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E Bouffet

Publications and source records attributed to E Bouffet.

At least 19 recordsLinked to original sources

Outcome of children treated with preradiation chemotherapy for a high-grade glioma: results of a French Society of Pediatric Oncology (SFOP) Pilot Study.

BACKGROUND: To evaluate the efficacy of BCNU, cisplatin, and vincristine (BCV regimen) in a prospective nonrandomized study among newly diagnosed children with high-grade glioma. PROCEDURE: Following surgery, patients received a combination of BCNU + cisplatin + VP16 (BCV), over 3 consecutive days. Patients with residual tumor continued this regimen unless no further improvement was observed on MRI, for a maximum of six courses. Patients who underwent complete surgical resection received six courses of adjuvant BCV. RESULTS: Seventy-three patients were enrolled. Out of 66 eligible patients with central pathology review, the diagnosis of high-grade glioma was confirmed in 53 cases. The response rate was 20%. With a median follow-up of 128 months, 5- and 10-year event free survival rates are 16 +/- 9 and 13.3 +/- 9.4%. In univariate analysis, two prognostic factors were statistically significant: extent of resection and tumor location, while macroscopic total resection was the only significant prognostic factor in the multivariate analysis. The response to BCV did not translate into improved event free survival. Interstitial pneumonitis occurred in seven patients, leading to six deaths. CONCLUSION: This BCV regimen could not be recommended in the treatment of high-grade gliomas in children, according to its lack of efficacy and its unacceptable pulmonary toxicity.

Adolescent↗

Epidemiological survey of central nervous system germ cell tumors in Canadian children.

OBJECTIVES: To determine the incidence and characteristics of pediatric patients with central nervous system (CNS) germ cell tumors (GCT) in Canada. METHOD: A national retrospective review of hospital charts was done on all patients with CNS GCT diagnosed between 1990 and 2004. Patients had to be under age 18 years at the time of diagnosis of a CNS germ cell tumor and be a resident of Canada. Information extracted included age and year of diagnosis, pathological diagnosis, location of tumor, evidence of disseminated disease at time of diagnosis and biological markers. RESULTS: One hundred and twenty-one cases were identified (83 germinoma; 38 non-germinoma germ cell tumor). The mean annual incidence of CNS GCT was 1.06 per million children (0.7 per million for germinoma; 0.3 per million for NGGCT). Though yearly incidences varied, there was no clear trend to increased incidence. Male predominance was noted (2.4:1 for germinoma; 11:1 for NGGCT). The primary locations were the pineal and suprasellar regions. At the time of diagnosis, disseminated disease was not uncommon (22% germinoma; 32% NGGCT). Beta human gonadotrophin was elevated in the serum, cerebrospinal fluid (CSF) or both in 7% of patients with germinoma and 36% of patients with NGGCT. Elevation of alpha-fetoprotein in serum, CSF or both was seen in 34% of patients with NGGCT. CONCLUSION: The incidence of CNS germ cell tumors in Canadian children is similar to that observed in other Western countries.

Adolescent↗

Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours.

The aims of this study were to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetics of oral temozolomide administered over 42 d in children with recurrent/refractory brain tumours. Cohorts of 3-6 patients were treated for 42 d, followed by a 7-d rest period for a maximum of 6 cycles. Patients were stratified as heavily pre-treated (HPT) and non-heavily pre-treated (NHPT). Starting doses were 50 mg/m2 (HPT) or 75 mg/m2 (NHPT). Out of 28 patients enrolled, 20 were evaluable for toxicity and 19 for pharmacokinetics. Three patients in the NHPT group developed grade 3/4 haematological toxicity, 2 experienced dose-limiting toxicity (thrombocytopenia) at 100 mg/m2, and 9/20 developed grade 3 lymphopenia. MTD in both strata was 85 mg/m2. Responses were observed in 4 patients: 2 complete responses (CR) in medulloblastoma and supratentorial primitive neuroectodermal tumours (PNET), and 2 partial responses (PR) in high-grade glioma, respectively. Overall cumulative exposure was at least 1.5 times higher than in the 5-d administration schedule. In conclusion, the recommended dose of temozolomide is 85 mg/m2 x 42 d. Dose-limiting toxicities are thrombocytopenia and lymphopenia. The observed response rate warrants phase II studies.

Administration, Oral↗

Risk of ventriculoperitoneal shunt infections due to gastrostomy feeding tube insertion in pediatric patients with brain tumors.

OBJECTIVE: To determine the risk of ventriculoperitoneal (VP) shunt infections after percutaneous retrograde gastrostomy feeding tube (GT) placement in children with brain tumors. PATIENTS AND METHODS: All children (age 0-18 years) with primary brain tumors diagnosed and treated at the Hospital for Sick Children, Toronto, Canada, were subjected to a retrospective analysis. Two groups were identified: the study group included children with a VP shunt and a GT; the control group included children with VP shunts only. Each study patient was matched with 2 controls to compare the rate of infections (cohort comparative study). RESULTS: There were 1,167 children diagnosed and treated with primary brain tumors during the study period (1988-2003); 174 (15%) had a VP shunt and 23 (2%) children had both, a VP shunt and a GT. In the study group (n=17), GTs were inserted at a median time of 80 days (range 6-204 days) after VP shunts. VP shunt infection rate was 23.5% (4/17) compared to 8.8% (3/34) in the control group (OR 3.18; 95% CI 0.622-16.54, p=0.16). Three (75%) of the infection episodes in the study group presented with an ascending VP shunt infection directly related to the GT insertion or manipulation in the first 6 weeks. These GTs were inserted at 13, 47 and 49 days after VP shunt insertion. CONCLUSION: Placement of percutaneous retrograde GTs, in the acute phase, in children with brain tumors and VP shunts may increase the risk of ascending meningitis especially if there are early GT-related complications.

Adolescent↗

Acute neurotoxicity in children with advanced stage B-non-Hodgkin's lymphoma and B-acute lymphoblastic leukaemia treated with the United Kingdom children cancer study group 9002/9003 protocols.

We reviewed the pattern of acute neurotoxicity in children with B-non-Hodgkin's lymphoma (B-NHL) and B-acute lymphoblastic leukaemia (ALL) treated with the UKCCSG 9002/9003 protocols. Among 175 patients, 21 (12%) developed acute neurotoxicity: 9002 protocol (n=11/112) and 9003 (n=10/63). There were 20 boys and the median age was 10 years. Patients with neurological symptoms due to other causes were excluded. Acute neurological symptoms developed following induction chemotherapy in 7 patients, or after a more intensive course of chemotherapy containing high-dose methotrexate (n=14). Nine patients required their chemotherapy to be altered because of the acute neurotoxicity. One patient died of cerebral haemorrhage but none of the remaining six deaths was attributed to acute neurotoxicity. We conclude that acute neurotoxicity is common in children treated with the 9002/9003 protocols and tends to be transient. Intrathecal and systemic chemotherapy including high-dose methotrexate is probably the most common predisposing factor. Modification of subsequent chemotherapy is not invariably necessary.

Acute Disease↗

Central nervous system tumours in adolescents.

Adolescents with brain tumours have been, and in most cases still are, haphazardly assigned, on referral, to either 'paediatric' or 'adult'-based treatment centres. In this age group, there is therefore a history of inconsistent treatment, delivery of inappropriate 'maturity-related' care and a reduced chance of gathering vital biological, clinical and treatment-related information germane to this group of patients and their tumours. These days, adolescents with brain tumours should be actively targeted for recruitment into clinical trials and admission into dedicated neuro-oncology centres or programmes that can deliver the necessary and age appropriate multidisciplinary management.

Adolescent↗

Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique.

Childhood malignant brain stem tumours have a very poor prognosis with a median survival of 9 months despite radiotherapy. No chemotherapy has improved survival. However, carboplatin has been reported to have activity in glial tumours as well as antitumour synergy with radiation. Our aims were to test the response rate of these tumours to carboplatin alone and to evaluate the efficacy on survival of carboplatin alone followed by concurrent carboplatin and radiotherapy. Patients younger than 16 years with typical clinical and radiological presentation of infiltrating brain stem tumour, as well as histologically-documented cases in the atypical forms, were eligible. Two courses of carboplatin (1050 mg/m2 over 3 days) were administered initially. This treatment was followed by a chemoradiotherapy phase including five weekly carboplatin courses (200 mg/m2) and conventional radiotherapy. 38 eligible patients were included. No tumour response was observed after the initial phase. This schedule of first-line carboplatin followed by concurrent carboplatin and radiotherapy did not improve survival.

Adolescent↗

What have we learnt from previous phase II trials to help in the management of childhood brain tumours?

Contrary to major advances in cure rates observed for almost all childhood cancers, progress in reducing brain tumour survival rates remains very limited. Although new drug development in oncology is founded on principles outlined in the organised methodology of phase I, II, and III trials, based on rigorous study design using standardised criteria, this approach has been applied very slowly in the field of neuro-oncology. There are multiple explanations for the paucity of well-conducted prospective clinical trials, such as the rarity and the heterogeneity of these tumours, and the reluctance of some investigators to enroll their patients in constraining trials. Data from the past two decades shows that several methodological problems preclude the drawing of any definite conclusions for the majority of drugs assessed. Among them, the necessity of a central neuropathological and neuroradiological review has been highlighted in, at least, two multicentric studies. Changes in histological diagnosis and grade have been reported in a proportion as high as 20%, and changes in response rate in 14% of the cases. This review of phase II trials for brain tumours reveals a wide array of sometimes arbitrary response definitions, that is if response is defined at all, and most series have enrolled small numbers of patients. We report on the different problems encountered in childhood brain tumours in these phase II trials, and their impact on phase III trials.

Antineoplastic Agents↗

[School reinsertion of children treated for tumors of the brain: experience of the Léon-Bérard center].

School integration of children with brain tumor is part of the quality of their life. It may also become a nightmare both for the child and for the teacher when no recommendation has been addressed to the latter. In France, official recommendations allow the meeting and information exchanges in the school between teachers and all the people who take care medically of the child. We report our experience in Centre Léon-Bérard of Lyon, concerning 38 children with brain tumors (102 meetings). Though difficult to assess scientifically, the benefit from these meetings is obvious. For the teachers: the knowledge and understanding of the physiopathology of brain tumors and secondary sequellae facilitates teaching. For the child: the disappearance of surrounding fears and fantasms make life easier. This experience is so rich that it should be extended to other pathologies.

Adolescent↗

Parenchymal pineal tumors: a clinicopathological study of 76 cases.

PURPOSE: The aim of this study was to identify factors that could lead to optimization of the management of pineal parenchymal tumors (PPT) which remains equivocal and controversial. METHODS AND MATERIALS: In order to determine factors that influence PPT prognosis, a series of 76 consecutive patients from 12 European centers with histologically proven tumors was retrospectively reviewed. The clinical records and material for histologic review were available in all cases. Follow-up was achieved in 90% of cases. RESULTS: According to WHO classification, there were 19 pineocytomas, 28 intermediate and mixed PPT, and 29 pineoblastomas. According to a four-grade institutional classification, there were 11 Grade 1, 27 Grade 2, 20 Grade 3, and 18 Grade 4. Surgical resection was attempted in 44 patients, whereas 30 had biopsy only. In one case, diagnosis was made at autopsy and in another on spinal deposits. Forty-four patients were irradiated following surgery, 15 patients received chemotherapy. Forty-one patients were alive (median follow-up: 85 months); 9 patients died perioperatively; 26 patients relapsed. Univariate analysis showed a good outcome correlated with age above 20 years, tumor diameter less than 25 mm, and low-grade histology. Multivariate analysis confirmed histology and tumor volume to be significant independent prognostic factors. The extent of surgery and radiotherapy had no clear influence on survival. CONCLUSIONS: This review highlights the prognostic features of PPT and may help to determine treatment strategies based on radiologic and pathologic characteristics.

Adolescent↗

Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas.

BACKGROUND: The role of high dose chemotherapy (HDC) in patients with pediatric brain tumors currently is ill-defined. The purpose of this pilot study was to assess the feasibility and the benefit of HDC after radiotherapy in a group of children with newly diagnosed diffuse pontine gliomas. METHODS: Patients eligible for study were ages 3-18 years with diffuse intrinsic tumors arising in the pons, who were not treated previously with radiotherapy or chemotherapy. Histologic confirmation was not mandatory, provided clinical findings and magnetic resonance imaging were typical. Patients were given focal radiotherapy followed 2-3 months later by HDC. Busulfan (150 mg/m(2) on Days 8, 7, 6, and 5) and thiotepa (300 mg/m(2) on Days 4, 3, and 2) were administered prior to autologous bone marrow transplantation. Survival was the endpoint, and the statistical procedure was based on sequential subgroup analysis. RESULTS: Thirty-six patients were entered on to the study, 12 of whom underwent stereotactic biopsy or open surgery at the time of diagnosis. One patient eventually was excluded due to inappropriate eligibility criteria. All 35 eligible patients received irradiation. Early progression (9 patients) and parental refusal (2 patients) precluded the use of HDC in 11 patients. Three patients died of HDC-related complications. All 21 patients who survived HDC eventually died of disease progression. The median survival time was 10 months for the study group. The median survival time in the subgroup of patients who received HDC was 10 months (range, 3-26 months). Statistical analysis did not suggest any evidence of survival benefit. CONCLUSIONS: For patients with diffuse pontine gliomas, survival using this aggressive treatment modality does not appear to be any better than that reported for conventional radiotherapy.

Adolescent↗

Initial measurements of ifosfamide and cyclophosphamide in patients using (31)P MRS: pulse-and-acquire, decoupling, and polarization transfer.

Ifosfamide and cyclophosphamide are (31)P-containing alkylating agents used widely in the treatment of cancer. In this communication it is demonstrated that signals from these agents may be detected in the livers of patients undergoing treatment using (31)P MRS at 1.5 T. In vitro, signals are enhanced 4-fold by use of (1)H-decoupling, with a B(1) field of 100 Hz at -150 Hz relative to water. Polarization transfer (BINEPT) enhances signals in vitro by a further factor of 5.5. Preliminary results using the double-resonance methods in vivo show that the technique is practicable although enhancements may be less than observed in vitro. Factors affecting signal enhancement in vivo are evaluated. Magn Reson Med 44:180-184, 2000.

Antineoplastic Agents, Alkylating↗

[Academic future of children treated for brain tumors. Single-center study of 27 children].

UNLABELLED: Brain tumours constitute the most common type of solid malignancy in childhood. Despite intensive efforts developed since the mid-1970s in paediatric neuro-oncology, survivors still have a wide range of sequelae leading to frequent failure in academic achievements. Very few studies have detailed the educational outcome of these children. PATIENTS AND METHODS: The study was based on a questionnaire sent to the parents of children diagnosed with a brain tumour and treated at the Centre Léon-Bérard between 1987 and 1993. Children had to be under 12 years old at the time of diagnosis and with at least three years of follow-up since diagnosis. Questions focused on the child's education before diagnosis, his progress during and after treatment, the measures taken when the child experienced learning difficulties and their consequences on the child's socioprofessional integration. RESULTS: Twenty-seven responses were obtained out of 34 questionnaires. Twenty-six children were reported to experience learning difficulties. Only four children had a normal education. The main problems are associated with slowness, memory and comprehension difficulties. The main disciplines affected are mathematics, reading and spelling. Fifteen children did benefit from extra support, with large interindividual variations in the amount and the quality of this support. Half of the parents play an active role in their child's extra support. CONCLUSIONS: This study provides additional information to previous reports on progressive I.Q. decline following the treatment of a brain tumour in childhood. Learning difficulties are nearly constant and adversely influence the child's curriculum. They also affect the parents who experience questions about the future of their ideal child. The severity and complexity of these learning difficulties urge for an early multidisciplinary educational and psychological management. The main characteristics of these remedial efforts should be assessed in prospective studies.

Adolescent↗

Assessment of percutaneous fine needle aspiration cytology as a technique to provide diagnostic and prognostic information in neuroblastoma.

The International Neuroblastoma Staging System (INSS) criteria for diagnosis requires an unequivocal pathological diagnosis and favours the identification of prognostic markers in the samples. Surgical biopsies of the primary tumour and bone marrow (BM) sampling in metastatic disease constitute the major sources of tumour material for the laboratory. We analysed the possibility of percutaneous fine needle aspiration cytology (FNAC) constituting an alternative procedure to the conventional technique of sampling of the primary tumour in children with advanced neuroblastoma. From July 1987 through July 1998, 64 consecutive children suspected of having advanced neuroblastoma and referred to our institution underwent percutaneous FNAC of deeply located tumours. FNAC was performed using 22-gauge needles under ultrasound guidance, before any chemotherapy and within the first days following admission. No complication occurred after FNAC. The median number of the extracted tumour cells was 2.3x10(6) (range: 0-40.6x10(6)). Cytology analysis was possible in 59/64 cases (92%) and immunocytochemistry in 56/64 (88%) allowing confirmation of the diagnosis. N-Myc analysis was available in 46/64 (72%). In addition, the presence of a partial deletion of chromosome 1p (del 1p) was assessed, since 1992, in 24/47 cases (51%), where enough cells were available. FNAC of deeply located advanced neuroblastoma is safe and information is available in a few hours after admission. The provided material is reliable for confirmation of diagnosis and analysis of biological prognostic markers in the majority of cases. More invasive tumour sampling procedures are required only in selected cases.

Adolescent↗

Non-seminomatous ovarian germ cell tumours in children.

In this study, we report the results of two consecutive protocols. TGM 55 and TGM 90, of the Société Fran¿aise d'Oncologie Pédiatrique ( SFOP) for patients with non-seminomatous germ cell tumours of the ovary and analyse the rationale for surgical indications. neoadjuvant or adjuvant chemotherapy. TGM 55 and 90 both utilised six drugs, bleomycin, cyclophosphamide, vinblastine, dactinomycin, etoposide and either cisplatin (TGM 55) or carboplatin TGM 90). Chemotherapy was given in ease of unresectable or incompletely resected tumour. Patients who had a complete resection of a localised tumour underwent expectant management and were only treated if progression occurred. 63 patients aged less than 18 sears old were enrolled between January 1955 and December 1994. 49 patients had alpha-fetoprotein (alphaFP) +/- beta-human chorionic gonadotropic hormone (betaHCG) secreting tumours and 14 had immature teratomas. Median follow-up for surviving patients is 60 months (range: 19-154). The 5-year overall survival is 85% +/- 5%. 13 out of 14 patients (93%) with immature teratoma are alive, including 3 of 4 patients (75%) who received chemotherapy for advanced disease. 41 patients (54%) with secreting tumours are alive, including 2 patients who required salvage treatment. Most failures occurred amongst patients with high initial alphaFP secretion ( > 15,000 ng/ml). 39 of 41 survivors (95%) in thc non-teratoma group had conservative surgery, allowing the possibility of future pregnancy. High cure rate can he achieved with a conservative approach in non-seminomatous germ cell tumour of the ovary. Whenever possible, fertility should he preserved during the primary operation in children suffering from these tumours.

Adolescent↗

Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases.

The WHO classification of CNS tumors divides pineal parenchymal tumors (PPT) into pineocytoma (PC), pineoblastoma (PB) and mixed pineocytoma-pineoblastoma or PPT with intermediate differentiation. The reported incidence of mixed/intermediate PPT varies and this may reflect the difficulty in classifying tumors of this type. In an attempt to overcome the problem of the classification of PPT with intermediate differentiation, we describe the relationship between histological features and patient survival in a large cooperative series of 66 PPT from 12 neurosurgical centres. All tumors were studied with both light microscopy and immunohistochemically using antibodies against glial markers or neural/neuroendocrine markers. Our series included 11 PC, 39 mixed/intermediate PPT and 16 PB. A number of mitoses greater than 6 and the presence of necrosis were associated with a poorer outcome, while positive immunostaining for neurofilaments was associated with a better survival. We propose a new prognostic grading of 4 grades, grade I for PC, grade II for PPT with fewer than 6 mitoses and positive immunolabelling for neurofilaments, grade III for PPT with either 6 or more than 6 mitoses or fewer than 6 mitoses but without immunostaining for neurofilaments and grade IV for PB.

Adolescent↗