Temozolomide Versus Radiotherapy as First-Line Therapy for Low-Grade Glioma: Mature Results of a Randomized Phase III Trial (EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU).

This trial was comparing single-modality therapies in patients who often survive for years or decades and investigating differential responses according to molecular markers.

这项试验比较了单一治疗方式在通常能存活数年或数十年的患者中的效果，并研究了根据分子标志物的不同反应。

Methods

Four hundred seventy-eight patients with clinical high-risk LGG (WHO grade 2) were randomly assigned to standard radiotherapy (RT; 28 × 1.8 Gy) or dose-dense temozolomide (TMZ; 75 mg/m2 once daily × 21/28 days, up to 12 cycles).

478名临床高风险LGG（WHO 2级）患者被随机分配接受标准放疗（RT；28次×1.8 Gy）或密集剂量的替莫唑胺（TMZ；每日75 mg/m2，连续21/28天，最多12个周期）。

Results

There was no significant difference in progression-free survivalor overall survival(OS) between study arms.

研究组之间在无进展生存期或总生存期（OS）上没有显著差异。

Analyzable tumor tissue in 73% (351/478) of patients allowed for post hoc reclassification according to the 2021 WHO pathologic criteria.

在73%（351/478）的患者中，可分析的肿瘤组织允许根据2021年WHO病理标准进行事后重新分类。

In astrocytoma, IDHmt/1p/19q noncodeleted (n = 178), median OS was similar, 6.6-6.7 years irrespective of arm (0.67-1.44, P = .93).

在星形细胞瘤，IDHmt/1p/19q非共删除（n = 178）中，中位OS相似，无论组别如何均为6.6-6.7年（0.67-1.44，P = .93）。

In oligodendroglioma, IDHmt/1p/19q codeleted (n = 109), median OS was 12.9 years (9.4-not reached) with RT and 14.9 years (10.1-number of events not reached) with TMZ (hazard ratio[HR], 0.88 [0.52-1.49], P = .63).

在少突胶质细胞瘤，IDHmt/1p/19q共删除（n = 109）中，中位OS为RT组12.9年（9.4-未达到）和TMZ组14.9年（10.1-事件未达到）（风险比[HR]，0.88 [0.52-1.49]，P = .63）。

In 64 tumors without isocitrate dehydrogenase (IDH) mutations, survival favored the TMZ arm: OS 2.5 (1.8-3.3) versus 4.7 (2.2-7.2) years (HR, 0.47 [0.27-0.82], P = .0068).

在64个没有异柠檬酸脱氢酶（IDH）突变的肿瘤中，生存期倾向于TMZ组：OS为2.5（1.8-3.3）年对比4.7（2.2-7.2）年（HR，0.47 [0.27-0.82]，P = .0068）。

Patients age 40 years and older fared better than patients younger than 40 years, challenging the current notion of age alone as a negative prognostic factor.

年龄在40岁及以上的患者比40岁以下的患者表现更好，这挑战了当前仅将年龄作为不良预后因素的观念。

Conclusions

The assigned initial treatment modality did not affect progression-free survivalor OS, regardless of the molecular subtype.

分配的初始治疗方式并未影响无进展生存期或总生存期，无论分子亚型如何。

Combined-modality therapy was not tested in this trial but has since become a standard of care for IDH-mutant astrocytoma.

本试验未测试联合治疗模式，但此后已成为IDH突变型星形细胞瘤的标准治疗方法。

With emerging novel therapeutic options, rational treatment strategies tailored at the individual clinical and pathologic recurrence risk profiles will be needed.

随着新的治疗方案的出现，需要根据个体的临床和病理复发风险特征制定合理的治疗策略。

The validity of an age cutoff as prognostic factor is challenged when tumors are molecularly classified.

当肿瘤进行分子分类时，年龄作为预后因素的有效性受到挑战。