A Primer on RECIST 1.1 for Oncologic Imaging in Clinical Drug Trials

Abstract

M easuring changes in tumor size with imaging can help determine if patients are responding to therapy, as well as if and when disease progression occurs. In the clinical trial setting, there is blending of patient care and scientific discovery. Quantification of radiologic changes in tumor size extends beyond contributing to individual patient treatment decisions. It can also provide a method to perform statistical analyses and attain regulatory drug approval of promising investigational therapeutic agents by objective clinical trial endpoints. Image-based treatment outcome measures are commonly used to assess if treatments are effective and, in the past few decades, have played an increasing role in the regulatory drug approval of a growing number of oncologic therapies. Therefore, it is imperative that the imaging community understands the application of these rule-based response criteria during image interpretation and how reported findings inform clinical trial results. Oncology Innovation: Drug Development ProcessThe drug discovery and approval paradigm is a very timeand resource-intensive process. For U.S. Food and Drug Administration (FDA) approval of one therapy, typically anywhere between 5000 to 10 000 initial compounds are rigorously investigated in a structured process that usually takes more than $1 billion and 10 years to complete (2-4). Beyond the initial concept and basic drug development, promising agents must undergo extensive preclinical evaluation and endure multiple phases of clinical trials to ensure safety and efficacy. Preclinical testing is performed both in This copy is for personal use only. To order printed copies, contact reprints@rsna.org 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 marke...

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“…Traditionally, the rate of “best overall response” gives an indication of patients’ early response to treatment based on repeatedly quantifying the size of one or several cancer lesions by radiographic imaging. The overall response rate (ORR) is the percentage of patients achieving a complete or partial response through RECIST 1.1 at any time of the treatment ( Ruchalski et al, 2021 ). Observing a high ORR in early clinical studies is encouraging and often ungates further studies and investment.…”

“…Based on the data from Weber et al (2021), which were shared with us without further obligations according to the policy of the Journal of Clinical Oncology Precision Oncology, we show in Figure 2A Kaplan-Meier curves of patients' overall survival as a function of early change in ctDNA. We selected the commonly used 50% ctDNA reduction from baseline as the cut-off (Nabet et al, 2020;Weber et al, 2021;Zou et al, 2021).…”

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“…RECIST measurements play a pivotal role in the development of novel oncological drugs ( 136 ). In most registered randomised controlled trials (RCTs), studies are powered to meet primary endpoints such as OS/PFS, which determines the number of patients recruited.…”

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“…To obtain FDA regulatory approval, a drug must show evidence of clinical benefit, the gold standard being overall survival (OS). Crucially, objective response rate (ORR) and progression-free survival (PFS) have been deemed by the FDA as adequate markers of clinical benefit sufficient to inform drug approval decisions, greatly expediting drug development [77] , [78] . Comparisons of these parameters (frequently defined over an interval such as 6-month PFS) can then be carried out among the arms of the trial to establish drug efficacy.…”

“…The four specific response categories of RECIST 1.1 include the disappearance of all lesions and reduction of pathological lymph nodes to < 10 mm, or complete response (CR); the reduction of at least 30% in the sum of diameters of all target lesions, or partial response (PR) (assuming non-target lesions do not show unequivocal progression); an increase by 20% in the sum the diameters of all target lesions, or progressive disease (PD); if the change in size of lesions fails to qualify as PD or PR, the timepoint response is stable disease (SD) [77] , [80] . Unequivocal progression in non-target lesions or the appearance of new lesions constitute PD, regardless of the target-lesion response.…”