Response assessment in cancer clinical trials

Most anticancer agents developed over the last four decades are cytotoxic drugs inducing tumor regression, sometimes also resulting in prolongation of survival. Historically, the direct therapeutic efficacy of such treatments has been monitored through successive evaluations of the tumor burden quantified through the measurement of the size of tumor lesions that were clinically or radiologically evaluable. By the end of the 1970’s, a group of breast cancer specialists, under the auspices of International Union Against Cancer (UICC), set the principles under which response to treatment in breast cancer should be evaluated. This work was subsequently adopted and integrated into the recommendations set by the World Health Organisation (WHO) for the evaluation of cancer treatment in solid tumors. After 1981, many new anticancer drugs have been developed, and many researchers have also started to investigate different combinations of treatments. The experience acquired over the years and the lack of details in the WHO recommendations has stimulated the development of modified versions of the WHO criteria. Over the years, the use of the different versions of the original WHO criteria have rendered the accuracy of the relative comparison of the results of investigations based on the same therapy very unreliable. The evolution of cancer imaging, the importance given to “response rate” as an endpoint of early clinical trials and the rapidly increasing number of new anticancer agents to be tested have also justified the initiative to revisit, update the existing response criteria. This thesis focuses on the development and the implementation of a new set of response criteria (RECIST).