The 10th International

Symposium on

Pediatric Oncology

Written by Jeanne Young,

Reviewed by Kenneth Cohen, M.D., Deborah Lafond and Roger J. Packer, M.D.

The Childhood Brain Tumor Foundation was pleased to be a sponsor for the 10^th International Symposium on Pediatric Neuro-Oncology. The medical symposium is held every two years and was held on June 9-12, 2002 in London, England at the Hilton Metropole. In the following paragraphs we have outlined some of the highlights of the 3-day meeting. The focus of this year’s symposium was Advances and Direction for Research and Treatment for Pediatric Brain Tumors were the focus of this conference. The following is a brief overview of some of the many interesting topics presented.

The program was divided into several sessions. Dr. Archie Blyer, MD Anderson Cancer Center, Houston, Texas gave the opening keynote address. He updated the attendees with current information regarding Central Nervous System Tumor Epidemiology and Outcome in the Young, 2000-2009 and provided 10 predictions for/from the United States.

One prediction of interest: Progress will relate directly and proportionately to the number and proportion of patients entered into rigorous clinical trials and those with translational research, particularly in regard to children less than five-years-old and in adolescents and young adults. Another prediction: Survival length will likely increase after diagnosis in children, but plateau on the survival cure will not occur.

Chromosomal Imbalances in Choroid Plexus Tumors, was the topic of Dr. Christian Rickert from the Institute of Neurology, Germany. In summary, the results from the study indicated that aberrations differ between choroid plexus papillomas and choroid plexus carcinomas and also between pediatric patients and adults.

The Role of Comparative Genomic Hybridization in the Diagnosis and Management of Pediatric Brain Tumors was presented by Dr. Uri Tabori, Sheba Medical Center, Israel. He stated that molecular diagnostic technique, for example: comparative genomic hybridization (CGH) may add to prognosis, detection, and classification of pediatric brain tumors and could ultimately play a relevant role in evaluation and treatment of pediatric tumors.

During session 2, a few of the topics presented were:

Tumor Biology of Primitive Neuroectodermal Tumor (PNET) - Advances and Relevance were presented by Dr. Tobey MacDonald, Children’s National Medical Center (CNMC), Washington, D.C. The embryonal tumors in this study included, medulloblastoma, supratentorial PNET, and ependyblastoma, all sharing common features. PNET is the most common malignancy in central nervous system (CNS) tumors and histologic features do not reliably predict their behavior. Oligonucleotide microarray gene expression studies have recently shown that medullobalstoma is molecularly different from supratentorial PNET. Better analysis of gene expression is a more reliable means of predicting behavior.

Molecular Genomics of Central Nervous System Embryonal Tumors, presented by Dr. Scott Pomeroy, Children’s Hospital, Boston, MA, stressed that CNS embryonal tumors are poorly understood. DNA microarray gene expression profiles have provided biological insights for embryonal tumors. Dr. Pomeroy stated that medulloblastoma is distinctly different from other tumor types, such as, PNET, atypical teratoid/rhabdoid, and malignant tumors. He concluded that response to treatment is genetically predictable.

Management Strategies for Medulloblastoma/PNET Medulloblastoma, was presented by Dr. Roger J. Packer, CNMC. Dr. Packer was the Session 3 chair, and stated that medulloblastoma, the most common brain neoplasm of childhood, occurs in the cerebellum, is embryonal and varies in malignancy and aggressiveness. He reported that treatment approaches for this tumor have rapidly evolved. Adjuvant therapies, such as, chemotherapy has improved survival. Sequencing of treatment has not proven to improve survival. Evidence suggests that reduction of cranial spinal radiation dose may be acceptable for children with localized disease. Treatment for infants and young children have shown significant strides, and that possibly 30% of these children can be cured, but other patients will have progression. Patient stratification is based on clinical observations, such as, age at diagnosis, degree of resection and eventually will probably include or be replaced by molecular genetic classification.

Surveillance Scanning for Medulloblastoma: Is it Worth It? A Ten-Year Experience at Alder Hey, was a topic covered by Dr. McDowell, Liverpool, UK. In general, the study concluded and supported the perspective that earlier detection of asymptomatic recurrence provides a better outcome for patients than those that are flagged because of clinical symptoms.

Marrow Ablative Chemotherapeutic Strategies in the Treatment of High Risk Brain Tumors of Early Childhood was addressed by Dr. Jonathan Finley, Sloan-Kettering Cancer Center, NY. Children with a localized tumor have fared better, contrary to those with disseminated disease.

The session on High Grade Gliomas and other “Difficult” Tumors was chaired by Dr. D. Frappaz, Centre Leon Berard, France and Dr. Eric Bouffet, Hospital for Sick Children, Toronto, Canada. Dr. Frappaz spoke on High Grade Gliomas (HHG) in Children; Ongoing Debates. He stressed that clearly, high grade gliomas are a major challenge in terms of quality and quantity of life and that a major cooperative effort could perhaps lead to major breakthroughs. He added that surgical debulking appears to improve quality of life and survival.

Anti-Angiogenic Therapy in Brain Tumors, was presented by Dr. Mark Kieran, Dana-Farber Cancer Institute, Boston, MA, presented. Dr. Kieran emphasized the issue of difficulties in clinical designs and the fact that there are no known good surrogate;, thus, the dosage is ambiguous. Greater understanding of these agents is becoming known as clinical trials in humans are now ongoing.

The Role of Imaging in Tumors of the Brainstem and Spinal Cord, presented by Dr. Gilbert Vezina, CNMC, addressed the development of imaging technology. Imaging offers valuable information to the clinician, such as, tumor characterization, spatial location, definition of extent and, at times, limited classification. In addition, tumor staging, assessments of response to treatment, treatment planning and general surveillance scanning are all important in patient care. Another investigative tool is tissue biochemistry that can be investigated with spectroscopy and perfusion imaging.

The Influence of Activity on the Brain in Development and Disease was presented by Dr. Colin Blakemore, University of Physiology, Parks Road, Oxford, UK. Dr. Blakemore, in his presentation, stated that the cortex has long been considered a highly dynamic structure, although many aspects are determined genetically, and that some of the input and output connectivities and major sensory areas are affected by epigenetic influences. These influences are involved at pre birth in most mammals.

Final Outcome of a Phase I Trial of Low-Dose Temozolomide given concurrently with Radiation Therapy in Children and Adolescents with Brain Tumors was presented by Dr. Kenneth Cohen, pediatric oncologist from Johns Hopkins University Hospital, Baltimore, MD. In Dr. Cohen’s presentation, he spoke about patients carrying the diagnosis of brainstem glioma, anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, pilomyxoid astrocytoma, and well-differentiated astrocytoma who were enrolled in a study at one of three dose levels. In general, therapy was well tolerated, including therapy in young children. The regimen for young children was designed to administer the drug as open capsules for safety of administration. At the conclusion of the study, they determined a maximum allowable dose of temozolomide given over a six week period for children receiving focal radiation.

On day 3 of the Symposium, the co-chairs of Session 11, Low-Grade Astrocytomas-Role of Radical Surgery and what does Chemotherapy Achieve? were Dr. Georgio Perliongo, University Hospital of Padova, Italy and Dr. Jeffrey Wisoff, New York University, NY. Jeffrey Wisoff presented the topic, Surgical Management of Optic Pathway (OP) Tumors. He reported that OP tumors carry a variable natural history, particularly those involving the chiasm and hypothalamus, that may ultimately progress to gradual visual loss, cognitive compromise, and if untreated, death. The management of optic pathway tumors continues to remain controversial, especially with their erratic behavior causing difficulty in evaluation of efficacy of treatment regimens.

Dr. Perliongo presented the topic Low-Grade Astrocytomas (LGA) of the Optic Chiasm and Hypothalamus (OCH) ... what does Chemotherapy Achieve? Low-grade astrocytomas are chemo-treatable despite the tumor site; however, for the children with OCH LGA certain features, such as, the dimension, structures involved, resectability, exophytic/cystic component, distant spread and MRI presentation, should be considered to ascertain the appropriate treatment plan. Most of the children will need comprehensive, long-lasting treatment care from experts with multi-disciplinary teams.

The Clinical Impact of accurate diagnosis of NF1 was presented by Ian Cohen, Schneider Children’s Medical Center of Israel. Neurofibromatosis 1 (NF1) is a common autosomal dominantly inherited cancer. Approximately half of these patients represent new mutations and exhibit some variability in clinical expression even amongst family members. He concluded that it may be possible to predict an association between type of tumor and the site of NF1 germline mutations. Tumors may develop in some individuals before clinical diagnosis is made.

In Session 13, Pediatric Neuro-Oncology and the Developing Brain was the theme. Dr. Carlos de Sousa chaired this session and the keynote speaker for the session was Dr. Colin Kennedy, Southampton General Hospital, UK. The topic presented by Dr. Kennedy was Neuro-Endocrine and Neuropsychological Effects. In his talk, Dr. Kennedy outlined the risk factors for patients including adverse neuro-psychological outcomes, stunted growth from radiation therapy, cognitive decline, emotional and behavioral issues. Thorough follow-up with repeated measurements for the pediatric brain tumor patients over time will aid clinicians in determining if problems are continuing, temporary or if they only become noticeable over time.

Defects in Visual Short-Term Memory in Survivors of Pediatric Brain Tumors: Predictive Factors, was the topic presented by Dr. Marta Macedoni-Luksic, University Pediatric Hospital, Slovenia. Pediatric brain tumor patients, regardless of tumor type, often have issues with memory, visual-spatial functioning, balance, coordination and speech. Children with visual short-term memory loss are often impacted regarding school performance, especially since more classroom information is presented visually. For these reasons, it is important for pediatric brain tumor patients to have neuropsychological testing, including age-appropriate subtests.

Unfortunately, as space is limited it is impossible for us to summarize a great deal of the excellent information presented at the medical symposium. However, we have tried to highlight many of the symposium presentations and hope that you have found this overview of the symposium informative, interesting, and useful.