Glioblastoma multiforme in children: report of 13 cases and review of the literature

We present clinical and histopathologic data from 13 children who underwent craniotomy for newly diagnosed glioblastoma multiforme. Clinical characteristics were compared to those in adult patients (n = 403). The mean age of the children was 10.4 years. The male/female ratio was 3.3:1. The localization was infratentorial in 6 cases (brainstem, n = 4; cerebellum, n = 2) and supratentorial in 7 cases (frontal, n = 2; parietal, n = 3; temporal, n = 2). Infratentorial localization was observed solely in children from 0-10 years, whereas supratentorial location was found in children between the age of 11 and 21 years. Surgical resection was followed by radiotherapy in 11 cases and additional chemotherapy in 8 cases. Giant cell glioblastoma multiforme was found in 2 cases (15%, vs 1-5% in adults). The mean Ki-67 proliferation index was 29.4% (vs 25.6% in adults). There were no significant differences in histologic morphology between children and adults. The total survival time was 90 weeks (vs 47 weeks in adults). One patient is still alive after 8 years. Predictive factors of prolonged survival were the extent of tumor resection and radio- and/or chemotherapy after resection. Multidisciplinary treatment of glioblastoma in childhood might lead to better median survival than in adults. Infratentorial tumor location was observed exclusively in children younger than 11 years old.     

Outcome of children with posterior fossa medulloblastoma: a single institution experience over the decade 1994–2003

Aim While the impact of radiotherapy in the management of medulloblastoma was recognised, the introduction of chemotherapy was investigated in clinical trials and shown to confer an additional advantage. We reviewed the outcome of a series of consecutive patients to assess the impact in a population-based clinical establishment. Materials and methods A series of 38 children treated for medulloblastoma at Birmingham Children’s Hospital between 1994 and 2003 was analysed. The effect of surgery, radiotherapy, chemotherapy and metastasis on survival was analysed. Results The overall 5-year survival rate was 61.4% for the 36 patients who had resective surgery, while 2 patients had biopsy only and died within a few months. There was no operative mortality. The incidence of hydrocephalus needing permanent shunting was higher in the first 3 years of life (p = 0.007, chi-square). The 5-year survival rate of patients with total and sub-total excision of medulloblastoma was 61.1% and 61.8%, respectively. The 5-year survival rate of patients older than 3 years was 73.4% and for patients under 3 years was 36.3% (p = 0.007, log rank). Metastases at presentation did not influence survival. All deaths occurred in the first 32 months. Conclusion The contribution of chemotherapy in the improvement of the overall survival appears more evident in children younger than 3 years or presenting with metastases. The absence of significant difference in survival between patients with total or sub-total excision of medulloblastoma supports the view that total excision of medulloblastoma can be avoided when the risk for potential intra-operative damage and consequent neurological deficits is high.     

Outcome of teenagers and young adults with ependymoma: The Royal Marsden experience

Background  The outcome and clinical characteristics of teenagers and young adults (TYA) with ependymoma have not been well documented. We report the Royal Marsden Hospital experience treating TYA with ependymoma. Materials and methods  Sixteen TYA were treated for ependymoma from 1971 to 2004 and are compared to 24 children (not infants) treated in the same period. Results  Twelve TYA (75%) received treatment in a neuro-oncology unit. Average time from symptoms to diagnosis was 183 days for TYA vs. 61.2 for children (p = 0.005). Two TYA (12.5% vs. 41.6% for children, p = 0.08) were enrolled in a clinical trial. Only 25% of TYA achieved gross total resection, all of them received radiotherapy and five of them received chemotherapy. There were five relapses; all of them were local. Five-year overall survival was 84.6% ± 10 for TYA vs. 78.1% ± 8.7 for children (p = 0.15), and 5-year progression-free survival was 66.6% ± 12.3 for TYA vs. 44.4% ± 10.3 for children (p = 0.08). Up to 56% of patients treated in the paediatric unit received psychosocial support vs. 42.9% of patients treated in the adult unit. Discussion  Ependymoma in adolescents and young adults is an infrequent entity, with perhaps better outcome compared to children. The extent of surgical resection as seen in children is an important prognostic factor. Providing adolescents with ependymoma the appropriate neuro-oncologic care, including access to multidisciplinary teams, full access to clinical trials and age-appropriate neuro-oncologic ancillary support services, remains a challenge.     

Neurological outcome after resection of intramedullary spinal cord tumors in children

Objective With modern surgical advances, radical resection of pediatric intramedullary spinal cord tumors (IMSCT) can be achieved with preservation of long-term neurological function. Clinical and radiographic risk factors predictive of postoperative neurological outcome may serve as a guide for surgical risk stratification. Materials and methods We prospectively reviewed the outcomes of 16 consecutive cases of pediatric IMSCT resection at a single institution. Clinical, radiographic, and operative variables were analyzed as predictors of postoperative neurological function defined by the modified McCormick score (MMS). Results Sixteen children 10 ± 5 years old presented with median (interquartile range) MMS score of 2 (1–2) with IMSCTs (eight cervical, eight thoracic) involving 4 ± 2 levels. Pathology revealed astrocytoma in 12 cases (three pilocytic, four grade II, three gradeIII, two GBM), gangliogliomas in two, ependymoma in one, and gliosis in one case. At median follow-up of 7 months, six (38%) patients experienced improved neurological function, eight (50%) remained stable, one (6%) experienced a delayed decrease in neurological function (GBM progression), and one (6%) died (GBM progression). Five (31%) patients developed persistent dysesthetic symptoms. Four (80%) patients with cystic tumors experienced neurological improvement compared to only two (18%) patients with noncystic tumors, p < 0.05. Preoperative steroid use (odds ratio, OR [95% confidence interval, CI] = 18.0 [1.24–260.1], p = 0.03) and cystic tumor (OR [95%CI] = 18.0 [1.24–260.1], p = 0.03) predicted neurological improvement after surgery. Conclusion Radical resection of pediatric IMSCTs can be achieved with low incidence of neurological injury. Sensory syndromes frequently occur after pediatric IMSCT resection and frequently affect patient’s quality of life. Tumors with compressive cysts may identify patients more likely to experience improved neurological function after surgical resection.     

Extended focal radiotherapy of 30 Gy alone for intracranial synchronous bifocal germinoma: a single institute experience

Objects  To evaluate the disease characteristics and treatment outcomes for patients with intracranial synchronous bifocal germinomas treated with extended focal irradiation alone. Methods  Between January 1996 and March 2007, seven patients (three males and four females) with intracranial synchronous bifocal germinomas treated at Taipei Veterans General Hospital were reviewed. The median age at diagnosis was 14 years (range, 11–28 years). Four patients had surgery before radiotherapy. All patients underwent extended focal irradiation encompassing the whole ventricle system with a total radiation dose of 30 Gy (2 Gy daily). No patient received scheduled systemic chemotherapy before or after radiotherapy. Disease characteristics, treatment outcomes, and the impact of lesion numbers (single vs. bifocal) on survivals were investigated. Results  With a median follow-up time of 49 months (range, 20–66 months), the 2- and 5-year survival rates were both 100%. After treatment, all patients had good performance without recurrence. No severe complication was observed. In comparison, the overall survival (OS, p = 0.475) and the disease-free survival (DFS, p = 0.537) rates were not significantly different between bifocal- and single-lesion groups. Lesion numbers did not affect both OS and DFS. In addition, the incidence of neuraxial seeding was not higher in patients with bifocal germinomas as compared to those with single lesion. Conclusions  Intracranial germinomas are extremely radiosensitive. Young patients with synchronous bifocal germinomas could be successfully treated with extended focal 30-Gy radiotherapy alone. The therapeutic advantage using this regimen needs to be further evaluated with larger sample size and longer follow-up time. Pin-I Huang, Yi-Wei Chen, and Tai-Tong Wong contributed equally to this work.     

Intracranial ependymomas in children

During a 20-year period (1964–1983), the authors managed 60 children with intracranial ependymomas. In 37 patients the tumors were located in the posterior cranial fossa, and in the remaining 23 they were supratentorial. The histological examination in 26 children revealed ependymoblastomas. The average duration of the clinical evolution was 4 months and 5 days in the supratentorial neoplasms and 3 months and 6 days in the subtentorial. Besides the intracranial hypertension, present in about 80% of the patients, specific localizing signs were seen in 70% of the children with subtentorial and in 40% of those with supratentorial tumors. Because of the growth pattern in posterior fossa ependymomas and despite the prevalence of histologically benign neoplasms, radical resection was accomplished in only 21.6% of the cases, as compared with 30.4% in supratentorial tumors. The postoperative mortality remains high: 29.7% in subtentorial tumors and 17.4% in supratentorial. The 1-year survival rate in subtentorial neoplasms was 70.3%, the 3-year survival 29.7%, and the 5-year survival 16.2%. The corresponding figures for supratentorial ependymomas were more favorable: 82.6%, 43.5%, and 26.1%, respectively. The most important factors for improving the outcome at the present time appear to be as radical a resection as possible, supplemented with postoperative radiotherapy and chemotherapy.     

Pineal and nonpineal supratentorial primitive neuroectodermal tumors

Pineal region supratentorial primitive neuroectodermal tumors (SPNETs; pineoblastomas) and nonpineal SPNETs are rare tumors that historically have carried a very poor prognosis. With multimodality therapy, including maximal surgical resection, craniospinal radiation therapy and chemotherapy, the survival for patients with pineal PNETs has significantly improved. Chemotherapy alone, at least in conventional doses, appears to be insufficient treatment for younger children with pineoblastomas, in whom there is almost universal rapid tumor progression and death. Survival of patients with nonpineal SPNETs remains in the order of 30–35% despite multimodality therapy. Unlike those with pineal SPNETs, a significant percentage of infants with nonpineal SPNETs who undergo gross total surgical resection followed by chemotherapy will be long-term survivors. This article gives an overview of the natural history, prognostic factors and treatment of both pineal and nonpineal SPNETs. Received: 12 April 1999     

Intraspinal high-grade astrocytoma in a child – rationale for chemotherapy and more intensive radiotherapy?

Intraspinal high-grade astrocytoma in children is an extremely rare tumor entity with disappointingly short survival times despite multimodality treatment. We report on a girl with anaplastic astrocytoma at level T9–11, who was treated with tumor resection, multidrug chemotherapy and irradiation. Local recurrence was diagnosed after 16 months. With reference to other cases reported in the literature, the course of disease, achievements and limitations of currently available therapeutic options, and potential future strategies are discussed.     

Responsiveness of progressive optic pathway tumors to cisplatin-based chemotherapy in children

Background  Though the pathology of optic pathway tumor is mostly pilocytic astrocytoma, the benign tumor behaves like malignant tumor because total resection is not feasible. Adjuvant chemotherapy might be a reasonable strategy for management of these low grade tumors which keep growing. We evaluate the responsiveness of optic pathway tumor to cisplatin-based chemotherapy. Methods  Patients with unresectable and progressive optic pathway tumors received conventional chemotherapy including cisplatin, etoposide, and vinblastine were enrolled in this study from 1992 to 2007. Patients treated with radiotherapy previously were excluded. Brain MRI was performed every 3 months to evaluate the objective response to chemotherapy. Results  There are seven girls and nine boys enrolled in this study. The median age at diagnosis was 30 months old (range from 3 months to 11 years old). The median follow-up duration was 81.5 months (range from 24 months to 14.5 years). The pathology showed pilocytic astrocytomas in 11 patients, astrocytoma in one patient, and anaplastic astrocytomas in two patients. The 6-month progression-free survival (PFS) is 100%, 12-month PFS is 81.3%, 3-year PFS is 71.4% and 5-year PFS is 55.5% respectively. The toxicity of the cisplatin-based chemotherapy showed mild bone marrow suppression in 13 patients (81.3%), infection in nine patients (56.3%), gastrointestinal discomfort in seven patients (43.8%), renal insufficiency in two patient (12.5%), cerebral salt wasting syndrome with hyponatremia in one patient (6.25%) and high pitch hearing loss in two patients (12.5%). Conclusion  Cisplatin-based chemotherapy is an effective regimen for control of progressive optic pathway tumors. Ting-Rong Hsu and Kai-Ping Chang contributed equally to this paper.     

The impact of extent of resection in the management of malignant gliomas of childhood

Radical surgical resection of newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) in children is the most powerful favorable predictor of outcome when followed by radiation therapy and chemotherapy. In the largest study of childhood malignant gliomas (Children's Cancer Group Study, CCG-945), which was conducted between 1985 and 1992, a radical surgical resection was defined as greater than 90% resection of tumor as seen on imaging studies, predominantly using MRI. Of note is that the training of the neurosurgeon (i.e. in pediatric versus adult neurosurgery) had a significant impact on the extent of surgical resection in patients enrolled on this study. In children with recurrent malignant glial tumors, radical surgical resection has been shown to predict a more favorable survival for children, both with GBM and AA, undergoing high-dose (marrow-ablative) chemotherapy with hematopoietic stem cell rescue. In these studies, radical surgical resection was defined as resection leaving less than 3 cm maximal diameter of enhancing tumor mass in place.     

Therapeutic results of eight patients with intracranial ependymomas]

Between 1985 and 2001, eight patients with intracranial ependymomas underwent surgery at our hospital. The cases included six infratentorial ependymomas, one supratentorial ependymoma and one supratentorial anaplastic ependymoma. Infratentorial ependymomas were classified according to origin and extension. The lateral type tumors originated from the lateral part of the fourth ventricle in four cases. The midfloor type tumors originated from the inferior half of the fourth ventricular floor in two cases. The three totally resected tumors were the lateral type tumors. The remaining one case with the lateral type tumor underwent nearly total resection of the tumor, since the tumor involved lower cranial nerves. All patients with the midfloor type tumors underwent incomplete resections of the tumors, because the tumors infiltrated into brain stem. Lower cranial nerve involvement and brain stem invasion implied incomplete resection and had the poor prognosis. In intracranial ependymomas, all four patients with total resections have been alive, whereas three of four patients with incomplete resections have died. The mean survival time of all patients with intracranial ependymomas was 127 months from the time of the initial surgery. There were no deaths in the patients with tumors showing MIB-1 index < 10% (n = 4). The mean survival time of the patients with tumors showing MIB-1 index > or = 10% (n = 4), was 30 months. The extent of the resection, the age of the patients and MIB-1 index are important factors in the outcome in patients with intracranial ependymomas. Two representative children aged less than 3 years with the midfloor type tumors were presented. In a patient treated with conventional radiation and chemotherapy, residual tumor repeatedly enlarged within 12 months despite several resections of the tumor. The patient died 32 months after the initial resection. In contrast, the other patient received multidisciplinary treatment including Linac stereotactic radiotherapy (SRT) with a marginal dose of 27 Gy in 9 fractions, have been still alive for 45 months after the initial resection. The residual tumor slightly decreased in size and remained stable without evident growth 12 months after SRT. SRT may provide good local control for patients with intracranial ependymomas and have a favorable impact on survival.     

Is the ancillary chemotherapy approach of any value in the treatment of infratentorial primitive neuroectodermal tumors with surgery and radiotherapy?

A retrospective historical analysis of patients under 18 years of age with the histopathological diagnosis of infratentorial primitive neuroectodermal tumor (PNET) is presented. The survey embraced two different groups of children. Group 1 was defined as those patients treated from 1972 to 1984 with surgical resection plus neuraxis radiotherapy alone. Group 2 was made up of children treated from 1990 to 1996 with the same approach but with the addition of adjuvant chemotherapy: cisplatin (day 1) and etoposide (days 1–3) every 3 weeks for 6 months. Group 1 embraced 42 children with an age range of 1– 16 years (mean 6 years, SD 4.4 years). In group 2 there were 34 children, their ages ranging from 1 to 18 years (mean 7.2, SD 4.6 years). The prevalence of stages T2M0 and T3M0 was similar in both groups, but in group 1 there were 4 patients (9.5%) whose spinal fluid was positive for tumor cells (M1), while in group 2 there were 7 children (20.5%) with positive spinal fluid. There was an unequivocal initial response to treatment in 86% of these children in group 1 and in 79% in group 2. The event-free survival (EFS) was 30% at 252 months in group 1, while for group 2 the EFS was 67.6% at 63 months (P 0.002). Mortality from tumor activity was noted in 26 patients (70%) in group 1, while in group 2 mortality attributable to tumor progression was documented in 11 children (32%). We conclude that the use of adjuvant chemotherapy in these patients improves survival without any significant morbidity. Received: 28 October 1997     

Pineal tumors: experience with 48 cases over 10 years

The authors retrospectively reviewed 48 patients treated at Seoul National University Hospital (SNUH) between 1986 and 1995. There were 35 children and 13 adults, accounting for 10.1% of 345 pediatric and 0.68% of 1914 adult brain tumors in SNUH during the same period. The 48 cases consisted of 33 cases of germ cell tumor (69%, GCT); 6 of pineoblastoma (PB, 12.5%); 3 of pineocytoma (PC, 6.3%); 3 of anaplastic astrocytoma (6.3%); 1 of astrocytoma; 1 of glioblastoma; and 1 of ependymoma. The median age was 13 years (range 1–59) and the male-to-female ratio was 3.36:1. The most frequent presenting symptom was due to increased intracranial pressure (90%), followed by Parinaud syndrome or diplopia (50%). Patients with a benign tumor, such as teratoma (TE), astrocytoma, or ependymoma, underwent surgery by the occipital transtentorial approach (OTT) for attempted radical resection without adjuvant therapy, while patients with immature teratoma (imTE), PC, and anaplastic astrocytoma underwent regional radiotherapy (RT) after debulking via OTT. Seven patients with nongerminomatous malignant GCT (NG-MGCT) and 3 with germinoma (GE) underwent craniospinal radiation only, 6 with GE, a NG-MGCT, and 2 with GE+TE received craniospinal radiotherapy (CSRT) after debulking via OTT. Three patients with GE, 4 with NG-MGCT, and 3 with PB underwent radiochemotherapy after debulking via OTT. Forty-four patients were followed up after treatment. The median follow-up period was 36 months. All patients with GE were alive after RT at 36 months (median) of follow-up (range 7–70 months). All with GE+TE and TE were alive. Three patients with PC or astrocytoma were also alive with stable or no evidence of disease. In 1 of the 3 cases of imTE there was a recurrence. However, 4 patients with NG-MGCT died, all of whom had undergone CSRT only; 2 PB patients were alive (12, 19 months), 1 in a moribund status (36 months), and 2 were dead (6, 60 months). The overall mean survival time with pineal tumors was 66 months and the 3-year survival rate was 84% with minimal posttreatment complications. It is concluded that pineal region tumors have male and childhood predominances, and the most common tumor is GCT. The majority of pineal region tumors are malignant. Pineal region tumors can be approached safely and effectively and the surgical complications are mostly transient. Their prognosis is dependent on the pathologies and treatment modalities.     

Treatment and survival of supratentorial and posterior fossa ependymomas in adults

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan–Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3 years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p < 0.0001), high tumor grade (HR 1.82, p = 0.005), and large tumor size (HR 1.66, p = 0.008) were associated with poor survival. Females compared to males (HR 0.67, p = 0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p = 0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.     

Medulloblastoma in children – the Ottawa experience

A retrospective review of 36 children diagnosed with medulloblastoma in the Ottawa area between 1974 and 1997 was completed (mean age 7.8±4.2 years, range 1.2–15.3 years). Via a suboccipital approach, complete tumor resection was achieved in 75% and subtotal resection (>90%) in 25%, without any operative mortality. The tumor was located in the vermis in 39% and in the cerebellar hemisphere in 11%; it occupied both locations in 50%. In 47% of the children a ventriculoperitoneal shunt was required. Postoperatively, craniospinal radiation at 3600 cGy with a boost to the posterior fossa was administered. Chemotherapy was used in 56%. The 1-year survival rate was 92%, and survival plateaued at 54% at 5 years. Children less than 3 years of age fared worse than those over 3 years old. While the male-to-female ratio was 1.6:1, there was no gender difference in survival. Chang’s classification was used to grade the tumors. T stage did not have an impact on survival, but M stage did. No statistically significant difference in survival was found between the patients who had a total resection and those who had a subtotal resection. There was no difference in survival in terms of tumor location, hydrocephalus or ventriculoperitoneal shunt. Chemotherapy showed no survival benefit. The recurrence rate was 26%, and its timing followed Collin’s law. Recurrence led to death within 1–9 months. GH deficiency was diagnosed in 5 patients and hypothyroidism in 4 patients. The mean follow-up time was 4.4±3.7 years, with a range of 2.5 months to 16.5 years. Fourteen patients died, 5 were lost to follow-up, and 7 were transferred to adult care without persistent disease. Ten children are presently being followed up by the Neuro-oncology Clinic. Four children continue to be followed through psychology services. Our results are comparable to those in larger series, and are similar to those of the Montreal Children’s Hospital. Received: 13 December 1999     

Significance of beaten copper appearance on skull radiographs in children with isolated sagittal synostosis

Aims and Objectives The significance of beaten copper appearance (BCA) on skull radiographs in children following surgery for isolated sagittal craniosynostosis has not been studied. This study was designed to look for any correlation between BCA and symptoms suggestive of intracranial hypertension in this group of patients. Materials and Methods Forty-eight consecutive children, who were operated for isolated sagittal synostosis from1987 to 2000 and had postoperative skull radiographs, were included. Patients were divided into: (a) BCA group (n = 20), consisting of children who had beaten copper appearance on skull radiographs at last follow up, and (b) Non-BCA group (n = 28), consisting of children who did not have this finding. Records were reviewed to look for symptoms suggestive of intracranial hypertension, such as headache, head banging, and irritability. Results Median age at surgery was 4.8 months for BCA group and 4 months for the non-BCA group. Follow up ranged from 4 to 156 months with a mean of 36.2 months. Total of 28.6% (n = 6) of the children with follow up radiographs done at ≤18 months of age had BCA. The incidence of BCA increased to 83.3% in children with skull radiographs performed after 48 months of age. In 18 (90%) children, the BCA was ‘diffuse’ with 5 (25%) children having the maximum possible score of 8. In the BCA group, 45% (n = 9) had symptoms compared to 10.7% (n = 3) in the control group (p = 0.0068). Conclusions This study suggests a significant number of children with BCA on radiographs develop symptoms suggestive of raised ICP following surgical treatment in infancy and prolonged follow up may be warranted in this group of patients.     

Central nervous system atypical teratoid rhabdoid tumor: experience at the National Institute of Pediatrics,Mexico City

Objective The purpose of this study is to present our experience with ten cases of Central nervous system atypical teratoid rhabdoid tumor (CNS/ATRT). Patients and methods A series of ten patients with CNS/ATRT, were diagnosed and treated between 1990 and 2005, at the National Institute of Pediatrics, in Mexico City. The gender, age of presentation, clinical features, tumor localization, imaging studies, grade of tumor resection, complications, adjuvant therapy, and survival are presented. Results The mean age at diagnosis was 37.8 months, seven cases were male, and their average clinical course was 1.3 months. The more common clinical presentation was intracranial hypertension with cranial nerve deficits; location was infratentorial in four patients and supratentorial in six. Hydrocephalus was present as the most common complication (seven cases). In nine patients, the grade of resection was total or subtotal. In one case, it was only possible to perform a biopsy. There were two cases with longer survival (9 and 16 months), and their tumors were resected in total or subtotal manner and received adjuvant therapy (radiotherapy and chemotherapy). Conclusions Preliminary results, show that in older children, we can improve their survival with the subtotal or total resection of the tumor and the addition of chemotherapy and radiotherapy.     

基于美国SEER数据库的儿童胶质瘤临床特点和预后分析

目的基于美国SEER数据库回顾总结儿童胶质瘤的临床特点,并探究不同组织学类型的生存预后相关影响因素。方法纳入SEER数据库中2000-2015年经组织病理学证实的胶质瘤患儿共7759例,根据组织学类型分为毛细胞型星形胶质瘤、髓母细胞瘤、室管膜瘤、胶质母细胞瘤及其他类型胶质瘤,绘制Kaplan?Meier生存曲线,比较毛细胞型星形细胞瘤、髓母细胞瘤、室管膜瘤和胶质母细胞瘤患儿的5年生存率;采用单因素log?rank检验和多因素向前引入法Cox回归分析筛查上述4种组织学类型患儿生存预后相关影响因素。结果本组7759例患儿根据组织学类型分为毛细胞型星形细胞瘤2585例(33.32%)、髓母细胞瘤2061例(26.56%)、室管膜瘤777例(10.01%)、胶质母细胞瘤443例(5.71%)、其他类型胶质瘤1893例(24.40%)。不同组织学类型之间性别(χ²=60.390,P=0.000)、年龄分布(χ²=600.318,P=0.000)、肿瘤大小(χ²=90.773,P=0.000)和原发部位(χ²=2117.948,P=0.000)、病理分级(χ²=1233.506,P=0.000)差异均有统计学意义,其中,髓母细胞瘤和胶质母细胞瘤好发于男性[60.89%(1255/2061)和57.56%(255/443)];学龄期为高峰发病年龄[35.48%(2753/7759)];毛细胞型星形细胞瘤和髓母细胞瘤以小肿瘤为主[31.30%(809/2585)和33.77%(696/2061)]且好发于小脑[42.24%(1092/2585)和59.58%(1228/2061)],室管膜瘤和胶质母细胞瘤则较大[32.43%(252/777)和29.57%(131/443)]且多发生于幕上及脑室[36.81%(286/777)和65.91%(292/443)],仅毛细胞型星形细胞瘤以低级别为主[24.06%(622/2585)]。生存分析显示,毛细胞型星形细胞瘤、髓母细胞瘤、室管膜瘤和胶质母细胞瘤患儿5年生存率分别为97.41%(2518/2585)、64.39%(1327/2061)、76.83%(597/777)和16.25%(72/443),不同组织学类型之间差异有统计学意义(χ²=2145.672,P=0.000)。单因素log?rank检验和多因素Cox回归分析显示,不同组织学类型胶质瘤预后相关影响因素不尽一致,主要包括确诊年龄、肿瘤大小和原发部位、病理分级、手术切除和放疗,除毛细胞型星形细胞瘤外,髓母细胞瘤、室管膜瘤和胶质母细胞瘤患儿接受手术切除均对生存预后有积极意义;放疗可降低髓母细胞瘤患儿死亡风险,但可能增加毛细胞型星形细胞瘤患儿的死亡风险。结论毛细胞型星形细胞瘤比例最高,预后较好;胶质母细胞瘤发病率相对较低,预后较差。人口统计学信息、肿瘤特征和治疗方案均为儿童胶质瘤患者生存预后的预测因素,手术切除可降低除毛细胞型星形细胞瘤外的其他组织学类型胶质瘤患儿的死亡风险;放疗可降低髓母细胞瘤患儿的死亡风险,但有可能增加毛细胞型星形细胞瘤患儿的死亡风险。     

Preirradiation ifosfamide,carboplatin, and etoposide (ICE) for the treatment of high-grade astrocytomas in children

Background Astrocytomas are the most common form of primary intracranial tumor; however, survival of patients with high-grade tumors has not changed much compared with that reported in the early 1970s.Objective Our objective was to assess the efficacy, security, and survival rate of postoperative chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with anaplastic astrocytomas (AA) and glioblastoma multiforme (GM).Methods In a phase II study, we evaluated 25 children with AA or GM. The proposed treatment was four courses of chemotherapy with ICE followed by hyperfractionated radiotherapy, and then four more courses of ICE. Patients were evaluated using MRI after surgery, after the second course of chemotherapy, and again after the last. Toxicity was determined before each course.Results The overall and disease-free survival at 60 months was 67% and 56% respectively. For supratentorial localization it was 92% at 60 months and 20% at 18 months for brain stem tumors. Fourteen patients had a complete response and 9 died as a result of tumor progression.Conclusions Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity.A commentary on this paper is available at     

Posterior fossa tumors in children: how long does it take to establish the diagnosis?

Objective The aim of this study is to evaluate, for our patient population, the time interval from the first chart-documented symptom to the radiological diagnosis in children and infants with posterior fossa tumors. Materials and methods We retrospectively analyzed 50 consecutive children (36 men, 14 women) with posterior fossa tumor treated at our department between January 1999 and December 2003. The mean age at time of diagnosis was 98 months (6 months–16 years). The mean follow up was 27 months (6–61 months). The diagnoses included astrocytoma (n = 17), medulloblastoma (n = 15), ependymoma (n = 6), and other tumors (n = 12). Results The mean time interval between onset of symptoms and radiographic diagnosis was 142 days (5–535 days), the median was 59 days. The mean time for Grade I and II tumors was 238 days (n = 19) and for tumors Grade III and IV 117 days (n = 31). The most common presenting symptoms were headache, nausea, vomiting, ataxia, and oculomotor deficits. Approximately half of the patients were initially diagnosed and treated for other diseases (gastrointestinal infection, appendicitis, psychological behavioral problems, cervical spine strains, different ophthalmologic entities). Specialists (ophthalmologists, orthopedics) tended to diagnose and treat their specific diagnoses (e.g., strabism, torticollis). Parents play a significant role in the process of establishing the correct diagnosis. Conclusion We conclude that further information and education regarding symptomatology and diagnosis of posterior fossa tumors in children is necessary. Communication has to be improved between parents and referring physicians of all specialties and neurosurgeons.