Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539.
Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539.
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DOI：
10.3171/2016.11.jns161170
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发表时间：
2018-07
影响因子：
4.1
通讯作者：
Mehta MP
中科院分区：
文献类型：
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作者：
Rogers L;Zhang P;Vogelbaum MA;Perry A;Ashby LS;Modi JM;Alleman AM;Galvin J;Brachman D;Jenrette JM;De Groot J;Bovi JA;Werner-Wasik M;Knisely JPS;Mehta MP
这是 NRG 肿瘤学 RTOG 0539 的第一份临床结果报告，详细介绍了主要终点，即 3 年无进展生存期 (3yPFS)，与中危脑膜瘤的预定义历史对照进行比较，其次评估了总体生存期 (OS)、局部失败和前瞻性评分不良事件 (AE)。 NRG Oncology RTOG 0539 是一项 II 期临床试验，根据 WHO 分级、复发状态和切除范围，将脑膜瘤患者分配到 3 个预后组和管理策略中的一组。对于中危组（第 2 组），符合条件的患者要么患有新诊断的 WHO II 级脑膜瘤并进行了大体全切除（GTR，Simpson I-III），要么患有任意切除范围的复发性 WHO I 级脑膜瘤。病理学和影像学进行了集中审查。患者接受放射治疗 (RT)，调强放射治疗 (IMRT) 或 3D 适形放射治疗 (3DCRT)，54 Gy，分 30 次。 RT 靶区定义为肿瘤床和任何结节强化（例如复发性 WHO I 级患者），边缘最小 8 毫米，最大 15 毫米，具体取决于肿瘤部位和 RT 方法设置的可重复性。主要终点是 3yPFS。将结果与历史对照进行比较（单独 GTR 后的 3yPFS 为 70%，GTR + RT 后的 3yPFS 为 90%）。使用 NCI 通用毒性标准对 AE 进行评分。 56名患者入组为中危组； 3人不符合资格。此外，1 例未接受 RT，4 例在 3 年前退出且未复发。因此，52 名患者接受了方案治疗，其中 48 名患者的主要终点可评估，即 3 年 PFS 为 93.8% (p=.0003)。 3年内发生了3起PFS事件：1名WHO II级患者死于疾病，1名WHO II级患者病情进展并仍存活，1名复发性WHO I级患者死于不明原因但未进展。三年局部失败率为 4.1%，三年总生存率为 96%。 3年后，另外2名患者出现进展：1名复发性WHO I级，另一名WHO II级；两人都还活着。在接受方案治疗的 52 名可评估患者中，36 名 (69.2%) 为 WHO II 级 GTR，16 名 (30.8%) 为复发性 WHO I。这些亚组之间的 PFS 无显着差异（p=.52，HR 0.56，95% CI 0.09 至 3.35），验证了其巩固性。在 52 名可评估的患者中，44 名 (84.6%) 接受了 IMRT，50 名 (96.2%) 接受了按照方案或接受可接受变异的治疗。 AE（肯定、可能或可能与方案治疗相关）仅限于 1 级或 2 级，没有报告 3 级事件。这是 NRG 肿瘤学 RTOG 0539 的第一份临床结果报告。接受放疗治疗的中危脑膜瘤患者获得了出色的 3 年无进展生存期 (3yPFS)，局部失败率低，不良事件风险低。这些结果支持对新诊断的完全完全切除的 WHO II 级脑膜瘤或复发性 WHO I 级脑膜瘤使用术后放疗，无论切除范围如何。他们还证明了 IMRT 的毒性最小，肿瘤控制率高。该方案 (NRG Oncology RTOG 0539) 已在 ClinicalTrials.gov 注册 (https://clinicaltrials.gov/ct2/show/NCT00895622?term=RTOG+0539&rank=1)。 ClinicalTrials.gov 标识符为 NCT00895622。
This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (3yPFS), compared to a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). NRG Oncology RTOG 0539 was a phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO grade II meningioma with gross total resection (GTR, Simpson I-III) or recurrent WHO grade I of any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g. recurrent WHO grade I patients) with a minimum 8 mm and maximum 15 mm margin, depending upon tumor locale and set-up reproducibility of RT method. The primary endpoint was 3yPFS. Results were compared to historical controls (3yPFS 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. Fifty-six patients enrolled in the intermediate-risk group; 3 were ineligible. Additionally, 1 did not receive RT, and 4 withdrew without recurrence before 3 years. Thus 52 patients received protocol therapy, and 48 were evaluable for the primary endpoint, 3y PFS which was 93.8% (p=.0003). Within 3 years there were 3 PFS events: 1 WHO grade II patient died of disease, 1 WHO grade II patient progressed and remained alive, and 1 recurrent WHO grade I patient died from undetermined cause without progression. Three-year local failure was 4.1%, and 3-year OS 96%. After 3 years 2 additional patients progressed: 1 recurrent WHO grade I, and the other WHO grade II; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) were WHO II with GTR, and 16 (30.8%) recurrent WHO I. There was no significant difference in PFS between these subgroups (p=.52, HR 0.56, 95% CI 0.09 to 3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably or possibly related to protocol treatment) were limited to grade 1 or 2, with no reported grade 3 events. This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT experienced excellent 3yPFS with a low rate of local failure, and a low risk of adverse events. These results support the use of post-operative RT for newly diagnosed gross totally resected WHO grade II, or recurrent WHO grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT. This protocol (NRG Oncology RTOG 0539) is registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT00895622?term=RTOG+0539&rank=1). The ClinicalTrials.gov Identifier is NCT00895622.