RANO 2.0 criteria: concepts applicable to the neuroradiologist's clinical practice

Abstract

Purpose of review: The Response Assessment in Neuro-Oncology (RANO) 2.0 criteria aim at improving the standardization and reliability of treatment response assessment in clinical trials studying central nervous system (CNS) gliomas. This review presents the evidence supporting RANO 2.0 updates and discusses which concepts can be applicable to the clinical practice, particularly in the clinical radiographic reads.

Recent findings: Updates in RANO 2.0 were supported by recent retrospective analyses of multicenter data from recent clinical trials. As proposed in RANO 2.0, in tumors receiving radiation therapy, the post-RT MRI scan should be used as a reference baseline for the following scans, as opposed to the pre-RT scan, and radiographic findings suggesting progression within three months after radiation therapy completion should be verified with confirmatory scans. Volumetric assessments should be considered, when available, especially for low-grade gliomas, and the evaluation of nonenhancing disease should have a marginal role in glioblastoma. However, the radiographic reads in the clinical setting also benefit from aspects that lie outside RANO 2.0 criteria, such as qualitative evaluations, patient-specific clinical considerations, and advanced imaging.

Summary: While RANO 2.0 criteria are meant for the standardization of the response assessment in clinical trials, some concepts have the potential to improve patients' management in the clinical practice.

Figure 1.. Representative cases to discuss the adoption of RANO 2.0 concepts in clinical radiographic reads for glioblastoma.

While RANO 2.0 recommend to abandon the evaluation of non-enhancing progression of glioblastoma in clinical trials, it is reasonable that unequivocal non-enhancing progression is still reported in the clinical routine (e.g., a new cortical T₂-FLAIR signal alteration, arrowhead in A). Of note, subsequent follow-up scans showed enhancing progression in the same region (arrows in A). RANO-defined pseudoprogression consists in growth or new appearance of CE tissue that does not additional grow on the confirmation scan obtained after ≥4 weeks (arrows in B). Conversely, PD is confirmed when the confirmation scan shows additional growth compared to preliminary PD (arrows in C). CE = contrast-enhancing, PD = progressive disease, PsP = pseudoprogression.

Figure 2.. Representative cases to discuss the adoption of RANO 2.0 concepts in clinical radiographic reads for low-grade gliomas (LGG).

When the baseline scan shows no measurable disease, radiographic progression is defined by the appearance of RANO-defined measurable disease (≥1 × ≥1 cm with in-plane perpendicular diameters, on two consecutive slices) (A). While this rule should be applied in clinical trials, in the clinical routine a more subjective approach that takes into account the gradual changes over time may also be adopted (A). When the baseline scan shows the presence of measurable disease, the tumor burden should be tracked with quantitative measurements in clinical trials, in order to evaluate to evaluate whether the lesion size change meets criteria for radiographic progression. In the clinical practice, a more qualitative and subjective approach may also be adopted, for instance when assessing lesions with infiltrative growth pattern, that are challenging to measure (B). Qualitative hallmarks of tumor growth include progressive thickening of grey matter structures (arrow in B), infiltrative growth causing an overall tissue enlargement (asterisks in B), and the effacement of CSF spaces due to mass effect (arrowheads in C).