Child ; Child Welfare ; Humans ; Medulloblastoma ; drug therapy ; epidemiology ; surgery ; Mortality ; Radiotherapy ; Singapore ; epidemiology ; Treatment Outcome

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.
Arm ; Brain Neoplasms ; Child ; Classification ; Computational Biology ; Drug Therapy ; Hedgehogs ; Humans ; Medulloblastoma ; Mortality ; Neurosurgery ; Pediatrics ; Population Characteristics ; Recurrence

The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates +/-95% confidence intervals (CI) were 33.3+/-12.2% and 26.7% +/-11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates +/-95% CI was 40.0+/-15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.
Adolescent ; Cerebellar Neoplasms/drug therapy/mortality/*therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; Disease-Free Survival ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Medulloblastoma/drug therapy/mortality/*therapy ; Neoplasm Recurrence, Local/drug therapy/mortality/*therapy ; Republic of Korea ; Salvage Therapy ; Transplantation, Autologous ; Young Adult

We analyzed the 43 cases of the posterior fossa tumors at the Busan Paik Hospital, Inje Medical College from January 1980 to December 1986. The posterior fossa tumors included 12 cases of cerebellar astrocytoma, 10 cases of acoustic neurinoma, 5 cases of medulloblastoma, 5 cases of brain stem glioma, 2 cases of meningioma, 2 cases of hemangioblastoma, 2 cases of tuberculoma, 1 case of glioblastoma multiforme, 1 case of oliodendroglioma, 1 case of rhabdomyosarcoma, 1 case of glomus jugulare tumor and 1 case of arteriovenous malformation. The posterior fossa tumors were occupied on the cerebellar hemisphere in 18 cases, the cerebellar vermis in 8 cases, the cerebellar pontine angle in 12 cases and the brain stem in 5 cases. The 25 cases out of the 43 cases of the posterior fossa tumors were accompanied with hydrocephalus. The 10 cases received the radiation therapy and/or the chemotherapy after operation. After treatment of the posterior fossa tumors, 52.6% favorable outcome, 34.2% unfavorable outcome and 13.2% mortality were estimated.
Arteriovenous Malformations ; Astrocytoma ; Brain Stem ; Busan ; Drug Therapy ; Glioblastoma ; Glioma ; Glomus Jugulare Tumor ; Hemangioblastoma ; Hydrocephalus ; Infratentorial Neoplasms* ; Medulloblastoma ; Meningioma ; Mortality ; Neuroma, Acoustic ; Rhabdomyosarcoma ; Tuberculoma

Medulloblastoma, once a tumor with a dismal prognosis, is one of the most common primary brain tumors of childhood. As the methods of treatment have been continuously refined, the outcome has improved remarkably during the last few decades. The outcome of 78 medulloblastoma patients, which were managed from 1972 to 1992 at the Department of Neurosurgery of Seoul National University Hospital, were analyzed to calculate the 3-year and 5-year survival rates (3yS and 5yS). Of those, 52 cases which were treated after July 1982 were studied 1) to calculate the 3yS and 5yS, 2) to figure out the prognostic factors of survival, and 3) to investigate the role of adjuvant chemotherapy ('8-drugs-in-a-day' protocol: CCNU, cisplatin, vincristine, hydroxyurea, procarbazine, cytosine arabinoside, methylprednisolone and cyclophosphamide). The 3yS and 5yS of the 78 patients were 57.4% and 47.3%, respectively. Of the 52 patients treated after July 1982, the 3yS and 5yS were 67.8% and 64.1%, respectively. The latest recurrence was at 56 months after surgery. All the recurrences were within the risk period of Collins' rule. Of the prognostic factors studied by univariate analysis (age, sex, Chang's classification T- and M-stages, extent of surgical removal, and chemotherapy), Chang's classification M-stage and sex were the statistically significant factors (p = 0.028 and 0.024 respectively). On multivariate analysis, only the M-stage was statistically significant (p = 0.004). Adjuvant chemotherapy had different influences in different patient groups. Only in the 'poor risk' group, did adjuvant chemotherapy have a strong tendency to better outcome (p = 0.069). Further data collection and analysis will lead to better treatment modalities and better outcome for this most common primary malignant brain tumor in childhood.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cerebellar Neoplasms/*drug therapy/mortality/radiotherapy ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Medulloblastoma/*drug therapy/mortality/radiotherapy ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Survival Rate ; Treatment Outcome

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