A Novel Metric of Patient-specific Response to Treatment for Glioblastoma Discriminates Patients With Pseudo-progression

Purpose/Objective(s): A complete resolution of enhancing tumor on T1 weighted contrast MRI of patients with glioblastoma following resection and chemoradiation has been demonstrated to predict for longer survival. We have developed a novel method for discriminating time to progression following therapy for glioblastoma using computational models of the proliferative and diffusive tumor burden that account for the unique geometry and biology of each patient’s tumor. Using kinetic models informed by patient-specific measurements, we simulate the growth of an untreated tumor and estimate the number of “Days Gained” by the therapy. The goal of this study was to determine whether this metric of patient response would assist in evaluating patients who have residual T1-enhancing lesions following treatment with concurrent chemoradiation for glioblastoma. Materials/Methods: Twenty-eight patients with glioblastoma were prospectively enrolled prior to chemoradiation in our IRB approved image database study from 2003 to 2009. All patients underwent chemoradiation therapy at the University of Washington and had evidence of residual enhancing tumor on T1 weighted images in the first postradiation MRI study. Upon examination of subsequent images and clinical interventions we found evidence of pseudo-progression in 6 of these patients. We created individualized models of tumor growth for these 28 patients and computed their “Days Gained” score a measure of deflection of actual tumor growth from the model-predicted untreated tumor burden. Results: Based on a reporter-operator curve, we found that 104 Days Gained was an optimal discriminating cutoff (area under curve [AUC] Z 76.1%). We found that all patients with pseudo-progression (n Z 6) had Days Gained scores of 104 or above, with an odds ratio of 5.5 (p Z 0.03). None of the patients with Days Gained scores less than 104 (n Z 11) had pseudo-progression. There was no significant difference between the patients with greater than 104 Days Gained and no pseudo-progression (n Z 11) and those who had pseudo-progression. Additionally, patients with a higher Days Gained score had a longer predicted survival (median 610 vs. 376 days, p Z 0.04). Conclusions: Our novel method for measuring the predicted impact of treatment on both diffuse and proliferative tumor burden for glioblastoma discriminates those patients who are likely to have true progression on their first post-treatment scan. While we anticipated that patients with pseudo-progression would have the lowest estimate of Days Gained due to nonspecific imaging changes, we find instead that these patients are indistinguishable from the long-term responders. This difference in Days Gained may indicate that there is a robust biological response underlying the patients with an increased survival probability that is the subject of further investigation. Author Disclosure: A.D. Trister: None. M.L. Neal: None. T. Cloke: None. A.L. Baldock: None. S. Ahn: None. M.M. Mrugala: None. J.K. Rockhill: F. Honoraria; Elekta. R. Rockne: None. K.R. Swanson: None.