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NIMG-01. DIFFUSION MRI PHENOTYPES PREDICT OVERALL SURVIVAL BENEFIT FROM ANTI-VEGF MONOTHERAPY IN GLIOBLASTOMA AT FIRST OR SECOND RELAPSE

ABSTRACT: Abstract Anti-VEGF therapies remain controversial in the treatment of recurrent GBM. In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an OS advantage when treated with anti-VEGF therapy at first or second recurrence. These findings were then validated using data from a separate trial. METHODS A total of 258 patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate phase II clinical trials were included. Data from 4 trials were used as training data and a fifth for validation: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929). Apparent diffusion coefficient (ADC) double-Gaussian histogram analysis was performed prior to therapy to estimate “ADCL”, the mean of the lower ADC distribution. Pre-treatment ADCL, enhancing volume, and clinical variables were tested as independent prognostic factors for OS. RESULTS The coefficient of variance in double baseline ADCL measurements was 2.5% and did not significantly differ (P=0.454). An ADCL cut-off value of 1.24 um2/ms produced the largest OS differences between patients (HR~0.5), with an ADCL>1.24 um2/ms resulting in better OS. Training and validation data confirmed baseline ADCL as an independent predictive biomarker for OS in all anti-VEGF therapies (P<0.05), but not lomustine (P=0.1455), after accounting for age and baseline enhancing tumor volume. Results suggest pre-treatment diffusion MRI is a predictive imaging biomarker for OS in patients with recurrent GBM treated with anti-VEGF monotherapy at first or second relapse.

SUBMITTER: Ellingson B

PROVIDER: S-EPMC5692227 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe optimal treatment approach to patients with acute myeloid leukemia (AML) who relapse after an allogeneic hematopoietic cell transplant (allo-HCT) remains elusive. No randomized clinical trial comparing survival outcomes of a second allo-HCT (allo-HCT2) vs donor lymphocyte infusion (DLI) has been conducted to date.ObjectiveTo compare overall survival (OS) after an allo-HCT2 or DLI in relapsed AML after a first allo-HCT.Design, setting, and participantsA retrospective registry study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation involving 418 adults who received an allo-HCT2 (n?=?137) or DLI (n?=?281) for postallograft-relapsed AML. Analysis was assessed on the principle of intent-to-first received intervention. The data were collected from November 21, 2015, to May 15, 2017, and analysis was performed June 1, 2017.Main outcomes and measuresNumber of patients with relapsed AML who are alive after 2 years and 5 years from receiving an allo-HCT2 or DLI.ResultsOf the 418 patients, 228 (54.5%) were men; mean age was 46.2 years (interquartile range, 36.5-56.9 years). There was no apparent difference in OS whether an allo-HCT2 or DLI was prescribed (2-year OS with allo-HCT2, 26%; 5-year OS with allo-HCT2, 19%; 2-year OS with DLI, 25%; 5-year OS with DLI, 15%; P?=?.86). Overall survival was better if either of these procedures was offered when the patient was in complete remission (hazard ratio, 0.55; 95% CI, 0.41-0.74; P?<?.001). Conversely, OS was low for patients relapsing within less than 6 months after an allo-HCT1, regardless of the treatment prescribed (5-year OS: allo-HCT2, 9%; 95% CI, 1%-17% vs DLI, 4%; 95% CI, 1%-8%; P?=?.86).Conclusion and relevanceHeterogeneity of the patient-, disease-, and treatment-related characteristics limit the ability to recommend one approach over another. Findings of this study highlight that best outcomes seem to be achieved in patients relapsing 6 or more months from an allo-HCT1 or those in complete remission at the time of either allo-HCT2 or DLI.

Dataset Information

NIMG-01. DIFFUSION MRI PHENOTYPES PREDICT OVERALL SURVIVAL BENEFIT FROM ANTI-VEGF MONOTHERAPY IN GLIOBLASTOMA AT FIRST OR SECOND RELAPSE

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