Transient Enlargement in Meningiomas Treated with Stereotactic Radiotherapy

SIMPLE SUMMARY: Accurate assessment of treatment efficacy is a prerequisite for the improvement in therapeutic outcomes in clinical trials. However, it is very challenging to accurately track the size of meningiomas after radiotherapy, because of their complex shapes and often slow growth. Measuring the whole tumor volume as opposed to simple diameter measurements to assess treatment efficacy, therefore, is very promising but little is known on expected volumetric changes of meningiomas following radiotherapy. Therefore, in this study, we meticulously investigated volumetric changes in meningiomas following radiotherapy incorporating volumetric measurements from 468 MRI studies and evaluated newly proposed RANO volumetric criteria in the context of radiotherapy. We found that temporary tumor enlargement after radiotherapy overall was rare but occurred significantly more frequently after high than after low single doses of radiation, represented an important differential diagnosis to tumor progression and would have skewed results in a clinical trial if not accounted for. ABSTRACT: To investigate the occurrence of pseudoprogression/transient enlargement in meningiomas after stereotactic radiotherapy (RT) and to evaluate recently proposed volumetric RANO meningioma criteria for response assessment in the context of RT. Sixty-nine meningiomas (benign: 90%, atypical: 10%) received stereotactic RT from January 2005–May 2018. A total of 468 MRI studies were segmented longitudinally during a median follow-up of 42.3 months. Best response and local control were evaluated according to recently proposed volumetric RANO criteria. Transient enlargement was defined as volumetric increase ≥20% followed by a subsequent regression ≥20%. The mean best volumetric response was −23% change from baseline (range, −86% to +19%). According to RANO, the best volumetric response was SD in 81% (56/69), MR in 13% (9/69) and PR in 6% (4/69). Transient enlargement occurred in only 6% (4/69) post RT but would have represented 60% (3/5) of cases with progressive disease if not accounted for. Transient enlargement was characterized by a mean maximum volumetric increase of +181% (range, +24% to +389 %) with all cases occurring in the first year post-RT (range, 4.1–10.3 months). Transient enlargement was significantly more frequent with SRS or hypofractionation than with conventional fractionation (25% vs. 2%, p = 0.015). Five-year volumetric control was 97.8% if transient enlargement was recognized but 92.9% if not accounted for. Transient enlargement/pseudoprogression in the first year following SRS and hypofractionated RT represents an important differential diagnosis, especially because of the high volumetric control achieved with stereotactic RT. Meningioma enlargement during subsequent post-RT follow-up and after conventional fractionation should raise suspicion for tumor progression.