Clinical-patient studies Osmotic blood–brain barrier disruption chemotherapy for diffuse pontine gliomas Walter A. Hall 1 , Nancy D. Doolittle 2 , Megan Daman 1 , Patti K. Bruns 1 , Leslie Muldoon 2 , David Fortin 4 and Edward A. Neuwelt 2,3 1 Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN, USA; 2 Department of Neurology and; 3 Department of Neurosurgery, Oregan Health & Science University, Portland, OR, USA; 4 Depart- ment of Neurology and Neuro-Oncology, Sherbrooke University, Sherbrooke, Quebec, Canada Key words: blood–brain barrier, brain stem glioma, midbrain, pontine glioma Summary The prognosis for patients with diffuse pontine gliomas (DPG) remains poor. New aggressive innovative treat- ments are necessary to treat this disease. From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG were treated with monthly osmotic blood–brain barrier disruption (BBBD) chemotherapy using intraar- terial carboplatin or methotrexate and intravenous cytoxan and etoposide. Patients presented for a median duration of 6 weeks with increased intracranial pressure, long tract signs, diplopia, ataxia, and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging in seven patients and on CT in one. Two patients had biopsies that showed an astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR imaging after contrast administration. Three patients had radiation therapy before BBBD chemotherapy and four afterwards. Two patients had chemotherapy (tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In general, patients were evaluated with MR imaging every 3 months to monitor for a response to treatment. The median number of chemotherapy cycles that were administered by BBBD was 10, mean 10. Three patients also received one, two, or three cycles of intraarterial chemotherapy without BBBD. One patient that was started on carboplatin was converted to methotrexate, and five that were started on the methotrexate protocol were later converted over to carboplatin. One patient received monthly methotrexate followed by 14 days of procarbazine and one patient started on methotrexate was switched to navelbine. MR imaging demonstrated two partial responses, five patients with stable disease, and one with disease progression. The median time to tumor progression was 15 months with the range from <1 to 40 months. The median survival from the time of diagnosis was 27 months, ranging from 7 to 80 months. The median survival time from the first BBBD or intraarterial treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost to follow-up with an unknown date of death. Although the sample size is small, the TTP and survival times are longer than those previously reported in other DPG series. In addition, the ability to demonstrate stable disease or partial responses in DPG on MR imaging argues for the therapeutic benefit of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by osmotic BBBD supports the further examination of this treatment modality for patients with DPG. Introduction Brainstem gliomas are a heterogeneous group of tumors that involve different parts of the brainstem. Depending on their location within the brainstem, these tumors require different treatment modalities and have signifi- cantly different prognoses. Gliomas located in the brainstem comprise 10–20% of pediatric central nervous system (CNS) tumors with an annual incidence in the United States of 150–300 tumors [1]. Although these tumors can occur at any age, the majority are seen in children between the ages of 7 and 9 years and there is no gender predilection. The brainstem is comprised of the midbrain, pons, and medulla oblongata and with the advent of the magnetic resonance (MR) imaging; it is possible to more accurately categorize the location from which these tumors arise. Tumors located in the midbrain or tectum carry a good prognosis and rarely require surgical intervention or adjuvant treatment. Tumors located at the cervicomedullary junction also portend a good prognosis because they are often exophytic and ame- nable to safe surgical resection in the modern era of neuronavigation. Unfortunately, the most common brainstem tumor is the diffuse pontine glioma (DPG), which makes up 85% of these lesions and is associated with a very poor prognosis. Treatments for DPG have included biopsy occasion- ally, chemotherapy, and a variety of radiation therapy treatment regimens. Biopsy has been performed if a portion of the tumor can be safely accessed without a risk of significant neurological morbidity. Tumors located completely within the pons are usually diag- nosed and treated based entirely on their MR imaging characteristics. These imaging characteristics have supplanted the necessity for stereotactic biopsy [2]. Various radiation therapy regimens have been used to treat DPG either before or after the administration of Journal of Neuro-Oncology (2006) 77: 279–284 Ó Springer 2005 DOI 10.1007/s11060-005-9038-4