title: Comparative Effects of CT Imaging Measurement on RECIST End Points and Tumor Growth Kinetics Modeling.
abstract: Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, USA.|Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, Indiana, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Li
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, USA.|Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, Indiana, USA.|Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Bies
authors.affiliation: Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Sharma
authors.affiliation: University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
authors.forename: S
authors.initials: S
authors.lastname: Karovic
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|Duke University, Durham, North Carolina, USA.
authors.forename: L
authors.initials: L
authors.lastname: Werk
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|University of Maryland Greenebaum Cancer Center, School of Medicine, Baltimore, Maryland, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Edelman
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Miller
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
authors.forename: A
authors.initials: A
authors.lastname: Oto
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ratain
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Schwartz
authors.affiliation: Alliance for Clinical Trials in Oncology, Boston, Massachusetts, USA.|University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Maitland
mesh_terms: D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D011786:Quality Control; D066066:Response Evaluation Criteria in Solid Tumors; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden
keywords: Response Evaluation Criteria in Solid Tumors; antineoplastic agents/pharmacology; clinical trials; humans; lung neoplasms/drug therapy; models; statistical; tomography; x-ray computed