This is our final blog of the pediatric glioma series, presenting the International Response Assessment in Pediatric Neuro-Oncology Working Group (RAPNO WG) recommendations for diffuse intrinsic pontine glioma (DIPG), an aggressive brainstem tumor of children1. Consistent with response determination for high grade and low grade gliomas, the working group recommendations include brain and spine MRI, neurological evaluation, and review of anti-inflammatory or antiangiogenic treatments for DPIGs. Similar to our blog coverage for Parts 1 and 2, we will focus on the recommendations for clinical imaging and standardized response assessments2,3.
On MRI, these expanding pontine tumors are hypo or isointense on T1W images, and hyperintense on T2W and fluid attenuated inversion recovery (FLAIR) sequences. This appearance serves as the foundation for the recommended MRI imaging sequences, planes, and parameters necessary to characterize the tumor (Table 11). Additional sequences or imaging methods (e.g. diffusion tensor imaging, perfusion, PET, etc.) may also be acquired as the clinical situation dictates. The WG suggests that baseline brain and spine images be performed within 4 weeks of study entry, with post treatment images obtained every 2 cycles (defined as ≤6 weeks duration). For patients without spinal disease at baseline, follow-up imaging is only required when directed by clinical suspicion. For both anatomic areas, the WG provides for some permitted adjustments based on clinical interventions and concurrent treatment.
DIPGs are challenging to measure accurately and reliably, since they are infiltrative tumors with poorly defined lesion borders. Based on their clinical experiences and published DIPG studies, the RAPNO WG advises against using local radiologist measurements as the basis for RAPNO classification1. Additionally, the WG recommends using centralized review, by neuroradiologists with expertise in pediatric central nervous system imaging, for confirmation of the DIPG diagnosis before a patient is enrolled in a clinical trial.
Use of steroids and antiangiogenic therapies, as well as pseudoprogression (an increase in apparent tumor size related to treatment which may simulate progressive disease) and intratumoral therapies, may complicate measurement of tumors in patients with DIPG for application of response criteria. The response criteria recommended by the RAPNO-WG are summarized below.
RAPNO DIPG Response Criteria (derived from Table 2)1
- Complete Response* – complete disappearance of enhancing or non enhancing TL and NTL on brain and/or spine MRI; absence of new lesions; off angiogenesis and steroids (or physiological doses), improved or stable neurological exam
- Partial Response*:
- MRI Imaging:
- Pontine lesions – ≥25% decrease (compared to baseline) in lesions on T2 or FLAIR images; imaging of the spine considered not applicable; or
- Extrapontine lesions – ≥50% decrease (compared to baseline) in measurable lesions on brain (up to 3 lesions) and/or spine MRI using T2W or FLAIR image;
- improving or stable neuro exams; stable/reduced steroid dose than baseline dosing and off angiogenesis
- MRI Imaging:
- Stable disease* – imaging changes do not qualify as PD, PR or MR; off angiogenesis and stable/reduced steroid dosing from baseline levels; improving or stable neurological condition
- Progressive disease (only one criteria must be met):
- Pontine lesions – ≥25% increase (compared to nadir) on T2W or FLAIR images; spinal imaging not required; neurological status deterioration
- Extrapontine lesions – ≥25% increase (compared to nadir) in any measurable brain or spine lesion (PD confirmation follow up imaging performed 4-8 weeks when changes of pseudo progression may be present)
*All criteria must be met
The rationale for incorporating treatment information into radiographic response criteria is strong: response criteria must accommodate features of the disease process (and its variability within and between patients with the same malignancy), and be relevant to patient-centered outcomes. In fact, the WG suggests future incorporation of rigorously validated quality of life measures into a future version of response criteria. This creates a dilemma for determination of response. As noted above, centralized imaging assessment is still perceived as essential for standardization of measurements. Therefore, further work is needed to address whether it is practical and feasible to maintain central readers’ blinding to subject treatment.
- 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
- 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
- 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