Defining tumor growth in vestibular schwannomas: a volumetric inter-observer variability study in contrast-enhanced T1-weighted MRI

Objective: For patients with vestibular schwannomas (VS), a conservative observational approach is increasingly used. Therefore, the need for accurate and reliable volumetric tumor monitoring is important. Currently, a volumetric cutoff of 20% increase in tumor volume is widely used to define tumor growth in VS. The goal of this study is to investigate the tumor volume dependency on the limits of agreement (LoA) for volumetric measurements of VS by means of an inter-observer study. Methods: This retrospective study included 100 VS patients who underwent contrast-enhanced T1-weighted MRI. Five observers volumetrically annotated the images. Observer agreement and reliability was measured using the LoA, estimated using the limits of agreement with the mean (LOAM) method, and the intraclass correlation coefficient (ICC). Influence of imaging parameters and tumor characteristics were assessed using univariable and multivariable linear regression analysis. Results: The 100 patients had an average median tumor volume of 903 mm3 (IQR: 193-3101). Peritumoral cysts were found in 6 (6%) patients. Patients were divided into four volumetric size categories based on tumor volume quartile. The smallest tumor volume quartile showed a LOAM relative to the mean of 26.8% (95% CI: 23.7, 33.6), whereas for the largest tumor volume quartile this figure was found to be 7.3% (95% CI: 6.5, 9.7) and when excluding peritumoral cysts: 4.8% (95% CI: 4.2, 6.2). Of all imaging parameters and tumor characteristics, only tumor volume was associated with the LoA (adjusted B=-0.001 [95% CI: -0.001, 0.000; P=0.003]). Conclusions: Agreement limits within volumetric annotation of VS are affected by tumor volume, since the LoA improves with increasing tumor volume. As a result, for tumors larger than 200 mm3, growth can reliably be detected at an earlier stage, compared to the currently widely used cutoff of 20%. However, for very small tumors, growth should be assessed with higher agreement limits than previously thought. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Stefan Cornelissen, Sammy M. Schouten, and Patrick P.J.H. Langenhuizen are funded by the Highly Specialised Care & Research programme (TZO programme), (partly) financed by the Netherlands Organisation for Health Research and Development (ZonMw). Grant number: 10070012010006' ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The IRB of Radboud University Medical Center waived ethical approval of this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study will not be publicly available