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Rapid Early Tumor Progression is Prognostic in Glioblastoma Patients

Palmer, Joshua D., MD*; Bhamidipati, Deepak, MD; Shukla, Gaurav, MD, PhD; Sharma, Dinesh, MD§; Glass, Jon, MD; Kim, Lyndon, MD; Evans, James J., MD; Judy, Kevin, MD; Farrell, Christopher, MD; Andrews, David W., MD; Wang, Zi-Wuan, PhD#; Peiper, Stephen C., MD#; Werner-Wasik, Maria, MD**; Shi, Wenyin, MD, PhD**

American Journal of Clinical Oncology: May 2019 - Volume 42 - Issue 5 - p 481–486
doi: 10.1097/COC.0000000000000537
Original Articles: Central Nervous System
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Objectives: Determine the prognostic significance of rapid early tumor progression before radiation and chemotherapy for glioblastoma patients.

Methods: A retrospective review of glioblastoma patients was performed. Rapid early progression (REP) was defined as new enhancing tumor or >25% increase in enhancement before radiotherapy. The pre/postoperative magnetic resonance imaging was compared with the preradiation magnetic resonance imaging to determine REP. A blinded review of imaging was performed. Kaplan-Meier curves were generated to compare progression-free and overall survival (OS). Univariate analysis was performed using the log-rank test for categorical variables and Cox proportional hazards for continuous variables. Multivariable logistic regression was performed to assess factors related to early progression and Cox proportional hazards model was used for multivariate analysis of OS.

Results: Eighty-seven patients met entry criteria. A total of 52% of patients developed REP. The OS in the REP group was 11.5 months (95% confidence interval [CI]: 7.4-17.6) and 20.1 months (95% CI: 17.8-26.1) without REP (P=0.013). On multivariate analysis including significant prognostic factors, presence of REP was found to increase the risk of death (hazard ratio: 2.104, 95% CI: 1.235-3.583, P=0.006). A total of 74% of patients recurred in the site of REP.

Conclusions: REP was common and independently predicted for a worse OS. Integrating REP with MGMT promotor methylation improved prognostic assessment. The site of REP was a common site of tumor progression. Our findings are hypothesis generating and may indicate a particular subset of glioblastoma patients who are resistant to current standard of care therapy. Further study to determine other molecular features of this group are underway.

*Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center, Columbus, OH

Department of Medicine, Baylor College of Medicine, Houston, TX

Department of Radiation Oncology, Christiana Care Helen F. Graham Cancer Center, Newark, DE

Departments of §Radiology

Neuro-Oncology

Neurosurgery

#Pathology

**Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Supported by the Alpha Omega Alpha Post-graduate research award.

J.D.P.: received research grant funding from the Alpha Omega Alpha Honors Medical Society. The other authors declare no conflicts of interest.

Reprints: Joshua D. Palmer, MD, Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute, The Ohio State Wexner Medical Center, 460 W. 10th Ave., Columbus, OH 43215. E-mail: joshua.palmer@osumc.edu.

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