Quality of end-of-life care in patients with hematologic malignancies: A retrospective cohort study
To the authors' knowledge, only limited data are available regarding the quality of end-of-life care for patients with hematologic malignancies. In this retrospective cohort study, the quality of end-of-life care was compared between patients with hematologic malignancies and those with solid tumors.
All adult patients who died of advanced cancer between September 1, 2009 and February 28, 2010 while under the care of the study institution were included. The authors collected baseline demographics and end-of-life care indicators, including emergency room visits, hospitalization, intensive care unit admissions, and systemic cancer therapy use within the last 30 days of life.
Of a total of 816 decedents, 113 (14%) had hematologic malignancies. In the last 30 days of life, patients with hematologic malignancies were more likely to have emergency room visits (54% vs 43%; P = .03), hospital admissions (81% vs 47%; P < .001), ≥ 2 hospital admissions (23% vs 10%; P < .001), > 14 days of hospitalization (38% vs 8%; P < .001), intensive care unit admissions (39% vs 8%; P < .001) and death (33% vs 4%; P < .001), chemotherapy use (43% vs 14%; P < .001), and targeted therapy use (34% vs 11%; P < .001) compared with patients with solid tumors. Patients with hematologic malignancies were also less likely to have palliative care unit admissions (8% vs 17%; P = .02). The composite score for aggressiveness of care (with 0 indicating the best and 6 indicating the worst) was significantly higher among patients with hematologic malignancies compared with those with solid tumors (median, 2 vs 0; P < .001). On multivariate analysis, hematologic malignancy was found to be a significant factor associated with aggressive end-of-life care (odds ratio, 6.6; 95% confidence interval, 4.1-10.7 [P < .001]).
The results of the current study indicate that patients with hematologic malignancies received more aggressive care at the end of life. Cancer 2014;120:1572–1578. © 2014 American Cancer Society.
Patients with hematological malignancies often experience significant physical symptoms such as fatigue, insomnia, drowsiness, pain, dyspnea, and neuropathy as a result of complications from progressive cancer and antineoplastic treatments.[1, 2] Cytopenias, infections, and coagulopathies are particularly common in these patients, necessitating frequent hospitalizations, invasive investigations, monitoring, and therapies.[3-5] Moreover, patients with hematological malignancies are often treated with intensive antineoplastic regimens that may continue until the last days of life.[6, 7] Understandably, these patients and their caregivers frequently experience psychological distress.[8, 9]
Although symptom burden in patients with hematologic malignancies has been studied by our group and others,[1, 2] to the best of our knowledge, the quality of end-of-life care has not been well examined in these patients. We found only 2 population-based studies on this topic, both reporting that the diagnosis of a hematological malignancy was one of the factors associated with more aggressive end-of-life care based on composite scores.[10, 11] However, to our knowledge no study to date has specifically documented the rates of emergency room visits, hospitalization, and intensive care unit (ICU) use with a focus on those patients with advanced hematological malignancies. A better understanding of how patients with hematologic malignancies were managed in the last 30 days of life would help clinicians, administrators, and policy makers to identify gaps in care and potential areas for improving the quality of end-of-life care for these patients. In this retrospective cohort study, we compared the quality of end-of-life care indicators between patients with hematologic malignancies and those with solid tumors.
MATERIALS AND METHODS
This retrospective cohort study was a secondary analysis of an inclusive institutional cohort we previously used to examine the patterns of palliative care referral. Briefly, we reviewed the medical records of 816 consecutive patients who were treated at The University of Texas MD Anderson Cancer Center (MDACC) in Houston who died as a result of advanced cancer between September 1, 2009 and February 28, 2010 and had a postal address within the 7-county Houston metropolitan area, which was defined as the central county (Harris) and the 7 surrounding counties (Brazoria, Chambers, Fort Bend, Galveston, Liberty, Montgomery, and Waller). We defined advanced cancer as locally advanced, metastatic, or recurrent disease for patients with solid tumors and as incurable disease at presentation or first recurrence for patients with hematologic malignancies (ie, leukemia, lymphoma, and myeloma). We also included patients who refused all curative treatments, who were referred to the phase 1 program, and who had an incurable (or refractory) cancer or were not eligible for potentially curative treatment as per oncology notes. For patients with > 1 malignancy, we used the data pertaining to the cancer most responsible for death. Patients who were aged < 18 years, whose death was unrelated to advanced cancer, or whose last contact with MDACC was > 3 months before their death were excluded. This retrospective study was approved by the Institutional Review Board at MDACC.
Baseline demographics such as age, sex, race, marital status, cancer diagnosis, and date of advanced cancer diagnosis had been collected previously. For this secondary study, we retrieved multiple quality of end-of-life care indicators that were well established in the peer-reviewed literature,[10, 11, 13-15] and endorsed by the National Quality Forum (NQF) and the American Society of Clinical Oncology (ASCO).[16, 17] These indicators included any emergency room visit within the last 30 days of life, ≥ 2 emergency room visits within the last 30 days of life, any hospital admission within the last 30 days of life, ≥ 2 hospital admissions within the last 30 days of life, > 14 days of hospitalization within the last 30 days of life, hospital death, ICU admission within the last 30 days of life, and ICU death. These data were retrieved from our institutional database, and further verified by chart review to ensure the accuracy of data collection. Furthermore, we reviewed the last date of administration of palliative chemotherapy and/or targeted agents, and determined the percentage of patients who received these treatments in the last 14 and 30 days of life as documented previously. Targeted agents are defined in the current study as drugs or other substances that interfere with specific molecular pathways related to tumor proliferation or progression, and include a variety of monoclonal antibodies, tyrosine kinase inhibitors, and other small molecules.
We summarized the data using descriptive statistics, including means, medians, ranges, interquartile ranges, and frequencies. We compared the patient characteristics and quality of end-of-life care indicators between patients with solid tumors and those with hematological malignancies using the Student t test for normally distributed continuous variables, the Mann-Whitney U test for nonparametric continuous variables, and the chi-square test or Fisher exact test for categorical variables.
A composite score for the aggressiveness of end-of-life care has been reported previously, with 1 point for each of the following 6 ASCO/NQF indicators in the last 30 days of life: ≥ 2 emergency room visits, ≥ 2 hospital admissions, > 14 days of hospitalization, an ICU admission, death in a hospital, and use of chemotherapy. The total score ranged from 0 to 6, with a higher score indicating more aggressive care. We used a multivariate logistic regression model with backward elimination to identify factors associated with the presence of any of the above 6 indicators. Variables included in the model were age, sex, race, hematologic malignancy, and marital status.
A P value of <.05 was considered to be statistically significant. The Statistical Package for the Social Sciences software (IBM SPSS version 19.0; SPSS Inc, Chicago, Ill) was used for statistical analysis.
Among the 816 patients, 113 (14%) had hematological malignancies. These included 34 patients with acute myelogenous leukemia (30%), 28 with multiple myeloma (25%), 27 with B-cell non-Hodgkin lymphoma (24%), 7 with T-cell non-Hodgkin lymphoma (6%), 7 with acute lymphocytic leukemia (6%), 5 with chronic lymphocytic leukemia (4%), 3 with chronic myelogenous leukemia (3%), and 2 with Hodgkin lymphoma (2%). We found no significant difference in the baseline demographics between those patients with hematologic malignancies and those with solid tumors. The mean age of the patients was 62 years. Approximately 48% were female and 61% were white (Table 1).
Table 1. Patient Characteristics (N=816)
|Mean age (range), y||62 (22-97)||61 (21-88)||.31||62 (21-97)|
|Female sex||341 (49)||49 (43)||.31||390 (48)|
|Race|| || || || |
|White||431 (61)||68 (60)||.69||499 (61)|
|Black||154 (22)||24 (21)|| ||178 (22)|
|Hispanic||80 (11)||17 (15)|| ||97 (12)|
|Asian||28 (4)||4 (4)|| ||32 (4)|
|Other||10 (1)||0 (0)|| ||10 (1)|
|Married||437 (62)||67 (60)||.68||504 (60)|
|Christian religion||535 (95)||81 (94)||.79||616 (95)|
|Education|| || || || |
|≤High school||252 (36)||32 (28)||.02||284 (35)|
|College||225 (32)||31 (27)|| ||256 (31)|
|Postgraduate||56 (8)||7 (6)|| ||63 (8)|
|Not available||170 (24)||43 (38)|| ||213 (26)|
|Cancer type|| || ||<.001|| |
|Breast||71 (10)||0 (0)|| ||71 (9)|
|Gastrointestinal||178 (25)||0 (0)|| ||178 (22)|
|Genitourinary||89 (13)||0 (0)|| ||89 (11)|
|Gynecologic||61 (9)||0 (0)|| ||61 (7)|
|Head and neck||48 (7)||0 (0)|| ||48 (6)|
|Hematologic||0 (0)||113 (100)|| ||113 (14)|
|Other||94 (13)||0 (0)|| ||94 (12)|
|Respiratory||162 (23)||0 (0)|| ||162 (20)|
|Median time between advanced cancer diagnosis and death (IQR), mo||11.8 (4.5-23.8)||12.7 (4.4-39.8)||.27||11.7 (4.5-25.2)|
We found significant differences in the quality of end-of-life care indicators between patients with hematologic malignancies and those with solid tumors (Table 2). In the last 30 days of life, patients with hematological malignancies were more likely than patients with solid tumors to have any emergency room visits (54% vs 43%; P = .03), hospital admissions (81% vs 47%; P < .001), ≥ 2 hospital admissions (23% vs 10%; P < .001), ICU admissions (39% vs 8%; P < .001), > 14 days of hospitalization (38% vs 8%; P < .001), hospital deaths (47% vs 16%; P < .001), and death in the ICU (33% vs 4%; P < .001). Furthermore, patients with hematological malignancies were more likely to receive chemotherapy (43% vs 14%; P < .001) and targeted therapy (34% vs 11%; P < .001) within the last 30 days of life and also within the last 14 days of life.
Table 2. Quality of End-of-Life Care Indicators (N=816)
|Within last 30 d of life|| || || |
|Any ER visit||300 (43)||61 (54)||.03|
|≥2 ER visitsb||83 (12)||17 (15)||.35|
|Any hospital admission||333 (47)||91 (81)||<.001|
|≥2 hospital admissionsb||73 (10)||26 (23)||<.001|
|>14 d of hospitalizationb||54 (8)||43 (38)||<.001|
|Hospital deathb||110 (16)||53 (47)||<.001|
|ICU admissionb||55 (8)||44 (39)||<.001|
|ICU death||30 (4)||37 (33)||<.001|
|Chemotherapy useb||98 (14)||49 (43)||<.001|
|Targeted therapy use||78 (11)||38 (34)||<.001|
|Chemotherapy and targeted agent use||160 (23)||60 (53)||<.001|
|Palliative care unit admission||116 (17)||9 (8)||.02|
|Within last 14 d of life|| || || |
|Chemotherapy use||40 (6)||24 (21)||<.001|
|Targeted therapy use||37 (5)||19 (17)||<.001|
|Chemotherapy and targeted agent use||70 (10)||32 (28)||<.001|
|Composite score for aggressiveness of end-of-life care|| || || |
|0||457 (65)||25 (22)||<.001|
|1||119 (17)||26 (23)|| |
|2||58 (8)||14 (12)|| |
|3||44 (6)||21 (19)|| |
|4||16 (2)||20 (18)|| |
|5||8 (1)||5 (4)|| |
|6||1 (0)||2 (2)|| |
| Median score (IQR)||0 (0-1)||2 (1-3)||<.001|
|Any palliative care consultation||329 (47)||37 (33)||.006|
| Outpatient palliative care consultation (among patients seen by palliative care)||159 (48)||8 (22)||.003|
| Median time between advanced cancer diagnosis and palliative care consultation (IQR), mo||10.7 (3.9-22.1)||15.6 (4.4-43.4)||.06|
| Median time between palliative care consultation and death (IQR), mo||1.7 (0.6-4.6)||0.4 (0.1-1.2)||<.001|
Patients with hematological malignancies were less likely to be admitted to a palliative care unit (17% vs 8%; P = .02), or to receive any palliative care consultation (47% vs 33%; P = .006) or outpatient palliative care consults (48% vs 22%; P = .003) within the last 30 days of life.
The composite score for aggressive end-of-life care was significantly higher for patients with hematological malignancies compared with those with solid tumors (2 vs 0; P < .001).
On multivariate regression analysis, the presence of a hematological malignancy (odds ratio [OR], 6.63; P < .001) and age (OR, 0.97 per year increase; P < .001) were found to be independent predictors for aggressive end-of-life care (Table 3).
Table 3. Multivariate Logistic Regression Analysisa
|Age (per y increase)||0.97 (0.96-0.99)||<.001|
|Hematologic malignancy||6.63 (4.11-10.72)||<.001|
We found that patients with hematological malignancies were more likely to have multiple emergency room visits, ICU admissions and death, and cancer treatments in the last weeks of life compared with patients with solid tumors. We also identified a relative lack of palliative care involvement among patients with hematologic malignancies. The findings of the current study highlight the need to develop programs to improve the quality of end-of-life care for patients with hematologic malignancies.
Although quality of end-of-life care is closely related to quality of life at the end of the life, these are conceptually and operationally distinct measures to assess end-of-life outcomes. Both were recognized by the NQF and ASCO as important outcomes.[16, 17] Indeed, longitudinal monitoring of symptom distress and quality of life until the end of life is important, although this is not currently being done consistently for all patients with cancer. Further efforts are needed to document these important outcomes for clinical care and research purposes.
In the last 30 days of life, patients with hematological malignancies were found to be more likely than those with solid tumors to have emergency room visits, hospital admissions, ICU stays, and > 2 weeks of hospitalization. This is consistent with the findings of the study by Ho et al, which reported that patients with hematological malignancies were 85% more likely to require hospital admissions in the last month of life compared with patients with prostate cancer. The high rate of use of acute care facilities in patients with hematologic malignancies in the last weeks of life is likely related to the high frequency of hematologic complications such as anemia and thrombocytopenia requiring transfusions, neutropenia with infections necessitating antibiotics, and bleeding and thromboembolic events requiring acute interventions.[3-5] These are further compounded by our observation that patients with hematologic malignancies often receive systemic therapies in the last days of life, which adds another layer of treatment-related adverse effects and the need for hospitalization for treatment administration and monitoring.
In addition to higher rates of hospitalization, patients with hematologic malignancies are also more likely to die in a hospital. Remarkably, we found that nearly one-half of these patients died in an acute care facility, whereas a vast majority of patients with solid tumors died outside of a hospital. These findings are consistent with a recent meta-analysis of 16 studies from various countries demonstrating that patients with hematologic malignancies were more likely to die in a hospital (OR, 2.25; P < .0001). In addition to hospital deaths, the rate of deaths in the ICU was significantly higher in patients with hematologic malignancies compared with those with solid tumors (33% vs 4%). Patients with hematological malignancies are often admitted to the ICU with severe sepsis requiring vasopressor support, respiratory insufficiency requiring mechanical ventilation, and multiorgan system failure on hemodialysis. Compared with patients who died at home with hospice care, patients who died in an ICU or hospital had greater physical and emotional distress and worse quality of life, and their caregivers had a high risk of prolonged grief.[21, 22] Thus, active efforts are needed to improve the transition to home care at the end of life for patients with hematologic malignancies.
We previously reported that patients with hematologic malignancies had limited access to palliative care compared with patients with solid tumors, with a smaller percentage of palliative care referrals, delayed involvement, and predominantly inpatient consultations instead of outpatient visits. The results of the current study also found that patients with hematologic malignancies had fewer admissions to the institution's acute palliative care unit, despite previous studies by our group and others demonstrating a similarly high symptom burden among patients with both hematologic malignancies and solid tumors.[1, 2] Staffed by an interprofessional team, acute palliative care units provide intensive symptom control, psychosocial care, and transition to end-of-life care as well as assist with complex discharges,[23, 24] and represent an appropriate alternative to the ICU for some patients with hematological malignancies.
We found that patients with hematological malignancies had higher mean composite scores for aggressive end-of-life care. On multivariate logistic regression analysis, the diagnosis of a hematological malignancy was also strongly associated with aggressive end-of-life care. The findings of the current study are similar to 2 population-based studies that reported a poorer quality of end-of-life care among patients with hematologic malignancies in Taiwan and Canada.[10, 11] It is important to note that neither of these studies adjusted for the stage of disease; thus, patients with curable cancer who died unexpectedly (eg, of treatment complications or noncancer causes) were also included in the analyses. In addition to bringing a US perspective, we believe the current study is unique because it includes consecutive patients regardless of Medicare coverage, and also focuses on patients with advanced incurable cancer for whom these aggressive end-of-life criteria are more applicable. Furthermore, instead of examining the aggressiveness of end-of-life care as an aggregate outcome (present or absent), we were able to provide a more in-depth examination of the magnitude of each indicator.
The findings of the current study highlight the need to address end-of-life care among patients with hematological malignancies. Hematologists and oncologists caring for patients with advanced hematological malignancies need to ensure that their patients and caregivers have a good understanding of the incurable nature of their illness and their general prognosis. This would form the basis for discussions surrounding goals of care and advance care planning. The presence of end-of-life discussions has been shown to be associated with less aggressive end-of-life care in patients with advanced cancer. Given that palliative care referral is often initiated within days before death, if at all, among patients with hematologic malignancies,[12, 25-27] the early involvement of palliative care in the outpatient setting may facilitate these complex communications and decisions.[28, 29] The palliative care team may also be able to provide the necessary screening, monitoring, treatment, and education for various symptoms, thus reducing the need for symptom crisis requiring emergency room visits and hospital stays.[1, 30] Because referral to palliative care is highly heterogeneous, clinical care pathways aimed at integrating palliative care early in the disease trajectory may be useful. In contrast to the treatment guidelines for solid tumors, palliative care has not yet been fully incorporated into the National Comprehensive Cancer Network guidelines for patients with hematologic malignancies. For example, the term “palliative care” appeared only twice in latest guidelines for multiple myeloma and non-Hodgkin lymphoma, and not at all in the guidelines for Hodgkin lymphoma, acute lymphoblastic leukemia, and acute myeloid leukemia. Changes in reimbursement policy may help hematologists and oncologists to limit the prescribing of systemic therapies in patients with a limited prognosis. Finally, we urgently need more research to document the impact of various interventions on end-of-life outcomes.
The current study has several limitations. First, this was a cohort study from a single tertiary care cancer center. The characteristics of the patients and health care providers may differ from those in the community setting. Therefore, the findings of the current study may not be generalizable to other settings. Second, we only included patients treated over a span of 6 months between 2009 and 2010. It may be possible that the quality of care has changed since that period. Third, we conducted many hypothesis-driven statistical tests, although these findings should be considered preliminary given the multiple testing. Fourth, some of these patients might have received acute care services at an outside facility, which would not be captured by our institutional database. This could result in an underestimation of the aggressiveness of care in our cohorts. However, we expect this to represent a small percentage of patients because we specifically included only those patients who resided locally for our analysis. Fifth, we were not able to collect reasons for emergency room visits and hospitalizations. Sixth, we excluded patients not seen in our hospital 3 months before their death, which may result in an overestimation of the degree of aggressiveness of end-of-life care if these individuals were enrolled onto hospice early. Given that the median time from hospice referral to death is reported to be only 19 days, we believe the findings of the current study are valid.
Patients with hematologic malignancies were found to be managed aggressively in the last 30 days of life, with high rates of emergency room visits, hospitalizations, ICU stays, and use of systemic therapy. The findings of the current study highlight the need for clinicians to minimize aggressive interventions at the end of life, and the need for further research to optimize care in the last days of life for patients with hematological malignancies.
Supported by The University of Texas MD Anderson Cancer Center Support Grant (CA 016672). The sponsors had no role in study design, data collection, analysis, interpretation, or writing of the report.
CONFLICT OF INTEREST DISCLOSURES
Dr. Bruera was supported in part by National Institutes of Health grants RO1NR010162-01A1, RO1CA122292-01, and RO1CA124481-01. Dr. Hui was supported in part by an institutional startup fund.