304 - Genomic Mutation-Driven Stratification of Treatment Response to Stereotactic Spine Radiosurgery in Spinal Metastases
Presenter(s)
A. Al-Sharfeen1, O. Haisraely2, E. P. Damron3, M. Florez2, S. Vedala4, K. Huntoon5, S. Perni6, M. F. F. McAleer1, D. N. Yeboa2, T. Beckham7, C. Wang2, J. Li7, B. Amini8, T. M. Briere9, M. C. Tom7, C. Tatsui10, L. D. Rhines10, B. De7, and A. J. Ghia7; 1MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3The University of Texas McGovern Medical School, Houston, TX, 4Texas A&M University, College Station, TX, 5The University of Texas MD Anderson Cancer Center, Houston, TX, 6Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 7Department of CNS Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 8Department of Musculoskeletal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 9MD Anderson Cancer Cancer, Houston, TX, 10Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
Stereotactic spine radiosurgery (SSRS) is an effective treatment strategy for achieving durable local control (LC) and alleviating pain in patients with spinal metastases. While the relationship between tumor histology and radioresistance continues to be explored, the impact of specific genomic mutations on SSRS resistance remains unclear. This study investigates the association between histology-independent primary tumor mutations and clinical outcomes following SSRS, providing valuable perspectives on the genetic factors influencing LC and overall survival (OS) to identify potential genetic predictors of treatment response.Materials/Methods:
A retrospective analysis was conducted on 268 patients with accessible primary tumor mutation profiles who were treated with SSRS for 418 spinal metastases at a single institution between 2007 and 2022. Univariate and multivariable Cox proportional hazards models were used to determine correlations between primary tumor mutations and clinical outcomes, including LC and OS, while controlling for clinicopathologic and treatment-related variables. To reinforce the statistical reliability of the results, multiple comparison corrections were utilized.Results:
The median patient age at the time of SSRS was 59 years (range: 17–88), with 46% being male. The most frequently observed primary tumor sites were head and neck (15%), lung (18%), and genitourinary (16%). Spinal metastases were predominantly located in the thoracic (54%) and lumbar (30%) regions. The median SSRS dose delivered to the gross tumor volume was 24 Gy, reflecting a biologically effective dose (BED10) of 82 Gy (range: 46–113), administered in a median of one fraction (range: 1–5). Prior conventional radiation therapy (RT) had been received by 27% of patients. The most frequently identified genomic mutations included TP53 (30%), KIT (13%), PIK3CA (14%), and KRAS (10%). Mutations in ATM (7%) and FGFR2 (3%) were also observed. At a median follow-up of 15 months (range: 1–139), LC at one and two years following SSRS were 88% and 77%, respectively. The median OS was 27 months (95% CI: 22–32). On multivariable analysis, LC was significantly more durable in patients with FGFR2 mutations (HR 0.10; 95% CI: 0.02–0.76; P=0.027) but less durable in those with ATM mutations (HR 2.02; 95% CI: 1.04–3.90; P=0.036), after adjusting for prior RT and RT dose. Additionally, TP53 (HR 1.60; 95% CI: 1.19–2.10; P=0.002) and KRAS mutations (HR 1.60; 95% CI: 1.07–2.50; P=0.02) were associated with shorter OS after adjusting for age.Conclusion:
Primary tumor site mutations in TP53 and KRAS were associated with shorter OS and less durable LC, respectively, whereas FGFR2 mutations correlated with more durable LC. These findings highlight the need for further investigation into incorporating genomic profiling into personalized SSRS dose regimens to tailor therapeutic strategies based on tumor-specific genetic characteristics.