title: Prediction of tumour response induced by chemotherapy using modelling of CA-125 kinetics in recurrent ovarian cancer patients.
abstract: BACKGROUND
  The main objective of the present study was to establish the relationships between CA-125 kinetics and tumour size changes during treatment.
  
  
  METHODS
  The data from the CALYPSO-randomised phase III trial, comparing two platinum-based regimens in recurrent ovarian cancer (ROC) patients, was randomly split into a 'learning data set' to estimate model parameters and a 'validation data set' to validate model performances. A kinetic-pharmacodynamic semi-mechanistic model was built to describe tumour size and CA-125 kinetics during chemotherapy. The ability of the model to predict tumour response induced by chemotherapy, based on CA-125 values, was assessed.
  
  
  RESULTS
  Data from 535 ROC patients were used to model CA-125 kinetics and tumour size changes during the first 513 days after treatment initiation. Using the validated model, we could predict with accuracy the tumour size changes induced by chemotherapy based on the baseline imaging assessment and longitudinal CA-125 values (mean prediction error: 0.3%, mean absolute prediction error: 10.6%).
  
  
  CONCLUSIONS
  Using a semi-mechanistic model, the dynamic relationships between tumour size changes and CA-125 kinetics induced by chemotherapy were established in ROC patients. A modelling approach allowed CA-125 to be assessed as a biomarker for tumour size dynamics, to predict treatment efficacy for research and clinical purposes.
authors.affiliation: EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 69600 Oullins, France.
authors.forename: M
authors.initials: M
authors.lastname: Wilbaux
authors.affiliation: EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 69600 Oullins, France.
authors.forename: E
authors.initials: E
authors.lastname: Hénin
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5T2M9, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Oza
authors.affiliation: EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 69600 Oullins, France.
authors.forename: O
authors.initials: O
authors.lastname: Colomban
authors.affiliation: Hôpital Hôtel Dieu, Place du Parvis Notre-Dame, 75004 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.affiliation: 1] EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 69600 Oullins, France [2] Service d'Oncologie Médicale, Investigational Center for Treatments in Oncology and Hematology of Lyon, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, F-69310 Pierre-Bénite, France.
authors.forename: G
authors.initials: G
authors.lastname: Freyer
authors.affiliation: EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 69600 Oullins, France.
authors.forename: M
authors.initials: M
authors.lastname: Tod
authors.affiliation: 1] EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 69600 Oullins, France [2] Service d'Oncologie Médicale, Investigational Center for Treatments in Oncology and Hematology of Lyon, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, F-69310 Pierre-Bénite, France.
authors.forename: B
authors.initials: B
authors.lastname: You
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011379:Prognosis
chemical_list: D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin