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1.
Artigo em Inglês | MEDLINE | ID: mdl-31411521

RESUMO

Background: Management of Adolescent and Young Adults (AYAs) cancer is very heterogeneous. In the case of lymphomas, outcomes are mostly favorable but there is still room for improvement. Design: We retrospectively collected the pattern of care of all institutional 13- to 25-year-old AYAs patients with classical Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) diagnosed in the Rhône-Alpes region between the years 2000 and 2005. Management, including adherence to Clinical Practice Guidelines (CPGs), and long-term survival were analyzed by comparing adult units (AU) and pediatric units (PU). Results: 278 patients were included: 198 treated for HL (median age of 19 years), 80 treated for NHL (median age of 20 years). Among them, 74% were managed in AU and 26% in PU. The median time between diagnosis and starting treatment was significantly lower in PU than in AU. Sixty-five patients (23%) were included in clinical trials, mostly in AU. Five-year overall survival was 96% for HL [14 deaths, median follow-up 91 months (9-180)] and 90% for NHL [nine deaths, median follow-up 80 months (3-180)]. Secondary cancers occurred for 2% (n = 3) of HL patients and for none in NHL. Other major late complications included cardiovascular accidents in two patients and fatal pulmonary fibrosis in one patient. Major differences in chemotherapy and radiotherapy use are emphasized. Global management conformed to CPGs by 56%. Conclusions: Important differences between adult and pediatric management were reported, without any impact on survival. A few patients can be included in clinical trials: Homogeneity in management could improve specific care for AYAs.

2.
Cancer Causes Control ; 30(10): 1075-1085, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31399828

RESUMO

PURPOSE: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated. METHODS: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. RESULTS: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings. CONCLUSION: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier.

3.
J Pediatr ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30442413

RESUMO

OBJECTIVE: To evaluate the association between medical and social environmental factors and the risk of repeating a grade in childhood leukemia survivors. STUDY DESIGN: A cross-sectional study of childhood leukemia survivors, recruited through the LEA cohort (Leucémie de l'Enfant et de l'Adolescent [French Childhood Cancer Survivor Study for Leukemia]) in 2014. An adjusted logistic regression model was used to identify variables linked to repeating a grade after the diagnosis among the survivors, and the rates of repeating a grade were compared between the survivors and their siblings using a multilevel logistic regression model. RESULTS: The mean age at inclusion of the 855 participants was 16.2 ± 7.0 years, and the mean duration of follow-up from diagnosis to evaluation was 10.2 ± 6.2 years. After disease onset, 244 patients (28.5%) repeated a grade, with a median interval of 4 years (IQR, 2-8 years). Independent factors associated with repeating a grade were male sex (OR, 1.78; 95% CI, 1.21-2.60), adolescence (OR, 2.70; 95% CI, 1.63-4.48), educational support during the treatment period (OR, 3.79; 95% CI, 2.45-5.88), low parental education level (OR, 2.493; 95% CI, 1.657-3.750), and household financial difficulties (OR, 2.62; 95% CI, 1.607-4.28). Compared with siblings, survivors were at greater risk of repeating a grade (OR, 1.87; 95% CI, 1.48-2.35). CONCLUSIONS: The most vulnerable patients seemed to be adolescents and those with parents of low socioeconomic status. Improving the schooling career of leukemia survivors will require that the medical community more carefully consider the social status of patients.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30136876

RESUMO

PURPOSE: Survival rate of childhood cancers is now reaching 80% overall. However, early or late complications related to surgery, chemotherapy, and radiotherapy remain at a high rate and greatly increase the risk of late mortality. The objective of this study is to assess the autonomic nervous system (ANS) activity, measured through heart rate variability indices in childhood cancer survivors compared with healthy controls. METHODS: This prospective study included 51 long-term childhood cancer survivors diagnosed before 15 years of age between 1987 and 1992 and controlled for age and sex with healthy volunteers. RESULTS: We observed a significant increase in spontaneous heart rate (beats per minute) (67 ± 10 vs. 60 ± 10, p = 0.001), and all the studied parameters showed a significantly altered ANS activity in cases compared with healthy controls. In both groups, the main cofactors of dysautonomia (tobacco, drugs, cannabis, estro-progestative pills, alcohol, limited physical activity) were analyzed without any significant difference. The effect of cancer treatments received was not analyzed due to the small number of participants. CONCLUSION: The results showed a significant ANS dysfunction in childhood cancer survivors compared with healthy controls and suggested the value of autonomic screening to underscore and possibly quantify the effect of the cancer treatments in a larger cohort. This evaluation could lead to the recommendation to increase physical activity, the most efficient way known to improve ANS activity, as already shown in other pathologies (breast cancer).

5.
J Adolesc Young Adult Oncol ; 7(4): 415-423, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29851372

RESUMO

PURPOSE: To describe fecundity in female survivors of childhood cancer and consider the correlation with quality of life (QOL). MATERIALS AND METHODS: Of 1744 women treated for childhood cancer before the age of 15 years at one of eight French cancer treatment centers between 1948 and 1992, 1187 who were alive in 2005 were sent a self-administered questionnaire, including questions about health status, QOL (MOS SF-36), and fecundity. A standardized fecundity ratio (SFR) was calculated (SFR: observed/expected number of children) for each individual based on a national reference. RESULTS: Of the 972 individuals (82%) who responded, 53% had at least 1 child. The overall SFR, 0.65, was dependent upon the initial diagnosis, more decreased in Central Nervous System tumors (0.24; p < 10-3) than in Germ cell (0.46; p = 0.03) or Sympathetic Nervous System tumors (0.79; p = 0.02). The average QOL motor score was 72.5 ± 19.5, and the average mental score was 61.4 ± 16.7. After adjusting for age, pathology, and self-reported sequelae in the questionnaires, it was determined that SF-36 mental (p = 0.002) and motor (p < 0.0002) scores correlated positively with fecundity, and SF-36 scores correlated negatively with locomotor late effects (p < 0.0001), growth insufficiency (p = 0.002), and psychological disorders (p < 0.001). Gonadal insufficiency was correlated with neither motor nor mental scores. CONCLUSION: Women treated for childhood cancer demonstrated impaired fecundity that correlated with poor QOL, as registered by the SF-36. Patients should be warned of the risk of impaired fecundity early during the follow-up. If possible, preservation of fertility should be prioritized at initiation of therapy.

6.
J Clin Pharmacol ; 58(12): 1541-1549, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29791011

RESUMO

Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (PK). This prospective study aimed to develop a population PK-pharmacogenetic model to evaluate the part of between-subject variability due to single-nucleotide polymorphisms (SNPs) in transporters and enzyme genes implicated in MTX distribution and elimination. MTX concentrations and 54 SNPs (located in ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC19A1, SLCO1B1, and UGT1A1 genes) were analyzed in patients treated with MTX included in the OS2006/sarcoma-09 trial (a multicenter, open-label, phase III trial, ClinicalTrials.gov. Identifier: NCT00470223). PK data were analyzed using the nonlinear mixed-effect modeling software program Monolix. The influence of each SNP was evaluated using a stepwise procedure under additive, recessive, or dominant genetic model. The likelihood ratio test was used to test the effect of each SNP on PK parameters. Overall, 187 patients with 7898 MTX blood concentrations were included in the PK-pharmacogenetic analysis. A 2-compartment model adequately described the data. Although high-dose MTX dosing recommendations in pediatric patients are currently based on body surface area, body weight was more predictive of clearance between-subject variability than body surface area. The most significant polymorphism associated with MTX clearance was rs13120400 (on the ABCG2 gene) under the recessive genetic model (P < .0001). GG genotype carriers for rs13120400 appeared to have a moderate decrease in MTX exposure compared to AA or GA carriers.

7.
Int J Cancer ; 142(3): 489-497, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28949017

RESUMO

Some previous epidemiological studies have suggested that pesticide exposure during pregnancy may have a possible role in the development of childhood brain tumors (CBT). We pooled data from two French national population-based, case-control studies to investigate the association between maternal residential use of pesticides during pregnancy and the risk of CBT. The mothers of 437 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, answered a structured telephone interview conducted by trained interviewers. Unconditional logistic regression was used to estimate pooled odds ratio (OR) and 95% confidence intervals (95% CI). CBT was significantly associated with the maternal home use of pesticides during pregnancy (OR 1.4, 95% CI 1.2-1.8) and, more specifically, with insecticide (OR 1.4, 1.2-1.8). We could not draw any conclusions about herbicides and/or fungicides because few women used them during pregnancy and most of these mothers also used insecticides. Although potential recall bias cannot be excluded, our findings of this pooled analysis support the hypothesis that residential maternal use of pesticides during pregnancy and particularly insecticides may increase the risk of CBT. Future investigations to verify these findings and to explore for CBT subtypes and dose-response are necessary to have a better understanding of the possible role of pesticides in etiology of CBT.


Assuntos
Neoplasias Encefálicas/epidemiologia , Exposição Materna/estatística & dados numéricos , Praguicidas/envenenamento , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Exposição Ambiental , Feminino , França/epidemiologia , Humanos , Masculino , Gravidez , Risco , Adulto Jovem
8.
Cancer Epidemiol ; 52: 1-9, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29128708

RESUMO

BACKGROUND: Few studies have investigated whether early infections and factors potentially related to early immune stimulation might be involved in the aetiology of childhood brain tumours (CBT). In this study, we investigated the associations between CBT with early day-care attendance, history of early common infections, atopic conditions (asthma/wheezing, eczema, allergic rhinitis), early farm residence/visits and contact with animals. METHODS: We pooled data from two nationwide French case-control studies, the ESCALE and ESTELLE studies. Children with a CBT diagnosed between 1 and 14 years of age were identified directly from the French National Registry of Childhood Cancers, while population controls were recruited from telephone subscribers. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression adjusted for potential confounders. RESULTS: The analyses included 469 cases and 2719 controls. We found no association between attending a day-care centre (OR: 0.9, 95%CI: 0.7-1.2) or having had repeated common infections (OR: 0.9, 95%CI: 0.7-1.2) in the first year of life and the risk of CBT. There was also no association with a history of asthma/wheezing (OR: 0.8, 95%CI: 0.56-1.1). Farm visits (OR: 0.6, 95%CI: 0.5-0.8) as well as contact with pets (OR: 0.8, 95%CI: 0.6-1.0) in the first year of life were inversely associated with CBT. CONCLUSIONS: Our findings suggest a protective effect of early farm visits and contact with pets, but not with other markers of early immune stimulation. This might be related to immune stimulation but needs further investigation.

10.
J Adolesc Young Adult Oncol ; 6(4): 524-534, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28541785

RESUMO

PURPOSE: We evaluated the satisfaction of adult survivors of childhood cancers and their general practitioners (GP) after a long-term consultation. METHODS: The first Long-term Follow-up Study in Oncology (SALTO1) is a prospective cohort study of survivors of childhood cancers (except leukemia) diagnosed between 1987 and 1992 in the Rhône-Alpes and Auvergne regions of France. Of the 481 patients eligible for the study, 150 participated in a long-term consultation with a pediatric oncologist and an internist, after which survivors and their GPs received long-term plans and recommendations based on consultation findings. A year after the consultation, survivors and their GPs assessed their satisfaction with the process. RESULTS: Of the 150 survivor participants in the long-term follow-up, 120 (80%) completed the satisfaction form, with 107 (89%) reporting satisfaction. Forty-eight (32%) expressed strengthening their follow-up as a consequence of the consultation. Of the 79 survivors sent recommendations, 76 (96%) reported reading them, most (n = 68; 86%) found them useful, and 56 (71%) followed recommendations. Of the 107 GPs of the survivors, 82 (77%) conceded having been poorly informed about long-term complications for their patients after chemotherapy, and 93 (88%) appreciated having a hospital contact available for these patients. CONCLUSION: The long-term consultations ultimately enhanced medical follow-up of survivor participants, improving knowledge of both patients and family physicians regarding the patients' early disease, its treatments, and possible concerns, and offering consultative resources of medical specialists. The levels of participation of survivors and their physicians and reported satisfaction encourage the adoption of such consultations throughout France.


Assuntos
Sobreviventes de Câncer/psicologia , Encaminhamento e Consulta/normas , Estudos de Coortes , Feminino , Seguimentos , França , Clínicos Gerais , Humanos , Estudos Prospectivos , Inquéritos e Questionários
11.
BMC Cancer ; 17(1): 326, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28499444

RESUMO

BACKGROUND: Survival of childhood, adolescent and young adult (CAYA) cancers has increased with progress in the management of the treatments and has reached more than 80% at 5 years. Nevertheless, these survivors are at great risk of second cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non-interventional study whose aim is to organize a national screening for thyroid cancer and breast cancer in survivors of CAYA cancers. It will study the compliance with international recommendations, with the aim, regarding a breast screening programme, of offering for every woman living in France, at equal risk, an equal screening. METHOD: DeNaCaPST trial is coordinated by the INSERM 1018 unit in cooperation with the LEA (French Childhood Cancer Survivor Study for Leukaemia) study's coordinators, the long term follow up committee and the paediatric radiation committee of the SFCE (French Society of Childhood Cancers). A total of 35 centres spread across metropolitan France and la Reunion will participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central registry will be interrogated to identify eligible patients. To participate, centers agreed to perform a complete "long-term follow-up consultations" according to good clinical practice and the guidelines of the SFCE (French Society of Children Cancers). DISCUSSION: As survival has greatly improved in childhood cancers, detection of therapy-related malignancies has become a priority even if new radiation techniques will lead to better protection for organs at risk. International guidelines have been put in place because of the evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is based on these international recommendations but it is important to recognize that they are based on expert consensus opinion and are supported by neither nonrandomized observational studies nor prospective randomized trials in this specific population. Over-diagnosis is a phenomenon inherent in any screening program and therefore such programs must be evaluated.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Mama/patologia , Feminino , França , Humanos , Glândula Tireoide/patologia
12.
Cancer Causes Control ; 28(7): 719-732, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28477209

RESUMO

PURPOSE: To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT. METHODS: We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender, were interviewed through telephone, which included questions about prenatal parental smoking and maternal consumption of alcohol, coffee and tea. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex and study of origin. RESULTS: No association was seen between CBT and the mother smoking or drinking alcohol, coffee, or tea during the index pregnancy. The OR between CBT and paternal smoking in the year before birth (as reported by the mother) was 1.25 (95% CI 1.03, 1.52) with an OR of 1.09 (0.99, 1.19) for every 10 cigarettes per day (CPD) smoked. The association between paternal smoking and CBT appeared to be stronger in children diagnosed before the age of five years (OR 1.52, 95% CI 1.14, 2.02) and for astrocytoma (OR 1.86, 95% CI 1.26, 2.74). CONCLUSION: We found some evidence of a weak association between paternal smoking in the year before the child's birth and CBT, especially astrocytomas. These findings need to be replicated in other samples, using similar classifications of tumour subtypes.


Assuntos
Astrocitoma/epidemiologia , Neoplasias Encefálicas/epidemiologia , Pai , Adolescente , Adulto , Consumo de Bebidas Alcoólicas , Estudos de Casos e Controles , Criança , Pré-Escolar , Café , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Mães , Razão de Chances , Gravidez , Fatores de Risco , Fumar , Chá
13.
Int J Cancer ; 140(8): 1757-1769, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28054353

RESUMO

Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes.


Assuntos
Peso ao Nascer , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/fisiopatologia , Adolescente , Adulto , Índice de Massa Corporal , Neoplasias Encefálicas/diagnóstico , Aleitamento Materno , Estudos de Casos e Controles , Criança , Feminino , França , Humanos , Modelos Logísticos , Masculino , Mães , Gravidez , Fatores de Risco
14.
Biol Blood Marrow Transplant ; 22(11): 2003-2010, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27522039

RESUMO

We compared the long-term impact of donor type (sibling donor [SD] versus matched unrelated donor [MUD] or umbilical cord blood [UCB]) on late side effects and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic stem cell transplantation. We included 314 patients who underwent transplantation from 1997 to 2012 and were enrolled in the multicenter French Leucémie de l'Enfant et de L'Adolescent ("Leukemia in Children and Adolescents") cohort. More than one-third of the patients were adults at last visit; mean follow-up duration was 6.2 years. At least 1 late effect was observed in 284 of 314 patients (90.4%). The average number of adverse late effects was 2.1 ± .1, 2.4 ± .2, and 2.4 ± .2 after SD, MUD, and UCB transplantation, respectively. In a multivariate analysis, considering the SD group as the reference, we did not detect an impact of donor type for most sequelae, with the exception of increased risk of major growth failure after MUD transplantation (odds ratio [OR], 2.42) and elevated risk of osteonecrosis after UCB transplantation (OR, 4.15). The adults and children's parents reported comparable QoL among the 3 groups. Adult patient QoL scores were lower than age- and sex-matched French reference scores for almost all dimensions. We conclude that although these patients are heavily burdened by long-term complications, donor type had a very limited impact on their long-term health status and QoL.


Assuntos
Nível de Saúde , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Qualidade de Vida , Doadores de Tecidos , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas/psicologia , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Doadores não Relacionados
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