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Temozolomide and valproic acid in combination with vinorelbine for treatment of pediatric high-grade gliomas: a prelliminary analysis of a study protocol

Maurizio Lucchesi, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy; Alessia Stival, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy; Sabrina Becciani, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy; Milena Guidi, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy; Silvia Scoccianti, Radiation Oncology, Careggi Hospital, Florence, Italy; Daniela Greto, Radiation Oncology, Careggi Hospital, Florence, Italy; Silvia Farina, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy; Maurizio de Martino, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy; Lorenzo Genitori, Neurosurgery Unit, Department of Neuroscience, Meyer Children's Hospital, Florence, Italy; Iacopo Sardi, Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's Hospital, Florence, Italy.


The prognosis for children with high-grade gliomas (HGGs: anaplastic astrocytoma, AA; glioblastoma multiforme, GBM) remains poor despite aggressive surgical resection and, in older children, radiotherapy with concomitant and adjuvant temozolomide.

Our proposal for pediatric HGG was a chemoradiotherapy protocol developed by EORTC/NCIC for adults (Neurology, 2011), with Vinorelbine (20 mg/sqm iv weekly during radiotherapy, and 30 mg/sqm iv bi-weekly in the adjuvant phase). Moreover, the adjuvant phase was prolonged to 12 months.

We treated 15 pediatric patients. Eleven (73,4%) have completed treatment at the time of analysis. The median age was 10 years (range 6-24). Five (33%) patients had a GBM, and 10 (67%) had an AA. We have considered 12 (80%) supratentorial (5, 42% in hemispheres and 7, 58% in diencephalon) and 3 (20%) infratentorial (2, 67% in brainstem and 1, 33% in cerebellum) tumors. Surgery was performed in 13 (86,7%) patients. It was radical without residual in 5 (38,4%) cases. Five patients (33,3%) had a disease progression during the adjuvant phase.
There are no significant differences in PFS (not reached, NR vs 9,05 months, p:0,16) and OS (NR vs 14,3 months, p:0,29) between AA and GBM, with a favorable trend for AA. There are no differences also for primary tumor site (p:0,76), and for radicalness of surgery (p:0,07). Patients who experienced disease progression during the adjuvant phase had a significant worse survival (12,1 months vs NR, p:0,0009).

In pediatric HGG, a disease progression which occurs during an induction treatment represents a negative prognostic factor for survival. This identifies a subgroup of patients with a marked chemoresistance despite of treatment line.

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Format: Oral communication

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