Current standards for response evaluation by imaging techniques

Response evaluation by means of response rates using radiological imaging techniques is well established and plays a pivotal role in the development of new anti-cancer agents. It is typically employed in phase II clinical trials and acts as a surrogate for patient benefit, thereby allowing potentially active agents to be fast tracked; at the same time, inactive agents can be discarded earlier, with fewer patients being exposed to them. Response evaluation has evolved over the past 25 years, and various imaging stipulations have been introduced to try and add some uniformity to the process and enable a comparison to be made between different studies. However, imaging still requires a well-defined anatomical lesion or lesions to be viewed and relies on the measurement of a reduction in tumour size during treatment as the basis for presumed clinical benefit. This implies a cytocidal mode of action of the agent under review, but over the past 5 years increasing numbers of new cytostatic agents have been developed, such as anti-angiogenesis agents and specific enzyme receptor antagonists, where the overall effect is to prevent new tumour cells from growing or developing rather than directly killing pre-existing tumour cells. Anatomical imaging alone is therefore inappropriate as the tumour would not necessarily be expected to reduce in size. Other surrogates of tumour growth and metabolism have to be utilised. Functional studies are therefore necessary; anatomical imaging modalities such as computed tomography (CT) and magnetic resonance imaging can be modified so that dynamic studies can be undertaken, and newer techniques such as positron emission tomography scanning can be employed. The latter has poor spatial resolution but when combined with CT it has the ability to measure function while the anatomical site is accurately determined. The aim now is to devise new response evaluation techniques and criteria incorporating functional imaging to enable accurate assessment of active new anti-cancer agents.