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Pediatrics Clinical Research

2011, Neuro-Oncology

Neuro-Oncology 13:iii95 – iii101, 2011. doi:10.1093/neuonc/nor156 NEURO-ONCOLOGY Abstracts 35 patients. Median time to progression in 9 patients was 5.7 months (range 1.6-17.7). The 6-month PFS was 84.5% (SE, + 6.5%). Common toxicities related to BVZ included grade I-II hypertension in 24 patients, grade I-III fatigue in 16, and grade I-III proteinuria in 12. The median enhancing tumor volume decreased significantly following two doses of BVZ (p , 0.0001). A similar decrease was observed over time during the first year of treatment (p , 0.003). Similar improvements were seen in volume FLAIR and MR perfusion permeability parameters. Pharmacokinetics and correlative biologic studies will be presented. CONCLUSION: BVZ + CPT-11 seems to be an effective combination in children with recurrent/progressive LGG. PEDIATRICS CLINICAL RESEARCH INTRODUCTION: Primitive neuroectodermal tumor (PNET) is the most common primary malignant childhood brain tumor and is usually seen as an intraparenchymal lesion, typically arising in the cerebellum (as a medulloblastoma). Peripheral PNET (PPNET), a member of the Ewing’s sarcoma (ES) family of tumors, is a tumor of putative parasympathetic neural histogenesis, typically developing in the soft tissue and skeletal structures of the trunk and extremities. We report here four cases of atypical primary ES/PPNET in very young children involving pericranial structures, two with significant intracranial involvement. METHODS: Following IRB approval, we compiled the clinical, imaging, and pathology records from four children with aggressive pericranial ES/PPNET. RESULTS: Ages at diagnosis were 1 day (female), 5 days (male), 12 months (male), and 13 months (female). Two patients had orbitofacial tumors with significant bony erosion but no intracranial extension, one patient had a temporal bone lesion with significant middle cranial fossa extension, and one patient had an intracranial temporal lobe-based tumor without extracranial extension. Immunohistochemical evidence of the EWS/FLI-1 chimeric protooncogene, typical of PPNET, was identified in one patient; genetic analysis in two patients revealed EWSR1 gene rearrangement in one patient and a novel t(20;22)(q11.2;q12) translocation in the other. All tumors were relatively large (for body size), measuring 3-8 cm in maximal dimension. Treatment included tumor resection and sarcoma-style combination chemotherapy. Two patients are alive and continue therapy, whereas two have died of sepsis and progressive disease at 3 and 6 months after diagnosis, respectively. CONCLUSIONS: Pericranial primary ES/PPNET is a rare tumor, heretofore typically described only in pre-school and school-aged children. Our study suggests this entity can occur in very young children, in whom it has a poor prognosis. It appears to be more infiltrative and to violate the usual tissue compartments. Further awareness and reporting of this rare tumor will aid understanding of histogenesis, prognosis, and optimal therapy. PC-02. EFFICACY OF BEVACIZUMAB 1 CPT-11 IN CHILDREN WITH RECURRENT LOW-GRADE GLIOMA (LGG) - A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY Sridharan Gururangan1, Jason Fangusaro2, Tina Young-Poussaint3, Shawn Lesh4, Arzu Onar4, Richard Gilbertson4, Roger Packer5, Roger McLendon1, Henry S. Friedman1, James Boyett4, and Larry E. Kun4; 1 Duke University Medical Center, Durham, NC; 2Children’s Memorial Hospital, Chicago, IL; 3Children’s Hospital Boston, Boston, MA; 4St. Jude Children’s Research Hospital, Memphis, TN; 5Children’s National Medical Center, Washington, DC PURPOSE: A Phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent/progressive LGG to measure rates of sustained stable disease ( ≥ 6 months) (SSD) and progression-free survival (PFS). METHODS: Thirty-five eligible patients received two doses of single-agent BVZ (10 mg/kg) 2 weeks apart and then BVZ + CPT-11 every 2 weeks (4 weeks ¼ 1 course) until progressive disease, unacceptable toxicity, or 2 years of treatment. Correlative studies included neuroimaging (diffusion weighted and T1 DCE permeability imaging), BVZ pharmacokinetics, estimation of changes in VEGF receptor-2 (VEGF-R2) phosphorylation in peripheral blood mononuclear cells following single-agent BVZ, and tumor immunohistochemistry for VEGF-A and B, hypoxia inducible factor 2a, VEGFR-2, and carbonic anhydrase -IX expression. RESULTS: The 35 evaluable patients (median age 8.4 years, range 0.6-17.6; pilocytic astrocytoma 43%) received a median of nine courses of BVZ + CPT-11 (range 1-25). SSD was observed in 26 (74%) of PC-03. OUTCOME OF INFANTS AND YOUNG CHILDREN WITH NEWLY DIAGNOSED EPENDYMOMA TREATED ON “HEAD START” III PROTOCOL Rajkumar Venkatramani1, Kelley Haley1, Floyd Gilles1, Richard Sposto1, Lingyun Ji2, Randal Olshefski3, James Garvin4, Tanya Tekautz5, Gloria Kennedy6, Rod Rassekh7, Theodore Moore8, Sharon Gardner9, Jeffrey Allen9, Richard Shore10, Chris Moertel11, Mark Atlas12, Joseph Lasky8, and Jonathan Finlay1; 1Children’s Hospital Los Angeles, Los Angeles, CA; 2 University of Southern California, Los Angeles, CA; 3Columbus Children’s Hospital, Columbus, OH; 4Columbia-Presbyterian, New York, NY; 5 Cleveland Clinic, Cleveland, OH; 6SUNY Upstate, Syracuse, NY; 7British Columbia’s Children’s Hospital, Vancouver, BC, Canada; 8Mattel Children’s Hospital at UCLA, Los Angeles, CA; 9New York UMC, New York, NY; 10Children’s Mercy Hospital, Kansas City, MO; 11 University of Minnesota, Minneapolis, MN; 12Schneider Children’s, New Hyde Park, NY PURPOSE: To describe the outcome in children ,10 years old with ependymoma treated on “Head Start” III, a prospective multinational clinical trial. METHODS: Between April 2003 and December 2009, 19 children with newly diagnosed ependymoma were enrolled amongst 11 participating institutions. All children were to receive five induction cycles (vincristine, cisplatin, cyclophosphamide, etoposide, and high-dose methotrexate in cycles 1, 3, and 5, and vincristine, cyclophosphamide, oral VP-16, and temozolomide in cycles 2 and 4), followed by one consolidation cycle of myeloablative chemotherapy (thiotepa, carboplatin, etoposide) and autologous stem cell rescue. Only children 6 -10 years old or with residual tumor preconsolidation were to receive irradiation after consolidation. RESULTS: Median age of 19 children (8 female) was 20 months. Median follow-up was 32 months. Tumors were infratentorial in 11 and supratentorial in eight. Three infratentorial tumors were metastatic to spinal cord. Ten patients (five supratentorial) underwent gross total resections; nine had residual disease. The pathology was cellular in six patients and anaplastic in 13. After high-dose chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response, whereas only one of the six infratentorial patients with residual disease achieved a complete response. Four of the five infratentorial patients with residual disease went on to receive autologous peripheral blood stem cell transplant, with none of them achieving complete response. Four patients (three infratentorial) received radiation therapy after chemotherapy. There was 100% eventfree (EFS) and overall survival (OS) for supratentorial ependymoma at 3 years. The 3-year EFS and OS for infratentorial ependymoma were 27 + 13% and 73 + 13%, respectively. CONCLUSIONS: High-dose chemotherapy may be helpful in avoiding irradiation in children with supratentorial ependymoma with residual disease following surgery. High-dose chemotherapy is ineffective in children with infratentorial ependymoma. PC-04. ARE PATIENTS WITH ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS AT INCREASED RISK OF DEVELOPING LOW-GRADE ASTROCYTOMAS? Elvis T. Valera, Maria S. Brassesco, Carlos A. Scrideli, Ricardo S. Oliveira, Helio R. Machado, and Luiz G. Tone; Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP, Ribeirao Preto, Brazil INTRODUCTION: Encephalocraniocutaneous lipomatosis (ECCL) is an exceedingly rare genetic syndrome, with approximately 60 patients reported to date. Clinically, ECCL is characterized by cutaneous and ocular lesions, together with ipsilateral cerebral malformations that may lead to mental retardation, seizures, and behavioral problems. OBJECTIVE: to report two unrelated Brazilian patients affected by ECCL presenting pilocytic astrocytomas. METHODS: Case #1: A 2-month-old boy was seen with alopecia and failure to thrive. Encephalic magnetic resonance imaging (MRI) revealed encephalocraniocutaneous lipoma in the posterior fossa. At 3 years of age he developed sudden strabismus, vomiting, headaches, and seizures. A new Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2011. Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 PC-01. PRIMARY PERICRANIAL EWING’S SARCOMA/ PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMOR (ES/PPNET) IN VERY YOUNG CHILDREN Jeffrey C. Murray1, Nino Rainusso2, Richard A. Roberts1, Ana M. Gomez1, Rachel Egler2, Heidi Russell2, and M.F. Okcu2; 1Cook Children’s Medical Center, Fort Worth, TX; 2Texas Children’s Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX Abstracts PC-05. TRANSFORMATION OF PEDIATRIC NON-PILOCYTIC LOW-GRADE ASTROCYTOMAS TO MALIGNANT GLIOMAS: PRELIMINARY RESULTS OF THE CHILDREN’S HOSPITAL LOS ANGELES (CHLA) RETROSPECTIVE REVIEW, 1985-2010 Jonathan L. Finlay, Sarah Kreimer, Jennifer Dagri, John Grimm, Stefan Bluml, Barbara Britt, Girish Dhall, and Floyd Gilles; Children’s Hospital Los Angeles, Los Angeles, CA INTRODUCTION: Low-grade glial (LGG) tumors represent the largest group of all childhood brain tumors. About one-third are pure non-pilocytic diffuse astrocytomas of significantly poorer outcome than other LGG; the pace and frequency of malignant transformation of non-pilocytic LGG in children is poorly understood. Only one prior study addressed this, finding a 15-year cumulative incidence of malignant transformation of 6.7 + 3.5%. METHODS: To date, we have reviewed CHLA databases of all children with diagnoses of glial tumors of the central nervous system diagnosed between 1985 and 2010. All patients with WHO grade I tumors (pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and subependymal giant cell astrocytomas) as well as oligodendroglial tumor (either pure or mixed) and glioneuronal tumors (including gangliogliomas) were then excluded from further analysis. A total of 303 patients remained, with details of their original pathological diagnoses tabulated. Charts of the patients with non-pilocytic purely astrocytic tumors were then reviewed to document evidence of transformation to malignant gliomas. RESULTS: Of 303 patients with non-pilocytic pure astrocytic tumors, the pathological diagnoses were as follows: 140 astrocytoma, not otherwise specified (NOS), 12 glioma NOS, 3 fibrillary astrocytoma, and 1 protoplasmic astrocytoma, totaling 156 low-grade non-pilocytic astrocytomas (51.5%). The other 48.5% were high-grade astrocytic tumors (102 anaplastic astrocytoma, 22 glioblastoma multiforme, 23 malignant glioma NOS). Of the 156 patients with nonpilocytic low-grade astrocytomas, we have preliminarily identified 21 patients (13.5%) fulfilling criteria for low-grade gliomas that underwent malignant transformation. Specifics of timing from diagnosis to transformation will be presented. CONCLUSIONS: We have found a higher than previously reported incidence (13.5%) of malignant transformation of pediatric non-pilocytic astrocytomas. Comprehensive pathology and imaging (MRI and MR spectroscopy) reviews are being undertaken to consolidate this finding, and additionally include patients presenting with malignant gliomas in the setting of previously unrecognized low-grade astrocytomas. PC-06. ALLOGENEIC MARROW-ABLATIVE HEMATOPOIETIC CELL TRANSPLANTATION (HCT) FOR TREATMENT OF RECURRENT MEDULLOBLASTOMA Jonathan L. Finlay, Robert J. Brown, Girish Dhall, Ami Shah, Neena Kapoor, and Hisham Abdel-Azim; Children’s Hospital Los Angeles, Los Angeles, CA INTRODUCTION: Marrow-ablative chemotherapy with autologous HCT benefits a minority of patients with medulloblastoma recurring after prior irradiation. Allogeneic HCT following intensive chemotherapy for medulloblastoma has been reported in three publications over 20 years, describing two adult patients and one child with a short-lived response. We report our encouraging experience to date in one child with recurrent metastatic anaplastic/large cell (A/LC) medulloblastoma. PATIENT DATA: A 2.5-year-old boy presented in December 2008 with disseminated iii96 NEURO-ONCOLOGY † NOVEMBER 2011 A/LC medulloblastoma. He received multi-agent induction chemotherapy January-April 2009, with radiographic MRI response, followed by consolidation chemotherapy through June 2009, when brain and spine MRI demonstrated widespread leptomeningeal recurrence. He received 3600 cGy of craniospinal irradiation with a 5400-cGy posterior fossa boost July-August 2009. Within 4 months he began complaining of back and leg pains; brain and spine MRI were negative for CNS tumor; pelvic and spine MRI demonstrated widespread bone metastases. Iliac crest biopsy results were positive for medulloblastoma. He received salvage chemotherapy April-August 2010 with achievement of minimal tumor burden but incomplete remission. Attempt at harvesting autologous hematopoietic progenitor cells was unsuccessful. His 9-year-old brother was histocompatible, and the patient received marrow-ablative chemotherapy with thiotepa, melphalan, etoposide, and fludarabine followed by HCT with his brother’s bone marrow in September 2010. RESULTS: The patient tolerated treatment uneventfully and was discharged from hospital on day +47. He subsequently developed mild, transient skin chronic graft-versus-host disease (GvHD). The most recent evaluation (April 2011, at 7 months following HCT) found no evidence of disease by brain and spine MRI, lumbar CSF cytology, bone marrow aspirates and biopsies, or PET/CT imaging. He displays full marrow reconstitution, no GvHD, no bone pain, and an excellent quality of life with a Lansky PS of 80. CONCLUSIONS: Allogeneic HCT following marrow-ablative chemotherapy may be a consideration for appropriate high-risk recurrent medulloblastoma patients. PC-07. CUMULATIVE CISPLATIN DOSE DOES NOT CORRELATE WITH EVENT-FREE AND OVERALL SURVIVAL OUTCOMES IN CHILDREN WITH NEWLY DIAGNOSED AVERAGE-RISK MEDULLOBLASTOMA TREATED WITH CISPLATIN-BASED ADJUVANT CHEMOTHERAPY Amulya A Nageswara Rao1, Dana Wallace2, James Boyett2, Amar Gajjar2, and Roger J. Packer1; 1Childrens National Medical Center, Washington, DC; 2 St. Jude Children’s Research Hospital, Memphis, TN INTRODUCTION: Survival rates for children with medulloblastoma have risen over the past decade, in part due to the addition of cisplatincontaining post-radiation adjuvant chemotherapy. However, cisplatin is often associated with significant, irreversible, high-frequency hearing loss related to the total cumulative dose. The total dose of cisplatin required for optimal treatment is unknown. This study evaluated survival outcomes based on cumulative cisplatin doses in children with newly diagnosed average-risk medulloblastoma. METHODS: The cumulative cisplatin dose data were reviewed on 363 patients enrolled in a prospective study evaluating patients between 3 years and 21 years with newly diagnosed average-risk medulloblastoma and treated with craniospinal radiation and post-radiation adjuvant chemotherapy with one of the following two regimens: cisplatin, lomustine, and vincristine (Regimen A) or cisplatin, cyclophosphamide, and vincristine (Regimen B). RESULTS: Eight-year event-free survivals (EFS) were 74.9 + 3.8% and 81.6 + 3.6% for Regimens A and B, respectively. Only 73 patients received the protocol-specified cumulative cisplatin dose of 600 mg/m2, primarily due to mandated cisplatin toxicity-related dose reductions. The median cumulative cisplatin dose given in those patients without relapse or death was 487.5 mg/m2. Median follow-up for 306 patients alive at last follow-up is 8.9 years. Cox proportional hazards model showed that cumulative cisplatin dose, as a time-dependent covariate, was not associated with EFS (p ¼ 0.54). The 343 patients who did not have treatment failure during chemotherapy treatment were categorized according to cumulative cisplatin dose into four groups: 0-150 mg/m2 (N ¼ 10), 151-300 mg/m2 (N ¼ 26), 301-450 mg/m2 (N ¼ 113), and 451-600 mg/m2 (N ¼ 194). There were no statistically significant differences in EFS (p ¼ 0.53) or overall survival (OS) (p ¼ 0.49) among these four groups. CONCLUSIONS: Cumulative cisplatin dose does not correlate with EFS and OS. This study suggests that lower doses of cisplatin can be incorporated into future medulloblastoma protocols, which may limit its toxicity profile without affecting survival outcome. PC-08. RESPONSE OF PROGRESSIVE PEDIATRIC BIFRONTAL GLIOBLASTOMA MULTIFORME TO A COMBINATION OF TARGETED THERAPY USING TEMSIROLIMUS AND BEVACIZUMAB Michael L. Pearlman, Zsila Sadighi, Rachel Bingham, Trib Vats, and Soumen Khatua; The University of Texas MD Anderson Cancer Center, Houston, TX Survival of children with progressive or recurrent glioblastoma multiforme (GBM) continues to be dismal. No defined therapeutic strategy exists for these tumors, and current endeavors continue to profile combined Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 MRI showed an expanding lesion located at the suprasellar region and extending throughout the hypothalamus and third ventricles. The patient underwent a craniotomy with near-total resection. Pathological exam revealed a pilocytic astrocytoma. Tumor karyotype was normal, and comparative genomic hybridization (CGH) also showed a normal hybridization pattern. Three months later, an MRI revealed a short-term disease recurrence. He again underwent surgery with subtotal resection. No adjuvant treatment was offered, and disease remains stable. Case#2: A 1-month-old girl was seen due to frontal alopecia and a right palpebral nodule. This solid lesion displayed progressive enlargement with orbit involvement and was resected. The pathologic exam revealed lipoma. Epileptic status was also diagnosed. An MRI showed a tumor in the thalamic region, and biopsy revealed a pilocytic astrocytoma. CONCLUSION: Approximately 10% of children with brain tumors have a genetic disorder that increases the risk of developing cancer. Very few brain tumors other than nonprogressive benign lipomas have been reported in association with ECCL, including lipoastrocytoma, primitive neuroectodermal tumor with glioblastomatous differentiation and papillary glioneuronal tumor, but not pilocytic astrocytomas. Whether ECCL may be a genetic condition predisposing children to brain cancer, including low-grade gliomas, strongly needs to be addressed. Financial support: FAPESP (proc.2010/15717-0). Abstracts PC-09. TREATMENT OF NON-MIDLINE GERMINOMAS WITH A COMBINATION OF CHEMOTHERAPY AND REDUCED DOSE AND VOLUME IRRADIATION: A REPORT OF THREE CASES AND REVIEW OF THE LITERATURE Richard H. Ko1, Sharon O’Neil1, Robert S. Lavey2, Jonathan L. Finlay1, and Girish Dhall1; 1Children’s Hospital Los Angeles, Los Angeles, CA; 2Moffitt Cancer Center, Tampa, FL BACKGROUND: Central nervous system (CNS) germ cell tumors (GCTs) compose 3% of all brain tumors in children, of which approximately 70% are pure germinomas. These are usually found in midline structures (pineal and suprasellar areas) and are much less common in non-midline sites such as the basal ganglia and fourth ventricle. Historically, treatment of germinomas with craniospinal irradiation (CSI) plus primary site boost to 50 Gy has resulted in 5- and 10-year overall survival ranging from 86% to 100%. Lately, a combined chemotherapy and reduced dose and volume irradiation approach has been favored and shown to be efficacious by many groups for midline tumors. Treatment of non-midline germinomas, however, remains controversial. In the recently closed North American Children’s Oncology Group study, patients with non-midline germinomas were treated with CSI; in the Japanese Cooperative Group study, such patients were treated with whole-brain irradiation. METHODS: We retrospectively reviewed for treatment and outcome the medical records of three patients who were diagnosed with localized germinoma in non-midline sites [fourth ventricle (1 patient) and basal ganglia (2 patients)] at Children’s Hospital Los Angeles between 2003 and 2008. RESULTS: All three patients received four 28-day courses of carboplatin (300 mg/m2/day × 2 days/course) and etoposide (150 mg/m2/day × 3 days/course) followed by whole ventricular irradiation (WVI) between 21-25 Gy and 30 Gy to the primary tumor bed (basal ganglia primaries) or the entire posterior fossa (fourth ventricle primary). Neuropsychological testing showed that none of these patients had any significant decline in function. In addition, none have any endocrine issues. They are all alive and well, without evidence of disease at 4, 5, and 6 years from diagnosis. CONCLUSION: We report the successful treatment of three patients with non-midline germinomas using a combination of chemotherapy and reduced dose WVI with preservation of intellectual function. PC-10. EXTRANEURAL METASTASES IN PEDIATRIC MYXOPAPILLARY EPENDYMOMA Tom B. Davidson, Floyd Gilles, Jason Tovar, John Grimm, Kenneth Wong, Arthur Olch, Girish Dhall, and Jonathan L. Finlay; Children’s Hospital Los Angeles, Los Angeles, CA INTRODUCTION: Spinal myxopapillary ependymomas (MxEp) most commonly arise in young adulthood, less commonly in childhood or adolescence. Standard treatment is surgical resection, with survival exceeding 10 years following subtotal or complete resection. Irradiation is beneficial in patients with large residual or recurrent tumors. MxEp are considered benign due to their long natural history and predilection for local containment. A small proportion of patients develop leptomeningeal and less commonly intracranial tumor. Extraneural metastases (ENM) in MxEp have been rarely reported, usually developing years to decades after the initial diagnosis in adult patients; pediatric reports are anecdotal. CASE REPORT: We present the case of a child with multiple recurrent MxEp who died of ENM 54 months after the initial MxEp diagnosis. Our patient presented at 6 years of age with progressive radiating right leg pain, with MRI revealing a 2-cm intradural mass at L1-L2 below the level of the conus medullaris. Gross total tumor resection revealed MxEp with focally increased MIB-1. He remained disease-free for 21 months before developing three intradural nodules at L2. Near gross total resection was achieved. Pathology confirmed MxEp with increased diffuse MIB-1 of 30%. He then received 4500 cGy of irradiation to the T10-S4 levels with boost to 5400 cGy at T12-S3. Nine months later, tumor recurred at L2. Resection revealed MxEp with elevated MIB-1 of 50%. Tumors continued to reappear in the thoraco-lumbar spine despite multiple courses of chemotherapy requiring two more surgeries. By age 10 years, the patient had lower extremity paraplegia and bowel/bladder dysfunction due to progressive tumor. Just prior to his 11th birthday, he developed widespread lung metastases. The ENM progressed rapidly for 3 months until he died of pulmonary failure. At autopsy, tumor was found throughout his lungs, pleura, liver, kidney, bone, and bone marrow. CONCLUSION: This report demonstrates the potentially aggressive nature of MxEp in pediatric patients. PC-11. CONGENITAL SPINAL CANAL TUMORS: A REPORT OF TWO INFANTS WITH UNUSUAL NEUROIMAGING AND HISTOPATHOLOGY Jeffrey C. Murray, John H. Honeycutt, David J. Donahue, Hayden W. Head, and Ajit J. Alles; Cook Children’s Medical Center, Fort Worth, TX Congenital spine abnormalities are usually non-neoplastic and related to aberrant embryogenesis. Tumors of the spine are extraordinarily rare. Following IRB approval, records from two infants with congenital spinal canal tumors were reviewed. Case One: A 35-week-gestation female developed respiratory distress at birth and was found to have hemidiaphragmatic paralysis and unilateral upper extremity paresis. Brain MRI results were normal. Spine MRI revealed a C3-C4 enhancing spinal canal mass, compressing the cord and appearing intradural but extramedullary. Via C2-C5 laminectomies, an intradural, intra-/extra-medullary tumor was resected. Histopathology revealed a tumor descriptively classified as ‘myofibroblastic proliferation,’ densely adherent to the cord, with immunoreactivity to alpha-actin and negative for desmin. The tumor karyotype was normal (46XX). Adjuvant therapy was not given. The infant required postoperative rehabilitation and has had no evidence of recurrent tumor. Case Two: A 3 month-old female presented with vague abdominal symptoms and decreased lower extremity movement. Brain MRI results were normal. Spine MRI revealed an expansile, enhancing, C7-T11 tumor appearing to be intramedullary, with bipolar edema, hypervascularity or infiltration of the cord. Via C6-T11 laminectomies, a 7.6-cm tumor was removed, en bloc, ‘peeling’ away from the compressed cord yet with some foci of adherence/ invasion of the cord. Histopathology revealed a cellular, heterogeneous tumor, descriptively classified as a ‘malignant tumor with glial, neuronal and mesenchymal differentiation’ with focal peripheral GFAP positivity, scattered synaptophysin-positive ganglion cell nodules, and islands of cartilage and osteoid. MIB1 was focally increased. A clonal tumor karyotype was identified: 47,XX, + mar?der(20)t(1;20)(p32;q13)[19]/ 48,idem,der(11)t(7;11)(q11.2;q23), + mar[1]. The child recovered well from surgery, remains paraparetic, and is receiving adjuvant chemotherapy. Congenital spinal canal tumors are rare and often atypical in their neuroimaging and histologic characterization. Extramedullary location might be predominant. Aggressive resection is often feasible. Further reporting of these rare congenital tumors will permit increased understanding of the histology, molecular biology, and neurodiagnostics. PC-12. DEVELOPMENT OF EPENDYMOMA FOLLOWING ALLOGENEIC CORD BLOOD TRANSPLANTATION IN A SICKLE CELL PATIENT Anish Ray, M. Pearlman, T. Vats, and Soumen Khatua; The University of Texas MD Anderson Children’s Cancer Center, Houston, TX The etiology of ependymomas remains ill-defined beyond a genetic predisposition. A causal relation between oncogenesis of high-grade gliomas and infections with Epstein-Barr (EB) and SV40 virus following immunosuppression for bone marrow transplant (BMT) has been reported. Similar correlations for intracranial ependymomas have not been described. We report a case of a 16-year-old male with sickle cell disease who developed stroke at 5 years of age and received 6/6 matched related cord blood transplant (CBT) at 10 years. His transplant went well without major complications NEURO-ONCOLOGY † NOVEMBER 2011 iii97 Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 molecular-targeted therapy against different signaling pathways in GBM. We report a novel case of a pediatric patient with refractory, progressive bifrontal GBM with a dramatic response to a combination of temsirolimus and bevacizumab after failure of multiple prior chemotherapeutic regimens. A 16-year-old male presented with complex partial seizure and altered consciousness. Brain MRI showed a left frontal lesion. A subtotal resection was performed, with the pathologic results consistent with GBM. His initial therapeutic regimen included radiation with concurrent temozolomide. As the tumor progressed he received irinotecan and bevacizumab. Owing to irinotecan toxicity, he received monotherapy with bevacizumab. Following this he received different therapeutic regimens, which included antineoplastins, CCNU and temozolomide, topotecan and temozolomide along with steroids for tumor progression. Neuroimaging showed a progressive tumor, however, and he had significant clinical deterioration. His regimen was changed to temsirolimus 25 mg weekly and bevacizumab 15 mg/kg every 3 weeks. Brain MRI after his first cycle of therapy demonstrated a substantial decrease in tumor burden. He continues to remains stable clinically with no evidence of disease progression on MRI scans over the last 2 months on this regimen. To our knowledge this is the first case report that illustrates the potential role of combining targeted agents against m-TOR and VEGF using temsirolimus and bevacizumab, respectively, in progressive pediatric GBM. Molecular diversity and diverging and converging signaling pathways have hindered single-agent targeted therapy by inducing therapeutic resistance in GBM. This successful combined targeted therapy with likely synergistic effects needs to be evaluated further in larger prospective studies. Abstracts PC-13. EVALUATION OF AVAILABLE RESOURCES FOR OPTIMAL CARE OF CHILDREN WITH BRAIN TUMORS IN CENTRAL AMERICA Jacquelyn Baskin1, Ibrahim Qaddoumi2, Maria Sabina Ahchu3, Soad Fuentes Alabi4, Ingrid Carolina Arambu5, Mauricio Castellanos6, Yessika Gamboa7, Roxana Martinez8, Margarita Montero9, Enrique Ocampo10, Scott C. Howard2, and Jonathan L. Finlay1; 1Children’s Hospital Los Angeles, Los Angeles, CA; 2St. Jude Children’s Research Hospital, Memphis, TN; 3Hospital del Niño de Panama, Panama City, Panama; 4Hospital del Niño Benjamin Bloom, San Salvador, El Salvador; 5 Hospital Materno Infantil Escuela, Tegucigalpa, Honduras; 6Unidad Nacional de Oncologı́a Pediátrica, Guatemala City, Guatemala; 7Hospital Nacional de Niño, San Jose, Costa Rica; 8Hospital Mario C. Rivas, San Pedro Sula, Honduras; 9Hospital Infantil Dr. Robert Reid Cabral, Santo Domingo, Dominican Republic; 10Hospital Infantil La Mascota, Managua, Nicaragua Advances in pediatric cancer in low-income countries have focused on management of acute leukemia, treatment of which requires chemotherapy and adequate supportive care. These improvements have not been matched for childhood brain tumors, which require complex multidisciplinary management. A needs assessment questionnaire to evaluate resources required to deliver multidisciplinary care for pediatric brain tumors was administered to the eight major pediatric oncology programs in Central America, in Costa Rica, Dominican Republic, El Salvador, Guatemala, Nicaragua, Panama, and two centers in Honduras. All eight centers had access to pediatric oncologists, specialized oncology nurses, and data managers. None had a neuroradiologist or a neuropathologist, and only one had access to all essential immunohistochemical stains. There was a disparity in available neurosurgical services (two did not have access and four lacked adequate equipment), timely radiological tests, and optimal radiation therapy (delays ranging from 2 to 12 weeks at least some of the time in seven centers, and three centers with only cobalt machines available). These barriers likely translate into poor outcomes with variance in overall survival: 50% in three centers, less than 35% in three centers, 70% in one center, and unknown in another. The majority of respondents commented on both the lack of multidisciplinary care and delayed diagnosis, the latter of which may contribute to high rates of advanced disease on presentation, In 50% of the centers, at least half of the patients present with disseminated disease. Common as well as particular deficiencies in available resources essential for the management of children with brain tumors have been identified in the major treatment facilities in Central America. Potential interventions include regionalized protocols with caveats to accommodate individual barriers, strategies to increase awareness and promote communication among community health care workers, and development of regional training centers for essential disciplines based on programs with well established services. PC-14. A PHASE I STUDY OF THE COMBINATION OF VANDETANIB AND DASATINIB ADMINISTERED DURING AND AFTER RADIOTHERAPY (RT) IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) Alberto Broniscer1, Sharyn D. Baker1, Justin N. Baker1, Atmaram Pai Panandiker1, Arzu Onar-Thomas1, Thomas K. Chin2, Thomas E. Merchant1, Andrew Davidoff1, Sue C. Kaste1, Amar Gajjar1, and Clinton F. Stewart1; 1St. Jude Children’s Research Hospital, Memphis, TN; 2 University of Tennessee Health Sciences Center, Memphis, TN iii98 NEURO-ONCOLOGY † NOVEMBER 2011 The prognosis of children with DIPG is poor. PDGFRA is the most commonly amplified oncogene in DIPG. We conducted a Phase I study in children with newly diagnosed DIPG to evaluate the safety, maximum tolerated dose, and pharmacokinetics of the combination of vandetanib (VEGFR2 and EGFR inhibitor) and dasatinib (PDGFR inhibitor) during and after local RT (54 Gy). We tested increasing doses of vandetanib (65 and 85 mg/m2 once daily) and dasatinib (65 and 85 mg/m2 twice daily). Dose-limiting toxicities (DLTs) were evaluated during the first 6 weeks of therapy. Dasatinib alone was administered on days 1-8, and vandetanib was started on day 9. Pharmacokinetic studies were obtained from all patients on days 8 and 42 (+3). Twenty-five patients were enrolled in the study (median age 5.9 years). One of six patients treated with vandetanib and dasatinib at 65 mg/m2 (dosage level 1) experienced a DLT (grade 3 increased amylase). Two of three patients treated with vandetanib at 85 mg/m2 and dasatinib at 65 mg/m2 (dosage level 2a) experienced DLTs consisting of grade 3 thrombocytopenia (n ¼ 1) and grade 3 increased amylase/lipase (n ¼ 1). Although no DLTs were observed among the first three patients treated with vandetanib at 65 mg/m2 and dasatinib at 85 mg/m2 (dosage level 2b), all experienced significant toxicities within 8 weeks of starting therapy (grade 3 colitis and grade 4 neutropenia/thrombocytopenia; grade 4 neutropenia and grade 3 neutropenic fever; grade 2 intolerable diarrhea). One of 10 additional patients treated at dosage level 1 experienced a DLT (grade 3 hypoalbuminemia). The median steady-state AUC0-24 and apparent oral clearance of vandetanib at 65 mg/m2 were 18,282 ng/ml hr and 3.2 L/hr/ m2, respectively. The exposure to dasatinib decreased on day 42 (AUC0-12 were 567 and 368ng/ml hr on days 8 and 42, respectively; P ¼ 0.045). The recommended Phase II dose of this combination in children is vandetanib at 65 mg/m2 daily and dasatinib at 65 mg/m2 b.i.d. PC-15. FINAL REPORT ON OUTCOME OF CHILDREN WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (HGG) TREATED WITH MULTI-DRUG INDUCTION CHEMOTHERAPY FOLLOWED BY CONSOLIDATIVE MYELOABLATIVE CHEMOTHERAPY AND AUTOLOGOUS HEMATOPOIETIC PROGENITOR CELL RESCUE (AuHPCR) ON THE “HEAD START” II AND III PROTOCOLS Juan Espinoza1, Kelley Haley1, Neha Patel2, Girish Dhall1, Sharon Gardner3, Allen Jeffrey3, Joseph Torkildson4, Albert Cornelius5, Rod Rassekh6, Antranik Bedros7, Morris Etzl8, James Garvin9, Kamnesh Pradhan10, Robin Corbett11, Michael Sullivan11, Geoffrey McGowage12, Diane Puccetti2, Dagmar Stein13, Rama Jasty13, Lingyun Ji14, Richard Sposto1, and Jonathan L. Finlay1; 1Children’s Hospital Los Angeles, Los Angeles, CA; 2University of Wisconsin, Madison, WI; 3New York University Medical Center, New York, NY; 4Children’s Hospital of Oakland, Oakland, CA; 5DeVos Children’s Hospital, Grand Rapids, MI; 6Brittish Columbia Children’s Hospital, Vancouver, BC, Canada; 7Loma Linda University Medical Center, Loma Linda, CA; 8Phoenix Children’s Hospital, Phoenix, AZ; 9Columbia Children’s Hospital, New York, NY; 10Riley Children’s Hospital, Indianapolis, IN; 11University of Otago, Christchurch, New Zealand; 12 Children’s Hospital at Westmead, Sidney, Australia; 13Mercy Children’s Hospital, Toledo, OH; 14USC Norris Comprehensive Cancer Center, Los Angeles, CA BACKGROUND: Survival for all children with HGG remains poor, and quality of survival is particularly poor in the youngest of children. OBJECTIVE: We present the final analysis of survival outcomes for children with newly diagnosed HGG treated on the “Head Start” II and III protocols with primary chemotherapy and the intent to avoid irradiation in children ,6 years old. METHODS: Between 1997 and 2009, 32 eligible children were enrolled in Head Start II or III with anaplastic astrocytoma (AA, n ¼ 18), glioblastoma multiforme (GBM, n ¼ 12), or other malignant gliomas (n ¼ 2). Seventy-one percent of patients have undergone central review of pathology to date. Patients with predominantly brainstem gliomas were excluded. Patients were treated uniformly with “Head Start” protocol Regimen C. Patients were to undergo maximal surgical resection, followed by four cycles of intensive induction chemotherapy with vincristine, carboplatin, and temozolomide. Following induction, patients underwent myeloablative chemotherapy and AuHPCR. Irradiation was recommended after consolidation only for patients either with residual tumor or .6 years old, or otherwise at tumor progression. RESULTS: The 3-year EFS and OS for all HGG patients were 31 + 9% and 51 + 10%, respectively. The 3-year EFS and OS for AA and GBM patients were 31 + 12% and 46 + 13%, and 40 + 15% and 51 + 16%, respectively. Children ,36 months old experienced a trend towards relatively improved 3-year EFS and OS, with values of 44 + 17% and 63 + 17%, compared with children 36-71 months old (37 + 14% and 50 + 15%) and children .72 months old (13 + 12% and 45 + 17%). CONCLUSIONS: Irradiation-avoiding treatment strategies should be evaluated further in young children with HGG, given survival rates similar to those for older children receiving standard Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 or infections with EB or BK virus, which are known to induce secondary malignancies. His graft versus host disease (GVHD) prophylaxis included methotrexate and cyclosporine, which was discontinued after 100 days after transplant. Six years later, he presented with headache and ataxia. Brain MRI showed a tumor in the posterior fossa. A gross total resection was performed, and the pathology was consistent with anaplastic ependymoma. The patient’s spinal neuroimaging and CSF cytology results were negative for metastatic spread. He is receiving proton radiation to the tumor bed and tolerating therapy well. To date, the risk factors for development of ependymoma have remained obscure beyond genetic predisposition in neurofibromatosis and Li-Fraumeni syndrome, neither of which is present in this patient. Secondary solid tumors including meningiomas and astrocytomas are described as long-term sequelae of myeloablative allogeneic BMT for leukemia, especially for patients who received cranial irradiation and had significant GVHD. To our knowledge, this is the first case report of an ependymoma presenting as a secondary malignancy following CBT for a hematological disorder. Further studies are needed to determine a causal relation between oncogenesis of ependymomas and immunosuppression following uncomplicated CBT, which could potentially disrupt the CNS immune system, predisposing patients to these tumors. Abstracts irradiation-containing therapies. Whether such outcome differences reflect aggressiveness of treatment interventions or intrinsic biological differences between the younger and older children remains unclear. BACKGROUND: The prognosis for patients with recurrent intracranial ependymoma, which recurs in almost half of patients, is poor. METHODS: We retrospectively reviewed the medical records of 22 patients (9 males, 13 females) with a total of 59 recurrences of intracranial ependymoma treated at Children’s Hospital Los Angeles or New York University between January 1997 and December 2009. RESULTS: Median duration of follow-up after primary diagnosis was 52 months (7-171 months). Median age at initial diagnosis was 4 years (0.3-19 years), with eight patients younger than 3 years at presentation. Eleven patients had anaplastic and 11 cellular pathologies. Four patients had supratentorial and 18 infratentorial tumors. Four patients (all primary infratentorial) had spinal cord involvement at presentation. Neither cerebrospinal fluid nor extra-neural involvement was identified at diagnosis. All primary tumors were initially radically resected, with 13 gross total resections (GTR) and nine subtotal resections (STR). Eighteen patients received additional therapy for their primary tumor (11 chemotherapy, 9 irradiation, 2 both irradiation and chemotherapy). Median time to first recurrence was 16 months (1.3 to 115 months). The number of recurrences in each patient ranged from one to nine (median two recurrences). Thirty-seven recurrences (63%) were detected asymptomatically during radiographic follow-up. Fourteen recurrences (24%) arose outside the primary tumor site. GTR was achieved in 30 of 45 recurrences treated by resection. Thirty recurrences were treated with irradiation and 24 with various oral chemotherapies with (9) or without (15) conventional chemotherapy. The 5- and 10-year overall survival rates from first recurrence were 41 + 14% and 27 + 14%, respectively. One of two patients undergoing myeloablative chemotherapy is alive at 144 months following treatment. CONCLUSIONS: Prolonged (5-10 year) survival from first relapse was noted in over one-quarter of our patients. It remains unclear whether early radiographic diagnosis or differing treatment modalities beyond radical surgical resection contributed towards this prolonged survival. PC-17. A CHILD WITH ROBIN SEQUENCE, NF2 AND DEL(22)(Q12.2) ENCOMPASSING THE FACIAL DEVELOPMENT-ASSOCIATED GENE, MN1 Tom B. Davidson, Pedro A. Sanchez-Lara, Linda M. Randolph, Mark D. Krieger, ShiQi Wu, Ashok Panigrahy, Hiroyuki Shimada, and Anat Erdreich-Epstein; Children’s Hospital Los Angeles, Los Angeles, CA Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutation in the NF2 gene on chromosome 22q12.1. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas, gliomas, and juvenile cataracts. Robin sequence (RS) is defined by micro- and/or retrognathia, glossoptosis, and cleft soft palate, either caused by deformational defect (e.g., Potter sequence) or as part of a malformation syndrome (e.g., Stickler syndrome). To date, NF2 and Robin sequence have not been described together in the same patient. We report a female with Robin sequence (RS; micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation, and bilateral conductive hearing loss, diagnosed at age 15 years with NF2 and bilateral cerebellopontine schwannomas. High-resolution karyotype revealed 46,XX,del(22)(q12.1q12.3), FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3693-kb deletion encompassing multiple genes including NF2 and MN1. This is the first published report of a child with both RS and NF2. Only four other patients have been reported with mental retardation, craniofacial dysmorphism, and deletion in chromosome 22-adjacent or containing NF2. The chromosomal deletion in these patients also encompassed MN1, PITPNB, and TTC28. Interestingly, Mn1-knockdown mice have abnormal skull development and cleft palate. Moreover, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with cleft palate in mice and humans. Thus, our report introduces a novel NF2-adjacent chromosome 22q12 deletion syndrome and is the first to report association of MN1 deletion in humans with abnormal craniofacial development and/or cleft palate. Cancer-associated retinopathy (CAR) is a rare ocular paraneoplastic process in which tumor-expressed antibodies cross-react against retinal antigens. Clinical findings include progressive visual loss, constriction of visual fields, reduced electroretinogram response, and retinal degenerative changes. The most common malignancies associated with CAR include small cell lung cancer, gynecologic tumors, melanoma, and leukemia. CAR has rarely been reported in children, with only one published case in the pediatric age group. Our case is an 8-year-old girl with a diagnosis of a suprasellar pilocytic astrocytoma. Her initial vision exam demonstrated mild temporal optic nerve pallor, and Goldmann visual field demonstrated a right homonymous hemianopia with constriction of her peripheral vision. She experienced radiographic progression after her partial resection and received chemotherapy with vincristine and carboplatin. Her tumor did regress in size based on MRI scans, and she remained free of any visual symptoms. Nine months after completion of her chemotherapy, repeat Goldmann visual fields revealed a significant constriction of her peripheral vision in each eye. A multifocal visual evoked potential test confirmed profound reduced amplitudes of her remaining visual hemifields. Brain MRI did not show any evidence of progressive disease. Chemotherapy was re-instituted with weekly vinblastine, and we assessed her for the presence of anti-retinal cancer-associated antibodies. A Western blot was positive for autoantibodies against a 20-kDa retinal protein. Monthly visual fields were obtained, and 4.5 months later her visual fields demonstrated expansion in each eye, with steady improvements over the next several months. An electroretinogram (ERG) performed several months later demonstrated normal scotopic and photopic responses. We hypothesize that the chemotherapy’s immunosuppressive effects led to her visual improvement. Although rare in children, CAR should be considered in the setting of a malignancy and unexplained vision loss. PC-19. TREATMENT OUTCOMES OF CHILDREN AND ADOLESCENTS WITH AVERAGE-RISK MEDULLOBLASTOMA: MULTICENTER STUDY IN KOREA Hyeon Jin Park1, Jong Hyung Yoon1, Hyo Seop Ahn2, Hee Young Shin2, Seung Ki Kim3, Ho Joon Im4, Young Shin Ra5, Sung Chul Won6, Hee Jo Baek7, Ki Woong Sung8, Jung Ok Hah9, Young Tak Lim10, Gun Soo Lee11, Young Ho Lee12, Heung Sik Kim13, Ji Kyung Park14, Moon Kyu Kim15, Jun Eun Park16, Nak Gyun Chung17, and Hyung Soo Choi18; 1Center for Pediatric Oncology, National Cancer Center, Goyang, Republic of Korea; 2 Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5 Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 6Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 7Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Republic of Korea; 8Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 9 Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Republic of Korea; 10Department of Pediatrics, Pusan National University College of Medicine, Pusan, Republic of Korea; 11Department of Pediatrics, Kyungpook National University College of Medicine, Daegu, Republic of Korea; 12Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea; 13Department of Pediatrics, Keimyung University, Dongsan Medical Center, Daegu, Republic of Korea; 14 Department of Pediatrics, Pusan Paik Hospital, Inje University College of Medicine, Pusan, Republic of Korea; 15Department of Pediatrics, CHA Medical School Hospital, Seongnam, Republic of Korea; 16Department of Pediatrics, Ajou University School of Medicine, Suwon, Republic of Korea; 17 Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 18Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Medulloblastoma (MBL) is the most common primary malignant brain tumor of childhood. Because there are no definite estimates and analyses for clinical outcomes in average-risk MBL in Korea, we investigated the clinical characteristics and treatment outcomes of children and adolescents with average-risk MBL. Questionnaires about the demographics, clinical characteristics, treatments, and outcomes of children and adolescents diagnosed with average-risk MBL between 2000 and 2010 were sent to the member hospitals of the Korean Society of Pediatric Neuro-Oncology (KSPNO). NEURO-ONCOLOGY † NOVEMBER 2011 iii99 Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 PC-16. RECURRENT INTRACRANIAL EPENDYMOMA AS CHRONIC DISEASE: A RETROSPECTIVE ANALYSIS Reuben Antony1, Sharon Gardner2, Moneil Patel1, Kenneth E. Wong1, Barbara Britt1, Girish Dhall1, John Grimm1, Mark Krieger1, Gordon McComb1, Floyd Gilles1, Richard Sposto1, and Jonathan L. Finlay1; 1 Children’s Hospital Los Angeles, Los Angeles, CA; 2New York University Medical Center, New York, NY PC-18. CANCER-ASSOCIATED RETINOPATHY IN A CHILD WITH PILOCYTIC ASTROCYTOMA Diane M. Puccetti1, Neha Patel1, Tabassum Kennedy2, Shahriar Salamat2, and Yasmin Bradfield2; 1American Family Children’s Hospital, Madison, WI; 2University of Wisconsin Hospital and Clinics, Madison, WI Abstracts PC-20. CONCURRENT CYCLOPHOSPHAMIDE AND CRANIOSPINAL RADIATION IN PEDIATRIC EMBRYONAL BRAIN TUMORS Cynthia J. Campen and Paul G. Fisher; Stanford University, Stanford, CA PURPOSE: Embryonal tumors are an aggressive subtype of high-grade, pediatric brain tumors with a tendency to metastasize and often dismal patient survival rates. The 5-year survival for children with highest-risk embryonal tumors may be as low as 10%. We report the feasibility and efficacy from our experience using intravenous cyclophosphamide given concurrently with craniospinal radiation (CSI) in high-risk embryonal brain tumors of childhood. METHODS: Seven children (age 3.5-15.5 years, median 10 years) with high-risk embryonal tumors, including four with large cell/anaplastic medulloblastoma, one with atypical teratoid rhabdoid tumor, and two with leptomeningeal primitive neuroectodermal tumor (PNET), were treated with intravenous cyclophosphamide on days 1 and 2 of CSI. Following 36-Gy CSI plus tumor boosts, adjuvant treatment then consisted of alkylator-based chemotherapy from 5 to 8 cycles. RESULTS: Of those treated, four remain alive with no evidence of disease and thyree have died. Mean follow-up was 5.7 years (range 5 months-12 years 9 months) in the three patients with progression, and mean time to progression was 1.8 years (range 5 months-3 years). Complications of all treatments included myelosuppression (3), hypothyroidism, cerebellar mutism (2), and cavernoma (1). CONCLUSION: In high-risk embryonal tumors, cyclophosphamide given concurrently with CSI is well tolerated and may improve 5-year progression and overall survival. Further, prospective trials are necessary to establish improved survival. PC-21. STEREOTACTIC BRACHYTHERAPY WITH 125 IODINE SEEDS (SBT) FOR THE TREATMENT OF INOPERABLE LOW-GRADE GLIOMAS IN CHILDREN: LONG-TERM OUTCOME OF 147 PATIENTS Maximilian I. Ruge1, Thorsten Simon1, Bogdana Suchorska2, Ralph Lehrke3, Christina Hamisch1, Frederike Koerber1, Harald Treuer1, Frank Berthold1, Volker Sturm1, and Juergen Voges4; 1University Clinics of Cologne, Cologne, Germany; 2University Clinic Munich Grosshadern, Munich, Germany; 3 St. Barbara Clinics Hamm, Hamm, Germany; 4University Clinics of Magdeburg, Magdeburg, Germany OBJECTIVE: Resection is generally considered the gold standard for treatment of low-grade gliomas (LGG) (WHO grades I and II) in childhood. However, approximately half of these patients cannot undergo surgery due to tumor localization in highly eloquent brain areas. Scarce reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 (125I) seeds as a safe and effective local treatment alternative. This single-center study summarizes the long-term outcome after SBT in one of the largest reported series. METHODS: All pediatric patients treated with SBT (125I seeds, cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG I&II with follow-up .6 months were included. Clinical and radiological outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky Performance Status (KPS), tumor volume/histology) for survival and disease progression were investigated. For statistical analysis, iii100 NEURO-ONCOLOGY † NOVEMBER 2011 Kaplan-Meier estimates, the log-rank test, and the chi-square test were used. RESULTS: A total of 160 patients underwent SBT (1982-2009). Among the 147 patients further evaluated, no procedure-related mortality was found. The 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93% and 82%, respectively, with no significant difference between WHO8I and WHO II (median follow-up 67.1 + 57.7 months). Twenty-one (14.3%) of 147 patients presented with tumor relapse; 11 died after multimodal treatment. Of the remaining 126 patients, 24.6% had complete response, 31.0% had partial response, and 29.6% had stable disease. Neurological status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had a significant effect on the study’s endpoints, except for tumor volume .15 ml causing significantly higher rates of tumor recurrence (p , 0.05). CONCLUSION: We demonstrated that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO8I and II. PC-22. FEASIBILITY AND TOLERABILITY OF THIOTEPA-BASED MYELOABLATIVE CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS HEMATOPOIETIC CELL RESCUE IN CHILDREN WITH DOWN SYNDROME Tom B. Davidson, Jonathan L. Finlay, and Girish Dhall; Children’s Hospital Los Angeles, Los Angeles, CA INTRODUCTION: Children with Down syndrome (DS) are considered to be at increased risk for toxicity from high-dose chemotherapy. We report the first two cases of patients with DS treated with thiotepa-based myeloablative chemotherapy (thiotepa 300 mg/m2 IV and etoposide 500 mg/m2 IV × 3 days) followed by autologous hematopoietic cell rescue (AuHCR) in order to consolidate remission and in an attempt to reduce the dose and volume of irradiation. Patient #1 is a 13-year-old female with DS and intracranial mixed malignant germ cell tumor (MMGCT). MRI revealed a lobulated, enhancing lesion involving the sella turcica, left cavernous sinus, suprasellar cistern gland, and pituitary stalk. The patient had elevated AFP and normal HCGb in the serum and the CSF. Chemotherapy was initiated as per Children’s Oncology Group (COG) study ACNS0121. She had a complete radiographic and tumor marker response (CR) to six cycles of induction chemotherapy. She underwent myeloablative chemotherapy with AuHCR and tolerated it well except for mucositis and fever that lasted 8 days with no positive cultures. She engrafted on day +13 and remains without sequelae 7 months post-AuHCR. Patient #2 is a 7-year-old female with DS diagnosed with intracranial multifocal MMGCT. MRI revealed an enhancing suprasellar mass, a pineal region mass, and ependymal enhancement in the third ventricle. She had highly elevated HCGb and mildly elevated AFP in serum and CSF. Chemotherapy was initiated as per COG study ACNS0121. She achieved chemical and radiographic CR to induction chemotherapy. She then underwent myeloablative chemotherapy with AuHCR. Treatment was tolerated well with the exception of Streptococcus anginosus bacteremia and mucositis. She was engrafted by day +13 and is doing well 8 months post-AuHCR. CONCLUSION: Thiotepa-based myeloablative chemotherapy followed by AuHCR is well tolerated in children with Down syndrome. PC-23. CHOROID PLEXUS TUMORS IN THE PEDIATRIC POPULATION Matthias Kirsch, Claudia Lindner, and Gabriele Schackert; Universitätsklinikum Dresden, Dresden, Germany Plexus adenomas and carcinomas are known to be highly vascularized and pose a major risk during surgery. This study considers a series of 13 pediatric choroid plexus tumors that were resected over a 14-year period and focuses on the surgical procedure and the risks involved. METHODS: Thirteen patients were included (age range 3 months to 23 years). Five patients had plexus carcinomas (patient age 3 months to 3 years), seven had plexus papillomas (age 5 to 23 years), and one had chondrosarcoma (age 13 years). All plexus carcinomas and the chondrosarcoma were located in the temporal and occipital horn of the ventricle; plexus papillomas were also found in the fourth ventricle. The supratentorial tumors had a median diameter of 4.5 cm. Neurological signs leading to the diagnosis of the tumors were mainly due to the mass effect. RESULTS: All tumors were approached through a temporo-occipital craniotomy or a suboccipital craniectomy. Complete tumor resection was performed in 12 of 13 cases. None of the tumors was embolized preoperatively. The blood loss was high in cases of plexus carcinomas, which mandated major blood transfusions and caused temporary cerebro-vascular destabilization and difficulties in hemostasis. Because the plexus carcinomas all occurred in neonates and early infants, high blood loss was a serious risk during surgery. There was no mortality, and no patient showed a major neurological deficit after surgery. The Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 From 16 hospitals, 159 patient records were collected, and retrospective review and analysis of them were performed. The median age at diagnosis was 8.5 years, and the male:female ratio was 102:57. Their histological subtypes were as follows: 107 classic, 14 large cell/anaplastic, 10 desmoplastic, and 28 unknown or other types. All patients had undergone surgery, and radiation therapy (RT) was performed in 153 patients. Fifty-three patients were initially treated with the KSPNO-M051 treatment protocol, and 106 patients were treated with other protocols. Median follow-up was 40 months, and 5-year event-free survival (EFS) and overall survival (OS) were 66.2 + 4.3% and 80.0 + 3.9%, respectively. Forty-eight patients showed events, with the majority being relapse or progression of disease. Compared with the patients without the large cell/anaplastic subtype (5-year EFS and OS of 68.4 + 4.4% and 81.3 + 4.0%, respectively), patients with the large cell/anaplastic subtype showed a tendency toward poor outcomes (EFS 49.0 + 13.6%, OS 68.8 + 13.1%) without reaching statistical significance. Comparison of outcomes between groups treated with craniospinal RT .3000 cGy (36 patients) and ,3000 cGy (98 patients), with EFS of 73.8 + 7.5% and 63.5 + 6.2% and OS of 90.7 + 5.1% and 81.3 + 5.0%, showed no significant differences. The clinical outcomes of childhood average-risk MBL in Korea were acceptable but slightly lower than those of patients in Western countries. These results demonstrate the need for prospective multicenter studies and further biologic investigations of average-risk MBL in Korea. Abstracts dignity of the tumor determined the adjuvant therapy and survival time. One patient developed intraventricular spread/metastasis and underwent surgery several times. CONCLUSIONS: Tumors of the choroid plexus are highly vascularized. Preoperative embolization of the main tumor feeder may be of advantage. However, the risk of embolization in neonates and infants must be weighed against the risk of high blood loss and consequent cardiovascular decompensation during surgery. Complete surgical resection is nearly always possible. INTRODUCTION: Few treatments exist for recurrent craniopharyngioma after resection and irradiation. We investigated the tolerability and response to bevacizumab in such patients. PATIENTS: Three patients with recurrent adamantinomatous craniopharyngioma were referred for management. Patient 1 was a 16-year-old female with diagnosis at age 9 years, who had undergone a partial resection followed by irradiation subsequently requiring five further surgical procedures, before beginning oral temozolo- NEURO-ONCOLOGY † NOVEMBER 2011 iii101 Downloaded from https://academic.oup.com/neuro-oncology/article-abstract/13/suppl_3/iii95/1287512 by guest on 16 June 2020 PC-24. BEVACIZUMAB FOR THE MANAGEMENT OF RECURRENT CRANIOPHARYNGIOMA IN ADOLESCENTS AND YOUNG ADULTS Robert J. Brown, Mark Krieger, Girish Dhall, and Jonathan L. Finlay; Children’s Hospital Los Angeles, Los Angeles, CA mide that caused significant myelosuppression without radiographic response. Patient 2 was a 20-year-old male with diagnosis at age 13 years, who underwent partial resection and irradiation and four further neurosurgical procedures before developing tumor progression. Patient 3 is a 16-year-old male with diagnosis at age 11 years; he underwent partial resection followed by irradiation and subsequently four surgeries before demonstrating tumor progression. RESULTS: Patient 1 received 4 months of bevacizumab complicated by headaches, leading to discontinuation, and later resumption at a lower dose with no adverse effects. Her MRI at 3 months demonstrated slight interval decrease and remains stable 18 months after initiation of therapy. Patient 2 received 6 months of therapy complicated by hypertension that was controlled with anti-hypertensives. His MRI at 3 and 6 months demonstrated significant decreases in the cystic component, and his family stopped treatment. MRI at 9 months was stable but at 12 months demonstrated interval increase, resulting in resumption of therapy. Patient 3 received 3 months of therapy with interval decrease in the cystic component of his tumor, but therapy was discontinued following exacerbation of a wound infection. His MRI is stable 3 months later, and he has resumed therapy without further complications. CONCLUSIONS: Bevacizumab is a well-tolerated agent for recurrent craniopharyngioma and, despite development of transient complications of hypertension, headaches, and wound breakdown and infection, can slow the rate of progression and decrease tumor-associated cysts. These data support a clinical trial of bevacizumab in patients with recurrent craniopharyngioma.