
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.101
vdae090.101
Final Category: Radiation Therapy Advances
AcademicSubjects/MED00300
AcademicSubjects/MED00310
RADT-07 IMPACT OF KEAP1/NFE2L2 VARIANTS ON LOCAL CONTROL IN NSCLC BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Chen Mark Duke University Medical Center, Durham/NC, USA

Carpenter David Wellstar Health, Hiram/GA, USA

Leng Jim Duke University Medical Center, Durham/NC, USA

Qazi Jamiluddin Duke University Medical Center, Durham/NC, USA

Wan Zihan Duke University Medical Center, Durham/NC, USA

Niedzwiecki Donna Duke University Medical Center, Durham/NC, USA

Alder Laura Duke University Medical Center, Durham/NC, USA

Clarke Jeffrey Duke University Medical Center, Durham/NC, USA

Kirkpatrick John Duke University Medical Center, Durham/NC, USA

Floyd Scott Duke University Medical Center, Durham/NC, USA

Reitman Zachary Duke University Medical Center, Durham/NC, USA

Mullikin Trey Duke University Medical Center, Durham/NC, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i30i31
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-like 2 (NFE2L2) reactive oxygen species processing pathway may be a useful biomarker of clinical radioresistance in localized non-small cell lung cancer (NSCLC). It is unknown whether KEAP1/NFE2L2 variants impact the response of brain metastases from NSCLC to radiotherapy. Here, we tested whether KEAP1/NFE2L2 variants associate with rates of local control in patients with NSCLC brain metastases undergoing stereotactic radiosurgery (SRS). We hypothesize KEAP1/NFE2L2 pathogenic variants (PV) are associated with decreased local control (LC) and increased time to intracranial progression (ICP). 541 patients undergoing SRS for NSCLC brain metastases at a single institution were retrospectively identified; n=269 underwent clinical next generation sequencing. Kaplan-Meier analyses were calculated for LC and ICP; results across variant status were compared using the log-rank test. Comparisons were performed for variant versus no mutation, and by variant type (PV and variant of unknown significance (VUS)). At 12 months, LC was 90.8% (95% CI, 79.2-96.1%) among patients with variants, compared to 90.6% (84.4-94.4%) in patients without. There was no significant difference in median time to ICP between patients with variants (5.1 months; 95% CI, 3.3-9.5 months) compared to those without (7.2 months; 95% CI, 5.7-9.5 months). 12-month LC was 92.15±5.33% in PV, 89.43±5.89% in VUS, and 90.6±2.46% in patients without mutations. LC and ICP displayed a non-significant trend for differences when KEAP1/NFE2L2 PV and VUS were compared. Overall, KEAP1/NFE2L2 variant status did not demonstrate a statistically significant difference in LC or ICP after SRS for brain metastases in this cohort. On the basis of these data, KEAP1/NFE2L2 variant status should not impact clinical management of NSCLC brain metastasis patients. Larger cohorts are needed to examine KEAP1/NFE2L2 status association with outcomes among NSCLC brain metastasis patients. Thus, the impact of KEAP1/NFE2L2 mutations may differ in the localized versus metastatic setting.
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