title: Reproducibility of tumor response evaluation in patients with high-grade malignant non-Hodgkin's lymphoma.
abstract: Estimation of complete response (CR) and partial response (PR) in patients with non-Hodgkin's lymphoma (NHL) is associated with a number of potential sources of error. The aim of this study was to define the reproducibility of response evaluation performed by an independent review committee (RC). In a phase III study of patients >60 yr with aggressive NHL, 60 patients who were already evaluated by the independent review committee (RC 1) for response were randomized to three groups and re-evaluated (RC 2). The assessment was classified into one of seven mutually exclusive categories, where the important borderlines with regard to one of the major end-points of the study, the CR rate, were between CR, "CR uncertain" (CR(U)), and PR. A discrepancy between RC 1 and 2 was found in 8/60 patients (13.3%), influencing the CR/CR(U) status in four of these patients. Two CR and two PR patients were reclassified as CR(U). Thus, CR/CR(U) was changed in 4/60 (6.7%). The reports of the local investigators were compared with that of RC 1 in 254 patients. The CR/CR(U) status was affected in 41 of these patients (16.1%). It is concluded that an independent RC is a major prerequisite for a uniform response evaluation in phase III clinical trials. However, the good RC reproducibility does not motivate a second assessment. Moreover, in the phase III setting end-points other than the CR rate, such as time to treatment failure, cause specific and overall survival are preferred.
authors.affiliation: Department of Medicine, Division of Hematology, Karolinska Hospital and Institute, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Osby
authors.forename: A
authors.initials: A
authors.lastname: Taube
authors.forename: E
authors.initials: E
authors.lastname: Cavallin-Ståhl
authors.forename: H
authors.initials: H
authors.lastname: Hagberg
authors.forename: M
authors.initials: M
authors.lastname: Björkholm
mesh_terms: D000328:Adult; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome