Yogendran Lalanthica V, Kareddy Abhinav, Abbas Salma O, Scharf Zachary, Patrie James, Patel Sohil H, Schiff David
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, 3133 Bellvue Ave, Cincinnati, OH, 45219, USA.
Department of Neurology, Division of Neuro-Oncology, University of Virginia School of Medicine, 1240 Lee St, 3rd Floor, Charlottesville, VA, 22903, USA.
J Neurooncol. 2025 Aug 20. doi: 10.1007/s11060-025-05087-w.
Patients with WHO grade 2 and 3 isocitrate dehydrogenase mutation (IDHmt) gliomas commonly receive temozolomide (TMZ), with or without radiation therapy, as initial therapy. At progression, TMZ is sometimes reinstated despite a paucity of data on effectiveness.
We reviewed imaging outcomes of patients with WHO 2016 grade II/III IDHmt gliomas re-treated with TMZ at first progression between 2007 and 2019. Tumor growth rates were calculated over the year preceding re-treatment and throughout the re-treatment period, ranging from 3 to 41 months. RANO criteria were utilized to assess TMZ response rate.
15 subjects included six grade II, five grade III oligodendrogliomas, one grade II and three grade III astrocytomas. Median time between completion of the first TMZ course and initiation of re-treatment was 47 months. Median progression-free survival with TMZ re-treatment was 27.4 months and median overall survival was 47.8 months. Mean rate of tumor growth by bidimensional product increased from 0.29 cm /month, in the year prior to first tumor progression, to 0.47 cm/month during re-treatment, ranging from 3 to 41 months, with monotherapy TMZ. Volumetric mean rate of tumor growth was 1.12 cc/month in the year prior to first tumor progression versus 1.29 cc/month during TMZ re-treatment. Five patients experienced tumor growth rate reduction, of whom 3 patients experienced tumor shrinkage as measured by 2D; 2 of these 3 patients also experienced tumor shrinkage as measured by 3D. There was no radiographic response by RANO criteria.
These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to TMZ, underscoring the need for alternative approaches.
世界卫生组织（WHO）2级和3级异柠檬酸脱氢酶突变（IDHmt）胶质瘤患者通常接受替莫唑胺（TMZ）治疗，无论是否联合放疗，作为初始治疗。疾病进展时，尽管关于有效性的数据有限，但有时仍会恢复使用TMZ。
我们回顾了2007年至2019年间首次进展时接受TMZ再治疗的2016版WHO II/III级IDHmt胶质瘤患者的影像学结果。在再治疗前一年以及整个再治疗期间（3至41个月）计算肿瘤生长率。采用RANO标准评估TMZ反应率。
15名受试者包括6例II级、5例III级少突胶质细胞瘤、1例II级和3例III级星形细胞瘤。首次TMZ疗程结束至开始再治疗的中位时间为47个月。TMZ再治疗的中位无进展生存期为27.4个月，中位总生存期为47.8个月。二维乘积法计算的肿瘤平均生长率从首次肿瘤进展前一年的0.29 cm/月增加到再治疗期间（3至41个月）的0.47 cm/月，采用TMZ单药治疗。首次肿瘤进展前一年的肿瘤体积平均生长率为1.12 cc/月，而TMZ再治疗期间为1.29 cc/月。5例患者肿瘤生长率降低，其中3例患者经二维测量肿瘤缩小；这3例患者中有2例经三维测量肿瘤也缩小。根据RANO标准，无影像学反应。
这些发现表明，先前接受过治疗且进展的IDHmt胶质瘤通常对TMZ耐药，强调了需要采用替代方法。
