2175 - Predictors of Toxicity after Re-Irradiation for Recurrent Grade 3-4 Glioma: A Multi-Institutional Analysis
Presenter(s)
J. Petersen1, G. Russell2, L. R. Kleinberg3, J. Huang4, J. A. Hattangadi-Gluth5, L. M. Halasz6, S. G. Soltys7, J. D. Palmer8, T. J. C. Wang9, W. Shi10, S. E. Braunstein11, C. Shen12, J. E. Mignano13, A. H. Masters14, M. C. LeCompte15, W. Liu16, A. B. Hopper5, A. B. Barbour17, 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, 4WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 5Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, 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, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, 9Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, 10Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, PA, 11Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 12Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, 13Tufts Medical Center, Department of Radiation Oncology, Boston, MA, 14Department of Radiation Oncology, University of Louisville, Louisville, KY, 15Southeast Radiation Oncology Group, Charlotte, NC, 16University of Iowa, Iowa City, IA, 17Duke University, Durham, NC, 18Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 19Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
Purpose/Objective(s):
To evaluate predictors of toxicity following re-irradiation (reRT) for recurrent Grade 3-4 glioma (HGG), including the impact of cumulative dose and treatment related factors.Materials/Methods:
A multi-institutional retrospective cohort of patients treated with fractionated reRT for recurrent HGG was analyzed. Inclusion criteria were in-field recurrent HGG treated with =3 fractions of reRT, completion of reRT and = 6 months between RT courses. Endpoints were grade =2 adverse radiation effects (ARE) and a composite grade =3 toxicity endpoint including ARE, new neurologic deficits and new or worsening seizures. RT doses were calculated as biological effective doses (BED) using an a/b ratio of 2. Cumulative dose was calculated using an assumption of 25%, 50%, 60% and 70% at 6, 12, 24 and 36 months respectively with no further recovery after 36 months and interpolation of recovery in between time points. Associations between toxicity and cumulative dose, tumor diameter, treatment factors and systemic therapy were evaluated using logistic regression.Results:
215 patients in the dataset met inclusion criteria. Of those 215 patients, 61 (28%) developed grade =2 ARE and 58 (27%) developed the composite grade =3 toxicity measure. Median cumulative RT dose was 134.3 Gy BED2. 20% of patients received proton reRT (PRT), 46% received bevacizumab (BEV), 55% received TMZ and 56% had tumors >5cm in diameter. On multivariable analysis, cumulative dose was not associated with grade =2 ARE (OR 1.02 per 10 Gy BED2, p = 0.75); TMZ exposure (OR 1.20, p = 0.62) and a maximal tumor diameter > 5cm (OR 1.08, p = 0.83) were not associated with increased grade =2 ARE. PRT (OR 2.98, p = 0.01) and BEV exposure (OR 2.24, p=0.03) were associated with higher rates of = grade 2 ARE. No factors were associated with the grade =3 composite endpoint on multivariate analysis. Patients receiving PRT had similar median survival (13 vs 10 months, p = 0.067), a longer time between RT courses (median 55 vs 22 months, p < 0.01), were less likely to have a tumor > 5 cm at reRT (37% vs 61%, p < 0.01), and receive TMZ with reRT (28% vs 49%, p = 0.02) and had similar rates of reRT regimens greater than 35 Gy / 10 fraction equivalent (12% vs 5%, p = 0.18). Patients receiving BEV with reRT had a shorter time between RT courses (median 11 vs 34 months, p < 0.01) and were less likely to receive TMZ with reRT (27% with TMZ vs 59% with BEV, p < 0.01).Conclusion:
Cumulative reRT dose was not associated with clinically significant toxicity with adjustments for tissue recovery after initial radiation. PRT and BEV were associated with increased grade =2 ARE. While these findings may reflect patient and treatment selection factors, PRT patients were more likely to have multiple clinical factors previously reported to be associated with decreased ARE. Prospective studies are needed to better define patient specific toxicity risk after reRT to guide reRT dose, use of PRT and BEV.