Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Minnesota Oncology, St. Paul, MN, USA.
J Neurooncol. 2022 Jul;158(3):323-330. doi: 10.1007/s11060-022-04011-w. Epub 2022 May 18.
In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS).
Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus F-DOPA PET defined tumor.
Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed.
F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.
颅内高级别胶质瘤（HGG）复发是一种常见的挑战，治疗选择有限，包括再放疗。示踪剂 3,4-二羟基-6-[18F]-氟-L-苯丙氨酸（F-DOPA）可穿透血脑屏障，在肿瘤中有高摄取，但在正常组织中摄取低。本研究旨在探讨 F-DOPA 正电子发射断层扫描（PET）和 MRI 引导下对复发性 HGG 进行再放疗是否能改善无进展生存期（PFS）。
入组标准为既往接受过放疗的复发性或进展性 HGG 成人患者。主要终点是与单独全身治疗相比，3 个月时（PFS3）的无进展生存期（PFS3）提高 20%（PFS3 为 20%）。再放疗剂量为 35Gy，分 10 次进行。靶区为 MRI T1 对比增强定义的肿瘤加 F-DOPA PET 定义的肿瘤。
20 例患者按方案完成了治疗。诊断最常见的是胶质母细胞瘤，IDH-野生型（60%）。利用 F-DOPA PET，MRI 定义的肿瘤体积中位数增加了 43%（0-436%）。PFS3 为 85%（95%CI 63.2-95.8%），达到 PFS3≥40%的主要终点。中位随访 9.7 个月时，17 例（85%）患者进展，15 例（75%）患者死亡。再放疗后中位总生存期为 8.8 个月。再放疗失败的部位位于 MRI 和 PET 肿瘤体积内的有 75%，仅在 MRI 内的有 13%，仅在 PET 内的有 0%，均不在的有 13%。有 4 例（20%）患者出现 3 级毒性，包括中枢神经系统坏死（2 例，均因影像学发现而开始使用贝伐单抗，无症状）、癫痫发作（1 例）、疲劳（1 例）和恶心（1 例）。未观察到 4-5 级毒性。
F-DOPA PET 引导下对进展性高级别胶质瘤进行再放疗似乎是安全的，有进一步研究的前景。
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