Discussion
The aims of the current study were to evaluate group differences in
social adjustment across three groups of children (survivors of ALL,
survivor siblings, controls, control siblings), to examine
disease-related predictors of social adjustment in survivors, and to
explore executive functioning as a potential mediator of these
relationships. Results suggested that survivors of ALL had greater
social withdrawal (i.e., poorer social adjustment) compared to controls
and the siblings of those controls. This finding was consistent with our
hypothesis and with previous literature that has identified social
adjustment difficulties among survivors of pediatric
ALL.6-8 Importantly, when we examined the frequency of
those reporting social difficulties within the clinical range (i.e.,
>60) 26% of survivors did report social withdrawal within
the clinical range compared to only 10% of controls. Thus, the social
adjustment of survivors of ALL warrants greater clinical and research
attention.
Importantly, our hypothesis that executive functioning would be
associated with social adjustment among survivors as proposed by the
Social Competence Model,9 was supported by our second
aim. The current study provides preliminary evidence for the application
of the Social Competence Model to survivors of pediatric ALL. What is
unique about the current study from previous literature, however, is
that none of our current sample of survivors of ALL had received
radiotherapy. This finding suggests, therefore, that despite a move
towards less toxic therapy for survivors of ALL, social adjustment
difficulties remain.
The story does appear to be slightly more complex, however, among
survivors of ALL. Although executive function emerged as a significant
predictor of social adjustment among survivors of ALL, executive
function did not explain differences in social withdrawal between
survivors, siblings and controls. This has important implications for
the Social Competence Model as well as for our understanding of social
adjustment difficulties in survivors of ALL. First, our findings
strengthen the applicability of the Social Competence Model by
confirming the relationship of executive function to social adjustment,
irrespective of acquired brain injury. In other words, this relationship
holds among clinical and healthy populations. In order to understand the
difference in social adjustment scores between survivors and healthy
controls, therefore, consideration of treatment-related variables may be
key. For example, it might be important to consider chemotherapy dosage.
In addition, little research has explored the indirect effects of a
diagnosis of ALL and the consequences of the several years of treatment
required to cure ALL and the implications this might have on social
development.
The literature exploring non-treatment factors associated with social
adjustment in survivors of pediatric ALL is more variable. Some evidence
suggests that demographic variables such as ethnicity, marital status,
parent education, and household income may play a role in social
adjustment outcomes.34-37 The literature examining sex
and social adjustment outcomes in survivors of ALL has revealed
inconsistent findings.22,37,38 Individual and family
factors, such as survivor and parent mental health (e.g., mood, anxiety,
posttraumatic growth),39,40 and parenting
stress,36 have been associated with social adjustment
in this population and require further investigation. Importantly, given
our current findings, it would be critical to also explore how such
family factors may be related to sibling social adjustment. Knowledge
about both treatment and non-treatment factors associated with social
adjustment are important to inform risk-based screening guidelines and
targets for intervention.
One of the most surprising findings from the study was that survivors
did not differ in their social adjustment compared to their siblings.
This finding was not consistent with our hypotheses. Certainly, the
siblings of pediatric cancer patients are not immune to the experience
of cancer within the family and have been shown to exhibit increased
levels of emotional distress and behavioral
problems.41,42 In addition, previous research among a
heterogenous sample of pediatric cancer survivors found no differences
between survivors and siblings with respect to social
adjustment.43 It is important to keep in mind,
however, our population of survivors in the acute survivorship phase
(2-7 years post treatment). Knowing the extensive literature documenting
the delayed onset of cognitive deficits, so too might we expect to see
the social adjustment of survivors worsen the further off treatment they
might be.
This study was not without limitations. To begin, we had small samples
to test for these effects, specifically for the survivor sibling group.
This study is limited by its cross-sectional design which precludes any
conclusions to be made about causal factors of social adjustment
difficulties. Mediation models typically imply a sequence of events
occurring over time; in the current study we were not able to capture
potential ‘true’ mediation given this design limitation. Longitudinal
research is needed to explore the trajectory of social adjustment
difficulties for survivors of pediatric ALL and to being to explore
mechanisms that may explain this relationship. In addition, although the
control groups were a relative strength of the study, we did not compare
survivors of ALL to survivors of cancer who do not receive toxic
therapies directed at the CNS. Survivors of childhood cancer who did not
receive toxic therapies directed at the CNS would have provided a more
conservative control group as they have both experienced a traumatic
cancer diagnosis and been treated with chemotherapies that lead to
socially limiting side effects (e.g., hair loss and compromised immunity
limiting their ability to be in public places or school environments).
However, without having received therapies believed to be centrally
neurotoxic, the effects of CNS-directed treatment on social adjustment
could have been more clearly differentiated in survivors of ALL. In
addition, while we were able to examine outcomes of survivors based on
disease risk status, we did not have specific dosage information for
therapies known to be neuro-toxic, including methotrexate and
intrathecal chemotherapies. Finally, the study did not explore
non-treatment-related factors that might also contribute to social
functioning in this population. Future research should aim to explore
the other factors that might be related to social function among this
population with a specific focus on both treatment- and
non-treatment-related factors.
In conclusion, survivors of pediatric ALL are at risk of more social
difficulties compared to non-cancer controls. Predictors of social
adjustment among survivors included executive functioning and time off
treatment. However, executive functioning did not explain any of the
observed group differences in social adjustment. This is an important
finding among a sample of survivors 2-7 years from the completion of
therapy who did not receive CRT and highlights the potential persistent
toxicity of therapy for pediatric ALL despite efforts to reduce
treatment-related toxicity. Based on the current findings, survivors of
pediatric ALL presenting to follow-up programs should be screened for
difficulties with social adjustment. Future research should aim to more
comprehensively examine the potential multiple factors that may
contribute to poorer social adjustment outcomes in order to identify
modifiable targets for interventions.
Acknowledgements: This work was supported by the Alberta Children’s
Hospital Research Institute 2015-16 ARC Award in Family Centered Care.
Conflict of Interest Statement
None to disclose.
Data Availability Statement
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
References
1. Phillips SM, Padgett LS, Leisenring WM, et al. Survivors of childhood
cancer in the United States: prevalence and burden of morbidity.Cancer Epidemiol Biomarkers Prev. 2015;24(4):653-663.
2. Cooper SL, Brown PA. Treatment of pediatric acute lymphoblastic
leukemia. Pediatr Clin North Am. 2015;62(1):61-73.
3. van der Plas E, Nieman BJ, Butcher DT, et al. Neurocognitive Late
Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia:
Focus on Methotrexate. J Can Acad Child Adolesc Psychiatry.2015;24(1):25-32.
4. Kerr JZ, Berg S, Blaney SM. Intrathecal chemotherapy. Crit Rev
Oncol Hematol. 2001;37(3):227-236.
5. Phillips NS, Cheung YT, Glass JO, et al. Neuroanatomical
abnormalities related to dexamethasone exposure in survivors of
childhood acute lymphoblastic leukemia. Pediatr Blood Cancer.2019:e27968.
6. Gurney JG, Krull KR, Kadan-Lottick N, et al. Social Outcomes in the
Childhood Cancer Survivor Study Cohort. Journal of Clinical
Oncology. 2009;27(14):2390-2395.
7. Gunn ME, Lahteenmaki PM, Puukko-Viertomies LR, Henriksson M,
Heikkinen R, Jahnukainen K. Potential gonadotoxicity of treatment in
relation to quality of life and mental well-being of male survivors of
childhood acute lymphoblastic leukemia. J Cancer Surviv.2013;7(3):404-412.
8. Schultz KAP, Ness KK, Whitton J, et al. Behavioral and social
outcomes in adolescent survivors of childhood cancer: a report from the
childhood cancer survivor study. Journal of clinical oncology :
official journal of the American Society of Clinical Oncology.2007;25:3649-3656.
9. Yeates KO, Bigler ED, Dennis M, et al. Social outcomes in childhood
brain disorder: A heuristic integration of social neuroscience and
developmental psychology. Psychological Bulletin.2007;133:535-556.
10. Noll RB, Bukowski WM, Davies WH, Koontz K, Kulkarni R. Adjustment in
the peer system of adolescents with cancer: A two-year study.Journal of Pediatric Psychology. 1993;18:351-364.
11. Katz LF, Leary A, Breiger D, Friedman D. Pediatric cancer and the
quality of children’s dyadic peer interactions. J Pediatr
Psychol. 2011;36(2):237-247.
12. Pendley JS, Dahlquist LM, Dreyer Z. Body image and psychosocial
adjustment in adolescent cancer survivors. J Pediatr Psychol.1997;22(1):29-43.
13. Robison LL. Late effects of acute lymphoblastic leukemia therapy in
patients diagnosed at 0-20 years of age. Hematology Am Soc Hematol
Educ Program. 2011;2011:238-242.
14. Mitby PA, Robison LL, Whitton JA, et al. Utilization of special
education services and educational attainment among long-term survivors
of childhood cancer: a report from the Childhood Cancer Survivor Study.Cancer. 2003;97:1115-1126.
15. Mody R, Li S, Dover DC, et al. Twenty-five-year follow-up among
survivors of childhood acute lymphoblastic leukemia: a report from the
Childhood Cancer Survivor Study. Blood. 2008;111(12):5515-5523.
16. Janson C, Leisenring W, Cox C, et al. Predictors of marriage and
divorce in adult survivors of childhood cancers: a report from the
Childhood Cancer Survivor Study. Cancer epidemiology, biomarkers
& prevention : a publication of the American Association for Cancer
Research, cosponsored by the American Society of Preventive Oncology.2009;18:2626-2635.
17. Schatz J, Kramer JH, Ablin A, Matthay KK. Processing speed, working
memory, and IQ: A developmental model of cognitive deficits following
cranial radiation therapy. Neuropsychology. 2000;14:189-200.
18. Mulhern RK, Butler RW. Neurocogntive sequelae of childhood cancers
and their treatment. Pediatric Rehabilitation. 2004;7:1-14.
19. Campbell LK, Scaduto M, Sharp W, et al. A meta-analysis of the
neurocognitive sequelae of treatment for childhood acute lymphocytic
leukemia. Pediatr Blood Cancer. 2007;49(1):65-73.
20. Iyer NS, Balsamo LM, Bracken MB, Kadan-Lottick NS. Chemotherapy-only
treatment effects on long-term neurocognitive functioning in childhood
ALL survivors: a review and meta-analysis. Blood.2015;126(3):346-353.
21. Krull KR, Cheung YT, Liu W, et al. Chemotherapy Pharmacodynamics and
Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of
Childhood Acute Lymphoblastic Leukemia. J Clin Oncol.2016;34(22):2644-2653.
22. Moyer KH, Willard VW, Gross AM, et al. The impact of attention on
social functioning in survivors of pediatric acute lymphoblastic
leukemia and brain tumors. Pediatric blood & cancer.2012;59:1290-1295.
23. Robinson KE, Fountain-Zaragoza S, Dennis M, et al. Executive
functions and theory of mind as predictors of social adjustment in
childhood traumatic brain injury. Journal of neurotrauma.2014;31:1835-1842.
24. Heverly-Fitt S, Rubin KH, Dennis M, et al. Investigating a Proposed
Model of Social Competence in Children With Traumatic Brain Injuries.J Pediatr Psychol. 2016;41(2):235-243.
25. Anderson V, Gomes A, Greenham M, et al. Social competence following
pediatric stroke: contributions of brain insult and family environment.Soc Neurosci. 2014;9(5):471-483.
26. Rantanen K, Eriksson K, Nieminen P. Social competence in children
with epilepsy–a review. Epilepsy Behav. 2012;24(3):295-303.
27. Schulte F, Vannatta K, Barrera M. Social problem solving and social
performance after a group social skills intervention for childhood brain
tumor survivors. Psychooncology. 2014;23(2):183-189.
28. Russell KB, Merz EL, Reynolds K, Schulte F, Tomfohr-Madsen L. Sleep
Disturbances in Survivors of Pediatric Acute Lymphoblastic Leukemia and
Their Siblings. J Pediatr Psychol. 2020;45(7):707-716.
29. Reynolds CR, Kamphaus RW. Behavior Assessment System for
Children (BASC-3). 3rd Edition ed. Bloomington: NCS Pearson Inc.; 2015.
30. Wolfe-Christensen C, Mullins LL, Stinnett TA, Carpentier MY, Fedele
DA. Use of the behavioral assessment system for children 2nd Edition:
Parent report scale in pediatric cancer populations. Journal of
Clinical Psychology in Medical Settings. 2009;16:322-330.
31. Gioia GA, Isquith PK, Guy SC, Kenworthy l. Behavior Rating
Inventory of Executive Function (BRIEF-2). 2nd Edition ed. Lutz, FL:
PAR Inc.; 2015.
32. Kenny DA, Kashy DA. Dyadic data analysis using multilevel modeling.
In: Hox JJ, Roberts JK, eds. European Association for Methodology
series: Handbook for advanced multilevel analysis. Routledge/Taylor &
Francis Group; 2010:335-370.
33. Hayes AF. Introduction to mediation, moderation, and
conditional process analysis. 2nd Edition ed. New York: The Guilford
Press; 2017.
34. Choo CC, Chew PKH, Tan P, et al. Health-Related Quality of Life in
Pediatric Patients with Leukemia in Singapore: A Cross-Sectional Pilot
Study. Int J Environ Res Public Health. 2019;16(12).
35. Hamidah A, Sham Marina M, Tamil AM, et al. Parental reports of
behavioural outcome among paediatric leukaemia survivors in Malaysia: a
single institution experience. Trop Med Int Health.2014;19(10):1177-1184.
36. Hile S, Erickson SJ, Agee B, Annett RD. Parental stress predicts
functional outcome in pediatric cancer survivors. Psychooncology.2014;23(10):1157-1164.
37. Kunin-Batson A, Kadan-Lottick N, Neglia JP. The contribution of
neurocognitive functioning to quality of life after childhood acute
lymphoblastic leukemia. Psychooncology. 2014;23(6):692-699.
38. Vannatta K, Gerhardt CA, Wells RJ, Noll RB. Intensity of CNS
treatment for pediatric cancer: prediction of social outcomes in
survivors. Pediatr Blood Cancer. 2007;49(5):716-722.
39. Kazak AE, Barakat LP, Meeske K, et al. Posttraumatic stress, family
functioning, and social support in survivors of childhood leukemia and
their mothers and fathers. J Consult Clin Psychol.1997;65(1):120-129.
40. Khalifa AS, Bishry Z, Tantawy AA, et al. Psychiatric morbidity in
Egyptian children with acute lymphoblastic leukemia and their care
providers. Hematol Oncol Stem Cell Ther. 2014;7(2):76-84.
41. Alderfer MA, Long KA, Lown EA, et al. Psychosocial adjustment of
siblings of children with cancer: a systematic review.Psychooncology. 2010;19(8):789-805.
42. Schulte F, Wurz A, Reynolds K, Strother D, Dewey D. Quality of Life
in Survivors of Pediatric Cancer and Their Siblings: The Consensus
Between Parent-Proxy and Self-Reports. Pediatr Blood Cancer.2016;63(4):677-683.
43. Schulte F, Wurz A, Russell KB, Reynolds K, Strother D, Dewey D.
Social adjustment and repressive adaptive style in survivors of
pediatric cancer. J Psychosoc Oncol. 2018;36(3):274-286.