OS08.6.A Glioblastoma treatment response machine learning monitoring biomarkers: a systematic review and meta-analysis

BACKGROUND The aim of the systematic review was to assess recently published studies on diagnostic test accuracy of glioblastoma treatment response monitoring biomarkers in adults, developed through machine learning (ML). MATERIAL AND METHODS PRISMA methodology was followed. Articles published 09/2018-01/2021 (since previous reviews) were searched for using MEDLINE, EMBASE, and the Cochrane Register by two reviewers independently. Included study participants were adult patients with high grade glioma who had undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide) and subsequently underwent follow-up imaging to determine treatment response status (specifically, distinguishing progression/recurrence from progression/recurrence mimics - the target condition). Risk of bias and applicability was assessed with QUADAS 2. A third reviewer arbitrated any discrepancy. Contingency tables were created for hold-out test sets and recall, specificity, precision, F1-score, balanced accuracy calculated. A meta-analysis was performed using a bivariate model for recall, false positive rate and area-under the receiver operator characteristic curve (AUC). RESULTS Eighteen studies were included with 1335 patients in training sets and 384 in test sets. To determine whether there was progression or a mimic, the reference standard combination of follow-up imaging and histopathology at re-operation was applied in 67% (13/18) of studies. The small numbers of patient included in studies, the high risk of bias and concerns of applicability in the study designs (particularly in relation to the reference standard and patient selection due to confounding), and the low level of evidence, suggest that limited conclusions can be drawn from the data. Ten studies (10/18, 56%) had internal or external hold-out test set data that could be included in a meta-analysis of monitoring biomarker studies. The pooled sensitivity was 0.77 (0.65–0.86). The pooled false positive rate (1-specificity) was 0.35 (0.25–0.47). The summary point estimate for the AUC was 0.77. CONCLUSION There is likely good diagnostic performance of machine learning models that use MRI features to distinguish between progression and mimics. The diagnostic performance of ML using implicit features did not appear to be superior to ML using explicit features. There are a range of ML-based solutions poised to become treatment response monitoring biomarkers for glioblastoma. To achieve this, the development and validation of ML models require large, well-annotated datasets where the potential for confounding in the study design has been carefully considered. Therefore, multidisciplinary efforts and multicentre collaborations are necessary.