Intracranial disease control and survival among patients with KRAS-mutant lung adenocarcinoma and brain metastases treated with stereotactic radiosurgery Journal Article
| Authors: | Gaeta, B.; Eichholz, J. E.; Walch, H.; Ilica, A. T.; Boe, L.; Kratochvil, L.; Yu, Y.; Gomez, D. R.; Imber, B. S.; Li, B. T.; Murciano-Goroff, Y. R.; Arbour, K. C.; Schultz, N.; Lebow, E. S.; Pike, L. R. G. |
| Article Title: | Intracranial disease control and survival among patients with KRAS-mutant lung adenocarcinoma and brain metastases treated with stereotactic radiosurgery |
| 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. © 2025 Elsevier Inc. |
| Keywords: | adult; cancer survival; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; survival analysis; unclassified drug; gene mutation; major clinical study; overall survival; genetics; mutation; mortality; chemotherapy; brain tumor; follow up; brain neoplasms; progression free survival; lung neoplasms; proportional hazards models; radiotherapy; cohort analysis; lung cancer; pathology; protein p53; lung tumor; electronic medical record; lung adenocarcinoma; proportional hazards model; brain; myc protein; diagnosis; radiosurgery; clinical evaluation; brain metastasis; atm protein; hazard ratio; stereotactic radiosurgery; cyclin dependent kinase inhibitor 2a; kaplan meier method; disease control; k ras protein; protein p21; proto-oncogene proteins p21(ras); diseases; kras protein, human; programmed death 1 ligand 1; progression-free survival; genetic alterations; virus oncogene; adenocarcinoma of lung; clinical outcome; protein kinase lkb1; stk11 protein, human; procedures; brg1 protein; retinoblastoma binding protein 2; kelch like ech associated protein 1; very elderly; humans; human; male; female; article; rbm10 protein; multi variables; kelch-like ech-associated protein 1; keap1 protein, human; amp-activated protein kinase kinases; hydroxymethylglutaryl coenzyme a reductase kinase kinase; cox's regression model; intracranial progression free survival |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 122 |
| Issue: | 2 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-06-01 |
| Start Page: | 424 |
| End Page: | 434 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2025.01.033 |
| PUBMED: | 39929348 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Luke Pike Source: Scopus |
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