Les améliorations dans les protocoles de traitement pour la majorité des cancers pédiatriques ont augmenté de façon marquée les taux de survie. Cependant, des risques élevés de multiples problèmes de santé chez les survivants sont bien documentés. En ce qui concerne spécifiquement les problèmes neuropsychologiques, les principaux facteurs de risque individuels connus à ce jour (l’âge au diagnostic, le genre du patient, l’exposition aux radiations) demeurent insuffisants pour cibler efficacement et prévenir les séquelles à long terme. Les objectifs généraux de cette thèse étaient : 1) la caractérisation des trajectoires individuelles de problèmes de comportement chez une population de patients pédiatriques atteints de leucémie lymphoblastique aiguë; 2) l’identification des principaux déterminants génétiques, médicaux et psychosociaux associés aux problèmes de comportements. Les hypothèses étaient : 1) Il existe une association entre les trajectoires individuelles de problèmes de comportement et a - des facteurs psychosociaux liés au fonctionnement familial, b - des polymorphismes dans les gènes modérateurs des effets thérapeutiques du méthotrexate et des glucocorticoïdes, c - des variables liées aux traitements oncologiques. 2) L'utilisation de modèles statistiques multi-niveaux peut permettre d’effectuer cette caractérisation des trajectoires individuelles et l’identification des facteurs de risque associés. 138 patients pédiatriques (0-18 ans) ayant reçu un diagnostic de leucémie lymphoblastique aiguë entre 1993 et 1999 au CHU Ste-Justine ont participé à une étude longitudinale d’une durée de 4 ans. Un instrument validé et standardisés, le Child Behavior Checklist, a été utilisé pour obtenir un indice de problèmes de comportement, tel que rapporté par la mère, au moment du diagnostic, puis 1, 2, 3 et 4 ans post-diagnostic. Des données génétiques, psychosociales et médicales ont aussi été collectées au cours de cette même étude longitudinale, puis ont été exploitées dans les modélisations statistiques effectuées. Les résultats obtenus suggèrent que les problèmes de comportement de type internalisés et externalisés possèdent des trajectoires et des facteurs de risque distincts. Les problèmes internalisés sont des manifestations de troubles affectifs chez le patient, tels que des symptômes dépressifs ou anxieux, par exemple. Ceux-ci sont très prévalents tôt après le diagnostic et se normalisent par la suite, indiquant des difficultés significatives, mais temporaires. Des facteurs médicaux exacerbant l'expérience de stress, soit le risque de rechute associé au diagnostic et les complications médicales affectant la durée de l'hospitalisation, ralentissent cette normalisation. Les problèmes externalisés se manifestent dans le contact avec autrui; des démonstrations d’agression ou de violence font partie des symptômes. Les problèmes externalisés sont plus stables dans le temps relativement aux problèmes internalisés. Des variables pharmacologiques et génétiques contribuent aux différences individuelles : l'administration d’un glucocorticoïde plus puissant du point de vue des effets pharmacologiques et toxicologiques, ainsi que l’homozygotie pour l’haplotype -786C844T du gène NOS3 sont liés à la modulation des scores de problèmes externalisés au fil du temps. Finalement, le niveau de stress familial perçu au diagnostic est positivement corrélé avec le niveau initial de problèmes externalisés chez le patient, tandis que peu après la fin de la période d’induction, le niveau de stress familial est en lien avec le niveau initial de problèmes internalisés. Ces résultats supportent l'idée qu'une approche holistique est essentielle pour espérer mettre en place des interventions préventives efficaces dans cette population. À long terme, ces connaissances pourraient contribuer significativement à l'amélioration de la qualité de vie des patients. Ces travaux enrichissent les connaissances actuelles en soulignant les bénéfices des suivis longitudinaux et multidisciplinaires pour comprendre la dynamique de changement opérant chez les patients. Le décloisonnement des savoirs semble devenir incontournable pour aspirer dépasser le cadre descriptif et atteindre un certain niveau de compréhension des phénomènes observés. Malgré des défis méthodologiques et logistiques évidents, ce type d’approche est non seulement souhaitable pour étudier des processus dynamiques, mais les travaux présentés dans cette thèse indiquent que cela est possible avec les moyens analytiques actuels. / Recent improvements in pediatric cancers treatment have led to marked increases in patient survival rate. However, it has been well documented that pediatric cancer survivors are at elevated risk for various other health problems. With respect specifically to neuropsychological side effects, known predictors (mainly: age at diagnosis, patient gender, exposure to radiation therapy) remain insufficient so far to target, and prevent efficiently, long term sequelae in this population. General objectives related to this thesis were: 1) characterization of individual trajectories of behavioral problems in pediatric patients with acute lymphoblastic leukemia; 2) the identification of genetic, medical and psychosocial determinants of behavioral problems in this population. This research program was based on the following hypotheses: 1) there is an association between the trajectories of individual behavioral problems and a – familial well-being-related psychosocial factors, b – gene polymorphisms involved in the therapeutic responses to methotrexate and glucocorticoids, c – anti-cancer treatments-related variables. 2) Multilevel statistical modeling can be used to characterize patient groups according to their individual behavioral problem trajectories, and can also identify predictive factors. 138 pediatric patients (0-18 years old) who received an acute lymphoblastic leukemia diagnosis between 1993 and 1999 at CHU Ste-Justine participated in this 4 years-long longitudinal study. A standardized and validated instrument, the Child Behavior Checklist, was used to measure behavior problems, as reported by the mother, at diagnosis, and then 1, 2, 3 and 4 years post-diagnosis. Genetic, psychosocial and medical data were also collected during this longitudinal study; these data were exploited in the context of the statistical modeling performed. Results obtained suggest that internalized and externalized behavioral problems have distinct trajectories and have different predictive factors. Internalized problems are affective issues presented by the patient, such as depressive or anxious symptoms. They are highly prevalent post-diagnosis and normalize over the following years, suggestive of temporary yet significant problems. Stress-enhancing medical variables such as a higher relapse risk at diagnosis and medical complications requiring a longer hospitalization slow down the normalization process. Externalized problems need interpersonal contact to occur; violence or aggressiveness manifestations are some examples. Compared to internalized problems, externalized problems are much more stable across time. However, pharmacological and genetic variables do contribute to individual differences in trajectories. In particular, administration of a more potent glucocorticoid (from pharmacological and toxicological perspectives) and being homozygous for NOS3 gene -786C844T haplotype are linked to modulation of externalized problems in time. Finally, the level of perceived family stress at time of diagnosis is positively correlated with initial externalized problems, while shortly after the induction period, the level of familial stress is linked with the initial internalized problems. Together, these results support the idea that a holistic care strategy is essential to develop efficient, preventive interventions in this population, due to the multifactorial nature of these behavioral problems. The knowledge generated in the present studies could contribute to better quality of life for these patients. This thesis also brings a more holistic contribution to our current knowledge of behavioral problems in this population, by highlighting the need for individual, multidisciplinary follow-ups, with particular emphasis on repeated measurements and appropriate statistical analyses. More than ever, knowledge de-compartmentalization appears essential in reaching a certain comprehension level of observed phenomena, rather than adhering to descriptive settings. It indicates that, despite obvious methodological and logistic challenges, this type of research is not only desirable in studying dynamic processes, but is certainly achievable with current analytical tools.

Les améliorations dans les protocoles de traitement pour la majorité des cancers pédiatriques ont augmenté de façon marquée les taux de survie. Cependant, des risques élevés de multiples problèmes de santé chez les survivants sont bien documentés. En ce qui concerne spécifiquement les problèmes neuropsychologiques, les principaux facteurs de risque individuels connus à ce jour (l’âge au diagnostic, le genre du patient, l’exposition aux radiations) demeurent insuffisants pour cibler efficacement et prévenir les séquelles à long terme. Les objectifs généraux de cette thèse étaient : 1) la caractérisation des trajectoires individuelles de problèmes de comportement chez une population de patients pédiatriques atteints de leucémie lymphoblastique aiguë; 2) l’identification des principaux déterminants génétiques, médicaux et psychosociaux associés aux problèmes de comportements. Les hypothèses étaient : 1) Il existe une association entre les trajectoires individuelles de problèmes de comportement et a - des facteurs psychosociaux liés au fonctionnement familial, b - des polymorphismes dans les gènes modérateurs des effets thérapeutiques du méthotrexate et des glucocorticoïdes, c - des variables liées aux traitements oncologiques. 2) L'utilisation de modèles statistiques multi-niveaux peut permettre d’effectuer cette caractérisation des trajectoires individuelles et l’identification des facteurs de risque associés. 138 patients pédiatriques (0-18 ans) ayant reçu un diagnostic de leucémie lymphoblastique aiguë entre 1993 et 1999 au CHU Ste-Justine ont participé à une étude longitudinale d’une durée de 4 ans. Un instrument validé et standardisés, le Child Behavior Checklist, a été utilisé pour obtenir un indice de problèmes de comportement, tel que rapporté par la mère, au moment du diagnostic, puis 1, 2, 3 et 4 ans post-diagnostic. Des données génétiques, psychosociales et médicales ont aussi été collectées au cours de cette même étude longitudinale, puis ont été exploitées dans les modélisations statistiques effectuées. Les résultats obtenus suggèrent que les problèmes de comportement de type internalisés et externalisés possèdent des trajectoires et des facteurs de risque distincts. Les problèmes internalisés sont des manifestations de troubles affectifs chez le patient, tels que des symptômes dépressifs ou anxieux, par exemple. Ceux-ci sont très prévalents tôt après le diagnostic et se normalisent par la suite, indiquant des difficultés significatives, mais temporaires. Des facteurs médicaux exacerbant l'expérience de stress, soit le risque de rechute associé au diagnostic et les complications médicales affectant la durée de l'hospitalisation, ralentissent cette normalisation. Les problèmes externalisés se manifestent dans le contact avec autrui; des démonstrations d’agression ou de violence font partie des symptômes. Les problèmes externalisés sont plus stables dans le temps relativement aux problèmes internalisés. Des variables pharmacologiques et génétiques contribuent aux différences individuelles : l'administration d’un glucocorticoïde plus puissant du point de vue des effets pharmacologiques et toxicologiques, ainsi que l’homozygotie pour l’haplotype -786C844T du gène NOS3 sont liés à la modulation des scores de problèmes externalisés au fil du temps. Finalement, le niveau de stress familial perçu au diagnostic est positivement corrélé avec le niveau initial de problèmes externalisés chez le patient, tandis que peu après la fin de la période d’induction, le niveau de stress familial est en lien avec le niveau initial de problèmes internalisés. Ces résultats supportent l'idée qu'une approche holistique est essentielle pour espérer mettre en place des interventions préventives efficaces dans cette population. À long terme, ces connaissances pourraient contribuer significativement à l'amélioration de la qualité de vie des patients. Ces travaux enrichissent les connaissances actuelles en soulignant les bénéfices des suivis longitudinaux et multidisciplinaires pour comprendre la dynamique de changement opérant chez les patients. Le décloisonnement des savoirs semble devenir incontournable pour aspirer dépasser le cadre descriptif et atteindre un certain niveau de compréhension des phénomènes observés. Malgré des défis méthodologiques et logistiques évidents, ce type d’approche est non seulement souhaitable pour étudier des processus dynamiques, mais les travaux présentés dans cette thèse indiquent que cela est possible avec les moyens analytiques actuels. / Recent improvements in pediatric cancers treatment have led to marked increases in patient survival rate. However, it has been well documented that pediatric cancer survivors are at elevated risk for various other health problems. With respect specifically to neuropsychological side effects, known predictors (mainly: age at diagnosis, patient gender, exposure to radiation therapy) remain insufficient so far to target, and prevent efficiently, long term sequelae in this population. General objectives related to this thesis were: 1) characterization of individual trajectories of behavioral problems in pediatric patients with acute lymphoblastic leukemia; 2) the identification of genetic, medical and psychosocial determinants of behavioral problems in this population. This research program was based on the following hypotheses: 1) there is an association between the trajectories of individual behavioral problems and a – familial well-being-related psychosocial factors, b – gene polymorphisms involved in the therapeutic responses to methotrexate and glucocorticoids, c – anti-cancer treatments-related variables. 2) Multilevel statistical modeling can be used to characterize patient groups according to their individual behavioral problem trajectories, and can also identify predictive factors. 138 pediatric patients (0-18 years old) who received an acute lymphoblastic leukemia diagnosis between 1993 and 1999 at CHU Ste-Justine participated in this 4 years-long longitudinal study. A standardized and validated instrument, the Child Behavior Checklist, was used to measure behavior problems, as reported by the mother, at diagnosis, and then 1, 2, 3 and 4 years post-diagnosis. Genetic, psychosocial and medical data were also collected during this longitudinal study; these data were exploited in the context of the statistical modeling performed. Results obtained suggest that internalized and externalized behavioral problems have distinct trajectories and have different predictive factors. Internalized problems are affective issues presented by the patient, such as depressive or anxious symptoms. They are highly prevalent post-diagnosis and normalize over the following years, suggestive of temporary yet significant problems. Stress-enhancing medical variables such as a higher relapse risk at diagnosis and medical complications requiring a longer hospitalization slow down the normalization process. Externalized problems need interpersonal contact to occur; violence or aggressiveness manifestations are some examples. Compared to internalized problems, externalized problems are much more stable across time. However, pharmacological and genetic variables do contribute to individual differences in trajectories. In particular, administration of a more potent glucocorticoid (from pharmacological and toxicological perspectives) and being homozygous for NOS3 gene -786C844T haplotype are linked to modulation of externalized problems in time. Finally, the level of perceived family stress at time of diagnosis is positively correlated with initial externalized problems, while shortly after the induction period, the level of familial stress is linked with the initial internalized problems. Together, these results support the idea that a holistic care strategy is essential to develop efficient, preventive interventions in this population, due to the multifactorial nature of these behavioral problems. The knowledge generated in the present studies could contribute to better quality of life for these patients. This thesis also brings a more holistic contribution to our current knowledge of behavioral problems in this population, by highlighting the need for individual, multidisciplinary follow-ups, with particular emphasis on repeated measurements and appropriate statistical analyses. More than ever, knowledge de-compartmentalization appears essential in reaching a certain comprehension level of observed phenomena, rather than adhering to descriptive settings. It indicates that, despite obvious methodological and logistic challenges, this type of research is not only desirable in studying dynamic processes, but is certainly achievable with current analytical tools.

OBJETIVO: Analisar a frequência da submissão do protocolo de pesquisa aos Comitês de Ética em Pesquisa e da aplicação do Termo de Consentimento Livre e Esclarecido do projeto intitulado “Protocolo Brasileiro para o Tratamento de Pacientes com Tumores da Família de Sarcoma de Ewing”. MÉTODOS: Trata-se de estudo transversal retrospectivo. Através das fichas clínicas dos pacientes foi realizada uma análise do trâmite regulatório, bem como, do processo de obtenção do Termo de Consentimento Livre e Esclarecido de 180 pacientes de 16 instituições. RESULTADOS: Dez dos dezesseis centros submeteram o Protocolo ao Comitê de Ética em Pesquisa local. Em relação ao Termo de Consentimento Livre e Esclarecido, 161 dos 180 pacientes e/ou seus representantes legais consentiram e assinaram o Termo aplicado pelo pesquisador. Destes, 123 assinaram o Termo de Consentimento específico do protocolo e 38 assinaram o Termo de Consentimento institucional. Em relação à data da assinatura do consentimento, 141 dos 161 pacientes assinaram o Termo de Consentimento após receberem as informações referentes ao estudo clínico e antes de iniciar o tratamento. CONCLUSÃO: A maioria das instituições participantes apresenta uma estrutura adaptada ao assistencialismo e não estavam familiarizadas com aspectos éticos, legais e regulatórios que envolvem um projeto desta natureza. / OBJECTIVE: To analyze the frequency of submission of the research protocol to the Institutional Research Board and application of Informed Consent Form related to a clinical trial entitled “Treatment of Patients with Ewing Sarcoma Family of Tumors: A study of the Brazilian Cooperative Group”. METHODS: Retrospective cross-sectional study. Through patient records were performed an analysis of the regulatory proceeding and the signing of the Informed Consent Form by 180 patients from 16 institutions. RESULTS: Ten of the sixteen centers submitted the Protocol to the local Institutional Review Board. Regarding the Informed Consent Form, 161 of 180 patients and/or their legal representatives consented and signed the Form applied by the researcher. Of these, 123 signed the consent form specific to the protocol and 38 signed an institutional form. Regarding the date the consent form was signed, 141 of 161 patients signed it after receiving information about the trial and before starting treatment. CONCLUSION: Most of the participating institutions had a structure adapted to welfare and were not familiar with the ethical, legal and regulatory systems involved in a project like this.

This work aims to propose a recommendation model of prescription items for Pediatric Oncology based on data extraction from Electronic Patient Record. These data are used as indexed cases to aid providers of medical service based on the similarity of prescriptions, according to the patient's history. From the viewpoint of aid medical education, the modeling objective support the student or health professional in understanding the decision-making process during the prescription items oncological medical treatment, for example drugs, laboratory exams or images exams, diet, gases, care, chemotherapy, radiotherapy. To develop the model, was used the approach of Case Based Reasoning (CBR), through the representation of prescription medical base-case, indexed by their treatment items. During the recovery phase of cases, we used the tool. Data Mining by applying the model of association rule, together with the algorithm "apriori" for obtaining the similarity between cases. To update the case base, a procedure database for performing the process of Extraction, Transformation and Load of the database was developed. The developed model was applied in the database of the Electronic Patient Record of the Santa Casa de Misericordia de Maceio, based on Hospital Management Systems “MV Sistemas”, deployed in the unit since 2005. For the presentation of results, was used the Oracle Data Miner tool, which allowed access to the database and analysis of selected cases by identifying key words contained in the evolution of the clinical condition of the patient. The application of the experiments validate the occurrence of allowed combined application of items of treatment according to the keywords, which can be used as input in the process of making medical decision and tutoring. / Este trabalho tem como objetivo propor um Modelo de Recomendação de itens de prescrição para Oncologia Pediátrica baseado na extração de dados do Prontuário Eletrônico do Paciente. Esses dados são utilizados como casos indexados, para auxiliar os prestadores de serviço médico baseados na similaridade de prescrições, de acordo com o histórico do paciente. Do ponto de vista do apoio a educação médica, a modelagem objetiva apoiar o estudante ou o profissional de saúde no entendimento do processo de tomada de decisão durante a fase de prescrição de itens de tratamento médico oncológico, como, por exemplo: medicamentos, exames de laboratório ou de imagens, dieta, gases, cuidados, quimioterapia, radioterapia. Para o desenvolvimento do modelo, utilizou-se a abordagem de Raciocínio Baseado em Casos (RBC), através da representação de uma base de casos de prescrição médica, indexada por seus itens de tratamento. Durante a fase de recuperação de casos, utilizou-se a ferramenta de Mineração de Dados aplicando-se o modelo de regra de associação, em conjunto com o algoritmo “apriori” visando a obtenção da similaridade entre casos. Para a atualização da base de casos, foi desenvolvido um procedimento de banco de dados para execução do processo de Extração, Transformação e Carga da base de dados. O modelo desenvolvido foi aplicado na base de dados do Prontuário Eletrônico do Paciente da Santa Casa de Misericórdia de Maceió, baseado no sistema de gestão hospitalar MV Sistemas, implantado na unidade desde 2005. Para a apresentação dos resultados, utilizou-se a ferramenta Oracle Data Miner, que possibilitou o acesso ao banco de dados e a análise dos casos selecionados pela identificação de palavras chaves contidas na evolução do estado clínico do paciente. A aplicação dos experimentos permitiu validar a ocorrência de aplicação conjunta de itens de tratamento de acordo com as palavras chaves, o que pode ser utilizado como elemento para o processo de tomada de decisão médica e tutoria.

OBJETIVO: Analisar a frequência da submissão do protocolo de pesquisa aos Comitês de Ética em Pesquisa e da aplicação do Termo de Consentimento Livre e Esclarecido do projeto intitulado “Protocolo Brasileiro para o Tratamento de Pacientes com Tumores da Família de Sarcoma de Ewing”. MÉTODOS: Trata-se de estudo transversal retrospectivo. Através das fichas clínicas dos pacientes foi realizada uma análise do trâmite regulatório, bem como, do processo de obtenção do Termo de Consentimento Livre e Esclarecido de 180 pacientes de 16 instituições. RESULTADOS: Dez dos dezesseis centros submeteram o Protocolo ao Comitê de Ética em Pesquisa local. Em relação ao Termo de Consentimento Livre e Esclarecido, 161 dos 180 pacientes e/ou seus representantes legais consentiram e assinaram o Termo aplicado pelo pesquisador. Destes, 123 assinaram o Termo de Consentimento específico do protocolo e 38 assinaram o Termo de Consentimento institucional. Em relação à data da assinatura do consentimento, 141 dos 161 pacientes assinaram o Termo de Consentimento após receberem as informações referentes ao estudo clínico e antes de iniciar o tratamento. CONCLUSÃO: A maioria das instituições participantes apresenta uma estrutura adaptada ao assistencialismo e não estavam familiarizadas com aspectos éticos, legais e regulatórios que envolvem um projeto desta natureza. / OBJECTIVE: To analyze the frequency of submission of the research protocol to the Institutional Research Board and application of Informed Consent Form related to a clinical trial entitled “Treatment of Patients with Ewing Sarcoma Family of Tumors: A study of the Brazilian Cooperative Group”. METHODS: Retrospective cross-sectional study. Through patient records were performed an analysis of the regulatory proceeding and the signing of the Informed Consent Form by 180 patients from 16 institutions. RESULTS: Ten of the sixteen centers submitted the Protocol to the local Institutional Review Board. Regarding the Informed Consent Form, 161 of 180 patients and/or their legal representatives consented and signed the Form applied by the researcher. Of these, 123 signed the consent form specific to the protocol and 38 signed an institutional form. Regarding the date the consent form was signed, 141 of 161 patients signed it after receiving information about the trial and before starting treatment. CONCLUSION: Most of the participating institutions had a structure adapted to welfare and were not familiar with the ethical, legal and regulatory systems involved in a project like this.

OBJETIVO: Analisar a frequência da submissão do protocolo de pesquisa aos Comitês de Ética em Pesquisa e da aplicação do Termo de Consentimento Livre e Esclarecido do projeto intitulado “Protocolo Brasileiro para o Tratamento de Pacientes com Tumores da Família de Sarcoma de Ewing”. MÉTODOS: Trata-se de estudo transversal retrospectivo. Através das fichas clínicas dos pacientes foi realizada uma análise do trâmite regulatório, bem como, do processo de obtenção do Termo de Consentimento Livre e Esclarecido de 180 pacientes de 16 instituições. RESULTADOS: Dez dos dezesseis centros submeteram o Protocolo ao Comitê de Ética em Pesquisa local. Em relação ao Termo de Consentimento Livre e Esclarecido, 161 dos 180 pacientes e/ou seus representantes legais consentiram e assinaram o Termo aplicado pelo pesquisador. Destes, 123 assinaram o Termo de Consentimento específico do protocolo e 38 assinaram o Termo de Consentimento institucional. Em relação à data da assinatura do consentimento, 141 dos 161 pacientes assinaram o Termo de Consentimento após receberem as informações referentes ao estudo clínico e antes de iniciar o tratamento. CONCLUSÃO: A maioria das instituições participantes apresenta uma estrutura adaptada ao assistencialismo e não estavam familiarizadas com aspectos éticos, legais e regulatórios que envolvem um projeto desta natureza. / OBJECTIVE: To analyze the frequency of submission of the research protocol to the Institutional Research Board and application of Informed Consent Form related to a clinical trial entitled “Treatment of Patients with Ewing Sarcoma Family of Tumors: A study of the Brazilian Cooperative Group”. METHODS: Retrospective cross-sectional study. Through patient records were performed an analysis of the regulatory proceeding and the signing of the Informed Consent Form by 180 patients from 16 institutions. RESULTS: Ten of the sixteen centers submitted the Protocol to the local Institutional Review Board. Regarding the Informed Consent Form, 161 of 180 patients and/or their legal representatives consented and signed the Form applied by the researcher. Of these, 123 signed the consent form specific to the protocol and 38 signed an institutional form. Regarding the date the consent form was signed, 141 of 161 patients signed it after receiving information about the trial and before starting treatment. CONCLUSION: Most of the participating institutions had a structure adapted to welfare and were not familiar with the ethical, legal and regulatory systems involved in a project like this.

Thèse présentée à l’Université de Montréal, Faculté de médecine, École de kinésiologie et des sciences de l’activité physique et à l’Université Paris Nanterre, Département de Psychologie dans le cadre de la cotutelle internationale de thèse entre les deux établissements / La promotion de l’activité physique en oncologie pédiatrique est un aspect essentiel des soins pour le patient. En effet, l'activité physique améliore significativement la capacité fonctionnelle, le système musculosquelettique, le système immunitaire, le système cardiovasculaire, ainsi que la santé psychologique des patients atteints. La place de l’activité physique en oncologie pédiatrique est au coeur de cette thèse qui s’est inscrite dans une démarche de cotutelle internationale de thèse répondant à plusieurs questions que se posent les patients atteints de cancer pédiatrique et les survivants de cancer pédiatrique, notamment ceux de la leucémie lymphoblastique aiguë (LLA). Entre autres, « comment le cancer et ses traitements affectent ma santé à court, moyen et long terme ? » Et « comment l’activité physique peut-elle me venir en aide ? » L’objectif principal est de mieux comprendre le déconditionnement physique et les mécanismes potentiels qui en découle chez les survivants de la LLA, tandis que le second objectif est d’explorer l’impact du diagnostic du cancer et d’un programme d’activité physique sur le comportement en activité physique d’enfants atteints de cancer. Pour répondre à ces questions, cette thèse s’intéresse aux paramètres tant physiologiques que psychologiques. Ainsi, les travaux réalisés au sein de cette thèse sont au nombre de cinq. Ils viennent préciser les effets des traitements contre le cancer sur la santé physique et psychologique des patients atteints ou ayant été atteints de cancer pédiatrique. La première étude de cette thèse vise à explorer les différences physiologiques entre les survivants de la LLA et la population canadienne en santé. Pour ces deux populations, les données en activité physique, ainsi que les données de condition cardiorespiratoire ont été comparées afin de fournir une meilleure compréhension des défis auxquels font face les survivants de la LLA au quotidien. La seconde étude vient apporter des réponses au déconditionnement physique des survivants de la LLA. Elle constitue la première étude au monde d’association génétique entre la condition cardiorespiratoire des survivants de la LLA et les gènes de l’aptitude à l’entraînement physique (trainability genes). Son impact auprès des cliniciens, des survivants, des patients et de leur famille est significatif puisqu’elle pourrait permettre, dans un futur proche, d’offrir un meilleur suivi aux patients atteints de la LLA en adéquation avec leur profil génétique et leur condition cardiorespiratoire. La troisième étude de cette thèse explore les effets néfastes à long terme des traitements contre le cancer sur les paramètres électrophysiologiques. Cette étude vise à mieux comprendre le déconditionnement physique des survivants de la LLA, notamment en ce qui a trait à leur système nerveux autonome qui subit d’importants changements. Ces paramètres, étroitement liés au système nerveux sympathique et parasympathique, sont d’une importance capitale dans la pratique sécuritaire d’une activité physique. Finalement, les deux dernières études sont étroitement liées et font suite au constat alarmant observé chez les survivants de la LLA. En ce sens, ces études découlent aussi de l’intérêt de proposer un programme d’activité physique en oncologie pédiatrique. Ces travaux viennent s’intéresser aux mesures de la théorie du comportement planifié, de l’estime de soi et de la condition physique perçue d’enfants atteints de cancer qui sont en cours de traitements. Le quatrième article de cette thèse documente les effets du diagnostic de cancer sur les paramètres psychologiques cités précédemment et montre l’importance de fournir aux enfants atteints de cancer un support en activité physique dès leur diagnostic. Le cinquième article peut être considéré comme une suite au quatrième article puisqu’il vient proposer un programme d’activité physique supervisé. Cette dernière étude montre les effets positifs de six semaines d’activité physique sur les paramètres physiologiques et psychologiques. Elle montre l’importance du support familial pour améliorer le comportement lié à l’activité physique des enfants et alerte les cliniciens sur le besoin réel et pressant de fournir aux enfants atteints de cancer un support en activité physique dès leur diagnostic. / Physical activity promotion in pediatric oncology is an essential aspect of patient care. Indeed, physical activity significantly improves the functional capacity, musculoskeletal system, inflammatory system, immune system, cardiovascular system, as well as the psychological health of patients. Physical activity in pediatric oncology is central to this thesis, which was part of an international joint supervision approach, answering several questions posed by children with cancer and childhood cancer survivors, in particular those with acute lymphoblastic leukemia (ALL). Among other things, "How does cancer and its treatments affect my health in the short, medium and long term?" And "How can physical activity help me?". The first aim is to better understand the physical deconditioning of childhood ALL survivors and the potential mechanisms that result from it. The second aim is to explore the impact of cancer diagnosis, as well as a supervised physical activity program on children's physical activity behavior during treatments. To answer these questions, this thesis focuses on physiological, epidemiological, genetic, electrophysiological and psychological parameters. There are five works carried out within this thesis. They specify the effects of cancer treatments on the physical and psychological health of children with cancer and childhood ALL survivors. The first study in this thesis aims to explore the physiological differences between childhood cancer survivors (i.e., ALL survivors) and the healthy Canadian population. For these two populations, physical activity data, as well as cardiorespiratory fitness data, were compared in order to provide a better understanding of the daily challenges faced by childhood ALL survivors. The second study in this thesis provides answers to childhood ALL survivors’ physical deconditioning. This study is the first in the exercise and oncology field to explore the genetic association between childhood ALL survivors’ cardiorespiratory fitness and their trainability genes. These findings have an important impact on clinicians, patients, survivors and their families since they could allow, in the near future, to offer better follow-up to ALL patients, in line with their genetic profile and their cardiorespiratory fitness. The third study in this thesis explores the harmful long-term effects of cancer treatments on the electrophysiological parameters of ALL survivors. This study aims to better understand the physical deconditioning of these survivors, especially in regard to their autonomic nervous system which undergoes significant changes. These parameters, closely linked to the sympathetic and parasympathetic nervous system, are of paramount importance in the safe practice of physical activity. Finally, the last two studies are closely linked and follow up on the alarming observation made in ALL survivors. In this sense, these studies also stem from the interest of proposing a physical activity program in pediatric oncology. This work focuses on measures of the theory of planned behavior, self-esteem and perceived physical condition of children with cancer who are undergoing treatment. The fourth article of this thesis documents the effects of cancer diagnosis on the psychological parameters mentioned above and shows the importance of providing children with cancer with physical activity support as soon as they are diagnosed. The fifth article can be considered as a follow-up to the fourth article since it proposes a supervised physical activity program in pediatric oncology. This latest study shows the positive effects of six weeks of physical activity on the physiological and psychological parameters. It shows the importance of family support to improve behavior linked to physical activity in children and alerts clinicians to the real and pressing need to provide children with cancer with support in physical activity as soon as they are diagnosed.

El desarrollo físico y emocional de las personas empieza en la etapa de la niñez, es por ello, que es necesario enfatizar en la salud física y psicológica de los niños. El Instituto Oncológico Pediátrico se da como respuesta a la necesidad de salud pública que se ve en el país. No obstante, es necesario diferenciar el tratamiento que se da en un niño y un adulto para obtener mejores resultados. El presente proyecto mediante una simbiosis entre la arquitectura y el uso del énfasis arquitectónico “neuroarquitectura”, genera espacios intermedios donde los pacientes puedan recuperarse de forma psicológica y física. Es por ello que el proyecto toma como objetivo principal la importancia de que los niños tengan acceso a establecimientos de salud con espacios eficientes que mejoren la autoestima de los niños. Esto se ve a través de la iluminación y ventilación natural, ambientes para la integración y el encuentro entre los niños y familiares. Sin perder la funcionalidad de un hospital debido a su alto nivel de complejidad. / The physical and emotional development of people begins at the childhood stage, which is why it is necessary to emphasize the physical and psychological health of children. The Pediatric Oncology Institute is created in response to the need for public health seen in the country. However, it is necessary to differentiate the treatment given to a child or an adult to obtain better results. The present project, through a symbiosis between architecture and the use of the architectural emphasis “neuroarchitecture”, generates intermediate spaces where patients can recover psychologically and physically, Therefore the main project’s objective is the importance of children having access to health facilities with efficient spaces that improve children's self-esteem. This is achieved through natural lighting and ventilation, meeting areas for children and their families without losing the functionality of a hospital due to its high level of complexity. / Tesis

La recherche est imbriquée dans les soins cliniques en oncologie, de sorte que la dualité de rôles (clinicien, investigateur) est une réalité connue des oncologues. Vu l'importance de la génomique pour guider les soins en oncologie pédiatrique, la plupart des patients sont enrôlés dans des études génomiques au Québec. En pratique, l'oncologue, par sa présence aux réunions d'oncogénomique, participe avec les chercheurs à l'interprétation des résultats génétiques ainsi qu'aux décisions de divulgation au patient. Ce projet vise à identifier et caractériser les enjeux éthico-légaux soulevés par la dualité de rôles de l'oncologue durant ce partage de résultats génétiques en amont du patient. Un questionnaire incluant six vignettes narratives a été diffusé électroniquement à tous les oncologues pédiatres du Québec. Des entrevues semi-dirigées ont été effectuées avec un sous-groupe de participants. Vingt-huit oncologues ont complété le questionnaire et cinq oncologues ont participés aux entrevues. Les niveaux de confort des oncologues étaient influencés par le type de résultat génétique, par le contenu discuté lors du consentement et par le rôle de l'oncologue envers le patient (oncologue traitant ou non). Le fait d'être informé d'un résultat génétique de recherche suffisait pour déclencher un sentiment de responsabilité par rapport à celui-ci. La dualité de rôles est incontournable et donne à l’oncologue un accès privilégié à l'information génétique, au-delà de ce à quoi aura accès le patient. Les responsabilités et les devoirs de l’oncologue dans le cadre de la relation thérapeutique sont au centre des enjeux éthiques et légaux soulevés par la dualité de rôles. / Research is heavily integrated in oncology care, with oncologists well acquainted with the concept of duality of roles (doctor, researcher). Given the importance of genomics in pediatric oncology, most patients are offered genomic sequencing via research initiatives in Quebec. Practical experience reveals that oncologists, by attending molecular tumour board meetings, participate with the research team in the interpretation of genetic research results and decisions regarding disclosure to patients. This project aims to identify and characterise the ethical and legal issues related to the duality of roles of oncologists during this process of genetic information sharing, prior to informing the patient. A questionnaire including six narrative case vignettes was electronically distributed to all pediatric oncologists in Quebec. A semi-structured interview was then conducted with a sub-group of participants. Twenty-eight oncologists completed the questionnaire and five oncologists participated in the interviews. Oncologists' comfort levels were influenced by the type of genetic result, by the content of prior consent discussions and by their specific role regarding the patient (treating oncologist or not). The state of becoming aware of a result was sufficient to trigger a feeling of responsibility regarding that genetic research result. Duality of roles is inevitable and provides the oncologist with privileged access to genetic information, above what will be accessible to the patient. Responsibilities and duties of the oncologist in the setting of a therapeutic relationship are central to the ethical and legal issues raised by the duality of roles.

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