Determination of response in treatment of hepatic neoplasia

Abstract

The determination of objective antitumor response by therapeutic modalities is a complex process limited by the resolution of available tools. Nonetheless, within these limitations objective measurements are critical to the identification of effective therapies. The determination of complete regression of hepatic metastases should not be difficult clinically, but such an event occurs only rarely. More commonly, there is no clinically measurable response, although some degree of tumor cell kill may be achieved. The recognition of such effects is limited by the inadequacy of clinical assessment tools, and the concomitant application of multiple parameters is necessary if not essential. Of the presently employed methods to measure objective antitumor response as outlined in Table 1, only the monitoring of hepatomegaly and the quantitative criteria indicated in Fig. 7 has met the critical requirement of correlation with survival. Nonetheless, the method is a relatively gross estimate and subject to major interobserver variation. Radiologic studies have similar limitations and resolution power precludes adequate assessment of small lesions. The biochemical parameters are indirect tumor effects and may modulate as a consequence of therapy on normal tissue without tumor effects. Tumor antigens and particularly sequential monitoring of plasma CEA is theoretically the most optimal means of measuring tumor growth or regression. Practical clinical application is preliminarily encouraging, but precise quantitative guidelines must be established and meet the standards of a cost-benefit analysis. The high tumor response rate in hepatic artery infusion programs offers the opportunity to determine the usefulness of plasma CEA as a specific determinant of tumor activity, and such studies are ongoing.