Medical, psychological, cognitive and educational late‐effects in pediatric low‐grade glioma survivors treated with surgery only

Turner, Christopher D.; Chordas, Christine; Liptak, Cori; Rey‐Casserly, Celiane; Delaney, Brian L.; Ullrich, Nicole J.; Goumnerova, Liliana; Scott, R. Michael; Begley, Heather C.; Fletcher, William J.; Yao, Xiaopan; Chi, Susan; Kieran, Mark W.

doi:10.1002/pbc.22081

Cited by 60 publications

(55 citation statements)

References 26 publications

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“…In our opinion, several factors increase the strength of the present study; firstly, separate studies in survivors of low incidence cancers are rare but needed to recognize late effects specific for each cancer type and its treatment. As opposed to ALL and brain tumors, AML, IA and WT have only rarely been subject to separate studies of social/ psychosocial outcomes [10,[24][25][26][27][28][29]. Also, the treatment in the Nordic countries is based upon the same protocols, which provides the opportunity to study a representative sample size.…”

Section: Discussionmentioning

confidence: 96%

“…Mackie et al found that mean overall work and educational performance in 35 WT survivors was similar to that of age-matched controls from local hospitals [24]. Studies on psychosocial outcomes among survivors of IA have mainly addressed quality of life and some social outcomes in relatively small samples [10,[27][28][29]. The latter studies have used various comparison groups which makes it difficult to ascertain if IA survivors have a social functioning different from the general population.…”

Section: Introductionmentioning

confidence: 94%

“…The treatment of WT is in general less intensive than for AML but more intensive than for IA and includes chemotherapy and surgery, sometimes supplemented with radiotherapy [23]. These three cancers have only rarely been subject to separate studies on social/psychosocial status after cure [10,[24][25][26][27][28][29]. As a part of the Childhood Cancer Survival Study (CCSS) Mulrooney et al reported poorer social status in 272 AML survivors than in their siblings, but similar to the general population [25].…”

Section: Introductionmentioning

confidence: 99%

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Social outcomes in young adult survivors of low incidence childhood cancers

et al. 2010

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Social outcomes in young adult survivors of low incidence childhood cancers

et al. 2010

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“…Furthermore, survivors of pilocytic astrocytomas commonly suffer long-term sequelae related to disease and treatment. 9–13 Thus, a better understanding of pilocytic astrocytoma biology is needed to guide the development of new therapies to decrease morbidity and improve survival.…”

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confidence: 99%

Activation of the Hedgehog pathway in pilocytic astrocytomas

et al. 2010

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Pilocytic astrocytoma is commonly viewed as a benign lesion. However, disease onset is most prevalent in the first two decades of life, and children are often left with residual or recurrent disease and significant morbidity. The Hedgehog (Hh) pathway regulates the growth of higher WHO grade gliomas, and in this study, we have evaluated the activation and operational status of this regulatory pathway in pilocytic astrocytomas. Expression levels of the Hh pathway transcriptional target PTCH were elevated in 45% of tumor specimens analyzed (ages 1–22 years) and correlated inversely with patient age. Evaluation of a tissue array revealed oligodendroglioma-like features, pilomyxoid features, infiltration, and necrosis more commonly in specimens from younger patients (below the median patient age of 10 years). Immunohistochemical staining for the Hh pathway components PTCH and GLI1 and the proliferation marker Ki67 demonstrated that patients diagnosed before the age of 10 had higher staining indices than those diagnosed after the age of 10. A significant correlation between Ki67 and PTCH and GLI1 staining indices was measured, and 86% of Ki67-positive cells also expressed PTCH. The operational status of the Hh pathway was confirmed in primary cell culture and could be modulated in a manner consistent with a ligand-dependent mechanism. Taken together, these findings suggest that Hh pathway activation is common in pediatric pilocytic astrocytomas and may be associated with younger age at diagnosis and tumor growth.

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“…Studies on long-term functional outcomes are conflicting, with some suggesting patients perform well [5,6] whereas others report higher than expected rates of cognitive and psychosocial difficulties [7-10]. Variability in functioning occurs in patients treated with surgery [6,11,12] as well as those treated with chemotherapy [13,14], irradiation [13,15], or combination.…”

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confidence: 99%

Prospective longitudinal evaluation of emotional and behavioral functioning in pediatric patients with low-grade glioma treated with conformal radiation therapy

Willard

Conklin

et al. 2015

J Neurooncol

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Background Patients with low-grade glioma (LGG) who are successfully treated with irradiation are at increased risk for cognitive and psychosocial late effects. Conformal radiation therapy (CRT) allows sparing of cognitive deficits, but how it affects emotional and behavioral functioning remains unclear. We performed a prospective longitudinal study of the emotional and behavioral functioning of pediatric patients with LGG in the first 5 years post-CRT. Methods Ninety-five pediatric patients with LGG treated on an institutional Phase II trial (August 1997– June 2009) underwent neuropsychological assessments pre-CRT and 6, 12, 24, 36, 48, and 60 months post-CRT. Parent-reported scores on the Child Behavior Checklist (CBCL) were analyzed. Three competence scales (School Competence, Social Competence, and Activities), 2 summary scales (Internalizing Problems and Externalizing Problems), and 2 subscales of theoretical interest (Attention Problems and Social Problems) from the CBCL were used. Results Among 80 eligible patients [44 female, 68 white], 51 had pilocytic astrocytoma and 13 had optic pathway glioma. Mean age at diagnosis was 6.8 years (SD=4.3 years) and at CRT initiation was 8.9 years (SD=3.4 years). Before CRT, deficits were demonstrated on the competence scales (mean scores below normative mean) and the Attention Problems and Social Problems subscales (mean scores above normative means). This trend continued at 5 years post-CRT. Longitudinal trajectories of emotional and behavioral functioning were stable over 5 years. Conclusions Emotional and behavioral deficits remain relatively stable over the 5 years post-CRT in patients with LGG, suggesting that CRT may not exacerbate pre-existing psychosocial difficulties in this population.

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Medical, psychological, cognitive and educational late‐effects in pediatric low‐grade glioma survivors treated with surgery only

Abstract: "Surgery-only" LGG survivors may be more affected by their tumor and its resection than previously appreciated. A prospective study is needed to address this survivor population.

Cited by 60 publications

References 26 publications

Social outcomes in young adult survivors of low incidence childhood cancers

Social outcomes in young adult survivors of low incidence childhood cancers

Activation of the Hedgehog pathway in pilocytic astrocytomas

Prospective longitudinal evaluation of emotional and behavioral functioning in pediatric patients with low-grade glioma treated with conformal radiation therapy

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