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. 2025 Jun 1;122(2):424-434.
doi: 10.1016/j.ijrobp.2025.01.033. Epub 2025 Feb 8.

Intracranial Disease Control and Survival among Patients with KRAS-mutant Lung Adenocarcinoma and Brain Metastases Treated with Stereotactic Radiosurgery

Benjamin Gaeta  1 , Jordan E Eichholz  2 , Henry Walch  3 , Ahmet T Ilica  4 , Lillian Boe  5 , Leah Kratochvil  6 , Yao Yu  7 , Daniel R Gomez  8 , Brandon S Imber  7 , Bob T Li  9 , Yonina R Murciano-Goroff  9 , Kathryn C Arbour  10 , Nikolaus Schultz  5 , Emily S Lebow  11 , Luke R G Pike  12
Affiliations

Intracranial Disease Control and Survival among Patients with KRAS-mutant Lung Adenocarcinoma and Brain Metastases Treated with Stereotactic Radiosurgery

Benjamin Gaeta et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: Precision medicine according to molecularly defined subgroups offers great potential to improve outcomes for patients with metastatic lung adenocarcinoma. This study describes clinical outcomes and the impact of co-occurring genetic alterations on outcomes following stereotactic radiosurgery (SRS) among patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma.

Methods and materials: A total of 195 patients with KRAS-mutant lung adenocarcinoma were treated with SRS for brain metastases (BMs) between 2014 and 2018 with follow-up until 2022 or death. Coprimary outcomes were median overall survival (OS) and intracranial progression-free survival (iPFS); univariable and multivariable Cox regression models and Kaplan-Meier survival analysis were used.

Results: Median follow-up from the date of BM diagnosis was 11 months. Median OS and iPFS for the cohort were 27.7 months (95% CI, 19.7-36.8) and 22.1 months (95% CI, 16.8-48.9), respectively. Lesion-level local control at 12 and 24 months was 89.9% and 87.5%, respectively. In a multivariable Cox regression model, inferior OS was associated with coalterations in KEAP1 and STK11 (hazard ratio [HR], 1.94; 95% CI, 1.04-3.62; q = 0.087), progressive (HR, 3.41; 95% CI, 1.38-8.39; q = 0.087), and mixed response (HR, 3.52; 95% CI, 1.2-10.3; q = 0.092) extracranial disease, and 6 or more BMs at time of diagnosis (HR, 2.58; 95% CI, 1.22-6.63; q = 0.087). Positive programmed death ligand 1 status was associated with improved OS (HR, 0.57; 95% CI, 0.37-0.87; P = .01). Inferior iPFS was associated with chemotherapy before SRS (HR, 2.69; 95% CI, 1.42-5.09; q = 0.04) and age >65 years (HR, 2.21; 95% CI, 1.25-3.93; q = 0.055). KRAS G12C was not associated with differences in iPFS, OS, or type of intracranial progression event following SRS.

Conclusions: Coalteration of KRAS and KEAP1/STK11 was associated with inferior OS, but not iPFS. Similar outcomes were found in patients harboring KRAS G12C and non-G12C mutant non-small cell lung cancer BMs. Further understanding of molecularly characterized subgroups will be critical in driving personalized radiation therapy for patients with lung cancer BMs.

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Conflict of interest statement

B. Imber reports honoraria from GT Medical Technologies, Inc.; and employment at Memorial Sloan Kettering Cancer Center. Y. Yu reports research funding from EMD Serono and royalties from Springer and employment at Memorial Sloan Kettering Cancer center. Y.R. Murciano-Goroff reports travel, accommodation, and expenses from AstraZeneca and Loxo Oncology/ Eli Lilly; honoraria from Virology Education and Projects in Knowledge (for a CME program funded by an educational grant from Amgen; associated research funding to the institution from Mirati Therapeutics, Loxo Oncology at Eli Lilly, Elucida Oncology, Taiho Oncology, Hengrui USA, Ltd/ Jiangsu Hengrui Pharmaceuticals, Luzsana Biotechnology, Endeavor Biomedicines, and AbbVie; being employed Memorial Sloan Kettering Cancer Center, which has an institutional interest in Elucida; royalties from Rutgers University Press and Wolters Kluwer; food/beverages from Endeavor Biomedicines; receipt of training through an institutional K30 grant from the NIH (CTSA UL1TR00457); funding from a Kristina M. Day Young Investigator Award from Conquer Cancer, the ASCO Foundation, endowed by Dr. Charles M; and employment at Memorial Sloan Kettering Cancer Center. D. Gomez reports research funding from Varian, AstraZeneca, Merk, and Bristol-Meyers Squib; consultant fees from GRAIL, Olympus, Johnson & Johnson, Varian, and Medtronic; speaker fees from MedLearning Group and Varian, and employment at Memorial Sloan Kettering Cancer Center. K.C. Arbour reports consultancies at G1 Therapeutics, AstraZeneca, Novartis, and Sanofi US Services Inc.; research grants from Genetech, Mirati, and Revolution Medicines; and employment at Memorial Sloan Kettering Cancer Center. L.R.G. Pike reports funding from Caris Life Sciences, Delfi Diagnostics, and Harbinger Health, and consulting agreements with Monte Rosa Therapeutics and Monograph Capital.

References

    1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941–1953. doi: 10.1002/ijc.31937 - DOI - PubMed
    1. Barta JA, Powell CA, Wisnivesky JP. Global Epidemiology of Lung Cancer. Ann Glob Health. 85(1):8. doi: 10.5334/aogh.2419 - DOI - PMC - PubMed
    1. Soffietti R, Ahluwalia M, Lin N, Rudà R. Management of brain metastases according to molecular subtypes. Nat Rev Neurol. 2020;16(10):557–574. doi: 10.1038/s41582-020-0391-x - DOI - PubMed
    1. Sacks P, Rahman M. Epidemiology of Brain Metastases. Neurosurgery Clinics of North America. 2020;31(4):481–488. doi: 10.1016/j.nec.2020.06.001 - DOI - PubMed
    1. Collisson EA, Campbell JD, Brooks AN, et al. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543–550. doi: 10.1038/nature13385 - DOI - PMC - PubMed

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