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5 The Impact of Sex and Associations With Treatment Exposures on Neurocognitive Impairment in Pediatric Cancer Survivors: A report from the Childhood Cancer Survivor Study
- Rachel K Peterson, Yan Chen, Kevin Oeffinger, Yutaka Yasui, Wendy Leisenring, Gregory T Armstrong, Leslie L Robison, Rebecca M Howell, Sogol Mostoufi-Moab, Jordan Gilleland Marchak, Kevin R. Krull, Kim Edelstein
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 315-316
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- Article
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Objective:
Sexual dimorphism in human brain structure and behavior is influenced by exposure to sex hormones during critical developmental periods. In children, cancer and cancer treatments may alter hormone activity and brain development, impacting neurocognitive functions.
Participants and Methods:Five-year survivors of childhood cancer (N=15,560) diagnosed at <21 years from 1970 to 1999, and 3,206 siblings from the Childhood Cancer Survivor Study completed the Neurocognitive Questionnaire (NCQ), a measure of self-reported task efficiency (TE), emotion regulation (ER), Organization, and working memory (WM). We compared rates of cognitive impairment (i.e., NCQ scores >90th percentile) in survivors and same-sex siblings, and sex differences in risk factors for cognitive impairment (i.e., treatment exposures, chronic health conditions (CHCs), cancer diagnosis, age at diagnosis) using modified Poisson regressions.
Results:Survivors were more likely to report cognitive impairment than same-sex siblings (Males: TE OR=2.3, p<.001; ER OR=1.7, p=.008; Organization OR=1.5, p=.04; WM OR=2.3, p<.001. Females: TE OR=2.6, p<.001; ER OR=1.9, p<.001; Organization OR=1.5, p=.02; WM OR=2.6, p<.001). Within survivors, females were more likely than males to report impairment in TE (OR=1.2, p=.001), ER (OR=1.5, p<.001), and WM (OR=1.2, p<.001). There were no sex differences in symptom severity in siblings (all ps>.05). Risk factors for cognitive impairment in survivors included cranial radiation dose (TE <20Gy OR=1.5, p=.008, ≥20Gy OR=2.5, p<.001; ER OR=1.5, p<.001; Organization <20 Gy OR=1.4, p<.001; < WM 20 Gy OR=1.8, p<.001, ≥20Gy OR=2.7, p<.001), presence of moderate to severe CHCs (TE 1 CHC OR=1.9, p<.001, >1 CHC OR=3.6, p<.001; ER 1 CHC OR=1.7, p<.001, >1 CHC OR=2.2, p<.001; Organization 1 CHC OR=1.5, p=.001, >1 CHC OR=2.5, p<.001; WM 1 CHC OR=1.8, p<.001, >1 CHC OR=4.1, p<.001). There were sex differences in cognitive impairment risk factors in survivors. In females, cranial radiation dose (<20 Gy TE OR=1.6, p=.02; ≥20Gy TE OR=1.4, p=.01), leukemia diagnosis (TE OR=1.4, p=.02), or diagnosis age between 3-5 years (WM OR=1.4, p=.02) conferred higher risk for cognitive impairment compared to males with the same history. Females diagnosed with Hodgkin’s lymphoma (Organization OR=0.61, p=.05) or non-Hodgkin’s lymphoma (Organization OR=0.55, p=.03) were at lower risk for cognitive impairment compared to males.
Conclusions:We found sex-specific differences in rates of, and risk factors for, neurocognitive impairment, suggesting a sex vulnerability. Future studies examining interactions between sex hormones and treatment exposures during brain development will enable tailoring treatments follow-up interventions to ensure that quality of life is maximized.
Impact of enucleation on adult retinoblastoma survivors’ quality of life: A qualitative study of survivors' perspectives
- Smita C. Banerjee, Elaine Pottenger, Mary Petriccione, Joanne F. Chou, Jennifer S. Ford, Charles A. Sklar, Leslie L. Robison, Ruth A. Kleinerman, Kevin C. Oeffinger, Jasmine H. Francis, David H. Abramson, Ira J. Dunkel, Danielle Novetsky Friedman
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- Journal:
- Palliative & Supportive Care / Volume 18 / Issue 3 / June 2020
- Published online by Cambridge University Press:
- 08 November 2019, pp. 322-331
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Objectives
Retinoblastoma is the most common primary intraocular tumor of childhood with >95% survival rates in the US. Traditional therapy for retinoblastoma often included enucleation (removal of the eye). While much is known about the visual, physical, and cognitive ramifications of enucleation, data are lacking about survivors' perception of how this treatment impacts overall quality of life.
MethodsQualitative analysis of an open-ended response describing how much the removal of an eye had affected retinoblastoma survivors' lives and in what ways in free text, narrative form.
ResultsFour hundred and four retinoblastoma survivors who had undergone enucleation (bilateral disease = 214; 52% female; mean age = 44, SD = 11) completed the survey. Survivors reported physical problems (n = 205, 50.7%), intrapersonal problems (n = 77, 19.1%), social and relational problems (n = 98, 24.3%), and affective problems (n = 34, 8.4%) at a mean of 42 years after diagnosis. Three key themes emerged from survivors' responses; specifically, they (1) continue to report physical and intrapersonal struggles with appearance and related self-consciousness due to appearance; (2) have multiple social and relational problems, with teasing and bullying being prominent problems; and (3) reported utilization of active coping strategies, including developing more acceptance and learning compensatory skills around activities of daily living.
Significance of resultsThis study suggests that adult retinoblastoma survivors treated with enucleation continue to struggle with a unique set of psychosocial problems. Future interventions can be designed to teach survivors more active coping skills (e.g., for appearance-related issues, vision-related issues, and teasing/bullying) to optimize survivors' long-term quality of life.
3 - Epidemiology and etiology
- from Section 1 - History and general issues
- Edited by Ching-Hon Pui
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- Book:
- Childhood Leukemias
- Published online:
- 05 April 2013
- Print publication:
- 21 June 2012, pp 49-71
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Summary
Introduction
The acute leukemias of childhood are a heterogeneous group of diseases. In this review of the descriptive and analytic epidemiology of these malignancies, specific subgroups are emphasized, as defined by morphology, cytogenetic features, or molecular markers. There is evidence that specific leukemic subgroups may have distinct etiologies, and that molecular abnormalities associated with particular subgroups may be linked with specific causal mechanisms. Moreover, the mutations produced at the successive stages of leukemogenesis, from initiation through induction to promotion, may all involve separate etiologic processes.
It is also important to note that changes over time in diagnostic practice and precision may account in part for some reported epidemiologic trends. Moreover, changes in terminology and classification schemes for leukemia make it difficult to make direct comparisons between studies, particularly if risk factors differ for different subgroups. However, in assessing risk factors, studies of the childhood leukemias present several methodologic advantages. The interval between exposure to putative risk factors and onset of leukemia may be shorter, recall of exposures is likely to be better, and intervening factors may be fewer than those associated with adult leukemias. These characteristics of childhood leukemia may facilitate identification of the most likely risk factors for the various leukemic subgroups. Furthermore, they lend themselves to an approach that includes both population studies and molecular epidemiologic techniques, permitting the design of research to assess genetic–environmental causal interactions. As studies of potential environmental causes of childhood leukemia have now accumulated to a degree that allows data synthesis, and in order to succinctly summarize the literature, recent meta-analyses rather than individual studies are cited preferentially below.
3 - Epidemiology and etiology
- from Part I - History and general issues
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- By Logan G. Spector, Assistant Professor, Division of Pediatric Epidemiology & Clinical Research, Julie A. Ross, Professor, Division of Pediatric Epidemiology & Clinical Research, Leslie L. Robison, Professor, Division of Pediatric Epidemiology & Clinical Research, Smita Bhatia, Director Epidemiology and Outcomes Research, Division of Pediatrics, City of Hope National Medical Center, Duarte, CA, USA
- Edited by Ching-Hon Pui
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- Book:
- Childhood Leukemias
- Published online:
- 01 July 2010
- Print publication:
- 02 February 2006, pp 48-66
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Summary
Introduction
The acute leukemias of childhood are a heterogeneous group of diseases. In reviewing the descriptive and analytic epidemiology of these malignancies, we have emphasized specific subgroups, as defined by morphology [the French-American-British (FAB) classification], cytogenetic features, or molecular markers. There is evidence that specific subtypes of leukemia may have distinct etiologies, and that molecular abnormalities associated with particular subtypes may be linked with specific causal mechanisms. Moreover, the mutations produced at the successive stages of leukemogenesis, from initiation through induction to promotion, may all involve separate etiologic processes.
It is also important to note that changes over time in diagnostic practice and precision may account in part for some reported epidemiologic trends. Moreover, changes in terminology and classification schemes for leukemia make it difficult to perform direct comparisons among studies, especially if risk factors differ for different subgroups. However, in assessing risk factors, studies of the childhood leukemias present several methodologic advantages. The interval between exposure to putative risk factors and the onset of leukemia may be shorter, recall of exposures is likely to be better, and intervening factors may be fewer than those associated with adult leukemias. These characteristics of childhood leukemia may facilitate identification of the most likely risk factors for each leukemia subtype. Furthermore, they lend themselves to an approach that includes both population studies and molecular epidemiologic techniques, permitting the design of research to assess genetic-environmental causal interactions.