Cumulative burden of chronic health conditions among adolescent and young adultsurvivors of childhood cancer: identification of vulnerable groups at key medical transitions

Abstract

The cumulative burden of chronic health conditionsaschildhood cancer survivorstransition to adult healthcare and insurance systems is unknown. We estimatedthe cumulative burden(N=4,612 survivors, 625 controls) in the St. Jude Lifetime Cohort. At 18- and 26-years-old, survivors experienced (per 100 individuals) an average of 22.3(95% CI:17.2–27.4) and 40.3(95% CI:34.8–45.8) disabling conditions versus3.5(95% CI:2.0–5.0) and 5.7(95% CI:3.7–7.7) in controls, and128.7(95% CI 119.5–137.8) and 240.5(95% CI:229.9–251.0) lower severity conditions versus12.4(95% CI:8.9–16.0) and 51.3(95% CI:43.1–59.4) in controls. Survivors experience a high cumulative burdenat key healthcare transition ages, underscoring the need to optimize access to care.

Introduction

Childhood cancer survivors are at increased risk for chronic health conditions,reflected by the cumulative burden methodology, which accounts for multiple and recurrent conditions of varying severity.¹ The cumulative burden in survivors transitioningfrom pediatric to adult care providers and from parental to self-insurance plans is unknown. Around age 18, adolescents move from pediatric to adult healthcare systems. This is particularly salient given that primary care providers are largely responsible for managing the healthcare of long-term childhood cancer survivors.²Insurance coverage and benefits may change during this period, as young adults move from family to individual plansor between public and private systems.^3,4In the general population, young adults with disabling conditions are at increased risk of losing insurance coverage and medical adversity,⁴ while uninsured young adults are 8-times more likely to delay or miss needed care than insured peers.³These transitions leave medically complex individuals vulnerable to lapses in care that potentially jeopardize preventative and intervention-based health measures, raising concern for childhood cancer survivors given their early and increased risk of chronic conditions. However, the burden of morbidity, in particular potentially disabling diseases, has not been defined during these key transitions.

We report the cumulative burden of chronic health conditions forsurvivors of childhood cancer compared to community controls at key transition ages (i.e., 18 and 26 years) in order to identify implications for policy and practice.

Methods

We utilized the St. Jude Lifetime Cohort (SJLIFE) of ≥5-year childhood cancer survivors treated at St. Jude Children’s Research Hospital (SJCRH) and age-, sex-, and frequency-matched community controls selected from the same geographic population.^5,6Participantsundergo prospective medical assessments upon study entry and at approximately 5-year intervals thereafter,in addition to a retrospective review of all previous SJCRH records to identify major health events. Health conditions occurring between SJCRH visits are validated by medical record requisition. The severity of chronic health conditions isgraded according to a modified version of the Common Terminology Criteria for Adverse Events.⁷For the current study, we reportthe cumulative burden of chronic health conditions in survivors only at key transition ages (i.e., 18 and 26 years). We compiled a list of conditions graded in SJLIFE that overlapped with those conditions most frequently contributing tomedical disability adjusted life years in the United States (cancer, cardiovascular, neurologic, musculoskeletal, and respiratory conditions, stroke, and chronic kidney disease).^8–10Higher grade conditions expected to impair activities of daily living were considered disabling. Lower grades of the same conditions were considered to be of lesser severity with the potential to progress to disabling conditions, but potentially amenable to intervention (Supplemental Table). A separate analysis of lower grade conditionswas performed thatadditionally included hypercholesterolemia, hypertriglyceridemia, abnormal glucose metabolism, and overweight/obesity, as these represent potentially intervenable conditions which left untreated, contribute to the development of a number of disabling conditions, however in and of themselves were not considered disabling.

Survivors entered the cohort at 5 years from primary cancer diagnosis and ended on the last contact date or date of death. Demographics between survivors and controls were compared using χ² tests. The cumulative burden of chronic health conditions was estimated at ages 18 and 26 years using the mean cumulative count methodology, representing the number of recurrent or multiple health events an individual has, on average, by a specified timepoint accounting for competing risks.^1,11The bootstrap method was used to estimate 95% confidence intervals (CI).

Results

There were 4,612 survivors and 625 controls in our study(Table 1). The median (range) ages at cancer diagnosis and evaluation were6.6 (0–24.8) and 32.1 (7.5–71.1) years, respectively. The majority of survivors were male (52%), and 16% were black. Survivors experienced,on average, 22.3 (95% CI:17.2–27.4)and 40.3 (95% CI:34.8–45.8)disabling conditions per 100 individuals compared to 3.5 (95% CI:2.0–5.0) and 5.7 (95% CI:3.7–7.7)in community controls at ages 18 and 26 years, respectively. Similarly, survivors experienced, on average,128.7 (95% CI:119.5–137.8) and 240.5 (95% CI:229.9–251.0)conditions of lower severity per 100 individuals compared to 12.4(95% CI:8.9–16.0) and 51.3(95% CI:43.1–59.4) in community controls.

Table 1.

Characteristics of study cohort

	SJLIFE Participants		Controls		p
	N = 4,612		N = 675
	N	(%)	N	(%)
Race/ethnicity					<.001
White non-Hispanic	3,614	78	515	82
Black non-Hispanic	736	16	39	6
Hispanic	158	3	24	4
Other	104	2	47	8
Sex					<.001
Male	2,417	52	278	44
Female	2,195	48	347	56
Age at assessment (years)					<.001
5–14	353	8	12	2
15–24	944	20	153	24
25–34	1,461	32	217	35
35–44	1,117	24	156	25
≥45	737	16	87	14
Annual household income**					<.001
<$60,000	2,079	59	239	44
≥$60,000	1,433	41	306	56
Employment status**					<.001
Unemployed	1,054	27	71	12
Partial/full-time/home care providers, students	2,798	73	504	88
Insurance status**					0.008
Uninsured	645	17	72	12
Insured	3,236	83	514	88
Age at cancer diagnosis (years)
0–4	1,914	42
5–9	1,021	22
10–14	965	21
15–19	675	15
20+	37	1
Decade of cancer diagnosis (years)
1960–1969	98	2
1970–1979	569	12
1980–1989	1,103	24
1990–1999	1,319	29
2000+	1,523	33
Cancer diagnosis
Acute lymphoblastic leukemia	1,361	30
Acute myeloid leukemia	194	4
Hodgkin lymphoma	496	11
Non-Hodgkin lymphoma	297	6
Central nervous system tumors	654	14
Bone tumors	289	6
Soft tissue sarcoma	291	6
Wilms	287	6
Neuroblastoma	224	5
Retinoblastoma	253	5
Germ cell	96	2
Other*	170	4

^*Included other leukemia (n=39), melanoma (n=35), nasopharyngeal carcinoma (n=32), liver malignancy (n=30), other carcinoma (n=28), and colon carcinoma (n=6)

^**Applicable only to participants ≥18 years of age at SJLIFE assessment.

The cumulative burden of disabling, disease-specific conditions at ages 18 and 26 years was most notable for survivors of bone tumors (musculoskeletal: 99.9 [95% CI:77.9–124.4] and 121.7 [95% CI:102.1–141.3]),soft tissue sarcoma (musculoskeletal: 49.5 [95% CI:5.7–93.3] and 54.1 [95% CI:11.2–97.1]), and central nervous systemtumors (neurologic 24.7 [95% CI 13.1–36.4] and 36.8 [95% CI 24.9–48.8]) (Fig.1A).

Figure 1.

A) Distribution of cumulative burden of higher severity, potentially disabling chronic health conditions in the St. Jude Lifetime Cohort (SJLIFE) at ages 18 and 26 years, and B) Distribution of cumulative burden of lower severity chronic health conditions in SJLIFE at ages 18 and 26 years. ALL=acute lymphoblastic leukemia, AML=acute myeloblastic leukemia, HL=Hodgkin lymphoma, NHL=non-Hodgkin lymphoma, CNS=central nervous system, STS=soft tissue sarcoma, NB=neuroblastoma, RB=retinoblastoma

The cumulative burden of lesser severity conditions potentially amenable to intervention at ages 18 and 26 years weremost notable for neurologic conditions across most cancer subgroups, with the highest cumulative burden in central nervous systemtumor survivors (95.2 [95% CI:87.0–103.4] and 162.3 [95% CI:153.1–171.5]) (Fig.1B). When considering hypercholesterolemia, hypertriglyceridemia, abnormal glucose metabolism, and overweight/obesity, lower grade cardiovascular conditions were observed to be more prominent at both ages (Supplemental Figure S1).

Discussion

Childhood cancer survivors are at increased risk for multiple disabling and chronic conditions at ages 18 and 26 years, key ages surrounding transition to adult care settings and likely insurance coverage changes. We report a high burden of lower severity conditions with potential to progress into disabling conditions without proper management, highlighting a need for seamless, high quality medical transitions. Our findings raise concern regarding potential health consequences facing childhood cancer survivors at healthcare transition ages. Survivors are more likely to be dependent upon public insurance plans,¹² report greater difficulty obtaining coverage,¹³ and experience “job lock” in order to maintain existing coverage.¹⁴ Survivors transitioning between pediatric and adult care may therefore be more vulnerable to gaps in coverage, highlighting a critical need to maintain access to high quality medical care for childhood cancer survivors at these key ages.

Two notable groups emerged. First are those groups in which many have already developed disabling conditions by age 18 that are likely to persist at 26 years (e.g., bone tumor survivors). The second are those with lower severity conditions at risk for progression to higher grade, disabling conditions. Early intervention for the latter may improve outcomes, minimally delaying onset of disability.

Our study has limitations to be considered. First, we were unable to confirm disability status in our participants;therefore,our assignment of disabling conditions may not reflect thecriterion for public programs or the degree of functional impairment. Second, we assumedearly intervention for lower severity conditions would delay or prevent the occurrence of disabling conditions. While this has been demonstrated in the general population for many conditions, they may not equally apply to survivors for whom the underlying disease pathophysiology may differ. In addition, we demonstrated patterns of the cumulative burden of health conditions to raise immediate awareness of this potentially vulnerable population; however, future analyses to determine associations with higher burden are necessary to direct critical resources to groups at highest risk. Lastly, SJLIFE reflects individuals from a single center, therefore our results may not be generalizable to survivors who differ in race, ethnicity, and social risk.

In summary, we report a high cumulative burden of chronic health conditions in 18- and 26-year-old survivors of childhood cancer compared to community controls. These findings underscore the importance of seamless, high-quality medical transitions that optimize insurance coverage and health care access for this medically complex and vulnerable group.

Supplementary Material

FIG S1

Supplemental Figure S1. Distribution of cumulative burden of lower severity chronic health conditions (with the addition of hypertriglyceridemia, hypercholesterolemia, abnormal glucose metabolism, and overweight/obesity) in the St. Jude Lifetime Cohort (SJLIFE) at ages 18 and 26 years. ALL=acute lymphoblastic leukemia, AML=acute myeloblastic leukemia, HL=Hodgkin lymphoma, NHL=non-Hodgkin lymphoma, CNS=central nervous system, STS=soft tissue sarcoma, NB=neuroblastoma, RB=retinoblastoma

Abbreviations

SJLIFE

St. Jude Lifetime Cohort

CI

confidence interval

ALL

acute lymphoblastic leukemia

AML

acute myeloblastic leukemia

HL

Hodgkin lymphoma

NHL

non-Hodgkin lymphoma

CNS

central nervous system

STS

soft tissue sarcoma

NB

neuroblastoma

RB

retinoblastoma