Results of the treatment of children with recurrent gliomas with lomustine and vincristine

Gliomas comprise over 50% of all childhood brain tumors. Treatment of recurrent childhood gliomas has been disappointing and the effectiveness of therapy has been difficult to judge because of the variable natural history of the disease. Information gathered recently has suggested that treatment with [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea)] (CCNU) and vincristine (VCR) after radiotherapy is effective in prolonging survival in children with newly diagnosed anaplastic gliomas. The authors have used these same drugs--CCNU (100 mg/m2) and VCR (1.5 mg/m2 up to a maximum dose of 2 mg)--in 6-week cycles for a maximum of eight cycles in children with recurrent gliomas. To date, 15 patients have been treated; five patients had malignant gliomas and ten low-grade gliomas. Three children showed improvement, five had stable disease, and seven had progressive disease. Of the five patients with malignant gliomas, four progressed within two cycles of treatment and one had stable disease for 7 months on treatment and then relapsed. Seven of ten children with low-grade gliomas benefitted from treatment and six remain in continuous remission a median of 16 months after initiation of therapy. Three of these children are off all therapy 21, 30, and 30 months after treatment, respectively. Therapy was well tolerated and toxicity consisted primarily of reversible bone marrow suppression. The authors conclude that CCNU and VCR chemotherapy is effective in children with recurrent low-grade gliomas and can result in relatively long-term disease stabilization. In limited experience of the authors, it is not of benefit in children with recurrent anaplastic lesions.     

Evaluation of dietetic intervention in children with medulloblastoma or supratentorial primitive neuroectodermal tumors

BACKGROUND: Malnutrition is a common complication of cancer treatment; it can affect energy levels and, as a consequence, quality of life. The goal of the current study was to evaluate the effect of dietetic intervention in a cohort of children treated for medulloblastoma and supratentorial primitive neuroectodermal tumors (PNET) over a 10-year period. METHODS: A retrospective chart review (1992-2002) of newly diagnosed cases of medulloblastoma/supratentorial PNET was performed. Hospital records were reviewed for data, including demographic characteristics, patient heights and weights, and information on treatment modalities and the use of dietetic intervention. Percent changes in body weight were calculated at time points associated with particular stages of treatment or dietetic intervention. RESULTS: One hundred three of 112 cases were evaluable. Treatment methods included surgery only (7.8%), surgery + radiotherapy (16.5%), surgery + chemotherapy (14.5%), and surgery + radiotherapy + chemotherapy (61.2%). There was no significant change in patient weight due to surgery (median change in body weight [MCBW], -0.35%) or radiotherapy (MCBW, -0.78%). In contrast, children experienced significant weight loss (MCBW, -4.35%; P < 0.0001) 3 months after starting chemotherapy. A dietician saw 53 of the 103 children in the study cohort. There were 84 dietetic interventions (oral, 36%; parenteral, 27%; enteral, 37%) among these 53 patients. Oral diets did not result in weight gain. Parenteral nutrition was associated with significant weight gain at 1 month (MCBW, +2.7%; P = 0.03), but not at 3 months. The use of enteral feeds resulted in significant weight gain at 1 month (MCBW, +4.8%; P = 0.006) and at 3 months (MCBW, +11.8%; P < 0.0001). CONCLUSIONS: Current multimodality treatment of intracranial PNET results in significant nutritional morbidity, primarily due to the use of intensive chemotherapy regimens. Dietetic input for pediatric patients with medulloblastoma/PNET is essential, and the implementation of enteral feeding in these children can help to reverse their nutritional morbidity.     

High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors

Current treatment for high risk and recurrent medulloblastoma (MB) and supratentorial primitive neuroectodermal tumors (stPNET) has a very poor prognosis in children. High dose chemotherapy (HDCT) and autologous stem cell rescue have improved survival rates. We present 19 patients (thirteen classified in the high risk group and six patients with recurrent disease) that received HDCT and autologous stem cell rescue.In the high risk group [Med Pediatr Oncol 38 (2002) 83], all patients underwent neurosurgical debulking. Standard chemotherapy was prescribed in 10 patients. Radiotherapy was given to 4 patients (all older than 4years old). In the recurrence disease group [Childs Nerv Syst 15 (1999) 498], five patients underwent surgery. Radiotherapy was given to those who were not previously irradiated. The HDCT in twelve patients consisted of busulfan 4mg/kg/day, orally over 4days in 6-hourly divided doses and melphalan at a dose of 140mg/m²/day by intravenous infusion over 5min on day –1. Three patients additionally received thiotepa 250mg/m²/day intravenously over 2days and four patients additionally received topotecan 2mg/m²/day over 5days by intravenous infusion over 30min. The other seven patients received busulfan and thiotepa at the same doses.Patients stem cells were mobilized with granulocyte colony-stimulating factor at a dose of 12g/kg twice daily subcutaneously for four consecutive days. Cryopreserved peripheral blood progenitor cells were re-infused 48h after completion of chemotherapy. With a median follow-up of 34months (range 5–93) eight complete responses and one partial response were observed. Three patients died of treatment-related toxicities (15%). The 2 year event-free survival was 37.67±14% in all patients and 57±15% for the high risk group.Therefore we conclude that HDCT may improve survival rates in patients with high risk/recurrent MB and stPNET despite treatment toxicity.     

High‐dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors

BACKGROUND:

The role of myeloablative chemotherapy in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST‐PNET) is controversial, in particular in patients who develop recurrent disease after craniospinal radiotherapy.

METHODS:

In this retrospective analysis, the authors investigated the outcome of children with recurrent MB/ST‐PNET who were referred for myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue at Childrens Hospital Los Angeles.

RESULTS:

Thirty‐three children were referred for myeloablative chemotherapy: Fourteen of those children were never transplanted because of pre‐transplant adverse events, and 19, including 6 without and 13 with previous irradiation, underwent transplant. Conditioning regimens included a backbone of thiotepa, which was given either in a single cycle or in multiple sequential cycles. The 3‐year post‐transplant event‐free survival rate in unirradiated versus previously irradiated children was 83% ± 15% versus 20% ± 12%, respectively (P = .04). One child who had never been exposed to radiotherapy died of toxicity; the other children received post‐transplant radiotherapy and remained disease free. Nine previously irradiated children experienced 4 toxic deaths and 6 tumor recurrences (1 patient had both): An interval of <1 year between initial radiotherapy and myeloablative chemotherapy predicted a greater risk of toxic death (P = .02), whereas a history of meningeal metastases at diagnosis and a poor response to the initial rescue therapy predicted a greater risk of post‐transplant recurrence (P = .03 and P = .08, respectively).

CONCLUSIONS:

Myeloablative doses of thiotepa‐based chemotherapy and radiotherapy were able to cure most children who had radiotherapy‐naive, chemoresponsive recurrences. Children who developed recurrences after craniospinal radiotherapy had poorer outcomes; however, cure was possible in those who had good prognostic features at presentation, chemoresponsive recurrences, and a long interval between initial radiotherapy and myeloablative chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

Effectiveness of intensive chemotherapy in the treatment of medulloblastoma/primitive neuroectodermal tumor in children

Standard and high-risk groups of 77 children with neuroectodermal medulloblastoma were given sandwich chemotherapy. The former group was treated with high-dose chemotherapy complemented with autotransplantation of bone marrow and peripheral stem cells. The treatment proved effective: 7-year recurrence-free survival (0.66 +/- 0.05) (overall survival--0.67 +/- 0.05; recurrence-free--0.62 +/- 0.06). Sandwich chemotherapy administered in standard risk group was followed by 7-year recurrence-free survival (0.84 +/- 0.08). High-dose chemotherapy complemented with autotransplantation of bone marrow and peripheral stem cells in conjunction with high-dose chemotherapy resulted in 6-year recurrence-free survival: 0.77 +/- 0.08 in patients after high-dose chemotherapy and 0.46 +/- 0.10--without it.     

Late recurrence of primitive neuroectodermal tumor/medulloblastoma

The period of risk for recurrence of primitive neuroectodermal tumor/medulloblastoma (PNET/MB) is not clearly defined. With current treatment since more than 50% of children with PNET/MB can be expected to survive for at least 5 years after diagnosis, determining the evidence of "late" recurrence is of increasing concern. Collins has stated that patients with embryonal tumors who survive, disease free, for a period of time equal to the age at diagnosis plus 9 months can be declared cured. This, so-called Collins' law has been applied to patients with PNET/MB. To determine the incidence of "late" recurrence, factors which impact on recurrence and applicability of Collins' law, the authors studied all patients diagnosed with PNET/MB at the Children's Hospital of Philadelphia, Hospital of the University of Pennsylvania, Philadelphia, and Geisinger Medical Center, Danville, Pennsylvania, between 1970 and 1984. For the 44 patients in this study, the disease-free survival at 5, 10, and 12 years was 54%, 41% and 30%, respectively. For children surviving 5 years, the actuarial survival at 10 years was 75% and at 12 years, 51%. Age, sex, dose of radiotherapy, chemotherapy, or extent of surgery were not predictive of late relapse. Recurrence in three of seven patients (43%) occurred outside the "period of risk" as predicted by Collins. It appears that the "period of risk" for recurrent central nervous system tumors after PNET/MB is as yet undefined and probably indefinite.     

Suprateutorial primitive neuroectodermal tumors in children

A retrospective review of 36 children diagnosed with a supratentorial primitive neuroectodermal tumor (PNET) at the Hospital for Sick Children was performed for the period 1970-1995. All children but one received their initial treatment at our institution. There were 18 males and 18 females and the median age at diagnosis was 35 months. Twenty-two PNETs were lobar, 3 were deep in the hemisphere, and 10 were located in the pineal region. One child presented with intracranial leptomeningeal disseminated disease. The tumors were mostly undifferentiated although 22 had some evidence of differentiation along one or more neuroepithelial lines. Five children had a biopsy, 24 had subtotal resection, and 7 had gross total resection. Twenty-six children had adjuvant radiotherapy and 13 had chemotherapy. At last follow-up 30 patients were dead and 6 were alive. The median survival was 23 months and the 2, 3, and 5 year survivals were 50%, 34%, and 18% respectively. All of the survivors received craniospinal radiation and 4 received chemotherapy. There was a statistically significantly worse survival in young children. There was a trend to better survival in children treated since 1984, and in children undergoing gross total resection. Because of the extremely poor survival, we recommended that all children undergo gross total resection followed by chemotherapy. For children older than 3 years of age craniospinal radiation should also be given.     

Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors

: This single-institution Phase I/II study conducted from 1989 to 1995 evaluates the feasibility of a multimodality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system.: All 23 patients had a histogically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3–25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4–6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44–56 Gy were administed to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months.: All patients completed radiotherapy as planned. Only three patients lost > 10% of their body weight. One patient had clinically apparent radiation-induced esophagitis. The mean white blood count (WBC) nadir was 2.5/dl, and hematologic recovery occurred in all within 4 weeks of completing HFRT without the need of granulocyte-colony-stimulating factor. Two patients refused adjuvant chemotherapy, 3 patients experienced tumor progression during chemotherapy, and 2 of 18 remaining patients could not tolerate the full 9 months owing to hematologic toxicity. Of the 15 patients (93%) in Group 1, 14 remain in continuous remission for a median of 78 months, and more have died. Two of the four patients in Group 2 are in continuous remission at 67 and 35 months, and two died at 18 and 30 months. One of the two patients in Group 2 who died refused adjuvant chemotherapy and developed tumor progression in the bone marrow. None of the three patients in Group 3 with evaluable disease (M3) had a complete response to therapy, and eventually all four died of progressive or recurrent disease.: This multimodality protocol is feasible in the short term, and long-term monitoring of neurocognitive and neuroendocrine effects are in progress. Excellent long-term disease control has been achieved for medulloblastoma patients with high T stages who were M0 at diagnosis (Group 1), the majority of whom had gross total resections. This group has a progression-free survival of 95% after a median period of follow-up of 6.5 years. Alternative treatment strategies must be developed for patients with high M stages, as five of seven patients died of progressive or recurrent disease.     

Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study

BACKGROUND: An open-label Phase II study of oxaliplatin was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB), supratentorial primitive neuroectodermal tumors (SPNET), and atypical teratoid rhabdoid tumor (ATRT). METHODS: Patients were stratified as follows: stratum IA, first recurrence MB with measurable disease; IB, recurrent MB with only cerebral spinal fluid (CSF) positivity or linear leptomeningeal disease (LLD); IC, MB > or =second recurrence; stratum II, recurrent SPNET; stratum III, recurrent ATRT. Patients received oxaliplatin, 130 mg/m(2) intravenously over 2 hours every 3 weeks. The primary objective was to estimate the sustained response rate in stratum 1A. Plasma ultrafiltrate platinum pharmacokinetics were evaluated. RESULTS: A total of 43 patients with a median age of 8.5 years (range, 0.6-18.9 years) were enrolled. In stratum 1A, 2 of 15 had partial responses (PRs, 1 sustained PR). No responses were observed in other strata. The most frequent Grade 3 and 4 toxicities included thrombocytopenia (25.6%), neutropenia (16.3%), leukopenia (12%), increase in serum alanine transaminase (ALT) (7%), vomiting (4.7%), and sensory neuropathy (4.7%). No severe ototoxicity or nephrotoxicity was reported. Plasma ultrafiltrate platinum pharmacokinetic parameters were similar to adults, with a median clearance of 12.2 L/hr (range, 4.4-30 L/hr) and median area under the curve (AUC(0-infinity)) of 9.4 microg/mL/hr (range, 6.2-13.9 microg/mL/hr). CONCLUSIONS: Oxaliplatin was well tolerated in children but has limited activity in children with recurrent CNS embryonal tumors previously treated with platinum compounds.     

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial

Background

The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days.

Methods

Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m²/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment.

Results

Median age was 10 years (range, 2–21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%).

Conclusions

TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile.     

外周性原始神经外胚层肿瘤的诊断及治疗

目的：探讨外周性原始神经外胚层肿瘤（peripheral primitive neuroectodermal tumors,pPNETs）的诊断及治疗。方法：回顾性分析我院收治的5例经病理证实的 pPNETs 患者的诊治过程,并复习文献。结果：本组病例均为软组织,1例位于颈部,1例位于肩部,1例位于腋窝,2例位于胸壁。CT 平扫显示肿物多呈不均匀的等、低密度,所有肿瘤增强后均可见不均匀强化。3例患者行 MRI,显示 T1WI 呈与肌肉类似的混杂信号, T2WI 表现为不均匀的高信号。2例患者行 B 超检查,显示肿物局部低密度影,内可见血流信号,未压迫周围血管。镜下可见肿瘤细胞形成典型的 Homer －Wright 菊形团。免疫组化显示肿瘤均表达 CD99和 VIM,NSE和 Syn 多数阳性,CK 阴性,并且不表达 LCA,部分低表达 S100。结论：pPNETs 是一种少见的小圆细胞恶性肿瘤。CT 及 MRI 检查可评估肿瘤可切除性。B 超可了解肿物的血供及与周围血管的位置关系。pPNETs 的确诊依靠病理及免疫组化,尤其是 Homer －Wright 菊形团及神经内分泌标记物对肿瘤的确诊有重要意义。手术是直接有效的治疗手段,术前新辅助化疗可以减少 pPNETs 局部淋巴结转移。     

Successful treatment of low-grade oligodendroglial tumors with a chemotherapy regimen of procarbazine, lomustine, and vincristine

BACKGROUND: Anaplastic oligodendroglioma (OD) tumors, especially those with the combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), are sensitive to chemotherapy. Only limited data are available on the role of chemotherapy in low-grade OD. The authors retrospectively studied the outcome of the procarbazine, lomustine, and vincristine (PCV) chemotherapy regimen in a group of 16 patients with newly diagnosed OD and 5 patients with recurrent low-grade OD. METHODS: Two groups of patients were studied: newly diagnosed patients with large OD and mixed oligoastrocytomas (OA) and patients with recurrent OD and OA after radiotherapy who still showed nonenhancing tumors. Treatment consisted of standard PCV chemotherapy. In the newly diagnosed and responding patients, radiotherapy was withheld until the time of disease recurrence. Responses were assessed by T2-weighted magnetic resonance image (MRI) scans. Loss of chromosome 1p and 19q was assessed using fluorescent in situ hybridization with locus-specific probes. RESULTS: Three of five patients with recurrent tumors responded. Thirteen of the 16 newly diagnosed patients showed evidence of response. The median time to disease progression in this group was >24 months. Only one of these patients experienced disease progression while receiving chemotherapy. Several patients showed a signficant clinical improvement despite only a modest improvement of the tumor on the MRI scans. Even patients without loss of 1p or 19q showed satisfactory responses. No TP53 mutations were found. CONCLUSIONS: Newly diagnosed patients with OD tumors, with or without loss of 1p/19q, responded to PCV chemotherapy. Up-front chemotherapy may be indicated especially for patients with large tumors. MRI scans were of limited value for the assessment of response. A Phase III trial should be initiated to compare radiotherapy with chemotherapy.     

Outcome for children with supratentorial primitive neuroectodermal tumors treated with surgery, radiation, and chemotherapy

BACKGROUND: The outcome of a child with a primitive neuroectodermal tumors arising supratentorially (SPNET) is not well characterized and may differ from the outcome of a patient with a histologically similar cerebellar tumor (medulloblastoma [MB]). Recently, 5-year progression free survival rates as high as 80% have been reported for children with MB treated with craniospinal radiation (CRT) and chemotherapy including cisplatin, lomustine (CCNU), and vincristine (VCR). METHODS: The authors reviewed the outcome of 22 consecutive patients age 3 years and older (mean age, 10 years; range, 3-18 years) with SPNET who were treated at the study institutions between 1981 and 1996. Tumor location included was 13 pineal, 6 cortical, and 3 thalamic or suprasellar. Five patients had disease dissemination at diagnosis. All patients underwent surgery and staging, followed by CRT and chemotherapy with cisplatin, CCNU, and VCR. RESULTS: Of the 22 patients, 13 had developed disease progression and 10 had died at the time of last follow-up. Overall progression free survival (PFS) was 47% +/- 11% at 3 years and 37% +/- 11% at 5 years. There was a significant difference in PFS between patients with localized disease versus those with disseminated disease (P = 0.04). There was no statistical association between tumor location and survival. Although not significant (P = 0.21), there was a trend toward better survival of those patients with complete or near-complete resection compared with those with partial resection or biopsy. CONCLUSIONS: The results of the current study demonstrate that the outcome for children with SPNET treated with radiation and chemotherapy appears worse than for children with MB treated with identical therapy. This suggests that there may be biologic differences between supratentorial and infratentorial primitive neuroectodermal tumors, thus requiring refinements in treatment.     

Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors.

PURPOSE: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to radiation- and alkylator-induced cytotoxic abasic sites in human cells. We assayed apurinic/apyrimidinic endonuclease activity in medulloblastomas and primitive neuroectodermal tumors (PNET) to establish correlates with tumor and patient characteristics and with response to adjuvant radiation plus multiagent chemotherapy. EXPERIMENTAL DESIGN: Ap endo activity was assayed in 52 medulloblastomas and 10 PNETs from patients 0.4 to 21 years old. Ape1/Ref-1, the predominant human Ap endo activity, was measured in 42 medulloblastomas by immunostaining. Cox proportional hazards regression models were used to analyze the association of activity with time to tumor progression (TTP). RESULTS: Tumor Ap endo activity varied 180-fold and was significantly associated with age and gender. Tumor Ape1/Ref-1 was detected almost exclusively in nuclei. In a multivariate model, with Ap endo activity entered as a continuous variable, the hazard ratio for progression after adjuvant treatment in 46 medulloblastomas and four PNETs increased by a factor of 1.073 for every 0.01 unit increase in activity (P < or = 0.001) and was independent of age and gender. Suppressing Ap endo activity in a human medulloblastoma cell line significantly increased sensitivity to 1,3-bis(2-chlororethyl)-1-nitrosourea and temozolomide, suggesting that the association of tumor activity with TTP reflected, at least in part, abasic site repair. CONCLUSIONS: Our data (a) suggest that Ap endo activity promotes resistance to radiation plus chemotherapy in medulloblastomas/PNETs, (b) provide a potential marker of treatment outcome, and (c) suggest clinical use of Ap endo inhibitors to overcome resistance.     

Second-line treatment with carboplatin for recurrent or progressive oligodendroglial tumors after PCV (procarbazine, lomustine, and vincristine) chemotherapy: a phase II study

BACKGROUND: The efficacy of second-line chemotherapy for patients with recurrent or progressive oligodendroglial tumors is limited. In the current study, the authors investigated the use of carboplatin as a second-line chemotherapeutic agent against these types of tumors. METHODS: Twenty-three patients with recurrent or progressive oligodendrogliomas or oligoastrocytomas after first-line PCV (procarbazine, lomustine, and vincristine) chemotherapy were enrolled in a single-institution Phase II study of second-line carboplatin chemotherapy. All patients had undergone surgery, and most also had undergone conventional radiotherapy. Carboplatin was administered at a dose of 560 mg/m2 intravenously every 4 weeks. Responses were evaluated according to conventional criteria, based on magnetic resonance imaging (MRI) findings. RESULTS: Three of 23 patients (13%) had partial responses, with neurologic improvement. Twelve patients (52%) had stable disease; in 2 of these 12 patients, a minor response was seen on MRI. Eight patients (35%) had progressive disease. The median time to tumor progression was 3 months for all patients and 9 months for patients who experienced responses to treatment. Progression-free survival rates at 6 and 12 months were 34.8% and 8.7%, respectively. Among the salvage treatment plans followed after carboplatin chemotherapy were supportive care alone, radiotherapy, third-line chemotherapy, and reoperation. The median survival duration from the start of carboplatin administration was 16 months. Myelotoxicity was severe, with Grade 3 or 4 thrombocytopenia in 60% of patients and Grade 3 or 4 neutropenia in 48% of patients. CONCLUSIONS: When administered according to a monthly schedule, carboplatin exhibited modest activity in adult patients with recurrent or progressive oligodendroglioma or oligoastrocytoma who experienced treatment failure after PCV chemotherapy; the current treatment regimen also was associated with severe toxicity. Further improvement of second-line chemotherapy for the patient group examined in the current study is necessary.     

Chemotherapy for medulloblastomas and primitive neuroectodermal tumors

Summary In the past two decades, chemotherapy has proven to be an increasingly more effective modality in the treatment of medulloblastoma. Current evidence suggests that chemotherapy be included as part of standard treatment for all patients with high-risk medulloblastoma. Ongoing multi-centre trials are determining whether chemotherapy should be added to reduced dose radiotherapy as a substitute therapy for standard-dose radiotherapy. The major randomized and non-randomized chemotherapy trials for newly diagnosed patients with medulloblastoma or for patients at recurrence are presented. It is hoped that the addition of chemotherapy will eventually lead to improved survival rates as well as the reduction in the craniospinal radiotherapy dose for patients with medulloblastoma.     

原始神经外胚层瘤16例临床分析

目的:分析原始神经外胚层瘤(primitive neuroectodermal tumors,PNET)的病理学特征、诊断及治疗。方法:收集16例PNET患者的临床资料,肿瘤位于颅内4例,纵隔4例,眶内2例,胸髓2例,下肢2例,颈部1例,腹腔1例。6例单纯手术切除,10例行术后放、化疗。结果:16例中14例死亡,中位生存期为22个月,6例单纯手术切除组及10例术后放、化疗组的中位生存期分别为13个月、28个月,2组相比差异有统计学意义(P=0.0194)。结论:PNET是一种高度恶性的神经上皮瘤,侵袭性强,手术加放疗加化疗是PNET治疗的最佳选择。     

Ewing's sarcoma and primitive neuroectodermal family of tumors

Ewing's sarcoma (ES) initially was believed to be of perivascular endothelial origin. The Ewing's sarcoma family of tumors (EFT) includes ES of bone (ESB), extraosseous ES (EES), peripheral primitive neuroectodermal tumor of bone (pPNET), and malignant small-cell tumor of the thoracopulmonary region, or Askin's tumor, all of which are now known to be neoplasms of neuroectodermal origin. The degree of neuronal differentiation has been used for histopathologic subclassification of the EFT as classical ES (ESB or EES), which is characterized by minimal evidence of neural differentiation, and pPNET, which displays evidence of neural differentiation by standard microscopy, electron microscopy, or immunohistochemistry. Because the behavior, prognosis, and treatment appear to be similar for all subsets of EFT, this histopathologic subclassification may not be clinically significant, though some debate remains whether neural differentiation predicts for inferior outcome.     

Ewing's sarcoma and extracranial primitive neuroectodermal tumors.

Ewing's sarcoma and primitive neuroectodermal tumor of bone and soft tissue are rare tumors, considered with the small round blue cell tumors of childhood. Recent advances link Ewing's sarcoma and primitive neuroectodermal tumor, and support the concept that these tumors represent stages of differentiation in a neoplasm of neuroectodermal origin. Advances in chemotherapy have resulted in the survival of the majority of patients presenting with these tumors. This review briefly outlines the year's literature regarding the histogenesis, biology, and treatment of this tumor.