287 - Predictive Factors for Survival after Reirradiation of IDH Wild Type 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): Dose at reirradiation (reRT) for recurrent IDH wild type (IDHwt) high grade glioma (HGG) has been reported to be associated with improved survival outcomes. However, the ideal dose remains unknown as does which patients benefit from high dose reRT.
Materials/Methods: A retrospective review of patients undergoing fractionated (>3 fractions) reRT for HGG was conducted at 12 institutions. An iterative model was utilized to find the optimal cut-off for the continuous covariates of interest 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. Single variable Cox proportional hazards regression models were created to assess the relationship between patient characteristics and treatment measures with overall survival. Any variable with a p-value < 0.10 was included in a backward stepwise Cox model; the criterion for remaining in the final model was a p-value <0.05. To assess progression-free survival among the eligible patients, a competing-risk Cox proportional hazards model was used in a similar fashion to the approach used for overall survival and independent factors. The Kaplan-Meier method was used to estimate survival times. SAS (version 9.4, Cary, NC, USA) was used for all analyses.
Results: 252 patients were identified with IDHwt HGG. Median overall and disease free survival were 8.0 months and 4.8 months respectively. Age, time from the end of the initial RT course to first recurrence (time interval) and dose at reRT cut points of = 57 years, = 18 months, and > 51.44 Gy BED10 (approximately 43.2 Gy in 24 or 40.05 Gy in 15 fractions) were identified. On multivariate analysis, a time interval of < 18 months (HR 2.03, p < 0.01), dose at reRT = 51.44 Gy BED10 (HR 1.9, p <0.01), tumor diameter of = 5cm (HR 1.97, p < 0.01), in-field only recurrence (HR 0.68, p = 0.02), and use of adjuvant temozolomide (TMZ) (HR 0.57, p < 0.01) were associated with OS. Among tumors with MGMT methylation all factors except adjuvant TMZ remained significant. Among tumors without MGMT methylation all factors except adjuvant TMZ and in-field recurrence remained significant. Time interval < 18 months (HR 1.54, p < 0.01) and dose at reRT = 51.44 Gy BED10 (HR 1.77, p < 0.01) were associated with PFS. Patients with a time interval of = 18 months were more likely to receive higher dose reRT (34.2% vs 20%, p = 0.03). Patients with a time interval of = 18 months were found to have longer OS with high dose reRT (median OS 22.0 months vs 10.0 months, p < 0.01), with no effect seen in those with a shorter time interval (median OS 9.3 vs 6.1 months, p = 0.11).
Conclusion: ReRT dose > 51.44 Gy BED10, a time interval of =18 months, tumor diameter < 5cm, in-field only recurrence, and the use of adjuvant TMZ are associated with OS after reRT for IDHwt HGG. ReRT dose > 51.44 Gy BED10 is beneficial only in patients with = 18 months from the end of initial RT to the first recurrence.