Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userCan tumor location on pre-treatment MRI predict likelihood of pseudo-progression versus tumor recurrence in Glioblastoma? A feasibility study
69
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
A significant challenge in Glioblastoma (GBM) management is identifying pseudo-progression (PsP), a benign radiation-induced effect, from tumor recurrence, on routine imaging following conventional treatment. Previous studies have linked tumor lobar presence and laterality to GBM outcomes, suggesting that disease etiology and progression in GBM may be impacted by tumor location. Hence, in this feasibility study, we seek to investigate the following question: Can tumor location on treatment-naive MRI provide early cues regarding likelihood of a patient developing pseudo-progression versus tumor recurrence? In this study, 74 pre-treatment Glioblastoma MRI scans with PsP (33) and tumor recurrence (41) were analyzed. First, enhancing lesion on Gd-T1w MRI and peri-lesional hyperintensities on T2w/FLAIR were segmented by experts and then registered to a brain atlas. Using patients from the two phenotypes, we construct two atlases by quantifying frequency of occurrence of enhancing lesion and peri-lesion hyperintensities, by averaging voxel intensities across the population. Analysis of differential involvement was then performed to compute voxel-wise significant differences (p-value<0.05) across the atlases. Statistically significant clusters were finally mapped to a structural atlas to provide anatomic localization of their location. Our results demonstrate that patients with tumor recurrence showed prominence of their initial tumor in the parietal lobe, while patients with PsP showed a multi-focal distribution of the initial tumor in the frontal and temporal lobes, insula, and putamen. These preliminary results suggest that lateralization of pre-treatment lesions towards certain anatomical areas of the brain may allow to provide early cues regarding assessing likelihood of occurrence of pseudo-progression from tumor recurrence on MRI scans.
rate research
Read More
With growing emphasis on personalized cancer-therapies,radiogenomics has shown promise in identifying target tumor mutational status on routine imaging (i.e. MRI) scans. These approaches fall into 2 categories: (1) deep-learning/radiomics (context-based), using image features from the entire tumor to identify the gene mutation status, or (2) atlas (spatial)-based to obtain likelihood of gene mutation status based on population statistics. While many genes (i.e. EGFR, MGMT) are spatially variant, a significant challenge in reliable assessment of gene mutation status on imaging has been the lack of available co-localized ground truth for training the models. We present Spatial-And-Context aware (SpACe) virtual biopsy maps that incorporate context-features from co-localized biopsy site along with spatial-priors from population atlases, within a Least Absolute Shrinkage and Selection Operator (LASSO) regression model, to obtain a per-voxel probability of the presence of a mutation status (M+ vs M-). We then use probabilistic pair-wise Markov model to improve the voxel-wise prediction probability. We evaluate the efficacy of SpACe maps on MRI scans with co-localized ground truth obtained from corresponding biopsy, to predict the mutation status of 2 driver genes in Glioblastoma: (1) EGFR (n=91), and (2) MGMT (n=81). When compared against deep-learning (DL) and radiomic models, SpACe maps obtained training and testing accuracies of 90% (n=71) and 90.48% (n=21) in identifying EGFR amplification status,compared to 80% and 71.4% via radiomics, and 74.28% and 65.5% via DL. For MGMT status, training and testing accuracies using SpACe were 88.3% (n=61) and 71.5% (n=20), compared to 52.4% and 66.7% using radiomics,and 79.3% and 68.4% using DL. Following validation,SpACe maps could provide surgical navigation to improve localization of sampling sites for targeting of specific driver genes in cancer.
Understanding the dynamics of brain tumor progression is essential for optimal treatment planning. Cast in a mathematical formulation, it is typically viewed as evaluation of a system of partial differential equations, wherein the physiological processes that govern the growth of the tumor are considered. To personalize the model, i.e. find a relevant set of parameters, with respect to the tumor dynamics of a particular patient, the model is informed from empirical data, e.g., medical images obtained from diagnostic modalities, such as magnetic-resonance imaging. Existing model-observation coupling schemes require a large number of forward integrations of the biophysical model and rely on simplifying assumption on the functional form, linking the output of the model with the image information. In this work, we propose a learning-based technique for the estimation of tumor growth model parameters from medical scans. The technique allows for explicit evaluation of the posterior distribution of the parameters by sequentially training a mixture-density network, relaxing the constraint on the functional form and reducing the number of samples necessary to propagate through the forward model for the estimation. We test the method on synthetic and real scans of rats injected with brain tumors to calibrate the model and to predict tumor progression.
Computational systems and methods are being applied to solve biological problems for many years. Incorporating methods of this kind in the research for cancer treatment and related drug discovery in particular, is shown to be challenging due to the complexity and the dynamic nature of the related factors. Usually, there are two objectives in such settings; first to calibrate the simulators so as to reproduce real-world cases, and second, to search for specific values of the parameter space concerning effective drug treatments. We combine a multi-scale simulator for tumor cell growth and a Genetic Algorithm (GA) as a heuristic search method for finding good parameter configurations in reasonable time. The two modules are integrated into a single workflow that can be executed in a parallel manner on high performance computing infrastructures, since large-scale computational and storage capabilities are necessary in this domain. After using the GA for calibration, our goal is to explore different drug delivery schemes. Among these schemes, we aim to find those that minimize tumor cell size and the probability of emergence of drug resistant cells in the future. Results from experiments on high performance computing infrastructure illustrate the effectiveness and timeliness of the approach.
The aim of the systematic review was to assess recently published studies on diagnostic test accuracy of glioblastoma treatment response monitoring biomarkers in adults, developed through machine learning (ML). Articles were searched for using MEDLINE, EMBASE, and the Cochrane Register. Included study participants were adult patients with high grade glioma who had undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide) and subsequently underwent follow-up imaging to determine treatment response status. Risk of bias and applicability was assessed with QUADAS 2 methodology. Contingency tables were created for hold-out test sets and recall, specificity, precision, F1-score, balanced accuracy calculated. Fifteen studies were included with 1038 patients in training sets and 233 in test sets. To determine whether there was progression or a mimic, the reference standard combination of follow-up imaging and histopathology at re-operation was applied in 67% of studies. The small numbers of patient included in studies, the high risk of bias and concerns of applicability in the study designs (particularly in relation to the reference standard and patient selection due to confounding), and the low level of evidence, suggest that limited conclusions can be drawn from the data. There is likely good diagnostic performance of machine learning models that use MRI features to distinguish between progression and mimics. The diagnostic performance of ML using implicit features did not appear to be superior to ML using explicit features. There are a range of ML-based solutions poised to become treatment response monitoring biomarkers for glioblastoma. To achieve this, the development and validation of ML models require large, well-annotated datasets where the potential for confounding in the study design has been carefully considered.
Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis. Other mutations, however, do not change the phenotype of the cell or even decrease cellular fitness. While much experimental effort is being devoted to the identification of the different functional effects of individual mutations, mathematical modeling of tumor progression generally considers constant fitness increments as mutations are accumulated. In this paper we study a mathematical model of tumor progression with random fitness increments. We analyze a multi-type branching process in which cells accumulate mutations whose fitness effects are chosen from a distribution. We determine the effect of the fitness distribution on the growth kinetics of the tumor. This work contributes to a quantitative understanding of the accumulation of mutations leading to cancer phenotypes.
suggested questions
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
