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Master Thesis

Valeur descriptive et pronostique d'un modèle mathématique mécanistique de l'évolution métastatique du Neuroblastome de Haut-Risque

Abstract : Background: High Risk Neuroblastoma (HRNB), is the second most frequent solid tumor in children. Its prognosis remains poor even with multimodal therapies and risk-adapted strategies (5years Event Free Survival (EFS) <50%). Several mathematical models were developed over recent years to describe primary and metastatic tumor burden, but none in neuroblastoma and their prognosis value has yet to be determined. Aims: to build a mechanistic model, check its validity, and assess its prognostic value. Material and methods: We established a mechanistic mathematical model for HRNB, using the tumor size associated with 2 coefficients: μ (dissemination) and α (growth). The model was calibrated using the lactate dehydrogenase (LDH) circulating level and the MIBG SIOPEN score. Data from a cohort of 49 HRNB patients treated according to the HRNBL1 recommendations over the last 10 years were used. Results: The model was able to describe the metastatic burden of the disease. We found existence of a subgroup of HRNB with poorer prognosis in PFS and OS for a high LDH level (70-80th) and SIOPEN score at diagnosis (90th percentile) with a p < 0.05 with classical survival analysis, confirmed in our model for the LDH rate. We found also that a high μ value is associated with a better OS (p < 0.05) Conclusion: Mathematical mechanistic model can describe and predict tumoral burden using clinico-biologic data in human patients. It allowed the identification of a new µ risk factors, associated with better outcomes in OS in our population. The physiological substrate underlying these results have yet to be explored.
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https://dumas.ccsd.cnrs.fr/dumas-02404062
Contributor : Faculté de Médecine Amu <>
Submitted on : Wednesday, December 11, 2019 - 10:15:55 AM
Last modification on : Friday, October 23, 2020 - 4:41:22 PM
Long-term archiving on: : Thursday, March 12, 2020 - 3:38:37 PM

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Coline Sentis. Valeur descriptive et pronostique d'un modèle mathématique mécanistique de l'évolution métastatique du Neuroblastome de Haut-Risque. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02404062⟩

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