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Introduction: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990–1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhone district (1.5 M inhabitants, 26 000 births per year). Methods: Vanillyknandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffe's kinetic method on Technicon RA-XT(™). VMA and HVA were expressed as μg/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. Results and discussion: The overall participation rate for the 5-year period was 82.2%. Out of 105 293 infants tested from 128 126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastoma as it is presently being followed up.

Resume Le syndrome de Bloom associe un retard staturo-ponderal, des anomalies cutanees, une dysmorphie faciale, un deficit immunitaire et une fragilite chromosomique excessive; ce syndrome rare predispose aux affections malignes. Observation . - Morgan, atteint de ce syndrome, developpe une turneur de Wilms a 4 ana. Il est traite selon le protocole SIOP 9 mais avec des doses reduites de chimiotherapie en raison d'une mauvaise tolerance (infectious). Il decede 2 ans plus tard du non-controle de sa tumeur. Conclusion . - Le nephroblastome s'ajoute a la liste variee des neoplasies associees au syndrome de Bloom, justifiant la surveillance reguliere par echographie abdominale des patients atteints.

Resume La mission d'accueil et d'education de l'ecole vis-a-vis des enfants et adolescents atteints de cancer aeteprecisee par la loi d'orientation de 1989. L'objectif est de contribueral'insertion socioprofessionnelle des enfants exclus temporairement d'un cursus scolaire classique. Pour les enfants atteints de maladies incurables, le processus de reinsertion est illusoire. La scolariten'en est pas moins possible,acondition d'en definir les objectifs et les modalites. Malades et methodes. - Le suivi scolaire de 30 enfants en fin de vie aetecolligeprospectivement. Les donnees recueillies concemaient l'intereˆt scolaire, le type de scolariteet l'evolution de la demande au cours du temps. Resultats. - Soixante pour cent des enfants ont manifesteun desir reel de scolaritejusqu'aun stade avancede leurevolution. La lecture, les mathematiques et le travail sur ordinateuretaient preferentiellement choisis. Le handicap physique et la fatigue influencaient la demande au cours du temps. Un refus de scolariteetait observechez 40 % des enfants, qui presentaient des poˆles d'intereˆt extrascolaires, ou une douleur mal calmee. Conclusion. - La scolaritede fin de vie est une realite. Elle appartient au cadre des soins palliatifs et doiteˆtre definie en tant qua projet specifique medical eteducatif.

Medulloblastomas is an orphan disease in adults. Standard treatment of completely removed localised adult medulloblastoma includes a craniospinal, irradiation with 36 Gy to axis and 54 Gy to whole posterior fossa. Pediatric randomized study demonstrated that a decreased dose of 24 Gy to axis with 54 Gy limited to tumoral bed gives similar result as standard therapy, provided chemotherapy is associated. May this pediatric experience be extended to adult population?

The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors are different (mostly glioma and meningiomas in adults, versus medulloblastomas, germ cell tumors and ependymomas). And because the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro oncologists are warranted to share expertise.

Patients with lysosomal storage disorders have visceral, skeletal, and neurological abnormalities and a limited life expectancy. Bone marrow transplantation has been used to correct the metabolic defects and leads to metabolic improvements in most patients. However, the long-term effect of such therapy is uncertain. We analysed the data from 63 patients transplanted for lysosomal storage diseases. The transplant-related mortality was 10% if an HLA-identical sibling marrow donor was available (n = 40) and 20-25% if mismatched tissue was used. Data on the effect of bone marrow transplantation on biochemical and clinical disease variables were available in 29 of the 63. 28 had a follow-up duration of 1.0-10.2 years; 1 patient died of disease progression in the first year after stable engraftment. 13 patients who had severe neurological symptoms at the time of transplantation showed disease progression. Engraftment of bone marrow in 5 patients with non-neuronopathic Gaucher's disease led to complete disappearance of symptoms. 11 patients had skeletal symptoms because of various mucopolysaccharidoses (MPSs). There was stabilisation of the skeletal lesions during the observation period of 1.4-6.4 years, but none of the patients showed significant regression of the skeletal symptoms. The visceral features (hepatosplenomegaly, cardiac hypertrophy, and upper airway obstruction) in these patients abated after transplantation. We could not evaluate the biochemical and clinical variables in 34 patients because of graft rejection, transplant-related mortality, or follow-up of less than 1 year. There were significant beneficial effects of bone marrow transplantation in patients with non-neuronopathic Gaucher's disease. Stabilisation of disease was observed in patients with MPS-I and MPS-II; this potential benefit needs to be confirmed by longer follow-up. Bone marrow transplantation was not effective if severe neurological symptoms were already present at the time of transplantation.

Gliomatosis cerebri (GC) is a rare neoplasm including a variety of tumors, with extremely variable evolution and heterogeneity of prognosis. It may appear either de novo or after a focal glioma, involve predominantly the white or the gray matter, and concern either pediatric or adult patients. We focused on primary GC involving exclusively gray matter in a pediatric population in order better to define the presentation and outcome of this disease.We reviewed the databases of seven Departments of Pediatric Oncology to identify pediatric cases of GC between 1990 and 2007. Patients were included if they demonstrated a diffuse infiltrative process involving gray matter in magnetic resonance imaging (MRI) and histological tissue analyses, confirming a proliferative glial disorder.Fourteen patients with a median age of 8 years were identified. Epilepsy was the main presenting symptom. Brain MRI showed a lesion of the temporal and insular cerebral cortex associated with tumoral infiltration of the thalami and the basal ganglia. Histological examination confirmed the diagnosis of high-grade glioma. Prognosis was always very gloomy in the short term, with a median survival of less than a year.This rare entity, whose prognosis is appalling whatever the treatment proposed, should be clearly identified within the heterogeneous group of GC in the same way as diffuse intrinsic pontine gliomas have been identified among brain stem tumors. Systematic biopsies appear essential to permit the molecular studies which will assist in guiding the choice of future targeted treatments.

Retinoblastoma is the most common primary cancer of the eye in children. The prognosis for survival is excellent. The current therapy includes an improved survival rate and decreased iatrogenic sequelae. The relative risk of a second tumor in survivors of retinoblastoma is documented, especially in those who carry a germline RB mutation. It is strongly increased in case of radiation therapy. The most common types of second primary tumor are sarcoma of soft tissues and osteosarcoma. We present here a rare case of a retinoblastoma patient who received radiation therapy as a part of his treatment and developed a papillar thyroid cancer as a second malignancy. Papillar thyroid cancer has a good prognosis. Systematic screening for thyroid carcinoma should be undertaken in patients irradiated for congenital retinoblastoma.

Burkitt's lymphoma and L3-ALL are different forms of the same disease: B-cell disease. Therapeutic improvement has been considerable over the past 10 years. In France, four consecutive multicentre LMB studies of the SFOP greatly contributed to this improvement. An overall cure rate of 90% can now be achieved in children with a short intensive risk adapted polychemotherapy regimen based on high-dose fractionated CPM, HD MTX (3 g/m2), Ara-C in continuous infusion. For patients with ALL or with CNS involvement, the addition of CNS-directed therapy with a higher dose of MTX (8 g/m2), HD Ara-C (3 g/m2 x 4), VP 16, triple intrathecal injections and cranial irradiation greatly improved survival: 87% for ALL and 73% for patients with CNS involvement. In adults, the application of the paediatric protocol is possible with acceptable toxicity and a retrospective study of 41 cases treated according to a LMB protocol showed a cure rate of 71%. Such a regimen should now be proposed to adults and studied prospectively.

Introduction Malignant sacrococcygeal (SC) germ cell tumours (GCT) may be diagnosed as primary pelvic tumour or malignant recurrence of foetal SC teratoma (FSCT) operated during the neonatal period. In order to evaluate the difference between these two populations, the authors report their experience with SC-GCT registered in the French TGM 95 protocol. Population and methods The protocol comprised risk-adapted-chemotherapy (CT) followed by surgery. Standard risk (SR: localized tumour completely resected) had no adjuvant therapy. Intermediate-Risk (IR: localized tumour, incomplete or no initial surgery with αFP 15,000 ng/ml and/or metastases) received Etoposide–Ifosfamide–Cisplatin. Results Fifty-seven patients with SC-GCT, aged 0–80 months (median 16), were registered between 1995 and 2005. Nineteen patients had secondary SC-GCT after FSCT. All patients received CT: 17 IR and 1 SR after reevolution; 39 HR (25 with metastases). 51 patients underwent delayed surgery, which was incomplete in 8 patients. Evolution Seventy-two percent of the secondary SC-GCT had systematic biological follow-up. αFP increasing was the first presenting sign in 80% of the cases. Patients with secondary SC-GCT had a lower median αFP level at diagnosis, were less frequently classified as HR and received less CT. The two groups with secondary vs. primary SC-GCT had a statistically similar favourable outcome (Overall Survival: 93.8% vs. 86.2%; Event-Free Survival: 89.2 vs. 78.2%; p > 0.34 and >0.32), respectively, but with less burden of therapy. Conclusions SC-GCT has a good overall prognosis provided complete surgery is achieved and CT is administered to IR and HR patients. SC-GCT in patients followed by αFP after treatment for FSCT had less tumour extension than newly-diagnosed patients, probably because of earlier detection of the disease.

Pineal parenchymal tumours (PPTs) are rare neoplasms that are divided into pineocytoma (PC), pineoblastoma (PB) and PPT of intermediate differentiation (PPTID). Factors affecting the survival of patients with PPTs are morphological subtype and histological grading according to mitotic index and neurofilament immunostaining. Grading criteria to distinguish PPTIDs are difficult to define, particularly when using small specimens. The Ki67 labelling index (LI) might be helpful in distinguishing between grade II and III PPTIDs. Our study was performed to assess the predictive value of the Ki67 LI in a large cooperative series of PPTs and to evaluate whether inclusion of this data would improve and refine the World Health Organization classification.A retrospective analysis of 33 PPTs was performed. The histological features of the tumours were reviewed and Ki67 LI scoring was evaluated by immunohistochemistry. Data were correlated with the patients' survival.The mean Ki67 LI was significantly different for tumour grades (0 in PC, 5.2 ± 0.4 in PPTID grade II, 11.2 ± 2.0 in PPTID grade III, 36.4 ± 6.2 in PB; P0.0001). However, there was no statistically significant difference in either overall or disease-free survival evaluated by the Kaplan-Meier method for patients with different grade tumours or Ki67 LI, possibly due to the different clinical management of patients in different centres.The Ki67 LI may be a useful additional tool for grading PPTs, more particularly in small tumour samples.

In the LMCE1 study using a single course of megatherapy most of the relapses occurred during the first 2 years after autologous bone marrow transplantation. A second pilot study (LMCE2) was therefore set up using a double harvest/double graft approach with two different megatherapy regimens. Objectives were to test the role of increased dose intensity on response status, relapse pattern and overall survival. Thirty-three patients (20 boys, 13 girls) with a median age of 53 months at first megatherapy (range, 17-202 months) entered this study. They were cases either with refractory disease in partial response after second line treatment for stage 4 neuroblastoma (n = 25) or after relapse from stage 4 (n = 5) or stage 3 disease (n = 3). All patients received Etoposid and/or Cisplatinum (or Carboplatin) containing treatments before megatherapy. The first megatherapy regimen was a combination of Tenoposid, Carmustine and Cisplatinum (or Carboplatin), the second applied Vincristin, Melphalan and Total Body Irradiation. The first harvest was scheduled 4 weeks after the last chemotherapy, the second 60 to 90 days after megatherapy. All marrows were purged in vitro by an immunomagnetic technique. Median follow up time since first megatherapy is 56 months. Response rates for evaluable patients were 65% (complete response rate: 16%) for megatherapy 1 and 60% (complete response rate: 25%) for megatherapy 2. Considering that only patients with delayed response or relapse were eligible for this pilot study the overall survival was encouraging with 36% at 2 years and still 32% at 5 years. The costs for these survival rates were high in terms of morbidity (four early and four late toxic deaths; toxic death rate: 24%). Double harvesting may have the disadvantage of delayed engraftments related in part to a disturbance of marrow microenvironment by megatherapy 1. This double megatherapy approach achieved a prolonged relapse free interval (median 11 months, range 2-31 months) in patients reaching megatherapy 2 and justifies further evaluation of concepts with consecutive dose-escalation.

The term of "medulloblastoma" refers to cerebellar tumors belonging to the family of primitive neuro-ectodermic tumors (PNET). Medulloblastomas represent 40% of cerebellar tumors, 15 to 20% of brain tumors and the first cause of malignant brain tumors in childhood. Seventy to 80% of cases are diagnosed in children versus 20 to 30% in adults.Diagnosis is based on clinical and radiological exams, and proved on pathological analysis in association with molecular biology. Treatment comprises surgery, craniospinal radiotherapy except for children under five years of age and chemotherapy according to age and high-risk criteria. Medulloblastoma is a rare case of a central nervous system tumor which is radio- and chemo-sensitive. Treatment goals are, on one hand, to improve the survival rates and, on the other hand, to avoid late neurocognitive, neuroendocrine and orthopedic side effects related to radiation therapy, notably in children. The prognosis is relatively good, with a five year survival rate over 75% after complete resection of a localized tumor although sequelae may still compromise outcome.Management of patients with medulloblastoma implies a multidisciplinary approach combining the contributions of neurosurgery, neuroradiology, pediatric oncology, neuro-oncology and radiotherapy teams.

Les tumeurs germinales malignes (TGM) intracrâniennes sont rares. Leur histologie est similaire a celle des TGM extracrâniennes. Elles concernent principalement l’adolescent et leur pronostic est excellent. Le traitement vise a une guerison avec aussi peu de sequelles que possible.

We report 2 cases of multifocal cystic (type 1) pleuropulmonary blastoma, diagnosed during the first 6 months of life. This rare entity must be recognized before evolution into the prognostically unfavorable type 2 or type 3 pleuropulmonary blastoma.

Burkitt's lymphoma, a pathological entity initially described in Africa, is the most common childhood lymphoma in western countries and represents approximately 5% of all adults lymphomas. This high grade small non-cleaved diffuse lymphoma is a model with which to study the relations between cancer and viruses, the chromosomes and the genes. Burkitt's lymphoma is also a model for clinical research which allows evaluation of the dose effect concept with chemotherapy and the role of megatherapy with autologous bone marrow rescue.

We report the case of a 12-year-old boy with chemoresistant stage IV Hodgkin's lymphoma. A 67 Gallium scan was performed when his fever did not diminish following intensification of therapy. Apart from a known bone lesion, it showed diffuse bilateral lung uptake which could well be interpreted as an extension of his disease. But further investigations brought evidence of a Pneumocystis carinii infection. Because of the underlying disease, it was an important pitfall with clinical implications.

The population of survivors of childhood cancer is currently growing. Studies from other countries have shown an increased risk of late mortality. In order to measure this risk within a French cohort, the mortality of children who had survived five years from a cancer diagnosis were compared to the mortality of the general population, according to follow-up interval and cancer and treatment characteristics.The study population consisted of 635 children diagnosed with cancer before the age of 15 who had survived at least five years, and were registered in the Rhone-Alpes region cancer registry from 1987 to 1992. Mortality was compared with general population rates of the Rhone-Alpes region to assess age and sex standardized mortality ratio (SMR) and absolute excess risk of death.The median follow-up of children was 14.0 years. Among the 42 observed deaths, 71.4% were attributed to a recurrence of the original cancer, 9.5% to a second cancer. The 15-year cumulative risk of death, all causes, was 7.1%. The overall mortality of the cohort was 20.7 fold greater than the general population (95% CI: 14.9-27.9), and the absolute excess risk of 6.9 per 1000 persons-years. The long term excess-mortality was higher in case of recurrence of original cancer (SMR=99.9, 95% CI: 67.9-141.9, absolute excess risk 35.4 per 1000 persons-years); it was raised during the five to nine years follow-up interval after diagnosis (SMR=33.8, 95% CI: 23.2-47.3) mainly due to the primary malignancy, and decreased after (10-14 years follow-up interval SMR=6.5, 95% IC 2.4-14.2).The late mortality of childhood cancer is significantly increased during the five to nine years following diagnosis and decreases after, but the cohort follow-up has to be extended in order to assess outcome beyond 15 years after diagnosis.

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

We assessed the contribution of diffusion, perfusion and spectroscopy imaging for the diagnosis and follow-up of intraaxial tumors, suspected to be grade II gliomas. Twenty-four patients were included from April 2005 to July 2006, 17 initially and seven during their follow-up. The diagnosis was reconsidered in a first group of six patients: a high-grade tumor was suspected and confirmed in five. These patients presented a lipid peak; the perfusion results and the CHO/Cr and CHO/NAA ratios were not pathological. The second group included patients with grade II gliomas: these 18 patients had a radiographic work-up, initially, then at three months and every six months. For this group, no evidence of a change of grade were observed. Abnormal findings were noted in seven patients: among these patients, one developed radiographic progression, one other had radiographic progression associated with a spectroscopy lipid peak; only spectroscopy changes were noted in the third patient; the last patient had radiographic progression with perfusion and spectroscopy abnormalities; these four patients were treated. These observations suggest that diffusion, perfusion and spectroscopy can provide supplementary information for diagnosis and follow-up of glial tumors. The presence of a lipid peak is of particular value. The limitations of this work must also be taken into consideration: the follow-up was too short for slow-growing gliomas; the population was small and patients may have undergone surgery during the study, leading to structural modifications which may have compromised comparisons. This work should be continued with new examinations every six months and inclusion of new patients.

Cancer is rare in children, and pediatric malignancies represent only 1% of all cancers.The cure rate is high and increasing, and ongoing data collection is therefore warranted.Here we report the incidence and survival rates of childhood cancers between 1987 and 1999 in the Rhône-Alpes region of France.A total of 1945 cases were recorded during the study period, with an average of 149.6 new cases per year. The approximate incidence rate was 134.1/10(6) per year and the age-standardized incidence rate was 139.2/10(6) per year. The histological distribution and 5-year survival rates were respectively 30.2 and 73% for leukemia, 12.3 and 91.6% for lymphoma, 24.7 and 60.1% for CNS tumors, 9.1 and 71.1% for neuroblastoma, 2.5 and 94.1% for retinoblastoma, 5.8% and 89.9% for renal tumors, 1 and 75% for liver tumors, 6.1 and 60.9% for bone tumors, 4.1 and 58.6% for soft-tissue tumors, 1.1 and 71% for germ cell tumors, and 2.4 and 85.1% for carcinomas.The overall survival rate was 75%. Long-term treatment complications warrant further studies of children who survive into adulthood.

Dear editor, For many years, in case of suspicion of a germ cell tumor (GCT), human chorionic gonadotropin (HCG), its beta subunit and alpha-fetoprotein (AFP) have been used as specific markers in the blood and/or cerebrospinal fluid (CSF) for clinical decision-making [4]. A positive test is an indication for treatment, without requiring histological confirmation [5]. We report a first description of CSF HCG elevation in a non-cystic suprasellar craniopharyngioma, contradicting this dogma. A 52-year-old male with a history of arterial hypertension and tinnitus complained of a decrease in left-side visual acuity over a few weeks, associated with polyuro-polydipsia syndrome. MRI examination revealed a suprasellar lesion of 16×18×16 mm, with a moderate hyper-T2 signal and an iso-T1 signal with homogeneous gadolinium enhancement. The lesion did not have a cystic component (see Fig. 1). Spinal MRI was negative, and the cerebral CT scan did not show any calcification of the tumor. Hormone analysis revealed a pituitary deficiency. Biological analysis of the CSF performed as part of the etiological assessment revealed an elevation of HCG to 10.8 IU/l (normal levels

Complete staging (extensive marrow investigation and meta-iodo benzylguanine (MIBG) scan) is considered as mandatory both at diagnosis and after chemotherapy for assessment of metastases in neuroblastomas. However the correlation between bone marrow invasion and uptake of MIBG at metastatic sites remains unclear. This study investigates whether MIBG alone is sufficiently sensitive to make these procedures redundant.20 children over one year of age, with histologically proven metastatic neuroblastoma were studied. Extensive bone marrow assessment and MIBG bone scan performed both at diagnosis and after completion of induction chemotherapy were reviewed.At diagnosis metastases were detected by marrow investigation alone in 2, MIBG alone in 2 and both procedures in 16. After induction chemotherapy metastases were detected by only marrow investigation in 2, by only MIBG in 3, by both procedures in 6 patients, and by none in 9.Whether marrow investigations and MIBG scan explore the same phenomenon remains unclear. However it appears that marrow disease that is histologically detectable may remain MIBG negative both at diagnosis and after treatment. Both procedures are still justified at time of diagnosis and evaluation of response.

The goal of our study is to identify significant prognostic factors for a series of intracranial ependymomas in an adult population. Age, location, histology, preoperative clinical status, extent of resection and radiotherapy were examined.Our series includes 34 patients. Ten tumors were located in the brain parenchyma, 5 in the lateral ventricle, 8 in the third and 11 in the fourth ventricle. Seventeen ependymomas were grades 2 and 17 were anaplastic. Surgical resection was gross-total in 27 patients and partial in 7.At a mean follow-up of 9 years (+/- 1 year) 16 patients died and, among the 18 survivors 14 are in complete remission and 4 present a local recurrence. The 5- and 10-year overall survival rates were respectively 62% and 43%. The 5- and 10-year progression-free survivals were 47% and 43%. Univariate analysis revealed that location in the brain parenchyma and anaplasia are the only statistically significant predictors of poor outcome.We can make out three groups of patients from our series: the first encompasses patients operated on for an intraparenchymal tumor, in all our cases an anaplastic ependymoma, with a 5-year rate of tumor-related deaths of 100%. The second group includes fourth ventricle ependymomas, which are mostly grade 2 tumors. They display a 10-year survival rate of 90%. Last group entails lateral and third ventricle ependymomas, of both low and high grade, with a 10-year survival rate of 60% for lateral ventricle and 35% for third ventricle tumors.

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m2 on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.

Background To determine the effectiveness of multiagent chemotherapy as sole post-operative treatment of supratentorial central nervous system (CNS) embryonal tumors in young children. Procedure The data of 25 children under 5 years of age diagnosed with supratentorial embryonal tumors (17 primitive neuroectodermal tumors, four pinealoblastomas, and four medulloepitheliomas) treated exclusively by postoperative chemotherapy (CT) between 1990 and 1997 were reviewed. Results Fifteen tumors were hemispheric and 10 were deeply seated. Four children presented with disseminated leptomeningeal disease. Total resection was performed in nine patients, subtotal in 9, partial in 3, and a diagnostic biopsy only in 2. Two children did not undergo surgery. Twenty-four children relapsed with a median time of 5.5 months. The median overall survival was 12 months, and the 2-, and 5- year survivals were 30 and 14y, respectively. The 2- year disease-free survival was 4%. There was a significantly worse prognosis in patients undergoing incomplete resection and in the group with deeply situated tumors. Four relapses were treated by second surgery followed by high-dose chemotherapy and radiotherapy. Two of them remain in CR2, and all these children are free of late sequelae. Conclusions CT alone failed to maintain disease-free survival in most of the children, although, disease progression was delayed to some extent. Children under 5 years with supratentorial embryonal tumors should undergo total surgical resection if possible. Med Pediatr Oncol 2002;38:83–90. © 2002 Wiley-Liss, Inc.

The Lyon-Marseille-Curie-Est (LMCE) of France cooperative group has previously reported successive series of unselected stage four children older than 1 year at diagnosis with metastatic neuroblastoma (LMCE 1 and 3). The goal of LMCE 5 study was to increase progression free survival rate as compared to LMCE 1 and 3. Based on improvements reported with post induction chemotherapy, the LMCE 5 used post induction for all children, but omitted total body irradiation and immunomagnetic purging in megatherapy regimen for all children. Twenty-five sequentially diagnosed children received an induction regimen which compared with previous induction included an increased dose of etoposide and cyclophosphamide, delivered similar dose of cisplatinum, and deleted doxorubicin and vincristin. After surgery treatment was stratified based on response and eligible children received etoposide carboplatin (LMCE 5A : n=10)±doxorubicin (LMCE 5B–C n=13) followed by megatherapy (melphalan without total body irradiation and unpurged peripheral blood stem cell rescue). The increase in drug doses during induction did not improve remission rate. The progression free survival at 6 years is 8%. It is significantly worse than LMCE 3, and equivalent to LMCE 1 study though toxic death rate has decreased with increasing experience. Failure to improve the response rate during induction and reducing the megatherapy regimen may be the main factors in this disappointing result. Modified strategies for induction, non toxic alternative to total body irradiation, and post megatherapy regimen should be developed. British Journal of Cancer (2002) 87, 1197–1203. doi:10.1038/sj.bjc.6600627 www.bjcancer.com © 2002 Cancer Research UK

In the SFOP protocol TGM-TC90 for localised tumours, craniospinal (CS) prophylactic radiotherapy fields were replaced by carboplatin-based chemotherapy together with focal irradiation of the initial tumour volume (40 Gy). Metastatic tumours received CS irradiation and a local boost. In order to refine radiation-treatment volumes, patterns of relapse with respect to radiation technique were documented.

The previous SFOP TGM85 and TGM90 studies showed that carboplatin (400 mg/m2) was less efficient that cisplatin (100 mg/m2), that patients with AFP levels over 15000 ng/ml had a worse outcome, and that the VIP regimen (VP 16, Ifosfamide, cisplatin) was an efficient salvage therapy [1–3]. Based on these results, the SFOP developed the TGM95 protocol, a cisplatin-based chemotherapy adapted to initial resection, serum AFP and presence of metastases. Patients are stratified into three risk groups with the following guidelines: low risk (LR) patients with complete resection of a localized tumour (pSl): “watch and wait” with chemotherapy only in cases of tumour marker increase; median risk (MR) patients: non metastatic incompletely resected or unresectable tumour with AFP less than 15000: VBP (Vinblastine, Bleomycine, cisplatin) regimen; high risk (HR) patients: AFP 15000 or more, and/or metastasis: VIP regimen. In both groups, patients received two additional courses of chemotherapy after normalization of tumour markers. The residual tumour or the organ initially involved (if not previously done) were excised after normalization of tumour markers.

The significance of residual lesions after therapy for intracranial germinomas remains a controversial issue [1]. We therefore assessed: a) the frequency of residual tumour after surgery, b) the frequency of residual abnormalities after radiotherapy (RT) and during follow-up and c) the impact of residual lesions on patient outcome.

In the SFOP TC-90 and TC-92 protocols, patients with intracranial germinomas and secreting germ cell tumours (sGCT) were treated with a combination of chemotherapy and focal radiotherapy. One chemotherapy cycle included alternating Carboplatin-VP16 and Ifosfamide-VP16. Germinoma patients received two cycles followed by 40 Gy focal radiotherapy, and sGCT three or four cycles followed by focal 55 Gy. Metastatic patients received craniospinal radiotherapy.

A European protocol for malignant CNS GCTs was initiated in 1996. The purpose was to compare patients with germinoma treated either with reduced craniospinal irradiation (CSI) (24 Gy craniospinal/16 Gy tumour boost) or with a combined therapy (2 courses Carbo PEI) and focal irradiation (40 Gy). In non-germinomatous malignant tumours (choriocarcinoma, yolk sac tumours, embryonal carcinoma) (sGCTs) the efficacy of intensive preoperative chemotherapy (4 courses PEI) followed by radiotherapy was investigated. Irradiation was either focal (54 Gy) if negative spinal MRI and negative CSF-cytology, or CSI in metastatic patients (30 Gy CSI/24 Gy tumour boost). Measurement of markers was mandatory. Elevated markers in serum or CSF (s-HCG > 50 IU/1, AFP > 25 ng/ml) together with an intracranial primary suggested the clinical diagnosis of a sGCTs.

Le melanome pediatrique est extremement rare et il n’existe pas d’AMM pour les inhibiteurs de B-Raf dont l’efficacite, y compris en cas d’atteinte du systeme nerveux central, est pourtant demontree chez l’adulte en cas de mutation V600E de B-Raf. Nous rapportons l’observation d’un garcon de 15 ans ayant presente un melanome cerebral primitif V600E mute avec meningite tumorale clinique, radiologique et biologique. Apres exerese incomplete de la lesion et progression sous temozolomide, l’instauration d’une monotherapie par vemurafenib a permis une amelioration des symptomes (douleurs rebelles, photophobie, paralysie faciale) en quelques jours et une remission complete clinique et radiologique pendant 9 mois. La qualite de vie a ete excellente et les effets secondaires observes ont ete uniquement dermatologiques (phototoxicite). La survie a ete de 14 mois, alors qu’elle n’excede habituellement pas 10 semaines dans cette pathologie Une telle efficacite dans le cadre d’un melanome cerebromeninge primitif n’a ete a notre connaissance rapportee qu’une fois dans la litterature chez un adulte. Il semble important que le recours a cette therapeutique ciblee en pediatrie dans le melanome ou d’autres tumeurs B-Raf mutees puisse devenir possible.

Introduction La survie des enfants atteints de tumeur cerebrale (TC) s’est amelioree ces dernieres annees avec des morbidites non negligeables. Objectifs L’etude des facteurs influencant les resultats scolaires des patients, et la comparaison de ces resultats aux donnees nationales. Patients et methodes Notre travail consiste en une etude retrospective descriptive de 1955 a 1992, portant sur 215 patients ayant presente une TC et ayant repondu a l’auto-questionnaire provenant de l’etude Wyeth. Les parametres etudies ont ete le sexe, l’âge au diagnostic, le groupe de naissance, le traitement administre, le niveau d’education des parents et leur situation socioeconomique. Resultats 20,3% obtiennent le bac. Ce taux de reussite moins eleve par rapport a la population generale francaise de meme âge et sexe, est statistiquement significatif chez les 25–44 ans pour les 2 sexes. Les 2 parents bacheliers, au moins 1 des 2 parents bachelier, ingenieur, ou enseignant sont des facteurs de reussite au bac. La radiotherapie et un âge de diagnostic inferieur a 10 ans sont des facteurs d’echec. Conclusion Les patients atteints de TC dans l’enfance reussissent moins bien leur scolarite. Reperer et aider les groupes a risque doit etre realise precocement par une equipe multidisciplinaire.

Objectifs Determiner les facteurs influencant les resultats scolaires des patients survivants d’une tumeur solide non cerebrale dans l’enfance. Methodologie Nous avons compare les resultats d’un auto-questionnaire provenant de l’etude Wyeth portant sur le devenir de ces patients, aux donnees nationales INSEE en fonction du sexe et de l’âge. Resultats 58% des 1609 patients diagnostiques entre 1948 et 1992 obtiennent le baccalaureat. Ce taux est plus eleve (observe/attendu 0.99–1.66) et le pourcentage de patients ayant un diplome superieur est plus important (observe/attendu 1.6–2.35) que dans la population generale. Le taux de reussite est influence par la profession et le niveau d’etude des parents. Pour le baccalaureat, si un des parents est instituteur (OR: 3.082, p En analyse multivariee, le pourcentage de reussite au baccalaureat est augmente si un des parents est instituteur (OR : 2.9, p Conclusion Les patients survivants de notre etude reussissent mieux leur scolarite que la population generale. Le statut des parents a un impact dans la reussite de celui-ci.

High grade gliomas usually show a transient response to standard therapy by radiation. A local evolution leads to patient death in most of the cases. Necropsic series suggest that metastatic evolution is rather frequent in lungs, lymph nodes, bones or bone marrow. Are these metastatic deposits present initially? The authors retrospectively reviewed the bone marrow smears performed in 20 patients and the bone scans in 10 patients with high grade gliomas at time of diagnosis. None of these investigations showed metastatic deposits. It is thus suggested that metastatic deposits are probably a late event in the natural history of high grade gliomas. However, if local treatment could reach local control, metastases would probably become a major problem. Thus definitive cure of high grade glioma may require multidisciplinary approach.

There is no agreement on immunization of children treated with chemotherapy (CT) for solid tumors. Based on a review of the literature, we have attempted to establish guidelines on this subject. Except for hepatitis B vaccine, there is no argument to support the use of vaccine during CT. After a standard CT, a 3-month washout period appears to be necessary before starting an immunization program for a child not previously vaccinated, or to proceed with the recommended booster injections for diphteria anatoxin, tetanus vaccine, poliomyelitis inactivated vaccine, pertussis vaccine, and haemophilus influenza type b vaccine if the child is less than 5 years old. For mumps, measles, and rubella live vaccines, a longer post-CT washout of 6 months is suggested for the initial immunization, or for a revaccination of a child proved to be negative for all three serologies. Following high-dose CT a minimal 12-months term and a normalization of the blood lymphocytes count is necessary before planning booster injections once having checked for antidiphteria, tetanic, polio, measles, mumps, rubella and +/- haemophilus antibody titles. We don't find any reason to recommend a systematic varicella immunization in pediatric oncology. Pneumococcal vaccine is recommended in case of asplenia. Any other vaccination (BCG, influenza, yellow fever) must be evaluated individually.

Infants with neuroblastoma (NB) were assessed according to INSS recommendations, including MIBG scan and extensive bone marrow staging to eliminate metastatic spread. Patients with unresectable tumour received chemotherapy, including two courses of carboplatin-etoposide (CE) and two of vincristinecyclophosphamide-doxorubicin (CAdO). Post-operative treatment was to be given only in infants with MYCN amplification. Between 1990 and 1994, 52 consecutive children were registered.Among the 44 patients who received CE as a first course, the response rate was (66%) and the primary could be removed in all children but one, who was in remission. The toxicity was mainly haematological and was always manageable. The 5 year overall survival (OS) and event-free survival (EFS) were 94 and 90 +/- 8%, respectively, with a median follow-up of 48 months. The outcome of infants with no MYCN amplification was excellent; OS and EFS were, respectively, 97 and 94%.Chemotherapy allows surgical excision and excellent outcome in infants with localised and unresectable NB. Less intensive Chemotherapy should be investigated in such patients.

The presence of multifocal or diffuse nephrogenic rests (NRs) in one or both kidneys is termed nephroblastomatosis (Nbm). Nbm may be a predisposing factor for Wilms' tumour (WT). The aim of this retrospective study was to evaluate the impact of Nbm on the outcome of WT in children. We assessed the outcome of 81 children with Wilms tumours and practical implications of Nbm in the treatment and follow-up. All the pathology slides have been reviewed in 1997. 63 had WT without Nbm (group A) and 18 had WT associated with Nbm (group B). There was no statistical difference between the two groups according to the age at diagnosis and histology. Clinical abnormalities were more frequent in group B (33 versus 8%). There was no statistical difference between the percentage of stage IV in both groups, but bilaterality (stage V) was present only in the group B. Relapse was observed in 20/81 patients (25%): 11 (17%) in group A and 9 (50%) in group B. Mean delay of relapse was longer (25 months) in group B than in group A (10 months). For the whole population, with a median follow-up of 9 years, the event-free survival (EFS) and the overall survival (OS) probabilities were respectively 74%±10 and 83%±9 at 120 months. The difference in EFS between groups A (82±9%) and B (38%±29) was significant ( P =0.004). The discovery of Nbm in the non-tumoral part of the kidney with WT can be an adverse factor and in particular favours the subsequent development of a new Wilms tumour. It justifies separate follow-up guidelines.

The authors report three cases of stage IV-S neuroblastoma in infants aged 4, 6, and 8 weeks, who despite chemo- and radiotherapy required surgical intervention to urgently relieve major thoracoabdominal compression secondary to massive hepatomegaly. The results were successful, with abdominal expansion being achieved by the introduction of a polytetrafluoroethylene prosthesis, which was removed during the 2nd, 3rd and 7th postoperative month, respectively, after tumor regression. Two children were in complete remission 32 and 38 months later, the 3rd died after 16 months of tumor progression.

In children over 1 year of age with metastatic neuroblastoma, clearance of metaiodobenzylguanidine (MIBG) skeletal uptake after four courses of induction chemotherapy is one of the most powerful prognostic factors. How subjective is quantification of MIBG uptake, and can earlier MIBG scintigraphy separate good and bad responders?The data from 47 patients who received uniform induction therapy were reviewed. A novel scoring system of MIBG update intensity was proposed. Initial, intermediate (after two courses), and final (after four courses) intensities were scored (0 to 21 points) independently by six different observers. The initial global score and the relative score (calculated by dividing the global score after two courses by the initial score) were compared to the final score. Good responders were those who scored 0 at final MIBG.Between two observers, the correlation coefficient for the global score was superior to 0.80, in nine of ten comparisons established between observers 1-5. The initial score did not predict the final score insofar as only nine of fourteen patients with low initial scores were good responders. The relative score also failed to predict outcome; only six of ten patients with favorable relative score (i.e.,20%), were good responders.This scoring system is reliable and may be used in multicentric trials. However, both initial and relative scores failed to predict final outcome. Thus, intermediate MIBG may be omitted during induction therapy assessment.

Objectif Etudier de maniere prospective et multicentrique le role de la radiotherapie bifractionnee focale (RBF) post-operatoire dans les ependymomes de l’enfant. Materiel et Methode Dans les differents centres de la SFCE, une RBF etait proposee aux enfants âges de plus de 5 ans au diagnostic, porteurs d’un ependymome intracrânien localise. L’irradiation etait realisee en 2 fractions quotidiennes de 1 Gy pour une dose totale de 60 Gray (Gy) apres exerese complete (EC) et 66 Gy apres exerese partielle (EP). La qualite de l’exerese etait jugee par chaque centre sur la base du compte rendu operatoire et de l’imagerie post operatoire. Une relecture centralisee retrospective de l’imagerie a ete realisee par la suite. Resultats De novembre 1996 a decembre 2002, 24 enfants porteurs d’un ependymome infratentoriel (20) ou supratentoriel (4) ont ete inclus. L’âge moyen de ces enfants etait de 8.6 ans (de 5 a 17 ans). Le grade histologique (selon la classification de l’OMS) etait anaplasique dans 10 cas, et non determine dans 1 cas sur 24. Apres relecture centralisee de l’imagerie, les patients etaient en EC dans 16 cas, en EP dans 4 cas. La qualite de l’exerese etait douteuse dans 4 cas. La dose de radiotherapie delivree etait de 60 Gy dans 18 cas (1 EP apres relecture), 66 Gy dans 5 cas (1 EC apres relecture) et 54 Gy dans 1 cas (EC apres relecture). La survie globale a 5 ans etait de 74.8 % et la survie sans progression de 54.2 %. Onze patients ont rechute, 7 rechutes etaient purement locales, 4 etaient metastatiques ou mixtes. Le grade histologique, ainsi que la qualite de la resection n’ont pas ete retrouves comme des facteurs pronostiques. Plus de des survivants n’ont pas de sequelles de la radiotherapie, apres un suivi d’au moins 7 ans (CI95 % : 66.4 – 90.0 mois). Conclusion La RBF est une technique qui n’accroit pas le risque de sequelles, mais ne semble pas apporter de benefice en terme de survie sans progression si on la compare aux strategies d’irradiation classique.

Resume Une fungemie a Candida rugosa (CR) a ete constatee chez un patient recevant une allogreffe de moelle osseuse (AGM). La persistance de ce germe inhabituel, malgre une triple association antimycotique, et apres ablation du catheter veineux central, la pathogenicite d'un tel germe sont discutees. Une breve revue de la litterature est presentee.

Neuroblastoma is a major contributor to childhood cancer mortality, but its prognosis varies with age and stage of disease, and some tumours regress spontaneously. Urinary screening programmes or clinical examination may detect the disease before symptoms appear, but the benefit of early diagnosis is uncertain. We examined the incidence, pattern, and presentation of neuroblastoma in four European countries.Population-based incidence rates were derived for France, Austria, Germany, and the UK. Age, sex, and stage distribution were analysed by Mantel-Haenszel techniques and Poisson regression. The proportion of incidental diagnoses (cases without symptoms found at routine health checks or during investigation of other disorders) and mortality rates were also compared.Between 1987 and 1991, 1672 cases of neuroblastoma were diagnosed in children under 15 years old (France, 624; Austria, 69; Germany, 493; UK, 486). Age-standardised annual incidence was significantly lower in the UK (10.1/million) than in France (12.5) and Germany (11.4). In the UK a deficit of low-stage disease in infants was accompanied by an excess of stage IV in older children. The UK had significantly fewer incidental diagnoses (8%) than Austria (27%) and Germany (34%). UK mortality rates were significantly higher than German or French rates.In the UK, neuroblastoma diagnosis is delayed, possibly because of a less rigorous system of health checks for children. Although some overdiagnosis occurs in mainland Europe, our data suggest that in the UK some low-stage cases, undetected in infancy, may later present as advanced disease. This finding has implications for screening programmes and organisation of routine surveillance of infant health in the UK.

Between March 1990 and December 1994, 316 consecutive children with localised neuroblastoma were registered in the French NBL 90 study. In addition to the assessment of a new chemotherapy regimen in unresectable neuroblastoma, we evaluated the prognostic significance of MYCN amplification and loss of the short arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and associated with unfavourable clinical features such as age at diagnosis1 year and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of whom some had favourable prognostic factors such as age at diagnosis1 year (n = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall survival (OS) and event-free survival (EFS) were, respectively, 56% and 22% (median follow-up: 36 months) for children with LOH1p compared with 97% and 94% for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN amplification and LOH1p relapsed and ultimately died of the disease. Among the 4 with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1 metastatic), all alive in second remission after salvage therapy (12-19 months after the relapse). In multivariate analysis, LOH1p was the strongest prognostic indicator for subsequent relapse. LOH1p appears more discriminant than MYCN amplification for predicting the risk of recurrence in children with localised neuroblastoma. However, its analysis was possible in only 30% of our patients and its final impact on survival should be confirmed in larger, prospective studies in order to stratify subsequent treatment.