Presenter(s)
V. Munlapudi1, J. Guzzino2, D. J. Crompton3, S. Agarwal4, E. J. Lehrer5, S. Kern6, A. W. Bogan7, S. A. Vora8, A. Quinones-Hinojosa9, T. Burns10, W. J. Sherman11, P. D. Brown12, N. N. Laack II5, J. L. Peterson3, J. H. Uhm13, M. Ruff13, U. Sener14, W. Breen5, and D. M. Trifiletti3; 1Florida Atlantic University, Boca Raton, FL, 2Florida State University College of Medicine, Tallahassee, FL, 3Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 4Tata Memorial Hospital (Mumbai Maharashtra), Mumbai, Maharashtr, India, 5Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 6Mayo Clinic, Rochester, MN, 7Department of Qualitative Health Sciences, Section of Biostatistics, Mayo Clinic, Scottsdale, AZ, 8Mayo Clinic, Phoenix, AZ, 9Department of Neurological Surgery, Jacksonville, FL, 10Department of Neurosurgery, Mayo Clinic, Rochester, MN, 11Mayo Clinic, Jacksonville, FL, 12Department of Neurologic Surgery,, Rochester, MN, 13Mayo Clinic, Department of Neurology, Rochester, MN, 14Department of Neurology, Mayo Clinic, Rochester, MN
Purpose/Objective(s): The current treatment of glioblastoma involves resection followed by radiotherapy (RT) and temozolomide. Subjective rapid early progression (REP) of tumor in the interim between surgery and radiotherapy has been described and is associated with inferior clinical outcomes. This study seeks to establish and validate a quantitative definition for REP and examine how REP could serve to inform future prognosis and therapy.
Materials/Methods: In this retrospective study, data from 587 glioblastoma patients were collected from electronic health records. All patients were treated at a multi-site academic center. Ultimately, 318 patients met inclusion criteria which included availability of MRIs at pre-operative, post-operative, and pre-radiotherapy (pre-RT) intervals. Volumes of tumor and resection cavity were contoured at each of these intervals among patients who had undergone maximal safe resection (gross total resection, subtotal resection, or biopsy) with subsequent RT and chemotherapy. Using Mantel Cox test for univariate analysis, a minimal (but clinically appreciable) threshold for defining REP based on change in tumor volume (cc or %) from post-operative to pre-planning was established by identifying the cutoff associated with the most significant hazard ratio for overall survival (OS). This threshold was then further used to assess for actionable predictors of REP such as residual tumor and length of surgery-to-radiotherapy interval by using binary logistic regression for multivariate analysis.
Results: The median patient OS was 18.1 months after resection. An increase of > 2cc in volume or a new satellite tumor between the post-operative to planning MRI was found to be a sensitive, pragmatic, and statistically significant cutoff on both univariate and multivariate analysis (p = 0.002, OR = 1.545). With this definition of REP, actionable predictors such as surgery to radiotherapy interval of 6 weeks (p = 0.01; OR = 15.474) and a > 5cc residual immediate post-operative tumor volume (p = 0.002; OR = 5.26) were found to be statistically significant predictors of REP. REP was also found to be a statistically significant prognostic indicator for OS (p = 0.002, OR = 1.545) and progression-free survival, PFS (p = <0.001, OR = 1.652).
Conclusion: These findings support that an increase in tumor volume between post-operative and pre-RT MRI of > 2 cc is the ideal working definition of REP in this clinical setting. Furthermore, based on this definition of REP, there was significant association between REP and OS and PFS giving credibility to its potential as a prognostic biomarker that could serve to track response to treatment. Additionally, two actionable and modifiable predictors of REP, post-op residual tumor volume and interval to radiotherapy, demonstrate how incidence of REP can potentially be minimized in clinical care.