122 research outputs found
Immune contexture monitoring in solid tumors focusing on Head and Neck Cancer
Forti evidenze dimostrano una stretta interazione tra il sistema immunitario e lo sviluppo biologico e la progressione clinica dei tumori solidi. L'effetto che il microambiente immunitario del tumore può avere sul comportamento clinico della malattia è indicato come "immunecontexture". Nonostante ciò, l'attuale gestione clinica dei pazienti affetti da cancro non tiene conto di alcuna caratteristica immunologica né per la stadiazione né per le scelte terapeutiche. Il tumore della testa e del collo (HNSCC) rappresenta il 7° tumore più comune al mondo ed è caratterizzato da una prognosi relativamente sfavorevole e dall'effetto negativo dei trattamenti sulla qualità della vita dei pazienti. Oltre alla chirurgia e alla radioterapia, sono disponibili pochi trattamenti sistemici, rappresentati principalmente dalla chemioterapia a base di platino-derivati o dal cetuximab. L'immunoterapia è una nuova strategia terapeutica ancora limitata al setting palliativo (malattia ricorrente non resecabile o metastatica). La ricerca di nuovi biomarcatori o possibili nuovi meccanismi target è molto rilevante quindi nel contesto clinico dell'HNSCC. In questa tesi ci si concentrerà sullo studio di tre possibili popolazioni immunitarie pro-tumorali studiate nell'HNSCC: i neutrofili tumore-associati (TAN), le cellule B intratumorali con fenotipo immunosoppressivo e i T-reg CD8+. Particolare attenzione è data all'applicazione di moderne tecniche biostatistiche e bioinformatiche per riassumere informazioni complesse derivate da variabili cliniche e immunologiche multiparametriche e per validare risultati derivati in situ, attraverso dati di espressione genica derivati da dataset pubblici. Infine, la seconda parte della tesi prenderà in considerazione progetti di ricerca clinica rilevanti, volti a migliorare l'oncologia di precisione nell'HNSCC, sviluppando modelli predittivi di sopravvivenza, confrontando procedure oncologiche alternative, validando nuovi classificatori o testando l'uso di nuovi protocolli clinici come l'uso dell'immunonutrizione.Strong evidences demonstrate a close interplay between the immune system and the biological development and clinical progression of solid tumors. The effect that the tumor immune microenvironment can have on the clinical behavior of the disease is referred as the immuno contexture. Nevertheless, the current clinical management of patients affected by cancer does not take into account any immunological features either for the staging or for the treatment choices. Head and Neck Cancer (HNSCC) represents the 7th most common cancer worldwide and it is characterized by a relatively poor prognosis and detrimental effect of treatments on the quality of life of patients. Beyond surgery and radiotherapy, few systemic treatments are available, mainly represented by platinum-based chemotherapy or cetuximab. Immunotherapy is a new therapeutical strategy still limited to the palliative setting (recurrent not resectable or metastatic disease). The search for new biomarkers or possible new targetable mechanisms is meaningful especially in the clinical setting of HNSCC. In this thesis a focus will be given on the study of three possible pro-tumoral immune populations studied in HNSCC: the tumor associated neutrophils (TAN), intratumoral B-cells with a immunosuppressive phenotype and the CD8+ T-regs. Biostatistical and bioinformatical techniques are applied to summarize complex information derived from multiparametric clinical and immunological variables and to validate in-situ derived findings through gene expression data of public available datasets. Lastly, the second part of the thesis will take into account relevant clinical research projects, aimed at improving the precision oncology in HNSCC developing survival prediction models, comparing alternative oncological procedures, validating new classifiers or testing the use of novel clinical protocols as the use of immunnutrition
Development and external validation of dual online tools for prognostic assessment in elderly patients with high-grade glioma: a comprehensive study using SEER and Chinese cohorts
BackgroundElderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making.MethodsWe scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram’s predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored.ResultsUsing multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts.ConclusionOur investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies
Cohort-based T-SSIM Visual Computing for Radiation Therapy Prediction and Exploration
We describe a visual computing approach to radiation therapy (RT) planning,
based on spatial similarity within a patient cohort. In radiotherapy for head
and neck cancer treatment, dosage to organs at risk surrounding a tumor is a
large cause of treatment toxicity. Along with the availability of patient
repositories, this situation has lead to clinician interest in understanding
and predicting RT outcomes based on previously treated similar patients. To
enable this type of analysis, we introduce a novel topology-based spatial
similarity measure, T-SSIM, and a predictive algorithm based on this similarity
measure. We couple the algorithm with a visual steering interface that
intertwines visual encodings for the spatial data and statistical results,
including a novel parallel-marker encoding that is spatially aware. We report
quantitative results on a cohort of 165 patients, as well as a qualitative
evaluation with domain experts in radiation oncology, data management,
biostatistics, and medical imaging, who are collaborating remotely.Comment: IEEE VIS (SciVis) 201
Roses Have Thorns: Understanding the Downside of Oncological Care Delivery Through Visual Analytics and Sequential Rule Mining
Personalized head and neck cancer therapeutics have greatly improved survival
rates for patients, but are often leading to understudied long-lasting symptoms
which affect quality of life. Sequential rule mining (SRM) is a promising
unsupervised machine learning method for predicting longitudinal patterns in
temporal data which, however, can output many repetitive patterns that are
difficult to interpret without the assistance of visual analytics. We present a
data-driven, human-machine analysis visual system developed in collaboration
with SRM model builders in cancer symptom research, which facilitates
mechanistic knowledge discovery in large scale, multivariate cohort symptom
data. Our system supports multivariate predictive modeling of post-treatment
symptoms based on during-treatment symptoms. It supports this goal through an
SRM, clustering, and aggregation back end, and a custom front end to help
develop and tune the predictive models. The system also explains the resulting
predictions in the context of therapeutic decisions typical in personalized
care delivery. We evaluate the resulting models and system with an
interdisciplinary group of modelers and head and neck oncology researchers. The
results demonstrate that our system effectively supports clinical and symptom
research
NNVA: Neural Network Assisted Visual Analysis of Yeast Cell Polarization Simulation
Complex computational models are often designed to simulate real-world
physical phenomena in many scientific disciplines. However, these simulation
models tend to be computationally very expensive and involve a large number of
simulation input parameters which need to be analyzed and properly calibrated
before the models can be applied for real scientific studies. We propose a
visual analysis system to facilitate interactive exploratory analysis of
high-dimensional input parameter space for a complex yeast cell polarization
simulation. The proposed system can assist the computational biologists, who
designed the simulation model, to visually calibrate the input parameters by
modifying the parameter values and immediately visualizing the predicted
simulation outcome without having the need to run the original expensive
simulation for every instance. Our proposed visual analysis system is driven by
a trained neural network-based surrogate model as the backend analysis
framework. Surrogate models are widely used in the field of simulation sciences
to efficiently analyze computationally expensive simulation models. In this
work, we demonstrate the advantage of using neural networks as surrogate models
for visual analysis by incorporating some of the recent advances in the field
of uncertainty quantification, interpretability and explainability of neural
network-based models. We utilize the trained network to perform interactive
parameter sensitivity analysis of the original simulation at multiple
levels-of-detail as well as recommend optimal parameter configurations using
the activation maximization framework of neural networks. We also facilitate
detail analysis of the trained network to extract useful insights about the
simulation model, learned by the network, during the training process.Comment: Published at IEEE Transactions on Visualization and Computer Graphic
Individualized outcome prognostication for patients with laryngeal cancer
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142424/1/cncr31087.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142424/2/cncr31087_am.pd
Pathway-Based Multi-Omics Data Integration for Breast Cancer Diagnosis and Prognosis.
Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017
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