Written by Jeanne Young, President, CBTF-MD
Excerpts taken from notes and the Neuro-Oncology, Vol. 11, Issue 3, June 2008
Reviewed by Debbie Lafond, Children’s National Medical Center, RN, RNCS, PNP, CPON
The Childhood Brain Tumor Foundation was proud to be a Silver Sponsor of the 13th International Symposium on Pediatric Neuro-Oncology (ISPNO), held at the Marriott Chicago June 30 – July 2, 2008. Over 900 medical professionals were in attendance from all over the globe. The symposium is held every two years to provide opportunities for clinicians and researchers to share outcomes from basic science and clinical practice, and to further progress for children suffering from brain tumors. Two Pre-Symposium Education Day sessions included: Neuro-Oncology and Neurosurgery, followed by Epidemiology. Organizers were Stewart Goldman, M.D. and Tadanori Tomita, M.D. of Children’s Memorial Hospital in Chicago. Although we are unable to cover every session, we have selected one session per topic, with highlights from the Family Education Day.
Epidemiology Moderators: Carol Kruchko and B. Diez
Pediatric Brain Tumors in Israel: Dr. Vered Shay noted that average age at diagnosis is eight, with the most common symptoms being headaches and vomiting. Infratentorial gliomas were the most common at 50%. Studies indicate that diagnosis delay is due to difficult diagnosis and delayed imaging, despite presenting symptoms. Imaging threshold for scans should be lower and clinicians need to be better educated in recognizing symptoms.
Medulloblastoma/PNET I: Moderators: Roger Packer, M.D. and Larry Kun, M.D.
Clinical Significance of Subtle Findings on MRI in Children Diagnosed with Medulloblastoma: Ute Bartels, M.D. ; Canada reported that subtle findings on spinal MRI at the time of diagnosis in children with medulloblastoma are commonly observed pre- and postoperatively. There was no evidence of increased risk of relapse and no indication for treatment intensification if M0 status and near total resection has been confirmed. (Neuro-Oncology, Vol. 11, Issue 3, June 2008, pg. 477).
Special Breakout: A Controversies in Neuro-Oncology: Do Brain Tumor Stem Cells Exist?
One participant asked, How do tumors in brains arise if it is an organ that is isolated? Some might say brain tumors arise from developmentally stalled neural progenitors. Solid tumors are fueled by minor subpopulations of cells with stem like cell properties. Stem cells live for a long time in the body, allowing time for multiple mutations. Others said that pediatric brain tumors are genetically calm. Brain tumors contain cells with stem-cell like properties; signaling pathways that contain growth of normal progenitor cells are suppressed in brain cancer. A lot of discussion produced no agreement on this topic.
Surgical Techniques: Moderated by A. Gajjar, M.D. and B. Pizer, M.D., Dr.
Reizo Shirani of Japan: Salvage Surgery and Reoperation after Radiation and Chemotherapy for Primary Brain Tumor in Children. Surgery is the primary treatment option for children with resectable brain tumors in Japan. Radiation treatments are used in children who have malignant or progressive brain tumors. Chemotherapy, although it plays a role, is a treatment for some tumors, but response is different for each tumor. For instance, ependymomas have not shown to benefit greatly from chemotherapy.
Low Grade Glioma: Moderators: Murali M. Chintagumpala, M.D.; S. Clifford, M.D.; M. Gilbertson, M.D.; and Mark Kieran, M.D.
Descriptive Epidemiology of Pilocytic Astrocytoma was presented by Bridget McCarthy, Ph.D., US. Pilocytic astrocytomas remain poorly studied because they have a relatively benign nature, although location can make them problematic. Pilocytic astrocytoma is most commonly in the cerebellum 35.7%; the brain lobes 13.1%; the brain stem 10.8%; spinal cord 4.8%; optic nerve 3.8% and17.1% in overlapping sites. (Neuro-Oncology, Vol. 10, Issue 3, June 2008, pg. 412). Optic nerve glioma is most commonly found in children 0-4 years of age and can occur in children with neurofibromatosis (NF-1). Long term survivor data and quality of life studies will be important in the years to define the clinical aspects of pilocytic astrocytoma.
Eric Bouffet, M.D., A Phase II Study of Weekly Vinblastine in Recurrent / Refractory Pediatric Low Grade Glioma. The Phase II study was initiated in 2002 and accrued 51 patients. Toxicity was manageable; there were some grade IV toxicities, however overall treatment was well tolerated.
Biology I: Biology of Gliomas and Malignant Tumors: Moderators: Tobey MacDonald, M.D. and R Grundy, M.D.
PDGF-CC and Medulloblastoma Migration, Brian Rood, M.D. states that molecularly targeted agents appear to be the most promising for improving treatment, while limiting toxicities. PDGF-C is a molecule with a functional effect upon cell migration that is widely expressed in medulloblastoma. (Neuro-Oncology Journal, Vol. 10, Issue 3, pg. 486). Efforts are being made to develop agents that target PDGF receptors.
Nursing Moderators: Deborah Lafond, RN, RNCS,PNP, CPON, and A. Bendel, M.D.
Jennifer Madden, RN, MS, CPNP, US, presented results of Randomized Study of Creative Art Therapy for Pediatric Brain Tumor Patients During Outpatient Chemotherapy. During art therapy sessions in outpatient clinic, patients participated in movement therapy using shaving cream and fingerpaint as a means of expression. Parents reported that children younger than seven-years-old reported less nausea and were less nervous. Nurse focus groups reported improved patient mood and withdrawn children interacted better.
Germ Cell Tumors: Moderators: Mateo Matsutani, M.D. and Jeffrey Allen, M.D.
Dr. Shingo Takano, Japan spoke about TherapeuticAdvancement for Pediatric Germ Cell Tumors. Treatment strategies are important for children with intracranial germ cell tumors because of the varying types of tumors in this category, ranging from low grade to highly malignant. Studies show that neoadjuvant radiation therapy before excision of residual tumor is beneficial for patients with nongermatous germ cell tumors. (Journal of Neuro-Oncology, Vol. 10, Issue 3, June 2008, pg.420)
Craniopharyngioma: Moderators: Concezio DiRocco, M.D. and Tadonori Tomita, M.D.
Quality of Life in Childhood Craniopharyngioma Patients with and without Hypothalamic Involvement was presented by Dr. Gabrielle Calaminus, Germany. Craniopharyngiomas are intracranial tumors that are considered low-grade, and are located in the hypothalamus and pituitary region. Treatment generally includes surgery and sometimes radiation for those that have progressive tumor. Adverse effects include, endocrinological deficiencies, obesity, hyperphagia, daytime sleepiness, and sometimes cognitive issues (memory and attention.) Overall survival is good. Patients without hypothalamic involvement have a better quality of life due to less severe adverse events.
High Grade Glioma: Moderators: Kenneth J. Cohen, M.D. and Maryam Fouladi, M.D.Â
The Treatment of High-Grade Gliomas in Pediatrics: Where Have We Been? Where Are We Going?, Kenneth Cohen, M.D., R.s, US, noted that although it is conceivable that biological behavior of Anaplastic Astrocytoma has changed in the past 30 years, it is possible the pathology criteria has changed, becoming more stringent over time so that these tumors are better classified today. Prognosis for children with high-grade gliomas remains dismal, inclusive of children with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Presented by, Danuta Perek, M.D., Ph.D., Poland, Treatment Failures in Children with High Grade Glioma (HGG), Results from The Polish Neuro-Oncology Study Group (PNOSG) study analyzed the failure rates in these children from 1996-2007. All pathology was carefully evaluated. Studies determined that progression and relapse occurred early in the AA and GBM patients and suggested they resist chemotherapy and radiation.
Leptomeningeal and Disseminated Disease: Moderators: Susan Blaney, M.D. and S. Gururangan, MRCPÃ
A Comparison of Intracranial and Lumbar CSF Cytology in Staging Pediatric Medulloblastoma, Supratentorial PNETs, and Ependymomas, Sergei Terterov, M.D., US; Cerebrospinal fluid dissemination is an ominous feature of pediatric brain tumors, occurring in approximately 25% of medulloblastomas and 11% of ependymomas. It is vital that this be detected early to influence treatment and survival; 83.3% of progression/relapses occurred early. (Neurosurgery, Vol. 11, Issue 3, pg. 443)
Late Effects: Moderators: Paul Graham Fisher, M.D. and D. Walker. M.D.Ã., Stephen Sands, Psy. D., US, Late Effects Follow-Up of “Head Start II” Survivors, a study that evaluated neuropsychological late effects in survivors enrolled in the Head Start II protocol. Study participants were<10 years of age. The investigator concluded that overall, neurocognitive functioning was good but survivors should continue follow-up for neuropsychological, behavioral and social emotional functioning.
Endocrine, Intellectual and Functional Outcomes of Adult Survivors of Childhood Posterior Fossa Tumours, was presented by Dr. Heather Spouedas, UK. She concluded her session stating that radiation-based therapies for pediatric brain tumors that are not positioned centrally are not the cause of much pituitary glandular deficiencies after 16 year follow-up. However, growth hormone deficiency may occur. Chemotherapy given adjuvant to radiation, adds to the risk of hypothyroidism, gonadotoxicity, sensory and motor late effects.
Ependymoma: Moderators: Nicholas Foreman, M.D. and M. Gilbert, M.D.
Conformal Radiation Therapy Pediatric Ependymoma: The St. Jude Experience. This study showed that patients with well-differentiated ependymoma benefit from aggressive surgery and post-operative high-dose conformal radiation therapy.
NF-1 Moderators: R. Listernick, M.D. and Brigitte Widemann, M.D.
Dr. Astrid Gnekow, Germany, Do Children and adolescents with NF-1 Associated Low-Grade Glioma Need a Separate Treatment Approach? Results indicate that progression free survival is essentially the same in children who have been treated with chemotherapy and radiation. In some patients, radiation therapy should be postponed to avoid vasculopathy. In the future, there may be possibilities that molecular research in genetics will provide information on natural history, and predict response to treatment.
Neuropathology Update Moderators: Peter C. Burger, M.D. and T. Pietsch, M.D.
Pilomyxoid Tumors with a Chronic Relapsing Course May Become More Cystic and Mature to Pilocytic Histology. Pilomyxoid astrocytoma (PA) is commonly found in children <2 year old and previously included in the category of PA, but are now defined by histology. PAs are typically solid, necrotic, and have abnormal signal intensity. Although there are differences in molecular biology between PMA and PA, there are overlaps in gene expression. This study indicated that chronic PMA become more cystic and mature to become PA.
Family Education Day Facilitated by Tadanori Tomita, M.D.
A special session, Ask the Experts was part of Family Education Day which was attended by approximately 100 families. Two panels of experts broke from the symposium to participate in a question and answer session for families. Panelists included Carol Kruchko, Stewart Goldman, M.D; Reema Habiby, M.D.; Roger J. Packer, M.D.; Tadanori Tomita, M.D.; Mark Kieran, M.D.; Chris Turner, M.D.; and Torunn Yock, M.D.
Radiation
Intensity Modulated Radiation Therapy (a photon technique), 3D, Conformal and Proton Beam Radiation. Parents are encouraged to delay radiation due to potential late effects, but when it is considered necessary, it is difficult for them to go forward with it. Roger J. Packer, M.D. suggested that in the next five years, new molecular genetics may show promise in determining which patients are more sensitive to radiation, and predicting which may be at higher risk for complications. There is no golden age for safe radiation – although radiated tissue may not develop normally, other factors contribute to late effects — tumor, hydrocephalus, and surgical intervention.
Benign vs Malignant
Chris Turner, M.D. explained that benign tumors are localized and can often be resected, whereas malignant tumors are more infiltrative and invasive. In the medical community the term brain tumor is preferred over brain cancer because a benign brain tumor in an unfavorable region can be devastating, whereas some malignant brain tumors respond well to aggressive treatments. Benign tumors that are not resectable have few options. Dr. Tomita stated that it is rare for tumors to spread outside of the brain and spinal cord.
Ã. Atypical Teroid Rhabdoid Tumor (ATRT) & Rare Tumors Moderators: Susan Chi, M.D. and Lucy Rourke, M.D.
Clinical features of ATRT Tumor in Japan, presented by Dr. Hideriro Oku. These tumors are extremely rare in early childhood and they are highly malignant. It is important that they be differentiated in clinical features from medulloblastoma/PNET. Children with ATRT tend to have increased intracranial pressure caused by large tumor and or obstructive hydrocephalus. Less that 50% have leptomeningeal dissemination. Prognosis is less favorable in patients with ATRT than those with medulloblastoma/PNET or germ cell tumor.
Brain Stem Tumors Moderators: Katherine Warren, M.D. and R. Kortmann, M.D.Ã.
Phase II Trial Thalidomide and Carboplatin for the Treatment of Brain Stem Glioma (CNS1099) presented by Stewart Goldman, M.D. This phase II combination, Thalidomide, an antiangiogenic agent and Carboplatin, was given with radiation therapy to improve progression free survival in this subset of patients. It was found to be well-tolerated.
Endocrinology
Reema Habiby, M.D. discussed endocrine issues post radiation therapy. Tumor location, treatments, especially those that affect brain cells in the pituitary region, may cause endocrine issues for children with brain tumors. Children may have delayed or accelerated puberty. Symptoms can be measured by following thyroid and growth hormones. There is concern in using growth hormone in children, but its role in stimulating tumor growth has not been validated by research studies. Endocrinologists are reluctant to use growth hormone in children with active tumor.
Hydrocephalus Shunt can be avoided in some children with brain tumors who present with hydrocephalus, due to advancements in neuro-navigational systems and techniques. Endoscopic techniques to open the pathway decreases the need for shunt surgery. Locating the tumor through intraoperative imaging aids during resection can avert the need for shunts.
Treatment Phases: Stewart Goldman, M.D. discussed the three phases of treatments: Phase 1 trials determine maximum tolerated dose (MTD); Phase II trials are for specific tumor types and look at the effectiveness of treatment; and Phase III trials investigate which treatment regimen in a head to head comparison, between two or more treatment options, is more effective.
Neuro-cognitive issues: Roger J. Packer, M.D. stated that although children face many challenges, new developments are in process. One particular area of interest is anti-cholesterol drugs that have may help children cognitively and improve their performance in school.
Epidemiology: Carol Kruchko, Central Brain Tumor Registry of US, emphasized the importance of epidemiology studies and the need for collaboration across disciplines.
The Complementary, Alternative Medicine & Research Panel included, Elena Ladas MS, RD, Integrative Pediatric Medicine, Columbia & Pieter Van Heule, Homeopath, D.C.
Pieter Van Heule promoted guided imagery during chemotherapy as a helpful complimentary and alternative medicine. He explained that holistic medicating refers to a philosophy where focus is on the patient, not the disease. Conventional and Holistic medicines are not incompatible. Structural approaches include: cardiopathy, musculoskeletal rebalancing, touch and sensory reintegration, and manual lymph drainage. Other treatments can be found in nutrition, homeopathy, acupuncture, emotional counseling, mediation and visualization. The NIH roadmap Epigenomics Program is emerging as a scientific study in the regulation of gene activity and expression. The epigenetic mechanisms control stem cell differentiation and organgenesis contribute to the biological response to endogenous and esogenous forms of stimuli that result in disease.Ã
The Childhood Brain Tumor Foundation organized the Outreach and Support for Families session in cooperation with New York’s Children’s Brain Tumor Foundation. Nicole Ronco, parent, emphasized the importance of creating a network of support through friends, family, community and institutional contacts. Jeanne Young discussed the needs for information and resources, support groups, Ombudsmen and Advocacy, Wish fulfillment, Camps, and assistance with treatment related travel and lodging. Jeanne and Nicole stressed the importance of checking authenticity of Web-based information. Regarding online support remember your child is an individual, comparing outcomes is not healthy and to be careful that online support group moderators are not biased, and monitor content. Check your sources or ask questions if you are not sure what you have read is accurate.
Other sessions included: Transitioning into Life; Quality of Life; and Family Voices for Research and Treatment Options.
Many of the CBTF Scientific Advisors were moderators and presenters at the comprehensive meeting. Dr. Roger J. Packer, CBTF’s Senior Scientific Advisor, was presented with the Founder’s Award at the ISPNO banquet, in recognition of his leadership and founding of the ISPNO more than 20 years ago. The Childhood Brain Tumor Foundation expresses its appreciation to Stewart Goldman, M.D. and Tadanori Tomita, M.D. for organizing this comprehensive symposium for medical professionals and for including a special day for patient information and family networking.
This article was written for the Childhood Brain Tumor Foundation, Germantown, Maryland, www.childhoodbraintumor.org.
