Psychosocial Late Effects in Adolescent and Young Adult Survivors of Childhood Cancer Diagnosed with Leukemia,Lymphoma,and Central Nervous System Tumor

Abstract

Purpose:

The prevalence of psychosocial late effects and quality of life in adolescent and young adult (AYA)-aged survivors of pediatric cancer have been studied.

Methods:

The study was conducted in AYA survivors who had been diagnosed with leukemia, lymphoma, or brain tumor, had completed treatment at least 1 year before the study, and were 15–39 years old at study enrollment. The control group consisted of healthy volunteers. A questionnaire comprised a demographic form, eight questions concerning mental health and the disease, and survey The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Controls received a questionnaire without questions concerning an illness.

Results:

Most of survivors believed that cancer treatment might have a serious influence on their health. Survivors significantly more frequently declared using drugs: neuroleptics, tranquilizers, and antidepressants than controls. Survivors of leukemia demonstrated significantly more problems in cognitive functioning than lymphoma survivors. Females were significantly more disabled in emotional functioning than males. Young adults more often reported dysfunction in emotional functioning compared to adolescents. Survivors who were assessed ≥10 years since therapy reported significantly more disadvantage in social functioning than those assessed <10 years since treatment completion. Survivors reported significantly more disadvantages in social functioning than controls. Allogeneic hematopoietic stem cell transplantation survivors more often suffered cognitive limitations. Irradiated survivors more often attended psychological therapy.

Conclusions:

Survivors of pediatric cancer are vulnerable to consequences of oncological treatment, making their quality life significantly worse in comparison with healthy controls. They need to be monitored, supported, and educated.

Introduction

The rapid progress in treatment of childhood cancers has contributed to a significant increase in survival. It is estimated that 5-year survival rates now reach 70%–80% (Ref.¹). Due to the growing number of survivors, there is much interest in monitoring long-term effects of treatment, taking into account the quality of life (QoL) and mental health.

Numerous studies have shown the presence of psychosocial difficulties affecting family relationships, employment, or education, the presence of post-traumatic stress disorder (PTSD) symptoms, increased suicide rates, alcohol, and cigarette abuse.^2–6

Due to the increased risk of long-term consequences of cancer and therapeutic process, the knowledge about the disease plays a crucial role in shaping health behaviors among patients. Often, people treated in the past for childhood cancers have limited access to information about illness, which may prevent them from seeking appropriate care after treatment.⁷

Due to the diversity of antineoplastic therapy side effects, there is a need to provide patients with long-term observation, including psychosocial aspects, as well as comprehensive care and education about the disease and its complications both at the stage of treatment and after its completion.

Screening for distress among cancer survivors has been recommended starting at cancer diagnosis and at appropriate intervals after that.^8–10 The provision of testing supports patients' wishes since childhood cancer survivors (CCS) has described psychological well-being as more critical than physical QoL dimensions.¹¹

Despite growing concern about late psychosocial effects, the theme has not been explored embracingly among the Polish population. Therefore we aimed to study the prevalence of late psychosocial effects and health-related QoL (HRQoL) in adolescent and young adult (AYA) survivors of childhood cancer in our department.

Patients and Methods

The study was conducted between 2017 and 2019. It was approved by the Poznan University of Medical Sciences Bioethics Committee. AYA survivors of childhood cancer were recruited from the medical records of the Department of Pediatric Oncology, Hematology and Transplantology, Karol Jonscher University Hospital, Poznan University of Medical Sciences. Survivors were eligible if they were diagnosed with leukemia, lymphoma, or central nervous system (CNS) tumor, were 15–39 years old at study enrollment, and completed treatment at least 1 year before the study. Two hundred fifty patients diagnosed in 2003–2015 met the inclusion criteria and were invited to participate. A comparison group was gathered using an online survey. This group consisted of 52 persons, aged 19–30 (median 23) years, with no history of cancer or chronic disease.

Study group

Fifty-seven patients participated in the study (46% females). Mean age was 20.8 ± 3.9 (range 15–30). The most numerous group was acute lymphoblastic leukemia survivors (33.33%). Fifteen patients (26.32%) had been treated with cranial radiation therapy (CRT); 9 (15.79%) had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mean age at the time of cancer diagnosis was 11.9 ± 3.6 (range 4–18). The mean time since treatment completion was 8.5 ± 3.1 years (range 2–13). On the purpose of the study the subjects were divided according to age at diagnosis into two groups (<12 years of age; ≥12 years of age), according to time since treatment completion into two groups (<10 years; ≥10 years), and according to age at the time of enrollment into two groups: AYAs (≤18 years of age; >18 years of age) (Table 1).

Table 1.

Baseline Characteristics of Childhood Cancer Survivor Population

Childhood cancer survivors	n = 57
Gender, n (%)
Female	26 (46)
Male	31 (54)
Diagnosis, n (%)
Leukemia
ALL	19 (33.33)
AML	6 (10.53)
CML	2 (3.51)
Lymphoma
HL	14 (24.56)
NHL	9 (15.79)
CNS tumor	7 (12.28)
Age at time of study
Mean ± SD	20.8 ± 3.9
Range	15–30
≤18 years of age, n (%)	19 (33.33)
>18 years of age, n (%)	38 (66.67)
Age at diagnosis
Mean ± SD	11.9 ± 3.6
Range	4–18
<12 years of age, n (%)	23 (40.35)
≥12 years of age, n (%)	34 (59.65)
Years since treatment completion
Mean ± SD	8.5 ± 3.1
Range	2–13
<10 years, n (%)	34 (59.65)
≥10 years, n (%)	23 (40.35)
Cranial radiotherapy
Used, n (%)	15 (26.32)
Leukemia, n (%)	8 (14.04)
CNS tumor, n (%)	7 (12.28)
Not used, n (%)	40 (70.18)
No data, n (%)	2 (3.51)
Allo-HSCT
Used, n (%)	9 (15.79)
Leukemia, n (%)	8 (14.04)
Lymphoma, n (%)	1 (1.75)
Not used, n (%)	43 (75.44)
No data, n (%)	4 (7.02)
Auto-HSCT, n (%)	1 (1.75)

ALL, acute lymphoblastic leukemia; Allo-HSCT, allogeneic hematopoietic stem cell transplantation; AML, acute myeloblastic leukemia; Auto-HSCT, autologous hematopoietic stem cell transplantation; CML, chronic myeloid leukemia; CNS, central nervous system; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

Control group

The comparison group consisted of 52 persons. Due to a lack of adolescent controls, the comparison was conducted between young adult CCS (n = 38) and controls. Median age of CCS was 24 (range 19–30) compared to median age of 23 of controls (range 19–30, p = 0.0312). Controls reported significantly more frequently higher levels of education than CCS (p = 0.0002). There was a significant difference in employment between both groups (p = 0.0016) (Table 2).

Table 2.

Characteristics and Differences between Young Adult Childhood Cancer Survivors and Controls

	Survivors (n = 38)	Controls (n = 52)	p
Gender, n (%)			0.4584^*
Female	16 (42.1)	26 (50.0)
Male	22 (57.9)	26 (50.0)
Median age at study	23 (20–25)	24 (23–25)	0.0312 ^†
Employment, n (%)			0.0016 ^‡
Employed	21 (55.3)	23 (44.2)
Student (academic institution)	9 (23.7)	28 (53.9)
Unemployed	4 (10.5)	1 (1.9)
Pupil (school)	4 (10.5%)	0 (0.0%)
Education level, n (%)			0.0002 ^†
Elementary	1 (2.6)	1 (1.9)
Secondary	24 (93.2)	12 (28.1)
Higher	13 (34.2)	39 (75.0)

Bold values are statistically significant.

Chi-square test.

†

Mann–Whitney U test.

‡

Fisher's exact test.

Procedures

Participants were sent the survey pack, which consisted of an invitation letter, an information sheet, a consent form, and a questionnaire. Of the 250 enrolled survivors, 57 (22.8%) returned completed survey. Each participant signed a consent form. For patients under 18 years of age, parent consent was obtained as well. Controls were invited to participate using an anonymous online questionnaire.

Measures

On the purpose of the study, a survey was designed to include information about patients' mental health and knowledge of the disease. The standardized survey The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) was attached to our questionnaire to assess the QoL. Controls received a questionnaire without questions concerning an illness. A demographic form assessed sex, age, education, household composition, and hometown size.

The survey designed by researchers

The questionnaire consisted of 8 questions concerning mental health and knowledge of the disease.

“Do you think that cancer treatment may have a serious influence on your health?”

“Did you attend educational sessions about cancer treatment and its side effects?”

“Did you participate in psychological therapy during cancer treatment?”

“Do you feel a need to talk about the disease?”

“Did you attend psychological therapy after cancer treatment?”

“Have you ever used drugs such as: neuroleptics, tranquilizers, antidepressants, anxiolytics etc.?”

“Have you ever had suicidal ideation, suicidal attempts, self-harm behaviors?”

“Do you think that cancer had a strong influence on your psychological status?”

EORTC QLQ-Core 30

The EORTC QLQ-C30 3.0 originally developed by Aaronson et al.¹² was used to measure the HRQoL. Details of the scoring procedure are described elsewhere.¹³ The QLQ-C30 consisted of 30 questions and includes 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each scale and single-item measure ranges in score from 0 to 100. A higher score for functional scale and the global health status/QoL represent a higher level of functioning and higher QoL, respectively, whereas a higher score for a symptom scale represents a higher level of symptomatology.

Statistical analyses

PQStat v1.6.8 was used to perform statistical analyses. Mann–Whitney U and Kruskal–Wallis tests were used to compare continuous variables with non-normal distribution for two and more than two groups, respectively. For categorical variables, the Chi-square test and Fisher–Freeman–Halton exact test were performed. A p-value of <0.05 was assumed as statistically significant.

Results

The survey designed by researchers

Study group

Most of the patients believed that cancer treatment might have a serious influence on their health. However, only one-third of them reported that they had attended educational sessions about cancer treatment and its side effects. Three-fourth of the participants claimed that cancer had strongly influenced their psychological status. Nevertheless, most of the patients declared no need to talk about the disease. Less than one-third of patients declared that they had attended psychological therapy after cancer treatment completion. Of the participants, 26.32% declared that they had ever used drugs such as neuroleptics, tranquilizers, antidepressants, or anxiolytics. A little over one-fifth of patients reported having at least one of those: suicidal ideation (SI), suicidal attempts, or self-harm behaviors (Fig. 1).

FIG. 1.

Survey designed by researchers: results.

Patients treated with CRT significantly more often attended psychological therapy than those who had not undergone irradiation (p = 0.0223). Women, young adults, and irradiated survivors more often declared using drugs (neuroleptics, tranquilizers, antidepressants, and anxiolytics) in comparison to men, adolescents, and nonirradiated survivors, respectively. However, this correlation was not statistically significant. CRT survivors significantly more often reported having SI, suicidal attempts, or self-harm behaviors than those who had not undergone radiotherapy (p = 0.0111). What is more, participants who declared using the drugs above significantly more often reported these behaviors (p = 0.00001) (Table 3).

Table 3.

Survey Designed by Researchers: Results

	Attending psychological therapy, n (%)	p	Using drugs, n (%)	p	Suicidal symptoms (self-harm behaviors, SI/attempts), n (%)	p
Sex		0.7709^*		0.7414^*		0.1169^*
Female	8 (30.77)		10 (38.46)		8 (30.76)
Male	8 (25.81)		5 (16.135)		4 (12.90)
Age		0.7713^*		0.9743^†		0.6631^‡
<12 years	7 (30.43)		6 (26.1)		6 (26.1)
≥12 years	9 (26.47)		9 (26.5)		6 (17.6)
Time since treatment completion		0.5493^*		1.0000^*		0.7441^*
<10 years	11 (32.55)		9 (26.47)		8 (23.52)
≥10 years	5 (21.74)		6 (26.09)		4 (17.39)
Age at time of study		0.4044^†		0.06495^*		1.0000^*
≤18 years	4 (21.1)		2 (10.53)		4 (33.33)
>18 years	12 (31.6)		13 (34.21)		8 (66.67)
Drugs	NA	NA	—	—		0.00001 ^*
Prescribed					10 (66.67)
Not prescribed					2 (4.76)
Comparison		0.2627^†		0.0040 ^†		0.4873^†
Survivors (n = 38)	12 (31.6)		13 (34.2)		8 (21.1)
Controls (n = 52)	11 (21.1)		5 (9.6)		8 (15.4)
Cranial radiotherapy		0.0223 ^*		0.0861^*		0.0111 ^*
Used	8 (53.33)		7 (46.67)		7 (46.67)
Not used	8 (20)		8 (20)		5 (12.5)
Allo-HSCT		1.0^*		0.6739^*		0.3782^*
Used	2 (22.22)		3 (33.33)		3 (33.33)
Not used	12 (27.91)		10 (23.26)		8 (18.61)

Bold values are statistically significant.

Fisher's exact test.

†

Chi-square test.

‡

Chi-square test with Yates correction.

NA, not analyzed.

CCS versus controls

CCS were more likely to attend psychological therapy than controls (31.6% vs. 21.1%), although the difference was not significant. Survivors significantly more frequently declared using drugs: neuroleptics, tranquilizers, antidepressants, or anxiolytics (p = 0.0040). CCS more often reported having SI, suicidal attempts, or self-harm behaviors than controls (21.1% vs. 15.4%), although the difference was not significant (Table 3).

EORTC QLQ-Core 30

Study group

Primary diagnosis

An analysis by primary diagnosis showed that survivors of leukemia were significantly more likely to be limited in cognitive functioning in comparison with lymphoma survivors (p = 0.0271). However, they were not significantly different in question concerning memorization (Table 4).

Table 4.

Cognitive Functioning in Childhood Cancer Survivors

	Cognitive functioning score median value (range)	p	Concentration, n (%)				p	Memorization, n (%)				p
	Cognitive functioning score median value (range)	p	1	2	3	4	p	1	2	3	4	p
Primary diagnosis		0.0271 ^*					0.01821 ^‡					0.0742 ^*
Leukemia	83.33 (66.67–100)		16 (59.3)	6 (22.2)	5 (18.5)	0 (0.0)		13 (48.1)	9 (33.3)	2 (7.4)	3 (11.1)
Lymphoma	100 (83.33–100)		16 (59.3)	6 (22.2)	5 (18.5)	0 (0.0)		13 (48.1)	9 (33.3)	2 (7.4)	3 (11.1)
			19 (82.6)	4 (17.4)	0 (0.0)	0 (0.0)		18 (78.26)	4 (17.4)	1 (4.3)	0 (0.0)
			7 (100)	0 (0.0)	0 (0.0)	0 (0.0)		4 (57.1)	2 (28.6)	1 (14.3)	0 (0.0)
CNS tumor	100 (83.33–100)		7 (100)	0 (0.0)	0 (0.0)	0 (0.0)		4 (57.1)	2 (28.6)	1 (14.3)	0 (0.0)
Sex		0.6852^†
Female	100 (66.67–100)
Male	100 (83.33–100)
Age at diagnosis		0.8862^†
<12 years	100 (83.33–100)
≥12 years	100 (83.33–100)
Time since treatment completion		0.4053^†
<10 years	100 (83.33–100)
≥10 years	83.33 (66.67–100)
Age at time of study		0.3517^†
≤18 years	100 (83.33–100)
>18 years	91.67 (83.33–100)
Cranial radiotherapy		0.1973^†
Used	83.33 (16.67–100)
Not used	100 (33.33–100)
Allo-HSCT		0.0594^†					0.1851^†					0.072^†
Used	83.33 (16.67–100)		5 (55.56)	3 (33.33)	1 (11.11)	0 (0.0)		3 (33.33)	4 (44.44)	1 (11.11)	1 (11.11)
Not used	100 (16.67–100)		34 (79.1)	5 (11.6)	4 (9.3)	0 (0.0)		28 (65.1)	11 (25.6)	3 (7)	1 (2.3)

Bold values are statistically significant.

Kruskal–Wallis test.

†

Mann–Whitney U test.

‡

Chi-square test NW.

Sex

Females were significantly more likely to report limitations in emotional functioning compared to males (p = 0.0026). Female sex was significantly associated with emotional dysfunction for the questions relating to being worried (p = 0.0017), feeling irritable (p = 0.0355), and depressed (p = 0.0093) (Table 5).

Table 5.

Emotional Functioning in Childhood Cancer Survivors

	Emotional functioning score median value (range)	p	Being worried, n (%)				p	Being irritable, n (%)				p	Being depressed, n (%)				p	Feeling tensed, n (%)				p
	Emotional functioning score median value (range)	p	1	2	3	4	p	1	2	3	4	p	1	2	3	4	p	1	2	3	4	p
Primary diagnosis		0.1089^*
Leukemia	75 (33.33–91.67)
Lymphoma	91.67 (66.67–100)
CNS tumor	83.33 (66.67–91.67)
Sex		0.0026 ^†					0.0017 ^†					0.0355 ^†					0.0093 ^†					0.2030^†
Female	70.83 (41.67–83.33)		7 (26.9)	9 (34.6)	5 (19.2)	5 (19.2)		8 (30.8)	9 (34.6)	7 (26.9)	2 (7.7)		9 (34.6)	9 (34.6)	5 (19.2)	3 (11.5)		14 (53.8)	6 (23.1)	5 (19.2)	1 (3.8)
Male	91.67 (75–100)		20 (64.5)	9 (29.0)	0 (0.0)	2 (6.5)		16 (51.6)	12 (38.7)	2 (6.5)	1 (3.2)		21 (67.7)	7 (22.6)	2 (6.5)	1 (3.2)		21 (67.7)	7 (22.6)	3 (9.7)	0 (0.0)
Age at diagnosis		0.9737^†
<12 years	91.67 (33.33–100)
≥12 years	83.33 (66.67–91.67)
Time since treatment completion		0.2583^†
<10 years	83.33 (66.67–100)
≥10 years	75.00 (41.67–91.67)
Age at time of study		0.0687^†					0.1417^†					0.2350^†					0.1780					0.0140 ^†
≤18 years	91.67 (66.67–91.67)		12 (63.2)	4 (21.1)	1 (5.3)	2 (10.5)		10 (52.6)	6 (31.6)	3 (15.8)	0 (0.0)		13 (68.4)	3 (15.8)	1 (5.3)	2 (10.5)		16 (84.2)	2 (10.5)	1 (5.3)	0 (0.0)
>18 years	75.00 (58.33–91.67)		15 (39.5)	14 (36.8)	4 (10.5)	5 (13.2)		14 (36.8)	15 (39.5)	6 (15.8)	3 (7.9)		17 (44.7)	13 (34.2)	6 (15.8)	2 (5.3)		19 (50)	11 (28.9)	7 (18.4)	1 (2.6)
Cranial irradiation		0.4376^†
Used	75 (25–100)
Not used	83.33 (16.67–100)
Allo-HSCT		0.6416^†
Used	75 (41.67–100)
Not used	83.33 (16.67–100)

Bold values are statistically significant.

Kruskal–Wallis test.

†

Mann–Whitney U test.

Age at the time of enrollment

Young adults more often reported a dysfunction in emotional functioning compared to adolescents, although this association was not statistically significant. Nevertheless, emotional dysfunction within the question about feeling tense differs relevantly by age at the time of enrollment. Survivors who were >18 years of age were significantly more likely to report feeling tense in comparison to younger participants (p = 0.0140) (Table 5).

Time since treatment completion

An analysis by time since cancer treatment completion showed that survivors who were assessed ≥10 years since anticancer therapy reported significantly more disadvantage in social functioning in comparison to those who were assessed <10 years since cancer treatment completion (p = 0.0164). Participants who were assessed ≥10 years since anticancer therapy were significantly more likely to declare dysfunction in both family life (p = 0.0331) and social activities (p = 0.0430) compared to those who were assessed <10 years since treatment completion (Table 6).

Table 6.

Social Functioning and Quality of Life in Childhood Cancer Survivors

	Social functioning score, median value (range)	p	Family life dysfunction, n (%)				p	Social activity dysfunction, n (%)				p	Global health status/QoL score median value (range)	p
	Social functioning score, median value (range)	p	1	2	3	4	p	1	2	3	4	p	Global health status/QoL score median value (range)	p
Primary diagnosis		0.1432^*												0.1134^*
Leukemia	100 (66.67–100)												66.67 (50–83.33)
Lymphoma	100 (100–100)												66.67 (50–83.33)
Lymphoma	100 (100–100)												83.33 (66.67–91.67)
CNS tumor	83.33 (66.67–100)												83.33 (66.67–91.67)
CNS tumor	83.33 (66.67–100)												66.67 (50–75)
Sex		0.5836^†												0.2188^†
Female	100 (66.67–100)												66.67 (50–83.33)
Male	100 (83.33–100)												66.67 (50–83.33)
Male	100 (83.33–100)												75.00 (66.67–91.67)
Age at diagnosis		0.7882^†												0.7927^†
<12 years	100 (66.67–100)												75 (50–91.67)
<12 years	100 (66.67–100)												75 (66.67–83.33)
≥12 years	100 (83.33–100)												75 (66.67–83.33)
Time since treatment completion		0.0164 ^†					0.0331 ^†					0.043 ^†		0.2711^†
<10 years	100 (100–100)		29 (85.3)	4 (11.8)	1 (2.9)	0 (0)		27 (79.4)	7 (20.6)	0 (0)	0 (0)		75 (66.67–91.67)
≥10 years	83.33 (66.67–100)		29 (85.3)	4 (11.8)	1 (2.9)	0 (0)		27 (79.4)	7 (20.6)	0 (0)	0 (0)		75 (66.67–91.67)
≥10 years	83.33 (66.67–100)		14 (60.9)	6 (26.1)	2 (8.7)	1 (4.3)		13 (56.5)	7 (30.4)	1 (4.3)	2 (8.7)		75 (41.67–83.33)
Age at time of study		0.2119^†												0.2281^†
≤18 years	100 (100–100)												75 (66.67–91.67)
>18 years	100 (66.67–100)												75 (66.67–91.67)
>18 years	100 (66.67–100)												75 (50–83.33)
Cranial irradiation		0.2489^†												0.0085 ^†
Used	100 (0–100)												66.67 (33.33–100)
Not used	100 (33.33–100)												66.67 (33.33–100)
Not used	100 (33.33–100)												83.33 (33.33–100)
Allo-HSCT		0.1505^†												0.8164^†
Used	83 (0–100)
Not used	100 (33.33–100)												66.67 (41.67–100)
Not used	100 (33.33–100)												75 (33.33–100)

Bold values are statistically significant.

Kruskal–Wallis test.

†

Mann–Whitney U test.

QoL, quality of life.

Age at cancer diagnosis

Age at cancer diagnosis was not statistically significantly associated with emotional functioning, social functioning, cognitive functioning, or global health status/QoL (Tables 4–6).

Treatment modalities

Allo-HSCT survivors reported more disadvantage in cognitive functioning than those who had not undergone this procedure (p = 0.0594). CRT was not associated with impaired cognitive functioning. Neither of procedures was statistically significantly correlated with emotional or social functioning. Irradiated survivors were significantly more likely to report poorer global health status/QoL than nonirradiated participants (p = 0.0085).

CCS versus controls

Survivors reported significantly more disadvantages in social functioning in comparison to healthy controls (p = 0.0062), declaring both impaired family life (p = 0.0399) and social activity (p = 0.0049). There were no statistically significant differences between both groups in emotional functioning, cognitive functioning, or global health status/QoL (Table 7).

Table 7.

The European Organization for Research and Treatment of Cancer: Comparison between Childhood Cancer Survivors and Controls

	CCS (n = 38)	Controls (n = 52)	p
Cognitive functioning score median value (range)	91.7 (83.3–100)	100 (83.3–100)	0.4767^*
Emotional functioning score, median value (range)	75 (58.3–91.7)	75 (66.7–91.7)	0.8204^*
Social functioning score median value (range)	100 (70.8–100)	100 (100–100)	0.0062 ^*
Dysfunction in family life, n (%)			0.0399 ^*
1	28 (73.7)	47 (90.4)
2	7 (18.4)	3 (5.8)
3	2 (5.3)	2 (3.8)
4	1 (2.6)	0 (0.0)
Dysfunction in social activities, n (%)			0.0049 ^*
1	24 (63.2)	46 (88.5)
2	12 (31.6)	5 (9.6)
3	1 (2.6)	1 (1.9)
4	1 (2.6)	0 (0.0)
Global health status/QoL score median value (range)	75 (52.1–83.3)	75 (66.7–83.3)	0.3470^*

Bold values are statistically significant.

Mann–Whitney U test.

Discussion

Malignancy and its treatment during childhood result in inevitable adverse effects that negatively affect mental health and QoL. Despite the growing interest in this topic, reports concerning the Polish population are sparse. For that reason, we studied the prevalence of late psychosocial effects and HRQoL in AYA-aged CCS in our department. We used a standardized survey and one that we have formed to aim more specific information about patients' psychosocial needs.

Although most patients believe that cancer has a significant impact on their health, few of them feel the need to talk about illness or seek psychological support. The results of Howard et al.¹⁴ study refer to this. They note that there are several attitudes to cope with a past illness. One of them is to repress the disease and the healing process. Some patients are aware of consequences of cancer and its treatment; however, they burden their doctors with responsibility for their health during follow-up.¹⁴ Most of our patients did not participate in educational sessions about the consequences of disease. Howard et al.¹⁴ emphasize that some emotional problems, including fear and distress, appear years after healing with the emerging effects of treatment. That is why it is important to educate patients about their disease and its complications and to take cognizance of patients' mental state during follow-up. Similar observations result from our study. Individuals who were >18 years of age significantly more often reported emotional dysfunction concerning the feeling of tension in comparison to younger participants. This finding corresponds with the study of Fidler et al., which suggested that the risk of poorer outcomes in terms of emotional functioning increases with age.¹⁵ Existing literature suggests that not only do CCS have to struggle with emerging physical limitations and disabilities but also they may experience significant psychological distress related to social difficulties, which can build over time.^16,17 Study delineates that having a history of childhood cancer is correlated with impaired family life. The result of Racine et al.¹⁸ research notes the impact of psychosocial family risk factors and parent psychological distress on the QoL of CCS. Parent distress and family functioning are essential to be surveyed as it may be helpful to moderate poor QoL of CCS and buffer the impact of parent psychological distress on patients' distant psychological adverse outcomes.¹⁸

The abovementioned physical and psychosocial limitations may put survivors at risk of participation in risky behavior, which may exacerbate already existing poor health outcomes.¹⁹ In addition, survivors affected by poor psychological and socioeconomic adjustment can also require pharmacological interventions. According to our study, adult survivors were found significantly more likely to have antidepressants, anxiolytics, or neuroleptics prescribed than a group of noncancer controls, which is consistent with previous studies.^20–23 Survivors who have been over 10 years after treatment completion significantly more often presented disorders in social functions, both in the sphere of family life and social activities. It is assumed that mental health dysfunction may increase with age as a consequence of the fact that the risk of multiple late effects emerging increases along with the time since treatment.¹⁵

A higher frequency of self-destructive behaviors and suicidal symptoms occurred in survivors, compared with individuals without a history of cancer. The study of Recklist et al. has shown that suicidality is associated with CNS cancer diagnosis, depression, and poor health outcomes.³ In our research, having a history of destructive behaviors or suicidal symptoms was strongly associated with having drugs above prescribed. These results have significant implications for developing follow-up guidelines. Routine psychological screening may serve in assessing suicidal risk. Therefore, clinicians should have regard to survivors' emotional functioning.

In our study, leukemia survivors tended to be more affected in cognitive functioning in comparison to lymphoma survivors. According to the literature, cognitive dysfunction occurs the most frequently among survivors of brain tumors or ALL.^24,25 In recent years, neurocognitive outcomes of ALL survivors have improved, since CRT was replaced with systemic and intrathecal chemotherapy. However, survivors treated on contemporary protocols are still at risk for cognitive deficits.^26,27 Our results do not fully match the expectations based on existing literature. The least numerous group in our study—brain tumor survivors—was not significantly more limited in cognitive functioning than other groups. This discrepancy may be a result of the disproportion between those groups.

Notably, we found that female survivors tended to have worse outcomes in emotional functioning compared to males. Our results are consistent with the literature. Female sex is highlighted as one of the significant risk factors of psychological distress, such as anxiety or depression.^2,28 Female CCS have a higher risk of psychiatric morbidity as a late effect of cancer.²⁹ These data emphasize the need for screening of psychological distress in CCS in their long-term follow-up.

In our study, allo-HSCT survivors reported more disadvantage in cognitive functioning than those who had not undergone this procedure; however, the correlation was not statistically significant. According to the literature, children undergoing HSCT endure behavioral symptoms correspondent to those of PTSD and suffer from numerous psychosocial limitations, which are often prolonged months after treatment.^30,31 It appears that age at transplantation and conditioning regimen, including total body irradiation, have crucial impact on cognitive impairment in HSCT survivors.³² It has been also well established that CNS-directed treatment, particularly CRT, is associated with poor psychological functioning and poor general health.^16,19 CRT is a risk factor for depression and post-traumatic stress symptoms.^33,34 In our study, CRT survivors significantly more often reported having SI or self-harm behaviors, were significantly more likely to attend psychological therapy, and reported poorer QoL than nonirradiated participants.

The results of the study should be considered within the context of several methodological limitations. The most meaningful limitation was a relatively low response rate. We are strongly convinced that there are many causes for this phenomenon. First of all, our institution does not manage a long-term follow-up care for young adult survivors of childhood cancer, which results in loss of continuity of care. Second, impeded contact with survivors may be a consequence of reaching the age of maturity by CCS, which entails moving out, going to college, or starting a family. Moreover, survivors tend to manage their psychological and medical challenges by adopting different approaches, including repressing the disease or putting it in the past and consequently downplaying long-term consequences and avoiding any discussion about the disease.¹⁴ Our results may not be confidently generalized to all CCS, since participants were recruited from records of a single institution. A notable limitation was a disproportion between the number of participants with each diagnosis. Our results concerning CNS tumor survivors may not be consistent with existing literature due to the prevalence of leukemia and lymphoma survivors. However, we aimed to obtain insight into psychosocial late effects among survivors of three most frequent childhood malignancies in as numerous study groups as possible, taking into account the heterogeneity of this group and trying to identify risk factors. Another limitation was lack of nonaged controls to which adolescent survivors could have been directly compared.

Conclusions

AYA-aged CCS are vulnerable to the late consequences of oncological treatment, making the quality of their psychosocial life significantly worse in comparison with healthy controls. They need to be monitored, supported, and educated. Diagnosis, sex, age, time since treatment completion, and treatment modalities are crucial factors for risk stratification and planning interventions.

Footnotes

Acknowledgments

The authors thank Monika Łęcka, MD, Paweł Małecki, MD, and Agnieszka Basiukajć, MD for their support in data collection process.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received.

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