Introdução: O câncer do esôfago é uma das neoplasias do aparelho digestivo com maior gravidade e que apresenta grande morbimortalidade, mesmo quando o diagnóstico é precoce. A maioria dos pacientes é diagnosticado nos estágios avançados. O tratamento depende do estadiamento da neoplasia que avalia a profundidade de invasão do tumor (T), a disseminação linfonodal (N) e a presença de metástases a distância (M) e segue as orientações da União Internacional Contra o Câncer (UICC). Nas últimas décadas o estadiamento era realizado convencionalmente pela tomografia computadorizada (TC) e atualmente com a utilização de equipamentos que avaliam o metabolismo glicolítico do tumor como o 18F-FDG-PET e o PET-CT. Este estudo teve como Objetivo avaliar a relação entre a tomografia computadorizada e os métodos metabólicos como o 18F-FDG-PET e PET-CT, no estadiamento e tratamento do Adenocarcinoma e do Carcinoma Espinocelular (CEC) do esôfago. Método: Foram avaliados 331 pacientes com diagnóstico de Adenocarcinoma e CEC do esôfago entre 2008 e 2014. Destes, 55 pacientes (16,6%) apresentaram Adenocarcinoma e 276 (83,4%) apresentaram CEC. A idade variou de 38 a 92 anos, com média de 62,9 (+/- 9,8) anos. Inicialmente foram submetidos ao estadiamento com TC e proposta de conduta cirúrgica curativa ou tratamento paliativo. Posteriormente foram avaliados com a inclusão do 18F-FDG-PET ou do PET-CT e foi definida a conduta final. Resultados: A proporção de linfonodos positivos (N+) na tomografia foi de 71%, enquanto que nos métodos metabólicos foi de 70,1% (p=0,834), contudo, com pequena concordância (Kappa=0,339). A proporção de metástases (M1) encontradas na TC foi de 44,1% e no PET-CT 47,1%. Para metástases, o teste Kappa mostrou que os dois métodos apresentam uma concordância regular (0,452), apresentando mudanças de estadiamento em 36,5% dos indivíduos, sendo 19,3% com sobre estadiamento e 17,2% com subestadiamento. Entretanto, apenas 63 pacientes (19%) apresentaram mudança de conduta final e esta foi maior nos pacientes com sobre estadiamento (67,2%) (p < 0,005). Nos pacientes com Adenocarcinoma, observou-se um número maior de subestadiamento (32,7%), comparado àqueles com CEC (15,4%) (p < 0,0001), entretanto, sem apresentar diferença estatisticamente significativa quando avaliada a mudança de conduta. Avaliando individualmente os 140 pacientes estadiados com 18F-FDG-PET, 52,9% apresentaram linfonodos positivos (N+), valor semelhante à tomografia (p=0,053), entretanto com concordância pequena, cerca de 32,9% destes com metástases (M1) (p=0,749) e com concordância regular entre os métodos. Após o estadiamento, ocorreu uma mudança de conduta de 23,6% quando avaliado por equipe multidisciplinar. Com o uso do PET-CT, a proporção de tumores T4 foi de 27,2% (p=0,071), porém, com concordância boa com a tomografia (Kappa=0,616). A proporção de linfonodos positivos (N+) foi de 82,7%, com pequena concordância com a tomografia (Kappa=0,392). A proporção de metástases (M1) no PET-CT foi de 57,6%, com concordância regular (Kappa=0,465). Apresentaram mudança de estadiamento 34% dos indivíduos, sendo 19,3% com sobre estadiamento e 14,7% com subestadiamento. Entretanto, dos 191 pacientes, apenas 30 (15,7%) apresentaram mudança de conduta final, sendo que 67,6% ocorreu nos casos com sobre estadiamento, quando comparada aos casos com subestadiamento (17,9%) (p < 0,005). Pacientes com Adenocarcinoma apresentaram um número maior de subestadiamento (30%), comparado àqueles com CEC (11,8%), (p < 0,0001), entretanto, sem apresentar diferença estatisticamente significativa. A sobrevida global, quando avaliados com PET-CT, foi em torno de 30% após 30 meses, sendo semelhante tanto no grupo de pacientes em que houve mudança de conduta quanto no grupo em que esta mudança de conduta não ocorreu. Conclusão: Conclui-se, portanto, que no estadiamento tomográfico com 18F-FDG-PET e com PET-CT foi identificado um número expressivo de pacientes em estágios avançados, entretanto estes achados muitas vezes diferem entre si. A mudança de conduta ocorre em número expressivo de pacientes e geralmente nos casos em que ocorre sobre estadiamento. Embora o Adenocarcinoma apresente um número maior de casos de subestadiamento que o CEC, esta mudança de estadiamento não se reflete na mudança de conduta quando comparados. Torna-se importante, portanto, a avaliação multiprofissional em serviço de excelência no momento de decisão sobre a melhor terapêutica. Por fim, observamos a mesma curva de sobrevida entre aqueles pacientes em que há certeza da conduta a ser tomada e aqueles em que a conduta foi mudada após o uso do PET-CT, o que corrobora a necessidade da utilização em conjunto desses dois métodos / Introduction: Esophagus cancer is one of the most serious neoplasms of the digestive tract that presents great morbidity and mortality even in early diagnosis. Most patients are diagnosed in advanced stages. Treatment depends on tumor staging, which evaluates the depth of tumor invasion (T), lymph node spread (N) and the presence of distant metastases (M) and follow the guidelines of Union for International Cancer Control (UICC). In the last decades, staging was performed conventionally by computed tomography (CT) and currently with the use of equipments that evaluates tumor glycolytic metabolism such as 18F-FDG-PET and PET-CT. This study has as main Objective to evaluate the relationship between computed tomography and metabolic methods such as 18F-FDG-PET and PET-CT in the staging and treatment of Adenocarcinoma and Spinocellular Carcinoma (SCC) of the esophagus. Method: A total of 331 patients diagnosed with adenocarcinoma and esophageal SCC were evaluated between 2008 and 2014. 55 of these patients (16.6%) had adenocarcinoma and 276 (83.4%) had CPB, ranging from 38 to 92 years, mean age of 62.9 (+/- 9.8) years. Initially they underwent staging with CT and it was proposed a curative surgical management or palliative treatment. Lately they were evaluated with the inclusion of 18F-FDG-PET or PET-CT and then the final management was defined. Results: The proportion of positive lymph nodes (N +) on the CT scan was 71%, whereas in the metabolic methods it was 70.1% (p=0.834), however, with a fair agreement (Kappa=0.339). The proportion of metastases (M1) found in CT was 44.1% and in PET-CT, 47.1%. For metastases, the Kappa test showed that the two methods presented a moderate agreement (0.452), presenting staging changes in 36.5% of subjects, being 19.3% with upstaging and 17.2% with downstaging. However, only 63 patients (19%) showed changes in the final management and this was higher in upstaging patients (67,2%) (p < 0,005). In patients with Adenocarcinoma, a greater number of downstaging was observed (32.7%), compared to those with CPB (15.4%) (p < 0.0001), however, without any statistically significant difference when the change of management was evaluated. Evaluating individually the 140 patients staged with 18F-FDG-PET, 52.9% presented positive lymph nodes (N +), data similar to tomography (p = 0.053), however with fair agreement, about 32.9% of these had metastases (M1) (P=0.749) and with moderate agreement between the methods. After the staging, a conduct change of 23.6% occurred when evaluated by a multidisciplinary team. With the use of PET-CT, the proportion of T4 tumors was 27.2% (p = 0.071), but with good agreement with tomography (Kappa=0.616). The proportion of positive lymph nodes (N+) was 82.7%, with fair agreement with the tomography (Kappa=0.392). The proportion of metastases (M1) in PET-CT was 57.6%, with moderate agreement (Kappa=0.465). 34% of the individuals presented staging change, 19.3% with upstaging and 14.7% with downstaging. However, only 30 (15.7%) out of 191 presented a final change of behavior, 67.6% of which occurred in cases with upstaging when compared to cases with downstaging (17.9%) (p < 0.005). Patients with adenocarcinoma had a greater number of downstaging (30%) compared to those with CPB (11.8%), (p < 0.0001), however, with no statistically significant difference. Overall survival when staged with PET-CT was around 30% after 30 months, being similar both in the group of patients where there was change of management and in the group where this change of management did not occur. Conclusion: It was concluded that in the tomographic staging with 18F-FDG-PET and with PET-CT an expressive number of patients in advanced stages was identified, however these findings often differ from each other. The change in management occurs in an expressive number of patients, and usually in cases where upstaging occurs. Although Adenocarcinoma presents a greater number of cases of downstaging than CPB, this change in staging is not reflected in the change of management when both are compared. It is important, therefore, the multiprofessional evaluation in service of excellence when deciding on the best therapeutics. Finally, we observed the same survival curve between those patients in which there is certainty of the management to be taken and those in which the management was changed after the use of PET-CT, which corroborates with the need to use these two methods together

La maladie d’Alzheimer (AD) est la principale cause de démence neurodégénérative, caractérisée à 95% par des formes tardives (LOAD) qui présentent des troubles mnésiques et progressent lentement. Cependant, environ 5% des patients atteints d’AD présentent une forme précoce de la maladie (EOAD) débutant avant 65 ans. Bien que le substratum lésionnel soit identique à la LOAD, l’EOAD est caractérisée par une plus grande sévérité des dépôts de plaques amyloïdes, des enchevêtrements neurofibrillaires et de l’atrophie cérébrale. De plus, l’EOAD est plus hétérogène que la LOAD, car même si la majorité des troubles sont mnésiques il existe une proportion importante de formes atypiques affectées par des troubles du langage, visuospatiaux ou exécutifs. Bien que de nombreuses études en imagerie TEP 18F-FDG aient permis de caractériser métaboliquement l’EOAD par rapport à la LOAD ou à un groupe de contrôles sains, très peu différentiaient pas les formes typiques (mnésiques) des formes atypiques. Dans ce travail de thèse, nous avons examiné les données d’imagerie TEP 18F-FDG, complémentées par l’IRM structurelle, afin d’améliorer la caractérisation et la compréhension des formes typiques et atypiques d’EOAD. Suite à un premier travail d’harmonisation des reconstructions TEP 18F-FDG entre deux machines GE et Siemens ayant toutes deux servies à l’acquisition des données patients, notre second objectif a été d’étudier à l’inclusion sur le cerveau entier les patterns hypométaboliques caractéristiques des différentes formes d’EOAD et leurs corrélations potentielles avec la performance neuropsychologique. Cette étude a montré que chaque forme clinique d’EOAD était caractérisée par des patterns hypométaboliques spécifiques fortement corrélés aux symptômes cliniques et aux scores neuropsychologiques du domaine cognitif associé. Par la suite, nous nous sommes intéressés à la progression sur 3 ans de l’hypométabolisme sur la surface corticale en fonction des formes typiques ou atypiques d’EOAD. Bien que des patterns similaires d’évolution de l’hypométabolisme entre les formes typiques et atypiques aient été observés au niveau du cortex pariétal, seules les formes atypiques ont présenté une réduction du métabolisme bilatérale plus importante au niveau du cortex orbito-frontal latéral associée à des déclins cognitifs plus sévères. Temporellement, les résultats suggèrent que l’hypométabolisme chez les formes typiques progresserait selon un axe antérieur-vers-postérieur en cohérence avec les stades de Braak et Braak, alors que l’hypométabolisme chez les formes atypiques progresserait selon un axe postérieur-vers-antérieur. Pris ensemble, ces résultats confortent l’hypothèse d’une distribution différente de la pathologie tau en termes de charge et d’évolution temporelle entre ces deux formes d’EOAD. Notre dernier objectif a été de déterminer les capacités discriminatives des données TEP 18F-FDG, seules ou combinées aux données de l’IRM structurelle, afin de classifier de manière automatique et supervisée des patients atteints d’EOAD en forme typique ou atypique. Nous avons mis en application des algorithmes de machine learning combinés à des méthodes de validation croisée afin d’évaluer les influences de diverses composantes sur les performances de classification. Des précisions équilibrées maximales égales à 80,8% en imagerie monomodale TEP 18F-FDG et 92,4% en imagerie multimodale TEP 18F-FDG/IRM T1 ont été obtenues, validant ainsi la TEP 18F-FDG comme un biomarqueur sensible de l’EOAD et soulignant l’apport incontestable de la multimodalité. En conclusion, nos travaux ont permis une meilleure caractérisation et compréhension des formes cliniques d’EOAD, ouvrant la voie à un management personnalisé du patient et des traitements plus efficaces pour ces formes distinctes. / Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia, characterized at 95% by late-onset forms (LOAD) which present episodic memory impairments and progress slowly. However, 5% of AD patients have an early-onset form (EOAD) of the disease whose onset begins before 65. Although the lesion substratum is similar between EOAD and LOAD, EOAD has more severe neuritic plaque deposits, neurofibrillary tangles and brain atrophy. Moreover, EOAD is more heterogeneous than LOAD, because even if most of the impairments are about episodic memory there is a high proportion of atypical forms impaired in language, visuospatial or executive functions. Although many 18F-FDG PET studies allowed to metabolically characterize EOAD compared to LOAD or healthy controls group, very few differentiated typical from atypical forms. In this thesis, we examined 18F-FDG PET data, complemented by structural MRI, in order to improve characterization and comprehension of typical and atypical forms of EOAD. Following a first harmonization work between 18F-FDG PET reconstructions from both GE and Siemens scanners used for the acquisition of patient data, our second aim was to study at baseline on the whole brain hypometabolic patterns characterizing the clinical forms of EOAD and their correlations with neuropsychological performance. This work showed that each clinical form of EOAD was characterized by specific hypometabolic patterns highly correlated with clinical symptoms and neuropsychological performance of the associated cognitive domain. Then, we focused on the 3-year hypometabolism progression on the cortical surface according typical or atypical forms of EOAD. Although similar patterns of hypometabolism evolution between typical and atypical forms were observed in parietal cortices, atypical only showed a more severe reduction of metabolism in lateral orbitofrontal cortices associated with more severe cognitive declines. Temporally, the results suggest that hypometabolism in typical forms would progress according to an anterior-to-posterior axis coherently with Braak and Braak stages, whereas in atypical forms hypometabolism would progress according a posterior-to-anterior axis. Taken together, results consolidate the hypothesis of a different tau distribution in terms of burden and temporal evolution between both forms of EOAD. Our last goal was to determine the discriminative power of 18F-FDG PET data, alone or combined to structural MRI data, in order to automatically classify in a supervised manner EOAD patients into typical or atypical form. We applied machine learning algorithms combined to cross-validation methods to assess influence of some components on classification performances. Maximum balanced accuracies equal to 80.8% in monomodal 18F-FDG PET and 92.4% in multimodal 18F-FDG PET/T1 MRI were obtained, validating 18F-FDG PET as a sensible biomarker of EOAD and highlighting the incontestable contribution of multimodality. In conclusion, our works allowed a better characterization and comprehension of clinical forms of EOAD, paving the way to personalized patient management and more effective treatments for these distinct clinical forms.