Evolution and implementation of radiographic response criteria in neuro-oncology

Abstract

Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In this review, we discuss the strengths and limitations of different neuro-oncology response criteria and summarize current research findings on the role of novel response methods in neuro-oncology clinical trials and practice.

Keywords: BT-RADS; RANO; RAPNO; Response Assessment; Volumetrics.

Figure 1.

Evolution of response criteria in neuro-oncology.

Figure 2.

Treatment-related radiographic changes. (A) Pseudoprogression in a 50-year-old IDH wild-type diffuse midline glioma patient before initiating Pembrolizumab showing axial FLAIR (i) and T1 postcontrast (iv) images. Twenty days after Pembrolizumab therapy, there is an increase in vasogenic edema on axial FLAIR (ii) and contrast enhancement on T1 postcontrast (v) concerning for true progression versus pseudoprogression. Two months after Pembrolizumab therapy, there is a significant decrease in FLAIR hyperintensity (iii) and contrast enhancement (vi) confirming the previous diagnosis as pseudoprogression. (B) Pseudoresponse in a 55-year-old IDH wild-type glioblastoma patient before initiating bevacizumab (Avastin) showing axial FLAIR (i) and T1 postcontrast (ii) images. Two months after Avastin therapy, FLAIR hyperintensity and mass effect are unchanged (iii), but there was interval decrease in tumor enhancement on T1 postcontrast (iv).

Figure 3.

Pediatric low-grade gliomas. (A) Heterogeneous tumors with coronal FLAIR (i) illustrating an irregular hyperintense mass in the right temporal lobe and temporal stem and axial T1 postcontrast (ii) showing another lesion with irregular and ill-defined enhancement in the cerebral peduncle and along the optic tracts and optic chiasm. (B) Cystic components of pLGG illustrated on axial T1 postcontrast images with differentiation of tumor cysts (yellow arrows) and nontumor cysts (red arrows) according to RAPNO criteria. (C) Bidimensional measurement variability in pLGG. Images (i and ii) illustrate different bidimensional measurements made on a tumor in the foramen magnum on sagittal T1 postcontrast (i) and axial T1 postcontrast (ii). Images (iii and iv) are from a different patient with an infiltrative tumor in the bilateral temporal lobes. Coronal T1 postcontrast images with an enhancing lesion marked by one reviewer (iii) may vary significantly from measurements made on a different coronal T1 postcontrast image (iv) by a different reader.

Figure 4.

BT-RADS response assessment flowchart.

Figure 5.

BT-RADS criteria used for response assessment of a WHO Grade 2, IDH wild-type astrocytoma. Axial FLAIR and T1 postcontrast images at 7 months (A, D), 10 months (B, E), and 13 months (C, F) after surgical resection are shown. At 10 months, a score of 3c (recommendation for decreased interval of follow-up) was assigned given worsening enhancement (E) and marginally increased FLAIR hyperintensity (B). At 13 months, a score of 4 (recommendation to change clinical management) was assigned given further worsening of both enhancement (F) and FLAIR hyperintensity (C) over multiple studies.

Figure 6.

Advanced imaging techniques to distinguish tumor recurrence from radiation necrosis in a 59-year-old glioblastoma patient 4 years after initial resection. (A) Baseline images (i–iii) showing FLAIR (i), T1 postcontrast (ii), and DSC cerebral blood volume (CBV) maps (iii). Subsequent follow-up 2 months post repeat resection (iv–vi) shows increased FLAIR hyperintensity (iv), increasing thickness of T1 postcontrast enhancement surrounding the resection cavity (v), and increase in CBV on DSC perfusion map (white circle, vi). These findings are suspicious for tumor recurrence. (B) MR spectroscopy results of the same patient reveal a Cho to NAA ratio >2 in the region of enhancement (right) compared to contralateral normal side (left), further supporting a diagnosis of tumor recurrence.