title: Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.
abstract: BACKGROUND
  We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not.
  
  
  METHODS
  A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps. Intermediate ADC (IADC) VOI represented voxels within the FLAIR VOI having ADC in the range of highly cellular tumor (0.7-1.1 × 10-3mm2/s) (IADC VOI). Therapeutic benefit was determined by tissue pathology and survival on trial. IADC VOI, pGdT1 VOI, FLAIR VOI, and RANO assessment results were correlated with patient benefit.
  
  
  RESULTS
  Five patients were deemed to have received therapeutic benefit and the other five patients did not. The average time on trial for the benefit group was 194 days, as compared to 81 days for the no benefit group. IADC VOI correlated well with the presence or absence of clinical benefit in 10 patients. Furthermore, pGd VOI, FLAIR VOI, and RANO assessment correlated less well with response.
  
  
  CONCLUSIONS
  MRI reveals an initial increase in volumes of abnormal tissue with contrast enhancement, edema, and intermediate ADC suggesting hypercellularity within the first 0-6 months of immunotherapy. Subsequent stabilization and improvement in IADC VOI appear to better predict ultimate therapeutic benefit from these agents than conventional imaging.
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, Boston, MA, USA.|Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Radiology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Radiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, Boston, MA, USA.|Department of Behavioral Neuroscience, College of Sciences, Northeastern University, Boston, MA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Stroiney
authors.affiliation: Department of Radiology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Radiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Helgager
authors.affiliation: CenterforNeuro-Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA. David_Reardon@dfci.harvard.edu.|Department of Medicine, Harvard Medical School, Boston, MA, USA. David_Reardon@dfci.harvard.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Department of Radiology, Harvard Medical School, Boston, MA, USA. gsyoung@partners.org.|Department of Radiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. gsyoung@partners.org.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Young
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D003287:Contrast Media; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D000077594:Nivolumab; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003287:Contrast Media; D000074324:Ipilimumab; D000077594:Nivolumab; C582435:pembrolizumab
keywords: ADC; GBM; Immunotherapy; MRI; Pseudoprogression