title: Comparison of ADC metrics and their association with outcome for patients with newly diagnosed glioblastoma being treated with radiation therapy, temozolomide, erlotinib and bevacizumab.
abstract: To evaluate metrics that describe changes in apparent diffusion coefficient (ADC) and to examine their association with clinical outcome for patients with newly diagnosed GBM who were participating in a Phase II clinical trial of treatment with radiation (RT), temozolomide, erlatonib and bevacizumab. Thirty six patients were imaged after surgery but prior to therapy and at regular follow-up time points. The following ADC metrics were evaluated: (1) histogram percentiles within the T2-hyperintense lesion (T2L) at serial follow-ups; (2) parameters obtained by fitting a two-mixture normal distribution to the histogram within the contrast-enhancing lesion (CEL) at baseline; (3) parameters obtained using both traditional and graded functional diffusion maps within the CEL and T2L. Cox Proportional Hazards models were employed to assess the association of the ADC parameters with overall survival (OS) and progression-free survival (PFS). A lower ADC percentile value within the T2L at early follow-up time points was associated with worse outcome. Of particular interest is that, even when adjusting for clinical prognostic factors, the ADC10% within the T2L at 2 months was strongly associated with OS (p < 0.001) and PFS (p < 0.007). fDM metrics showed an association with OS and PFS within the CEL when considered by univariate analysis, but not in the T2L. Our study emphasizes the value of ADC metrics obtained from the T2L at the post-RT time point as non-invasive biomarkers for assessing residual tumor in patients with newly diagnosed GBM being treated with combination therapy that includes the anti-angiogenic agent bevacizumab.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), 1700 4th Street, Byers Hall, Box 0775, San Francisco, CA, 94143-0775, USA, qiuting.wen@ucsf.edu.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Wen
authors.forename: Laleh
authors.initials: L
authors.lastname: Jalilian
authors.forename: Janine M
authors.initials: JM
authors.lastname: Lupo
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clarke
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069347:Erlotinib Hydrochloride; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000068258:Bevacizumab; D003606:Dacarbazine; D000069347:Erlotinib Hydrochloride; D000077204:Temozolomide