 2013). RIA is a developing field (Adam et al., 2018). To ensure our approach is relevant, we have involved people with experience of end of life care. We hope that by undertaking this process together, we will gain a better understanding of the research funding landscape and its interdependencies in this area, identify gaps and opportunities, and learn from and support each other. We believe that our project marks the first time that a collaborative RIA of this kind has been undertaken by research funders. We hope that by exchanging, reflecting and sharing our experiences, lessons learned and approach, it will aid discussion, promote shared learning and transparency around funders’ impact assessment processes and may help future collaborative projects. Our learning so far: Appropriate oversight, governance and data sharing is a must Identify organisational risks up front Review organisational factors including resource which may impact on capacity to deliver Use of similar tools for data collection enables joint analysis and efficient of data collection A clear and shared understanding of the project scope is important

Context Pain is one of the most prevalent symptoms associated with cancer. Strong opioids are commonly used in the analgesic management of the disease, but carry the risk of severe side effects. Cebranopadol is a first-in-class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. For cancer patients, frequently experiencing multimorbidities and often exposed to polypharmacy, cebranopadol is easy to handle given its once-daily dosing, the small tablet size that enables swallowing, and the option to flexibly titrate to an effective dose. Objectives We assessed the safety and tolerability of prolonged treatment with oral cebranopadol for up to 26 weeks in patients suffering from chronic moderate-to-severe cancer-related pain. Methods This was a non-randomized, multi-site, open-label, single-arm clinical trial with patients who had completed a double-blind trial comparing morphine prolonged release with cebranopadol. In this extension trial, patients were treated with oral cebranopadol for up to 26 weeks. Results Cebranopadol was safe and well tolerated in patients with chronic moderate-to-severe pain related to cancer in the dose range tested (200–1000 μg once daily). The median and mean pain levels remained in the range of mild pain during the treatment period. Conclusion Our data suggest that cebranopadol was safe and well tolerated when administered for up to 26 weeks in patients with chronic cancer-related pain who were previously treated with cebranopadol or morphine prolonged release.

Care of people in their last days of life should be based on compassion, respect and, wherever possible, on research evidence. Previously the Liverpool Care Pathway attempted to facilitate this but it was withdrawn after an independent government report found that its uncritical implementation could lead to poor care. This Concise Guideline overviews NICE Clinical Guideline (NG31), which addresses: recognising dying; communication and shared decision making; maintaining hydration; and pharmacological symptom control, including anticipatory prescribing. Doctors may need to change their attitudes to care of dying people and those important to them. Specific areas where practices will need to reflect the individualised approach to care are highlighted. Limitations of the guideline are discussed. Potential barriers to implementation include need for further training and 24/7 availability of specialist support to front-line clinicians.

Breathlessness is a distressing symptom that arises in many diseases. It has several pathophysiological causes involving peripheral and central receptors and modulated by cortical processing. Older people and patients with cachexia are more susceptible to breathlessness on exertion. Most patients can be assessed by physical examination, and simple investigations including haemoglobin concentration, oxygen saturation, electrocardiography and imaging (X-ray, ultrasound). Research has shown that careful use of opioids can reduce the sensation of breathlessness without compromising ventilatory control. Benzodiazepines also help, probably by their anxiolytic and sedative actions. The combination of an opioid and short-acting benzodiazepine is especially useful. Nebulized furosemide is a new approach that requires further research. Oxygen is indicated if oxygen saturation falls, but increased airflow around the face (e.g. with a fan) can also help. The combination of helium and oxygen can be more effective than oxygen alone. Non-invasive ventilation can be necessary in severe cases, such as neuromuscular disease. Non-medical approaches, including breathing training and relaxation, can also help. Infusions of carefully titrated opioid and midazolam can be used in the dying patient, together with an anticholinergic agent if there are noisy upper airways secretions (‘death rattle').

Background Cancer-related pain is a growing health problem given the increasing life expectancy of cancer patients. Opioids are commonly used to treat cancer-related pain, but carry the risk of severe side effects, limiting their use. Cebranopadol is a first-in-class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. This trial examined the analgesic efficacy of cebranopadol compared with morphine prolonged release (PR) in patients with moderate-to-severe cancer-related pain. Methods This double-blind, parallel-group, multiple-dose trial was designed as noninferiority trial for efficacy of cebranopadol versus morphine PR. Planned with 524 patients, finally 126 patients were treated for up to 7 weeks (low accrual). The primary efficacy endpoint was the average amount of daily rescue medication intake (morphine immediate release) over the last 2 weeks of treatment. Results For the primary endpoint, noninferiority of cebranopadol with and superiority over morphine PR were demonstrated (Full Analysis Set: ∆[95%CI] = -7.48 mg [-12.05, -2.92]; Per Protocol Set: ∆[95%CI] = -4.67 mg [-9.25, -0.10]). The vast majority of patients (≥75%, either treatment) had clinically relevant pain reduction, and noninferiority on this secondary endpoint was not shown. Mostly used doses were ≤800 μg cebranopadol or ≤120 mg morphine PR daily. A total of 83.1% of patients on cebranopadol and 82.0% on morphine PR experienced treatment-emergent adverse events. Conclusions Cebranopadol was effective, safe and well tolerated in the dose range tested (200-1,000 μg) in patients suffering from chronic moderate-to-severe cancer-related pain and was superior to morphine PR on the primary endpoint. Significance Cebranopadol presents a new approach to treat cancer pain. The drug candidate was easy to titrate, safe and well tolerated, and as effective as morphine PR in patients suffering from chronic moderate-to-severe cancer-related pain.

Many malignancies give rise to pulmonary complications resulting in symptoms such as breathlessness and cough. The presence of comorbidities, especially in older cancer patients, can also contribute to pulmonary symptoms. In addition, all modalities of anticancer treatments can be associated with pulmonary toxicities which cause similar symptoms and functional changes. These may be acute or develop slowly and may become chronic. Some pulmonary complications of anticancer treatments cause serious impairment of quality of life and may be life-threatening. In this chapter we review the pulmonary toxicities associated with conventional cytotoxic chemotherapeutic agents, as well as the newer biologically targeted treatments including the immune checkpoint inhibitors. Complications following surgery and radiation therapy are also reviewed.

Men don't talk about their health is a familiar trope. Evidence suggests that in the United States (US) and in the United Kingdom (UK) this is indeed the case. A survey of five hundred men in the US over the age of eighteen reported only 7% discussing their health with their peers [1]. Only 42% of men surveyed were prepared to consult a health care professional over a worrying symptom.

Contains fulltext : 153967.pdf (Publisher’s version ) (Open Access) BACKGROUND: Pain is a common symptom in patients with multiple myeloma (MM). Many patients are dependent on analgesics and in particular opioids, but there is limited information on the impact of these drugs and their side effects on health-related quality of life (HRQoL). METHOD: In a cross-sectional study, semi-structured interviews were performed in 21 patients attending the hospital with symptomatic MM on pain medications. HRQoL was measured using items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. RESULTS: Patients were able to recall a median of two (range 0-4) analgesics. They spontaneously identified a median of two (range 1-5) side effects attributable to their analgesic medications. Patients' assessment of HRQoL based on the EORTC QLQ-C30 questions 29/30 was mean 48.3 (95 % CI; 38.7-57.9) out of 100. Patients' assessment of their HRQoL in the hypothetical situation, in which they would not experience any side effects from analgesics, was significantly higher: 62.6 (53.5-71.7) (t test, p = 0.001). CONCLUSION: This study provides, for the first time, evidence that side effects of analgesics are common in symptomatic MM and may result in a statistically and clinically significant reduction of self-reported HRQoL.

Background: The potential of technology to aid integration of care delivery systems is being explored in a range of contexts across a variety of conditions in the United Kingdom. Prostate cancer is the most common cancer in UK men. With a 10-year survival rate of 84%, there is a need to explore innovative methods of care that are integrated between primary health care providers and specialist teams in order to address long-term consequences of the disease and its treatment as well as to provide continued monitoring for recurrence. Objective: Our aim was to test the feasibility of a randomized controlled trial to compare a model of prostate cancer continuing and follow-up care integration, underpinned by digital technology, with usual care in terms of clinical and cost-effectiveness, patient-reported outcomes, and experience. Methods: A first phase of the study has included development of an online adaptive prostate specific Holistic Needs Assessment system (HNA), training for primary care-based nurses, training of an IT peer supporter, and interviews with health care professionals and men with prostate cancer to explore views of their care, experience of technology, and views of the proposed intervention. In Phase 2, men in the intervention arm will complete the HNA at home to help identify and articulate concerns and share them with their health care professionals, in both primary and specialist care. Participants in the control arm will receive usual care. Outcomes including quality of life and well-being, prostate-specific concerns, and patient enablement will be measured 3 times over a 9-month period. Results: Findings from phase 1 indicated strong support for the intervention among men, including those who had had little experience of digital technology. Men expressed a range of views on ways that the online system might be used within a clinical pathway. Health care professionals gave valuable feedback on how the output of the assessment might be presented to encourage engagement and uptake by clinical teams. Recruitment to the second phase of the study, the feasibility trial, commenced March 2017. Conclusions: To our knowledge, this study is the first in the United Kingdom to trial an online holistic needs assessment for men with prostate cancer, with data shared between patients and primary and secondary care providers. This study addresses recommendations in recent policy documents promoting the importance of data sharing and enhanced communication between care providers as a basis for care integration. We anticipate that this model of care will ultimately provide important benefits for both patients and the National Health Service. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 31380482; http://www.isrctn.com/ISRCTN31380482 (Archived by WebCite at http://www.webcitation.org/6s8I42u5N) [JMIR Res Protoc 2017;6(7):e147]

Background: Inadequate information on translating guideline recommendations into clinical practice; resource limitations; lack of education of healthcare providers (HCPs)/policymakers/patients are factors contributing to the gap between best practices and actual clinical practice in cancer pain management (CPM). To address these gaps and optimize CPM in resource-limited settings (R-LS), we propose a two-step initiative – the development of practical resource-based CPM algorithms, and an education and advocacy framework to support effective implementation of the algorithms in R-LS. Methods: The CAPER WG–a global, multidisciplinary consortium of oncologists, pain specialists, and palliative care experts–has developed an education and advocacy framework for improving CPM in R-LS, stemming from literature review and a workshop held in February 2017.Results: We developed CPM algorithms incorporating guideline recommendations and expert opinion, applying a hierarchy of resource-based constraints to provide HCPs a tailored approach to manage patient needs. To support the implementation of these CPM algorithms, we formulated a framework comprising an educational program, pilot implementation, and an advocacy plan. The educational framework provides HCPs with clinically-relevant information, emphasizing the practical element of translating knowledge into practice and illustrating how optimal CPM can be provided despite resource limitations. Pilot implementation studies are essential to demonstrate the effectiveness of the algorithms and the educational program; the results will allow algorithm refinement, optimization of implementation strategies and development of advocacy plans. A strategic advocacy plan is imperative to achieve our ultimate goal of optimizing CPM in R-LS; effective advocacy will drive collaborative and multifaceted efforts amongst key stakeholders to ensure improvement of resource access and availability. Conclusions: The proposed framework for education and advocacy can guide the translation of our resource-based CPM algorithms into clinical practice in all settings,ultimately providing optimal CPM for all patients despite differential resources.

Objective Patient and public involvement (PPI) has become an established theme within the UK health research policy and is recognised as an essential force in the drive to improve the quality of services and research. These developments have been particularly rapid in the cancer field. Methods This paper outlines a model of PPI in research (known as the North Trent Cancer Research Network Consumer Research Panel, NTCRN CRP; comprising 38 cancer and palliative care patients/carers) and the key benefits and challenges to effective PPI in cancer research. Results The PPI model has become a sustainable, inclusive and effective way of implementing PPI within the cancer context. Challenges include (1) a lack of time and funding available to support the PPI model; (2) tensions between different stakeholder groups when developing and conducting health research; (3) panel members finding it difficult to effectively integrate into research meetings when their role and contribution is not made clear at the outset or when unfamiliar language and jargon are used and not explained; (4) some professionals remain unclear about the role and practical implications of PPI in research. However, notwithstanding its financial and organisational challenges, the way that the NTCRN CRP is supported has provided a solid base for it to flourish. Conclusions PPI provides considerable opportunities for patients and the public to work collaboratively with professionals to influence the cancer research agenda, with the contribution of PPI to the research process being integral to the entire process from the outset, rather than appended to it.

Aim To evaluate the long-term safety and efficacy of prolonged-release oxycodone/naloxone (OXN PR) and its impact on quality of life (QoL), in patients with moderate-to-severe cancer pain. Methods This was an open-label extension (OLE) of a 4 week, randomized, double-blind (DB) study in which patients with moderate-to-severe cancer pain had been randomized to OXN PR or oxycodone PR (OxyPR). During the OLE phase, patients were treated with OXN PR capsules (≤20/60 mg/day) for ≤24 weeks. Outcome measures included safety, efficacy and QoL. Results One hundred and twenty-eight patients entered the OLE, average pain scores based on the modified Brief Pain Inventory—Short Form were low and stable over the 24-week period. The improvement in bowel function and constipation symptoms as measured by the Bowel Function Index and patient assessment of constipation in patients treated with OXN PR during the 4-week DB study was maintained. In patients treated with OxyPR during the DB phase, bowel function and constipation symptoms were improved during the OLE. In the DB and in the OLE, health status and QoL were similar for patients treated with OXN PR and OxyPR. There were no unexpected safety or tolerability issues. Conclusions In patients with moderate-to-severe cancer pain, long-term use of OXN PR is well tolerated and effective, resulting in sustained analgesia, improved bowel function and improved symptoms of constipation.

Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

There is evidence to suggest that patients with cancer and other non-malignant chronic progressive illnesses can experience distressing symptoms, or concerns, which can often remain unrecognised. There is little disagreement that routine systematic questioning is useful in identifying supportive or palliative care needs that would otherwise not be identified. The purpose of this article is to provide an overview of holistic needs assessment in the fields of supportive and palliative care and to present evidence of the value of routine systematic questioning. Systematic questioning allows needs to be identified and addressed. There is at present no standardised systematic, evidence-based holistic approach to screening patients for supportive and palliative care needs.

Studies have demonstrated that whereas some opioids have little effect on immunity (eg, buprenorphine), others can be immunosuppressive (eg, morphine) or immunostimulatory (eg, tramadol). However, a variety of approaches have been used, especially in vitro and animal models, and the findings are variable. We hypothesised that opioids have differential effects on immunity via direct actions on neutrophils, monocytes, natural killer (NK) and T cells, and this is the first study to systematically evaluate the influence of eight opioids on neutrophil and monocyte phagocytosis and oxidative burst responses, NK cell cytotoxicity and T cell responsiveness in vitro.Peripheral blood was obtained from healthy volunteers, and the effects of clinically relevant concentrations of morphine, tramadol, fentanyl, buprenorphine, methadone, oxycodone, diamorphine and codeine on phagocytosis and oxidative burst responses were determined using whole blood flow cytometry. The influence of opioids on the capacity of resting and IL-2 stimulated isolated peripheral blood mononuclear cells (PBMCs) to kill NK cell-sensitive K562 cells, and the responsiveness of PBMC subpopulations to IL-2 and polyclonal stimulation were also evaluated.Methadone, oxycodone and diamorphine inhibited the production of IL-6 by IL-2 stimulated PBMCs. None of the opioids consistently influenced the other measured immune parameters, although there was a trend for morphine, tramadol, fentanyl and buprenorphine to inhibit phagocytosis and oxidative burst responses to Escherichia coli.Preliminary studies using standardised in vitro methodologies have demonstrated that some therapeutic opioids suppress IL-6 production. Although this might potentially suppress bacterial defence mechanisms, it would have little direct effect on anticancer immunity. These findings should be confirmed in larger in vitro and clinical studies.

Background: Non-invasive ventilation improves quality and quantity of life in patients with motor neurone disease who have respiratory failure. Use of non-invasive ventilation may, however, result in complex clinical issues for end-of-life care, with concerns as to whether and how it should be withdrawn. Aim: This study aimed to describe carer and health professional experiences of end-of-life care of motor neurone disease patients using non-invasive ventilation. Design/participants: This article reports data from qualitative interviews with family carers and professionals following the death of patients with motor neurone disease who were using non-invasive ventilation in the final phase of the disease. Results: Ten of the 20 patients initiated on non-invasive ventilation were using it in the end-of-life phase of their disease, with 5 using it for 24 h/day. Interviews were carried out with nine family carers and 15 professionals. Nine recurring themes were identified in the data. Both carers and health-care professionals perceived that the terminal phase of motor neurone disease was unexpectedly rapid and that this often led to unplanned interactions with the emergency services. Carers of patients who used non-invasive ventilation perceived non-invasive ventilation as aiding patient comfort and anxiety at the end of life. Conclusions: The use of non-invasive ventilation was described as beneficial and was not perceived by carers or most professionals to have adversely impacted patient’s end-of-life experience. This study highlights variation in patient wishes regarding usage towards the end of life, uncertainty regarding appropriate management among professionals and the importance of disseminating end-of-life wishes.

Introduction: Radiotherapy treatment for prostate cancer can cause bowel problems, which may lead to severe difficulties for cancer survivors including limiting travel, work or socialising. These symptoms can appear at any time following radiotherapy. This study focuses on the early identification and protocol-based management of effects known to cause long-term, or even permanent, changes to the well-being of prostate cancer survivors. The rationale of this study is to improve the care offered to men and their families following pelvic radiotherapy for prostate cancer.\ud Method and analysis: Implementation research methodology will be used to adopt a multicomponent intervention at three UK centres. The intervention package comprises a standardised clinical assessment of relevant symptoms in oncology outpatient clinics and rapid referral to an enhanced gastroenterological service for patients identified with bowel problems. Gastroenterology staff will be trained to use an expert practice algorithm of targeted gastroenterology investigations and treatments. The evaluation of the intervention and its embedding within local practices will be conducted using a mixed-methods design. The effect of the new service will be measured in terms of the following outcomes: acceptability to staff and patients; quality of life; symptom control and cost effectiveness. Data collection will take place at baseline, 6 months (±2 months), and 12 months (±2 months) after entry into the study.\ud Ethics and dissemination: The study has ethical approval from the North West-Liverpool East Research Ethics Committee and the appropriate NHS governance clearance. All participants provide written informed consent. The study team aim to publish the results of the study in peer-reviewed journals as well as at national and international conferences. \ud Trial registration number: UKCRN16974

Background Little is known regarding the burden of opioid-induced constipation (OIC) among patients who suffer from cancer-related pain. Methods A prospective longitudinal study was conducted among cancer patients in the United Kingdom (UK), Canada, and Germany, which included medical record data abstraction, Internet-based patient surveys, and physician surveys. Patients on daily opioid therapy (≥30 mg for ≥4 weeks) for treatment of cancer pain with self-reported OIC were recruited. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response. Descriptive statistics were used to evaluate outcomes, including the patient assessment of constipation-symptom (PAC-SYM), patient assessment of constipation-quality of life, EuroQOL-5 dimensions, and global assessment of treatment benefit, satisfaction, and willingness to continue. Results Recruitment was difficult for this study with only 31 participants completing the baseline survey and meeting criteria for opioid use and OIC (26 UK, 1 Canada, and 4 Germany). Fifty-two percent (n = 16) of participants were male, and all were White. Breast (23%, n = 7), pancreatic (13%, n = 4), and multiple myeloma (13%, n = 4) were the most common cancers. Mean duration of chronic pain and opioid use were 2.3 and 1.3 years, respectively. Participants reported having a mean of 4.4 bowel movements/week in the 2 weeks prior to baseline, of which a mean of 0.9 were spontaneous. Most participants (90%, n = 28) were using at least 1 lifestyle approach to manage their constipation; 65% (n = 20) were taking ≥1 over-the-counter laxative; 19% (n = 6) were taking ≥1 prescription laxative; 23% (n = 7) reported no laxative use in the prior 2 weeks. Moderate-to-severe constipation symptoms on the PAC-SYM were common, and mean scores on health-related quality of life outcomes were comparable to chronic pain populations. Conclusion In this primarily UK sample, there appears to be considerable unmet OIC treatment needs among cancer patients.

Objectives: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors.\ud \ud Methods: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation.\ud \ud Results: Thirty-two patients with a median duration of 6 years (range 2–12) from original diagnosis of myeloma and three lines (range 2–6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common.\ud \ud Discussion: Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age.\ud \ud Conclusion: This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients.

This study aimed to examine the experiences of patients with motor neuron disease and their carers following the recommendation to use non-invasive ventilation (NIV). Qualitative interviews were carried out with 20 patients and 17 carers within one month of NIV being initiated. The study identified a range of potential barriers to usage including: adverse impressions of the technology; sleep disturbance; the sensation of pressure and pulsing; dry mouth; and mask design issues. Patients/carers perceived benefits related to: increased energy; improved sleeping; enhanced carer well-being; improved breathing and increased speech clarity. A key factor described by patients and carers was the need to persevere to overcome the challenges associated with early NIV use. The study highlights the importance of patient perceptions of gains as a factor in their NIV usage decisions. While recognizing that older individuals with limb-onset disease were over-represented in the sample, key recommendations from the study are: availability of easily accessible in-person support for patients; for clinicians to pre-empt potential obstacles by discussing options such as humidification or alternative mask interfaces; the importance of discussing potential benefits in detail with patients; and optimization of secretion management prior to NIV trial.