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Author Manuscript
Pediatr Blood Cancer. Author manuscript; available in PMC 2018 April 25.
Published in final edited form as:
Pediatr Blood Cancer. 2015 May ; 62(5): 875–882. doi:10.1002/pbc.25396.
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Concentration, Working Speed and Memory: Cognitive Problems
in Young Childhood Cancer Survivors and Their Siblings
L. Wengenroth, Msc1, C. S. Rueegg, PhD1,2, G. Michel, PhD1,2, M. E. Gianinazzi, PhD1,2, S.
Essig, MD1,3,4, N. X. von der Weid, MD5, M. Grotzer, MD6, and Claudia E. Kuehni, MD,
Msc1,*,a for the Swiss Paediatric Oncology Group SPOG
1Swiss
Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern,
Switzerland 2Department of Health Sciences and Health Policy, University of Lucerne,
Switzerland 3Institute of Primary and Community Care, Lucerne, Switzerland 4Swiss Paraplegic
Research, Nottwil, Switzerland 5Pediatric Hematology/Oncology Unit, University Children’s
Hospital Basel (UKBB), University of Basel, Switzerland 6Department of Oncology, University
Children’s Hospital Zurich, Switzerland
Abstract
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Background—Cognitive problems can have a negative effect on a person’s education, but little
is known about cognitive problems in young childhood cancer survivors (survivors). This study
compared cognitive problems between survivors and their siblings, determined if cognitive
problems decreased during recent treatment periods and identified characteristics associated with
the presence of a cognitive problem in survivors.
Methods—As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was sent to all
survivors, aged 8–20 years, registered in the Swiss Childhood Cancer Registry, diagnosed at age
<16 years, who had survived ≥5 years. Parent-reported (aged 8–15 years) and self-reported (aged
16–20 years) cognitive problems (concentration, working speed, memory) were compared
between survivors and siblings. Multivariable logistic regression was used to identify
characteristics associated with cognitive problems in survivors.
Results—Data from 840 survivors and 247 siblings were analyzed. More often than their
siblings, survivors reported problems with concentration (12% vs. 6%; P = 0.020), slow working
speed (20% vs. 8%; P = 0.001) or memory (33% vs. 15%; P < 0.001). Survivors from all treatment
periods were more likely to report a cognitive problem than were siblings. Survivors of CNS
tumors (OR = 2.82 compared to leukemia survivors, P < 0.001) and those who had received
cranial irradiation (OR = 2.10, P = 0.010) were most severely affected.
*
Correspondence to: Claudia E. Kuehni, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, 3012
Bern, Switzerland. kuehni@ispm.unibe.ch.
aSwiss Paediatric Oncology Group (SPOG) Scientific Committee: Dr. med. R. Angst, Aarau; PD Dr. med. M. Ansari, Geneva; PD Dr.
med. M. Beck Popovic, Lausanne; Dr. med. P. Brazzola, Bellinzona; Dr. med. J. Greiner, St. Gallen; Prof. Dr. med. M. Grotzer,
Zurich; Prof. Dr. med. K. Leibundgut, Bern; Prof. Dr. med. F. Niggli, Zurich; PD Dr. med. J. Rischewski, Lucerne; Prof. Dr. med. N.
von der Weid, Basel.
Conflict of interest: Nothing to declare.
Wengenroth et al.
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Conclusion—Childhood cancer survivors, even those treated recently (2001–2005), remain at
risk to develop cognitive problems, suggesting a need to improve therapies. Survivors with
cognitive problems should be given the opportunity to enter special education programs.
Keywords
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childhood cancer; cognitive outcomes; cohort study; questionnaire survey; siblings; survivors
Introduction
Childhood cancer and its treatment may lead to various cognitive problems [1–4]. In
developed countries, continuous improvements in therapy have increased five-year survival
of childhood cancer to over 80% [5,6] leading to a growing population of long-term
survivors. Because cancer and its treatment can cause adverse effects after the illness has
been cured [7], it is increasingly important to assess long-term somatic outcomes, including
cognitive problems. Cognitive problems with concentration, working speed or memory can
be associated with learning difficulties and diminished educational achievements [8–10].
Previous studies from our group found that survivors of acute lymphoblastic leukemia
(ALL) and central nervous system (CNS) tumors were particularly prone to develop
problems with concentration, working speed and memory [11–14].
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Studies that assessed cognitive problems in survivors were conducted on small nonpopulation based samples [12–16] and included only specific diagnostic groups, like those
with ALL [1,11,17,18], tumors of the central nervous system (CNS) [2,19,20] or
neuroblastoma [21]. Studies that assessed cognitive problems in a large sample of survivors
from different diagnostic groups focused on adult survivors, treated decades ago with
treatment protocols that are no longer in use [3,4]. Young survivors are still attending school
or vocational training, where they need to learn new things every day. Cognitive problems
can severely interfere with a child’s learning process and influence their later educational
achievements [9,10]. There is no population-based study on cognitive problems in young
childhood cancer survivors of all diagnostic groups treated recently.
For our study, we used a representative nationwide cohort approach to (i) compare cognitive
problems (concentration, working speed, memory) in young childhood cancer survivors
including all diagnostic groups and their siblings; (ii) determine if cognitive problems have
decreased in recent treatment periods; and to (iii) identify characteristics associated with
cognitive problems in survivors.
Materials and Methods
The Swiss Childhood Cancer Survivor Study (SCCSS)
The Swiss Childhood Cancer Survivor Study (SCCSS) is a population-based long-term
follow-up study of all patients registered in the Swiss Childhood Cancer Registry (SCCR),
diagnosed 1976–2005 at ≤16 years, who survived ≥5 years after diagnosis [22]. The SCCR
includes all children and adolescents in Switzerland diagnosed with leukemia, lymphoma,
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CNS tumors, malignant solid tumors or Langerhans cell histiocytosis (LCH) before age 16
years [23].
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In 2007–2010, we traced addresses of all survivors who were eligible for the SCCSS,
according to the criteria mentioned above, and sent them a questionnaire [23]. Nonresponders were mailed a second copy of the questionnaire and, if they again failed to
respond, were contacted by phone. In 2010–2011, we again contacted survivors to obtain
consent to contact their siblings. We sent the same questionnaire without cancer related
questions to siblings; those who did not respond were sent a second copy 4–6 weeks after
the first, but were not contacted by phone. Parents of study participants aged ≤15 years
completed the questionnaires for their children. Study participants aged ≥16 years completed
their own questionnaires. Questionnaires were similar to those used in US and UK childhood
cancer survivor studies [24,25]. We added questions about health behaviors and sociodemographic measures from the Swiss Health Survey 2007 [26] and the Swiss Census 2000
[27]. For this study, we included all survivors and siblings from the SCCSS, who were aged
8–20 years at survey.
Approval of the study was granted through the general cancer registry permission of the
SCCR by the ethics committee of the canton of Bern.
Assessment of Socio-Demographic and Clinical Data
For the survivors, we extracted diagnosis, treatment modalities (surgery, chemotherapy,
radiotherapy, bone marrow transplantation), year of treatment start, age at diagnosis,
duration of treatment, time since diagnosis and relapse status from the SCCR. We coded
diagnosis according to international ICCC-3 code [28].
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The following socio-demographic variables for survivors and siblings were assessed by
questionnaire: gender; age at survey; migration background; language region of Switzerland;
parents’ educations; and, current educational situation. Participants who fulfilled one of the
following criteria were coded as having a migration background: not born in Switzerland; no
Swiss citizenship at birth; or, at least one parent with no Swiss citizenship. In Switzerland
different languages are spoken. Language region was coded as German, French, or Italian.
Parents’ education was divided into three categories: primary education (compulsory
schooling only; ≤9 years); secondary education (vocational training or upper secondary
education); and, tertiary education (university or technical college education).
Assessment of Cognitive Problems
In previous studies, we had investigated cognitive problems in subgroups of Swiss childhood
cancer survivors, using standardized instruments. These included the Wechsler test [29] in
150 ALL survivors [11]; and the child behavior checklist (CBCL) [30], the Paediatric quality
of life inventory (PedsQL™) [31], and the Munster Heidelberg Abilites Scale [32] in CNS
survivors [12,14,33]. We found that children were mainly affected in the areas of
concentration, working speed and memory [11,12,14,33]. For the current large-scale
epidemiological study, we thus asked participants the following three questions to assess
cognitive problems: (i) How good is your concentration at school/work? (“Poor” or “not
very good” were coded as reporting a concentration problem; “excellent,” “very good” or
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“good” were coded as no concentration problem); (ii) How fast do you work in comparison
to classmates or colleagues? (“Very slow” or “slow” were coded as reporting slow working
speed; “very fast,” “fast” or “average” were coded as no slow working speed); (iii) Do you
have trouble remembering things? (“Often” was coded as reporting a memory problem;
“never,” “rarely” or “sometimes” were coded as no memory problem).
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For the purpose of multivariable logistic regressions, we built the outcome variable cognitive
problem. Every participant who reported one or more of the three cognitive problems was
coded as reporting a cognitive problem, while participants who did not report any of the
three cognitive problems were coded as not reporting a cognitive problem.
Statistical Analysis
For all analyses, we standardized the sibling population for gender, age at survey, migration
background, language region, and parents’ education, based on the survivor population. To
achieve this standardization we used a multivariable logistic regression, for which survivor
status was used as an outcome to compute weights. These weights ensured that the weighted
marginal distribution of the sibling population was identical for gender, age at survey,
migration background, language region, and parents’ education to the survivor population.
Details on the weighting procedure are described elsewhere [34].
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First, we used F-tests to compare the socio-demographic data and cognitive problems of
survivors and siblings. Second, we calculated multivariable logistic regressions to determine
associations of period of treatment start, treatments and diagnostic groups in survivors with
cognitive problems, while siblings served as the reference population. We used robust
variance estimation for clustered data [35] to account for dependence of observations
between survivors and their siblings. A non-parametric Wilcoxon–type test for trend was
used to determine if cognitive problems have decreased in recent treatment years [36]. Third,
in survivors only, we fitted socio-demographic variables in a multivariable logistic
regression to determine their association with reporting a cognitive problem. Fourth, in
survivors only we added clinical variables to the multivariable logistic regression to
determine their associations with reporting a cognitive problem. Diagnostic groups with n <
50 were summarized in the category “other.” P-values <0.05 were considered as statistically
significant. All analyses were performed with Stata, version 12.1 (StataCorp LP, College
Station, Texas).
Results
Characteristics of the Study Population
We contacted the families of 1,326 survivors and 525 siblings (Fig. 1). Questionnaires were
returned for 882 survivors (67% of those contacted, 63% of those eligible) and 249 siblings
(47% of those contacted, 27% of those eligible). An abridged version of the questionnaire
was completed by 29 survivors; these were not included in this study. Thirteen more
survivors and two siblings had not started school yet, and were excluded. We included in our
analysis data on a total of 840 survivors (440 self-reported, 400 parent-reported) and 247
siblings (140 self-reported, 107 parent-reported).
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The weighting procedure in siblings for gender (P = 0.903), age groups (P = 0.983),
migration background (P = 0.356) language regions (P = 0.861) and parental education (P =
0.822) ensured similar distribution among survivors and siblings (Table I). Of the survivors,
21% attended primary school, 49% attended secondary school, and 30% had already
finished school. These proportions were comparable for siblings (P = 0.460). Of those who
finished school: 81% of survivors and 67% of siblings completed vocational training; 16%
of survivors and 26% of siblings were currently working; and 3% of survivors and 9% of
siblings went to university (P = 0.024). In survivors 5% attended special needs schools
compared to 2% in siblings (P = 0.067).
Leukemia (35%) was the most common cancer among survivors, followed by CNS tumors
(17%) and lymphoma (10%). Most survivors (81%) had received chemotherapy; 64% had
surgery; 23% had radiotherapy (9% including cranial irradiation); and, 5% had bone marrow
transplantations. Mean age at diagnosis was 4.5 years (SD = 3.4), mean duration of
treatment was 465 days (SD = 648) and mean time since diagnosis was 11.4 years (SD =
3.6); period of treatment start was between 1989 and 2005; 11% had a relapse.
Cognitive Problems in Survivors and Siblings
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Cognitive problems were more common in survivors than in siblings. Overall, 40% (n =
333) of survivors, and 22% (n = 54; P < 0.001) of siblings, reported a cognitive problem
(Table II). In survivors, 12% and 6% of siblings reported a concentration problem (P =
0.020); 20% of survivors and 8% of siblings reported slow working speed (P < 0.001); and,
33% of survivors and 15% of siblings reported a memory problem (P < 0.001). When we
stratified for age groups, we found that in children (aged 8–15 years), parent-reported
concentration problems and slow working speed were more frequent in survivors than in
siblings (concentration problem: 14% vs. 5%, P = 0.007; slow working speed: 24% vs. 10%,
P = 0.003). In adolescents (aged 16–20 years), self-reported slow working speed and
memory problems were more frequent in survivors than in siblings (slow working speed:
15% vs. 6%, P = 0.008; memory problem: 29% vs. 3%, P < 0.001). The results for each
answer category of the three cognitive problems are displayed in the supplement
(Supplemental Table I).
In general, survivors were more likely to report a cognitive problem than siblings (OR =
2.48, P < 0.001; Fig. 2), also when stratified by periods of treatment start (1989–1995: OR =
3.08, 1996–2000: OR = 2.41, 2001–2005: OR = 2.32; P < 0.001 each). There was a nonsignificant trend for less cognitive problems in more recent periods (non-parametric test for
trend; P = 0.062). Regardless of the type of treatment, survivors were significantly more
likely to report cognitive problems compared to siblings. Survivors of the following
diagnostic groups were mainly affected: Leukemia (OR = 2.33, P < 0.001); lymphoma (OR
= 1.83, P = 0.041); CNS tumors (OR = 6.27, P < 0.001); neuroblastoma (OR = 2.17, P =
0.024); and renal or hepatic tumors (OR = 2.16, P = 0.009).
Predictors for Cognitive Problems in Survivors
Among survivors, adolescents were less likely to report a cognitive problem than were
children (OR = 0.70, P = 0.015; Table III). Gender, migration background, language region
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and parents’ education were not significantly associated with reporting cognitive problems.
Compared to survivors of leukemia, survivors of CNS tumors were more likely to report a
cognitive problem (OR = 2.82, P < 0.001). Compared to survivors without radiotherapy,
survivors who had received cranial irradiation were more likely to report a cognitive
problem (OR = 2.10, P = 0.010). Among survivors treatment with chemotherapy or bone
marrow transplants, period of treatment start, age at diagnosis, duration of treatment, time
since diagnosis and relapse status were not significantly associated with reporting cognitive
problems.
Discussion
This survey of children and adolescents who had survived cancer found that survivors, even
those treated recently with modern protocols, reported cognitive problems more often than
siblings. Survivors of CNS tumors and those treated with cranial irradiation were most
affected. Although other studies looked at cognitive problems in specific diagnostic groups
of young survivors [1,11,17–21], we found no study that had surveyed concentration,
working speed and memory problems in young survivors of all diagnostic groups and
siblings.
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It is known that adult survivors report more cognitive problems than siblings [3]. In addition,
we found that in children, where cognitive problems were parent-reported, concentration
problems and slow working speed were more frequent in survivors than in siblings, while in
adolescents who self-reported cognitive problems, slow working speed and memory
problems were more frequent in survivors than in siblings. This difference may be due to a
different perception of cognitive problems. Teachers of children with low working memory
described these children as having poor concentration (highly inattentive, poor attention
span, high levels of distractibility) [37]. Further, those cognitive problems are closely
related. A study showed that children with attention problems also had impaired working
memory [38]. Among survivors, adolescents were less likely to report any cognitive problem
than were parents who reported for younger children. Adolescents may evaluate their
cognitive abilities differently than their parents. This has been shown for quality of life,
where parents sometimes report poorer quality of life for their children than these report for
themselves [39,40].
Survivors of CNS tumors had the highest risk for cognitive problems, which is well known
[19]. In an earlier SCCSS study, we also found lower levels of education in adult survivors
of CNS tumors than in healthy peers [41]. In this study, we additionally found that survivors
of leukemia, neuroblastoma, and renal or hepatic tumors were more likely to report cognitive
problems than siblings. For neuroblastoma survivors, especially those with hearing loss, an
increased risk of learning problems has also been reported from the US [21]. Survivors of
leukemia treated with cranial irradiation had significantly worse results for short-term verbal
memory, arithmetics, concentration and speed of processing [11]. A study from the US
found that memory problems were more frequent in survivors of non-CNS cancers (12.5%),
including survivors of leukemia, lymphoma and neuroblastoma than in siblings (7.6%) [4].
In this study, we surveyed only a small number of survivors of renal (n = 73) and hepatic
tumors (n = 11). Further research is necessary for these diagnostic groups. Survivors treated
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with cranial irradiation were more likely to report cognitive problems than survivors who
received no irradiation. These results accord with studies from other cohorts [16] and from
previous studies from our group: In 150 ALL survivors, we found that irradiated survivors
had worse scores on short-term verbal memory, arithmetics, concentration and speed of
processing than survivors who were not irradiated [11]. Survivors of medulloblastoma who
had been treated with cranial irradiation showed significant impairment in at least one
neurocognitive function (attention and processing speed, learning and memory, language,
visual perception, and executive functions) [12].
Survivors treated with radiotherapy, but also those treated with surgery or chemotherapy
alone were more likely to report cognitive problems than siblings. This has also been shown
for ALL survivors treated with chemotherapy alone: They had neurocognitive impairments
[42], smaller volumes of neocortical and subcortical grey matter, and lower hippocampal
memory performance [43]. Treatments for childhood cancer patients improved over time:
Modern protocols include less damaging irradiation, make use of stereotactic radiosurgery or
fractionated stereotactic radiotherapy for CNS tumors [44] and reduce prophylactic CNS
irradiation in patients of ALL [1]. Despite these improvements, we found cognitive
problems even in survivors treated recently. However, the OR decreased slightly from 3.08
(1989–1995) to 2.41 (1996–2000) and 2.32 (2001–2005), with a borderline significant test
for trend (P = 0.062). Continuous research is needed to determine whether these
newtreatments have really caused less cognitive impairments.
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Patients should be asked about cognitive problems during follow-up, since they can lead to
health-related unemployment and less-skilled work in adult survivors [45]. Assessing
cognitive problems in detail could assist hospital schools or special education services in
tailoring individual support. Intervention studies from the US showed that targeted
interventions can reduce cognitive problems in survivors [46–48]. Home-based
computerized working memory training increased visual memory and reduced parentreported learning problems in survivors of CNS tumors and ALL [46]. Cognitive
remediation programs increased survivors’ academic achievements [47], and changed brain
activity in survivors of CNS tumors [48]. Intervention programs and remediation programs
are feasible: 60% to 75% of survivors completed all training sessions [46,47]. Home-based
computerized training is also feasible [46] and allows survivors who live in remote areas
access to materials on their own schedule. Programs could be offered while patients are
treated in hospital schools, or as special education programs in mainstream schools soon
after the patient is finished with therapy.
Our study has some limitations. First, response in siblings was lower than in survivors, so
our sample might not accurately represent the whole sibling population. We tried to
overcome this limitation by weighing the sibling population for socio-demographic factors.
Second, because questions on cognitive problems were self-reported for adolescents, and
parent-reported for children, we cannot be sure if the lower risk of cognitive problems in
adolescents is due to the fact they were older at the time of survey, or due to bias introduced
by comparing self- to parent-reported cognitive problems. To differentiate the effect of age
and self-vs-parent-reports, we would need longitudinal data, with repeated parental and selfassessments for the same individuals. Further, our questions on cognitive problems are not
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validated, because we lacked the space to include lengthy standardized instruments in the
current multipurpose questionnaire. Thus we developed short questions covering the areas
which had been most affected in our previous studies, where we had used standardized
instruments, that is, concentration, working speed and memory [11–14]. Last, we could not
retrieve the exact dose of chemotherapy survivors had received, and so could not determine
if dosage affected cognitive impairment.
A strength of our study is its large representative population-based sample of 5-year
survivors covering all diagnostic groups. Further, we were able to include survivors who had
been treated in different time periods, including recent periods with modern treatment
protocols. Finally, we assessed different cognitive problems (concentration, working speed,
memory) separately and then combined them, in order to capture all types of cognitive
problems, irrespective of how they were perceived and described by the study participant.
Conclusion
Young survivors, between 8 and 20 years old, of several diagnostic groups were more likely
to report cognitive problems than were their siblings. In addition to survivors of CNS
tumors, survivors of leukemia, neuroblastoma and renal or hepatic tumors were also
affected. Cranial irradiation was confirmed as the most important treatment-related risk
factor for cognitive problems. Although our study population has been treated fairly recently
(between 1989 and 2005), cognitive problems were still common, suggesting a remaining
need to improve therapies. Survivors who report cognitive problems should be identified
early and be given the opportunity to enter special education programs.
Supplementary Material
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Refer to Web version on PubMed Central for supplementary material.
Acknowledgments
We thank all childhood cancer survivors and families for participating in our survey. We thank the study team of the
SCCSS (Erika Brantschen-Berclaz, Julia Koch, Fabienne Liechti), the data managers of the SPOG (Claudia
Anderegg, Nadine Beusch, Rosa-Emma Garcia, Franziska Hochreutener, Friedgard Julmy, Nadine Lanz, Heike
Markiewicz, Genevieve Perrenoud, Annette Reinberger, Renate Siegenthaler and Verena Stahel) and the team of the
SCCR (Vera Mitter, Elisabeth Kiraly, Marlen Spring, Christina Krenger, Priska Wölfli). We thank Ben Spycher and
Marcel Zwahlen for their statistical advice, and Kali Tal for her editorial assistance. This study was supported by
Cancer League Aargau, the Bernese Cancer League and Swiss Cancer Research (grant 02631-08-2010). GM and
SE were funded by the Swiss National Science Foundation (GM: Ambizione-Fellowship-grant PZ00P3_121682,
PZ00P3-141722, SE: MD-PhD-grant 323630-133897; www.snf.ch) and Swiss Cancer Research (SE: MD-PhDgrant 02606-06-2010; www.krebsforschung.ch; MG: grant 02631-08-2010). The work of the SCCR is supported by
the Swiss Paediatric Oncology Group, GDK, Swiss Cancer Research, Kinderkrebshilfe Schweiz, Ernst-Göhner
Stiftung, Stiftung Domarena, CSL Behring and National Institute of Cancer Epidemiology and Registration.
Grant sponsor: Cancer League Aargau; Grant sponsor: Bernese Cancer League; Grant sponsor: Swiss National
Science Foundation; Grant numbers: PZ00P3_121682; PZ00P3-141722; 323630-133897; Grant sponsor: Swiss
Cancer Research; Grant numbers: 02606-06-2010
Abbreviations
ALL
Acute lymphoblastic leukemia
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CBCL
Child behavior checklist
CNS
Central nervous system
ICCC-3
International Classification of Childhood Cancer, Third edition
LCH
Langerhans cell histiocytosis
PedsQL
Paediatric quality of life inventory
SCCR
Swiss Childhood Cancer Registry
SCCSS
Swiss Childhood Cancer Survivor Study
UK
United Kingdom
US
United States
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Fig. 1.
Study participants.
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Fig. 2.
Reporting of any cognitive problem in survivors compared to siblings, overall and stratified
by period of diagnoses, treatment and diagnoses. Odds ratios are retrieved from four
multivariable logistic regressions: 1. SURVIVORS: OR for being a survivor compared to
being a sibling; 2. PERIOD OF TREATMENT: OR for having had the diagnoses in the
period 2001–2005, 1996–2000 or 1989–1995 compared to being a sibling; 3. TREATMENT:
OR for having had surgery only, chemotherapy (may include surgery), radiotherapy (may
include surgery and/or chemotherapy or bone marrow transplantation (may include surgery,
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and/or chemotherapy and/or radiotherapy) compared to siblings; 4. DIAGNOSES: OR for
having a diagnosis of leukemia, lymphoma, CNS tumor, neuroblastoma, retinoblastoma,
renal/hepatic tumor, bone tumor, soft tissue sarcoma, germ cell tumor, other tumor or
Langerhans cell hystiocytosis compared to being a sibling. All regressions were controlled
for gender, age at survey, migration background, language region, parents’ education. The
siblings’ population is standardized on age, gender, migration background, language region
and parents’ education according to the survivor population. Family clusters were used to
adjust standard errors for the fact that siblings were not independent from survivors.
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Table I
Characteristics of Survivors and Siblings
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Survivors
Siblingsa
N=840
N=247
n
(%b)
n
(%b)
P-valuec
Socio-demographic characteristics used for standardization of sibling population
Female gender
379
(45)
110
(45)
0.903
8–15
400
(48)
118
(48)
16–20
440
(52)
129
(52)
0.983
113
(13)
27
(11)
0.356
German
578
(69)
173
(70)
French
234
(28)
66
(27)
Italian
26
(3)
8
(3)
Age at survey (years)
Migration background
Language region
0.861
Parental Education
Primary education
66
(8)
17
(7)
Secondary education
532
(66)
164
(67)
Tertiary education
211
(26)
62
(26)
Primary school
170
(21)
49
(20)
Secondary school
394
(49)
109
(46)
Finished school
237
(30)
82
(34)
0.822
Educational characteristics
Educational situation
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Vocational training
192
(81)
55
(67)
Work
37
(16)
19
(26)
University
0.460
8
(3)
8
(9)
0.024
42
(5)
4
(2)
0.067
I Leukemia
295
(35)
II Lymphoma
88
(10)
III CNS
145
(17)
n.ad
n.ad
n.ad
IV Neuroblastoma
59
(7)
V Retinoblastoma
38
(5)
VI Renal tumor
73
(9)
VII Hepatic tumor
11
(1)
VIII Bone tumor
20
(2)
IX Soft tissue sarcoma
47
(6)
X Germ cell tumor
22
(3)
XI & XII Other tumorse
10
(1)
Ever attended special needs school
Clinical characteristics
Diagnosis (ICCC-3)
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Survivors
Siblingsa
N=840
N=247
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n
(%b)
n
(%b)
P-valuec
32
(4)
Received chemotherapy
682
(81)
n.ad
n.ad
n.ad
Received surgery
539
(64)
n.ad
n.ad
n.ad
No
644
(77)
n.ad
n.ad
n.ad
Yes, excluding cranial
118
(14)
Yes, including cranial
78
(9)
38
(5)
n.ad
n.ad
n.ad
1989–1995
176
(21)
n.ad
n.ad
n.ad
1996–2000
296
(35)
2001–2005
368
(44)
0–5
595
(71)
n.ad
n.ad
n.ad
>5–10
187
(22)
>10–15
58
(7)
≤100
290
(35)
n.ad
n.ad
n.ad
>100–<500
267
(32)
≥500
280
(33)
5–10 years
353
(42)
n.ad
n.ad
n.ad
11–15 years
321
(38)
16–<20 years
166
(20)
95
(11)
n.ad
n.ad
n.ad
Langerhans cell histiocytosis
Received radiotherapy
Received bone marrow transplantation
Period of treatment start (calendar year)
Age at diagnosis (years)
Duration of treatment (days)
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Time since diagnosis (years)
Had relapse
CNS, Central Nervous System; ICCC-3, International Classification of Childhood Cancer, Third Edition; n, number; n.a., not applicable/not
available. Percentages are based upon available data for each variable.
a
Sibling population is standardized on age, gender, migration background, language region and parents’ education according to the survivor
population
b
c
P-value calculated from F-test statistics that compare survivors and siblings
d
e
Column percentages are given
Information on former cancer disease does not apply
Other malignant epithelial neoplasms, malignant melanomas, and other or unspecified malignant neoplasms.
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Table II
All (8–20 years) Parent- and self-reported
Survivors n (%)b
Concentration problem
Pediatr Blood Cancer. Author manuscript; available in PMC 2018 April 25.
a
Pc
Pc
Survivors n (%)b
Siblingsa n (%)b
59 (14)
6 (5)
0.007
Adolescents (16–20 years) Self-reported
Survivors n (%)b
Siblingsa n (%)b
39 (9)
10 (7)
Pc
98 (12)
16 (6)
0.020
0.589
Slow working speed
162 (20)
19 (8)
<0.001
96 (24)
11 (10)
0.003
66 (15)
8 (6)
0.008
Memory problem
269 (33)
37 (15)
<0.001
144 (37)
31 (29)
0.145
125 (29)
4 (3)
<0.001
Any cognitive problemd
333 (40)
54 (22)
<0.001
176 (45)
32 (31)
0.018
157 (36)
19 (14)
<0.001
Sibling population is standardized on age, gender, migration background, language region and parents’ education according to the survivor population
b
c
Siblingsa n (%)b
Children (8–15 years) Parent-reported
Wengenroth et al.
Cognitive Problems in Survivors and Siblings
Column percentages are given
P-value calculated from chi-square statistics comparing survivors and siblings
d
Any cognitive problem was coded as reporting at least one of the three problems (concentration problem, slow working speed, memory problem).
Page 17
Wengenroth et al.
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Table III
Predictors for reporting a Cognitive Problem in Survivors in Logistic Multivariable
Analysis
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ORa
95%CIb
P-value
0.62–1.11
0.201
0.52–0.93
0.015
0.47–1.22
0.253
Socio-demographic predictorsc
Gender
Male
1
Female
0.83
Age at survey
Children (8–15 years)
Adolescents (16–21 years)
1
0.70
Migration background
No
1
Yes
0.76
Language region
German
1
French
0.99
0.72–1.37
0.972
Italian
1.15
0.52–2.55
0.724
0.76
0.43–1.35
0.352
0.55–1.06
0.111
Parents’ education
primary
secondary
1
tertiary
0.76
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Clinical predictorsd
Diagnosis
Leukemia
1
Lymphoma
0.69
0.37–1.29
0.243
CNS
2.82
1.58–5.04
<0.001
Neuroblastoma
0.90
0.44–1.82
0.762
Renal/hepatic tumors
0.73
0.39–1.38
0.336
Other
0.61
0.36–1.06
0.078
0.96–2.66
0.072
Chemotherapy
No
1
Yes
1.60
Radiotherapy
No
1
Yes, excluding cranial
1.22
0.77–1.93
0.405
Yes, including cranial
2.10
1.20–3.68
0.010
0.52–2.23
0.838
Bone marrow transplantation
No
1
Yes
1.08
Period of treatment
start (calendar year)
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ORa
95%CIb
P-value
1989–1995
1.05
0.43–2.56
0.906
1996–2000
0.75
0.41–1.38
0.350
2001–2005
1
Age at diagnosis (years)
0–5
1
>5–10
1.00
0.61–1.62
0.990
>10–16
0.77
0.33–1.79
0.547
Duration of treatment (days)
<100
1
100–500
0.69
0.43–1.10
0.119
>500
0.73
0.39–1.38
0.336
Time since diagnosis (years)
5–10
1
11–15
1.42
0.78–2.59
0.251
16–<20
1.20
0.51–2.81
0.682
0.69–1.93
0.592
Relapse
a
1
Yes
1.15
Odds Ratio
b
c
No
95% confidence interval
ORs retrieved from multivariable logistic regression
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d
ORs retrieved from multivariable logistic regression controlled for gender, age at survey, migration background, language region and parents’
education.
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