Faculty Bibliography

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m(2). Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference

OBJECTIVES/HYPOTHESIS:: Medulloblastoma is the most common pediatric malignant tumor of the central nervous system in children. Treatment includes surgical excision, external beam radiation, and multiagent chemotherapy. Otologic sequelae are common and may result from radiation and/or chemotherapy. Profound sensorineural hearing loss (SNHL) is a known complication of neuro-oncologic treatment and may render these patients eligible for cochlear implantation (CI). Issues of CI in this population, including diagnosis, treatment of preoperative middle ear disease, operative and postoperative course, performance data, and long-term tumor surveillance are highlighted and reviewed. STUDY DESIGN:: Retrospective chart review. METHODS:: Three patients treated for pediatric medulloblastoma with surgical resection, postoperative hyperfractioned craniospinal radiotherapy, and multiagent adjuvant chemotherapy who underwent cochlear implantation were identified. Details of neuro-oncologic treatment and associated otologic complications are presented and analyzed. Primary outcome assessment includes treatment of middle ear pathology, perioperative cochlear implant course, and postimplantation performance data. RESULTS:: Each patient required surgical treatment of chronic ear disease 4 to 16 years after chemoradiation. All progressed to profound SNHL and were implanted 8 to 17 years post-neuro-oncologic treatment. There were no intraoperative complications, and full insertion of the cochlear implant electrode array was achieved in each patient. One patient developed postoperative wound dehiscence requiring operative closure. Postimplantation performance data support significant benefit in all patients. CONCLUSIONS:: Patients treated for pediatric medulloblastoma develop otologic sequelae, including profound SNHL, and may require cochlear implantation. Successful management of middle ear and mastoid pathology involves consideration of potential future cochlear implantation. Postoperative performance data supports cochlear implantation in this population. Laryngoscope, 2009

We discuss a posterior fossa tumor in a 15-month-old girl who presented with photophobia, epiphora, and torticollis. Early diagnosis and long-term follow-up were possible in this patient. Although the tumor was not treated, her symptoms improved by 6 years of age

INTRODUCTION: ACNS 0122 aimed to improve event-free survival (EFS) and OS (overall survival) for intracranial NGGCT, by increasing response rate (complete [CR] and partial [PR]) with neoadjuvant carboplatin/VP-16, alternating with ifosfamide/VP-16, followed by craniospinal irradiation (CSI) plus involved field boost. In patients not obtaining CR/PR by neuro-imaging and tumor marker response after neoadjuvant chemotherapy, second-look surgery was recommended. Patients with persistent radiographic disease or positive markers underwent myeloablative chemotherapy (thiotepa/VP-16) prior to CSI. OBJECTIVES: 1) To determine response rate following three cycles of neoadjuvant chemotherapy; 2) to determine EFS and OS; and 3) To determine whether additional CR can be achieved with high-dose thiotepa/VP-16 for patients not achieving CR/PR. RESULTS: 104 patients enrolled from 1/04-7/08. Median age was 12 (range 3-23) years. 76% were male,. No toxic deaths occurred. Among 84 evaluable patients, response rate was reported as 70% (33 CR, 26 PR). With central imaging review (58/84 patients reviewed to date) response rate was 90%. Nineteen patients underwent second-look surgery, 2 secondary to progression; reviewed pathology in 11 was malignant teratoma or mature teratoma (8), fibrosis (1), and NGGCT (2). Median follow-up for patients without events is 1.9 years (range 0.06-4.9). Fifteen patients have experienced recurrence or progression to date with 6 subsequent deaths. Two-year EFS and OS are 84.4%+/-4% and 93% +/-3%, respectively. Further stratification of responses will be presented. CONCLUSION: Neoadjuvant chemotherapy for NGGCT demonstrates a very high response rate and when administered before CSI may increase survival