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3 Clinical Utility of Neurocognitive Monitoring During Therapy in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)
- Rachel M Bridges, Lacey P Hall, Heather M Conklin, Kendra R Parris, Jason M Ashford, Ching-Hon Pui, Sima Jeha, Lisa M Jacola
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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. 511-512
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Objective:
Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.
Participants and Methods:Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.
Results:During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.
Conclusions:Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.
1 Ototoxicity and Cognitive Outcomes among Children Treated for Brain Tumors in Infancy
- Nicole A. Salman, Johnnie K. Bass, Jie Huang, Arzu Onar-Thomas, Jason M. Ashford, Jeanelle S. Ali, Thomas E. Merchant, Giles W. Robinson, Amar Gajjar, Heather M. Conklin
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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, p. 312
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Objective:
Treatment of childhood central nervous system (CNS) tumors can lead to sensorineural hearing loss (SNHL), with prior research indicating associations between SNHL and cognitive difficulties. Infants (0-3 years) treated for CNS tumors are at particular risk for neurocognitive deficits due to increased vulnerability of the developing brain and missed developmental opportunities secondary to prolonged treatment. This study expands upon existing research by examining the association between treatment-related SNHL and later neurocognitive outcomes among infants.
Participants and Methods:Serial audiology and neurocognitive assessments were conducted as part of a prospective, multisite, longitudinal trial (SJYC07). Children with newly diagnosed CNS tumors were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). SNHL was dichotomized based on hearing in the better ear as present versus not present (Chang grade ≥1a vs. <1a). Neurocognitive assessments included intellectual functioning (IQ), and parent ratings of executive functioning and behavioral functioning. Demographic and clinical variables investigated included: sex, age at diagnosis (years), treatment type (chemotherapy only vs. chemotherapy + RT), risk group (low vs. intermediate vs. high), and socioeconomic status (SES, continuous). Logistic regression models were used to identify factors associated with SNHL. Change point longitudinal models were used to examine the effect of each covariate individually and the potential impact of SNHL on trajectories of neurocognitive outcomes.
Results:Of 135 patients (median age at diagnosis= 1.5 years), 67% had mild-to-severe SNHL as defined by Chang grade ≥1a at last follow-up. SNHL occurred early after treatment with a 1-year cumulative incidence 63.0% ±4.3%. SNHL was associated with age at diagnosis (p <.001) but not sex, treatment exposure or study risk arm (p >.10). At pretreatment baseline, IQ was associated with age at diagnosis (older age= higher IQ) and SES (higher SES= higher IQ) with a change in the trajectory of IQ after SNHL (stable prior to SNHL and declined 1.46 points/year after SNHL), which was impacted by tumor location (patients with supratentorial tumors stable prior to SNHL and declined 2.84 points/year after SNHL; whereas, patients with infratentorial tumors increased 1.93 points/year prior to SNHL and were stable after SNHL). At pre-treatment baseline, adaptive functioning was associated with age at diagnosis (older age= higher skills) with a change in adaptive functioning after SNHL that varied by age. There was a change in trajectory of attention problems (stable before SNHL and worsening 1.39 points/year after SNHL). SNHL was not associated with parent report of emerging executive functioning.
Conclusions:Children with brain tumors experience SNHL and cognitive difficulties early in treatment that can worsen over time. Younger age at diagnosis is associated with greater risk for SNHL and cognitive difficulties. Analyses of the time course between the emergence of SNHL and cognitive late effects suggests even mild SNHL is associated with a clinically signficant decline in IQ and attention problems. These findings have notable implications with respect to refining monitoring guidelines, informing modifications to treatment, advocating for interventions, and helping educate parents, teachers, and providers about the significant impact of mild SNHL.
6 Feasibility and Perceived Benefit of an Interdisciplinary Rehabilitation Approach within a Tertiary Pediatric Hematology/Oncology Setting
- Darcy Raches, Jason M Ashford, Martina Bryndziar, Taylor Mule, April Huggins, Sherry Lockett, Allison Harris, Hannah Taylor, Ellen Bursi, Regina Winfrey, Sue B Lynn, Amar Gajjar, Giles W Robinson, Heather M Conklin
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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. 8-9
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Objective:
Medulloblastoma is the most common pediatric malignant brain tumor. Approximately 29% of medulloblastoma patients experience postoperative posterior fossa syndrome (PFS) characterized by impairments in speech, motor, and mood. An interdisciplinary rehabilitation approach is associated with greater rehabilitation gains than a single discipline approach for brain injury patients with significant rehabilitation needs. However, literature regarding the feasibility and utility of this approach within a tertiary care pediatric hematology/oncology setting is lacking. The Acute Neurological Injury (ANI) service was developed to coordinate care for neurologically complex hematology/oncology patients receiving active cancer treatment, including those with PFS. ANI care coordination includes bimonthly interdisciplinary team meetings, interdisciplinary goal implementation for each patient, parent psychoeducation about applicable brain-behavior relationships (including PFS) at treatment initiation, neuropsychological assessment at transition times throughout treatment, cognitive remediation, and coordinated end of treatment transition planning. We gathered caregiver perspective on this approach within a tertiary care pediatric hematology/oncology setting.
Participants and Methods:Parents of children and young adults (ages 4-20) with PFS after medulloblastoma resection who received coordinated care as part of the ANI program (n=20) were interviewed at least 4 months following completion of cancer treatment. 75% experienced postoperative mutism while the remainder experienced significantly decreased speech without mutism. All received cranial-spinal irradiation and focal boosts to tumor sites followed by chemotherapy per multi-institutional treatment protocol. Caregivers were interviewed regarding perceived feasibility and utility of ANI program components including parent psychoeducation, neuropsychological assessment, cognitive remediation, and interdisciplinary team coordination/goal setting, as well as parental supports. Yes/no responses were gathered as well as responses regarding the perceived utility of aspects of the interdisciplinary ANI program approach via a five-point Likert scale.
Results:Surveys were completed by 66% of families contacted. Mean age at first contact with neuropsychology as part of the ANI program was 9.45 years (SD=4.4 years). Mean time between end of treatment and parent interview was 3.20 years (SD=2.01 years). Most parents reported that initial psychoeducation about PFS helped to decrease their concerns (81%) and increased their understanding of their child’s functioning in the context of PFS (88%). They reported benefit from neuropsychological assessment reports prior to initiating adjuvant treatment (92%), at end of treatment (90%), and one year following initiation of cancer treatment (100%), though they perceived less benefit from assessments intended to inform provider interventions during treatment (81% and 66%). Reports were shared most often with schools (75%), behavioral therapists (50%), physicians (50%), and rehabilitation specialists (25%). Parents indicated that the interdisciplinary ANI program approach was helpful (94%) and the coordinated interdisciplinary goal was beneficial (92%). Most parents favored the weekly frequency of cognitive remediation sessions (83%). Much interest was voiced in establishing a formal mentoring program to offer peer support by parents whose children have previously experienced PFS to those acutely managing a new PFS diagnosis (95%). Of note, all participants indicated that they would be willing to serve in a peer mentor role (100%).
Conclusions:The interdisciplinary ANI program approach is feasible with perceived benefits to families managing new PFS and medulloblastoma diagnoses and receiving active cancer treatment.
Cognitive Performance, Aerobic Fitness, Motor Proficiency, and Brain Function Among Children Newly Diagnosed With Craniopharyngioma
- Heather M. Conklin, Kirsten K. Ness, Jason M. Ashford, Matthew A. Scoggins, Robert J. Ogg, Yuanyuan Han, Yimei Li, Julie A. Bradley, Frederick A. Boop, Thomas E. Merchant
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- Journal of the International Neuropsychological Society / Volume 25 / Issue 4 / April 2019
- Published online by Cambridge University Press:
- 03 May 2019, pp. 413-425
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Objectives: Craniopharyngioma survivors experience cognitive deficits that negatively impact quality of life. Aerobic fitness is associated with cognitive benefits in typically developing children and physical exercise promotes recovery following brain injury. Accordingly, we investigated cognitive and neural correlates of aerobic fitness in a sample of craniopharyngioma patients. Methods: Patients treated for craniopharyngioma [N=104, 10.0±4.6 years, 48% male] participated in fitness, cognitive and fMRI (n=51) assessments following surgery but before proton radiation therapy. Results: Patients demonstrated impaired aerobic fitness [peak oxygen uptake (PKVO2)=23.9±7.1, 41% impaired (i.e., 1.5 SD<normative mean)], motor proficiency [Bruininks-Oseretsky (BOT2)=38.6±9.0, 28% impaired], and executive functions (e.g., WISC-IV Working Memory Index (WMI)=96.0±15.3, 11% impaired). PKVO2 correlated with better executive functions (e.g., WISC-IV WMI r=.27, p=.02) and academic performance (WJ-III Calculation r=.24, p=.04). BOT2 correlated with better attention (e.g., CPT-II omissions r=.26, p=.04) and executive functions (e.g., WISC-IV WMI r=.32, p=.01). Areas of robust neural activation during an n-back task included superior parietal lobule, dorsolateral prefrontal cortex, and middle and superior frontal gyri (p<.05, corrected). Higher network activation was associated with better working memory task performance and better BOT2 (p<.001). Conclusions: Before adjuvant therapy, children with craniopharyngioma demonstrate significantly reduced aerobic fitness, motor proficiency, and working memory. Better aerobic fitness and motor proficiency are associated with better attention and executive functions, as well as greater activation of a well-established working memory network. These findings may help explain differential risk/resiliency with respect to acute cognitive changes that may portend cognitive late effects. (JINS, 2019, 25, 413–425)
The Utility of Parent Report in the Assessment of Working Memory among Childhood Brain Tumor Survivors
- Robyn A. Howarth, Jason M. Ashford, Thomas E. Merchant, Robert J. Ogg, Victor Santana, Shengjie Wu, Xiaoping Xiong, Heather M. Conklin
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- Journal of the International Neuropsychological Society / Volume 19 / Issue 4 / April 2013
- Published online by Cambridge University Press:
- 28 January 2013, pp. 380-389
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Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = −.24–.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment. (JINS, 2013, 19, 1–10)
Working Memory Performance among Childhood Brain Tumor Survivors
- Heather M. Conklin, Jason M. Ashford, Robyn A. Howarth, Thomas E. Merchant, Robert J. Ogg, Victor M. Santana, Wilburn E. Reddick, Shengjie Wu, Xiaoping Xiong
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- Journal of the International Neuropsychological Society / Volume 18 / Issue 6 / November 2012
- Published online by Cambridge University Press:
- 13 June 2012, pp. 996-1005
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While longitudinal studies of children treated for brain tumors have consistently revealed declines on measures of intellectual functioning, greater specification of cognitive changes following treatment is imperative for isolating vulnerable neural systems and developing targeted interventions. Accordingly, this cross-sectional study evaluated the performance of childhood brain tumor survivors (n = 50) treated with conformal radiation therapy, solid tumor survivors (n = 40) who had not received central nervous system (CNS) -directed therapy, and healthy sibling controls (n = 40) on measures of working memory [Digit Span and computerized self-ordered search (SOS) tasks]. Findings revealed childhood brain tumor survivors were impaired on both traditional [Digit Span Backward- F(2,127)= 5.98; p < .01] and experimental [SOS-Verbal- F(2,124)= 4.18; p < .05; SOS-Object- F(2,126)= 5.29; p < .01] measures of working memory, and performance on working memory measures correlated with intellectual functioning (Digit Span Backward- r = .45; p < .0001; SOS- r = −.32 to −.26; p < .01). Comparison of performance on working memory tasks to recognition memory tasks (computerized delayed match-to-sample) offered some support for greater working memory impairment. This pattern of findings is consistent with vulnerability in functional networks that include prefrontal brain regions and has implications for the clinical management of children with brain tumors. (JINS, 2012, 18, 1–10)
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