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Saut, O.

Publications and source records attributed to Saut, O..

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A novel imaging biomarker for survival prediction in EGFR-mutated NSCLC patients treated with TKI

EGFR-mutated non-small cells lung carcinoma are treated with Tyrosine Kinase Inhibitors (TKI). Very often, the disease is only responding for a while before relapsing. TKI efficacy in the long run is therefore challenging to evaluate. Our objective is to derive a new imaging biomarker that could offer better insights on the disease response to treatment. This study includes 17 patients diagnosed as EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI. The early response to treatment is evaluated with 3 computed tomography (CT) scans of the primitive tumor (one before the TKI introduction and two after). Using our knowledge of the disease, an imaging biomarker based on the tumor heterogeneity evolution between the first and the third exams is defined and computed using a novel mathematical model calibrated on patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker (p = 0.009). Using the ROC curve, the patients are separated into two populations hence the comparison of the survival curves is statistically significant (p = 0.025). Initial state of the tumor seems to have a role for the prognosis of the response to TKI treatment. More precisely, the imaging marker - defined using only the CT scan before the TKI introduction - allows us to determine a first classification of the population which is refined over time using the imaging marker as more CT scans become available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor.

cancer biology

Machine learning versus mechanistic modeling for prediction of metastatic relapse in breast cancer

PurposeFor patients with early-stage breast cancer, prediction of the risk of metastatic relapse is of crucial importance. Existing predictive models rely on agnostic survival analysis statistical tools (e.g. Cox regression). Here we define and evaluate the predictive ability of a mechanistic model for the time to metastatic relapse. MethodsThe data consisted of 642 patients with 21 clinicopathological variables. A mechanistic model was developed on the basis of two intrinsic mechanisms of metastatic progression: growth (parameter ) and dissemination (parameter ). Population statistical distributions of the parameters were inferred using mixed-effects modeling. A random survival forest analysis was used to select a minimal set of 5 covariates with best predictive power. These were further considered to individually predict the model parameters, by using a backward selection approach. Predictive performances were compared to classical Cox regression and machine learning algorithms. ResultsThe mechanistic model was able to accurately fit the data. Covariate analysis revealed statistically significant association of Ki67 expression with (p=0.001) and EGFR with (p=0.009). Achieving a c-index of 0.65 (0.60-0.71), the model had similar predictive performance as the random survival forest (c-index 0.66-0.69) and Cox regression (c-index 0.62 - 0.67), as well as machine learning classification algorithms. ConclusionBy providing informative estimates of the invisible metastatic burden at the time of diagnosis and forward simulations of metastatic growth, the proposed model could be used as a personalized prediction tool of help for routine management of breast cancer patients.

cancer biology