Impact of chemotherapy on disseminated low‐grade glioma in children and adolescents: Report from the HIT‐LGG 1996 trial

Hornstein, Stephan von; Kortmann, R.-D.; Pietsch, Torsten; Emser, Angela; Warmuth‐Metz, Monika; Soerensen, Niels; Sträeter, Ronald; Graf, Norbert; Thieme, Barbara; Gnekow, Astrid

doi:10.1002/pbc.23006

Cited by 54 publications

(66 citation statements)

References 43 publications

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“…Primary dissemination of LGG has been described to be an unfavourable prognostic factor [32], [33], confirmed by this report with an impaired PFS. The impact of dissemination is statistically noticeable, suggesting that patients with disseminated tumours experience progression more frequently even following non-progression at response assessment at week 24.…”

Section: Discussionsupporting

confidence: 85%

A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

Gnekow¹,

Kandels²,

Picton³

et al. 2017

European Journal of Cancer

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124

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BackgroundThe use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection.MethodsWithin the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology–Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02–7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.FindingsNo differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively.InterpretationThe addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of ‘duration of therapy’ and ‘age at stopping therapy’.

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Section: Discussionsupporting

confidence: 85%

A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

Gnekow¹,

Kandels²,

Picton³

et al. 2017

European Journal of Cancer

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124

155

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“…They are typically seen to be slow-growing, well-circumscribed tumors, which do not invade surrounding tissues and virtually never progress to higher malignancy grades. Dissemination into the spinal canal at diagnosis has been reported, but this is a rare event occurring in only 2–3% of cases [5]. As such, they are classified as malignancy grade I by the World Health Organisation, and prognosis in terms of overall survival is very good: >90% of patients survive beyond 10 years, and the majority of these long-term survivors are cured of their tumor [6, 7].…”

Section: Introductionmentioning

confidence: 99%

MAPK pathway activation in pilocytic astrocytoma

Jones

Gronych

Lichter

et al. 2011

Cell. Mol. Life Sci.

189

154

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Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions.

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“…Sixty-one patients (5.2%) were found to have tumor dissemination, with 2.8% being present at diagnosis. 8 Other reviews have found similar frequencies of dissemination ranging from 4% to 10%. 9,10 Various infectious and inflammatory lesions, immunemediated demyelinating or vascular disorders, and therapyinduced complications can produce lesions that mimic CNS neoplasms.…”

Section: Discussionmentioning

confidence: 77%

Nocardia farcinica Meningitis Masquerading as Central Nervous System Metastasis in a Child With Cerebellar Pilocytic Astrocytoma

Davis¹,

Kreppel²,

Brady

et al. 2015

Journal of Pediatric Hematology/Oncology

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Juvenile pilocytic astrocytoma, the most common pediatric central nervous system (CNS) neoplasm, characteristically displays an indolent growth pattern and rarely demonstrates metastatic dissemination. Reports of infections mimicking CNS metastatic disease are also rare and can impact treatment. We report the youngest known case of a child with a CNS Nocardia farcinica infection who had a known cerebellar pilocytic astrocytoma, review other infections that may masquerade as CNS neoplasms, and discuss N. farcinica CNS infections.

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Impact of chemotherapy on disseminated low‐grade glioma in children and adolescents: Report from the HIT‐LGG 1996 trial

Cited by 54 publications

References 43 publications

A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

MAPK pathway activation in pilocytic astrocytoma

Nocardia farcinica Meningitis Masquerading as Central Nervous System Metastasis in a Child With Cerebellar Pilocytic Astrocytoma

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