Palliative Care Involvement Is Associated with Less Intensive End-of-Life Care in Adolescent and Young Adult Oncology Patients

Abstract

Background:

Adolescent and young adult oncology (AYAO) patients often receive intensive medical care and experience significant symptoms at the end of life (EOL).

Objective:

This study aimed to describe the characteristics of AYAO patients aged 15–26 years who died as inpatients in a hospital and to compare the illness and EOL experiences of AYAO patients who did and did not receive palliative care (PC).

Design and Setting:

A standardized data extraction tool was used to collect information about demographics, treatment, terminal characteristics, and symptoms during the last month of life (LMOL) for 69 AYAO patients who died while hospitalized between 2008 and 2014.

Measurements and Results:

AYAO patients who died in the hospital required considerable medical and psychosocial care and experienced numerous symptoms during the LMOL. Compared to those patients who received no formal PC services, patients followed by the PC team were less likely to die in the intensive care unit (ICU) (38% vs. 68%, p = 0.024) and less likely to have been on a ventilator (34% vs. 63%, p = 0.028) during the LMOL. They also received fewer invasive medical procedures during the LMOL (median, 1 vs. 3 procedures, p = 0.009) and had a do not resuscitate order in place for a longer time before death (median, 6 vs. two days, p = 0.008).

Conclusions:

Involvement of the PC team was associated with the receipt of less intensive treatments and fewer deaths in the ICU.

Introduction

Adolescent and young adult (AYA) patients, defined by the National Cancer Institute as those patients aged 15–39 years,¹ have distinct physical and psychosocial needs^2,3 that are often inadequately addressed by a binary healthcare system that focuses primarily on pediatric versus adult care.^3,4 Recent studies indicate that AYA oncology (AYAO) patients often receive intense medical services at the end of life (EOL)^5,6 and experience numerous symptoms, many of which are poorly recognized, understood, or treated.^2,7–10 Symptom control in patients at the EOL is essential, given the negative effect of symptoms and suffering on patient and family quality of life (QOL).

The primary tenets of palliative care (PC) include providing high-quality communication, advance care planning, and assessing and treating physical and psychological symptoms in the context of an interdisciplinary team, with the goal of improving support for, and reducing the suffering of patients and caregivers.¹¹ PC consultation, symptom control, and advance care planning improves the QOL for both pediatric and adult patients with life-limiting conditions.^12–14 Pediatric patients who receive PC consultation concurrent with oncology care have improved QOL and are more likely to die at home than are patients who receive oncology care alone.¹⁵ Pediatric PC has been associated with more and earlier end-of-life care discussions, longer times between the placement of do not resuscitate (DNR) orders and death, and increased hospice enrollment in patients with advanced solid tumor malignancies.¹⁶ For AYAO patients, early PC involvement may be associated with less intensive therapy at the EOL and with longer overall survival.¹⁷

The literature on the AYA illness experience and AYA medical care at the EOL remains sparse, and tends to consider patients aged 15–39 years as a homogeneous population, despite their diverse levels of development, needs, and locations of care.¹⁸ Furthermore, limited data exist describing AYAO patients who died in the hospital. On the basis of our clinical experience caring for hospitalized AYAO patients at the EOL, we hypothesized that this population often receives intensive medical treatments, requires extensive medical and psychosocial resources, and experiences significant symptoms and distress at the EOL. To further characterize the treatment and end-of-life experience of AYAO patients and to investigate the differences between those AYAO patients who receive PC consultation and those who receive standard care, we conducted a descriptive, retrospective study of the psychosocial, demographic, treatment, and terminal characteristics and experiences of AYAO patients who died while hospitalized at a pediatric oncology institution. This is the largest study to comprehensively characterize the demographic and end-of-life characteristics of AYAO patients who died while hospitalized and one of the first to compare the end-of-life characteristics of AYAO patients who received PC services with those of patients who did not.

Methods

Study design

This study was conducted at St. Jude Children's Research Hospital (St. Jude). The hospital's Institutional Review Board deemed the study exempt because it was a retrospective analysis of a deceased cohort. A list of all patients aged 15 years or older who died between 2008 and 2014 was obtained, along with data about each patient's age at death, date of death, and primary medical service.

A data abstraction tool was created based on a literature review^2,8,17 and in consultation with oncology and PC experts. Two researchers independently collected the data on a standardized form and discussed any discrepancies to reach consensus. All medical record components from the last month of life (LMOL) were reviewed; other select portions of the medical record were reviewed to obtain the diagnosis and treatment-related components and the disease course and duration. For patients who died before mid-2012, data were obtained from both electronic medical records and hard-copy charts, as documentation did not become fully electronic until mid-2012.

Demographic data and information related to each patient's cancer and end-of-life experiences were collected. We chose four as a cutoff based on the distribution of the data; about half of patients in this study received four or more. Although we present the median and interquartile range, we wanted to highlight the actual percentage of patients that received four or more regimens. Medical procedures were defined as any potentially painful procedure that required analgesia or anesthesia. To assess symptom burden within this patient population, a comprehensive list of symptoms was compiled by reviewing the literature and consulting PC physicians.^2,8,17 Data on 24 symptoms were collected: 17 physical symptoms (pain, dyspnea, cough, increased secretions, edema/lymphedema, skin breakdown/wounds, pruritus, constipation, diarrhea, changes in bowel or bladder function/incontinence, nausea/vomiting, seizures, poor appetite, poor sleep, somnolence, bleeding, and fatigue) and seven psychological symptoms (depression, sadness, anxiety, irritability/personality changes, fear, confusion/delirium, and guilt). Each symptom was assessed in the context of three prescribed parameters: (1) addressed (i.e., an intervention was performed in response to the symptom), (2) refractory (i.e., an intervention was performed and the symptom did not respond to the intervention), and (3) status at the EOL (i.e., improved, worsened, or stable based on documentation from the last day of life and death summary note). If no further mention of a symptom was documented, then its response and status at the EOL was classified as “unknown.”

Statistical analysis

Data on the demographics, treatment, and end-of-life characteristics of AYAO patients were summarized using descriptive statistics. Either the chi-square test or Fisher's exact test (for sparse data) were used to examine differences in categorical variables between patients with and without PC team involvement. The Wilcoxon rank-sum test was used to examine differences in continuous variables between patients with and without PC team involvement. Statistical analyses were conducted by using SAS 9.3 (SAS Institute, Cary, NC). A 2-sided significance level of p < 0.05 was used for all statistical tests. p-Values are reported without adjustment for multiple testing as this is an exploratory retrospective study that aims to provide leads for future studies.¹⁹

Results

AYAO patient demographics and treatment

Patient population

Table 1 summarizes the characteristics of the 329 AYAO patients (aged 15–26 years) who died between 2008 and 2014. A total of 69 patients died while hospitalized at St. Jude, and 260 patients died at other locations. AYAO patients who died at St. Jude were slightly younger than those who died elsewhere (median age, 17.3 vs. 18.4 years, p = 0.023) and were more likely to have a diagnosis of leukemia/lymphoma (59% vs. 20%; p < 0.0001). Two patients had a diagnosis of a nonmalignant hematological disease: both of these patients underwent immunosuppressive treatment followed by allogeneic stem cell transplantation and were, therefore, included in this AYAO cohort.

Table 1.

Demographic Characteristics of Adolescent and Young Adult Oncology Patients Who Died at St. Jude Compared to Those of Patients Who Died at Other Locations

	Death at St. Jude (n = 69)	Death at a different location (n = 260)	p
Age at death (years)
Median (range)	17.3 (14.7–25.2)	18.4 (14.8–25.8)	0.023^a
Gender, n (%)
Female	24 (35)	95 (37)	0.787
Male	45 (65)	165 (63)
Cancer diagnosis, n (%)
Brain tumor	8 (12)	87 (33)	<0.0001^a
Hematology	2 (3)	17 (7)
Leukemia/lymphoma	41 (59)	53 (20)
Solid tumor	18 (26)	103 (40)

Statistically significant, p < 0.05.

Cancer-directed treatment history

The clinical characteristics of the 69 hospitalized AYAO patients are presented in Table 2. Patients received a median of 3 cancer-directed regimens; 34 patients (49%) received an allogeneic stem cell transplant as a part of their treatment.

Table 2.

Clinical Characteristics of Hospitalized Adolescent and Young Adult Oncology Patients (N = 69)

Primary or secondary malignant neoplasm, n (%)
Primary	60 (87)
Secondary	7 (10)
N/A	2 (3)
Number of cancer-directed regimens, n (%)
<4	39 (57)
≥4	30 (43)
Median (IQR)	3 (2–4)
Number of phase I/II trial enrollments, n (%)
0	34 (49)
1	29 (42)
2	5 (7)
Unknown	1 (1)
Received allotransplant as part of treatment	34 (49)
Days from diagnosis to death
Median (IQR) [range]	577 (306–1012) [13–5666]
Days from last hospitalization to death
Median (IQR) [range]	18 (6–46) [1–168]
Number of clinic visits during LMOL, n = 45^a
Median (IQR)	4 (1–7)
Cause of death, n (%)
Progressive disease	45 (65)
Treatment complications	24 (35)
Location of death, n (%)
Treatment floor	37 (54)
ICU	32 (46)
Days in ICU
Median (IQR) [range]	11.5 (4–23.5) [0–51]
POST/DNR order in place	60 (87%)
Days to death from POST/DNR order, n (%)
Median (IQR) [range]	4.5 (2–15) [0–368]
Received CPR before death	8 (12)
Diagnosis: leukemia/lymphoma	8 (100)
Received an allotransplant	7 (88)

Only applicable for those patients who were not hospitalized the entire LMOL, n = 45.

IQR, interquartile range; LMOL, last month of life; ICU, intensive care unit; POST, physician scope of treatment; DNR, do not resuscitate; CPR, cardiopulmonary resuscitation.

AYAO patient experiences at the EOL

General characteristics

The median time from diagnosis to death for this cohort was 577 days (range, 13–5666 days). The patients were hospitalized for a median of 18 days (range, 1–168 days) before death; 35% of patients were hospitalized throughout their entire LMOL. Most patients (65%) died of progressive disease; of the 24 patients in this cohort who died from treatment-related complications, 23 (96%) of them had received an allogeneic SCT. Thirty-two patients (46%) died in the intensive care unit (ICU). The median ICU length of stay before death was 11.5 days (range 0–51 days).

Psychosocial and medical care and interventions

Table 3 summarizes the treatment characteristics during the LMOL for the 69 AYAO patients who died while hospitalized. During the LMOL, 49% of the AYAO patients received chemotherapy, 16% received radiation therapy, 42% were mechanically ventilated, 86% had some form of oxygen delivered, 26% received dialysis, 71% underwent at least 1 medical procedure, and 83% received at least 1 blood-product transfusion.

Table 3.

Treatment Characteristics of Hospitalized Adolescent and Young Adult Oncology Patients at the End of Life (N = 69)

Palliative care involvement during course of treatment	50 (72%)
Days of involvement, median (IQR) [range]	19 (5–83) [1–679]
No. of encounters during LMOL, median (IQR)	4 (2–5)
Pain service involvement during LMOL	18 (26%)
No. of encounters, median (IQR)	9 (4–17)
Psychology involvement during LMOL	44 (64%)
No. of encounters, median (IQR)	4 (2–6)
Received chemotherapy during LMOL	34 (49%)
Enrolled on phase I/II trial during LMOL	2 (3%)
Received radiation therapy during LMOL	11 (16%)
Curative	1 (9%)
Palliative	10 (91%)
Received medical procedure during LMOL	49 (71%)
No. of procedures, median (IQR)	3 (2–4)
Received mechanical ventilation during LMOL	29 (42%)
Duration in days, median (IQR) [range]	8 (5–18) [1–31]
Received dialysis during LMOL	18 (26%)
Duration in days, median (IQR) [range]	16.5 (4–24) [2–31]
Received any type of transfusion during LMOL	57 (83%)
PRBC transfusion [no. in LMOL, median (IQR)]	55 (80%) [8 (3–13)]
Platelet transfusions [no. in LMOL, median (IQR)]	52 (75%) [17.5 (7.5–49)]
FFP transfusion [no. in LMOL, median (IQR)]	29 (42%) [9 (3–20)]
Cryoprecipitate transfusion [no. in LMOL, median (IQR)]	9 (13%) [2 (1–5)]
Received enteral feeds during LMOL	22 (32%)
Duration in days, median (IQR) [range]	14.5 (5–26) [2–31]
Received TPN during LMOL	36 (52%)
Duration in days, median (IQR) [range]	20 (8.5–30.5) [1–31]
Received IVFs during LMOL	58 (84%)
Duration in days, median (IQR) [range]	15 (7–28) [1–31]
Received corticosteroids during LMOL	63 (91%)
Duration in days, median (IQR) [range]	19 (7–30) [1–31]
Received antibiotics during LMOL	61 (88%)
Duration in days, median (IQR) [range]	25 (13–31) [1–31]
Received benzodiazepines during LMOL	54 (78%)
Duration in days, median (IQR) [range]	6 (2–15) [1–31]
Received oxygen during LMOL	59 (86%)
Duration in days, median (IQR) [range]	16 (6–27) [1–31]
Received opioids during LMOL	67 (97%)
Duration in days, median (IQR) [range]	25 (8–31) [1–31]

PRBC, packed red blood cell; FFP, fresh frozen plasma; TPN, total parenteral nutrition; IVFs, intravenous fluids; PRN, as needed.

Advance care planning and cardiopulmonary resuscitation

Sixty (87%) of the patients who died in the hospital had a physician order for scope of treatment (POST) or DNR order in place at the time of death; these orders were placed a median of 4.5 days before death. Of the eight patients (12%) who received cardiopulmonary resuscitation (CPR) during their final admission, none had a DNR order in place at the time of resuscitation. Two patients who survived the initial resuscitation later had a signed DNR/POST form. Seven (88%) of the patients who received CPR at the EOL had previously received an allogeneic stem cell transplant; 3 (37%) of the patients who received CPR at the EOL died of progressive disease.

Symptoms present in the LMOL

Table 4 summarizes the symptom characteristics during the LMOL for the 69 AYAO patients who died while hospitalized, and Figure 1 shows the prevalence of each symptom. A median of 11 symptoms were documented during the LMOL. The three most common symptoms present in the LMOL were pain (99%), fatigue (85%), and edema (78%).

FIG. 1.

Prevalence of symptoms of hospitalized adolescent and young adult oncology patients during the last month of life, last week of life, and last day of life (N = 69).

Table 4.

Symptom Characteristics of Hospitalized Adolescent and Young Adult Oncology Patients During the Last Month of Life (N = 69)

Any symptom^a	69 (100%)
No. of symptoms, median (IQR)	11 (10–14)
Any refractory symptom^a	59 (86%)
No. of symptoms, median (IQR)	2 (1–3)
Physical symptoms^b	69 (100%)
No. of symptoms, median (IQR)	9 (8–11)
Refractory physical symptoms^b	58 (84%)
No. of refractory physical symptoms, median (IQR)	2 (1–3)
Psychosocial symptoms^c	60 (87%)
No. of symptoms, median (IQR)	3 (2–4)
Refractory psychosocial symptoms^c	13 (22%)
No. of symptoms, median (IQR)	2 (1–2)

Refers to all physical and psychosocial symptoms (total = 24).

Physical symptoms (total = 17): pain, dyspnea, cough, increased secretions, edema/lymphedema, skin breakdown/wounds, pruritus, constipation, diarrhea, changes in bowel or bladder function/incontinence, nausea/vomiting, seizures, poor appetite, poor sleep, somnolence, bleeding, and fatigue.

Psychosocial symptoms (total = 7): depression, sadness, anxiety, irritability/personality changes, fear, confusion/delirium, and guilt.

Characteristics of AYAO patients who received PC consultations

Table 5 summarizes the characteristics of hospitalized AYAO patients with PC team involvement. Of note, there was no difference between the percentages of patients who died from treatment-related complications versus those that died from progressive disease in the cohorts of patients who did and did not receive PC consultation. During the LMOL, AYAO patients with PC involvement were less likely than those without PC involvement to die in the ICU (38% vs. 68%, p = 0.024) or be on a ventilator (34% vs. 63%, p = 0.028), and they underwent fewer medical procedures (median of 1 vs. 3, p = 0.009). Among adolescents with a POST/DNR order, the time between the order and death was significantly longer for patients with PC involvement than for those without such involvement (median of 6 vs. two days, p = 0.008).

Table 5.

Characteristics of Hospitalized Adolescent and Young Adult Oncology Patients by Palliative Care Team Involvement

	Palliative care team involvement
	No (n = 19)	Yes (n = 50)	p
Cancer diagnosis, n (%)
Brain tumor	2 (11)	6 (12)	0.924
Hematology	1 (5)	1 (2)
Leukemia/lymphoma	11 (58)	30 (60)
Solid tumor	5 (26)	13 (26)
Days from diagnosis to death, median (IQR) [range]	491 (308–2122) [135–5666]	597.5 (305–1012) [13–4081]	0.835
Location of death, n (%)
Treatment floor	6 (32)	31 (62)	0.024^a
ICU	13 (68)	19 (38)
Cause of death, n (%)
Progressive disease	13 (68)	32 (64)	0.731
Treatment complications	6 (32)	18 (36)
POST/DNR order in place	16 (84%)	44 (88%)	0.699
Days to death, median (IQR) [range]	2 (1–4) [0–18]	6 (2–21) [0–368]	0.008^a
Received CPR before death	4 (21%)	4 (8%)	0.203
Received chemotherapy during LMOL	10 (53%)	24 (48%)	0.731
Received opioids during LMOL	19 (100%)	48 (96%)	1.000
Received benzodiazepines during LMOL	17 (89%)	37 (74%)	0.207
Received mechanical ventilation during LMOL	12 (63%)	17 (34%)	0.028^a
Received dialysis during LMOL	7 (37%)	11 (22%)	0.232
No. of medical procedures during LMOL, median (IQR)	3 (2–4)	1 (0–3)	0.009^a
No. of documented symptoms during LMOL,^b median (IQR)	11 (10–13)	12 (10–14)	0.490
No. of documented refractory symptoms during LMOL, median (IQR)	2 (1–2)	2 (1–3)	0.467
No. of documented physical symptoms during LMOL,^c median (IQR)	9 (8–11)	9 (8–11)	0.781
No. of documented psychosocial symptoms during LMOL,^d median (IQR)	2 (0–3)	3 (2–4)	0.117

Statistically significant, p < 0.05.

Refers to all physical and psychosocial symptoms (total = 24).

Psychosocial symptoms (total = 7): depression, sadness, anxiety, irritability/personality changes, fear, confusion/delirium, and guilt.

Discussion

In this study, AYAO patients who died while hospitalized were more likely to have a diagnosis of leukemia or lymphoma than were AYAO patients who died elsewhere. This finding is consistent with prior studies in the literature,^20,21 suggesting that patients with a hematological malignancy have a different treatment course at the EOL than do patients with other cancer diagnoses. These patients may have more symptoms or refractory symptoms, requiring closer assessment and treatment.

“Aggressive” treatment at the EOL of adult oncology patients has been associated with poor-quality care in three major domains: (1) overuse of chemotherapy very near death; (2) possible misuse of treatment, resulting in frequent emergency room visits, hospitalization, or ICU stays for terminal patients; and (3) underuse of hospice services.^22,23 AYAO patients in this cohort received extensive medical and psychosocial support throughout their treatment and especially during the LMOL, as evidenced by the large number who received specialty and subspecialty care (e.g., pain service, psychology, and PC); the percentage of patients who required intravenous fluids, total parenteral nutrition, antibiotics, or oxygen; and the number of medications documented during the LMOL. AYAO patients in this study also received intensive medical interventions at the EOL (e.g., nearly half received mechanical ventilation and a quarter of the patients received dialysis), consistent with recent reports of high treatment intensity at the EOL in AYA patients.^5,6

Markers of quality end-of-life care used in adult oncology patients that may be applicable to the AYA patient population include ICU stays for patients with progressive or incurable diseases, which are frequently associated with mechanical ventilation, CPR, and the underuse of hospice services. However, other quality markers, including death in the hospital or chemotherapy administration in the final weeks of life, may be less-applicable to younger patients and/or those with hematological malignancies.²⁴ Death in a preferred place suggests advance care planning and high-quality interdisciplinary care,²⁵ whereas death in the ICU suggests increased intensity of care. Patients of all ages generally prefer to die at home,²⁵ and for pediatric and AYA patients, death at home correlates with better bereavement experiences for their parents.^26,27 However, death in a hospital may not always represent poor-quality care;²⁸ some AYAO patients may wish to receive end-of-life care in the hospital, including those with difficult-to-treat or refractory symptoms, those with psychological symptoms that are inadequately addressed by family or community organizations, or those seeking a safe, supportive, familiar place—which may be a hospital room, thereby limiting the utility of this quality indicator in this patient population.

Additionally, almost half of the patients in this cohort received chemotherapy during the LMOL. Chemotherapy—particularly in patients with hematological malignancies, who were the majority of patients in this cohort—may be used to control symptoms associated with progressive disease and prolong patient life, with a goal of improving patient QOL. Therefore, in some patients, chemotherapy at the EOL may not represent “aggressive” or inferior care, but well-contemplated, compassionate, patient-centered, and goal-directed care.

Although AYAO patients in this study had a long latency period between diagnosis and death, the median duration of PC involvement was only 19 days. Even so, those who received PC consultation received significantly less-intense treatments and fewer procedures at the EOL. At the institution highlighted in this study, the primary oncology team decides if and when to involve PC; no “trigger mechanism” existed during this timeframe to mandate consultation. However, given an increasing awareness and acceptance of PC at this institution, nearly all patients with incurable disease receive some form of palliative services (PC consultation and/or referral to hospice) before death.²⁹ The association between PC consultation and less intensive treatment at the EOL for hospitalized AYAO patients offers preliminary evidence in support of early PC integration as an important aspect of routine oncology care for these patients and suggests that PC involvement earlier in the disease course may improve end-of-life experiences for AYAO patients.³⁰

This study found extensive symptoms in AYAO patients during the LMOL, highlighting the importance of using an interdisciplinary PC team approach to manage symptoms in this high-risk population. Interestingly, there was no difference between the median number of symptoms documented in patients with PC involvement who died in the hospital and that in patients without PC involvement who died in the hospital. Although difficult to confirm, we hypothesize that this lack of difference may be due to the relatively short period of time between PC consultation and death. When PC is consulted to manage refractory or complex symptoms late in the treatment course, less time is available to adequately assess, treat, and control distressing symptoms. Therefore, we concur with both the European Society for Medical Oncology and the American Society of Clinical Oncology, which strongly endorse the idea that PC should be integrated early into the routine oncology care of all patients with high symptom burden, with the goals of improving patient and family QOL and striving for a “good death” in patients with incurable disease.^31,32

Our study has several limitations. First, the data are limited to information documented in the medical record. The study was conducted at an institution that primarily treats patients with cancer and has experimental and early phase trials available, potentially limiting the generalizability of our findings. No standardized assessment tool to identify and document patient symptoms is required at our institution; therefore, the medical record primarily reflects what clinicians observed or obtained from patient or parental reports. Additionally, assessments of symptom severity and associated distress were not included in this analysis given the limitations of this retrospective medical chart review. Finally, many patients in our cohort underwent hematopoietic stem cell transplant for hematologic malignancies, which has been associated with more-intensive end-of-life therapy¹⁷ and increased symptoms and distress.^33,34 Despite these limitations, we believe our findings provide meaningful preliminary insights into the characteristics and experiences of AYAO patients who die while hospitalized and provide evidence in support of integrating PC principles early into the treatment and management of AYAO patients.

Conclusions

Given the preliminary findings that PC is associated with the receipt of less-intensive treatments and fewer deaths in the ICU for AYAO patients who died in the hospital, we hypothesize that earlier integration of the PC team is useful in promoting goal-directed medical care, which may lead to less-intensive treatments at the EOL in this patient population. Additionally, we suggest that earlier involvement of PC clinicians with expertise in managing refractory symptoms may lead to improved symptom control. However, further prospective investigation using routine, patient-reported symptom and distress assessments is needed to ascertain causal relationships beyond the associations demonstrated in this study.

Footnotes

Acknowledgments

We would like to thank Deborah V. Gibson, MA, for her work in creating the Excel spreadsheet for use as the data extraction form and to Keith A. Laycock, PhD, ELS for his review and editing. This work was supported, in part, by ALSAC.

Author Disclosure Statement

No competing financial interests exist.

References

National Cancer Institute: Adolescents and young adults with cancer: www.cancer.gov/types/aya, 2016.

Cohen-Gogo

, Marioni

, Laurent

, et al.: End of life care in adolescents and young adults with cancer: Experience of the adolescent unit of the Institut Gustave Roussy. Eur J Cancer, 2011; 47:2735–2741.

Clark

, Fasciano

: Young adult palliative care: Challenges and opportunities. Am J Hosp Palliat Care, 2015; 32:101–111.

Pritchard

, Cuvelier

, Harlos

, et al.: Palliative care in adolescents and young adults with cancer. Cancer, 2011; 117(10 Suppl):2323–2328.

Mack

, Chen

, Boscoe

, et al.: High intensity of end-of-life care among adolescent and young adult cancer patients in the New York State Medicaid Program. Med Care, 2015; 53:1018–1026.

Mack

, Chen

, Cannavale

, et al.: End-of-life care intensity among adolescent and young adult patients with cancer in Kaiser Permanente Southern California. JAMA Oncol, 2015; 1:592–600.

Waldman

, Wolfe

: Palliative care for children with cancer. Nature reviews. Clin Oncol, 2013; 10:100–107.

Theunissen

, Hoogerbrugge

, van Achterberg

, et al.: Symptoms in the palliative phase of children with cancer. Pediatr Blood Cancer, 2007; 49:160–165.

Wolfe

, Grier

, Klar

, et al.: Symptoms and suffering at the end of life in children with cancer. N Engl J Med, 2000; 342:326–333.

10.

Wein

, Pery

, Zer

: Role of palliative care in adolescent and young adult oncology. J Clin Oncol, 2010; 28:4819–4824.

11.

Carney

, Meier

: Palliative care and end-of-life issues. Anesthesiol Clin N A, 2000; 18:183–209.

12.

O'Quinn

, Giambra

: Evidence of improved quality of life with pediatric palliative care. Pediatr Nurs, 2014; 40:284–288, 296.

13.

Wolfe

, Hammel

, Edwards

, et al.: Easing of suffering in children with cancer at the end of life: Is care changing?. J Clin Oncol, 2008; 26:1717–1723.

14.

Greer

, Jackson

, Meier

, et al.: Early integration of palliative care services with standard oncology care for patients with advanced cancer. CA Cancer J Clin, 2013; 63:349–363.

15.

Friedrichsdorf

, Postier

, Dreyfus

, et al.: Improved quality of life at end of life related to home-based palliative care in children with cancer. J Palliat Med, 2015; 18:143–150.

16.

Vern-Gross

, Lam

, Graff

, et al.: Patterns of end-of-life care in children with advanced solid tumor malignancies enrolled on a palliative care service. J Pain Symptom Manage, 2015; 50:305–312.

17.

Keim-Malpass

, Erickson

, Malpass

: End-of-life care characteristics for young adults with cancer who die in the hospital. J Palliat Med, 2014; 17:1359–1364.

18.

Nass

, Beaupin

, Demark-Wahnefried

, et al.: Identifying and addressing the needs of adolescents and young adults with cancer: Summary of an institute of medicine workshop. Oncologist, 2015; 20:186–195.

19.

Mantel

, Haenszel

: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 1959; 22:719–748.

20.

Bell

, Skiles

, Pradhan

, et al.: End-of-life experiences in adolescents dying with cancer. Support Care Cancer, 2010; 18:827–835.

21.

Hui

, Didwaniya

, Vidal

, et al.: Quality of end-of-life care in patients with hematologic malignancies: A retrospective cohort study. Cancer, 2014; 120:1572–1578.

22.

Earle

, Park

, Lai

, et al.: Identifying potential indicators of the quality of end-of-life cancer care from administrative data. J Clin Oncol, 2003; 21:1133–1138.

23.

Earle

, Landrum

, Souza

, et al.: Aggressiveness of cancer care near the end of life: Is it a quality-of-care issue?. J Clin Oncol, 2008; 26:3860–3866.

24.

Trevino

, Martin

, Prigerson

: Evaluating quality metrics for the care of patients with blood cancer who are near death. J Clin Oncol, 2016; 34:3117–3118.

25.

Howell

, Wang

, Roman

, et al.: Preferred and actual place of death in haematological malignancy. BMJ Support Palliat Care, 2015; 0:1–8.

26.

Thienprayoon

, Lee

, Leonard

, et al.: Hospice care for children with cancer: Where do these children die?. J Pediatr Hematol Oncol, 2015; 37:373–377.

27.

Bluebond-Langner

, Beecham

, Candy

, et al.: Preferred place of death for children and young people with life-limiting and life-threatening conditions: A systematic review of the literature and recommendations for future inquiry and policy. Palliat Med, 2013; 27:705–713.

28.

American Academy of Pediatrics Steering Committee on Quality Improvement and Management; American Academy of Pediatrics Committee on Practice and Ambulatory Medicine, Hodgson

, Simpson

, Lannon

: Principles for the development and use of quality measures. Pediatrics, 2008; 121:411–418.

29.

Levine

, Johnson

, Snyder

, et al.: Integrating palliative care in pediatric oncology: Evidence for an evolving paradigm for comprehensive cancer care. J Natl Compr Cancer Netw, 2016; 14:741–748.

30.

Kaye

, Friebert

, Baker

: Early integration of palliative care for children with high-risk cancer and their families. Pediatr Blood Cancer, 2015;(63):593–597.

31.

Cherny

, Catane

, Schrijvers

, et al.: European Society for Medical Oncology (ESMO) program for the integration of oncology and palliative care: A 5–year review of the Designated Centers' incentive program. Ann Oncol, 2010; 21:362–369.

32.

Smith

, Temin

, Alesi

, et al.: American society of clinical oncology provisional clinical opinion: The integration of palliative care into standard oncology care. J Clin Oncol, 2012; 30:880–887.

33.

Ullrich

, Dussel

, Hilden

, et al.: End-of-life experience of children undergoing stem cell transplantation for malignancy: Parent and provider perspectives and patterns of care. Blood, 2010; 115:3879–3885.

34.

Ullrich

, Lehmann

, London

, et al.: End-of-life care patterns associated with pediatric palliative care among children who underwent hematopoietic stem cell transplant. Biol Blood Marrow Transplant, 2016;(22):1049–1055.