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Response criteria for glioma

Nature Clinical Practice Oncology volume 5, pages 634–644 (2008)Cite this article

Abstract

The current method for assessing the response to therapy of glial tumors was described by Macdonald et al. in 1990. Under this paradigm, response categorization is determined on the basis of changes in the cross-sectional area of a tumor on neuroimaging, coupled with clinical assessment of neurological status and corticosteroid utilization. These categories of response have certain limitations; for example, cross-sectional assessment is not as accurate as volumetric assessment, which is now feasible. Disentangling antitumor effects of therapies from their effects on blood–brain barrier permeability can be challenging. The use of insufficient response criteria might be overestimating the true benefits of drugs in early-stage studies, and, therefore, such therapies could mistakenly move forward into later phases, only to result in disappointment when overall survival is measured. We propose that studies report both radiographic and clinical response rates, use volumetric rather than cross-sectional area to measure lesion size, and incorporate findings from mechanistic imaging and blood biomarker studies more frequently, and also suggest that investigators recognize the limitations of imaging biomarkers as surrogate end points.

Key Points

  • Volume rather than area measurements of tumor burden are now feasible and have less inter-observer variability

  • Non-volumetric reasons for progression including rate of clinical worsening and steroid dosing should be routinely reported in describing the results of clinical trials

  • Mechanistic biomarkers including imaging should be employed wherever posible, especially in early stage trials, to provide more meaning beyond response rates alone

  • Resolution is possible for previously ambiguous aspects of response criteria including minimum lesion size, degree of neurological worsening, definition of what 50% change in size means, degree of enhancement, etc.

  • The advent of new therapies such as antiangiogenic agents that directly affect tumor vessels and tumor enhancement require particular care in response evaluation. FLAIR and/or T2-weighted imaging should be used in addition to T1-weighted post-contrast images

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Figure 1: MRI scans demonstrating shortcomings of the diameter method of measuring a change in glioma size.
Figure 2: Shortcomings of the ellipsoid assumption used in the diameter method of measuring a change in glioma size.
Figure 3: Sensitivity of volume compared with area for the determination of change in tumor size.
Figure 4: When neuroimaging gliomas, 'daughter' lesions should be counted as part of the parent malignancy.
Figure 5: A schematic showing recommendations for glioma standardized response criteria.

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Acknowledgements

This work was funded by the US Public Health Service (grants M01-RR-01066, 1R21CA117079-01, 5T32CA009502-20, 5P41RR014075 and 5P01CA080124) and The MIND Institute. We wish to thank Craig Peterson for technical assistance, and Zariana Nikolova, Richard Parker, Wendy Hayes, and Steven Green for helpful discussions.

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Authors and Affiliations

  1. Department of Radiology, Department of Radiation Oncology at Massachusetts General Hospital, AG Sorensen is Associate Professor of Radiology, Havard Medical School, and Associate Professor of Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, and Co-Director, AA Martinos Center for Biomedical Imaging, at Massachusettes General Hospital. TT Batchelor is Associate Professor of Neurology, Harvard Medical School, and Executive Director, Stephen E and Catherine Pappas Center for Neuro-Oncology, Massachusettes General Hospital. PY Wen is Associate Professor of Neurology, Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Hospital, and Harvard Medical School. RK Jain is Andrew Werk Cook Professor of Tumor Biology and Director of the Edwin L Steele Laboratory of Tumor Biology, Harvard Medical School, Boston, MA.,

    A Gregory Sorensen, Tracy T Batchelor, Patrick Y Wen & Rakesh K Jain

  2. W Zhang is Research Fellow, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.,

    Wei-Ting Zhang

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Corresponding author

Correspondence to A Gregory Sorensen.

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Competing interests

AG Sorensen has received research support from, is a consultant for, or has spoken on behalf of the following companies or organizations: ACR ImageMetrix, Amgen, AstraZeneca, Breakaway Imaging, Bayer–Schering, Eli Lilly, EPIX Pharmaceuticals, Exelixis, Genentech, General Electric Healthcare, Mitsubishi Pharma, National Institutes of Health, Novartis, Northwest Biosciences, Pfizer, Schering–Plough, Siemens Medical Solutions, Takeda-Millennium and Thermal Technologies Inc. In addition, AG Sorensen has an equity position in and holds the position of Medical Advisor at EPIX Medical, a specialty pharmaceutical company the company is based in Cambridge, MA, USA, which is engaged in developing targeted contrast agents for cardiovascular MRI. TT Batchelor has spoken on behalf of Enzon and Schering–Plough. RK Jain is a consultant for AstraZeneca, Dyax and SynDevRx, and also receives research support from AstraZeneca and is a stockholder of SynDevRx. PY Wen receives research support from Amgen, AstraZeneca, Exelixis, Genentech, Novartis and Schering–Plough. W-T Zhang declared no competing interests.

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Sorensen, A., Batchelor, T., Wen, P. et al. Response criteria for glioma. Nat Rev Clin Oncol 5, 634–644 (2008). https://doi.org/10.1038/ncponc1204

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