Introduction
Pediatric cancer is one of the main causes of childhood
mortality and a public health threat of growing importance.[] Approximately 250.000 children aged 0-19
are diagnosed with cancer and 100.000 children die because
of the disease worldwide every year.[,]
Despite cancer is a physical disease, it has significant
mental and psychosocial impacts. When a family
member is diagnosed with cancer, this may also affect
all other members.[,] In families with multiple children,
pediatric cancer may be especially challenging
for healthy siblings.[] Numerous changes occur in the
daily lives of healthy siblings of children with cancer
(HSCC), including alterations in day-to-day routines,
family roles, and emotional/behavioral and educational
problems rise.[,] The daily routines of HSCC
are interrupted due to hospital visits and admissions
of the child diagnosed with cancer.[,] Roles within
the family are altered together with changes in the family
system. Individual responsibilities increase, and the
caregiver's assistance to the HSCC decrease as a result.
[,] HSCC experience more emotional problems than
the unaffected people such as fear, anxiety, shock, loneliness,
sadness, anger, guilt, and helplessness.[-]
Despite the growing interest in recent years, there
has been little agreement on the psychosocial impacts
(such as depression/anxiety and quality of life) and
associated risk factors of pediatric cancer on healthy
siblings.[,,] It can be seen that the studies conducted
on HSCC have suffered several methodological
limitations. In a recent review on the effects of pediatric
cancers on healthy siblings, the majority of studies
were reported to involve low numbers of participants
and no control groups whatsoever.[] In the controlled
few studies, there were non-matched control groups
due to using Cancer Survivor Study data in which most
subjects in control groups were either cancer survivors
or had cancer. Additionally, there has been a few studies
implementing validated surveys.[]
Cultural norms have been considered important
factors affecting the psychosocial outcomes of cancer
on the family system.[] However, most of the studies
on psychosocial effects of cancer come from the Western
countries with only few studies from non-Western
populations.[] In a current review study (2020), the
researchers found no articles on the psychosocial status
of siblings of children with cancer in Turkey.[] This
condition leaves a gap in the literature. In the current
study, the authors seek to obtain data which will help to
address these gaps.
Psychosocial effects of pediatric cancer on HSCC
have several different dimensions while depression/
anxiety and quality of life have been frequently investigated
issues with inconsistent findings across studies.
[,,] The purpose of this study was to investigate the
psychosocial effects of pediatric cancer on HSCC in a
non-Western population with particular attention to
the depression/anxiety and quality of life, and associated
factors.
This research considered the following questions:
I. Are depression/anxiety symptoms more common
in HSCC than in the unaffected population?
II. Is there any difference in quality of life scores between
case and control groups?
III. What is the relation between quality of life and depression/
anxiety symptoms in HSCC?
IV. What are the factors associated with impairment of
quality of life and presence of depression/anxiety?
Methods
Participants
This study was performed at the Gaziantep University
Medical Faculty, Turkey, between August 2018 and
January 2019. The study consisted of case and control
groups.
Inclusion criteria were a) age 8-16 years, b) no diagnosis
of cancer in either of the parents, c) absence
of any chronic medical or neurological disease in the
child and d) the parent being literate and possessing
sufficient Turkish language skills to complete the study
form. Further conditions were a diagnosis of cancer
in a sibling for at least three months prior in the case
group, and absence of any current or previous history
of cancer in any sibling for the control group. No exclusion
criteria were imposed concerning type or stage of
pediatric cancers. Parents unwilling to participate and
families with a parent suffering from psychotic disorder
or intellectual disability were excluded from the
study.
Parents of children with cancer were approached
during their clinical visits to pediatric hematology and
oncology clinics. Parents were provided information
about the study and healthy children of parents who
gave informed consent were enrolled in the case group.
If the children with cancer have more than one sibling,
only the nearest-age sibling was included in the study.
Control group consisted of children presenting to the
pediatric clinic due to upper respiratory tract infection
(URTI) or for routine health checks. They were
required to have similar sociodemographic characteristics to those of the case group and no diagnosis of
cancer in the family.
Of those parents (n=185) who were eligible for the
participation, 64.9 percent (n=120) were enrolled in
the study. Of those parents who did not give consent
for the participation (n=65) main reasons for refusing
were; not having enough time (n=43; 66.1 %), feeling
anxious or distressed (n=16; 24.6%) and the concern of
parents about it would not be useful (n=6; 9.2 %).
Parents completed a Personal Information Form,
the Revised Children's Anxiety and Depression Scale
(RCADS), and the Questionnaire for Quality of Life
Assessment for Children and Adolescents Parent
Form (Kid-KINDL). The scales were completed for the
HSCC in the case group and for the child presenting
for routine health checks in the control group. In accordance
with the Declaration of Helsinki, approval for
the study was obtained from the Gaziantep University
Ethics Committee on 01.08.2018 (No: 2018/180).
Measures
Personal Information Form
Parents agreeing to take part in the study completed
a personal information form prepared by the authors.
This form consisted of questions inquiring into sociodemographic
characteristics such as children"s age
and gender, parental education levels (years), and family
income status (below or above minimum wage as
declared by Turkish government).[] For the family
income status we defined the groups as low income
(below minimum wage) or normal income (above
minimum wage). The personal information form also
contained questions about the age and gender of the
child with cancer, the diagnosis, and the duration of
disease (months).
Revised Child Anxiety and Depression Scale (RCAD-S)
The RCAD-S was developed by Chorpita et al.[] The
validity and reliability of the Turkish language version
were established by Görmez et al.[] The Cronbach
alpha coefficiency of the Turkish-language form of the
scale was calculated as 0.95. The Cronbach α coefficiency
of the RCAD-S in the present study was 0.88.
The scale consists of 47 items. These are answered
by parents based on a four-point Likert (0=never,
1=sometimes, 2=frequently, and 3=never). The scale
screens for depression, and anxiety disorders (separation
anxiety disorder, panic disorder, generalized anxiety
disorder, and social phobia). The scale elicits Total Anxiety and Total Depression/Anxiety scores derived
from the total of the items concerning these disorders.
It provides categorical and dimensional data concerning
these disorders. The cut-off point for total depression/
anxiety score was 33 or above. Subjects with total
depression/anxiety scores of 33 or more were regarded
as having depression/anxiety.[]
Questionnaire for Quality of Life Assessment for
Children and Adolescents Parent Form (Kid-KINDL)
Kid-KINDL was developed by Ravens-Sieberer et al. to
assess health-related quality of life.[] The validity and
reliability of the Turkish language version were studied
by Eser et al.[] The Cronbach alpha coefficiency of
the Turkish-language form of the scale was calculated
as 0.78. The Cronbach α coefficiency of the RCAD-S in
the present study was 0.74. It consists of five categories
based on a five-point Likert scale (1: Never, 2: Rarely,
3: Sometimes, 4: Frequently, 5: Always). The scale
consists of 24 items in six dimensions, physical wellbeing,
emotional well-being, self-esteem, family, social
relations, and school. Mean Average scores for each
subgroup are calculated and converted into a value between
0 and 100. Scorings are positively oriented, with
high scores indicating good quality of life. A general
quality of life score was used for statistical analysis in
which a quality of life score for each domain and all
domains together were calculated. A cut-off point of 70
was adopted for the general quality of life score. Total
quality of life scores below 70 were regarded as a sign of
impaired quality of life.[,]
Treatment Intensity
The Intensity of Treatment Rating Scale 3.0 (ITR-3)
was used to determine the intensity of pediatric cancer
treatment. The content validity (r=0.88) and interrater
reliability (r=0.86) of ITR-3 were established by
Kazak et al. ITR-3 has four levels of treatment intensity
(1=least intenseive, 2=moderately intensive, 3=very intensive,
and 4=most intensive).[]
Data Analysis
Statistical analysis was performed on SPSS Windows
21.0 software. Percentage, arithmetic average, and
standard deviation were employed. Distribution of
data was assessed using the Kolmogorov Smirnov test.
Student"s t-test, with Pearson correlation analysis for
correlation, was applied for normally distributed data,
while the Mann-Whitney U test was used for non normally
distributed data. Relations between qualitative
variables were examined using the chi-square test.
p<0.05 was regarded as statistically significant. Factors
related to presence of depression/anxiety and impaired
quality of life were evaluated by composing models using
binary logistic regression analyses. Since there have
been no similar studies using the Turkish version of
the Revised Child Anxiety and Depression Scale in the
literature, power analysis could not calculate. Post-hoc
power analysis of 120 participants showed a power of
79.2% in total depression/anxiety scores using an independent
t-test with a 0.05 two-sided significance level.
Results
One hundred twenty subjects aged 8-16 years old were
included in the study. The study sample consisted of
case (12.08±2.61 years old) and control (11.40±2.11
years old) groups with each group including 60 subjects. The two groups were statistically similar in terms
of the age, gender, income level, and parental education
levels (p>0.05 for all). Table 1 shows the descriptive
characteristics of the study subjects.
Table 1: Descriptive characteristics of the case and control groups
The total RCAD-S score in our case group was significantly
higher than the control group (Independent
Sample t-test, t-score=2.742, p=0.007). RCAD-S subscale
analysis revealed significantly higher panic disorder,
social phobia, and depression scores in the case
group (p<0.05 in all measures). Case and control group
RCAD-S scores are summarized in Table 2.
Table 2: Revised Child Anxiety and Depression Scale
scores of case and control groups
In addition to anxiety and depression scores, total
quality of life scale score was also significantly lower in
the case group compared to the control group (Independent
Sample t-test, t-score=-3.040, p=0.003). Quality
of life scores in the school (Mann?Whitney U-test,
z-score=-2.932, p=0.003) and self-esteem (Independent
Sample t-test, t-score=-4.027, p<0.001) domains
were significantly lower compared to those in the control group. Case and control group quality of life scores
are summarized in Table 3.
Table 3: Questionnaire for Quality of Life Assessment for
Children and Adolescents Parent Form scores
of case and control groups
High Kid-KINDL scores indicate high quality of
life, while high RCAD-S scores indicate a high frequency
of psychiatric symptoms. Correlation analysis
revealed significant negative correlation between total
RCAD-S scores and Kid-KIND-T scores (p<0.001,
correlation coefficient=-0.545). Figure 1 shows a correlation
scatter plot of total RCAD-S and Kid-KIND-T
scores in case group.
A binary regression model was established for the
independent determination of predictors of presence
of depression/anxiety and impairment of quality of
life in HSCC. In producing that model, total depression/
anxiety scores (Total RCAD-S Scores) and total
quality of life scores (Total Kid-KINDL Scores) cut-off
points were used as dependent variables.[20,23,24] The
independent variables used in the study were the gender
of the healthy child (male?female), the child with
cancer and the healthy sibling being of the same gender
(absence?presence), the age of the healthy child
(years), the age difference between the siblings (years),
treatment intensity (1 (least intenseive) ? 4 (most intensive)),
recurrence (absence?presence), and low income
status (high/normal income status?low income
status). Significant relation was found between total
depression/anxiety and the siblings being of the same
gender (B=6.89 confidence interval (CI): 1.29; 36.72,
p=0.024) and also the intensity of treatment (B=3.55
CI: 1.12; 11.22, p=0.031). Predictive factors for impairment
of quality of life included age difference (B=1.34
CI: 1.08; 1.66, p=0.008) and the siblings being of the
same gender (B= 8.81 CI: 1.56; 49.65, p=0.014). Binary
logistic regression analysis concerning predictors affecting
anxiety, depression and quality of life is summarized
in Table 4.
Table 4: Binary logistic regression analysis for predictors of impairment in quality of life and presence of depression/anxiety
Fig 1: The correlation scatter plot for total Revised
Child Anxiety and Depression Scale (RCAD-S)
scores and total Questionnaire for Quality of Life
Assessment for Children and Adolescent Parent
Form (Kid-KINDL) scores in the case group.
Discussion
The study investigated the relationships between pediatric
cancer and depression, anxiety, and quality of life
in HCSS. We examined independent variables potentially
associated with depression, anxiety and quality of
life and found several important findings with clinical
and research implications.
We have found higher rates of depression and
anxiety symptoms among HSCC compared to control
group, the case group showing more significant depressive
symptoms. We further looked for the subtypes of
anxiety symptoms and found that symptoms of social
anxiety and panic disorders were significantly more in
HSCC. A literature review revealed that although HSCC
experience negative emotions like fear, anger, loneliness,
shock, jealousy, helplessness, guilt, sadness, and social
withdrawal, there is little clinical agreement among the
results of studies concerning the prevalence of depression
and anxiety symptoms in HSCC.[,,,] Houtzager
et al. (2004) reported significantly higher depression,
anxiety, and social withdrawal symptoms among
HSCC aged 12-18 years compared to a reference group.
[] Similarly, Alderfer et al. reported significantly higher
anxiousness/depression, withdrawal/depression, related,
somatic complaints and aggressive behavior in the
subscales of Child Behavior Checklist (CBCL) in HSCC
compared to the normal population.[] However, several
studies have reported that depression and anxiety
symptoms are within normative ranges in HSCC.
[,-] A recent review reported that the prevalence
of depression and anxiety in HSCC was clinically within
normal ranges and similar to that in the groups it was
compared.[] However, it may be important to note that
majority of the studies conducted on this topic come
from Western countries while current study was conducted
in a non-Western population with different sociocultural
and family characteristics yielding different
findings.[,] Additionally, these results are likely to
be associated with using a well-matched control group
in our study, unlike other studies.[]
Other notable findings of the current study were
that depression/anxiety scores were associated with the same gender between ill and healthy siblings and treatment
intensity for the sibling with cancer. Considering
that the family is a system, the gender of the healthy
child and the gender of the individual with cancer must
be evaluated together in assessing the psychosocial effects
on the healthy child. When one family member is
diagnosed with cancer, healthy child in the family may
be in different roles (such as sibling, offspring or grandchild).[,] These different roles should be considered
when evaluating the effects of gender on psychosocial
aspects of cancer. For example, several studies investigating
the effects of parental cancer on healthy offspring
have reported that girls are more at risk in terms
of psychological health. Since most of these studies have
involved parents with breast cancer, the affected parent
and offspring have generally been female.[] Findings
from these studies raise the question of whether
the psychological effects on healthy children are associated
with the female gender or with the ill family
member and healthy children being the same gender.
Mixed findings were reported for the effect of gender
on HSCC in pediatric cancer studies.[,,] In our
study, this was found to be associated with the siblings
(healthy and patient with cancer) being of the same
gender, rather than with female gender. To the best of
the author's knowledge, there have been no previous
studies considering the gender of the healthy child together
with that of the individual with cancer. Further
multi-dimensional studies of the effects of gender are
needed for a better understanding of this issue. In the
quantitative study of 30 HSCCs, Long et al. reported a
relation between distress in the HSCC and treatment
intensity.[] In line with this report we found an association
between depression/anxiety in HSCC and
the intensity of treatment in sibling with cancer. Therefore, clinicians treating children with cancer should
give particular attention for the healthy siblings if they
are the same gender and there is intensive treatment in
children with cancer.
The quality of life total score in the case group
(HSCC) was significantly lower than that of the control
group in the present study. This was particularly evident
in the school and self-esteem domains. In a systematic
review study, Alderfer et al. determined poorer
quality of life in HSCC.[] In addition, several other
studies have also determined impairment of quality of
life in HSCC.[,-] However, a review by Long et
al. reported that findings concerning quality of life of
HSCC were inconsistent across studies.[] In our study,
impairment of quality of life was found to be associated
with an increased age difference between healthy and
ill siblings. This result may be related to unmet needs
and increased responsibilities. Unmet needs are increased
in younger HSCCs as well as responsibilities
are increased in older HSCCs.[,] Both conditions
may be associated with increased age difference and
impairment in quality of life. This finding supports a
previous study, investigating the factors predicting psychological
distress and unmet needs in 106 adolescents
and young adults that reporting a greater age difference
between siblings among demographic variables
was particularly associated with unmet needs.[]
Confirmation of this finding by our study in a different
socio-cultural population may prompt clinicians to
be more cautious about quality of life issues in HSCC
when treating children with cancer.
Another finding in the present study was a significant
negative correlation between Total-RCADS
and Total-KidKINDL scores. The present finding is in
agreement with a previous study reporting that family
adjustment was positively correlated with anxiety
and negatively correlated with quality of life.[] To
date very few studies have investigated the relation between
depression /anxiety symptoms and quality of life
in HSCC.[] Despite we found a negative correlation
between depression/anxiety and quality of life total
scores, due to the cross-sectional design of our study, it
may not show a casual relationship between these variables
as bidirectional relation is quite possible.
Limitations
There are a number of limitations of this study, including
its cross-sectional design, relatively small sample
size, potential selection bias, and parental reports of
depression/anxiety and quality of life. Further studies with prospective design and larger samples in different
cultures with parental and self-reports are needed on
this topic.
Conclusion
Health professionals treating or working with children
with cancer should keep in mind that cancer itself and
treatment procedures may have negative psychological
impact and impairment in quality of life among healthy
siblings. Same gender and increased age difference between
the ill and healthy siblings, and treatment intensity
are among the important variables associated with
depression/anxiety and impairment of quality life.
Acknowledgements: The authors would like to thank all
parents and the HSCCs who agreed to take part and made
valuable help to the study.
Declaration of Conflicting Interests: The author(s) declared
no potential conflicts of interest with respect to the
research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the
research, authorship, and/or publication of this article.
Peer-review: Externally peer-reviewed.
Conflict of Interest: None declared.
Ethics Committee Approval: In accordance with the Declaration
of Helsinki, approval for the study was obtained from
the Gaziantep University Ethics Committee on 01.08.2018
(No: 2018/180).
Financial Support: None declared.
Authorship contributions: Concept - A.K., S.A., E.K.,
H.Ö.; Design - A.K., S.A., M.C., E.P.; Supervision - S.A.,
M.C., T.A.; Materials ? E.P., S.A., T.A., E.K.; Data collection
&/or processing - E.P., S.A., T.A., E.K.; Analysis and/or
interpretation - A.K., M.C., E.K.; Literature search - A.K.,
M.C., S.A., H.Ö.; Writing - A.K., M.C., H.Ö.; Critical review
- H.Ö., E.K., M.C.
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