Our past blog entitled “Assessing Neuro-Oncology Disease in Pediatric Clinical Trials” chronicled the evolution and focus of the International Response Assessment in Pediatric Neuro-Oncology Working Group (RAPNO-WG) and described initial guidance for gliomas in pediatric clinical trials.1 A series of recent follow-up publications provide more specific response criteria recommendations “for three tumor subtypes, namely high-grade glioma, low-grade glioma, and diffuse intrinsic pontine glioma, due to the inherent radiographic features of each”.2-4
This blog entry highlights recommendations for the most common pediatric brain tumor – low grade gliomas. The proposed committee guidance recommends the combined use of imaging, clinical, and when appropriate functional assessments to assess treatment response in clinical trials. Our focus is on imaging guidelines.
The committee presents the challenges of obtaining standardized baseline imaging when emergency symptoms of elevated intracranial pressure may dictate a non-contrast CT exam be performed before surgical invention preventing the acquisition of the standardized MRI imaging protocol (1.5T or 3.0T magnets; T1-W, T2-W, T2-W FLAIR, DWI/ADC and T1-W post macrocyclic gadolinium contrast enhancement; 2D or 3D imaging acquisitions are both used in the response assessment) which provides improved accuracy for determining tumor burden and surrounding involvement of adjacent structures. Measureable lesions should be visible on all 3 imaging planes and measure at least 10mm in each plane. Typically there will be only 1 target lesion identified and when multifocal disease occurs (a rare occurrence) the RAPNO committee recommends “a maximum of five lesions should be measured (the largest and most symptomatic lesions or those actively progressing at the time of treatment initiation are preferred).”2
When feasible baseline imaging should be performed prior to surgery and include MRI of the brain, optic chiasm, and the spine if indicated by tumor location and metastatic risk. The publication provides a detailed summary of the minimum MRI sequences to be obtained and instructs that these may be upgraded or complemented with additional imaging best suited for the clinical situation, with follow up imaging performed every 12 weeks2. Recommendations are also presented on performing post-surgical imaging prior to initiation of study driven therapies and guidelines on measuring “a cystic component of a mixed solid-cystic tumor or a true tumor cyst, it should be included in the measurement of a target lesion” when the tumor cyst is part of the solid tumor; is inseparable from the solid tumor; has an enhancing thickened cystic wall or has clusters of microcysts within a tumor2.
RAPNO Response Criteria (derived from Panel 3)2
- Complete Response# – complete disappearance of all T2W, T2-W FLAIR, and contrast lesions using the baseline MRI or best recorded response for comparison
- Partial Response# – 50% or greater reduction in the size of the target lesion on T2W and T2-W FLAIR, and variable changes in enhancement* using the baseline MRI or best recorded response for comparison.
- Minor response# (used in some studies) – 25% and 49% reduction in tumor measurement, usually on T2W and T2-W FLAIR and variable changes in enhancement*, using the baseline MRI or best recorded response for comparison
- Stable disease# – neither a decrease nor an increase in tumor size sufficient to qualify as PD or PR. [note, depending on whether the minor response category is used in a specific protocol, stable disease can also represent patients with 0–49% tumor shrinkage, and up to 24% enlargement, using the baseline MRI or best recorded response for comparison.
# require patients be clinically stable or improved on physical examination and functional or neurological assessment
* (both an increase and a decrease in enhancement do not contribute overall))
The RAPNO Low-Grade Gliomas committee recommendations represent an effort to standardize pediatric clinical trial response assessments together with standardized MRI imaging data collection for the most common pediatric CNS tumor and will require further validation in prospective trials.
- 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
- Jason Fangusaro et al., Imaging Guidelines for Paediatric Brain Tumours 1 Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol 2020; 21: e305–16
- 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