Papers by Georgios Stamatakos
Neuro-oncology, Nov 1, 2017
NEURO-ONCOLOGY • NOVEMBER 2017 microenvironment. This action by Toca 511 and Toca FC in animal mo... more NEURO-ONCOLOGY • NOVEMBER 2017 microenvironment. This action by Toca 511 and Toca FC in animal models generates durable anti-tumor immune responses that can be transferred to naïve, untreated animals. In the clinical study presented here, Toca 511 is injected into resection cavity walls at time of resection followed by multiple courses of oral Toca FC. Multi-year durable and ongoing objective responses are observed, including four complete responses and two partial responses. We plan to report temporal changes in peripheral immune cells between responding and non-responding patients, including baseline differences in peripheral blood cell populations as well as temporal shifts in leukocyte subsets, T-cell receptor clonality, and serum cytokine levels. Sustained markers of proliferation and immune activation are observed in patients with response or stable disease compared to those that progressed. Immunohistochemistry analysis of resident T-cells in patient tumors taken at time of resection show fewer T-cells in responding and stable disease patients before treatment compared to those that did not respond. Data are consistent with the induction of anti-tumor immune response after Toca 511 and Toca FC administration.
Anticancer Research, Apr 1, 2019
Background/Aim: The need for more effective treatment modalities that can improve the clinical ou... more Background/Aim: The need for more effective treatment modalities that can improve the clinical outcome of patients with glioblastoma multiforme remains imperative. Dendritic cell vaccination is a fast-developing treatment modality, currently under exploration. Functional immune cell subpopulations may play a role in the final outcome. Materials and Methods: Data from 101 patients drawn from the HGG-2010 trial, including baseline patient characteristics and fluorescence-activated cell sorting of immune cell subpopulations, were analyzed by statistical and machinelearning methods. Results: The analysis revealed strong correlations between immune profiles and overall survival, when the extent of resection and the vaccination schedule were used as stratification variables. Conclusion: A systematic, in silico workflow detecting strong and statistically significant correlations between overall survival and immune profilederived quantities obtained at the start of dendritic cell vaccination was devised. The derived correlations could serve as a basis for the identification of prognostic markers discriminating between potential long-and short-term survivors of patients with glioblastoma multiforme. High grade gliomas (HGG) are the most frequent primary tumors of the central nervous system and consist of anaplastic/malignant gliomas (WHO grade III) and glioblastoma multiforme (GBM, WHO grade IV). The average incidence of GBM is about 3 to 4 per 100,000 adults (1). Standard treatment of these patients consists of resection, radiotherapy and chemotherapy. Even after maximal treatment, prognosis for patients with GBM remains poor, with a median progressionfree survival of 6.9 months and a median overall survival (OS) of 14.6 months (2, 3). Relapse is universal and believed to be due to the extensive spread of tumor cells into the surrounding healthy brain tissue (4). Hence, there is a need for more effective treatment modalities that can improve clinical outcome. Dendritic cell (DC) vaccination is an emerging treatment modality currently being explored in preclinical research and clinical trials (5-11). With DCs being the most potent antigenpresenting cells of the immune system, DC vaccination aims to activate the patient's immune system against the tumor. Additionally, induction of immunological memory might theoretically establish long-term anti-tumoral protection. Despite the promising effect of DC-based immune therapy for HGG, its clinical benefit may be restricted to only a subgroup of patients emerging as a "tail in the OS curve" repetitively found in survival analyses of vaccinated patients (12-14). Unfortunately, biomarkers at diagnosis predicting long-term outcome after active specific immunotherapy as part of standard treatment fail. Here we investigated whether profiles of immune cells at diagnosis and prior to DC vaccination are correlated with the final OS of patients undergoing radiochemotherapy, maintenance chemotherapy and DC vaccination. Materials and Methods The Computational Horizon in Cancer (CHIC) platform. As part of the European CHIC research project (www.chic-vph.eu), data from 101 patients with GBM and treated according to the HGG-2010 phase IIb randomized clinical trial (EudraCT 2009-018228-14) and subsequently sampled in the retrospective Glioma Translat study 2043
... speaker and speech recognition evaluation corpus for challenging problems in the broadcast do... more ... speaker and speech recognition evaluation corpus for challenging problems in the broadcast domain. In: Hoeppner, Wolfgang (Ed ... Börding, Josef; Flintrop, Björn; Krause, Katrin; Leimbach, Thorsten; Petersen, Ulrike; Theidig, Gabriele; Fraunhofer-Institut Intelligente Analyse-und ...
PLOS Computational Biology, Sep 22, 2016
Funding: The research leading to these results has received funding from the European Union's Sev... more Funding: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements n°223979-"ContraCancrum" (http:// contracancrum.eu/), 270089-"p-medicine" (http://pmedicine.eu/), 600841-"CHIC" (http://www.chic-vph. eu/), 600929-"MyHealthAvatar" (http://www. myhealthavatar.eu/) and 600852-"DR THERAPAT" (http://drtherapat.eu/). The funders had no role in estimates with the molecular profile of patients could serve as a basis for reliable personalized predictions.
BMC Bioinformatics, Aug 27, 2019
Background: Contemporary biological observations have revealed a large variety of mechanisms acti... more Background: Contemporary biological observations have revealed a large variety of mechanisms acting during the expansion of a tumor. However, there are still many qualitative and quantitative aspects of the phenomenon that remain largely unknown. In this context, mathematical and computational modeling appears as an invaluable tool providing the means for conducting in silico experiments, which are cheaper and less tedious than real laboratory experiments. Results: This paper aims at developing an extensible and computationally efficient framework for in silico modeling of tumor growth in a 3-dimensional, inhomogeneous and time-varying chemical environment. The resulting model consists of a set of mathematically derived and algorithmically defined operators, each one addressing the effects of a particular biological mechanism on the state of the system. These operators may be extended or readjusted , in case a different set of starting assumptions or a different simulation scenario needs to be considered. Conclusion: In silico modeling provides an alternative means for testing hypotheses and simulating scenarios for which exact biological knowledge remains elusive. However, finer tuning of pertinent methods presupposes qualitative and quantitative enrichment of available biological evidence. Validation in a strict sense would further require comprehensive, case-specific simulations and detailed comparisons with biomedical observations.
Ecancermedicalscience, 2009
BMC Bioinformatics, Oct 16, 2019
Ejc Supplements, Sep 1, 2007
regardless their molecular mechanisms. Furthermore, we found the positive linear relationship bet... more regardless their molecular mechanisms. Furthermore, we found the positive linear relationship between relative activity of AKT and ERK1/2 combined and cell viability as r = 0.948 in the same manner. The results obtained suggest quantitative cross-talk between the main two pathways regardless molecular mechanisms, which may aid cancer drug selection to a patient. 396 POSTER Human papillomavirus (HPV) infection, p53 overexpression and histopathologic factors in colorectal cancer
Journal of Bioengineering and Biomedical Science, 2013
Inferring gene and protein interaction networks: involves applying dimensionality reduction techn... more Inferring gene and protein interaction networks: involves applying dimensionality reduction techniques such as principal component analysis, hierarchical clustering and tree constructions, differential equation based kinetic modeling, rules-based modeling, stochastic and Monte Carlo based modeling of network dynamics [13].
The Breast Journal
Background. Identifying and understanding modifiable factors for the well-being of cancer patient... more Background. Identifying and understanding modifiable factors for the well-being of cancer patients is critical in survivorship research. We studied variables associated with the exercise habits of breast cancer patients and investigated if the achievement of exercise recommendations was associated with enhanced quality of life and/or psychological well-being. Material and Methods. 311 women from Finland, Portugal, Israel, and Italy receiving adjuvant therapy for stage I–III breast cancer answered questions about sociodemographic factors and physical exercise. Quality of life was assessed by the EORTC C30 and BR23 questionnaires. Anxiety and depression were evaluated using the HADS scale. Results. At the beginning of adjuvant therapy and after twelve months, 32% and 26% of participants were physically inactive, 27% and 30% exercised between 30 and 150 minutes per week, while 41% and 45% exercised the recommended 150 minutes or more per week. Relative to other countries, Finnish parti...
Critical Reviews in Oncology/Hematology
SBML description of the model. (XML 573Â kb)
Detailed description of the model calibration criteria derivation process. (PDF 458Â kb)
Backgroundthe aim of this study is to perform an external validation for the Candiolo nomogram, a... more Backgroundthe aim of this study is to perform an external validation for the Candiolo nomogram, a predictive algorithm of biochemical and clinical recurrences in prostate cancer patients treated by radical Radiotherapy, published in 2016 on the journal “Radiation Oncology”.Methods561 patients, treated by Radiotherapy with curative intent between 2003 and 2012, were classified according to the five risk-classes of the Candiolo nomogram and the three risk-classes of the D’Amico classification for comparison. Patients were treated with a mean prostatic dose of 77.7 Gy and a combined treatment with Androgen-Deprivation-Therapy in 76% of cases. The end-points of the study were biochemical-Progression-Free-Survival (bPFS) and clinical-Progression-Free-Survival (cPFS). With a median follow-up of 50 months, 56 patients (10%) had a biochemical relapse, and 30 patients (5.4%) a clinical progression. The cases were divided according to D’Amico in low-risk 21%, intermediate 40%, high-risk 39%; ...
BACKGROUND Despite the continued progress of medicine, dealing with breast cancer is becoming a m... more BACKGROUND Despite the continued progress of medicine, dealing with breast cancer is becoming a major socio-economic challenge, particularly due to its increasing incidence. The ability to better manage and adapt to the entire care process depends not only on the type of cancer, but also on the patient's socio-demographic and psychological characteristics and on the social environment in which a person lives and interacts. Therefore, it is important to understand which factors may affect or booster a successful adaptation to breast cancer. To our knowledge, no studies have been already performed on the combination effect of multiple psychological, biological and functional variables in predicting the patient’s ability to bounce back from the stressful life event, such as a breast cancer diagnosis. OBJECTIVE The aim of the study will be to build a quantitative mathematical model of factors associated with optimal adjustment capacity to cancer and study resilience through the canc...
Pediatric Blood & Cancer, 2016
Scientific Reports, 2019
Apart from offering insight into the biomechanisms involved in cancer, many recent mathematical m... more Apart from offering insight into the biomechanisms involved in cancer, many recent mathematical modeling efforts aspire to the ultimate goal of clinical translation, wherein models are designed to be used in the future as clinical decision support systems in the patient-individualized context. Most significant challenges are the integration of multiscale biodata and the patient-specific model parameterization. A central aim of this study was the design of a clinically-relevant parameterization methodology for a patient-specific computational model of cervical cancer response to radiotherapy treatment with concomitant cisplatin, built around a tumour features-based search of the parameter space. Additionally, a methodological framework for the predictive use of the model was designed, including a scoring method to quantitatively reflect the similarity and bilateral predictive ability of any two tumours in terms of their regression profile. The methodology was applied to the datasets ...
Clinical Therapeutics, 2017
e107 2. Frenk, Julio, et al. Health professionals for a new century: transforming education to st... more e107 2. Frenk, Julio, et al. Health professionals for a new century: transforming education to strengthen health systems in an interdependent world.
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Papers by Georgios Stamatakos