2652 - Predictive Factors for Survival after Reirradiation of IDH Mutant High-Grade Glioma
Presenter(s)
J. Petersen1, G. Russell2, M. C. LeCompte3, W. Liu4, H. G. Jona5, L. M. Halasz6, S. G. Soltys7, S. E. Braunstein8, T. J. C. Wang9, W. Shi10, C. Shen11, J. E. Mignano12, A. H. Masters13, L. R. Kleinberg3, J. Huang14, A. B. Hopper15, A. B. Barbour16, M. A. Salans17, M. D. Chan18, and C. A. Helis19; 1Wake Forest University School of Medicine Department of Radiation Oncology, Winston-Salem, NC, 2Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, 3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 4University of Iowa, Iowa City, IA, 5University of California San Diego, San Diego, CA, 6Department of Radiation Oncology, University of Washington/ Fred Hutchinson Cancer Center, Seattle, WA, 7Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 8Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 9Columbia University, New York, NY, 10Thomas Jefferson University, Philadelphia, PA, 11Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, 12Tufts Medical Center, Department of Radiation Oncology, Boston, MA, 13Department of Radiation Oncology, University of Louisville, Louisville, KY, 14WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 15Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 16Duke University, Durham, NC, 17University of California San Francisco, San Francisco, CA, 18Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 19Alexander T. Augusta Military Medical Center, Fort Belvoir, VA
Purpose/Objective(s): In patients with recurrent IDH mutant (IDHmt) high grade glioma, high-dose reirradiation (reRT), defined as greater than 35 Gy in 10 fractions has been reported to be correlated with improved survival outcomes and to have similar toxicity to low dose reRT. However, the ideal patient population and dose fractionation scheme for dose-escalated reRT is unknown.
Materials/Methods: A retrospective review of patients receiving fractionated (>3 fractions) reRT for HGG was conducted across 12 institutions. Inclusion criteria for survival modeling were adult (age = 18 years) at diagnosis, HGG at diagnosis or recurrence, completion of reRT, a KPS = 70 at reRT, and at least 24 months between radiation courses. An iterative model using the Contal and O'Quigley Method and the Cox Model to find the smallest p-values and maximal hazard ratios by assessing all values observed in the patient population was used to find optimal cut-off points for the continuous variables of interest. Single variable Cox proportional hazards regression models were created to evaluate the relationship between patient characteristics and treatment factors with overall survival. Variables with a p-value < 0.20 were included in a backward stepwise Cox model; the criterion for remaining in the final model was a p-value <0.05. Additional models were specifically developed to assess the impact of concurrent and adjuvant temozolomide and bevacizumab and to assess only patients with a prolonged interval between RT courses. Survival times were estimated using the Kaplan-Meier method. SAS (version 9.4, Cary, NC, USA) was used for all analyses.
Results: Of 115 patients with IDHmt tumors, 75 were identified that met model inclusion criteria. Age, time from the end of the initial RT course to first recurrence (time interval), and dose at reRT cut points of = 44 years, > 69 months, and = 59.47 Gy BED10 (equivalent to 50.4 Gy in 28 fractions) were identified, respectively. Median overall survival in the high and low dose groups was 25.6 months and 14.6 months respectively (p = 0.01). There was no difference in age, KPS, tumor grade at diagnosis or recurrence, number of recurrences prior to reRT, and the interval between RT courses in the high vs low dose groups. Patients undergoing high dose reRT were more likely to have a GTR prior to reRT (33% vs 5%, p = 0.03). On multivariate analysis, a time interval of = 69 months (HR 0.30, p < 0.01), dose at reRT = 59.47 Gy BED10 (HR 2.72, p = 0.02), tumor grade (Grade 4 vs Grade 3) at recurrence (HR 2.94, p < 0.01), and the use of adjuvant bevacizumab (HR 0.50, p = 0.05) were associated with OS.
Conclusion: In recurrent IDHmt HGG patients with a KPS of = 70 and at least 24 months between RT courses, reRT dose = 59.47 Gy BED10, a time interval of = 69 months, Grade 3 tumor at recurrence and the use of adjuvant bevacizumab are associated with OS after reRT for IDHmt HGG.