Paľa Andrej, Coburger Jan, Scherer Moritz, Ahmeti Hajrullah, Roder Constantin, Gessler Florian, Jungk Christine, Scheuerle Angelika, Senft Christian, Tatagiba Marcos, Synowitz Michael, Wirtz Christian Rainer, Schmitz Bernd, Unterberg Andreas W
1Department of Neurosurgery.
2Department of Neurosurgery, University of Heidelberg.
J Neurosurg. 2019 Jul 19;133(2):273-280. doi: 10.3171/2019.4.JNS183395. Print 2020 Aug 1.
The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called "high-risk" patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery.
Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma.
One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8-6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance.
In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.
弥漫性世界卫生组织二级胶质瘤（低级别胶质瘤，LGG）辅助治疗的证据水平较低。在所谓的“高危”患者中，目前大多数中心在手术后采用早期积极的辅助治疗。本评估的目的是比较单纯接受放射治疗（RT）、单纯接受化疗（CT）、联合/序贯RT+CT的患者与手术后未接受主要辅助治疗的患者的无进展生存期（PFS）和总生存期（OS）。
基于一项对288例（≥18岁）弥漫性世界卫生组织二级胶质瘤患者的回顾性多中心队列研究，对确诊异柠檬酸脱氢酶（IDH）突变的患者进行亚组分析。使用Kaplan-Meier估计值和多变量Cox回归模型评估手术后主要辅助治疗对PFS和OS的影响，模型包括年龄（≥40岁）、肿瘤完全切除（CTR）、再次手术以及星形细胞瘤与少突胶质细胞瘤。
144例患者符合纳入标准。40例患者（27.8%）接受了辅助治疗。中位随访时间为6年（95%置信区间4.8 - 6.3年）。总体中位PFS为3.9年，OS为16.1年。未接受辅助治疗时，PFS和OS显著更长（p = 0.003）。即使在高危患者（年龄≥40岁或有残留肿瘤）中，也观察到有利于不进行辅助治疗的显著差异（3.9年对3.1年，p = 0.025）。在多变量模型（控制年龄、CTR、少突胶质细胞诊断和再次手术）中，与任何其他辅助治疗方案相比，未接受辅助治疗的患者对PFS（p = 0.030）和OS（p = 0.009）显示出显著的积极影响。如果应用RT+CT，这种效果最为明显（PFS的p = 0.004，风险比[HR]为2.7；OS的p = 0.001，HR为20.2）。CTR与更长的PFS独立相关（p = 0.019）。年龄≥40岁、组织病理学诊断和复发未达到统计学意义。
在这一系列IDH突变的LGG中，RT、替莫唑胺（TMZ）化疗或两者联合的辅助治疗在PFS和OS方面均未显示出显著优势。即使在高危患者中，作者也观察到辅助治疗对PFS和OS有类似的显著负面影响。这些结果强调了CTR在LGG中的重要性。尽管有CTR，≥40岁的患者是否应接受辅助治疗仍存在争议。应考虑IDH突变的LGG中早期使用TMZ、RT或RT+CT导致肿瘤去分化的可能性。然而，这些数据受回顾性研究设计以及辅助治疗潜在的异质性指征的限制。
