title: Modeling the efficacy of the extent of surgical resection in the setting of radiation therapy for glioblastoma.
abstract: Standard therapy for glioblastoma (GBM) includes maximal surgical resection and radiation therapy. While it is established that radiation therapy provides the greatest survival benefit of standard treatment modalities, the impact of the extent of surgical resection (EOR) on patient outcome remains highly controversial. While some studies describe no correlation between EOR and patient survival even up to total resection, others propose either qualitative (partial versus subtotal versus complete resection) or quantitative EOR thresholds, below which there is no correlation with survival. This work uses a mathematical model in the form of a reaction-diffusion partial differential equation to simulate tumor growth and treatment with radiation therapy and surgical resection based on tumor-specific rates of diffusion and proliferation. Simulation of 36 tumors across a wide spectrum of diffusion and proliferation rates suggests that while partial or subtotal resections generally do not provide a survival advantage, complete resection significantly improves patient outcomes. Furthermore, our model predicts a tumor-specific quantitative threshold below which EOR has no effect on patient survival and demonstrates that this threshold increases with tumor aggressiveness, particularly with the rate of proliferation. Thus, this model may serve as an aid for determining both when surgical resection is indicated as well as the surgical margins necessary to provide clinically significant improvements in patient survival. In addition, by assigning relative benefits to radiation and surgical resection based on tumor invasiveness and proliferation, this model confirms that (with the exception of the least aggressive tumors) the survival benefit of radiation therapy exceeds that of surgical resection.
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Leith
authors.initials: L
authors.lastname: Hathout
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.|UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California, Los Angeles, California, USA.|Department of Biomedical Physics, David Geffen School of Medicine, University of California, Los Angeles, California, USA.|Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ellingson
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Whitney
authors.initials: W
authors.lastname: Pope
mesh_terms: D001932:Brain Neoplasms; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D006801:Humans; D008954:Models, Biological; D015996:Survival Rate
keywords: Extent of resection; glioblastoma; mathematical modeling; radiation therapy; surgical therapy