The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab.
OBJECTIVE
The RANO criteria have not been assessed using outcome data from prospective trials. We examined the radiologic data of patients with recurrent glioblastoma from the randomized phase II trial (AVF3708g) to determine the effect of including T2/FLAIR evaluation as per RANO criteria on measurements of objective response rates (ORRs) and progression-free survival (PFS) compared with assessment based on contrast enhancement (Macdonald criteria).


METHODS
The ORRs and median PFS were determined using the RANO criteria and compared with those obtained using the Macdonald criteria. Landmark analyses were performed at 2, 4, and 6 months, and Cox proportional hazard models were used to determine the associations between OR and progression with subsequent survival.


RESULTS
The ORRs were 0.331 [95% confidence interval (CI), 0.260-0.409] and 0.393 (95% CI, 0.317-0.472) by RANO and Macdonald criteria, respectively (P < 0.0001). The median PFS was 4.6 months (95% CI, 4.1-5.5) using RANO criteria, compared with 6.4 months (95% CI, 5.5-7.1) as determined by Macdonald criteria (P = 0.01). At 2-, 4-, and 6-month landmarks, both OR status and PFS determined by either RANO or Macdonald criteria were predictive of overall survival [OS; hazard ratios for 4-month landmark (OR HR = 1.93, P = 0.0012; PFS HR, 4.23, P < 0.0001)].


CONCLUSIONS
The inclusion of T2/FLAIR assessment resulted in statistically significant differences in median PFS and ORRs compared with assessment of solely enhancing tumor (Macdonald criteria), although OR and PFS determined by both RANO and Macdonald criteria correlated with OS.
Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts. ryhuang@partners.org.
Raymond Y
RY
Huang
Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Rifaquat
R
Rahman
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Karla V
KV
Ballman
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Sara J
SJ
Felten
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
S Keith
SK
Anderson
Departments of Radiological Sciences and Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California.
Benjamin M
BM
Ellingson
Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Lakshmi
L
Nayak
Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Eudocia Q
EQ
Lee
F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Product Development Oncology, Basel, Switzerland.
Lauren E
LE
Abrey
Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Evanthia
E
Galanis
Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
David A
DA
Reardon
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Whitney B
WB
Pope
Departments of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California.
Timothy F
TF
Cloughesy
Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Patrick Y
PY
Wen
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab