Keap1 Mutation Is Correlated To Increased Rates Of Local Failure After Radiation Therapy For Spine Metastases From Non-Small Cell Lung Cancer

Progression of spine metastases from non-small cell lung cancer (NSCLC) after radiation therapy is common, yet molecular alterations associated with increased risk of progression are not known. We performed a retrospective review of an institutional database of patients who underwent spinal radiation therapy (RT) between 2012 and 2016. We identified those who had undergone targeted tumor mutational sequencing with the MSK-IMPACT platform. Patient demographics, treatment characteristics, local control and survival outcomes were collected via retrospective chart review. Treatment characteristics and mutational status were compared to cumulative rate of radiographic local progression after RT with death treated as a competing risk. Statistical evaluations were made using the log rank test, using Bonferroni correction for multiple comparisons of genes assayed by targeted sequencing. We identified 60 patients with metastatic NSCLC who underwent spine radiation therapy between 2012 and 2016, who also had tumor mutational analysis performed. RT treatment plans consisted of 35 conventional external beam radiation therapy (cEBRT) and 25 stereotactic body radiation therapy (SBRT). Of these 60 patients, 14 (23.3%) experienced local failure with a median time to local failure of 9.2 months. Local progression was more common in patients treated with cEBRT (cEBRT=24%, SBRT=8%; HR 4.35, 95% CI [1.54-12.3], p=0.02). Of the 468 genes assayed by the MSK-IMPACT platform, 14 were mutated at a frequency > 5% in this cohort. KEAP1 mutation was more frequently found in patients who experienced local progression, and was correlated to increased risk of in-field failure (HR= 7.17, 95% CI [2.45-21.0], p = 0.036). Patients with spine metastases from NSCLC experience a significant rate of radiation treatment failure with half of failures occurring in less than 12 months. Local progression is more common after cEBRT as compared to SBRT, and alterations in KEAP1 are associated with increased risk of local failure. Stratification by molecular signature may identify NSCLC patients with increased risk of local progression who would benefit from upfront SBRT, which will be investigated in future studies.