Management Of Pediatric Brain Tumors Research Articles

The Evolving Role of Surgery in the Management of Pediatric Brain Tumors

Surgery is an integral component and typically the first line of therapy for children with central nervous system tumors. The outcome with regard to surgical morbidity and disease control can be greatly influenced by the initial care that these children receive. Conventional aims of neurosurgery including tumor removal, management of hydrocephalus, and diagnostic sampling have been radically modified with innovative technologies such as navigational guidance, functional mapping, endoscopic surgery, second-look surgery, and physiologic imaging. The overall role of the pediatric neurosurgeon in caring for children with nervous system tumors is also expanding to include unconventional responsibilities including disease staging, tissue procurement, and drug delivery. It is thus anticipated that the pediatric neurosurgeon will be increasingly relied upon for oncologic therapeutic strategies and should thus remain abreast of forthcoming information and technologies.

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy in pediatric brain tumors

Brain tumors are the most common solid tumor in childhood. Surgery and/or fractionated radiotherapy are conventional treatment modalities. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are advanced radiation therapy techniques that have been frequently used in adults with brain tumors but they are less frequently used in pediatric patients. SRS and FSRT can potentially add to the armamentarium against brain tumors in children. This article will review the role of SRS and FSRT in the management of pediatric brain tumors.

Surgical management of pediatric brain tumors

Brain tumors are the most common cause of cancer-related death and the second most common form of cancer in pediatric patients. Many of these tumors are treated primarily with surgery, either alone or in combination with radiation or chemotherapy. Recent advances have lead to greater survival and decreased morbidities in childhood brain tumor patients. A full understanding of the biology and primary treatment modalities for the particular tumor are essential for any professional treating these patients, including the neurosurgeon. Each tumor type has features in common with, and unique from, other tumors that need to be understood prior to undertaking a rational treatment plan. This article summarizes some of these features.

PET imaging in the surgical management of pediatric brain tumors

The present article illustrates whether positron-emission tomography (PET) imaging may improve the surgical management of pediatric brain tumors (PBT) at different steps. Among 400 consecutive PBT treated between 1995 and 2005 at Erasme Hospital, Brussels, Belgium, we have studied with (18) F-2-fluoro-2-deoxy-D-glucose (FDG)-PET and/or L-(methyl-(11)C)methionine (MET)-PET and integrated PET images in the diagnostic workup of 126 selected cases. The selection criteria were mainly based on the lesion appearance on magnetic resonance (MR) sequences. Cases were selected when MR imaging showed limitations for (1) assessing the evolving nature of an incidental lesion (n = 54), (2) selecting targets for contributive and accurate biopsy (n = 32), and (3) delineating tumor tissue for maximal resection (n = 40). Whenever needed, PET images were integrated in the planning of image-guided surgical procedures (frame-based stereotactic biopsies (SB), frameless navigation-based resections, or leksell gamma knife radiosurgery). Like in adults, PET imaging really helped the surgical management of the 126 children explored, which represented about 30% of all PBT, especially when the newly diagnosed brain lesion was (1) an incidental finding so that the choice between surgery and conservative MR follow-up was debated, and (2) so infiltrative or ill-defined on MR that the choice between biopsy and resection was hardly discussed. Integrating PET into the diagnostic workup of these two selected groups helped to (1) take a more appropriate decision in incidental lesions by detecting tumor/evolving tissue; (2) better understand complex cases by differentiating indolent and active components of the lesion; (3) improve target selection and diagnostic yield of stereotactic biopsies in gliomas; (4) illustrate the intratumoral histological heterogeneity in gliomas; (5) provide additional prognostic information; (6) reduce the number of trajectories in biopsies performed in eloquent areas such as the brainstem or the pineal region; (7) better delineate ill-defined PBT infiltrative along functional cortex than magnetic resonance imaging (MRI); (8) increase significantly, compared to using MRI alone, the number of total tumor resection and the amount of tumor tissue removed in PBT for which a total resection is a key-factor of survival; (9) target the resection on more active areas; (10) improve detection of tumor residues in the operative cavity at the early postoperative stage; (11) facilitate the decision of early second-look surgery for optimizing the radical resection; (12) improve the accuracy of the radiosurgical dosimetry planning. PET imaging may improve the surgical management of PBT at the diagnostic, surgical, and post-operative steps. Integration of PET in the clinical workup of PBT inaugurates a new approach in which functional data can influence the therapeutic decision process. Although metabolic information from PET are valid and relevant for the clinical purposes, further studies are needed to assess whether PET-guidance may decrease surgical morbidity and increase children survival.

State of the art chemotherapeutic management of pediatric brain tumors

CNS tumors are the most common solid tumor of childhood. This article will review current treatments for pediatric brain tumors; low-grade gliomas, high-grade gliomas, medulloblastomas and ependymomas. It will also highlight the treatments that are used for brain tumors in very young children and in children with recurrent brain tumors. The management of recurrent pediatric brain tumors unresponsive to standard therapy will be discussed. The agents used in this setting are mainly biological modifiers, which attempt to provide molecularly targeted therapy. Future directions of therapy for pediatric brain tumors are described. Future treatment paradigms will need to consider examining the use of multiple biological modifiers. Similarly, these agents will need to be examined in combination with cytotoxic chemotherapy. Finally, the future direction of pediatric neuro-oncology and the focus of the field as it battles pediatric brain tumors is discussed.

1251 PUBLICATION Preliminary experience with intensity modulated radiotherapy (IMRT) in the management of pediatric brain tumors (PBT)

1251 PUBLICATION Preliminary experience with intensity modulated radiotherapy (IMRT) in the management of pediatric brain tumors (PBT)

Endoscopic management of pediatric brain tumors

Primary endoscopic procedures for children with intraventricular brain tumors include endoscopic tumor biopsy and endoscopic tumor removal. The simultaneous treatment of hydrocephalus with endoscopic third ventriculostomy (ETV) or endoscopic septostomy increases the appeal of a minimally invasive endoscopic approach. Eighty-five patients who underwent endoscopic management of an intraventricular brain tumor were identified from a prospective database. Of these patients, 26 were younger than 21 years of age at the time of diagnosis. The surgical technique, its success rate, and patient outcome were assessed. Illustrative cases are used in this study to detail the procedure of endoscopic tumor biopsy and resection. Endoscopic tumor procedures were successful in 96% of cases (23 of 24 endoscopic tumor biopsy samples and both endoscopic tumor removals). Fourteen simultaneous procedures were performed to treat hydrocephalus successfully. There was no recognized morbidity from the surgical procedures. Endoscopic surgery in children with intraventricular brain tumors is an effective and safe method for sampling of the lesion and, in select cases, its resection. This minimally invasive technique should be considered in situations in which the patient might thereby avoid a more conventional procedure, given the high rate of success and low morbidity associated with endoscopic management.

Pediatric brain tumors: management strategies

dren. They are thus a leading cause of death, disability, and heartache. Nevertheless, the news over the last decade has been hopeful. Through coordinated national and international studies, largely led by the Children’s Oncology Group, the prognosis has dramatically improved for many of these lesions, especially primitive neuroectodermal tumors and germ cell tumors. We have been steadily moving in the direction of more efficacious and less toxic therapies, and this has allowed us to save lives. The role of the neurosurgeon in the management of pediatric brain tumors is large. Only the neurosurgeon can make the diagnosis in the safest and surest fashion and effect the most appropriate resection. In many of these diseases, the extent of the resection directly impacts prognosis. Only the surgeon can apply the appropriate tools and judgment to address these entities. In the pediatric brain tumor section of the current edition of Neurosurgical Focus, these issues of relevance for the neurosurgeon are addressed. New technology has facilitated the management of brain tumors in children. The first three papers, by Drs. Souweidane, Li, and Luther, explore the use of endoscopic surgical techniques to address pediatric brain tumors and concomitant hydrocephalus. The paper by Dr. Krieger, et al., explores the use of magnetic resonance spectroscopy as a surgical adjuvant. Diseaseand site-specific approaches have facilitated the management of these tumors. Dr. Sandberg, et al., explore surgical outcomes for dysembryoplastic neuroepithelial tumors in terms of disease and seizure control. The paper by Dr. Jagannathan and colleagues discusses state of the art management strategies for sellar tumors. Drs. Komotar and Chen discuss the recently described entities of pilomyxoid astrocytomas and atypical teratoid/rhabdoid tumors, respectively. Accurate understanding of subtypes of tumors allows us to evaluate treatments and outcomes more appropriately. The debate over the management of craniopharyngiomas is not likely to end soon. The papers of Drs. Liu and Aryan describe logical approaches to this challenging disease entity. Last, the paper by Dr. Lee explores an experimental model for evaluating pediatric tumors. It is only through continued study that we will advance our field. Neurosurg Focus 18 (6a):Introduction, 2005

Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice

Advances in the management of pediatric brain tumors have increased survival rates in children, but their quality of life is impaired due to cognitive deficits that arise from irradiation. The pathogenesis of these deficits remains unknown, but may involve reduced neurogenesis within the hippocampus. To determine the acute radiosensitivity of the dentate subgranular zone (SGZ), 21-day-old C57BL/J6 male mice received whole brain irradiation (2–10 Gy), and 48 h later, tissue was assessed using immunohistochemistry. Proliferating SGZ cells and their progeny, immature neurons, were decreased in a dose-dependent fashion. To determine if acute changes translated into long-term alterations in neurogenesis, mice were given a single dose of 5 Gy, and 1 or 3 months later, proliferating cells were labeled with 5-bromo-2′-deoxyuridine (BrdU). Confocal microscopy was used to determine the percentage of BrdU-labeled cells that showed mature cell phenotypes. X-rays significantly reduced the production of new neurons at both time points, while glial components showed no change or small increases. Measures of activated microglia and infiltrating, peripheral monocytes indicated that reduced neurogenesis was associated with a chronic inflammatory response. Three months after irradiation, changes in neurogenesis were associated with spatial memory retention deficits determined using the Morris water maze. Behavioral training and testing increased the numbers of immature neurons, most prominently in irradiated animals. These data provide evidence that irradiation of young animals induces a long-term impairment of SGZ neurogenesis that is associated with hippocampal-dependent memory deficits.

Stereotactic radiosurgery for brain tumors in pediatric patients.

Brain tumors represent the most common solid tumor in children. Fractionated radiation therapy has been an important treatment modality in the multi-disciplinary management of these tumors. Stereotactic radiosurgery is the precise delivery of a single fraction of radiation and has been an important treatment option for adult brain tumor patients. Although the use of stereotactic radiosurgery in pediatric brain tumors is much less frequent, it represents an important alternative for patients with recurrent, surgically inaccessible or radioresponsive tumors. This article will review the results and logistical issues of this modality in the management of pediatric brain tumors.

Combined Positron Emission Tomography and Magnetic Resonance Imaging for the Planning of Stereotactic Brain Biopsies in Children: Experience in 9 Cases

Because brain tumors can be histologically heterogeneous, stereotactic brain biopsies (SBB) may lead to inaccurate diagnosis or grading. Positron emission tomography (PET) has been used in pediatric neuro-oncology to help in the understanding and management of brain neoplasms. We combined PET and magnetic resonance (MR) imaging in the planning of SBB in 9 children (5 males and 4 females, aged 2–14 years) with infiltrative, ill-defined brain lesions. Tracers used for PET were ¹⁸F-2-fluoro-2-deoxy-D-glucose in 4 cases, ¹¹C-methionine in 2 cases and both tracers in 3 cases. Biopsy targets were selected in hypermetabolic areas. PET-guided SBB provided accurate histological diagnosis in all patients and allowed a reduction of the number of trajectories in lesions located in functional areas. It also helped in better understanding and management of complex cases. This preliminary series suggests that combining PET and MR imaging in the planning of SBB in children (1) improves the diagnostic yield of SBB in infiltrative, ill-defined brain lesions, (2) makes it possible to reduce the sampling in high-risk/functional areas and (3) improves the quality of therapeutic management of pediatric brain tumors.

Surveillance imaging and cost effectivity in pediatric brain tumors

Objective: The purpose of this study was to determine the role and cost effectiveness of surveillance imaging at the management of pediatric brain tumors. Materials and methods: In this study, the imaging and clinical finding of 59 patients who had been diagnosed and followed by the Dokuz Eylul University Pediatric Oncology Group as primary central nervous system tumors between 1988 and 2000 were retrospectively evaluated. Results: We found that the 87.5% of tumor recurrence occurs within 21 months and 93.8% occur within 29 months. About 25% of these recurrences were asymptomatic and these (n=16) could be detected by surveillance imaging with a frequency rate of 1.59%. The cost of imaging for our patients was calculated to be 788 US$ (mean) for a follow-up period of 24 months which would have been 739 US$ if a standard surveillance protocol would have been followed. Conclusion: Surveillance imaging is an effective follow-up in detecting symptomatic recurrence in pediatric brain tumors.

Current Management of Pediatric Brain Tumors

Central nervous system (CNS) tumors are the most common solid neoplasms of childhood. Each year, approximately 1500 to 2000 children in the United States are diagnosed with brain tumors. Although the mortality rate for pediatric brain tumors exceeds many other childhood neoplasms, recent therapeutic advances are enabling an increasing percentage of affected children to survive into adulthood. Surgical intervention plays an important role in the treatment of many types of childhood brain tumors. Improvements in surgical management, coupled with focused radiotherapeutic techniques, and innovative approaches for chemotherapy are being incorporated in new treatment strategies for a variety of different histological groups. This review discusses contemporary treatment approaches for the most common pediatric brain tumors, highlighting recent developments that have significantly altered outcome, identifying areas of controversy, and discussing ongoing and future directions for therapeutic refinement.

Radiosurgery in the management of pediatric brain tumors

Objective: To describe the outcome of pediatric brain tumor patients following stereotactic radiosurgery (SRS), and factors associated with progression-free survival. Methods: We reviewed the outcome of 90 children treated with SRS for recurrent ( n = 62) or residual ( n = 28) brain tumors over a 10-year period. Median follow-up from SRS was 24 months for all patients and 55.5 months for the 34 patients currently alive. Results: The median progression-free survival (PFS) for all patients was 13 months. Median PFS according to tumor histology was medulloblastoma = 11 months, ependymoma = 8.5 months, glioblastoma and anaplastic astrocytoma = 12 months. Median PFS in patients treated to a single lesion was 15.4 months. No patient undergoing SRS to more than 1 lesion survived disease free beyond 2 years. After adjusting for histology and other clinical factors, SRS for tumor recurrence (RR = 2.49) and the presence of > 1 lesion (RR = 2.3) were associated with a significantly increased rate of progression ( p < 0.05). Three-year actuarial local control (LC) was as follows: medulloblastoma = 57%, ependymoma = 29%, anaplastic astrocytoma/glioblastoma = 60%, other histologies = 56%. Nineteen patients with radionecrosis and progressive neurologic symptoms underwent reoperation after an interval of 0.6–62 months following SRS. Pathology revealed necrosis with no evidence of tumor in 9 of these cases. Conclusion: SRS can be given safely to selected children with brain tumors. SRS appears to reduce the proportion of first failures occurring locally and is associated with better outcome when given as a part of initial management. Some patients with unresectable relapsed disease can be salvaged with SRS. SRS to multiple lesions does not appear to be curative. Serious neurologic symptoms requiring reoperation is infrequently caused by radionecrosis alone.

Radiosurgery in the management of pediatric brain tumors.

A total of 114 patients with benign and malignant intracranial tumors were treated by Valentino at the Flaminia Radiosurgical Center using a Philips 6-MeV linear accelerator between 1987 and 1995. The tumor locations break down as follows: 36 in the cerebral hemispheres, 14 in the region of the hypothalamus/optic chiasm, 21 in the III ventricle/pineal region, 3 in the basal ganglia, 27 in the posterior fossa, 13 in the brain stem. Seventy-nine patients had multivariate/combined treatment consisting of surgery or biopsy followed by chemotherapy, radiotherapy and/or radiosurgery. Thirty-five were not operated on or biopsied but were treated primarily by radiosurgery, which was associated with chemotherapy and conventional radiotherapy. The short- and long-term results were evaluated separately for each pathology in an attempt to derive guidelines for future treatment. For tumors of the pineal region, we are of the opinion that radiosurgery is the treatment of choice in children and that more than one-third of patients can be cured by this means. The remaining patients require surgery and/or chemotherapy in addition. For medulloblastomas radiosurgery may be useful to control local recurrence if coupled with chemotherapy. In the case of ependymomas, partly because of the extreme malignancy of the lesions in our series, radiosurgery did not succeed in controlling local recurrence. We fear that limiting treatment to radiosurgery, rather than prescribing conventional radiotherapy when indicated, could permit CNS seeding. For craniopharyngiomas radiosurgery proved useful for controlling solid remnants. In glial tumors radiosurgery helped either to "sterilize" the tumor bed after removal or to treat remnants of the lesions in critical areas; for diffuse brain stem gliomas it should be considered the treatment of choice.

Clinical impact of MR spectroscopy when MR imaging is indeterminate for pediatric brain tumors.

We undertook this study to determine if single-voxel proton (hydrogen) MR spectroscopy could have clinical impact on the management of pediatric brain tumors when MR findings were indeterminate. Eleven children (mean age, 9 years) being examined for brain tumors underwent MR imaging that revealed indeterminate criteria of enhancement, mass effect, and prolonged T1 and T2 signal. MR spectroscopy was then used to distinguish radiation necrosis from tumor in one patient, differentiate residual tumor from scarring in two patients, document early treatment response in three patients, and discriminate benign from malignant masses in five patients. In 10 of the 11 patients, spectra were successfully acquired. Based on the chemical analysis of the indeterminate area shown on MR imaging, clinical impact was achieved in these 10 patients. Clinical impact included treatment modification in five patients, follow-up studies replacing further treatment in three patients, and tumor characterization in the remaining two patients. Confirmation was by histology in four patients and by follow-up MR imaging and MR spectroscopy for up to 30 months in the remaining six patients. When MR imaging is indeterminate in evaluating pediatric brain tumors, MR spectroscopy can provide objective neurochemical information, thereby altering treatment.

2242 Stereotactic radiosurgery (SRS) in the management of pediatric brain tumors

2242 Stereotactic radiosurgery (SRS) in the management of pediatric brain tumors

Management of Pediatric Brain Tumors

Management of Pediatric Brain Tumors

The management of pediatric brain tumors in a tertiary center.

Between January 1982 and January 1990, 120 newly diagnosed pediatric patients were treated at The Chaim Sheba Medical Center. Sixty three (52.5%) tumors arose in the posterior fossa and 57 (47.5%) appeared supratentorially. A wide variety of histologic subtypes was seen, each requiring tumor-specific treatment. The modern imaging techniques-CT and MRI-offered better planning of operation, treatment and follow up. All children with highly malignant tumors were treated with combination chemotherapy besides the 'conventional radiotherapy'. Since 1987 the "eight in one day" protocol has been used extensively pre- and post-irradiation. Five-year survival, varied significantly according to tumor type, location and stage. The average delay from presentation of symptoms to diagnosis was 6 months. A multidisciplinary approach has been used in the treatment, rehabilitation and follow-up of these children. In this study, the results of treatment are presented and the role of chemotherapy is discussed.

Medical and oncological management of pediatric brain tumors.

Medical and oncological management of pediatric brain tumors.