Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee

Abstract

Lack of standard response criteria in clinical trials for medulloblastoma and other seeding tumors complicates assessment of therapeutic efficacy and comparisons across studies. An international working group was established to develop consensus recommendations for response assessment. The aim is that these recommendations be prospectively evaluated in clinical trials, with the goal of achieving more reliable risk stratification and uniformity across clinical trials. Current practices and literature review were performed to identify major confounding issues and justify subsequently developed recommendations; in areas lacking scientific investigations, recommendations were based on experience of committee members and consensus was reached after discussion. Recommendations apply to both adult and pediatric patients with medulloblastoma and other seeding tumors. Response should be assessed using MR imaging (brain and spine), CSF cytology, and neurologic examination. Clinical imaging standards with minimum mandatory sequence acquisition that optimizes detection of leptomeningeal metastases are defined. We recommend central review prior to inclusion in treatment cohorts to ensure appropriate risk stratification and cohort inclusion. Consensus recommendations and response definitions for patients with medulloblastomas and other seeding tumors have been established; as with other Response Assessment in Neuro-Oncology recommendations, these need to now be prospectively validated in clinical trials.

Keywords: RANO; brain; medulloblastoma; response; tumor.

Fig. 1

A 4-year-old boy with medulloblastoma. (A) Axial T2 image demonstrates T2 hypointense mass with posterior cysts in the fourth ventricle. (B) Axial apparent diffusion coefficient map image demonstrates restricted diffusion within the mass. (C) Axial T1 postcontrast image demonstrates enhancement in the mass, posterior cysts, and leptomeningeal seeding in bilateral internal auditory canals.

Fig. 2

(A) Axial T1-weighted image at the level of the carina. Image was obtained using an interleaved slice acquisition order. Prominent CSF pulsation artifacts (long black arrow) are present around the spinal cord (short black arrow). These pulsation artifacts can obscure subarachnoid metastatic deposits. (B) Axial T1-weighted image obtained a few days later, without use of interleaved image acquisition. The spinal cord is well demarcated from the surrounding T1 hypointense CSF. (C) Sagittal 2D FSE T2 of the upper spine of the same patient. Many hypointense artifacts (arrows) are evident within the CSF surrounding the spinal cord. These artifacts are produced by physiologic CSF pulsation and could obscure subarachnoid metastatic deposits. (D) Sagittal 3D FIESTA T2-weighted image obtained a few days later. CSF has a homogeneous T2 hyperintense (myelographic) appearance, which increases sensitivity to the presence of lesions within the thecal sac.

Fig. 3

A 4-year-old girl with medulloblastoma. (A) Sagittal T1 postcontrast image of cervical spine demonstrates large nodule on ventral surface of cervical spinal cord and leptomeningeal laminar seeding. (B) Sagittal T1 postcontrast image of thoracic spine demonstrates linear leptomeningeal seeding along surface of thoracic spinal cord. (C) Sagittal T1 postcontrast image of lumbar spine demonstrates nodule in distal thecal sac.