Abstract

Background

We report the analysis involving patients treated on the initial CODEL design.

Methods

Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm.

Results

Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months.

Conclusions

TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.

中文翻译：

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CODEL：针对新诊断的 1p/19q 共缺失少突胶质细胞瘤的 RT、RT + TMZ 或 TMZ 的 III 期研究。从最初的研究设计分析

摘要

背景

我们报告了涉及接受初始 CODEL 设计治疗的患者的分析。

方法

患有新诊断的 1p/19q 世界卫生组织 (WHO) III 级少突胶质细胞瘤的成人（>18 岁）被随机分配接受单独放疗（RT；5940 厘格雷）（A 组）；伴随和辅助替莫唑胺 (TMZ) 的放疗（B 组）；或单独使用 TMZ（C 臂）。主要终点是总生存期 (OS)，A 组与 B 组。对 OS 和无进展生存期 (PFS) 进行了二次比较，比较了联合 RT 组与单独 TMZ 组。

结果

36 名患者被平均随机分配。在 7.5 年的中位随访中，83.3% (10/12) 单独使用 TMZ 的患者取得进展，而 RT 组为 37.5% (9/24)。与 RT 患者相比，单独使用 TMZ 的患者的 PFS 显着缩短（风险比 [HR] = 3.12；95% CI：1.26、7.69；P = 0.014）。3/12 (25%) 的单独 TMZ 患者和 4/24 (16.7%) 的 RT 组患者死于疾病进展。OS 在手臂之间没有统计学差异（比较动力不足）。在使用 IDH 和 RT 治疗状态作为协变量的 Cox 回归模型中调整异柠檬酸脱氢酶 (IDH) 状态（突变/野生型）后（C 组对比合并的 A + B 组），未接受 RT 的患者的 PFS 仍然较短（HR = 3.33 ; 95% CI: 1.31, 8.45; P= 0.011），但不是 OS（（HR = 2.78；95% CI：0.58、13.22，P = 0.20）。25%、42% 和 33% 的患者（A 组、B 组、和 C). 与基线和 3 个月相比，手臂之间的神经认知能力下降没有差异。

结论

单独接受 TMZ 治疗的患者 PFS 明显短于接受 RT 治疗的患者。正在进行的 CODEL 试验已经过重新设计，以比较 RT + PCV 与 RT + TMZ。