The beginning of the end for conventional RECIST — novel therapies require novel imaging approaches

Abstract

Owing to improvements in our understanding of the biological principles of tumour initiation and progression, a wide variety of novel targeted therapies have been developed. Developments in biomedical imaging, however, have not kept pace with these improvements and are still mainly designed to determine lesion size alone, which is reflected in the Response Evaluation Criteria in Solid Tumors (RECIST). Imaging approaches currently used for the evaluation of treatment responses in patients with solid tumours, therefore, often fail to detect successful responses to novel targeted agents and might even falsely suggest disease progression, a scenario known as pseudoprogression. The ability to differentiate between responders and nonresponders early in the course of treatment is essential to allowing the early adjustment of treatment regimens. Various imaging approaches targeting a single dedicated tumour feature, as described in the hallmarks of cancer, have been successful in preclinical investigations, and some have been evaluated in pilot clinical trials. However, these approaches have largely not been implemented in clinical practice. In this Review, we describe current biomedical imaging approaches used to monitor responses to treatment in patients receiving novel targeted therapies, including a summary of the most promising future approaches and how these might improve clinical practice.

Key points

  • Targeted therapies require novel imaging techniques for the assessment of tumour response; the current Response Evaluation Criteria in Solid Tumors (RECIST) are inadequate because tumour diameter does not reflect all types of response.

  • Nuclear medicine-based approaches, such as immuno-PET, enable the detection of specific biomarkers expressed by tumour cells or cells located in the microenvironment, such as tumour-associated immune cells.

  • MRI enables the noninvasive determination of several characteristics of solid tumours including cellularity, stromal composition and fibrosis.

  • Imaging data comprise much more information besides allowing reconstruction of a morphological picture; methods such as magnetic resonance fingerprinting will likely facilitate response evaluation beyond measures of tumour diameter.

  • The integration of imaging biomarkers with other diagnostic tools such as genomics, proteomics and metabolomics is expected to enable more accurate response evaluation than that provided by RECIST in patients with solid tumours.

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Fig. 1: Biological example of the limitations of RECIST.
Fig. 2: Overview of selected current imaging approaches, described in the context of the hallmarks of cancer
Fig. 3: Early response assessment using 3΄-deoxy-3΄-18F-fluorothymidine.
Fig. 4: PSMA expression as a potential marker of neoangiogenesis.
Fig. 5: Early evaluation of response to tumour vessel-targeted tTF–NGR therapy using dynamic contrast-enhanced MRI.
Fig. 6: Multiparametric PET–MRI for assessment of early therapy response.
Fig. 7: Molecular profiling of a neuroendocrine tumour using PET.

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Acknowledgements

W.E.B. acknowledges grant support from the Deutsche Krebshilfe (grant no. Berdel-70111004) for the tTF-NGR study.

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Gerwing, M., Herrmann, K., Helfen, A. et al. The beginning of the end for conventional RECIST — novel therapies require novel imaging approaches. Nat Rev Clin Oncol 16, 442–458 (2019). https://doi.org/10.1038/s41571-019-0169-5

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