A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries.

Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS. Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

Pathways of care for adolescent patients with cancer in France from 2006 to 2007.

BACKGROUND: In France, as in other countries, there is a need for a population-based view of access to care and modalities of treatment for adolescents with cancer. PROCEDURE: Using a population-based registration, we report pathways of care for 15-19-year-old patients, diagnosed with cancer in 2006 and 2007, living in six French regions, accounting for 41% of the French population. RESULTS: The median times (inter-quartile range) for diagnosis and treatment of the 594 included adolescents were 8 weeks (3-17) and 3 days (0-16), respectively. First physicians met by the patients were mostly general practitioners (59%). Seventeen percent of patients were firstly seen on emergency wards. Most of the patients (82%) were treated in an adult environment. Management decisions were taken within the context of a multi-disciplinary team (MDT) in 54% of cases. Twenty-seven percent of patients were included in randomized or non-randomized clinical studies: percentage depended on the tumor type and on the number of on-going trials at the study period. Fifteen percent of patients were included in pediatric studies, 7% in adult studies, and 5% in studies including both adults and children. CONCLUSIONS: The pathways of care for French adolescent patients with cancer are heterogeneous. Our results reveal differences in MDT meetings according to tumor types and a lack of effective collaboration between pediatric and adult wards. Efforts must be made to develop cancer networks to ensure that adolescents receive the optimal care in a suitable environment.

Childhood cancer survival in France, 1990-1999.

The aim of this study was to describe the overall survival after childhood cancer in France using follow-up data from regional population-based registries. The survival of children (aged under 15 years) diagnosed with a cancer during 1990-1999 was analysed. For all cancers, the survivals were, respectively, 90.3% [89.4-91.3] at 1-year, 75.2% [73.8-76.6] at 5 years and 72.2% [70.7-73.7] at 10 years. During the 1990s, the average improvement in the 5-year survival was +1.2% per year. Adjusted for gender, age, area of residence and stage, children with cancer diagnosed between 1995 and 1999 had a 0.80 reduced risk of dying compared with those whose cancer had been diagnosed between 1990 and 1994. The increase of survival at the population level reflects a global improvement in childhood cancer care. The Paediatric Registries, in association with the French Society of Childhood Cancer, are now collecting data to quantify on a national basis the other events, at least relapse and second cancers.

Cancer adolescent pathway in France between 1988 and 1997.

We report an adolescent cancer pathway from referral, through diagnosis and treatment, to follow-up in France. All cases of cancer among 15-19 years, diagnosed from 1988 to 1997, recorded by nine French population-based cancer registries (10% of French population) were included. The management of adolescent cancer by paediatricians was rare. An adolescents' pathway through cancer care can be summarized as first visit to general practitioner, referral to adult oncologist for haematological malignancy and medical or surgical specialists for solid tumours, treatment in adult unit, and follow-up by adult oncologist, adult medical or surgical specialist, or general practitioner. Only 9% of the 15-19 years are entered into a clinical trial (respectively 6% and 3% into adult and paediatric clinical trial). The inclusion rate changes according to the diagnosis, higher for acute lymphoblastic leukaemia (39%), non-Hodgkin's lymphomas (NHL) (27%), and acute non-lymphoblastic leukaemia (20%). Only 4% of adolescent cancers were managed on shared adult/paediatric departments, especially for soft-tissue sarcomas (14.9%), malignant bone tumours (13.4), central nervous system tumours (6.2%), and NHL (4.4%). Whatever the reasons for lack of participation in clinical trials, an ideal model requiring communication and cooperation between all adult and paediatric specialists involved in adolescent cancer treatment should reduce the large gap in access to cooperative groups.

Cancer survival among adolescents in France.

Cancer is the third most significant cause of mortality in French adolescents. The aim of this study was to investigate survival of adolescents with cancer. Overall (OS), disease-specific (DSS) and event-free survival (EFS) were used for the outcome analysis of adolescents (15-19 years) with cancer, recorded by nine French population-based registries during the 1988-1997 period. Five-year OS, DSS and EFS were, respectively, 74.0% (70.7-77.4), 74.5% (71.2-77.9), and 69.0% (65.4-72.5). Five-year DSS was 94% for carcinomas, 89% for germ-cell tumours, 85% for lymphomas, 67% for soft-tissue sarcomas, 64% for CNS tumours, 55% for malignant bone tumours, and 41% for leukaemia. Compared with paediatric series, poor results in acute lymphoblastic leukaemia, malignant bone tumours, and soft-tissue sarcomas have to be highlighted, and deserve further studies concerning the type of regimens used for these patients. Multidisciplinary management of adolescent cancer in paediatric, adult, or specialized units will improve cure rates and treatment outcomes for these patients.

[Oncolor: a comprehensive cancer network in the Lorraine Region of France]. / Fonctionnement du réseau Oncolor: sa place au sein des réseaux de cancérologie.

Legislation governing patients' rights and health care quality (March 2002) provided for the creation of healthcare networks intended to improve the management of patients with complex and/or chronic diseases. As defined in the Cancer Plan, activated in March 2003, an oncological healthcare network covers a particular French region, with the aim of offering patients equal access to the best available care and accompaniment, based on caregiver coordination, shared multidisciplinary tools, and communication. ONCOLOR, the regional cancer network launched in the Lorraine region in 1993, complies with these objectives. Nevertheless, its future development depends on continued dynamism, durable financial support, and regular evaluation of the benefits for patients and caregivers. The key words are professionalism and consensus.

Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Société Française d'Oncologie Pédiatrique.

PURPOSE: To estimate the risk of secondary leukemia as a function of the dose of epipodophyllotoxins and anthracyclines. METHODS: We conducted a case-control study of the risk of secondary leukemia or myelodysplasia after a solid tumor in childhood within the Société Française d'Oncologie Pédiatrique, including 61 patients with leukemia matched with 196 controls. The characteristics of the first cancer, the patient's family history of cancer, and the treatment (type, cumulative dose of chemotherapy, schedule of etoposide administration, and radiation dose delivered to active bone marrow) were compared in the two groups. RESULTS: Only two factors were found to increase the risk of leukemia in multivariate analysis, namely, the type of the first tumor, with an excess risk in patients with Hodgkin's disease (relative risk 6.4; 95% confidence interval [CI], 1.6 to 24) or osteosarcoma (relative risk 5; 95% CI, 1.3 to 19), and exposure to epipodophyllotoxins and anthracyclines. The risk of leukemia increased regularly with the cumulative dose of etoposide. In summary, patients who received between 1.2 and 6 g/m(2) of epipodophyllotoxins or more than 170 mg/m(2) of anthracyclines had a seven-fold higher risk (95% CI, 2.6 to 19) compared with patients who received lower doses or none of these drugs. The risk of leukemia in patients who received more than 6 g/m(2) of epipodophyllotoxins was multiplied by 197 (95% CI, 19 to 2,058). The risk of leukemia was not increased by exposure to alkylating agents or radiotherapy. CONCLUSION: Both epipodophyllotoxins and anthracyclines increase the risk of secondary leukemia. The current challenge is to minimize the mutagenic effects of these drugs by diminishing cumulative doses without losing the therapeutic benefits.

Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy.

Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene-environment interactions were estimated using both case-control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0-4.9]) and with GSTM1 deletion (OR 2.3 [1.2-4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3-1.2] and 0.4 [0.1-1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.

Family history of autoimmune thyroid disease and childhood acute leukemia.

The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

Validation of the French version of the Childhood Health Assessment Questionnaire (CHAQ) in juvenile idiopathic arthritis.

OBJECTIVES: To translate, cross-culturally adapt, and validate the functional disability tool Childhood Health Assessment Questionnaire (CHAQ), a variant of the Health Assessment Questionnaire (HAQ), in children with juvenile idiopathic arthritis (JIA). CHILDREN AND METHODS: The disability index is the mean of the scores on the eight domains of the CHAQ and can range from 0 (no disability) to 3 (maximum disability). The CHAQ was first translated into French and adapted, then validated in a multicenter cross-sectional study in 306 children with JIA (systemic onset, 23%; polyarticular onset, 22%; extended oligoarticular subtype, 25%; and persistent oligoarticular subtype, 30%). RESULTS: Overall CHAQ scores discriminated between the four JIA subtypes (systemic: 1.1 +/- 0.9; polyarticular: 0.8 +/- 0.7, extended oligoarticular 0.8 +/- 0.7, and persistent oligoarticular: 0.4 +/- 0.5 [P < 0.0001]). Reproducibility evaluated by test-retest at a 7-day interval was excellent (intraclass coefficient, 0.91), as was agreement between the Parent's and Children's versions of the questionnaire (intraclass coefficient, 0.89). Significant correlations were found between the overall CHAO score and variables reflecting disease severity (joint counts, physician's and parent's global assessments, and erythrocyte sedimentation rate), indicating excellent convergent validity of the tool. CONCLUSION: The French version of the CHAQ displays good psychometric characteristics, although its sensitivity to change remains to be established. The French version of the CHAO should prove useful in international studies and can be expected to be helpful for monitoring individual patients with JIA.

[How to improve the initial management of adult patients with tumors of bone and soft tissues: the experience of a multidisciplinary committee from the Oncolor network before the distribution of regional guidelines]. / Comment améliorer la prise en charge initiale des patients adultes atteints de tumeurs des os et parties molles: expérience d'un comité de concertation pluridisciplinaire du réseau Oncolor, avant la diffusion des référentiels régionaux.

Tumors of bone and soft tissues in adults are rare accounting in France for 2000 to 2500 new cases per year. These tumors are heterogenous and their diagnosis is made after first surgery. Therefore, an early pluridisciplinary approach, by physicians who have acquired an expertise in this field, is advised before any biopsy or surgical resection and at all the further step in the subfrequent management. This paper describes the experience of a pluridisciplinary committee, specialized in malignant tumors of bone and soft tissues in adults, with a highly specialized team which is part of a network in the treatment of cancer in Lorraine, the Oncolor network, before the distribution of regional guidelines. After a description of the organisation of this committee, we made a retrospective analysis of all the cases submitted to these experts advice for the first time, between January and December 2000. This study reveals an insufficient pluridisciplinary coordination at the initial management, which has been done by making regional referentials available, and therefore some errors which lead in some cases to inadapted treatment. It underlines therefore the necessity to implement more actively the present data of science, and to develop the management in multidisciplinary committees. Oncolor aims to harmonize this pluridisciplinary approach as well as to diffuse standard recommendations.

[Thyroid metastases of an adrenocortical carcinoma 41 years after the diagnosis of the primary tumor]. / Métastases thyroïdiennes d'un corticosurrénalome 41 ans après le diagnostic de la tumeur initiale.

Thyroid metastasis are rare and represent less than 4% of malignant thyroid tumors in clinical series. They can develop many years after diagnosis of the primary tumor. We report a case of thyroid metastasis of adrenocortical carcinoma, 41 years after the diagnosis of the primary tumor. Such a long latent interval is exceptional. To our knowledge, this is the first case published. Based on current literature, we offer a brief review on thyroid metastasis and differential diagnosis of thyroid gland clear cell neoplasm.

[Epidemiology of childhood cancer]. / Epidémiologie des cancers de l'enfant.

The knowledge of the epidemiology of cancer in childhood is relevant of a strict methodology allowed by the activation of population-based specific registries, case-control and cohort studies. Descriptive epidemiology is a mean of survey and of public health, while analytic epidemiology contributes to define the role of genetic and environmental factors, along with their interaction. The collected data help indirectly to improve the care of the child with cancer and to a better understanding of the carcinogenesis.

Chronic pediatric diseases into adulthood and the challenge of adolescence.

One of the priorities of public health is to improve the equity of access to a continuous interdisciplinary medical and social survey of patients with chronic complex conditions, and, notably, the switch from pediatric to adult-oriented healthcare, including the specific issues of adolescence. In spite of the many barriers related to the patients, their family, pediatricians, and even adult health providers, the concept of a planned, dynamic, multidisciplinary transition program has to be designed around the adolescent with the aim of reinforcing his autonomy, coordinating medical care, and addressing his educational/professional and psychosocial needs. The primary care physician is the pivot of adult heathcare, and should have a close relationship with the private or hospital referent specialist and paramedical structures. A key worker may make an important contribution to the coordination, the registration, and the follow-up of some cohorts.

The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: a prospective validation study.

OBJECTIVE: To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). METHODS: In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordance in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS: The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent's global assessment of patient's well-being, 5) functional ability, and 6) health-related quality of life. CONCLUSION: The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European League Against Rheumatism, propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms.

BACKGROUND: Salivary gland tumors represent 1% of head and neck tumors, with only 5% of these occurring in patients younger than 20 years. Mucoepidermoid carcinoma (MEC) is one of the most frequent salivary gland cancers among adults and children. METHODS: This survey was conducted among 34 French pediatric oncology departments. From 1980 to 2000, 18 cases were reported. RESULTS: Treatment included surgery or radiotherapy, or both. The 5-year survival rate was 93.7%. Eleven patients had been previously treated by radiotherapy and/or chemotherapy for a first malignant tumor, specifically, lymphoid leukemia (n = 4), lymphoma (n = 3), brain tumor (n = 2), sarcoma (n = 1), and retinoblastoma (n = 1). CONCLUSIONS: MEC is very rare in the pediatric age group. Treatment involves surgical removal of the tumor plus radiotherapy, according to histologic staging. MEC has a good prognosis in young patients. The survival rate does not differ in the subgroup of patients with MEC as a secondary tumor.

Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease.

Transaldolase (TALDO) deficiency is a newly recognized metabolic disease, which has been reported so far in 2 patients presenting with liver failure and cirrhosis. We report a new sibship of 4 infants born to the same consanguineous parents; all presented at birth or in the antenatal period with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, splenomegaly, liver failure, hemolytic anemia, thrombocytopenia, and genitourinary malformations. The clinical courses were variable: the first child died of liver failure at 4 months of age; the second pregnancy was medically terminated at 28 weeks gestation because of hydrops fetalis with oligohydramnios. The third child is doing well at age 7 with liver fibrosis and mild kidney failure. The fourth child is now 21 months old and has hepatosplenomegaly, mild anemia, and thrombocytopenia. Urine assessment of polyols showed elevations of erythritol, arabitol, and ribitol consistent with TALDO deficiency. TALDO activity was undetectable in the patients' tissues, and mutation in the TALDO1 gene was found in the 4 patients.

Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukaemia.

INTRODUCTION: We investigated the role of maternal alcohol and coffee drinking and parental smoking on the risk of childhood acute leukemia in a multicenter case-control study. METHODS: The study included 280 incident cases and 288 hospitalized controls, frequency matched with the cases by age, gender and center. Data collection was completed by face-to-face standardized interviews of the case and control mothers. RESULTS: An association with maternal alcohol consumption during pregnancy was observed with acute lymphoid leukemia (ALL) (OR=2.0 [1.4-3.0]) and acute non-lymphoid leukemia (ANLL) (OR=2.6 [1.2-5.8]). Maternal coffee consumption during pregnancy was associated with childhood acute leukemia, ORs increasing in ALL with coffee consumption (OR=1.1 [0.7-1.8], OR=2.4 [1.3-4.7] and OR=3.1 [1.0-9.5], respectively, for < or =3, 4-8 and >8 cups/day). No association with maternal smoking during pregnancy or parental smoking before or after the index child's birth was observed. DISCUSSION: Our results suggest an association with maternal alcohol and coffee drinking during pregnancy and call for further investigations. Besides, the present study does not support the hypothesis of an increase in the risk of childhood leukemia related to parental smoking.

Cancer incidence among children in France, 1990-1999.

BACKGROUND: Cancer is the second most important cause of death for children aged less than 15 years in France, unintentional injuries being the leading cause. The aim of the present study was to estimate the incidence of childhood cancer from six Childhood Cancer Registries covering 32% of France. PROCEDURE: Incident cancer cases diagnosed between 1990 and 1999 in children (0-14 years) resident in the administrative areas covered by each Registry were included. Annual age-standardized rates (ASRs) were adjusted by the world population. The estimated annual percent change (EAPC) was used to measure trend towards changes in the annual age-standardized incidence rate. RESULTS: With 4234 registered cases, the ASRs per million children were 137.5 for all cancers combined, 42.3 for leukemia, 29.1 for central-nervous-system tumors, 15.6 for lymphomas, 14.1 for sympathetic-nervous-system tumors, and 9.1 for renal tumors. The ASR of all cancers combined was slightly higher in males (145.8 per million children) than in females (128.7 per million children) with an M/F ratio of 1.2. No significant incidence trend was observed, with an EAPC of +0.2% [IC 95% (-2.5; +3.0); P = 0.89]. CONCLUSIONS: The estimated incidence rates are similar to those reported in previous studies in European and North American countries. These results will contribute to the development of National Registration of Childhood Cancer in France and support the national research program on childhood cancer.