Reproducibility of tumor response evaluation in patients with high-grade malignant non-Hodgkin's lymphoma

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.