Elsevier

European Journal of Cancer

Volume 62, July 2016, Pages 138-145
European Journal of Cancer

Current Perspective
RECIST 1.1 – Standardisation and disease-specific adaptations: Perspectives from the RECIST Working Group

https://doi.org/10.1016/j.ejca.2016.03.082Get rights and content

Highlights

  • The level of evidence validate a new imaging biomarker as an end-point for a specific disease or in phase II trials is considerable.

  • This manuscript provides an overview of commonly described modifications of Response Evaluation Criteria in Solid Tumours (RECIST) with level of evidence using Oxford Centre for Evidence-Based Medicine approach.

  • RECIST Working Group supports the evaluation and validation of novel biomarkers in cancer therapy and will work to incorporate into RECIST as the techniques and therapeutics become widely used and globally available.

Abstract

Radiologic imaging of disease sites plays a pivotal role in the management of patients with cancer. Response Evaluation Criteria in Solid Tumours (RECIST), introduced in 2000, and modified in 2009, has become the de facto standard for assessment of response in solid tumours in patients on clinical trials.

The RECIST Working Group considers the ability of the global oncology community to implement and adopt updates to RECIST in a timely manner to be critical. Updates to RECIST must be tested, validated and implemented in a standardised, methodical manner in response to therapeutic and imaging technology advances as well as experience gained by users. This was the case with the development of RECIST 1.1, where an expanded data warehouse was developed to test and validate modifications. Similar initiatives are ongoing, testing RECIST in the evaluation of response to non-cytotoxic agents, immunotherapies, as well as in specific diseases.

The RECIST Working Group has previously outlined the level of evidence considered necessary to formally and fully validate new imaging markers as an appropriate end-point for clinical trials. Achieving the optimal level of evidence desired is a difficult feat for phase III trials; this involves a meta-analysis of multiple prospective, randomised multicentre clinical trials. The rationale for modifications should also be considered; the modifications may be proposed to improve surrogacy, to provide a more mechanistic imaging technique, or be designed to improve reproducibility of the imaging biomarker.

Here, we present the commonly described modifications of RECIST, each of which is associated with different levels of evidence and validation.

Introduction

Radiologic imaging of disease sites plays a pivotal role in the management of patients with cancer. It has been used to estimate disease burden to plan optimal treatment, as well as to evaluate response to treatment to inform medical decisions such as discontinuation and or switching to other therapies. These same clinical tools have been used to measure end-points in cancer drug trials to quantify efficacy in candidate compounds. This quantification assists in the decisions of moving an agent from phase I toward registration. The value of imaging in early clinical trials of potential new cancer therapeutics rests on the validation and reproducibility of the imaging biomarkers to serially and non-invasively assess the extent of tumour change during therapy as surrogates of the previously accepted gold standards of patient benefit of prolongation of survival or improvement in quality of life.

Response Evaluation Criteria in Solid Tumours (RECIST), introduced in 2000, and modified in 2009, has become the de facto standard for assessment of response in solid tumours. The standardisation and ubiquitous use of RECIST allows for easy historical comparisons, especially in phase II trials. While RECIST has served a critical role in drug development, the emergence of new classes of drugs, new treatment paradigms and new imaging modalities and techniques requires continued re-evaluation of RECIST as a response assessment tool.

The RECIST Working Group considers the ability of the global oncology community to implement and adopt any updates to RECIST in a timely manner to be critical. Updates to RECIST must be tested, validated and implemented in a standardised, methodical manner in response to therapeutic and imaging technology advances as well as experience gained by users. This was the case with the development of RECIST 1.1, where an expanded data warehouse was developed to test and validate modifications to the criteria. Similar initiatives are ongoing, testing RECIST in the evaluation of response to non-cytotoxic agents, immunotherapies, as well as specific diseases.

The RECIST Working Group has previously outlined the level of evidence considered necessary to formally and fully validate new imaging markers as an appropriate end-point for clinical trials [1]. The ideal level of evidence would require a series of prospective, randomised multicentre clinical trials, which is not feasible. The rationale for modifications should also be considered; the modifications may be proposed to improve surrogacy, to provide a more mechanistic imaging technique, or be designed to improve reproducibility of the imaging biomarker.

As reported by the RECIST survey in 2014, 60% of the responders also used other criteria or modified RECIST criteria, when RECIST was not applicable in certain disease types or novel therapies were involved [2]. In this paper, we summarise several of the commonly described modifications of RECIST, each of which is associated with different levels of evidence and validation. We used the Oxford Centre for Evidence-Based Medicine approach for categorising levels of evidence (level 1 consisting of systematic reviews of randomised clinical trials or individual clinical trials with narrow confidence intervals. Level 2 in general consists of systematic reviews of cohort studies, lower quality randomised trials and outcomes type research, while level 3 is case control type studies and level 4 is case series. Level 5 is expert opinion and consensus statements) [3].

In addition to being a useful summary of this field, the summary will assist the RECIST Working Group decisions regarding which future techniques and modifications may be relevant to incorporate into RECIST after appropriate validation.

Section snippets

Prostate cancer

In 2008, the Prostate Cancer Working Group (PCWG2) outlined principles for trial eligibility, design, and conduct in progressive metastatic castration resistant prostate cancer (CRPC) [4]. PCWG2 built upon the standards for baseline evaluations recommended by RECIST and provides guidelines for imaging and symptom assessment specific to prostate cancer. The requirement for target lesions for trial entry, as defined by RECIST, was not recommended by PCWG2 because it would shift the focus of

Conclusions

As previously noted, the level of evidence required to validate a new imaging biomarker as an end-point for a specific disease or in phase II trials is considerable, and is usually not accomplished. In several of the examples above, validation could only be achieved by evaluating retrospectively clinical trials conducted with novel therapeutics or in specific diseases. Given the increasing diversity of therapeutic agents, the increasing diversity of mechanisms of actions of these agents and the

Conflict of interest statement

E. de Vries: Research grants from Roche/Genentech, Amgen, Novartis, Pieris and Servier to the institute, data monitoring committee Biomarin, advisory board Synthon. R. Ford: Dr. Ford is not a stockholder in any pharmaceutical company and holds no options, grants or patents. He is currently or was previously a consultant for the following companies (either directly through Clinical Trials Imaging Consulting, LLC., or indirectly through other pharmaceutical service companies for which he

Acknowledgements

Canadian Cancer Trials Group participation was supported by the Canadian Cancer Society Research Institute (grant #021039). This publication was supported by the EORTC Cancer Research Fund and by the National Cancer Institute grant number 5U10-CA11488-45.

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