Harary Paul M, Hori Yusuke S, Persad Amit R L, Tayag Armine, Ustrzynski Louisa, Emrich Sara C, Rahimy Elham, Park David J, Li Gordon, Chang Steven D
Departments of Neurosurgery, Stanford University School of Medicine, Stanford, California.
Radiation Oncology, Stanford University School of Medicine, Stanford, California.
J Neurosurg Case Lessons. 2024 Sep 9;8(11). doi: 10.3171/CASE24387.
While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported.
The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS.
To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.
虽然肿瘤基因检测常用于指导全身治疗的选择，但关于脑癌放疗应用的证据有限。最近的研究表明， Kelch样ECH相关蛋白1（KEAP1）是细胞对氧化应激和亲电应激反应的关键调节因子，与多种癌症类型的放射抗性有关。多项研究报道了KEAP1突变在脑转移中的临床意义；然而，KEAP1突变对脑膜瘤放射反应的影响尚未见报道。
作者报告了一例40岁KEAP1突变阳性非典型脑膜瘤女性病例，最初接受手术切除，随后进行调强放射治疗（IMRT）。15个月时出现复发，需要再次手术和辅助立体定向放射外科治疗（SRS）。SRS后7个月观察到良好的治疗反应，报告症状有所改善，尽管SRS后2个月出现放射性坏死需要使用贝伐单抗来解决。
据作者所知，这是KEAP1突变型脑膜瘤的首例报告，包括综合治疗后的临床病程。值得注意的是，治疗包括IMRT联合SRS的多模式放疗。SRS在7个月随访时导致了良好的治疗反应。然而，两种放疗后均出现放射性坏死，提示对于KEAP1突变患者，调整放疗方案可能有益。https://thejns.org/doi/10.3171/CASE24387 。
