End point assessment in gliomas: novel treatments limit usefulness of classical Macdonald's Criteria

Abstract

Recent trials in glioma have revealed significant limitations in the end points used. This requires a critical and comprehensive review of how brain tumor trials are conducted, particularly of which end points are defined and how response and progression are defined.

Fig 1.

Example of pseudoprogression after radiotherapy only. (A) Patient with biopsy-proven gemistocytic astrocytoma showing mass effect on magnetic resonance imaging (MRI) < 2 months before start of radiotherapy underwent 50.4-Gy radiotherapy in fractions of 1.8 Gy. (B) On first follow-up MRI 2 months after end of radiotherapy, new enhancing lesions were present. (C) These disappeared 7 months later without any additional treatment. The patient was asymptomatic throughout this episode and did not receive steroids.

Fig 2.

Patient 57 years of age with secondary glioblastoma before ([A] T1-weighted magnetic resonance imaging (MRI) with contrast and [B] fluid-attenuated inversion recovery [FLAIR] –weighted MRI) and after 7 months of treatment with bevacizumab and irinotecan, showing reduction in size of initial contrast-enhancing mass but also demonstrating (C) subtle diffuse enhancement and (D) significantly increased FLAIR crossing the corpus callosum. This was associated with increased cognitive impairment. Patient was not receiving corticosteroids at time of either scan.

Fig 3.

Example of rebound enhancement after discontinuation of anti–vascular endothelial growth factor (VEGF) agent. (A) Axial T1-weighted magnetic resonance imaging with contrast of patient with recurrent right temporal glioblastoma who initially responded to aflibercept (VEGF Trap; Regeneron, Tarrytown, NY); (B) at recurrence when aflibercept was discontinued; and (C) 4 weeks after, showing significant increase in contrast enhancement. (D) Patient began receiving bevacizumab with significant reduction in enhancement 4 weeks later, suggesting that worsening was in part result of aflibercept discontinuation and not just of tumor progression.