Brandsma, Dieta

Abstract This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of tumor heterogeneity and patient-specific factors. These variables introduce challenges such as false positives, false negatives, and variability in the analysis of tumor signals, which can hinder the diagnostic and prognostic utility of liquid biopsies. Understanding the nuances of preanalytical variables is essential for the successful implementation of liquid biopsy in clinical settings. This paper delves into strategies aimed at mitigating the influence of preanalytical variables by emphasizing the importance of standardized sample collection protocols, optimized sample processing and storage, quality control measures, and the integration of multiple liquid biopsy modalities.

2026 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. Conclusions: 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.

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 interobserver 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.

Abstract BACKGROUND Validation of the 2016 LANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. The objective of this joint EORTC Brain Tumor Group and RANO effort was to validate the feasibility of the revised MRI scorecard for assessing response 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 (K) was used to evaluate inter-observer pairwise agreement. Statistical analyses were performed using SAS V9.4 software (Cary, NC). The sponsor of the study was the University Hospital Zurich (2018-00192). RESULTS Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among leptomeningeal metastases-related items at baseline, the best median concordance was noted for hydrocephalus (K=0.63), and the worst median for spinal linear enhancing disease (K=0.46). The median concordance for overall response was moderate (K=0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was minimal (K=0.29). Significant differences were observed when considering the specialty of the raters. Only 394 of 700 ratings (56%) were fully completed. Among 394 fully completed ratings, perfect concordance was noted in 293 ratings (74%) when comparing the overall response according to the guidelines provided in the scorecard and the overall response provided by the raters. The main discordances were noted for partial response according to the rater versus stable disease according to the guidelines (n=44), followed by progression according to the raters versus stable disease according to the guidelines (n=23). CONCLUSION Electronic case report forms with "blocking solutions" are probably required to enforce completeness and quality of scoring. These results confirm the necessity of central review and the need for training of MRI assessment in clinical trials.