Pediatr Blood Cancer 2009;52:476–480 Tumor Stabilization Under Treatment With Imatinib in Progressive Hypothalamic-Chiasmatic Glioma Andreas Peyrl, MD, 1 Amedeo Azizi, MD, 1 Thomas Czech, MD, 2 Mariella Gruber-Olipitz, MD, 1 Neil Jones, MD, 3 Christine Haberler, MD, 4 Daniela Prayer, MD, 5 Eva Autzinger, MD, 1 and Irene Slavc, MD 1 * INTRODUCTION Optic pathway gliomas with or without contiguous involvement of the hypothalamus account for 5% of childhood brain tumors. Approximately 65% of these tumors arise in children younger than 5 years of age [1]. Although these tumors are of low grade histology, they can have a variable natural history dependent upon location and patient age. Management strategies for hypothalamic-chiasmatic gliomas include watchful waiting, surgery, chemotherapy, and irradiation. Due to the proximity of unforgiving surrounding structures such as the hypothalamus, optic tracts, thalamus and brainstem a radical approach seeking gross total resection is generally not feasible in posterior lesions. In the 1980s the detrimental sequelae produced by radiation therapy on structures of the developing brain responsible for endocrine, intellectual and emotional functioning led to the development of chemotherapy as an alternative to radiotherapy. Currently, chemotherapy is the primary treatment of choice in progressive optic pathway tumors that are not amenable to surgical intervention and it is the only adjuvant to decompressive surgery in young patients. A combination of carboplatin with vincristine is the most typical regimen used in Europe and the USA. This treatment showed a reduction in tumor volume in 56% in a group of low-grade astrocytomas mostly located in the diencephalon, contributing to an overall 3-year progression-free survival of 63% [2]. While most children respond to chemotherapy, the clinical behavior of hypothalamic-chiasmatic gliomas is highly unpredictable. The two main clinical risk factors for poor outcome are young age and a poor response to chemotherapy [1,3]. Failure of primary chemotherapy is seen as an indication for radiation therapy. However, the toxicity of radiotherapy has directed attention towards novel chemotherapy treatment strategies. For patients with progressive disease who fail second or third line therapies alternative treatment approaches are needed. Imatinib mesylate is a potent small molecule inhibitor of the protein-tyrosine kinases abl, arg, c-kit, and platelet derived growth factor receptors (PDGFR-a and -b). Imatinib mesylate is an established and effective therapy for chronic myelogenous leukemia both in adults and children and has also shown efficacy in numerous other cancers [4–7]. In 2003, McLaughlin et al. [8] described a marked regression of refractory metastatic suprasellar pilocytic astrocytoma under empiric treatment with imatinib mesylate in a single patient who has failed multiple salvage regimens. To date there have been no additional clinical reports on the efficacy of imatinib for the treatment of refractory, progressive pilocytic astrocytomas. We report on our experience with imatinib in six patients who originally presented with an extensive pilocytic astrocytoma of the hypothalamic-chiasmatic region during infancy. All six patients had progressive disease and had previously been treated with carboplatin/vincristine according to the European Low-Grade- Glioma (LGG) protocol followed by additional surgeries and at least one or two additional chemotherapies including high-grade-glioma (HGG) regimens, vinblastine, and temozolomide prior to initiation of imatinib mesylate. PATIENTS AND METHODS Patients Six patients with progressive hypothalamic-chiasmatic glioma were treated with imatinib as salvage-therapy. Histology was pilocytic astrocytoma in six patients, including three patients with Background. Hypothalamic-chiasmatic gliomas (HCG) account for up to 20% of tumors in patients under the age of 3 years. While most children respond to chemotherapy, alternative treatment approaches are needed for those with progressive disease refractory to chemotherapy. Procedure. Six patients (median age: 5.5 years) with progressive HCG were treated with imatinib for 3 – 29 months at a median daily oral dose of 270 mg/m 2 . All patients initially presented with extensive tumors during infancy and had undergone two to three surgical resections and two to three prior chemo- therapies with multiple agents. Results. The best response achieved was stable disease in all six patients. Disease control lasted from 5 to 46 months and was sustained longer in comparison to their last prior chemotherapy. Toxicities possibly related to imatinib included edema, elevated liver enzymes and bowel problems. Immunohisto- chemistry in our patients’ tumor cells revealed focal expression of arg and PDGFR-a in one patient, in the remaining five patients no expression of any of the five known targets of imatinib could be detected. Expression of PDGFR-a and PDGFR-b was detected in endothelial cells of tumor capillaries of all six patients. Conclusions. We conclude that imatinib has possible activity in progressive HCG and may present an additional therapeutic option for patients who are too young or whose tumor is too extensive to receive radiotherapy. However, the optimal use of imatinib in this disease, its mechanism of action, and possible long-term effects remain unclear and will require additional study. Pediatr Blood Cancer 2009;52:476–480. ß 2008 Wiley-Liss, Inc. Key words: children; CNS tumor; imatinib; progressive hypothalamic-chiasmatic glioma ß 2008 Wiley-Liss, Inc. DOI 10.1002/pbc.21881 Published online 5 December 2008 in Wiley InterScience (www.interscience.wiley.com) —————— 1 Department of Pediatrics, Medical University of Vienna, Vienna, Austria; 2 Department of Neurosurgery, Medical University of Vienna, Vienna, Austria; 3 Department of Pediatrics, Paracelsus Private Medical University, Salzburg, Austria; 4 Institute of Neurology, Medical University of Vienna, Vienna, Austria; 5 Department of Radiology, Medical University of Vienna, Vienna, Austria *Correspondence to: Irene Slavc, Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail: irene.slavc@meduniwien.ac.at Received 30 September 2008; Accepted 30 October 2008