2595 - Rapid Early Progression after Surgery for IDH-Wildtype Glioblastoma and the Importance of the Pre-Radiation Planning MRI

J. J. Sackett¹, K. Ahmed², T. D. Struve III¹, L. E. Pater¹, N. Andaluz³, J. Forbes³, R. Chaudhary⁴, L. Yogendran⁵, S. Sengupta⁶, J. C. Breneman¹, G. Udstuen², and K. Wang¹; ¹Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, ²University of Cincinnati, Cincinnati, OH, ³Department of Neurosurgery, University of Cincinnati, Cincinnati, OH, ⁴Division of Oncology, University of Cincinnati, Cincinnati, OH, ⁵Department of Neurology, University of Cincinnati, Cincinnati, OH, ⁶Division of Neuro-Oncology, UNC-Chapel Hill, Chapel Hill, NC

Purpose/Objective(s): The use of pre-radiation therapy (RT) planning MRI for glioblastoma (GBM) is inconsistent. Current NCCN guidelines recommend treatment planning on preoperative or immediate postoperative MRI. We characterized and investigated implications of rapid early progression (REP) on pre-RT planning MRIs standardly performed at our institution. We hypothesized that REP is associated with worse survival, earlier need for intervention, and performs better than extent of resection as a prognostic variable for risk stratification. Materials/

Methods: We reviewed patients with a new pathologic diagnosis of IDH-wildtype GBM who received =40 Gy RT between 2016-2024. Inclusion required a pre-RT planning MRI =2 weeks after postoperative MRI. REP was defined as >1cm thickness of new enhancing disease between postoperative and pre-RT MRI. Extent of surgical resection was scored 1-4 as an ordinal variable, 1:gross total resection (GTR, >95%); 2: near total resection (NTR, 90-95%); 3: subtotal resection (STR); 4: biopsy only. Endpoints included overall survival (OS) and bevacizumab/re-resection. Cox proportional hazards model was used to analyzed age, extent of resection, MGMT methylation, short course RT, and presence of REP. Significant covariates were included in the multivariate analysis.
Results: The final cohort included 84 patients (median age 63). The median number of days from postoperative MRI to pre-RT MRI was 27 days, and 10 patients (12%) received short course RT. Surgical extent was GTR in 45 (54%), NTR in 15 (18%), STR in 17 (20%), and biopsy only in 7 (8%). REP occurred in 46% of patients and was less frequent after GTR (31%) vs. NTR (73%), STR (59%), or biopsy (57%). On univariate analysis, MGMT methylation, REP, and extent of resection were prognostic for OS and freedom from bevacizumab/re-resection (Table). On multivariate analysis, REP remained significant (HR 2.2, p=0.005 for OS; HR 2.7, p=0.002 for bevacizumab/re-resection) while extent of resection lost significance. Median OS was 1.1 years with REP vs. 1.7 years without.
Conclusion: REP occurs frequently in GBM patients, adds a measure of "growth rate", and may perform equal or better than surgical resection in predicting survival and need for bevacizumab or re-resection for fast progressing GBMs. These data have implications for clinical trial design and support pre-RT planning MRIs as standard of care for accurate tumor delineation, risk stratification, and identification of high risk patients who may need earlier intervention.

Endpoint: OS	Univariate p (HR)	Multivariate p (HR)
Surgery Extent	0.003 (1.5)	0.080 (1.3)
MGMT+	0.006 (0.5)	0.002 (0.4)
Rapid early progression	0.007 (2.0)	0.005 (2.2)
Endpoint: Bevacizumab/re-resection	Univariate p (HR)	Multivariate p (HR)
Surgery Extent	0.028 (1.4)	0.26 (1.2)
MGMT+	0.006 (0.5)	0.004 (0.4)
Rapid early progression	0.007 (2.0)	0.002 (2.7)