The microscopic surgical treatment for tumor of posterior cranial fossa in children

OBJECTIVE To analyze and discuss about the clinical characteristics, pathological types, surgical modalities and techniques, and postoperative complications in children with tumor of posterior cranial fossa.
METHODS Retrospective study was conducted on 102 cases of pediatric tumor of posterior cranial fossa, admitted and treated in our hospital during the period of January 1996 to January 2007. All patients underwent microscopic surgical treatment. Fiftyeight were male and 44 cases were female. The age ranged from 9 months to 14 years old, with an average of 6.1 ± 0.5 of age. Cranial CT or MRI examination was conducted before and after the surgery on all patients. RESULTS The primary manifestations for this group of patients were increased intracranial pressure and/or ataxia. Postoperative pathological diagnoses showed： 46 cases of medulloblastoma, 43 cases of astrocytoma, 11 cases of ependymoma （including 1 case of degenerative ependymoma）, 1 case of dermoid cyst, and 1 case of teratoma. In this group of the patients, radical surgery was used in 68 cases and subtotal surgical removal used in 31 cases, while surgical removal of large section was performed on 3 cases. There were no deaths from surgery reported. Ninety-one cases showed significant symptomatic improvement when compared with preoperative conditions, while 11 cases showed either no improvement or more severely affected afterward. For 6 cases, postoperative ventriculoperitoneal shunt was performed within 7 days to 2 months after the surgery. Sixty-three patients gained follow-up for 3 to 60 months in duration. Thirty-nine patients regained normal life and were able to learn well, while there were 7 patients who could not live normally on their own. During the follow-up period, there were 17 cases of recurrence and 7 cases of death. In 23 cases of medulloblastoma in children with age of 3 years old or above, 2 cases who underwent surgical removal of intracranial ependymoma received small dosage of postoperative X-ray radiotherapy on the the brain and spinal cord. Nine cases of medulloblastoma in children under age of 3 and 17 cases of astrocytoma diagnosed after the surgery received chemotherapy of Carmustine.
CONCLUSION Medulloblastomas and astrocytomas were the most common types of pediatric tumor of posterior cranial fossa, right followed by ependymoma, and dermoid cysts and teratomas were rare. Early correct diagnosis, proper selection of appropriate surgical modality and the surgical margin, proper treatment of postoperative complications, and the selecting right radiotherapy or chemotherapy were the key factors in influencing the prognostic outcome of children with tumor of posterior cranial fossa.     

显微手术治疗儿童第四脑室肿瘤

目的：对儿童第四脑室肿瘤的早期诊断、手术策略和技巧及术后并发症进行分析讨论.方法：回顾性分析中国医大盛京医院1993年1月至2008年12月儿童第四脑室肿瘤手术病例57例.所有患儿均经显微手术治疗.男33例,女24例.年龄9个月至14岁.所有患儿术前、术后均行头颅CT和（或）MRI检查.结果：本组手术全切除34例,次全切除20例,大部切除3例.症状较术前明显改善42例,无明显改善或加重5例;10例术后7d-2个月内行侧脑室-腹腔分流术.46例患者获得随访3-40个月,32例生活或学习良好,其中随访期内复发7例.对3岁以上的20例髓母细胞瘤,6例室管膜瘤切除术后行小剂量X线全脑脊髓神经轴放疗,6例星形胶质细胞瘤切除术后加化疗.结论：儿童第四脑室肿瘤以髓母细胞瘤最多见,其次为室管膜瘤和星形细胞瘤.早期正确诊断,术中恰当的手术策略选择及切除程度、术后并发症恰当处理和有选择性放疗是影响儿童第四脑室肿瘤预后的关键因素.     

Diffusion MRI in Evaluation of Pediatric Posterior Fossa Tumors

Background: To evaluate the role of diffusion MRI in differentiating pediatric posterior fossa tumors and determine the cut-off values of ADC ratio to distinguish medulloblastoma from other common tumors. Methods: We retrospectively reviewed MRI of 90 patients (7.5-year median age) with pathologically proven posterior fossa tumors (24 medulloblastoma, 7 ependymoma, 4 anaplastic ependymoma, 13 pilocytic astrocytoma, 30 diffuse intrinsic pontine glioma (DIPG), 4 ATRT, 3 diffuse astrocytoma, 2 high grade astrocytoma, 2 glioblastoma, and 1 low grade glioma). The conventional MRI characteristics were evaluated. Two readers reviewed DWI visual scale and measured ADC values by consensus.  ADC measurement was performed at the solid component of tumors. ADC ratio between the tumors to cerebellar white matter were calculated. Results: The ADC ratio of medulloblastoma was significantly lower than ependymoma, pilocytic astrocytoma and DIPG. The ADC cut-off ratio of ≤ 1.115 allowed discrimination medulloblastoma from other posterior fossa tumors with sensitivity, specificity, PPV and NPV of 95.8%, 81%, 67.6% and 97.9%, respectively. ADC ratio cut-off level to differentiate medulloblastoma from ependymoma was ≤ 0.995 with area under the curve (AUC)= 0.8693. ADC ratio cut-off level for differentiate medulloblastoma from pilocytic astrocytoma at ≤ 1.17 with AUC = 0.9936. ADC cut-off level for differentiate medulloblastoma from DIPG at ≤ 1.195 with AUC = 0.9681. The ADC ratio was correlated with WHO grading by the lower ADC ratio associated with the higher grade. Furthermore, High DWI visual scale was associated with high grade tumor. Conclusion: Diffusion MRI has a significant role in diagnosis of pediatric posterior fossa tumors. ADC ratio can be used to distinguish medulloblastoma from other posterior fossa tumor with good level of diagnostic performance.     

Serial MRI Scan of Posterior Fossa Tumours Predict Patients at Risk of Developing Neurocognitive Impairment

Background: Brain tumours are the most common solid tumours in children. More than 50% of these tumours develop in the posterior cranial fossa. Long term survivors of posterior fossa tumours (PFT) suffer from neurocognitive and memory issues. We hypothesized that serial MRI scanning of brain would show differences in hippocampal and ACC volume change in PFT patients treated with and without chemo-radiotherapy. Material and Methods: Twelve patients (8 females and 4 males) underwent 76 serial MR imaging examinations before and during treatment for posterior fossa tumours. Seven patients (4 medulloblastoma, 2 as ependymoma and 1 high grade glioma) were treated with maximum surgical resection followed by adjuvant radiotherapy and chemotherapy (Group 1). The other five patients were diagnosed as pilocytic astrocytoma who were treated only with surgery (Group 2). Hippocampal volumes were obtained manually on high-resolution 3Tesla T1-weighted images and normalised to intracranial volume, while ACC thickness and volume were obtained automatically using FreeSurfer software. Results: After the treatment period, the change in normalised hippocampal volume from baseline was significantly lower in group 1 patients compared to group 2 (mean change -0.0001470 ± 8.981e-005; Mean ± SEM vs 0.0002765 ± 9.151e-005; Mean ± SEM, respectively, P=0.004). Displayed graphically, the negative hippocampal growth trajectory in group 1 gradually returned to a positive growth pattern. There were no statistically significant changes in ACC volume and thickness. Both groups had similar rates of pre-operative hydrocephalus. Conclusion: Compared to PFT patients treated with surgery alone, PFT patients treated with chemo-radiotherapy showed lower hippocampal volumes and altered hippocampal growth trajectory. Serial quantitative MRI measures of brain may provide a neuroanatomical substrate for assessing functional impact on normal brain function following treatment of posterior fossa tumours.     

The local field in infratentorial ependymoma: does the entire posterior fossa need to be treated?

INTRODUCTION: In the past decade, there have been multiple reports indicating that the predominant problem in the curative treatment of intracranial ependymoma is local failure. As a result, many have recommended local field radiotherapy. For infratentorial ependymoma, there is controversy regarding what constitutes the local field. Some radiation oncologists advocate coverage of the entire posterior fossa, whereas others recommend radiotherapy to the tumor bed and a safety margin. METHODS AND MATERIALS: From 1984 to 1998, 28 patients with posterior fossa ependymoma were diagnosed at our institution. There were 18 males and 10 females with a median age of 12 years (range, 2-81 years). Four patients (14%) had high-grade ependymoma and 3 (11%) had M+ disease at initial diagnosis. Gross total resection was achieved in 17 (61%) and postoperative radiotherapy (RT) was given to 22 (77%). Radiotherapy fields were craniospinal in 10, whole brain in 1, posterior fossa in 2, and tumor bed with a 2-cm. margin in 9. Median dose to the primary site was 54 Gy (range, 45-55 Gy). All 4 patients with high-grade ependymoma received craniospinal RT. Six patients did not receive RT after surgery. Magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain at initial diagnosis were compared to MRI or CT scans of patients at relapse to determine if the local relapse was in the tumor bed or nontumor bed posterior fossa. Median follow-up was 127 months (range, 14-188 months). RESULTS: Six patients have relapsed. For the 11 patients who had craniospinal or whole brain radiotherapy (RT), 3 recurred (tumor bed 1, spine 1, nontumor bed posterior fossa + spine 1). Both patients who failed in the spine had high-grade tumors. Neither of the 2 treated with posterior fossa fields relapsed. For the 9 patients who had tumor bed RT alone and the 6 who did not receive RT, there were 3 relapses; all were in the tumor bed. There were no relapses in the nontumor bed posterior fossa. CONCLUSION: For nondisseminated, low-grade infratentorial ependymoma, the radiotherapy volume does not need to include the entire posterior fossa. This information can be used to minimize late effects of RT in the era of three-dimensional (conformal) radiotherapy. No conclusion can be reached regarding the appropriate local field for high-grade infratentorial ependymoma because of the small number of patients.     

Childhood brain tumors that occupy more than one compartment at presentation

Children whose brain tumor involves two or more compartments at presentation differ clinically and pathologically from children whose brain tumor is confined to one compartment. In this study of 3,291 children with a brain tumor, at least 10% had a tumor that occupied two or three compartments at first hospitalization. Infratentorial tumors occupying multiple compartments were 1.7 times more likely to involve the cervicomedullary junction than the mesodiencephalic junction. Younger children (1–3 years) were more likely to have had multiple compartment tumors than older children. Children whose tumor was limited to the infratentorial compartment had a longer survival than children whose tumor also occupied other compartments. Ependymoma, anaplastic ependymoma, and astrocytoma (nos) were over represented among infratentorial multiple compartment tumors. Pilocytic astrocytoma, primitive neuroectodermal tumor (medulloblastoma), and desmoplastic medulloblastoma were less likely to have occupied multiple compartments at the time of the first surgical exploration. The distributions of histologic features in tumors at the cervicomedullary junction differed from those in tumors limited to the posterior fossa or to the spinal canal. Seizures were more likely if the tumor was confined to the supratentorial compartment, whereas nausea or vomiting and headache were more likely if the tumor was confined to the infratentorial compartment. Children whose tumor was confined to the spinal canal were significantly more likely to have bladder symptoms and back and/or abdominal pain than those whose tumor also involved compartments above the foramen magnum. We conclude that brain tumors apparently confined to one compartment at presentation are biologically and structurally different from tumors evident in two or more compartments.     

Angiogenesis and Angiogenic Tyrosine Kinase Receptor Expression in Pediatric Brain Tumors

Tumor angiogenesis and receptor tyrosine kinases (RTK) are major novel targets in anticancer molecular therapy. Accordingly, we characterized the vascular network and the expression pattern of angiogenic RTK in the most frequent pediatric brain tumors. In a retrospective collection of 44 cases (14 astrocytoma, 16 ependymoma and 14 medulloblastoma), immunohistochemistry for VEGFR1, VEGFR2, PDGFRα, PDGFRβ, and c-Kit as well as microvessel labeling with CD34 and SMA were conducted on surgical specimens. We found a significantly higher vascular density in ependymoma. Glomeruloid formations were abundant in medulloblastoma but rare or almost absent in astrocytoma and ependymoma, respectively. C-Kit and VEGFR2 labeled blood vessels were more abundant in ependymoma than in the other two types of tumors. In contrast, medulloblastoma contained higher number of PDGFRα expressing vessels. In tumor cells, we found no VEGFR2 but VEGFR1 expression in all three tumor types. PDGFRα was strongly expressed on the tumor cells in all three malignancies, while PDGFRβ tumor cell expression was present in the majority of medulloblastoma cases. Interestingly, small populations of c-Kit expressing cancer cells were found in a number of medulloblastoma and ependymoma cases. Our study suggests that different angiogenic mechanisms are present in ependymoma and medulloblastoma. Furthermore ependymoma patients may benefit from anti-angiogenic therapies based on the high vascularization as well as the endothelial expression of c-kit and VEGFR2. The expression pattern of the receptors on tumor cells also suggests the targeting of specific angiogenic tyrosine kinase receptors may have direct antitumor activity. Further preclinical and biomarker driven clinical investigations are needed to establish the application of tyrosine kinase inhibitors in the treatment of pediatric brain tumors.     

Primitive neuroectodermal tumors in the central nervous system following cranial irradiation: a report of four cases

BACKGROUND: Radiation induced intracranial neoplasms are uncommon but well described and include gliomas, meningiomas, and sarcomas. The development of primitive neuroectodermal tumors (PNETs) following prophylactic craniospinal irradiation has been infrequently reported previously. The authors present four additional cases of PNETs that developed after previous cranial irradiation. METHODS: Four patients who had previously been irradiated were determined to have PNETs of the central nervous system characterized by histopathologic and immunohistochemical features. The average patient age at diagnosis of the initial tumors and cranial irradiation was 17 years. The PNETs developed 5, 11, 11, and 18 years after completion of radiation. RESULTS: Three patients had posterior fossa tumors, one pilocytic astrocytoma, one low grade astrocytoma, and one malignant ependymoma, which had been diagnosed and treated in childhood. Two of those patients developed supratentorial PNETs and the third a cerebellar hemispheric PNET. The fourth patient developed a posterior fossa PNET following irradiation for a temporal astrocytoma, which was initially diagnosed and resected at 37 years of age. Mean survival was 12 months after diagnosis. CONCLUSIONS: The development of PNETs after cranial irradiation may be more common than thought previously and should be considered in the differential diagnosis of irradiation induced neoplasms. Survival after diagnosis of these radiation induced PNETs was short, and this may reflect an inability to provide standard therapy used for primary PNETs.     

Concurrent chemotherapy and reduced-dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average-risk medulloblastoma: efficacy and patterns of failure

PURPOSE: To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated with concurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost. METHODS AND MATERIALS: Thirty-three patients with average risk (defined as < or =1.5 cm(2) of residual tumor after resection, age >3 years, and no involvement of the cerebrospinal fluid or spine [M0]) medulloblastoma were diagnosed at our institution between January 1994 and December 2001. They were enrolled in an institutional pilot protocol consisting of concurrent chemotherapy (vincristine), reduced-dose cranial spinal irradiation (2340 cGy), a conformal primary tumor bed boost (3240 cGy), followed by eight cycles of chemotherapy (vincristine, cisplatin, and lomustine or cyclophosphamide). The median age at diagnosis of the 33 patients was 7 years (range, 3-21 years). The male/female patient ratio was 2.4:1. The median follow-up of the entire group was 37 months (range, 6-96 months), and the median follow-up of the survivors was 44 months (range, 10-96 months). RESULTS: The 5-year estimated disease-free survival rate, as determined by Kaplan-Meier plots, was 86% (+/-12.6%, 95% confidence interval). The 5-year estimated disease-free posterior fossa control and primary tumor bed control rates were both 94% (+/-8.2%, 95% confidence interval). The patterns of failure included 2 patients with distant central nervous system failure only, 1 patient who developed local primary tumor bed failure, posterior fossa failure, and diffuse leptomeningeal spread simultaneously, and 1 patient with failure in the high-dose, primary tumor bed field. No patient experienced isolated posterior fossa failure outside the high-dose boost region. CONCLUSION: The treatment of average-risk medulloblastoma with chemotherapy, reduced-dose cranial spinal irradiation, and a conformal tumor bed boost results in survival rates and local control rates comparable to those in contemporary studies. A reduction in the amount of posterior fossa treated to the high dose is possible. These results need to be corroborated in a large, cooperative group study.     

Role of surgery for optic pathway/hypothalamic astrocytomas in children

Optic pathway/hypothalamic pilocytic astrocytomas in children are usually treated with chemotherapy following a surgical biopsy. In this report, we retrospectively considered the role of surgical intervention. In a series of 25 patients without neurofibromatosis type 1, the median age at initial treatment was 3.1 years (range, 0-15 years). Twenty cases were verified by histology, and five cases were diagnosed by MRI findings. Twenty-three patients received chemotherapy. All patients were alive at median follow-up of 66 months. Aims of surgery at the initiation of treatment were biopsy in 12 cases (1 stereotactic and 11 craniotomies) and debulking in 7 cases. The 11 open biopsies revealed pilocytic astrocytoma; however, noticeable complications occurred in five children after the biopsies. Review of preoperative MRIs showed that all had typical findings indicating pilocytic astrocytoma. The open biopsy offered no noteworthy benefit for the patients despite surgical risk and delay of chemotherapy. The extent of the seven resection surgeries was 70% or less removal, and postoperative adjuvant therapy was needed for six of the seven patients. The remaining six children who did not undergo surgery obtained remission with chemotherapy alone. After relapse in nine patients, 15 bulk-reduction surgeries were performed. Surgical resection was not curative in any patient. In five patients, mostly older children, cystic expansion of tumor was partially resected, resulting in additional remission. In conclusion, considering the risk of open surgery and the effectiveness of chemotherapy, the role of surgical intervention is restricted to bulk-reduction surgery only when it is inevitable, especially at relapse after chemotherapy.     

Radiotherapy of cerebellar medulloblastoma in children

Out of 108 children with brain tumors, aged 3-15, receiving radiotherapy in 191-1997, cerebral medulloblastoma was identified in 37 (34%). After total or subtotal excision of tumor, the latter were given 4-12 cycles of polychemotherapy. The brain and spinal marrow was exposed to 30-35 Gy followed by aiming 50-55 Gy irradiation of posterior cranial fossa. Three patients received radiation for recurrent tumor. One patient suffered demyelination as complication after repeated exposure. Out of 32 follow-up patients, 19 have survived an average of 33 months while 13 died having survived an average of 21 months. The main causes of failed therapy proved local progression of tumor and dissemination via liquor. Radical extent of surgery was used as the main prognostic factor.     

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.     

Flow cytometric DNA analysis of medulloblastoma. Prognostic implication of aneuploidy

Paraffin-embedded surgical specimens from 26 infants and children with medulloblastomas treated between 1972 and 1981 were examined for DNA ploidy by flow cytometry (FCM). All patients received a standard treatment (a combination of maximum debulking of medulloblastoma and postoperative craniospinal irradiation with a posterior fossa boost of 5000 rad or more). They were studied to correlate the results of the findings of FCM DNA analysis with their final outcome, DNA ploidy, and extent of tumor resection. All seven patients with totally resected aneuploid medulloblastoma are alive, whereas only one of six patients with subtotally resected diploid medulloblastoma is alive (P = 0.0047). The current study suggests both DNA ploidy and extent of surgical resection are the most important determinant of patients' prognosis. Patients in selected group, particularly those with subtotally resected diploid tumor, are advised to undergo aggressive adjuvant chemotherapy.     

Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience

A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 with histologically verified recurrent malignant brain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1, ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 with recurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patients with recurrent tumor had prior chemotherapy and/or irradiation. Each course of CPT-11 consisted of 125 mg/m ( 2 ) per week given i.v. for 4 weeks followed by a 2-week rest period. Patients with recurrent tumors received therapy until disease progression or unacceptable toxicity. Patients with newly diagnosed tumors initially received 3 cycles of treatment to assess tumor response and then were allowed radiotherapy at physician's choice; patients who demonstrated a response to CPT-11 prior to radiotherapy were allowed to continue the drug after radiation until disease progression or unacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IV toxicity. Responses were assessed after every course by gadolinium-enhanced MRI of the brain and spine. Twenty-two patients received a median of 2 courses of CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM or anaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (complete response in 2 patients with recurrent GBM lasting 9 months and 48+ months; partial response in one patient with a newly diagnosed midbrain GBM lasting 18 months prior to radiotherapy; and partial response lasting 11 months in 1 patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrent ependymoma (partial response initially followed by stable disease lasting 11 months), and none of 5 patients with recurrent diffuse pontine glioma. Two of 3 patients with medulloblastoma/primitive neuroectodermal tumor had stable disease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of 22 patients (50%) suffering grade II-IV neutropenia. Seven patients required dose reduction secondary to neutropenia. CPT-11, given in this schedule, appears to be active in children with malignant glioma, medulloblastoma, and ependymoma with acceptable toxicity. Ongoing studies will demonstrate if activity of CPT-11 can be enhanced when combined with alkylating agents, including carmustine and temozolomide.     

Preliminary results of conformal radiation therapy for medulloblastoma

Radiation therapy for medulloblastoma consists of postoperative irradiation of the intracranial and spinal subarachnoid volume with an additional boost to the primary site of disease in the posterior fossa. The entire posterior fossa is usually included in the boost volume. Conformal radiation therapy techniques may be used to boost the primary site alone and substantially reduce the dose received by normal tissues, including the supratentorial brain, the middle and inner ear, and the hypothalamus. Using these techniques to irradiate only the tumor bed or residual tumor and not the entire posterior fossa represents a new paradigm in the treatment of medulloblastoma. In this study, we examine the use of conformal radiation therapy in the treatment of 14 patients with medulloblastoma. These patients were treated with multiple static, individually shaped, noncoplanar beams directed at the primary site after craniospinal irradiation. Excluding two patients who had previously received irradiation to the posterior fossa, the mean dose delivered to the primary site was 5715 cGy. Among the medulloblastoma patients (n = 10) who received immediate postoperative radiation therapy, no failures have occurred with a median follow-up of 42 months (range from 30 to 54 months). To demonstrate the differences in the distribution of dose to normal tissues when comparing conventional and conformal techniques, dose-volume histograms of the total brain, middle and inner ear, hypothalamus, and temporal lobe were created and presented for an example case. The neurologic, neuroendocrine, and neurocognitive outcome for patients with medulloblastoma may be influenced with the use of conformal radiation therapy. The use of these techniques should be formally tested in prospective studies of rigorously staged patients with failure rate monitoring.     

Medulloblastoma and supratentorial primitive neuroectodermal tumors: an institutional experience.

BACKGROUND: To the authors' knowledge there are relatively few data concerning supratentorial primitive neuroectodermal tumors (PNET). The authors retrospectively reviewed all cases of PNET of the brain treated at the study institution to determine whether there was a difference in presentation, overall survival, and recurrence-free survival with regard to tumor location (supratentorium vs. posterior fossa). METHODS: Between 1977-1996 33 patients with PNET were diagnosed and treated at 1 radiotherapy center. The median age of the patients was 9 years. The location of the tumor was in the posterior fossa in 25 patients and the supratentorium in 8 patients. The tumor had spread to the neuraxis in six patients; four patients with disseminated neuraxis disease had a supratentorial PNET and two had a posterior fossa PNET. All but three patients received craniospinal irradiation. The primary tumor received > or = 5000 centigray in 27 patients and chemotherapy was employed in 26 patients. The median follow-up was 60 months. RESULTS: The 5-year overall and recurrence-free survival rates for all patients were 77.2% and 79.6%, respectively. The 5-year overall survival rates were 86.3% for patients with medulloblastoma (posterior fossa PNET) and 46.9% for patients with supratentorial PNET (P = 0.01, log rank test). For overall survival, prognostic factors included radiotherapy dose to the primary site, metastases (M) status, and location of the primary tumor. The 5-year recurrence free survival rates were 89.8% for patients with medulloblastoma and 46.9% for patients with supratentorial PNET (P = 0.003, log rank test). For recurrence free survival, prognostic factors included M status and primary tumor site location; radiation dose to the primary tumor site and patient gender were of borderline significance. In the ten patients with inadequate posterior fossa boost fields judged by Children's Cancer Group criteria, there were two failures, both of which were in the original tumor bed. CONCLUSIONS: Supratentorial PNET has a worse overall survival and recurrence free survival than medulloblastoma. There is a suggestion that radiotherapy boosts in medulloblastoma may not need to encompass the entire posterior fossa because posterior fossa failures primarily are in the tumor bed. Larger studies with longer follow-up are needed to determine whether craniospinal irradiation followed by a boost to the tumor bed is adequate for medulloblastoma patients.     

Pediatric brain tumours at a tertiary care hospital in Karachi.

The objectives of this study were to determine the epidemiology of brain tumors during infancy and childhood and to define and segregate childhood brain tumors vis-a-vis their morphological characteristics. The present study includes pediatric brain tumors, ICD-10 category C71 encountered during 10 years (January 1989 through December 1998) at a tertiary care hospital in Karachi. Eighty one cases were included, 58 (71.6%) in males and 23 (28.4%) in females with a male to female ratio of 2.5:1. The cases were divided into 3 age groups each covering five years of life (0-4, 5-9, 10-14 years), with the greatest number in the second age group i.e. 5-9 years followed by the third age group and the 0-4 year age group. The mean age for all cases, both genders was 8.8 years (95% CI 7.9; 9.6) with a marginal variation for cases occurring in the cerebrum and cerebellum. The malignancies occurred at a younger age in the males for each subcategory by site and morphology. The morphological distribution of cases was astrocytoma (28 cases, 34.6%), primitive neuroectodermal tumor or PNET (40 cases; 49.4%), ependymoma (8 cases, 10%), mixed glioma (4 cases; 5%) and a case of oligodendroglioma. The 81 malignancies included in this study were further categorized by site into two groups, supratentorial (27 cases; 33.3%) and infratentorial (54 cases; 66.7%). The morphological categorization of supratentorial tumors was astrocytoma (17 cases; 63%), ependymoma (5 cases; 18.5%), mixed glioma (2 cases; 7.4%). PNET with rhabdoid differentiation, oligodendroglioma and pinealoblastoma comprised 1 case (3.7%) each. The 17 supratentorial astrocytoma were sub-categorized as follows - pilocytic astrocytoma (5 cases; 29.4%), grade II astrocytoma (6 cases; 35.3%); grade III astrocytoma (2 cases; 11.8%), anaplastic astrocytoma (1 case; 5.9%) and glioblastoma multiforme (3 cases; 17.7%). The morphological categorization of infratentorial tumors was astrocytoma (11 cases; 20.4%), medulloblastoma (38 cases; 70.4%), ependymoma (3 cases; 5.6%) and mixed glioma - astroependymoma (2 cases, 3.7%). The morphological sub-categorization of infratentorial astrocytoma was pilocytic astrocytoma (7 cases, 63.6%), with gemistocytic astrocytoma, grade II, grade III and anaplastic astrocytoma comprising 1 (9.1%) case each. The morphological categorization of medulloblastoma was classical medulloblastoma (15 cases; 39.5%), desmoplastic medulloblastoma (8 cases; 21.1%), medulloblastoma with astrocytic differentiation (12 cases; 31.5%), medulloblastoma with neural differentiation (2 cases; 5.3%), and neuroblastic medulloblastoma (1 case; 2.6%). The pediatric brain tumors in Karachi reflect a developing country scenario, with a strong male predisposition and a late presentation with a peak in the 5-9 year age group. There is a predominance of medulloblastoma and a paucity of astrocytomas. The current study is a single institution study and needs cautious interpretation. Population-based studies are required to determine the cancer burden due to pediatric malignancies of the brain in this population and for the morphological categorization of brain tumors in Karachi.     

MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children

Infants and young children who have brain tumors have a poor rateof survival and high treatment associated morbidity. A trial of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone(MOPP) was performed to test the hypothesis that replacingradiotherapy with chemotherapy would improve survival and decreaselong term morbidity of infants who have brain tumors. Between 1976 and1988, 17 consecutive children less than 36 months old when diagnosed with medulloblastoma or ependymoma were treatedwith MOPP chemotherapy as primary therapy following surgical excision or biopsy of the tumor. Radiotherapy was reserved for recurrent disease. Ten of 17 children have survived without evidence of disease: medulloblastoma, eight of 12 with median survivaltime of 10.6 years (range, 6.2 to 15.2 yrs); and ependymoma, 2of 5 (at 13.0 and 16.0 yrs). Four of the 10 children with medulloblastomaand ependymoma who relapsed are now disease free at 7.5, 11.7, 12.2 and 13.5 yrs post relapse after receiving salvagetherapy with cisplatin (n = 1) or irradiation (n = 3). All relapsesoccurred within 26 months of diagnosis. Data on growth demonstrated heightless than the 5th percentile in all children who received cranial irradiation compared to 25 to 95th percentile for nonirradiated children. Intellectual ability for the groupwho did not require radiation was within normal range (mean IQ 100.1) and stable across annual assessments. Those who required radiation hadlower IQs which continued to decline over time (mean IQ 85 at mean age of 5.8 years, declining to 63 at 10 years).In young children with brain tumors, primary chemotherapy with MOPP, omitting radiotherapy, provides improved neurodevelopmental outcome and survival.     

Cerebellar medulloblastoma: results of a new method of radiation treatment.

Nine patients with medulloblastoma were referred to the Radiation Oncology Section at the University of Chicago from 1966 to 1976. In all patients, the tumor was situated in the posterior cranial fossa, projecting from the cerebellum into the fourth ventricle. After partial tumor resection and histological diagnosis, radiation treatment was instituted: a localized dose of 1000 rad to the posterior fossa through lateral opposing ports and a total dose of 4000-5000 rad through the "hockey-stick" port to the entire CNS. With this treatment, 9 patients yielded actuarial 3- and 5-year survival rates of 88% and 73%, respectively. Five of the patients possessed no history of neurologic or spinal growth deficits after treatment. Two patients had a slight retardation of spinal growth. The remaining patients had presented symptoms of a tumor mass in the posterior fossa for a period of over 8 months prior to treatment. They were found at craniectomy to have diffuse intracranial tumor involvement, and their survival times deteriorated rapidly. The "hockey-stick" port provided a uniform distribution of radiation exposure to the entire brain and spine. It was simple to use and posed little inconvenience to patients in the pediatric age group.     

Role of spinal MRI in the follow-up of children treated for medulloblastoma

BACKGROUND: The purpose of the current study was to describe the usefulness of spinal magnetic resonance imaging (MRI) in children with medulloblastoma or primitive neuroectodermal tumor (PNET) of the posterior fossa. METHODS: Children consecutively diagnosed with medulloblastoma/PNET and followed in the Hospital for Sick Children/Toronto were identified. A homogenous cohort of children treated with craniospinal irradiation as part of their initial treatment was considered. Contrast-enhanced spinal MRIs done concomitantly with cranial MRIs (doublets) were reviewed. Recurrence was defined as any new abnormal lesion (in the brain or in the spine) in symptomatic or asymptomatic patients. Doublets after the first recurrence were excluded in the final analysis. The utility of a spinal MRI in the presence of a negative cranial MRI was assessed. RESULTS: In all, 73 patients (21 females and 52 males; median age, 6.6 years, median follow-up time, 4.3 years) had at least 1 evaluable doublet during the follow-up period. Since concomitant cranial and spinal MRI was introduced as the standard evaluation for medulloblastoma/PNET in 1991, 286 doublets were evaluable. Fourteen spinal MRIs and 25 cranial MRIs showed new nodular or leptomeningeal lesions. In 2 patients, repeat MRIs ruled out recurrence (false-positive). All confirmed spinal recurrences were associated with intracranial recurrence. Of 261 doublets with negative cranial MRI, no new lesion was identified on spinal MRI. CONCLUSIONS: An absence of progression on cranial MRI is highly predictive of absence of progression on spinal MRI. There is little evidence that surveillance spinal MRI (in children who underwent craniospinal radiation as part of their initial treatment) improves the detection of recurrences in children with medulloblastoma.