Abstract
Fractional tumor burden better correlates with histologic tumor volume fraction in treated glioblastoma than other perfusion metrics such as relative CBV. We defined fractional tumor burden classes with low and high blood volume to distinguish tumor from treatment effect and to determine whether fractional tumor burden can inform treatment-related decision-making. Forty-seven patients with high-grade gliomas (primarily glioblastoma) with recurrent contrast-enhancing lesions on DSC-MR imaging were retrospectively evaluated after surgical sampling. Histopathologic examination defined treatment effect versus tumor. Normalized relative CBV thresholds of 1.0 and 1.75 were used to define low, intermediate, and high fractional tumor burden classes in each histopathologically defined group. Performance was assessed with an area under the receiver operating characteristic curve. Consensus agreement among physician raters reporting hypothetic changes in treatment-related decisions based on fractional tumor burden was compared with actual real-time treatment decisions. Mean lower fractional tumor burden, high fractional tumor burden, and relative CBV of the contrast-enhancing volume were significantly different between treatment effect and tumor (P = .002, P < .001, and P < .001), with tumor having significantly higher fractional tumor burden and relative CBV and lower fractional tumor burden. No significance was found with intermediate fractional tumor burden. Performance of the area under the receiver operating characteristic curve was the following: high fractional tumor burden, 0.85; low fractional tumor burden, 0.7; and relative CBV, 0.81. In comparing treatment decisions, there were disagreements in 7% of tumor and 44% of treatment effect cases; in the latter, all disagreements were in cases with scattered atypical cells. High fractional tumor burden and low fractional tumor burden define fractions of the contrast-enhancing lesion volume with high and low blood volume, respectively, and can differentiate treatment effect from tumor in recurrent glioblastomas. Fractional tumor burden maps can also help to inform clinical decision-making.
Highlights
BACKGROUND AND PURPOSEFractional tumor burden better correlates with histologic tumor volume fraction in treated glioblastoma than other perfusion metrics such as relative CBV
Mean low fractional tumor burden, high fractional tumor burden, and relative CBV of the contrast-enhancing volume were significantly different between treatment effect and tumor (P = .002, P, .001, and P, .001), with tumor having significantly higher fractional tumor burden and relative CBV and lower fractional tumor burden
The current practice standard, Response Assessment in Neuro-Oncology criteria, to determine the response to therapy of a tumor is largely based on the assessment of T2/FLAIR signal extent and the size of T1 gadolinium enhancement on MR imaging across time.[1]
Summary
Forty-seven patients with high-grade gliomas (primarily glioblastoma) with recurrent contrast-enhancing lesions on DSC-MR imaging were retrospectively evaluated after surgical sampling. Consensus agreement among physician raters reporting hypothetic changes in treatmentrelated decisions based on fractional tumor burden was compared with actual real-time treatment decisions. This retrospective study was approved by Stanford University's institutional review board. Oligodendrogliomas were excluded because elevated intratumoral rCBV has been shown to relate to fine capillaries and is not necessarily indicative of aggressive tumor.[11] Patients on bevacizumab at the time of an operation for suspected recurrence were not excluded because the presence of an enlarging contrast-enhancing mass while on bevacizumab suggests a refractory response to antiangiogenic therapy.[12] After screening and assessment of eligibility, 47 patients were included (Online Fig 1). Histopathologic and molecular information, and treatment history were obtained through the electronic medical record
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