Our previous blog introduced the updated guidance for gliomas in pediatric clinical trials published by the International Response Assessment in Pediatric Neuro-Oncology Working Group (RAPNO-WG).1 This blog focuses on Part 2 of the Imaging Guidelines for Pediatric Brain Tumors series recommendations for diffuse midline glioma and other high-grade gliomas2. Part 2 excludes anaplastic ependymoma and diffuse intrinsic pontine glioma, the subject of Part 3 recommendations which will be discussed in an upcoming blog3. Similar to Part 1, we will focus here on the imaging related recommendations.
The WG considered many of the challenges in response assessments by reviewing clinical practices and the literature. The guidance addresses imaging standardization across trials measuring disease extent, and other factors affecting radiological response assessments (e.g., impact of therapy, spinal disease, biopsies, etc).
The RAPNO-WG recommends standardization for MRI imaging of the brain and spine, reducing differences in the imaging process across clinical sites to emphasize collection of the imaging related changes attributable to disease response or progression. Important aspects of imaging standardization for high-grade glioma include (more imaging sequence details are cited in the publication)2:
- Using the same 1.5T or 3T scanner at all study time points
- Brain imaging sequences (pre and post contrast) including axial T1-weighted, T2-weighted, T2 FLAIR, and DWI with ADC imaging, acquiring 3D or 2D image sets in at least 2 imaging planes
- Spine imaging sequences (post contrast) including sagittal T1-weighted, axial T1-weighted, and sagittal CISS or FIESTA
Similar to other oncologic response criteria, RAPNO-WG classify lesions as target lesions (TL) and non-target lesions (NTL), and recommend following up to 3 TLs when more than one high grade glioma is present. Predominantly necrotic tumors can be selected if representative of the disease, and the WG suggests excluding cystic tumors unless the cyst is “integrated within the solid component or not readily separable from the solid tumor component”2.
The WG recommends clinical trials have MRI follow up imaging at least every 3 months for the first year and this interval may be increased thereafter. Should relapse occur, imaging would be performed more frequently (e.g. every 2 months). Brain and spine MRI imaging should be performed at baseline and followed concurrently (same time points) when disease is present in both locations. If no spinal disease is detected at baseline, brain imaging only is acceptable unless there is increased clinical suspicion of spinal involvement. Note that when Complete Response (CR) is being assessed, imaging of the brain and spine is required for confirmation.
A limited representation of the high grade glioma response criteria is shown below and the WG publication presents additional details or considerations for clinical trial development e.g., imaging post radiation or biopsy, use of biomarkers, treatment interventions (e.g. immunotherapy) and inclusion of advanced imaging techniques.
RAPNO Response Criteria (derived from Table 2)2
- Complete Response (CR)* – complete disappearance of TL and NTL on T1W, T2W, T2-W FLAIR, and contrast enhanced images; resolution on DWI imaging; absence of new lesions; off angiogenics and steroids, improved or stable clinical condition
- Partial (PR)* or Minor Response (MR)* – 50% or greater reduction in TL sum of the products using two perpendicular diameter measurements (SOM); Minor Response is defined as ≥25% and <50% reduction in SOM; decreased restricted diffusion on DWI imaging; no new lesions; off angiogenics and stable/reduced steroid dosing from baseline; improved or stable clinical condition
- Stable disease (SD) – imaging changes do not qualify as PD, PR or MR; no new lesions; off angiogenics and stable/reduced steroid dosing from baseline; improved or stable clinical condition
- Progressive disease (PD) – ≥25% increase in TL SOM or unequivocal increase in NTL from baseline or nadir; increased or new area of restricted diffusion on DWI imaging (not related to treatments or interventions); presence of new lesions; worsened clinical status
*response confirmed by repeated imaging ≥8 weeks apart
As discussed in Part 1 of this blog series, the WG recommendations on standardization of imaging and response assessments represents leading international experts suggestions to improve clinical studies in children with high grade glioma and will require further study and validation.
- Warren EW et al. Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee. NeuroOncology 20(1), 13–23, 2018
- Craig Erker et al., Imaging Guidelines for Paediatric Brain Tumours 2 Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21: e317–29
- Tabitha M Cooney et al., Imaging Guidelines for Paediatric Brain Tumours 3 Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21: e330–36