Gaeta Benjamin, Eichholz Jordan E, Walch Henry, Ilica Ahmet T, Boe Lillian, Kratochvil Leah, Yu Yao, Gomez Daniel R, Imber Brandon S, Li Bob T, Murciano-Goroff Yonina R, Arbour Kathryn C, Schultz Nikolaus, Lebow Emily S, Pike Luke R G
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Int J Radiat Oncol Biol Phys. 2025 Jun 1;122(2):424-434. doi: 10.1016/j.ijrobp.2025.01.033. Epub 2025 Feb 8.
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.
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.
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.
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.
根据分子定义的亚组进行精准医学，为改善转移性肺腺癌患者的预后提供了巨大潜力。本研究描述了 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）突变型肺腺癌患者接受立体定向放射外科治疗（SRS）后的临床结局以及同时发生的基因改变对结局的影响。
2014 年至 2018 年期间，共有 195 例 KRAS 突变型肺腺癌患者因脑转移（BMs）接受了 SRS 治疗，并随访至 2022 年或直至死亡。共同主要结局为中位总生存期（OS）和颅内无进展生存期（iPFS）；使用单变量和多变量 Cox 回归模型以及 Kaplan-Meier 生存分析。
从 BM 诊断日期起的中位随访时间为 11 个月。该队列的中位 OS 和 iPFS 分别为 27.7 个月（95%CI，19.7 - 36.8）和 22.1 个月（95%CI，16.8 - 48.9）。12 个月和 24 个月时的病灶水平局部控制率分别为 89.9%和 87.5%。在多变量 Cox 回归模型中，较差的 OS 与 KEAP1 和 STK11 的共改变（风险比[HR]，1.94；95%CI，1.04 - 3.62；q = 0.087）、进展性（HR，3.41；95%CI，1.38 - 8.39；q = 0.087）和混合反应（HR，3.52；95%CI，1.2 - 10.3；q = 0.092）的颅外疾病以及诊断时 6 个或更多的 BM 相关（HR，2.58；95%CI，1.22 - 6.63；q = 0.087）。程序性死亡配体 1 阳性状态与改善的 OS 相关（HR，0.57；95%CI，0.37 - 0.87；P = 0.01）。较差的 iPFS 与 SRS 前的化疗（HR，2.69；95%CI, 1.42 - 5.09；q = 0.04）和年龄>65 岁（HR，2.21；95%CI，1.25 - 3.93；q = 0.055）相关。KRAS G12C 与 SRS 后的 iPFS、OS 或颅内进展事件类型的差异无关。
KRAS 和 KEAP1/STK11 的共改变与较差的 OS 相关，但与 iPFS 无关。在携带 KRAS G12C 和非 G12C 突变的非小细胞肺癌 BM 患者中发现了相似的结局。进一步了解分子特征亚组对于推动肺癌 BM 患者的个性化放射治疗至关重要。
