Intensifled Doxorubicin-Based Regimen E-cacy in Residual Non-Hodgkin's Lymphoma Disease: Towards a Computationally Supported Treatment Improvement

Despite recent advances, treatment of patients with aggressive Non-Hodgkin's lymphoma (NHL 2 ) has yet to be optimally designed. Notwithstanding the contribution of molecular treatments, intensiflcation of chemotherapeutic regimens may still be beneflcial. Hoping to aid in the design of intensifled chemotherapy, we put forward a mathematical and computational model that analyses the efiect of Doxorubicin on NHL over a wide range of patho-physiological conditions. The model represents tumour growth both in difiusion-limited settings, that is, in small avascular tumours and tumour cords, and in perfusion-limited settings, e.g. in well-vascularized tumours. Model simulations indicated the presence of a critical regimen intensity below which treatment will fall short of tumour elimination. Taking this critical intensity into account, we compared two regimen intensiflcation strategies: Dose escalation and regimen densiflcation, i.e. reducing the inter-dosing interval. In the difiusion-limited setting, dose escalation was somewhat more e-cient than regimen densiflcation. In the perfusion-limited setting, both intensiflcation strategies yielded similar results. The present study coupled with a realistic myelotoxicity model may add insight on the optimisation of NHL intensifled chemotherapy design.