Prospective validation of a new imaging scorecard to assess leptomeningeal metastasis: A joint EORTC BTG and RANO effort

Abstract

Background Validation of the 2016 RANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. Accordingly, this joint EORTC Brain Tumor Group and RANO effort sought to prospectively validate a revised MRI scorecard for response assessment in leptomeningeal metastasis. Methods Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The Kappa coefficient was used to evaluate the inter-observer pairwise agreement. Results Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among single leptomeningeal metastases-related imaging findings at baseline, the best median concordance was noted for hydrocephalus (Kappa=0.63), and the worst median concordance for spinal linear enhancing disease (Kappa=0.46). The median concordance of raters for the overall response assessment was moderate (Kappa=0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was fair (Kappa=0.29) and virtually absent for their response to treatment. 394 of 700 ratings (20 patients x 35 raters, 56%) were fully completed. In 308 of 394 fully completed ratings (78%), the overall response assessment perfectly matched the summary interpretation of the single ratings as proposed in the scorecard instructions. Conclusion This study confirms the principle utility of the new scorecard, but also indicates the need for training of MRI assessment with a dedicated reviewer panel in clinical trials. Electronic case report forms with “blocking options” may be required to enforce completeness and quality of scoring.

Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan

“…Radiological assessment was based on the EORTC/RANO revised LM scorecard 3 and performed by a dedicated neuroradiologist at DFCI (HL) and Duke (CL). The scorecards were completed for each patient at each MRI re-evaluation; BrMs response was also reported (Supplementary Table 1).…”

“…Between 5-15% of patients with metastatic breast cancer (MBC) develop leptomeningeal metastases (LM) 1,2 with approximately 60% having no parenchymal brain metastases (BrMs) 3 . The presence of LM has a drastic impact on patients' function and quality of life, leading to poor survival outcomes, with a median survival of only 4.4 months in human epidermal growth factor receptor 2-positive (HER2+) MBC 4 .…”

“…The assessment of treatment-response of LM in clinical practice and clinical trials remains challenging. Recently, a joint effort of the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group and Response Assessment in Neuro-Oncology (RANO) prospectively validated a revised magnetic resonance imaging (MRI)-scorecard for response assessment in LM, showing a substantial interobserver agreement and associated prognostic significance 3 .…”

Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers: A systematic review and meta-analysis

“…MRI is a qualitative diagnostic tool and may have limitations of inter-reader variability and nonspecific findings 6 ; however, a recent report from EORTC BTG and RANO effort showed the usefulness of a new imaging scorecard. 9 , 10 Advances in technology, including the clinical usage of high-magnetic-field machines and pre- and post-contrast T2 fluid-attenuated inversion recovery (FLAIR) MRI, may refine and improve the imaging assessment of LM in the future. 32 We should be careful when using MRI to assess various primary malignancies, as Prommel et al 33 showed that the sensitivities of cytology and MRI were significantly influenced by the primary tumor type as solid or hematological malignancies.…”

“… 8 The diagnosis of LM is currently based on the three examination modalities: neurological evaluations, neuroimaging and cerebrospinal fluid (CSF) cytology. 9 , 10 However, the performance of these modalities is reportedly suboptimal. 5 CSF cytology remains the gold standard for the diagnosis of LM, but has been of low sensitivity.…”