Mitchell Macy, Restrepo-Orozco Andres, Verhey Leonard H, Vitaz Todd
College of Human Medicine, Michigan State University, Grand Rapids, Michigan.
Department of Neurological Surgery, Corewell Health, Grand Rapids, Michigan.
J Neurosurg Case Lessons. 2024 Nov 25;8(22). doi: 10.3171/CASE24539.
Li-Fraumeni syndrome (LFS) is characterized by p53 germline mutations and a high predisposition to cancers including glioblastoma (GBM), the most common and aggressive primary malignant brain tumor in adults. Despite current therapies, the 5-year survival rate is 5%-10%. The authors report a case with a durable long-term response to immunotherapy with checkpoint inhibition in a patient with LFS-associated GBM.
An 18-year-old female presented after a syncopal episode and left leg weakness and was found to have a right frontal tumor. She underwent gross-total resection of the tumor (grade IV giant cell GBM IDH-wildtype, MGMT unmethylated, associated with a p53 germline mutation), radiation, and chemotherapy. On later imaging, increased enhancement was demonstrated, which raised concerns for tumor recurrence, and she underwent stereotactic radiosurgery followed by lomustine and procarbazine. These agents were later replaced with bevacizumab after a second resection, negative for recurrent glioma. Subsequently, nivolumab was added, given concerns for tumor progression, and the patient showed improvement within 5 months. The patient has continued nivolumab monotherapy and has had progression-free survival for more than 7 years.
Despite advances in treatment, the median survival of patients with GBM is only 15 months. This case highlights the potential of immunotherapy with PD-L1 checkpoint inhibition in improving outcomes for LFS-associated GBM patients. https://thejns.org/doi/10.3171/CASE24539.
李-弗劳梅尼综合征（LFS）的特征是p53基因种系突变，并且极易患多种癌症，包括胶质母细胞瘤（GBM），这是成人中最常见且侵袭性最强的原发性恶性脑肿瘤。尽管有目前的治疗方法，但其5年生存率仅为5%-10%。作者报告了1例LFS相关GBM患者对免疫检查点抑制疗法产生持久长期反应的病例。
一名18岁女性在晕厥发作和左腿无力后就诊，被发现患有右额叶肿瘤。她接受了肿瘤的全切除（IV级巨细胞GBM，异柠檬酸脱氢酶野生型，O6-甲基鸟嘌呤-DNA甲基转移酶未甲基化，与p53基因种系突变相关）、放疗和化疗。在后来的影像学检查中，发现强化增加，这引发了对肿瘤复发的担忧，她接受了立体定向放射外科手术，随后使用洛莫司汀和丙卡巴肼。在第二次切除后，由于复发胶质瘤为阴性，这些药物后来被贝伐单抗取代。随后，鉴于对肿瘤进展的担忧，加用了纳武单抗，患者在5个月内病情有所改善。该患者继续接受纳武单抗单药治疗，无进展生存期已超过7年。
尽管治疗取得了进展，但GBM患者的中位生存期仅为15个月。该病例突出了PD-L1检查点抑制免疫疗法在改善LFS相关GBM患者预后方面的潜力。https://thejns.org/doi/10.3171/CASE24539 。
