Revised European Association for Palliative Care (EAPC) recommended framework on palliative sedation: An international Delphi study.

BACKGROUND: The European Association for Palliative Care (EAPC) acknowledges palliative sedation as an important, broadly accepted intervention for patients with life-limiting disease experiencing refractory symptoms. The EAPC therefore developed 2009 a framework on palliative sedation. A revision was needed due to new evidence from literature, ongoing debate and criticism of methodology, terminology and applicability. AIM: To provide evidence- and consensus-based guidance on palliative sedation for healthcare professionals involved in end-of-life care, for medical associations and health policy decision-makers. DESIGN: Revision between June 2020 and September 2022 of the 2009 framework using a literature update and a Delphi procedure. SETTING: European. PARTICIPANTS: International experts on palliative sedation (identified through literature search and nomination by national palliative care associations) and a European patient organisation. RESULTS: A framework with 42 statements for which high or very high level of consensus was reached. Terminology is defined more precisely with the terms suffering used to encompass distressing physical and psychological symptoms as well as existential suffering and refractory to describe the untreatable (healthcare professionals) and intolerable (patient) nature of the suffering. The principle of proportionality is introduced in the definition of palliative sedation. No specific period of remaining life expectancy is defined, based on the principles of refractoriness of suffering, proportionality and independent decision-making for hydration. Patient autonomy is emphasised. A stepwise pharmacological approach and a guidance on hydration decision-making are provided. CONCLUSIONS: This is the first framework on palliative sedation using a strict consensus methodology. It should serve as comprehensive and soundly developed information for healthcare professionals.

Ethical considerations in the relief of cancer pain.

The management of pain for patients with cancer and cancer survivors is a critical clinical task that involves a multitude of ethical issues at almost every phase of the cancer experience. This review is divided into three sections: In the first, we address rights and duties in the relief of pain from the perspective of patients, clinicians, health care institutions and organizations, and public policy. This section includes a detailed description of issues and duties in relation to opioid misuse and addiction. In the second section, we discuss the ethical consideration of therapeutic planning. The final section addresses ethical considerations in the management of pain at the end of life including a detailed discussion regarding ethical issues relating to the use of palliative sedation as a clinical intervention of last resort.

Automatic referral to standardize palliative care access: an international Delphi survey.

PURPOSE: Palliative care referral is primarily based on clinician judgment, contributing to highly variable access. Standardized criteria to trigger automatic referral have been proposed, but it remains unclear how best to apply them in practice. We conducted a Delphi study of international experts to identify a consensus for the use of standardized criteria to trigger automatic referral. METHODS: Sixty international experts stated their level of agreement for 14 statements regarding the use of clinician-based referral and automatic referral over two Delphi rounds. A consensus was defined as an agreement of ≥70% a priori. RESULTS: The response rate was 59/60 (98%) for the first round and 56/60 (93%) for the second round. Twenty-six (43%), 19 (32%), and 11 (18%) respondents were from North America, Asia/Australia, and Europe, respectively. The panel reached consensus that outpatient palliative care referral should be based on both automatic referral and clinician-based referral (agreement = 86%). Only 18% felt that referral should be clinician-based alone, and only 7% agreed that referral should be based on automatic referral only. There was consensus that automatic referral criteria may increase the number of referrals (agreement = 98%), facilitate earlier palliative care access, and help administrators to set benchmarks for quality improvement (agreement = 86%). CONCLUSIONS: Our panelists favored the combination of automatic referral to augment clinician-based referral. This integrated referral framework may inform policy and program development.

How skilled do Israeli nurses perceive themselves to be in providing palliative care? Results of a national survey.

BACKGROUND: In Israel, palliative care (PC) services are limited. This study assessed Israeli nurses' perceived competencies and educational needs in providing PC. DESIGN: Online administration of the End-of-Life Professional Caregiver Survey (EPCS). SETTING/SUBJECTS: Oncology and PC nurses were identified through the Israel Ministry of Health and Oncology Nurses' Society. MEASUREMENTS: Demographic and practice data were analysed using analysis of variance tests to determine differences between nurse characteristics by EPCS domains. RESULTS: The sample (n=105) was 94% female, had a mean age of 48 years (SD=10.5) and 83% were Jewish Israeli. Thirty-nine percent reported PC training in nursing school and 42% felt their workplace provided little to no PC education and resources to nurses. Those with advanced degrees and those who received post-graduate PC training had higher mean scores across EPCS domains (p<0.05 for all). CONCLUSIONS: Nursing education and workplace support in PC for Israeli nurses are limited. It is hoped that these findings may inform future PC nursing education and policy in Israel.

Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P<0.001) in the dexrazoxane group, but no significant difference in the incidence of treatment delays or cancellations. The incidence of cardiac events was the same in both treatment groups with and without dexrazoxane. There was a nonsignificantly lower mortality rate in the dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding dexrazoxane to doxorubicin in adjuvant therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions. No differences in events defined as cardiac toxicities were detected. Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the dexrazoxane group.

Referral criteria for outpatient specialty palliative cancer care: an international consensus.

Although outpatient specialty palliative-care clinics improve outcomes, there is no consensus on who should be referred or the optimal timing for referral. In response to this issue, we did a Delphi study to develop consensus on a list of criteria for referral of patients with advanced cancer at secondary or tertiary care hospitals to outpatient palliative care. 60 international experts (26 from North America, 19 from Asia and Australia, and 11 from Europe) on palliative cancer care rated 39 needs-based criteria and 22 time-based criteria in three iterative rounds. Nearly all experts responded in each round. Consensus was defined by an a-priori agreement of 70% or more. Panellists reached consensus on 11 major criteria for referral: severe physical symptoms, severe emotional symptoms, request for hastened death, spiritual or existential crisis, assistance with decision making or care planning, patient request for referral, delirium, spinal cord compression, brain or leptomeningeal metastases, within 3 months of advanced cancer diagnosis for patients with median survival of 1 year or less, and progressive disease despite second-line therapy. Consensus was also reached on 36 minor criteria for specialist palliative-care referral. These criteria, if validated, could provide guidance for identification of patients suitable for outpatient specialty palliative care.

Integration of oncology and palliative care: a systematic review.

BACKGROUND: Both the American Society of Clinical Oncology and the European Society for Medical Oncology strongly endorse integrating oncology and palliative care (PC); however, a global consensus on what constitutes integration is currently lacking. To better understand what integration entails, we conducted a systematic review to identify articles addressing the clinical, educational, research, and administrative indicators of integration. MATERIALS AND METHODS: We searched Ovid MEDLINE and Ovid EMBase between 1948 and 2013. Two researchers independently reviewed each citation for inclusion and extracted the indicators related to integration. The inter-rater agreement was high (κ = 0.96, p < .001). RESULTS: Of the 431 publications in our initial search, 101 were included. A majority were review articles (58%) published in oncology journals (59%) and in or after 2010 (64%, p < .001). A total of 55 articles (54%), 33 articles (32%), 24 articles (24%), and 14 articles (14%) discussed the role of outpatient clinics, community-based care, PC units, and inpatient consultation teams in integration, respectively. Process indicators of integration include interdisciplinary PC teams (n = 72), simultaneous care approach (n = 71), routine symptom screening (n = 25), PC guidelines (n = 33), care pathways (n = 11), and combined tumor boards (n = 10). A total of 66 articles (65%) mentioned early involvement of PC, 18 (18%) provided a specific timing, and 28 (28%) discussed referral criteria. A total of 45 articles (45%), 20 articles (20%), and 66 articles (65%) discussed 8, 4, and 9 indicators related to the educational, research, and administrative aspects of integration, respectively. CONCLUSION: Integration was a heterogeneously defined concept. Our systematic review highlighted 38 clinical, educational, research, and administrative indicators. With further refinement, these indicators may facilitate assessment of the level of integration of oncology and PC.

How well is palliative care integrated into cancer care? A MASCC, ESMO, and EAPC Project.

INTRODUCTION: The benefits of integration of palliative care into oncology have become evidence-based. How palliative care is perceived and structured in various settings and countries would be of interest. METHOD: We used a previously published questionnaire to survey multiple institutions with members in MASCC and ESMO. The survey was made available on the MASCC website for approximately 6 months and repeated requests were made to complete the survey. Comparisons were made between NCI/ESMO designated cancer centers, nondesignated cancer centers, and urban hospitals. RESULTS: One hundred eighty-three different institutions completed this survey, 28 % of ESMO designated centers. Most institutions had palliative care programs and most programs consisted of an inpatient consult service and outpatient clinics. A minority had inpatient palliative care beds and institution supported hospice services. Barriers to palliative care were largely financial. Integration of palliative care into oncology was highly desirable but only a minority of respondents felt that their institution would financially support expanded services and additional palliative care personnel. Designated centers were more likely to have expanded palliative care services. DISCUSSION: Our findings are very similar to those previously published. Multiple studies have demonstrated that though palliative care integration into oncology is highly beneficial as measured by patient related outcomes, there is a great concern about reimbursement for services and budget constraints which prevent expansion of services. CONCLUSION: Palliative care integration into cancer care is largely through consulting services for inpatients and outpatient clinics. Financial concerns limit integration and expansion of palliative care services. Designated cancer centers have more extensive palliative care services relative to nondesignated cancer centers and urban hospitals.

MASCC/ESMO/EAPC survey of palliative programs.

BACKGROUND: Palliative care program structure is important to integrating palliative services into cancer care. A first step in understanding the structure of palliative care programs is to survey existing programs. METHOD: This data was generated from members of MASCC, the European Society of Medical Oncology (ESMO), and the European Association of Palliative Care (EAPC) who completed the surveys on the website. A survey questionnaire was developed using the survey tool developed by Dr. Hui and colleagues by permission which was modified for the purposes of this study. Findings were described in number and percentages. Inferential statistics involved the Fisher's exact test for factors with two levels, chi-Square test for unordered categorical factors with greater than two levels, Cochran-Armitage trend test for ordered categorical factors, and the Wilcoxon rank sum test for measured factors. RESULTS: Sixty-two program leaders completed the survey. Most programs had been in existence greater than 5 years and were led by oncology trained physicians who had an additional specialty. Most programs had consultative services and outpatient clinics with fewer having inpatient beds and institutionally associated hospices. Most programs provided patient continuity. Patients were generally seen late in the course of illness with the average survival of 23 days when seen as inpatients and 40 days when seen as outpatients. Less than half had palliative care fellowship training programs. Most had research structures in place. DISCUSSION: These findings differ from results reported in a previous survey which may reflect a European palliative care program structure. However, there were similarities which include a high inpatient palliative care unit mortality and short survival of patients seen as outpatients, indicating that referrals to palliative care occur late in the course of cancer. CONCLUSIONS: This study not only differs in some respects to a previous survey of palliative care programs but also confirms the late referral of patients to palliative care.

Consensus-based standards for best supportive care in clinical trials in advanced cancer.

Best supportive care is poorly defined in clinical trials, and a standard framework for delivery of such care is needed, using best available evidence and allowing replication of studies. We convened a panel of 36 experts to develop consensus statements via the Delphi method. The first round included open-ended questions; subsequent rounds sought to develop consensus-based standards. Consensus was assessed by use of a 5-point Likert agreement scale; more than 70% of panellists had to give a score of 5 to meet a-priori levels of consensus. The panel identified four key domains of best supportive care in clinical trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. Consensus was reached on 11 statements within these four domains. For example, 24 (96%) panellists recommended that the intervals between symptom assessments should be identical for control and experimental groups. Availability of resources was cited as a challenge to implementation of best supportive care standards.

Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system.

Controversies in oncologist-patient communication: a nuanced approach to autonomy, culture, and paternalism.

Difficult dialogues with patients facing life-changing decisions are an intrinsic part of oncologic practice and a major source of stress. Having a sophisticated approach to the concepts of autonomy, paternalism, and culture can help in addressing difficult dilemmas that arise around the issues of disclosure and decision making. This article addresses some of the most common major challenges in oncologist-patient communication with a nuanced approach to the concepts of autonomy, paternalism, and culture. It introduces the new concept of"voluntary diminished autonomy" and describes the implications this concept has for the consent process. It also attempts to bring clarity to common problems and misconceptions relating to culture, paternalism, and therapeutic privilege as these pertain to the communication practices of oncologists.

An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed?

In 2016, the then US President Barack Obama announced the Cancer Moonshot with a view to making 10 years' worth of progress in cancer prevention, diagnosis and treatment in only 5 years. This Perspective evaluates the FDA approvals of therapeutic agents for use in solid tumour oncology for the period 2017-2021 against the aspirations of the Cancer Moonshot. In the past 5 years, the FDA issued an unprecedented 161 new approvals of therapeutic agents for various indications in adult patients with solid tumours. However, less than a third (27%) of the newly approved medicines are supported by unequivocal evidence of an overall survival benefit; most are supported by positive signals from surrogate end points. Herein, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 was used to evaluate the clinical value of the therapies granted FDA approval during the period 2017-2021. The results of this appraisal indicate a low level of clinical benefit for a substantial proportion (~20%) of the new indications, with most (~44%) providing intermediate benefit. The data suggest that, beyond increases in the sheer quantity of approvals, considerable improvement in the quality of the approved treatments is required to more confidently ensure that the clinical benefits are real and substantial enough to clearly justify the risks to patients.

Feasibility of Large-Scale Implementation of an Electronic Patient-Reported Outcome Remote Monitoring System for Patients on Active Treatment at a Community Cancer Center.

PURPOSE: The use of digital symptom monitoring with patient-reported outcomes (PROs) has been shown to improve patient outcomes. The evidence of benefit has been largely derived from research studies. The feasibility of adopting this technology in the real-world setting is unknown. METHODS: We report on the clinical implementation of a proprietary electronic patient-reported outcome (ePRO)-based digital symptom monitoring platform at the Highlands Oncology Group practice, a large community oncology practice. We present here our experience with patient enrollment, engagement, and retention; reasons for discontinued use; proportion of reports generating alerts and containing severe symptoms; and the responses to alerts including nursing telephone consultations and urgent office visits. RESULTS: Over an approximately 17-month period, 923 patients were successfully enrolled. Patients enrolled from June 20, 2020, through November 30, 2021, with follow-up through February 28, 2022. Retention rates at 3, 6, 9, and 12 months were 94%, 88%, 73%, and 67%, respectively, with greater retention at 12 months in patients age 65 years or older. Few patients discontinued use for reasons related to the platform (n = 47; 5%). Of the 25,311 ePRO reports submitted, 49% (n = 12,334) exceeded the predefined alert thresholds and 8% (n = 1,920) included severe symptoms. The nursing team responded within 24 hours by telephone to 31.2% (n = 3,910) of all reports with alerts. Of reports with severe symptoms, 72.7% (n = 1,395) received a call. Only 6.4% (n = 249) of phone calls required an office evaluation within 72 hours of the report. CONCLUSION: This single-center experience indicates that an ePRO-based digital symptom monitoring platform can be effectively implemented at a large scale with a high level of long-term patient engagement. Most reports could be effectively resolved by nurses, and physician intervention was infrequently required.

Factors influencing the attitudes and behaviors of oncologists regarding the truthful disclosure of information to patients with advanced and incurable cancer.

OBJECTIVE: To evaluate the attitudes of the European Oncologists to information disclosure to patients with advanced cancer, their self-reported behaviors, and the factors that influence both attitudes and behaviors. METHODS: ESMO members were invited to complete an online questionnaire to evaluate both attitudes and clinical behaviors relating to the disclosure of information to patients with advanced cancer. Data were analyzed to evaluate demographic, educational and social factors influencing attitudes and behaviors. RESULTS: Two hundred and ninety-eight completed surveys were returned. The survey demonstrated strong internal consistency construct validity. The responses indicate that individual clinicians generally display a range of behaviors including non-disclosive as well as disclosive behaviors depending on the dynamics of individual interactions between oncologist and specific patient. Although regional cultural norms influence oncologists' attitudes toward disclosure and, indirectly, their self-reported behaviors, the impact is influenced by other factors: in particular, perceived institutional professional norms, the degree of training in breaking bad news and the frequency of exposure to requests by family members to withhold information from the patient. CONCLUSIONS: Positive attitudes regarding disclosure of information to patients and disclosive behaviors can be encouraged, even in non-Western countries, by the development of strong professional norms and education in breaking bad news and coping with the emotional responses of patients.

Trends in opioid analgesics consumption, Israel, 2000-2008.

OBJECTIVE: To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. METHODS: Data for the 2000-2008 period (all treatment settings, private and public) were drawn from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration. The data were converted into a defined daily dose (DDD)/1,000 inhabitants/day. RESULTS: Consumption of the five strong opioids (requiring a special prescription form) increased by 47%, from 2.46 DDD/1,000 inhabitants per day in 2000 to 3.61 DDD/1,000 inhabitants per day in 2008. This rise was mainly the result of a 4-fold increase in fentanyl consumption from 0.32 DDD/1,000 inhabitants per day in 2000 to 1.28 DDD/1,000 inhabitants per day in 2008. Oxycodone and methadone consumption levels increased moderately, and buprenorphine and dextropropoxyphene consumption rose drastically, whereas morphine, pethidine, and codeine use significantly fell. CONCLUSION: There has been a modest increase in opioid consumption in the years 2000-2008. This has been associated with substantial changes in the pattern of differential opioid prescribing characterized by increased prescription of oxycodone, fentanyl, buprenorphine, and dextropropoxyphene, and decreases in morphine, pethidine, and codeine.

Is oral methadone better than placebo or other oral/transdermal opioids in the management of pain?

AIM: To address the question: is oral methadone better than placebo, or other oral/transdermal opioids in the management of cancer pain? METHOD: A literature search was performed to identify relevant studies. Search strategies included: (1) methadone (title) AND placebo (title or abstract) AND pain (title or abstract); (2) methadone (title) AND randomized (title or abstract) AND pain (title or abstract) AND cancer (title or abstract). Papers were reviewed for relevance to first-line opioid therapy. RESULTS: No studies were identified comparing methadone to placebo for cancer pain. A single study compared methadone to placebo for neuropathic pain and demonstrated evidence of analgesic effect at a dose of 20 mg/day but not at a dose of 10 mg/day. Four studies compared oral methadone to either oral morphine, or oral morphine and transdermal fentanyl in a first-line setting: Gourlay 1986 (N = 18), Ventafridda 1986 (N =54), Bruera 2004 (N = 106) and Mercadante 2008 (N = 108). All studies demonstrated comparable, but not superior, analgesia with, overall, a comparable adverse effect profile. The duration of the study period for the three largest studies was 28 days. Two of these studies, Ventafridda 1986 and Mercadante 2008, indicated that, over time, the opioid escalation index was lower for methadone than for morphine. One study that used a 2:1 dose ratio between morphine and methadone was associated with a high attrition rate in the first week because of excessive sedation. This effect was not seen in the study that used a 4:1 morphine to methadone dose ratio with dose titration. CONCLUSION: This limited data suggests that (1) methadone may be an equally effective candidate for first-line opioid therapy, (2) that it is possibly less expensive, (3) that there may be a propensity to sedation and dose accumulation unless there is close monitoring and conservative dose selection and (4) that it should be initiated with a calculated dose based on a morphine to methadone dose ratio of not less than 4:1.