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Abstract
Background Early palliative care together with standard haematological care for advanced patients is needed worldwide. Little is known about its effect. The aim of the review is to synthesise the evidence on the impact of early palliative care on haematologic cancer patients’ quality of life and resource use.
Patients and methods A systematic review was conducted. The search terms were early palliative care or simultaneous or integrated or concurrent care and haematological or oncohaematological patients. The following databases were searched: PubMed, Embase, Cochrane, CINHAL and Scopus. Additional studies were identified through cross-checking the reference articles. Studies were in the English language, with no restriction for years. Two researchers independently reviewed the titles and abstracts, and one author assessed full articles for eligibility.
Results A total of 296 studies titles were reviewed. Eight articles were included in the synthesis of the results, two controlled studies provided data on the comparative efficacy of PC interventions, and six one-arm studies were included. Since data pooling and meta-analysis were not possible, only a narrative synthesis of the study results was performed. The quality of the two included comparative studies was low overall. The quality of the six non-comparative studies was high overall, without the possibility of linking the observed results to the implemented interventions.
Conclusions Studies on early palliative care and patients with haematological cancer are scarce and have not been prospectively designed. More research on the specific population target, type and timing of palliative care intervention and standardisation of collected outcomes is required.
PROSPERO registration number CRD42020141322.
- cancer
- haematological disease
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Introduction
Palliative care (PC) is a holistic approach that aims to improve the quality of life of people with a life-threatening illness and of their families. PC should be integrated with curative treatment at every disease stage, from diagnosis to the end of life.1 A growing body of literature has identified significant challenges in the provision of PC in the haematological setting2 3; several barriers to integration are present, including haematologists’ difficulty in prognostication, no research on haematology-specific patient needs, and misperceptions about PC and end-of-life care.4–6 The haematological population consumes a large amount of resources, has a low quality of life, exhibits high aggressiveness at the end of life, and has late access to PC services.7–11
It is difficult to adopt the classic criteria used in the oncological population to refer to PC,12–15 namely, stage IV metastatic disease, with no curative treatment options or limited estimated prognosis. Moreover, the term ‘early’ is not used in a standardised, unequivocal way in oncological settings; some authors define it as ‘just after the diagnosis of metastatic disease’,12 while others call for ‘early’ integration based on the complexity of patients’ needs (a more complex situation early on should have access to PC).16
In the field of haematology, little is known about the target population of a PC approach, the right time for an ‘early’ referral to a PC service, the most appropriate PC interventions, or, the effect of integrating PC with standard care. A call for a new model of integration between PC and haematological services is strong17 18: from the beginning of advanced disease for some authors,19 or modelled on the different patient needs for other authors.2 16
In this context, this systematic review aims to compare the effects of early PC interventions versus usual care/standard care on health-related quality of life, depression, symptom intensity and resource spending among adults with a diagnosis of haematological cancer.
This review is the first step of the Medical Research Council framework framework for complex intervention,20 21 the so-called phase 0, preliminary to the piloting of a new integrative model of PC and haematology required to synthesise evidence on the intervention.
Methods
Eligibility criteria
Eligible studies included adult patients with a diagnosis of haematologic cancer. Studies on paediatric patients only were excluded; similarly, studies including a mixed population of haematologic and solid cancers were excluded if the proportion of the former group was lower than 75% and no subgroup analysis was reported.
For the purpose of this review, the term PC refers to every type of PC intervention, from consultations in the hospital setting to PC visits in the ambulatory settings, home care programmes, access to hospice care or any other PC service. Studies in which PC services were evaluated only as referral services were not considered to be interventions and were thus not included in the review.
For the purpose of this review, early PC means a PC intervention in haematological patients undergoing transplant or undergoing ongoing active treatment. In this review simultaneous care is a synonym for early PC.
Both studies comparing early PC interventions with usual care and studies without a comparator were considered eligible.
Moreover, to be included, studies needed to report outcomes related to health-related quality of life and resource use.
Only quantitative research studies were included; we excluded reviews, qualitative studies, mixed methods studies, editorials, letters, discussions/experts’ opinion papers and research protocols.
Information sources
The search was carried out using PubMed, Embase, Cochrane, CINHAL and Scopus. Reference lists of reviews or primary studies identified as relevant were cross-checked to identify further eligible studies. One author (CB) is an information specialist who guided the search criteria and the search itself. See online supplemental appendix 2 for the search strategy used.
Supplemental material
Search
Medical subject headings terms were (early OR integrated OR simultaneous care OR concurrent) AND palliative care OR early palliative care OR simultaneous care AND (haematologic* OR haematologic* OR onco-haematologic*). Studies were in English, and there was no restriction for years (until 7 February 2020).
Study selection
Two researchers (ST and SL) independently reviewed the studies’ titles and agreed on the studies to include. Screening for full texts was undertaken by two authors (ST and FV). Any discrepancy was discussed between the two authors, and when consensus was not reached, a third author was also involved in the discussion (FDM).
Data collection process
To extract data from each study, we set up a data collection form. Two authors independently (FDM and LB) extracted data from each published study. Extracted data were discussed by the entire research team, and any disagreement was discussed with FV to reach a final decision.
There was no need to contact study authors to retrieve additional information.
Data items
We collected information on the study design, setting, participants (including number of patients, disease, treatment stage), intervention details, outcomes, results, type of comparison and timing of PC intervention.
Risk of bias of included studies
The quality of the included studies was assessed only for comparative studies using the Cochrane Risk of Bias tool V.2.0 for randomised trials22 and the Newcastle Ottawa Scale for non-randomised studies (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp). CARE guidelines were used for non-comparative studies.23 Since no meta-analysis was feasible, we reported the quality appraisal criteria of individual studies for descriptive purposes. FV and ST discussed the studies included and their risk of bias.
Summary measures and synthesis of results
Since data pooling and meta-analysis were not possible, only a narrative synthesis of the study results was performed. The characteristics of the included studies are reported based on classic PICO criteria (patients, intervention, study design, comparison, patients, outcomes) in table 1. For descriptive and comparative purposes, details on patients’ characteristics and type of intervention are also reported (table 2).
Studies evaluating the efficacy of PC intervention and haematological patients
Patient characteristics and PC intervention
The summary statistics used in the included studies were used to report the results of comparative studies (table 3) and one-arm studies (table 4). A qualitative analysis of non-comparative studies was performed (online supplemental appendix 3). No additional analyses were performed.
Supplemental material
Efficacy of PC in haematologically advanced cancer patients
Narrative synthesis of the results of palliative care and haemtalogic patients
Results
Study selection
A total of 296 studies titles were reviewed.
Of the 28 full articles read, three were excluded because, being a description of experiences of haematologists and PC services, they lacked data.7–10 Four other studies were excluded because the haematological population enrolled was under 75% of the total.13 24–26 Another eight studies were excluded because only congress abstracts were available,27–34 and one study35 was excluded because it was an editorial.
Eight articles were included in the synthesis of the results (see Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram).
Characteristics of included studies
The study populations varied; they included haematological patients with or without specified diseases, those in different treatment phases or those who were inpatients or outpatients. In most of the studies, patients were admitted patients. PC service was an intervention arm/experimental arm in the two randomised controlled trials, set up as a classic PC unit with at least one specialised nurse and one physician. This basic team composition was present in all the studies analysed, but the type of services guaranteed differed between consultation services, home care programmes, hospice care, mobile teams and PC units. In most of the studies, PC services had no beds and functioned as consultation services. Haematologists sent patients to PC services at different time points to assess the suitability of PC services for patients candidate to transplantation very early in the disease stage,36–40 but there were also a similar number of studies in which the patients were referred in the last stage of disease, near death.35 41 42 Two controlled studies providing data on the comparative effectiveness of PC interventions and six one-arm studies were included. Different outcomes were measured: quality of life was collected in four studies,36–39 while aggressiveness in end-of-life care and length of stay in hospice or PC services were collected in the others. See table 1 for detailed characteristics.
Quality of included studies
The quality of the two included comparative studies was low overall. However, the quality of the RCTs was mainly affected by the intrinsic characteristics of experimental studies in this field, such as being almost necessarily open trials and assessing the impact on patient-reported outcomes, potentially affected by the lack of blinding.36 Details on the risk of bias assessment are reported in online supplemental appendix 1.
Supplemental material
The quality of the non-comparative studies was high overall. Two of the eight items included in the guidelines we adopted23 were not applicable to this kind of study (see online supplemental appendix 3).
Characteristics of haematological patients and PC interventions in included studies
Patient characteristics and PC interventions differed among the included studies (see table 2 for details).
Figure 1 illustrates how we grouped the studies based on outcome categories (patient centred or care centred) and treatment phase to present the overarching point of view of the topic of this article, namely, PC and patients with haematological cancer; most of the studies were care centred and in the early treatment phase (transplant and active phase).
Study characteristics grouped by outcomes and treatment phase. LES, lenght of stay; QoL, quality of life.
Results from included studies on health-related quality of life and resource use
Comparative studies
El-Jawahri et al 36 showed a significant improvement in the HADS-A hospital anxiety score (p<0.001) in the experimental arm. Intervention patients’ had depression increased less, there was no difference in fatigue and symptom burden increased less.
In Rodin et al,37 EASE was associated with significant reductions in traumatic stress symptoms and in clinically relevant symptoms of ASD or threshold ASD, pain intensity and pain interference compared with UC. There were also promising non-significant trends favouring EASE over UC on most of the other secondary outcomes.
Data are reported in table 3.
One-arm studies
Porta-Sales et al 39 showed a significant improvement in pain and depressive mood (p<0.0001 and p=0.001, respectively) between the first and third PC consultations (−68%, −92% and −62%, for the first, second and third consultations, respectively. The number of patients with no pain increased, and the interference of pain with insomnia and mood decreased.
In Loggers et al’s study,38 there were no statistically significant changes in scores over time in transplanted patients.
Selvaggi et al’s study40 showed an improvement from <5% to 41% in hospice referrals after programme implementation; the haematologists greatly appreciated the clinical recommendations of PC services on useful pain management.
In the Hung et al 43 study, haematological patients were significantly less frequently transferred to hospice than were solid cancer patients and were referred later to PCS after admission to the hospital (p<0.001).
In the Cartoni et al 41 study, patients discharged early and in the terminal phase required the highest mean monthly number of home visits (27.2 vs 24.1), transfusions (6.1 and 6.8) and days of care (22.8 and 19.7), respectively. Median monthly costs for terminal patients (€4300) and those discharged early (€3980) were higher than those for advanced (€2303) and chronic (€1488) patients.
In Cheung et al,42 2932 (26.4%) patients with haematologic cancer received PC and were able to spend more time at home than were patients who did not receive such services (median time at home increased by 3.2 days; p<0.0001).
The data are shown in table 4.
Discussion
Summary of evidence
Of the 296 titles screened, we included two studies providing evidence on the comparative effectiveness of early/simultaneous PC in patients with haematologic cancer. The randomised control trial compared the PC intervention for 160 transplanted patients to standard care. The primary outcomes for this review (efficacy) were assessed, but the only difference favouring the experimental arm was a reduction in anxiety. The other comparative study, by Rodin et al,37 assessed the improvement of clinically relevant symptoms of ASD or threshold ASD, pain intensity, and pain interference compared with standard care in 22 AL patients.
The other six studies included were single-arm studies that provided only information on the population, setting and intervention characteristics, without the possibility of linking the observed results to the implemented interventions.
The interpretation of the available evidence should also carefully consider the overall low quality of the comparative studies included and the limitations of retrospective one-arm studies in providing strong evidence on the efficacy of interventions.
Moreover, the studies analysed showed heterogeneity in the population, PC intervention, disease trajectory and treatment phase.
A summary of the main characteristics of the studies included is shown in table 1. The majority of patients were inpatients; hospitals or hospices seemed to be the appropriate setting for complex patients with haematologic cancer.
Different care settings led to different PC interventions. Overall, PC services differed in composition (nurse and physicians, other specialists, composition not specified), issues addressed (symptoms, goals of care, spiritual needs, etc), delivery modality (as consultation or phone calls) and frequency of consultations. Different models that integrate PC interventions with haematologic standard care are described; PC physicians could be consultants in the haematology department or in simultaneous care with ambulatory services or with dedicated beds of PC.
From this review, we cannot identify the right time to refer to PC services patients with haematologic cancer or the haematological population that would most benefit from a PC intervention.
The timing of referral to any PC service depends on the individual patient, ranging from some days for those at the end of life to a referral from diagnosis for patients receiving a transplant; studies are divided between PC at the end of life26–28 and a visionary concept of PC for non-advanced cancer patients.35–37 39 40
We identified two major criteria for identifying candidate patients for PC intervention: selection according to prognosis or high symptom burden (as in transplanted patients or in high-risk patients).
We identified an early approach in six studies.36–41 For the purpose of this review, an agreement was reached between the PC physician (ST) and haematologist (SL) who screened the title/abstract for the full text; patients receiving transplant and those with ongoing active treatment were included. In all the studies we identified as ‘early’, the basic components of a PC service of an expert PC physician and a specialised nurse were guaranteed.
During the screening phase of this review, while we did exclude some reviews, there was nevertheless general agreement on early integrated PC in haematology-malignancies assistance emerged.44–47
Moreno-Alonso et al 45 evidenced that haematology-oncology departments treating haematological malignancies involve palliative care services only at the end of life. The authors suggested that specific clinical features of haematological malignancies may impede timely referral to PC such as the hospice setting or home care. The authors of this review agree with Ruiz’s paper on an early PC needs-centred model. Prognosis-linked referral is difficult due to the uncertainty of prognostication in many patients as shown by Oechsle48 in his review; some specific symptomatic groups could benefit more from a PC assistance.
The model of integrating PC in haematology clinical practice is gaining much interest as a research question, and we also believe that haematological patients should not be evaluated for CP based on their prognosis but rather based on their needs, including symptom control needs, social and spiritual needs and the need to discuss and plan therapies and life choices.
Patient pathways and illness trajectories for haematological malignancies differ considerably for chronic or acute patients49; as a result, the type of integration with PC should be flexible.
The recent review article by El- Jawahri50 hypothesised a potential approach for identifying the appropriate PC integration strategy in patients with low, moderate or high symptom burden and mortality; PC involvement as disease progresses, early intermittent PC or early longitudinal PC, respectively.
Limitations
The low quality and the heterogeneity of the studies included make the combination of study results not unfeasible, limiting the evidence synthesis on right time and haematological patient’s eligibility criteria for referral to PC interventions.
Moreover, the retrospective study design of most of the included studies is not appropriate for the collection of patient-reported outcome measures from the patients themselves after a PC intervention or of the usual outcomes evaluated in PC to measure quality of life.
Despite several limitations, our review provides a comprehensive overview of PC interventions in haematological patients, pointing out the gaps in knowledge in this field.
Conclusion
While there are no prospective studies on early PC and haematological patients, some studies are ongoing; patients with acute leukaemia51 and patients with high-risk acute myeloid leukaemia52 experience relapse. Searching ClinicalTrial.gov, three ongoing studies were found that integrate our eligibility criteria (NCT03743480, NCT04248244, NCT03800095): on multiple myeloma patients, on haematological patients at their last active treatment53 and on early PC in haematological malignancies. This indicates an increasing interest in the topic.
Most studies agree that referrals to PC occur too late for complex, multifactorial reasons. PC referrals should be guided by a needs-centred approach, overcoming the uncertainty of prognosis or the sudden deterioration in health of these patients.29 PC specialists should be more confident in dealing with the specific clinical features of haematological malignancies. PC specialists and haematologists should collaborate to assist dying inpatients.
Research is needed, with randomised control trials on homogeneous haematologic cancer patients using standardised PC interventions to evaluate their efficacy based on the patients’ points of view.
Acknowledgments
The authors thanks Jaqueline M Costa for the English language editing.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.