多形性胶质母细胞瘤术后新辅助替莫唑胺序贯放化疗与直接放化疗的对比研究（NEOTEM试验）：中期结果
Postoperative NEOadjuvant TEMozolomide followed by chemoradiotherapy versus upfront chemoradiotherapy for glioblastoma multiforme (NEOTEM) trial: Interim results.
作者信息
Sharifian Azadeh, Kazemian Ali, Farzin Mostafa, Amirkhani Nikan, Farazmand Borna, Naderi Soheil, Khalilian Alireza, Pourrashidi Ahmad, Amjad Ghazaleh, Kolahdouzan Kasra, Abyaneh Romina, Jablonska Paola Anna, Ghalehtaki Reza
机构信息
Department of Radiation Oncology, Cancer Institute, IKHC, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Radiation Oncology Research Center, Cancer Research Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Neurooncol Adv. 2024 Nov 14;6(1):vdae195. doi: 10.1093/noajnl/vdae195. eCollection 2024 Jan-Dec.
BACKGROUND
Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor survival rates despite current treatments. The standard of care (SOC) includes surgery, followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide (TMZ). This phase II trial assessed the safety and efficacy of neoadjuvant TMZ (nTMZ) before and during chemoradiotherapy in newly diagnosed GBM patients.
METHODS
Newly diagnosed GBM patients who underwent maximal safe resection were randomized into 2 groups. One received nTMZ before standard chemoradiotherapy and adjuvant TMZ (intervention). The other received standard chemoradiotherapy followed by adjuvant TMZ (control). Primary endpoints were progression-free survival (PFS) at 6 and 12 months. Secondary endpoints included overall survival, radiological and clinical responses, and adverse events.
RESULTS
Of 35 patients, 16 were in the intervention group and 19 in the control group. Median PFS was 9 months (95% CI: 3.93-14.06) versus 3 months (95% confidence interval [CI]: 1.98-4.01) in the control and intervention groups ( = .737), with a high progression rate (73.4%) during nTMZ treatment. The 6-month PFS rates were 58% versus 25% ( = .042), and 12-month PFS rates were 26% versus 25% ( = .390) in the control and intervention groups, respectively. Patients with unmethylated O-methylguanine-DNA methyltransferase (MGMT) and those with good performance status (PS) had significantly worse PFS with nTMZ. However, those who underwent larger extent of resection exhibited significantly better PFS with nTMZ. Adverse events were similar between groups.
CONCLUSIONS
Neoadjuvant TMZ before SOC chemoradiotherapy did not improve outcomes for newly diagnosed GBM patients and is unsuitable for those with unmethylated MGMT and good PS. However, It may benefit patients with near or gross total resection. Further research is needed to refine GBM treatment strategies.
背景
多形性胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，尽管有当前的治疗方法，但其生存率仍很低。标准治疗方案（SOC）包括手术，随后进行放疗以及同步和辅助使用替莫唑胺（TMZ）化疗。这项II期试验评估了新诊断的GBM患者在放化疗前和放化疗期间使用新辅助TMZ（nTMZ）的安全性和有效性。
方法
将接受了最大安全切除的新诊断GBM患者随机分为两组。一组在标准放化疗和辅助TMZ之前接受nTMZ（干预组）。另一组接受标准放化疗，随后进行辅助TMZ（对照组）。主要终点是6个月和12个月时的无进展生存期（PFS）。次要终点包括总生存期、放射学和临床反应以及不良事件。
结果
35例患者中，干预组16例，对照组19例。对照组和干预组的中位PFS分别为3个月（95%置信区间[CI]：1.98 - 4.01）和9个月（95%CI：3.93 - 14.06）（P = 0.737），在nTMZ治疗期间进展率较高（73.4%）。对照组和干预组的6个月PFS率分别为25%和58%（P = 0.042），12个月PFS率分别为25%和26%（P = 0.390）。O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）未甲基化的患者和身体状况良好（PS）的患者使用nTMZ时PFS明显更差。然而，切除范围更大的患者使用nTMZ时PFS明显更好。两组间不良事件相似。
结论
在SOC放化疗前使用新辅助TMZ并不能改善新诊断GBM患者的预后，不适用于MGMT未甲基化和PS良好的患者。然而，它可能对接近全切或全切的患者有益。需要进一步研究以完善GBM的治疗策略。
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