RECIST persists despite flaws

Long-held notions about the use of anatomic measurement to gauge response to cancer therapy don't hold up in a world redefined by molecularly based medicine.

Dr. Wolfgang Weber brought that message to the 2005 Academy of Molecular Imaging meeting in March. Weber, an assistant professor of radiology at the University of California, Los Angeles, argued that the two most widely used standards for measuring therapeutic response no longer make the grade.

Weber's criticism was directed at criteria developed by the World Health Organization and the Response Evaluation Criteria in Solid Tumors (RECIST). Both use CT to measure anatomic changes in tumor size in order to calculate their response to chemo- and radiotherapy. The WHO criteria, developed in the 1970s, describe a positive response as a 50% reduction of two perpendicular tumor diameters drawn across the lesion (D1 x D2). RECIST, published in 1990, uses changes in the maximum tumor diameter for assessments. A positive response with RECIST equates to a 30% decrease in the maximum diameter.

Both systems are based on outdated notions about measurement accuracy and the limitations of resolution possible with circa-1975 CT scanners, according to Weber. The framers of the WHO and RECIST criteria could not have anticipated the performance of cytostatic drugs that kill cancers without affecting tumor size, he said.

These problems have led to assessment errors. RECIST criteria, for instance, concluded that the lung cancer drug erlotinib produced only an 8.9% positive response, while the clinical trial of 730 patients credited the drug for a nearly 50% increase in the median survival.

Weber admitted that oncologists still have good technical reasons to use the WHO and RECIST guidelines, but he asked the audience to consider how molecular imaging, especially quantitative measures such as standard uptake values, could do better.