Malignant Brain Tumours in Children : Present and Future Perspectives

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.

Malignant Brain Tumours in Children : Present and Future Perspectives

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.

Thyroid dysfunction in patients with childhood-onset medulloblastoma or primitive neuroectodermal tumor

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.

Response of Leptomeningeal Dissemination of Anaplastic Glioma to Temozolomide: Experience of Two Cases

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.

Current Trends in Management for Central Nervous System Germ Cell Tumor / 임상소아혈액종양

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.

Current Trends in Management for Central Nervous System Germ Cell Tumor / 임상소아혈액종양

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.

Neurocognitive Function and Health-Related Quality of Life in Pediatric Korean Survivors of Medulloblastoma

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.

Patterns of Failure Following Multimodal Treatment for Medulloblastoma: Long-Term Follow-up Results at a Single Institution / Journal of the Korean Cancer Association, 대한암학회지

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.

Understanding the Treatment Strategies of Intracranial Germ Cell Tumors: Focusing on Radiotherapy

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.

Coexistence of Radiation-induced Meningiomas and Shunt Related Pneumocephalus in a Patient with Successfully Treated Medulloblastoma

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.

Treatment of Supratentorial Primitive Neuroectodermal Tumors (PNETs) in Children

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.

High Risk Medulloblastoma in Childhood: Multidisciplinary Approach and Improved Outcome / 대한소아혈액종양학회지

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.

Analysis of the Causes of Subfrontal Recurrence in Medulloblastoma and Its Salvage Treatment / 대한방사선종양학회지

PURPOSE: Firstly, to analyze factors in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma. Secondly, to explore an effective salvage treatment for these relapses. MATERIALS AND METHODS: Two patients who had high-risk disease (T3bM1, T3bM3) were treated with combined chemoradiotherapy. CT-simulation based radiation-treatment planning (RTP) was performed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. RESULTS: Review of radiotherapy portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume. When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. CONCLUSION: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.

CT Simulation Technique for Craniospinal Irradiation in Supine Position / 대한방사선종양학회지

PURPOSE: In order to perform craniospinal irradiation (CSI) in the supine position on patients who are unable to lie in the prone position, a new simulation technique using a CT simulator was developed and its availability was evaluated. MATERIALS AND METHODS: A CT simulator and a 3-D conformal treatment planning system were used to develop CSI in the supine position. The head and neck were immobilized with a thermoplastic mask in the supine position and the entire body was immobilized with a Vac-Loc. A volumetric image was then obtained using the CT simulator. In order to improve the reproducibility of the patients' setup, datum lines and points were marked on the head and the body. Virtual fluoroscopy was performed with the removal of visual obstacles such as the treatment table or the immobilization devices. After the virtual simulation, the treatment isocenters of each field were marked on the body and the immobilization devices at the conventional simulation room. Each treatment field was confirmed by comparing the fluoroscopy images with the digitally reconstructed radiography (DRR)/digitally composite radiography (DCR) images from the virtual simulation. The port verification films from the first treatment were also compared with the DRR/DCR images for a geometrical verification. RESULTS: CSI in the supine position was successfully performed in 9 patients. It required less than 20 minutes to construct the immobilization device and to obtain the whole body volumetric images. This made it possible to not only reduce the patients' inconvenience, but also to eliminate the position change variables during the long conventional simulation process. In addition, by obtaining the CT volumetric image, critical organs, such as the eyeballs and spinal cord, were better defined, and the accuracy of the port designs and shielding was improved. The differences between the DRRs and the portal films were less than 3 mm in the vertebral contour. CONCLUSION: CSI in the supine position is feasible in patients who cannot lie on prone position, such as pediatric patients under the age of 4 years, patients with a poor general condition, or patients with a tracheostomy.

Postoperative External Beam Radiotherapy for Medulloblastoma / 대한방사선종양학회지

PURPOSE: This study was performed to evaluate the effectiveness and tolerance of craniospinal irradiation for patients with medulloblastoma and to define the optimal radiotherapeutic regimen. MATERIALS AND METHODS: We retrospectively analyzed the records of 43 patients with medulloblastoma who were treated with external beam craniospinal radiotherapy at our institution between May, 1984 and April, 1998. Median follow up period was 47 months with range of 18 to 86 months. Twenty seven patients were male and sixteen patients were female, a male to female ratio of 1.7 : 1. Surgery consisted of biopsy alone in 5 patients, subtotal excision in 24 patients, and gross total excision in 14 patients. All of the patients were treated with craniospinal irradiation. All of the patients except four received at least 5,000 cGy to the posterior fossa and forty patients received more than 3,000 cGy to the spinal cord. RESULTS: The overall survival rates at 5 and 7 years for entire group of patients were 67% and 56%, respectively. Corresponding disease free survival rates were 60% and 51%, respectively. The rates of disease control in the posterior fossa were 77% and 67% at 5 and 7 years. Gross total excision and subtotal excision resulted in 5 year overall survival rates of 76% and 66%, respectively. In contrast, those patients who had biopsy alone had a 5 year survival rate of only 40%. Posterior fossa was a component of failure in 11 of the 18 recurrences. Seven recurrences were isolated to the posterior fossa. Four patients had neuraxis recurrences, three had distant metastasis alone and four had multiple sites of failure, all involving the primary site. CONCLUSION: Craniospinal irradiation for patients with medulloblastoma is an effective adjuvant treatment without significant treatment related toxicities. There is room for improvement in terms of posterior fossa control, especially in biopsy alone patients. The advances in radiotherapy including hyperfractionation, stereotactic radiosurgery and 3D conformal radiotherapy would be evolved to improve the tumor control rate at primary site.

Radiation Therapy of Intracranial Germinomas: Optimum Radiation Dose and Treatment Volume / 대한방사선종양학회지

PURPOSE: To evaluate the possibility of decreasing the radiation dose and to determine optimum treatment volume in intracranial germinomas. MATERIALS AND METHODS: Forty five patients with pathologically-verified or presumed germinomas by a radiosensitivity test who had been treated with radiotherapy (RT) alone between 1971 and 1992 were retrospectively analyzed. The average age was 17.2 years with 68.9% of the patients being between the ages of 10-20. The male and female ratio was 2.2:1. The locations of the primary tumors were at the pineal regions in 14 patients; the suprasellar regions in 12 patients; and multiple sites in 12 patients. Treatment volumes varied from a small local field (10) to the whole brain (7) or entire neuroaxis irradiation(28). All the cases after 1982 received craniospinal irradiation (CSI). Radiation doses were 41-59 Gy (median 48.5 Gy) to the primary tumor site and 19.5-36 Gy (median 24 Gy) to the neuroaxis. The median follow-up period was 82 months with a range of 2-260 months. RESULTS: All the patients showed complete response after RT. Four patients sufferred from recurrence 14, 65, 76, and 170 months after RT, respectively, and two patients died with intercurrent disease. One of four recurrent cases was salvaged by re-irradiation. Therefore, a 5 and 10 year overall survival was 95.3 % and 84.7 % respectively. Five and ten year disease-free survival was 97.6 % and 88.8 % respectively. All the recurrences occurred in the patients who received local RT (3/10) or whole brain RT (1/7) with a radiation dose of 48-50 Gy. None of the patients who received CSI suffered recurrence. There was no recurrence among the 15 patients who received < or = 45 Gy to the primary site and the 18 patients who received < or = 24 Gy (6 patients received 19.5 Gy) to the neuroaxis. CONCLUSION: CSI is recommended for the treatment of intracranial germinomas. The radiation dose can be safely decreased to < or = 45 Gy on a primay tumor site and 19.5 Gy on the spine.

A Clinical Analysis of Primary Intracranial Germ Cell Tumors

Primary intracranial germ cell tumors(GCTs) are relatively rare brain tumors that show a diverse range of histologic features from benign to highly malignant conditions. To determine their clinical findings, pathology, treatment and outcome, we analyzed the medical records of 45 patients with primary intracranial GCTs treated at our hospital between June 1989 and December 1996. Thirty-two were males and 13 were females, and their ages ranged from three to 43 years. Fifteen cases were located in the pineal region and 13 in the suprasellar. The remaining locations were the basal ganglia in eight cases, both the pineal and suprasellar region in five, and others in four. In the pineal region, there was a male predominance(13:2), but in the suprasellar region, more cases(ten of 13) involved females. Of the 15 patients with tumors of the pineal region, increased intracranial pressure(IICP) was evident in 12 and six had Parinaud's syndrome. Of the 13 patients with tumors of suprasellar region, nine had diabetes insipidus; seven, visual deficit; and six, hypopituitarism. Germinoma was the most common histologic type. Other types of histology were two teratomas, three embryonal carcinomas, one endodermal sinus tumor, one choriocarcinoma, and five mixed GCTs. All patients except those with a teratoma underwent whole craniospinal irradiation. We performed gross total or subtotal removal in cases of non-germinomatous GCTs(NGGCTs) and mixed tumors, but biopsy or partial removal was preferred for the germinomas. Thirteen of 45 patients received adjuvant chemotherapy. All malignant NGGCT and mixed tumor patients were treated with adjuvant chemotherapy, as well as three of 33 germinoma patients. Three of five malignant NGGCT patients and two of five mixed tumor patients died of tumor progression. Two of 33 germinoma patients died not of disease progression but of other causes. Actuarial survival records showed that overall two-year and five-year survival rates were 89.9% and 71.9%, respectively. There were no statistically significant differences with regard to patient's age, sex, or tumor location. With regard to their histology and surgical extent, malignant NGGCTs and mixed tumors showed statistically significant differences. Five-year surival rates of germinoma and malignant NGGCT patients were 83.1% and 53.3%, respectively. We suppose that the appropriate combination of chemotherapy and surgery, with or without radiation therapy, remains to be defined, and that to determine the appropriate management protocol for malignant NGGCTs and mixed tumors, larger series of patients must be analyzed.

Malignant Rhabdoid Tumor of the Cerebellum in an Adult: A case report

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of infancy and childhood. Although it was originally described and most frequently reported in the kidney, it may occur in various extra-renal sites such as the liver, thymus, and soft tissue. In the last decade primary central nervous system (CNS) MRTs have been reported in both the supra- and infratentorial compartments. Patients with CNS MRT were generally below the age of two and reports in adults are extremely rare. This is a case of primary cerebellar MRT in a 24-year-old woman, who had presented with intermittent headache, vocal cord palsy, and cerebellar dysfunctions such as abnormal finger to nose test and tandem gait. By magnetic resonance imaging scan, a well-enhancing solid mass was demonstrated at the posterior fossa filling the 4th ventricle, which extended into the medulla and cervical cord via the foramen of Magendie. Histologically, the monotonous polygonal tumor cells were arranged in diffuse sheet with occasional hemorrhagic necrosis. The nuclei were vesicular and eccentrically located due to eosinophilic, PAS-positive, intracytoplasmic inclusions with prominent nucleoli. They were diffusely or focally immunoreactive for vimentin, neurofilament, cytokeratin, GFAP, synaptophysin, and smooth muscle actin, while epithelial membrane antigen and desmin were negative. Ultrastructurally, the polyhedral tumor cells were densely packed with primitive intercellular junctions. Scanty fibrillar intermediate filaments were intermingled with cellular organelles. Postoperatively, craniospinal irradiation and systemic chemotherapy have been done and she has been free of tumor recurrence during the 13 months' follow-up periods.

Two Cases of Thyroid Tumor after Radiation Therapy of Primary Malignancy / 대한소아내분비학회지

The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. The development of benign thyroid nodules, thyroid carcinoma and thyroid dysfunction following radiotherapy during childhood has been documented. Recently we experienced two cases of thyroid tumor after irradiation. One is a 14-year-old boy with thyroid follicular carcinoma who had received mantle irradiation(3,000cGy) eight years previously for Hodgkin' disease. The other is a 15-year- old boy with thyroid follicular adenoma who had received craniospinal irradiation (3,600cGy) seven years previously for CNS relapse of acute lymphoblastic leukemia. We recommend frequent sonographic evaluation and early suppression of thyroid stimulation in an attempt to arrest the development of neoplastic changes in long term survivors of childhood malignancies who received radiation therapy.

Radiation Therapy of Intracranial Germinoma / 대한치료방사선과학회지

PURPOSE: Intracranial germinoma is the most radiocurable tumor of the primary intracranial neoplasm. But, the optimum radiation dose and target volume remain controversial. In this retrospective study, we analysed the spreading pattern at presentation and the pattern of the failure and survival of intracranial germinoma. MATERIALS AND METHODS: From 1989 to 1996, 23 patients were treated for intracranial germinoma at Department of Radiation Oncology. Twenty-one patients were treated at their initial presentation and 2 patients were treated for recurrent disease. Six patients had multiple tumor masses on MRI and 7 patients had ventricular seeding on MRI. The examination of cerebrospinal fluid cytology was done in 15 patients and 3 out of 15 patients had positive cerebrospinal cytology. In tumor marker study of alpha-FP and beta-hCG, 6 patients had mildly elevated beta-hCG in serum or cerebrospinal fluid. Twenty-one patients were treated with whole craniospinal axis irradiation and 2 patients were given whole ventricular radiation therapy. The total dose was ranged between 4500cGy and 5600cGy to primary tumor site (median 5580 cGy). Dose to the entire ventricular system ranged from 1980cGy to 3960 cGy (median 2700cGy) and dose to the spinal axis ranged from 2160cGy to 3900cGy (median 2700cGy). RESULTS: Of 23 patients, 21 patients are alive without evidence of disease for median 4 years follow-up. One patient who had markedly elevated alpha-FP and beta-hCG suffered from persistent disease after radiation therapy and received 2 cycles of chemotherapy. She died 9 months after chemotherapy. One patient who developed ventricular seeding after gamma-knife was treated with whole craniospinal irradiation, he died after 1 year due to probably brain necrosis. The hematologic toxicity of 3 or 4 grade were seen in 7 patients, and patient's endocrinologic dysfunction was not deteriorated after radiation therapy. One patient had been treated with growth hormone replacement due to short stature. CONCLUSIONS: This retrospective study has confirmed the excellent result of radiation therapy in intracranial germinoma. The complication rate during or after radiation therapy is considered within acceptable range. It is necessary to further investigate the optimal dose and treatment volume of radiation therapy. The role of chemotherapy in the treatment of intracranial germinoma should be further investigated.