Long-term morbidity and mortality in 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies.

BACKGROUND AND AIMS: Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. METHODS: We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. RESULTS: With a median follow-up of 9.4 years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. CONCLUSIONS: With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.

Analysis of diagnosis announcements in Abidjan pediatric oncology unit 2 years after introduction of the African Pediatric Cancer Announcement Guideline.

INTRODUCTION: Announcing the diagnosis allows the therapeutic alliance between physicians and patients to be sealed and it prevents abandonment of treatment. To compensate for the deficit in information received by the families, the Franco-African Group of Pediatric Oncology (FAGPO) has published an "African Pediatric Cancer Announcement Guide" for the group's pediatric oncology units. OBJECTIVE: To analyze the announcements made to parents and children 2 years after the provision of this guide. METHODS: Cross-sectional survey conducted from March to July 2016. In total, 69 parents of children followed up in the pediatric oncology unit of Abidjan were interviewed regarding the characteristics of the announcement that was made to them and the information given to the sick child. RESULTS: Of all the accompanying individuals, 91% reported having benefited from the announcement made with empathy, mainly by a physician. In approximately one quarter of the cases the information had been given to a third party. The main barriers to information were: the negative experiences of parents, the medical terminology, and communication problems. The sick child was rarely informed. DISCUSSION: The information given was in accordance, in content and form, with the data from Western and African literature. The lack of information given to the child has a dual explanation: the primacy of the community over the individual advocated by African culture and the non-integration of the rights of children in the current code of ethics. CONCLUSION: The information provided could be improved by practical training of physicians in the technique of breaking bad news to patients and their families and the use of a code of ethics in accordance with the principle of autonomy.

Vancomycin in Pediatric Patients with Solid or Hematological Malignant Disease: Predictive Performance of a Population Pharmacokinetic Model and New Optimized Dosing Regimens.

BACKGROUND: The application of population pharmacokinetic models and Bayesian methods offers the potential to develop individualized therapeutic approaches. OBJECTIVES: The current study presents an external evaluation of a vancomycin pharmacokinetic model in a pediatric cancer population and proposes an easy-to-use chart for clinicians for a priori vancomycin schedule adaptation to achieve target concentration. METHODS: External evaluation of a population pharmacokinetic model of vancomycin administered via continuous infusion was realized in a new retrospective dataset of pediatric patients with cancer. The published population pharmacokinetic model was implemented in NONMEM 7.3 with the structural and variance parameter values set equal to estimates previously reported. Predictive performance was assessed by quantifying bias and accuracy of model prediction. Normalized prediction distribution errors were also evaluated. Dosage simulations were performed according to the target concentration. RESULTS: A total of 77 patients were included in this study, representing 146 vancomycin courses and 289 concentrations. The model adequately predicted vancomycin concentrations (median prediction error % of - 9.4%, median |PE|% of 24.1%). Based on simulation results, vancomycin dosage (mg/kg) should be adapted for each child on the basis of body weight and cyclosporine coadministration. CONCLUSION: The model previously proposed by Guilhaumou et al. in pediatric patients with solid or hematological malignant disease was externally validated. Simulations have enabled the description of new dosage schedules and creation of a chart to help clinicians adapt vancomycin dosage.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

[Multidisciplinarity, education, and training in pediatric oncology-hematology]. / Multidisciplinarité et formation des spécialistes à l'oncologie et à l'hématologie maligne pédiatrique.

INTRODUCTION: According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d'Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120h), on-site practical training in a specialist center, and a research project to be defended before an examining board. METHOD: All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects. RESULTS: From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0-22.6), 85% in English. CONCLUSION: DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer.

Surgical management of thymic epithelial tumors in children: lessons from the French Society of Pediatric Oncology and review of the literature.

PURPOSE: We report the results of a French multicenter retrospective study based on a period of more than 30 years and a review of the literature in order to more clearly define the surgical approach and specific pediatric risk factors. METHODS: Clinical data of children comprising all histologic subtypes of thymic epithelial tumors (TET) treated between 1979 and 2009 in French pediatric oncology centers were retrospectively analyzed and discussed in the light of a review of all pediatric cases reported in the literature. RESULTS: Nine cases were identified, corresponding to five females and four males with a median age of 13 years (range: 7.5-17). Histologic subtypes were type AB (n = 1), type B (n = 5) and type C (n = 3). Treatment consisted of tumor resection (4 R0, 4 R1, 1 R2) via right anterior thoracotomy, posterolateral thoracotomy, left thoracoscopy, sternotomy and cervicosternotomy, and/or chemotherapy, mainly cyclophosphamide-doxorubicin-cisplatin (CAP; n = 5), and/or radiotherapy (n = 4). Two patients with TET type C died. All other patients are alive with a median follow-up of 4 years (range: 1.5-20). Review of a total of 93 pediatric cases reported in the literature showed statistically significant associations between less favorable histologic subtypes and male gender (P = 0.012), advanced Masaoka stage (P < 0.001) and quality of resection (P < 0.001) respectively. CONCLUSIONS: A review of the literature and our series identified several risk factors to take into account in the therapeutically decision. Complete resection through a sternotomy is highly recommended.

[Managing pain in children with cancer in Africa: a survey from the French-African Pediatric Oncology group]. / Prise en charge de la douleur de l'enfant atteint de cancer en Afrique : état des lieux au sein du Groupe franco-africain d'oncologie pédiatrique.

INTRODUCTION: The French-African Pediatric Oncology group (GFAOP) has contributed to a significant improvement in the prognosis of pediatric cancers in Africa through the development of therapeutic protocols adapted to local conditions. In parallel, the development of supportive care such as pain management, is now a major priority of our group. OBJECTIVE: The main objective of this study was to evaluate the management of pain in children with cancer in sub-Saharan Africa. METHODOLOGY: A questionnaire was sent to both the doctor and nurse responsible for each of the 8 pilot units (PUs). RESULTS: All physicians and 2 nurses answered the questionnaire. Human resources (3 doctors and 4 nurses per PU) were modest compared to the size of the pediatric population (71 million) and the mean number of 102 cases of cancer/year per PU. Only six physicians had received specific training in pediatric oncology. Morphine was available in only 5 of the 8 PUs; major limitations for its prescription were mainly inconsistent availability (62.5%), fear of side effects (50%), and regulations (37.5%). During the curative phase, more than half of the parents had to buy analgesics when leaving the PU. Pain assessment relied mainly on clinical evaluation (8/8), but was generally concordant with parents' assessment. The majority of patients experienced pain at diagnosis and at a higher degree at relapse, cancer being the predominant etiology. Pain related to other causes such as medical procedures, mucositis, and neuropathic pain was detected; however, its management remained inadequate. Only 2 of 8 PUs had a written protocol for pain management. These deficiencies can be explained by limited resources, both human and financial, but also by cultural factors such as endurance against pain still advocated by many African traditions. CONCLUSION: In recent years, pain prevention and relief, whatever its origin, have become a priority for all medical teams, especially for children with cancer. With its profound sociocultural changes, Africa is no exception. All teams in our group are aware of the situation and hope for major improvement in pain management in the near future through increased resources and training.

[Pediatric non-Hodgkin's lymphoma: primary surgical management of patients presenting with abdominal symptoms. Recommendations of the Lymphoma Committee of the French Society to Combat Pediatric Cancers (SFCE)]. / Lymphome non-Hodgkinien de l'enfant: prise en charge chirurgicale lors d'un tableau abdominal révélateur.

Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.

[Evaluation of a screening strategy after occurrence of two simultaneous contaminating tuberculosis cases in a pediatric oncology department]. / Stratégie de prise en charge de contages tuberculeux dans un service d'oncologie-pédiatrique.

BACKGROUND: A medical staff and an administrative staff of our paediatric oncology department have contracted a pulmonary tuberculosis. This is a rare situation and the management of this infection threat in a paediatric oncology department is not clearly defined. Recommendations tell we must treat all patients. Nevertheless, antituberculosis agent expose to increased toxic effects and immunocompromised patients have an increased risk of experiencing progression of latent mycobacterium tuberculosis infection to active tuberculosis disease. OBJECTIVE: This study aims at the evaluation of a screening and a treatment strategy adapted for a paediatric oncology department. METHOD: From April 2004 to April 2005, 80 children with a solid tumour were screened for tuberculosis according to a screening and treatment protocol established by a multidisciplinary committee. Two risk groups were defined according to age and immunodepression status. The "high risk" group is composed of less than 2 years old children and children who underwent an haematological peripheral stem cell transplantation. All other children were included in the "low risk" group. The screening was based on clinical, biological and radiological data performed three times spaced out by 2 or 3 months. At the end of each part of screening, the multidisciplinary committee analyzed the results and discussed the utility of an antituberculosis treatment. RESULTS: 80 children (31 boys and 49 girl) with a median age of 7,3 years (0,3-24) participated to the screening. Sixty children were still undergoing anticancer treatments. Twenty belonged to the high risk group. The complete screening was performed in 32% of the patients. Three antituberculosis' treatment were initiated: 2 for prophylaxis purpose and 1 for a tuberculosis prime-infection. A child had an additional check-up because of an abnormal chest X-ray. Our management strategy allowed us to treat significantly less patients when compared to national guidelines (3 vs 80 test Chi-2 p<0.001). No side effects of antituberculosis agents were noted. No tuberculosis has been observed in our population 28 months after the completion of the treatment. CONCLUSION: The proposed screening allowed us to treat a minimum of children and thus, to reduce the potential toxicity induced by antituberculosis' treatments.

[Not Available]. / Lymphome non-Hodgkinien de l'enfant : prise en charge chirurgicale lors d'un tableau abdominal révélateur: Recommandations du « Comité lymphome ¼ de la Société française de lutte contre les cancers de l'enfant et de l'adolescent (SFCE).

A. Delarue, C. Bergeron, F. Mechinaud-Lacroix, C. Coze, M. Raphael, C. Patte, pour le « Comité Lymphome ¼ de la SFCE Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.

[Understanding nephroblastoma. Information dedicated to parents and relatives]. / Comprendre le néphroblastome. Information à l'usage des parents et des proches d'un enfant malade.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information developed in this program is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres,the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding nephroblastoma is an adapted version of various scientific publications and international clinical practice guidelines, validated by oncology experts and by the Nephroblastoma Committee of the French Society against Cancers and Leukaemias in children and adolescents (SFCE). It was elaborated with the active participation of parents and other family members. It is meant to provide a basis for the explanation of the disease, to help parents asking questions, and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 PARIS, Tel. (0033)1 76 64 78 00, www.fnclcc.fr). This document was validated at the end of 2005 and published in May 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding nephroblastoma and published in this edition of the Cancer et Radiothérapie, describe the physiopathology of nephroblastoma, as well as treatments and follow-up. The guide allows parents and relatives to better understand the disease and the treatments proposed. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

[Infectious complications postengrafment in the first year after autologous stem cell transplantation in children]. / Autogreffes de cellules souches hématopoïétiques en oncologie pédiatrique; étude des complications infectieuses survenant au cours de la première année après sortie d'aplasie.

BACKGROUND: Studies on the infectious complications postengrafment in pediatric stem cell transplantation patients are rare. The aim of this study was to assess the incidence, types, outcome and factors affecting late infections. PATIENTS AND METHODS: A single-institution retrospective analysis was done of infections recorded in the first year following engrafment in children who underwent autologous stem cell transplantation for solid tumors from January 1991 to December 2000. A systematic antimicrobial chemoprophylaxis of TMP/SMX was administered. Patients who were at high risk for varicella-zona virus infection received prophylactic acyclovir. RESULTS: Eighty-four assessable patients were enrolled. Fifty-four patients (64%) underwent autologous peripheral blood stem cell transplantation and 30 patients (36%) underwent bone marrow transplantation. Forty-nine episodes of infections were documented in 39 patients (46%) of whom 27 patients (32%) developed infections after the first 100 days post transplantation. Bacterial septicemia occurred in nine patients of whom four patients had a catheter-related septicemia. Twelve patients (14%) developed localized herpes zoster infection. Local fungal infection occurred in five patients. Infection-related death occurred in one patient with non-documented pneumonitis. Univariable analysis showed a correlation between the CD34(+) cell dose <7.5 10(6)/kg and the development of infections (P =0.04). Patients who did not go into remission after transplantation where at high risk for septicemia (P =0.007). Multivariate analysis showed that a history of varicella or pretransplant varicella-zona positivity was the only significant factor for development zoster infection (P =0.01). CONCLUSION: Our study shows that infections in the first year postengrafment following autologous stem cell transplantation for solid tumors have a good prognosis and that the use of TMP/SMX should be the single systematic antimicrobial prophylaxis. The CD34(+) cell dose seems to play a role in preventing late infections.

[Neonatal localized neuroblastoma: 52 cases treated from 1990 to 1999]. / Neuroblastomes localisés du nouveau-né: 52 cas traités de 1990 à 1999.

UNLABELLED: Neuroblastoma is the most frequent tumor observed in the newborn. The aim of this study was to review clinical features, treatment and outcome of newborns diagnosed with a localized neuroblastoma. POPULATION AND METHODS: Data from 52 cases treated according to the NBL 90 and 94 protocols between 1990 and 1999 in 18 French centers of pediatric oncology were analyzed. RESULTS: The median age at diagnosis was 12 days (range 0-28) with antenatal detection in 14 patients (27%). Tumor location was abdominal in 40 patients (adrenal in 20 of the 40), thoracic in eight, pelvic in three, and cervical in one. N-myc amplification was observed in one out of 40 evaluable cases. The size of the primary tumor was less than 5 cm in 25 cases, between 5 and 10 cm in 25 and more than 10 cm in two. Dumbbell tumor was observed in seven, of whom five had neurological deficit. One child died from hemorrhage after fine needle biopsy during diagnostic procedure. Primary surgical resection was attempted in 37 infants, of whom two died of surgery related complications and three had nephrectomy. Tumor was deemed as unresectable in 14 patients, and primary chemotherapy was given followed by surgical excision in 12. One of them died a few days after the beginning of chemotherapy. As a whole, continuous complete remission was achieved in 48 children, four of them after relapse. Overall survival was 92% with a median follow-up of 46 months (0-113 months). CONCLUSION: The excellent prognosis of localized NB in neonates needs very restrictive surgical indications, with well-established anatomic and imaging criteria. Indeed, chemotherapy based on weight and managed by expert teams should allow to perform surgical excision in safer conditions for unresectable tumors.

[Prognosis of neuroblastoma in childhood. Methods of assessment and clinical use]. / Le pronostic du neuroblastome de l'enfant. Méthodes d'étude et utilisation en pratique clinique.

Neuroblastoma and its benign counterpart, ganglioneuroma, are pediatric neuroblastic tumors arising in the sympathetic nervous system from neural-crest cells. Neuroblastoma, the most common extra-cranial solid tumour during childhood, is unique for its broad spectrum of clinical virulence from spontaneous remission to rapid and fatal progression despite intensive multimodality therapy. To a large extent, outcome could be predicted by the stage of disease and the age at diagnosis. However, a number of molecular events in neuroblastoma tumors, accounting for the variability of outcome and response to therapy, have been identified over the past decades. Among these, MYCN amplification is the most relevant prognostic factor and was the first genetic marker, in paediatric oncology, to be included in clinical strategies as a guide for therapeutic decision. This has allowed the most suitable intensity of therapy to be delivered according to a risk-stratified strategy, from observation to megadose chemotherapy with stem cell transplantation. Recent advances in understanding the biology and genetics of neuroblastoma will ultimately allow to select poor-risk patients for appropriate future biologically based therapies.

Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy.

The purpose of this study was to evaluate the efficacy of low-dose chemotherapy in infants with localised and unresectable neuroblastoma (NB). All consecutive infants with localised NB and no N-myc amplification were eligible in the SFOP-NBL 94 study. Primary tumour was deemed as unresectable according to imaging data showing any risk of immediate resection. Diagnostic procedures and staging were conducted according to INSS recommendations. For children, provided that they had no threatening symptom (i.e. vital risk or dumb-bell NB with neurologic deficit), chemotherapy consisted in low-dose cyclophosphamide (5 mg(-1)kg day(-1) x 5 days) and vincristine (0.05 mg kg(-1) at day 1)-CV and repeated one to three times every 2 weeks until surgical excision can be safely performed. No postoperative treatment was given. Between January 1995 and December 1999, 134 consecutive infants with localised NB were registered in the study, of whom 39 had an unresectable NB without N-myc amplification. Among them 28 had no threatening symptom and received CV according to the protocol. Objective response was observed in 14 (50%) and the other 14 were given second-line chemotherapy because of no response. Surgery was attempted in 38 patients including 14 after CV alone, leading to complete resection in 23. Relapses occurred in four patients all local. Survival and event-free survival were 100 and 90+/-5% with a median follow-up of 55 months (range 33-93). In conclusion primary low-dose chemotherapy without anthracyclines is efficient in about half of the infants presenting with an unresectable NB and no N-myc amplification, allowing excellent survival rates without jeopardising their long-term outcome even for nonresponding patients who received standard regimen.

The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis.

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.