Treatment response assessment by imaging plays a vital role in evaluating changes in solid tumors during oncology therapeutic clinical trials. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is the reference standard imaging response criteria and provides details regarding image acquisition, image interpretation and categorical response classification. While RECIST 1.1 is applied for the majority of clinical trials in solid tumors, other criteria and modifications have been introduced when RECIST 1.1 outcomes may be incomplete. Available criteria beyond RECIST 1.1 can be explored in an algorithmic fashion dependent on imaging modality, tumor type and method of treatment. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) is available for use with PET/CT. Modifications to RECIST 1.1 can be tumor specific, including mRECIST for hepatocellular carcinoma and mesothelioma. Choi criteria for gastrointestinal stromal tumors incorporate tumor density with alterations to categorical response thresholds. Prostate Cancer Working Group 3 (PCWG3) imaging criteria combine RECIST 1.1 findings with those of bone scans. In addition, multiple response criteria have been created to address atypical imaging responses in immunotherapy.

Drug discovery and approval in oncology is mediated by the use of imaging to evaluate drug efficacy in clinical trials. Imaging is performed while patients receive therapy to evaluate their response to treatment. Response criteria, specifically Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), are standardized and can be used at different time points to classify response into the categories of complete response, partial response, stable disease, or disease progression. At the trial level, categorical responses for all patients are summated into image-based trial endpoints. These outcome measures, including objective response rate (ORR) and progression-free survival (PFS), are characteristics that can be derived from imaging and can be used as surrogates for overall survival (OS). Similar to OS, ORR and PFS describe the efficacy of a drug. U.S. Food and Drug Administration (FDA) regulatory approval requires therapies to demonstrate direct evidence of clinical benefit, such as improved OS. However, multiple programs have been created to expedite drug approval for life-threatening illnesses, including advanced cancer. ORR and PFS have been accepted by the FDA as adequate predictors of OS on which to base drug approval decisions, thus substantially shortening the time and cost of drug development (1). Use of imaging surrogate markers for drug approval has become increasingly common, accounting for more than 90% of approvals through the Accelerated Approval Program and allowing for use of many therapies which have altered the course of cancer. Keywords: Oncology, Tumor Response  RSNA, 2021.

The Response Evaluation in Solid Tumors (RECIST) 1.1 provides key guidance for performing imaging response assessment and defines image-based outcome metrics in oncology clinical trials, including progression free survival. In this framework, tumors identified on imaging are designated as either target lesions, non-target disease or new lesions and a structured categorical response is assigned at each imaging time point. While RECIST provides definitions for these categories, it specifically and objectively defines only the target disease. Predefined thresholds of size change provide unbiased metrics for determining objective response and disease progression of the target lesions. However, worsening of non-target disease or emergence of new lesions is given the same importance in determining disease progression despite these being qualitatively assessed and less rigorously defined. The subjective assessment of non-target and new disease contributes to reader variability, which can impact the quality of image interpretation and even the determination of progression free survival. The RECIST Working Group has made significant efforts in developing RECIST 1.1 beyond its initial publication, particularly in its application to targeted agents and immunotherapy. A review of the literature highlights that the Working Group has occasionally employed or adopted objective measures for assessing non-target and new lesions in their evaluation of RECIST-based outcome measures. Perhaps a prospective evaluation of these more objective definitions for non-target and new lesions within the framework of RECIST 1.1 might improve reader interpretation. Ideally, these changes could also better align with clinically meaningful outcome measures of patient survival or quality of life.