Main Session
Sep
30
SS 47 - Spine SBRT: Risk, Safety, and Outcomes
360 - Impact of von-Hippel Lindau Mutations on Local Control after Spine Stereotactic Body Radiation Therapy for Renal Cell Carcinoma
Presenter(s)
Elisa Liu, MD - Memorial Sloan Kettering Cancer Center, New York, NY
E. K. Liu1, M. T. McMillan1, E. Bent1,2, A. Cornish2, Y. Yamada1, D. S. Higginson1, A. Schmitt1, J. Haseltine1, B. A. Mueller1, M. Vaynrub3, R. Bou-Nassif4, W. C. Newman4, O. Barzilai4, M. Bilsky4, E. Lis5, and C. B. Jackson1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 3Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY, 5Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Renal cell carcinoma (RCC) is commonly associated with spinal metastases. Mutations in von Hippel-Lindau (VHL) tumor suppressor gene may promote hypoxia signaling and confer radioresistance after spine stereotactic body radiation therapy (SBRT).
Materials/Methods:
This is a retrospective cohort study of 207 patients with RCC treated to 343 spinal metastases. All patients received at least 2 months of follow-up magnetic resonance imaging. Patients with prior overlapping radiotherapy to the spine were excluded. The primary outcome was local failure (LF), defined as radiographic progression within the treated vertebral level. Cumulative incidence of LF was estimated with death as a competing risk and compared using Gray’s test. Univariable and multivariable, cause-specific hazards, competing risk regression models were fit for LF using the Cox proportional hazards model, with the dosimetric and clinical variables as predictors. Biologically effective dose (BED10) was calculated using the linear–quadratic model (a/ß = 10 Gy) and modeled as a continuous variable. VHL mutations were classified using somatic genetic sequencing with MSK-IMPACT. Results: The median overall survival (OS) and follow-up after SBRT were 26 months and 16 months, respectively. Of the 122/207 (59%) patients with somatic genetic sequencing with MSK-IMPACT, 56 patients (46%) with 98 lesions (46%) had mutations in VHL (VHL-mut). A total of 108 lesions received 27 Gy in 3 fractions (35%), 115 lesions received 30 Gy in 3 fractions (34%), and 108 lesions received 24 Gy in 1 fraction (31%). Overall, the 2- and 5-year rates of LF were 12% and 14%, respectively. For 27 Gy/3 fx, 30 Gy/3 fx, and 24 Gy/1 fx, the 2- and 5-year risk of LF for RCC metastases treated with spine SBRT were 17%/23%, 14%/14%, and 2.8%/2.8%, respectively (p<0.001). For VHL-wildtype (wt) and VHL-mut lesions, the 2-year risk of LF after spine SBRT was 5.3% and 16%, respectively (p=0.003). Among VHL-wt lesions, 2-year risk of LF after 27 Gy/3 fx, 30 Gy/3 fx, and 24 Gy/1 fx were 7.3%, 6.8%, and 0% (p=0.3). Among VHL-mut lesions, 2-year risk of LF after 27 Gy/3 fx, 30 Gy/3 fx, and 24 Gy/1 fx were 28%, 15%, 0% (p<0.001). On multivariable competing risks regression adjusted for clustering at the patient level, higher BED10 was associated with lower LF (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.84-0.94, p<0.001). Conclusion: This is the largest series on local control after spine SBRT for RCC metastases. Spine SBRT for RCC is associated with excellent local control, with a 5-year cumulative incidence of LF of 14%. Higher BED10 regimens were associated with lower LF. VHL-mut lesions had higher LF than VHL-wt lesions and exhibited greater dose-dependent differences in local failure across SBRT regimens.