title: Increasing the Time Interval between PCV Chemotherapy Cycles as a Strategy to Improve Duration of Response in Low-Grade Gliomas: Results from a Model-Based Clinical Trial Simulation.
abstract: BACKGROUND
  We previously developed a mathematical model capturing tumor size dynamics of adult low-grade gliomas (LGGs) before and after treatment either with PCV (Procarbazine, CCNU, and Vincristine) chemotherapy alone or with radiotherapy (RT) alone.
  
  
  OBJECTIVE
  The aim of the present study was to present how the model could be used as a simulation tool to suggest more effective therapeutic strategies in LGGs. Simulations were performed to identify schedule modifications that might improve PCV chemotherapy efficacy.
  
  
  METHODS
  Virtual populations of LGG patients were generated on the basis of previously evaluated parameter distributions. Monte Carlo simulations were performed to compare treatment efficacy across in silico clinical trials.
  
  
  RESULTS
  Simulations predicted that RT plus PCV would be more effective in terms of duration of response than RT alone. Additional simulations suggested that, in patients treated with PCV chemotherapy, increasing the interval between treatment cycles up to 6 months from the standard 6 weeks can increase treatment efficacy. The predicted median duration of response was 4.3 years in LGGs treated with PCV cycles given every 6 months versus 3.1 years in patients treated with the classical regimen.
  
  
  CONCLUSIONS
  The present study suggests that, in LGGs, mathematical modeling could facilitate clinical research by helping to identify, in silico, potentially more effective therapeutic strategies.
authors.affiliation: Inria, Project-Team NUMED, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69007 Lyon Cedex 07, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Mazzocco
authors.affiliation: Hôpital Pierre Wertheimer, 59 boulevard Pinel, 69500 Bron, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.affiliation: Hôpital Pierre Wertheimer, 59 boulevard Pinel, 69500 Bron, France.
authors.forename: François
authors.initials: F
authors.lastname: Ducray
authors.affiliation: Inria, Project-Team NUMED, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69007 Lyon Cedex 07, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ribba
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002985:Clinical Protocols; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D019295:Computational Biology; D003198:Computer Simulation; D004334:Drug Administration Schedule; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008130:Lomustine / Q000008:administration & dosage; D055641:Mathematical Concepts; D008954:Models, Biological; D009010:Monte Carlo Method; D011344:Procarbazine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine