To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment

J Neurosurg 133:273–280, 2020

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.

METHODS 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.

RESULTS 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.

CONCLUSIONS 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.

 

Prognostic Importance of Age, Tumor Location, and Tumor Grade in Grade II Astrocytomas

World Neurosurg. (2019) 121:e411-e418

Previous work in anaplastic astrocytoma (AA) demonstrated that the survival benefit from gross total resection (GTR) is modified by age and tumor location. Here, we determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA).

METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database (1999-2010). We used Kaplan- Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. We determined the prevalence of the mutated isocitrate dehydrogenase (mIDH) using The Cancer Genome Atlas (TCGA).

RESULTS: We identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P [ 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P [ 0.002; age >50 years HR, 0.78; P [ 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P [ 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P [ 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P [ 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P [ 0.49).

CONCLUSIONS: Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts