PURPOSE: We investigated the clinical characteristics of patients who developed thyroid dysfunction and evaluated the risk factors for hypothyroidism following radiotherapy and chemotherapy in pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). METHODS: The medical records of 66 patients (42 males) treated for medulloblastoma (n=56) or PNET (n=10) in childhood between January 2000 and December 2014 at Seoul National University Children’s Hospital were retrospectively reviewed. A total of 21 patients (18 high-risk medulloblastoma and 3 PNET) underwent high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) RESULTS: During the median 7.6 years of follow-up, 49 patients (74%) developed transient (n=12) or permanent (n=37) hypothyroidism at a median 3.8 years of follow-up (2.9–4.6 years). Younger age ( < 5 years) at radiation exposure (P=0.014 vs. ≥9 years) and HDCT (P=0.042) were significantly predictive for hypothyroidism based on log-rank test. However, sex, type of tumor, and dose of craniospinal irradiation (less vs. more than 23.4 Gy) were not significant predictors. Cox proportional hazard model showed that both younger age (< 5 years) at radiation exposure (hazard ratio [HR], 3.1; vs. ≥9 years; P=0.004) and HDCT (HR, 2.4; P=0.010) were significant predictors of hypothyroidism. CONCLUSIONS: Three-quarters of patients with pediatric medulloblastoma or PNET showed thyroid dysfunction, and over half had permanent thyroid dysfunction. Thus, frequent monitoring of thyroid function is mandatory in all patients treated for medulloblastoma or PNET, especially, in very young patients and/or high-risk patients recommended for HDCT/ASCR.
Craniospinal Irradiation ; Drug Therapy ; Follow-Up Studies ; Humans ; Hypothyroidism ; Medical Records ; Medulloblastoma* ; Neuroectodermal Tumors, Primitive* ; Pediatrics ; Proportional Hazards Models ; Radiation Exposure ; Radiotherapy ; Retrospective Studies ; Risk Factors ; Seoul ; Stem Cells ; Thyroid Gland* ; Thyroid Hormones

In contrast to many of the malignant tumors that occur in the central nervous system in adults, the management, responses to therapy, and future perspectives of children with malignant lesions of the brain hold considerable promise. Within the past 5 years, remarkable progress has been made with our understanding of the basic biology of the molecular genetics of several pediatric malignant brain tumors including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumour, and high grade glioma/diffuse intrinsic pontine glioma. The recent literature in pediatric neuro-oncology was reviewed, and a summary of the major findings are presented. Meaningful sub-classifications of these tumors have arisen, placing children into discrete categories of disease with requirements for targeted therapy. While the mainstay of therapy these past 30 years has been a combination of central nervous system irradiation and conventional chemotherapy, now with the advent of high resolution genetic mapping, targeted therapies have emerged, and less emphasis is being placed on craniospinal irradiation. In this article, the present and future perspective of pediatric brain malignancy are reviewed in detail. The progress that has been made offers significant hope for the future for patients with these tumours.
Adult ; Biology ; Brain Neoplasms ; Brain ; Central Nervous System ; Child ; Classification ; Craniospinal Irradiation ; Drug Therapy ; Ependymoma ; Glioma ; Hope ; Humans ; Medulloblastoma ; Molecular Biology

The incidence of leptomeningeal dissemination (LMD) of anaplastic glioma has been increasing. LMD can be observed at the time of initial presentation or the time of recurrence. As a result of both rarity and unusual presentation, a standard therapy has not yet been suggested. In contrast to leptomeningeal carcinomatosis for systemic solid cancers, a relatively prolonged survival is observed in some patients with LMD of anaplastic gliomas. Treatment modalities include whole craniospinal irradiation, intra-cerebrospinal fluid (CSF) chemotherapy, and systemic chemotherapy. In some cases, response to temozolomide (TMZ), with or without combined radiation has been reported. Here, we report two cases of LMD of an anaplastic glioma. In one case LMD presented at the time of diagnosis, and in the other at the time of recurrence after radiation. CSF cytology was positive in both cases, and persisted in spite of intrathecal methotrexate chemotherapy. Later, TMZ was prescribed for progressing brain parenchymal lesions, and both radiological and cytological responses were obtained after oral TMZ treatment.
Brain ; Cerebrospinal Fluid ; Craniospinal Irradiation ; Diagnosis ; Drug Therapy ; Glioma* ; Humans ; Incidence ; Meningeal Carcinomatosis ; Methotrexate ; Recurrence

The neurocognitive function and quality of life of 58 Korean survivors of childhood medulloblastoma were assessed after surgery, cranial radiation and chemotherapy. All patients were evaluated with a battery of neurocognitive function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain Tumor Survivors, which consists of self-report questionnaires on quality of life. The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ scores were 90.2, 97.1, and 84.16, respectively. The mean memory quotient (MQ) score was 86.78, which was within 1 standard deviation of the average score of 100. Processing speed, attention, and executive function showed mild to moderate deficits. Intelligence, memory, executive function, visuospatial function, and simple motor function were significantly lower in the patients diagnosed before 8 years of age compared with those diagnosed after 8. The cognitive deficits in the patients diagnosed at younger ages might be related to earlier exposure to craniospinal irradiation and chemotherapy. The patient and parent proxy evaluations of attention, fine motor function, and quality of life did not differ. We found significant neurocognitive changes in a wide range of neurocognitive functional domains in Korean survivors of childhood medulloblastoma. Long-term follow-up studies of survivors of childhood medulloblastoma beginning at the time of their first diagnosis are required to better understand the deficits exhibited by survivors of childhood medulloblastoma, so that intervention strategies and treatment refinements that reduce the long-term neurocognitive decline can be developed.
Cognition ; Cognition Disorders ; Craniospinal Irradiation ; Diagnosis ; Drug Therapy ; Executive Function ; Follow-Up Studies ; Humans ; Intelligence ; Korea ; Medulloblastoma* ; Memory ; Parents ; Proxy ; Quality of Life* ; Survivors*

Central nervous system germ cell tumor is a rare but important tumor in childhood brain tumors. It requires a multidisciplinary approach to increase survival and promote quality of life, and all three treatment modalities including surgery, radiotherapy and chemotherapy has its own distinct role for germ cell tumor. For germinoma, radiotherapy alone can cure the disease but, the effort to limit the long term toxicity and the proper combination of chemotherapy and radiotherapy are under investigation. Craniospinal irradiation is reserved only for the disseminated germinoma or nongerminomatous germ cell tumor (NGGCT). For germinoma, craniospinal irradiation of 20 to 24 Gy is sufficient to control microscopic disease in the spinal axis. Chemotherapy and radiotherapy composed of 30 to 40 Gy of local field radiotherapy and 20 to 24 Gy of whole ventricular irradiation are required for localized germinoma, but the proper combination of two modalities has yet to be defined. For NGGCT, both the chemotherapy and radiotherapy should be performed, and survival rate is substantially increasing with modern treatment protocols. The omission of craniospinal irradiation is being tried for the localized NGGCT in international cooperative group trials. Surgery has its role for the resection of residual disease after the treatment, and the extent of resection in NGGCT has the prognostic implication. Bifocal germ cell tumors and basal ganglia germ cell tumor have distinctive clinical course and mandate special attention. To advance clinical and biological perspectives in central nervous germ cell tumor, the cooperation and communication of the multidisciplinary specialists are essential.
Axis, Cervical Vertebra ; Basal Ganglia ; Brain Neoplasms ; Central Nervous System ; Clinical Protocols ; Craniospinal Irradiation ; Drug Therapy ; Germ Cells ; Germinoma ; Neoplasms, Germ Cell and Embryonal ; Quality of Life ; Radiotherapy ; Specialization ; Survival Rate

PURPOSE: The purpose of this study is to investigate the long-term results and appropriateness of radiation therapy (RT) for medulloblastoma (MB) at a single institution. MATERIALS AND METHODS: We analyzed the clinical outcomes of 106 patients with MB who received RT between January 1992 and October 2009. The median age was 7 years (range, 0 to 50 years), and the proportion of M0, M1, M2, and M3 stages was 60.4%, 8.5%, 4.7%, and 22.6%, respectively. The median total craniospinal irradiation (CSI) and posterior fossa tumor bed dose in 102 patients (96.2%) treated with CSI was 36 Gy and 54 Gy, respectively. RESULTS: The median follow-up period in survivors was 132 months (range, 31 to 248 months). A gradual improvement in survival outcomes was observed, with 5-year overall survival rates of 61.5% in 1990s increasing to 73.6% in 2000s. A total of 29 recurrences (27.4%) developed at the following sites: five (17.2%) in the tumor bed; five (17.2%) in the posterior fossa other than the tumor bed; nine (31%) in the supratentorium; and six (20.7%) in the spinal subarachnoid space only. The four remaining patients showed multiple site recurrences. Among 12 supratentorial recurrences, five cases recurred in the subfrontal areas. Although the frequency of posterior fossa/tumor bed recurrences was significantly high among patients treated with subtotal resection, other site (other intracranial/spinal) recurrences were more common among patients treated with gross tumor removal (p=0.016). There was no case of spinal subarachnoid space relapse from desmoplastic/extensive nodular histological subtypes. CONCLUSION: Long-term follow-up results and patterns of failure confirmed the importance of optimal RT dose and field arrangement. More tailored multimodal strategies and proper CSI technique may be the cornerstones for improving treatment outcomes in MB patients.
Combined Modality Therapy* ; Craniospinal Irradiation ; Follow-Up Studies* ; Humans ; Infratentorial Neoplasms ; Medulloblastoma* ; Radiotherapy ; Recurrence ; Subarachnoid Space ; Survival Rate ; Survivors

Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients.
Biology ; Brain Neoplasms ; Chemoradiotherapy ; Child ; Craniospinal Irradiation ; Drug Therapy ; Germinoma ; Humans ; Neoplasms, Germ Cell and Embryonal* ; Proton Therapy ; Radiotherapy* ; Radiotherapy, Intensity-Modulated ; Recurrence ; Survival Rate ; Treatment Outcome

The authors encountered a case of simultaneous radiation-induced multiple meningiomas and ventriculoperitoneal (VP) shunt-related pneumocephalus. A 35-year-old man, who had undergone surgery for medulloblastoma 21 years previously and subsequently received high dose craniospinal irradiation with adjuvant chemotherapy and later underwent a VP shunt because of hydrocephalus, presented with a severe headache and weakness of both lower extremities. Computed tomography showed an air pocket lesion in the left temporal lobe and a large amount of pneumocephalus with a bony defect of the left tegmen tympani. In addition, a 3 cm sized well enhancing mass was noted in the in the right middle cranial fossa and additional small enhancing nodule in the left frontal pole. He was treated by left temporal craniotomy and repair of the bony and dural defects of the left tegmentum tympanum through extradural and intradural approaches, respectively. Afterwards, he underwent right temporal craniotomy and gross total removal of a rapidly growing right middle fossa mass and a left frontal mass. The histological examination was consistent with atypical meningioma, WHO grade II. In conclusion, physicians have to consider the serious long term complications of high dose radiation therapy and VP shunt placement and need to perform the neuroradiologic follow-up after such treatments for several decades.
Adult ; Chemotherapy, Adjuvant ; Cranial Fossa, Middle ; Craniospinal Irradiation ; Craniotomy ; Ear, Middle ; Follow-Up Studies ; Headache ; Humans ; Hydrocephalus ; Lower Extremity ; Medulloblastoma* ; Meningioma* ; Pneumocephalus* ; Temporal Lobe ; Ventriculoperitoneal Shunt

OBJECTIVE: Strategies for managing supratentorial primitive neuroectodermal tumors(PNETs) in children include surgical resection, craniospinal irradiation and chemotherapy. This study is performed in order to compare the efficacy of various methods of treatment and to describe its optimal management. METHODS: We have reviewed all medical records and pathology slides of six children(four males and two females) with supratentorial PNET from November, 1987 to May, 2003. The extent of resection was confirmed by computed tomography and magnetic resonance studies. RESULTS: The patients were aged 1 to 13 years and treated postoperatively with/without adjuvant therapy. Tumor location included was four cortical, one gangliobasal, and one pineal region. The presenting symptoms and signs consisted of increased intracranial pressure and focal neurological deficits such as seizure and hemiparesis. The treatment consisted of surgical resection alone in one patient, postoperative radiotherapy in one patient, postoperative chemotherapy in one, and postoperative radiotherapy with chemotherapy in three. Five patients lived more than 12 months after diagnosis and one patient among them has been living more than 5 years after diagnosis. CONCLUSION: We can improve the survival and prognosis of supratentorial PNET patients by radical gross total resection of tumor followed by craniospinal irradiation and aggressive chemotherapy. First of all, gross total resection of tumor is the most important among many factors.
Child* ; Craniospinal Irradiation ; Diagnosis ; Drug Therapy ; Humans ; Intracranial Pressure ; Male ; Medical Records ; Neural Plate ; Neuroectodermal Tumors, Primitive* ; Paresis ; Pathology ; Prognosis ; Radiotherapy ; Seizures

PURPOSE: Medulloblastoma is the most common malignant brain tumor in childhood. The standard treatments are composed of tumor resection, irradiation and chemotherapy. In this study, we analysed the outcome of high risk medulloblastoma patients who were treated with surgical resection followed by craniospinal irradiation and chemotherapy utilizing cisplatin, vincristine, cyclophosphamide and etoposide. METHODS: We conducted a retrospective analysis of medical record of twenty-five patients with high risk medulloblastoma, treated from January 1998 to April 2004 in the Department of Pediatrics, Neurosurgery and Radiation Oncology at Asan Medical Center. RESULTS: The median age at diagnosis was 9 years and 10 month. The 2-year overall survival rate was 80%, and 2-year progression-free survival rate was 71%. Degree of surgical resections or residual tumor did not show statistically significant differences of survival rate, but there was difference depending on metastasis staging. The side effects of chemotherapy were grade IV hematologic toxicity (n=20), SIADH (n=2), and severe paralytic ileus (n=1). The long-term sequelae were endocrinopathy (n=6) that include growth failure, precocious puberty and hypothyroidism. Neurological complications such as mild mental retardation and ataxia occurred in seven patients. There was no treatment-related mortality. Four patients died of tumor progression. CONCLUSION: Patients with high risk medulloblastoma treated with surgical resection followed by radiation and chemotherapy as described here show satisfactory outcome. In this high risk group, metastasis staging correlated with outcome but the degree of surgical resection and presence or absence of residual tumor at primary site did not correlate with outcome.
Ataxia ; Brain Neoplasms ; Child ; Chungcheongnam-do ; Cisplatin ; Craniospinal Irradiation ; Cyclophosphamide ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Etoposide ; Humans ; Hypothyroidism ; Inappropriate ADH Syndrome ; Intellectual Disability ; Intestinal Pseudo-Obstruction ; Medical Records ; Medulloblastoma* ; Mortality ; Neoplasm Metastasis ; Neoplasm, Residual ; Neurosurgery ; Pediatrics ; Puberty, Precocious ; Radiation Oncology ; Retrospective Studies ; Survival Rate ; Vincristine