Evaluation of RAPNO criteria in medulloblastoma and other leptomeningeal seeding tumors using MRI and clinical data

Abstract

Background Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated. Methods We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients with MBL diagnoses, high grade glioma, embryonal tumor, germ cell tumor, or choroid plexus papilloma. Interobserver agreement, objective response (OR) rates, and progression-free survival (PFS) were calculated. Landmark analyses were performed for OR and progression status at 0.5, 1.0, and 1.5 years after treatment initiation. Cox proportional hazards models were used to determine the associations between OR and progression with overall survival (OS). Subgroup analyses based on tumor subgroup and treatment modality were performed. Results The median follow-up time was 4.0 years. In all patients, the OR rate was .0.565 (95% CI: 0.505–0.625) by RAPNO. The interobserver agreement of OR determination between 2 raters (a neuroradiologist and a neuro-oncologist) for the RAPNO criteria in all patients was 83.8% (k statistic = 0.815; P < 0.001). At 0.5-, 1.0-, and 1.5-year landmarks, both OR status and PFS determined by RAPNO were predictive of OS (hazard ratios [HRs] for 1-year landmark: OR HR = 0.079, P < 0.001; PFS HR = 10.192, P < 0.001). In subgroup analysis, OR status and PFS were predictive of OS for all tumor subtypes and treatment modalities. Conclusion RAPNO criteria showed excellent consistency in the treatment response evaluation of MBL and other leptomeningeal seeding tumors. OR and PFS determined by RAPNO criteria correlated with OS.

Current state of pediatric neuro-oncology imaging, challenges and future directions

“…Standardization of image acquisition protocols and definitions in diagnosis and response assessment of pediatric brain tumors, as addressed in a few consensus recommendation studies in adult brain tumors can be helpful for reliable tumor response assessment [79 , 82] . The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has provided guidelines and recommendations [ [12] , [13] , [14] , [15] , [16] ], which if followed, can potentially help in reproducibility of extracted radiomic features among different scanners and centers, and further contribute to development of generalizable predictive models.…”

Development of Randomized Trials in Adults with Medulloblastoma—The Example of EORTC 1634-BTG/NOA-23

“…Data on the pharmacokinetics of sonidegib suggest favorable blood–brain barrier penetration [ 68 , 73 ]. As medulloblastomas are associated with a disrupted blood–brain barrier [ 74 ] that correlates to contrast enhancement in MRI [ 75 ], sufficient intra-tumoral drug levels can be anticipated. In addition, sonidegib will be given in combination with radiotherapy in EORTC 1634-BTG/NOA-23, which is thought to further disrupt the blood–brain barrier, at least in the short term [ 76 ].…”

“…Treatment decisions will be based on the adapted response assessment in pediatric neuro-oncology (RAPNO) criteria [ 75 ] as assessed by the local investigator. Imaging will be verified by a central review board at the time point of patient inclusion and suspected tumor progression.…”

Children's Oncology Group's 2023 blueprint for research: Central nervous system tumors

“…The rapid screening process also includes a COG‐wide effort for improved technical radiologic staging by magnetic resonance imaging (MRI) for CNS tumors prone to leptomeningeal dissemination 11–13 . Current and future clinical trials for children with CNS tumors are dependent on precise diagnosis and staging.…”

“…3 Retrospective molecular analyses of cohorts from the last generation of COG clinical trials have generated unprecedented, rich resources of clinical and molecular data [8][9][10] The rapid screening process also includes a COG-wide effort for improved technical radiologic staging by magnetic resonance imaging (MRI) for CNS tumors prone to leptomeningeal dissemination. [11][12][13] Current and future clinical trials for children with CNS tumors are dependent on precise diagnosis and staging. Proton therapy, increasingly available for children who require radiation therapy (RT), aims to spare healthy tissue and decrease late effects.…”