Finding predictors for successful opioid response in cancer patients: An analysis of data from four randomized controlled trials.

CONTEXT: There is no consensus on which "strong" (or step 3 WHO analgesic ladder) opioid to prescribe to a particular patient with cancer-related pain. A better understanding of opioid and patient characteristics on treatment response will contribute to a more personalized opioid treatment. OBJECTIVES: Assessment of potential predictors for successful opioid treatment response in patients with cancer pain. METHODS: An international partnership between four cancer pain research groups resulted in a combined individual-level database from four relevant randomized controlled trials (RCTs; n = 881). Together, these RCTs investigated the short-term (1 week) and medium-term (4 or 5 weeks) treatment responses for morphine, buprenorphine, methadone, oxycodone, and fentanyl. Candidate predictors for treatment response were sex, age, pain type, pain duration, depression, anxiety, Karnofsky performance score, opioid type, and use of anti-neuropathic drug. RESULTS: Opioid type and pain type were found statistically significant predictors of short-term treatment success. Sex, age, pain type, anxiety, and opioid type were statistically, significantly associated with medium-term treatment success. However, these models showed low discriminative power. CONCLUSION: Fentanyl and methadone, and mixed pain were found to be statistically significant predictors of treatment success in patients with cancer-related pain. With the predictors currently assessed our data did not allow for the creation of a clinical prediction model with good discriminative power. Additional - unrevealed - predictors are necessary to develop a future prediction model.

Public and patient involvement: a survey on knowledge, experience and opinions among researchers within a precision oncology European project.

BACKGROUND: Patient and Public Involvement (PPI) is slowly but steadily being implemented in all phases of clinical research. As part of the European project "Building Data Rich Clinical Trials" a survey was launched to investigate the knowledge, experiences and opinions on this topic of clinicians and researchers from seven European clinical and non-clinical centers (Cancer Core Europe). METHODS: An invitation to take part in a cross-sectional web survey was sent to 199 clinicians and researchers working in the field of precision oncology. The questionnaire was developed ad hoc because no existing questionnaires met the purpose of this study. The analysis takes account of whether respondents had experience on PPI or not. RESULTS: On a total of 101 respondents, this survey reveals that 76.2% of them knew about PPI before answering the questionnaire, 54.5% had experience in the previous five years and 86.1% were interested in a training course on this topic. PPI knowledge grew together with career seniority (peak of 86.5% for established career professionals), while the group most interested in a course was the early-career professionals (100.0%). Finally, the majority of respondents stated they had no training or education on PPI (67.3% of experienced and 82.6% of not-experienced respondents). CONCLUSIONS: This survey shows that most cancer researchers knew the term PPI, even if only a little more than half of them had any relative experience. Opinions on PPI benefits, negative effects, barriers and requirements differed between the groups of PPI experienced and not-experienced respondents, showing that experience itself can influence respondents' opinions. Most of respondents reported they would prefer a training course based on practical rather than theoretical tools.

Knowledge, use and attitudes of healthcare professionals towards patient-reported outcome measures (PROMs) at a comprehensive cancer center.

BACKGROUND: Despite evidence of the positive impact of routine assessment of patient-reported outcome measures (PROMs), their systematic collection is not widely implemented in cancer care. AIM: To assess the knowledge, use and attitudes of healthcare professionals (HCPs) towards PROMs and electronically collected PROMs (ePROMs) in clinical practice and research and to explore respondent-related factors associated with the above dimensions. METHOD: An ad hoc developed online survey was administered to all HCPs employed in clinical activity in an Italian comprehensive cancer center. The survey investigated which PROMs were known and used, as well as HCPs' opinions on the advantages and drawbacks of routine PROM assessment, including electronic assessment (ePROM). Linear and logistic regression models were used for association analyses. RESULTS: Five Hundred Eleven of nine hundred ninety-two invited HCPs (52%) provided analyzable responses. 68% were women, 46% were nurses and 42% physicians, and 52.5% had > 20 years seniority. The average number of PROMs known was six among 17 proposed. All proved to be under-used (< 28%) except unidimensional and multidimensional pain scales (77 and 36%). Respondents expressed an overall positive attitude towards PROMs, with strengths outweighing weaknesses (mean overall scores 3.6 and 2.9, respectively, on a 1-5 scale). 67% of respondents preferred electronic collection over paper and pencil. Profession was associated with knowledge and use (physicians reported knowing more PROMs than other professionals) and with a preference for electronic collection (nurses were less likely to prefer the electronic format than physicians). Senior HCPs were slightly more critical about both PROMs and electronic administration. CONCLUSIONS: This survey indicates an acceptable level of knowledge of common PROM tools but low usage in practice. Based on the generally positive attitude of HCPs, routine implementation of ePROMs can be promoted as long as adequate resources and training are provided. TRIAL REGISTRATION: Not registered.

Cancer pain: Results of a prospective study on prognostic indicators of pain intensity including pain syndromes assessment.

BACKGROUND: Pain is a prevalent symptom in patients with advanced cancer. Recognition of prognostic factors associated with pain intensity, could help provide better assessment, leading to better pain management. AIM: identifying prognostic factors which could guide improvements on cancer pain classification. DESIGN: a prospective observational study on chronic cancer pain, exploring the association between average mean pain intensity during a 28 days study follow-up and patients' clinical and pain-related characteristics, including pain syndromes. To evaluate these associations, a mixed model was built. SETTING/PARTICIPANTS: Patients attending a Palliative Care and Pain Outpatient Clinic from May 2015 to June 2019 were screened. Patients with moderate to severe cancer pain who were already receiving or needed treatment with third step WHO ladder opioids were enrolled in the study. Data from 342 patients with at least one follow-up visit were analyzed. RESULTS: Pain intensity decreased significantly for all patients during time (p < 0.001). Age, sex, emotional distress, pain duration and neuropathic pain presence evaluated by the Douleur Neuropathique 4 Questions (DN4) questionnaire were not significantly associated to pain intensity. Breakthrough/episodic pain was associated with higher pain intensity during follow-up (p < 0.001). The diagnosis of pain syndrome was overall significantly associated with mean pain intensity during follow-up (p = 0.016). Particularly, the concurrent presence of visceral and soft (p = 0.026) or soft and nervous tissue pain (p = 0.043) were significantly related to worse outcome, whereas pain due to only soft tissue damage with better outcome (p = 0.032). CONCLUSIONS: The recognition of specific pain syndromes may help to better classify cancer pain.

Development of the palliative care referral system: proposal of a tool for the referral of cancer patients to specialized palliative care.

BACKGROUND: Early palliative care (PC) has shown beneficial effects for advanced cancer patients. However, it is still debated what criteria to use to identify patients for PC referral. AIM: To document the initial steps of the development of the Palliative Care Referral System (PCRS), a tool to be used by oncologists in clinical practice. METHODS: A multiprofessional working group developed the PCRS based on the results of a scoping literature review on PC referral criteria. PCRS criteria were evaluated by experts via a nominal group technique (NGT). Descriptive statistics were used to summarize expert scores on relevance, appropriateness and perceived feasibility of the criteria proposed. Quotations of participants during the discussion were also reported. RESULTS: Sixteen studies, including PC referral criteria/tools, emerged from the scoping review. Severe symptoms, poor performance status, comorbidities and prognosis were the most commonly used criteria. The PCRS included nine major criteria and nine assessment methods; a scoring procedure was also proposed. Answers to the questionnaire during the NGT showed that five criteria reached full agreement on all items, while four did not, and were then discussed within the group. Participants agreed on the relevance of all criteria and on the appropriateness of methods proposed to assess most of them, while issues were raised about potential feasibility of the overall assessment of the PCRS in clinical practice. CONCLUSION: The PCRS has been developed as an help for oncologists to timely identify patients for specialized PC referral. Since feasibility emerged as the main concern, implementation strategies have to be tested in subsequent studies.

Development and field testing of a neuro psychomotor multidimensional grid for the assessment of children with cns tumor.

Central Nervous System (CNS) tumors are the most common pediatric solid tumor and development neuro psychomotor (DNPM) therapy can contribute to the rehabilitation of these children. This paper describes the development of a DNPM multidimensional assessment grid for children with CNS tumor (DNPM-CNS grid).The development process included 4 phases: (P1) literature review and grid development (Version 1.0), (P2) two rounds consultations with experts (Version 1.1 and 2.0), (P3) field testing, (P4) final revision (Version 3.0).(P1) The DNPM-CNS grid was developed based on previous tools and manuals and on clinical experience with this patient population. (P2) A total of 52 questionnaires were filled in by experts about relevance of assessment areas, pertinence, comprehensibility and feasibility of the grid. Average scores ranged from 7.6 to 10. (P3) At case level, good inter-rater agreement scores (78%) and limited non-evaluability rates (18%) emerged. At item level, 27% of items reached high disagreement and 26% high not-evaluability rates. The qualitative assessment was judged clinically useful for planning the neuro-oncology rehabilitation treatment and a good feasibility of the DNPM-CNS grid emerged both for preschool and school-age children. (P4) The final version of the grid consists of 8 assessment areas with 133 items.The DNPM-CNS grid is a comprehensive tool that can guide the overall DNPM assessment in a limited amount of time. It can be used as a screening tool to customize more specific assessments. Further research is needed to better characterize grid psychometric properties.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1948648 .

A Qualitative Study on the Needs of Women with Metastatic Breast Cancer.

Few studies have investigated the needs of patients with metastatic breast cancer (MBC), and none have been conducted in Italy. Three categories of needs have been identified from the literature: information, support, and practical resources. The present study aims to achieve an in-depth understanding of the patients' needs related to the MBC care pathway. In-depth interviews were conducted and analyzed by thematic analysis. The participants were 9 women with MBC (age range 36-74) who were enrolled at the Fondazione IRCCS Istituto Nazionalde dei tumori, in Milan. The analysis enabled us to identify four themes (which reflect the needs of the participants), each divided into numerous sub-themes: (1) the need for clinical recognition, (2) the need for more attention from healthcare professionals, (3) the need for more and better services to be available at the hospital, (4) the need for specific public health policies. Since the metastatic phase of breast cancer seems to elicit additional, specific needs and multi-level management, changes in attitudes and multidisciplinary practices should be tested in order to ascertain how these needs can be met.

A Prospective Observational Study of Multivisceral Resection for Retroperitoneal Sarcoma: Clinical and Patient-Reported Outcomes 1 Year After Surgery.

BACKGROUND: Primary retroperitoneal sarcoma (RPS) may require multivisceral resection (MVR). Clinical outcome (morbidity and renal function) and quality of life (QoL) are not as well reported as the oncologic outcome. METHODS: Patients with primary RPS who underwent surgery between 2014 and 2016 were prospectively enrolled in an observational longitudinal study. At baseline, then at 4 and 12 months, the study measured Clavien-Dindo morbidity, estimated glomerular filtration rate (EGFR), EORTC QLQ-C30, QLQ-CR29, DN4 (neuropathic pain [NP]), lower-extremity functional scale (LEFS), and the brief pain inventory. The primary end point was the difference in global health status (GHS/QoL). The secondary end points were EGFR changes, difference in other QLQ-C30 scales, pain intensity, NP, and LEFS. The study is registered at ClinTrials.gov (NCT03480399). RESULTS: Of 74 patients, 58 were evaluable. Morbidity grade 3 or higher was 24.1%, and mortality was 1.3%. After nephrectomy, the mean 1-year EGFR change was -33.9%. The GHS/QoL at baseline was 58.6 and had increased of 6.9 points at 1 year, comparable with that of the general population. A transient worsening in pain and diarrhea had recovered at 12 months. Average pain was mild and did not differ at 12 months. However, NP was found in 41.4% of the patients and was significantly associated with resection of the psoas muscle. At baseline, LEFS was already lower than the normative value, and worsening after surgery was not clinically relevant. CONCLUSION: A QoL measure after MVR in primary RPS is complex and requires multiple tools. Whereas overall MVR is safe and associated with an improvement in GHS/QoL, chronic NP is frequent and deserves specific attention. Pre-surgery rehabilitation tracks may help to prevent or reduce chronic NP.

Spiritual quality of life in family carers of patients with advanced cancer-a cross-sectional study.

PURPOSE: Caring affects carers' psychological and physical health, mortality, and quality of life (QoL) negatively. Lower spiritual QoL is associated with anxiety and depression, but the spiritual dimension is rarely investigated in carers. The present study aimed to explore which patient- and carer-related characteristics were associated with spiritual QoL in carers of patients with advanced cancer. METHODS: Secondary analyses were conducted using data from a prospective study investigating integration between oncology and palliative care. Adult patients with advanced cancer and their carers were included, and baseline data considering demographics, clinical characteristics, symptoms, social support, and religious meaning-making were registered. Spiritual QoL was measured using the Functional Assessment of Chronic Illness Therapy - Spiritual well-being (FACIT-Sp-12) questionnaire. Associations to spiritual QoL were explored by bivariate and multivariate regression models. RESULTS: In total, 84 carers were included, median age was 62.5 years, 52 (62%) were female, and the average spiritual QoL score was 23.3. In bivariate analyses, higher education, social support, and lower patients' symptom burden were significantly associated with higher spiritual QoL. The multivariate regression model (n=77) had an explained variance (R2) = 0.34 and showed a significant association for social support, higher education, having children < 18 years living at home, and patient's age. CONCLUSION: The study indicates that spiritual QoL in carers were low and were negatively affected by several factors related to both carers and patients. However, there could be other important factors not yet described. Health care professionals should be aware of the known associated factors, as carers who hold these may need extra support.

PATIENT VOICES, a project for the integration of the systematic assessment of patient reported outcomes and experiences within a comprehensive cancer center: a protocol for a mixed method feasibility study.

BACKGROUND: Listening to "patient voices" in terms of symptoms, emotional status and experiences with care, is crucial for patient empowerment in clinical practice. Despite convincing evidence that routine patient reported outcomes and experience measurements (PRMs) with rapid feed-back to oncologists can improve symptom control, patient well-being and cost effectiveness, PRMs are not commonly used in cancer care, due to barriers at various level. Part of these barriers may be overcome through electronic PRMs collection (ePRMs) integrated with the electronic medical record (EMR). The PATIENT VOICES initiative is aimed at achieving a stepwise integration of ePRMs assessment into routine cancer care. The feasibility project presented here is aimed at assessing the knowledge, use and attitudes toward PRMs in a comprehensive cancer centre; developing and assessing feasibility of a flexible system for ePRM assessment; identifying barriers to and developing strategies for implementation and integration of ePRMs clinical practice. METHODS: The project has been organized into four phases: a) pre-development; b) software development and piloting; c) feasibility assessment; d) post-development. A convergent mixed method design, based on concurrent quantitative and qualitative data collection will be applied. A web-survey on health care providers (HCPs), qualitative studies on patients and HCPs (semi-structured interviews and focus groups) as well as longitudinal and cross-sectional quantitative studies will be carried out. The quantitative studies will enroll 600 patients: 200 attending out-patient clinics (physical symptom assessement), 200 attending inpatient wards (psychological distress assessment) and 200 patients followed by multidisciplinary teams (patient experience with care assessment). The Edmonton symptom assessment scale, the Distress Thermometer, and a tool adapted from existing patient reported experience with cancer care questionnaires, will be used in quantitative studies. A multi-disciplinary stakeholder team including researchers, clinicians, health informatics professionals, health system administrators and patients will be involved in the development of potentially effective implementation strategies in the post development phase. DISCUSSION: The documentation of potential advantages and implementation barriers achieved within this feasibility project, will serve as a starting point for future and more focused interventions aimed at achieving effective ePRMs routine assessment in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03968718 ) May 30th, 2019.

An in-hospital clinical care pathway with integrated decision support for cancer pain management reduced pain intensity and needs for hospital stay.

PURPOSE: A clinical care pathway for pain management in a palliative care unit was studied with outcomes related to patients, physicians, and health care service. Mandatory use of patient-reported outcome measures (PROMs) and physician-directed decision support (DS) were integrated parts of the pathway. METHODS: Adult cancer patients with pain intensity (PI) ≥ 5 (NRS 0-10) at admission were eligible. The patients reported average and worst PI at admission, day four, and discharge. The physicians completed the DS at admission and day four. The DS presented potential needs for treatment changes based on pain severity and pathophysiology. The physicians reported treatment changes due to input from the DS system. The two primary outcomes were average and worst PI changes from admission to discharge. Hospital length of stay (LOS) was registered. RESULTS: Of 52 included patients, 41 were discharged alive. For those, the mean average PI at admission and at discharge was 5.8 and 2.4, respectively, a reduction of 3.4 points (CI 95% 2.7-4.1). The corresponding worst pain intensities were 7.9 and 3.8, a reduction of 4.1 points (CI 95% 3.4-4.8). The physicians completed DS forms for all patients. Fifty-five percent (CI 95% 41-69) of the patients had pain intervention changes based on the DS. A significant reduction in LOS (4.4 days, CI 95% 0.5-8.3) was observed during the study period. CONCLUSIONS: The interventions were implemented according to the intentions and PI was reduced as hypothesized. For evaluation of generalizability, the interventions should be studied in other settings and with a controlled design.

Pain management index (PMI)-does it reflect cancer patients' wish for focus on pain?

BACKGROUND: The pain management index (PMI) was developed to combine information about the prescribed analgesics and the self-reported pain intensity in order to assess physicians' response to patients' pain. However, PMI has been used to explore undertreatment of cancer pain. The present study explores prevalence of negative PMI and its associations to clinical variables, including the patient-perceived wish for more attention to pain. METHODS: A single-center, cross-sectional, observational study of cancer patients was conducted. Data on demographics and clinical variables, as well as patient-perceived wish for more attention to pain, were registered. PMI was calculated. Negative PMI indicates that the analgesics prescribed might not be appropriate to the pain intensity reported by the patient, and associations to negative PMI were explored by logistic regression models. RESULTS: One hundred eighty-seven patients were included, 53% had a negative PMI score. Negative PMI scores were more frequent among patients with breast cancer (OR 4.2, 95% CI 1.3, 13.5), in a follow-up setting (OR 12.1, 95% CI 1.4, 101.4), and were inversely associated to low performance status (OR 0.14, 95% CI 0.03, 0.65). Twenty-two percent of patients with negative PMI scores reported that they wanted more focus on pain management, versus 13% among patients with a non-negative PMI score; the difference was not statistically significant. CONCLUSION: A high prevalence of negative PMI was observed, but only 1/5 of patients with a negative PMI wanted more attention to pain by their physician. Our findings challenge the use of PMI as a measure of undertreatment of cancer pain.

A prospective study examining cachexia predictors in patients with incurable cancer.

BACKGROUND: Early intervention against cachexia necessitates a predictive model. The aims of this study were to identify predictors of cachexia development and to create and evaluate accuracy of a predictive model based on these predictors. METHODS: A secondary analysis of a prospective, observational, multicentre study was conducted. Patients, who attended a palliative care programme, had incurable cancer and did not have cachexia at baseline, were amenable to the analysis. Cachexia was defined as weight loss (WL) > 5% (6 months) or WL > 2% and body mass index< 20 kg/m2. Clinical and demographic markers were evaluated as possible predictors with Cox analysis. A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with a calibration plot, Harrell's c-statistic and receiver operating characteristic curve analysis. RESULTS: Six-hundred-twenty-eight patients were included in the analysis. Median age was 65 years (IQR 17), 359(57%) were female and median Karnofsky performance status was 70(IQR 10). Median follow-up was 109 days (IQR 108), and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A five-level model was created with each level carrying an increasing risk of cachexia development. For Risk-level 1-patients (WL < 3%, breast or hematologic cancer and no or little appetite loss), median time to cachexia development was not reached, while Risk-level 5-patients (WL 3-5%) had a median time to cachexia development of 51 days. Accuracy of cachexia predictions at 3 months was 76%. CONCLUSION: Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01362816 .

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.

A cross-sectional study examining the prevalence of cachexia and areas of unmet need in patients with cancer.

PURPOSE: The semantics of defining cancer cachexia over the last decade has resulted in uncertainty as to the prevalence. This has further hindered the recognition and subsequent treatment of this condition. Following the consensus definition for cancer cachexia in 2011, there is now a need to establish estimates of prevalence. Therefore, the primary aim of the present study was to assess the prevalence of cachexia in an unselected cancer population. A secondary aim was to assess patient-perceived need of attention to cachexia. METHODS: A cross-sectional study in hospital patients was undertaken. Key inclusion criteria were the following: age > 18 years, cancer diagnosis, and no surgery the preceding 24 h. Data on demographics, disease, performance status, symptoms, cachexia, and patients' perceived need of attention to weight loss and nutrition were registered. RESULTS: Data were available on 386 of 426 eligible patients. Median age (IQR) was 65 years (56-72), 214 (55%) were male and 302 (78%) had a performance status of 0-1 (Eastern Cooperative Oncology Group). Prevalence of cachexia (inpatients/outpatients) was 51/22%. Prevalence was highest in patients with gastrointestinal cancer (62/42%) and lung cancer (83/36%). There was no major difference in prevalence between patients with metastatic (55/24%) and localized disease (47/19%). Twenty percent of inpatients and 15% of outpatients wanted more attention to weight loss and nutrition. Cachexia (p < 0.001), symptoms of mood disorder (p < 0.001), and male gender (p < 0.01) were independently associated with increased need of attention. CONCLUSION: Cachexia is a prevalent condition, affecting both patients with localized and metastatic cancer. Clinical attention to the condition is a sizeable unmet need.

The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain.

BACKGROUND: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia. METHODS: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up. DISCUSSION: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02107664 , date of registration April 8, 2014 (retrospectively registered). TRIAL SPONSOR: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway.

Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project.

BACKGROUND: Bisphosphonates and denosumab are well-established therapies to reduce the frequency and severity of skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications on bone pain is uncertain. AIM: To identify, critically appraise and synthesize existing evidence to answer the following questions: 'In adult patients with metastatic bone pain, what is the evidence that bisphosphonates and denosumab are effective and safe in controlling pain?' and 'What is the most appropriate schedule of bisphosphonate/denosumab administration to control bone pain?'. This review also updates the 2002 Cochrane review 'Bisphosphonates for the relief of pain secondary to bone metastases'. DESIGN: Standard systematic review and narrative synthesis. DATA SOURCES: MEDLINE, EMBASE and Cochrane CENTRAL databases were searched for relevant articles published through 31 January 2014. A manual search was also performed. Study inclusion criteria were: a) conducted in adult patients; b) randomized controlled trial or meta-analisys; c) reported efficacy of bisphosphonates or denosumab on pain and/or decribed side effects versus placebo or other bisphosphonate; and d) English language. RESULTS: The database search yielded 1585 studies, of which 43 (enrolling 8595 and 7590 patients, respectively, in bisphosphonate and denosumab trials) met the inclusion criteria. Twenty-two (79%) of the 28 placebo-controlled trials found no analgesic benefit for bisphosphonates. None of the denosumab studies assessed direct pain relief. CONCLUSION: Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se.

Is it possible to detect an improvement in cancer pain management? A comparison of two Norwegian cross-sectional studies conducted 5 years apart.

PURPOSE: Cancer pain (CP) management is challenging. In recent years, efforts were undertaken to achieve better CP management, e.g. clinical research, new treatment modalities, development of guidelines, education and focus on implementation. The aim of the present study was to compare the prevalence and characteristics of pain and breakthrough pain (BTP) between cross-sectional studies conducted in 2008 and 2014. It was hypothesized that an improvement in pain control would be observed the years in between. METHODS: Two cross-sectional studies were conducted where adult cancer patients answered questions from Brief Pain Inventory and the Alberta Breakthrough Pain Assessment Tool for cancer patients. Physicians reported socio-demographic and medical data. Regression models were applied for analysis. RESULTS: In total, 168 inpatients, 92 in 2008 and 76 in 2014, and 675 outpatients, 301 in 2008 and 374 in 2014, were included. The patient characteristics of the samples were comparable. Prevalence of CP among inpatients was 55 % in 2008 and 53 % in 2014, and among outpatients, 39 and 35 %, respectively. Inpatients reported average pain intensity (0-10 numerical rating scale, NRS) of 3.60 (standard deviation, SD 1.84) (2008) and 4.08 (SD 2.11) (2014); prevalence of BTP was 52 % (2008) and 41 % (2014). For outpatients, average pain intensity was 3.60 (SD 2.04) (2008) and 3.86 (SD 2.20) (2014); prevalence of BTP was 43 % (2008) and 37 % (2014). None of the differences were statistically significant. CONCLUSION: Unexpectedly, no improvement in pain control was observed. Efforts are still needed to improve cancer pain management.

Liverpool Care Pathway for patients with cancer in hospital: a cluster randomised trial.

BACKGROUND: The quality of care provided to patients with cancer who are dying in hospital and their families is suboptimum. The UK Liverpool Care Pathway (LCP) for patients who are dying was developed with the aim of transferring the best practice of hospices to hospitals. We therefore assessed the effectiveness of LCP in the Italian context (LCP-I) in improving the quality of end-of-life care for patients with cancer in hospitals and for their family. METHODS: In this pragmatic cluster randomised trial, 16 Italian general medicine hospital wards were randomly assigned to implement the LCP-I programme or standard health-care practice. For each ward, we identified all patients who died from cancer in the 3 months before randomisation (preintervention) and in the 6 months after the completion of the LCP-I training programme. The primary endpoint was the overall quality of care toolkit scale. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01081899. FINDINGS: During the postintervention assessment, data were gathered for 308 patients who died from cancer (147 in LCP-I programme wards and 161 in control wards). 232 (75%) of 308 family members were interviewed, 119 (81%) of 147 with relatives cared for in the LCP-I wards (mean cluster size 14·9 [range eight to 22]) and 113 (70%) of 161 in the control wards (14·1 [eight to 22]). After implementation of the LCP-I programme, no significant difference was noted in the distribution of the overall quality of care toolkit scores between the wards in which the LCP-I programme was implemented and the control wards (score 70·5 of 100 vs 63·0 of 100; cluster-adjusted mean difference 7·6 [95% CI -3·6 to 18·7]; p=0·186). INTERPRETATION: The effect of the LCP-I programme in our study is less than the effects noted in earlier phase 2 trials. However, if the programme is implemented well it has the potential to reduce the gap in quality of care between hospices and hospitals. Further research is needed to ascertain what components of the LCP-I programme might be effective and to develop and assess a wider range of approaches to quality improvement in hospital care for people at the end of their lives and for their families. FUNDING: Italian Ministry of Health and Maruzza Lefebvre D'Ovidio Foundation-Onlus.

Seeking and experiencing meaning: exploring the role of meaning in promoting mental adjustment and eudaimonic well-being in cancer patients.

OBJECTIVE: The present study is the result of theory-driven research investigating the role of the search for and presence of meaning in enhancing both mental adjustment and eudaimonic well-being in cancer patients. METHOD: A cross-sectional study involved 266 cancer patients currently in the treatment and management phase of their illness. Data were collected by a written questionnaire. The search for meaning was assessed with the Seeking of Noetic Goals Test, and the presence of meaning was assessed using the Purpose in Life Test. Mental adjustment to a cancer diagnosis was assessed by two subscales of the Italian version of the Mini-Mental Adjustment to Cancer Scale, and eudaimonic well-being was assessed with the Psychological Well-Being Scale. Correlation and mediation analyses based on five thousand bootstrapping samples were performed. RESULTS: The mediation analyses showed that the presence of meaning totally or partially mediated the effect of the search for meaning on both mental adjustment and eudaimonic well-being. Further correlation analyses showed a high negative correlation between eudaimonic well-being and hopelessness. SIGNIFICANCE OF RESULTS: Our results appear relevant from both the theoretical and clinical points of view. They support a deeper understanding of the combined contribution of the search for and presence of meaning in promoting well-being in cancer patients. Simultaneously, they are consistent with suggestions from recent studies on the clinical psychology of posttraumatic growth and emphasize the relevance of eudaimonic well-being as a protective factor for hopelessness.