Abstract
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’.
Highlights
Childhood Low Grade Gliomas (LGGs) arise during brain growth, developing in all areas of the central nervous system (CNS)
Disseminated lesions were distributed throughout the intracranial and spinal leptomeningeal space; extra-neural manifestation was reported in five patients, all associated with the presence of a ventriculoperitoneal shunt (VP-shunt)
Childhood low grade glioma are predominantly pilocytic grade 1 tumours with a small proportion of grade 2 tumours and other rare entities, a proportion are diagnosed without biopsy on imaging characteristics
Summary
Childhood Low Grade Gliomas (LGGs) arise during brain growth, developing in all areas of the central nervous system (CNS). The SIOP Brain Tumour LGG Subcommittee had developed a comprehensive, multimodality treatment strategy for Childhood LGG, the International Society of Paediatric OncologyeLow Grade Glioma (SIOP LGG) committee, which was piloted and widely accepted clinically [3,4]. High initial tumour non-progression rates (approximately 70e90%) could be achieved, but 5-year PFS rates declined after stopping treatments, especially in children diagnosed who were less than 1 year of age [10]. Methods: Within the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric OncologyeLow 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 Â 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme.
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