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[多形性胶质母细胞瘤的多模态治疗:2003 - 2009年期间连续诊断的86例患者的结果]

[Multimodal treatment of glioblastoma multiforme: results of 86 consecutive patients diagnosed in period 2003-2009].

作者信息

Lakomý R, Fadrus P, Slampa P, Svoboda T, Kren L, Lzicarová E, Belanová R, Siková I, Poprach A, Schneiderová M, Procházková M, Sána J, Slabý O, Smrcka M, Vyzula R, Svoboda M

机构信息

Masarykův onkologický ústav, Brno.

出版信息

Klin Onkol. 2011;24(2):112-20.

Abstract

BACKGROUNDS

Glioblastoma multiforme is the most common malignant primary tumor of the brain in adults. Standard therapy consists in maximal surgical resection and adjuvant concurrent chemoradiotherapy and adjuvant therapy with temozolomid. This approach improves survival in comparison with postsurgical radiotherapy alone.

PATIENTS AND METHODS

Consecutive patients with histologically confirmed glioblastoma multiforme in the period from January 2003 to December 2009 underwent postoperative radiotherapy (1.8-2.0 Gy/d, total of 60 Gy) plus concurrent daily chemotherapy (temozolomide 75 mg/m2/d), followed by 6 cycles of temozolomide (150 to 200 mg/m2 for 5 days, every 28 days) and were analyzed retrospectively. The primary end point was to describe the correlation between known clinical factors, treatment and progression free survival (PFS) and overall survival (OS). We assessed the toxicity and safety of the chemoradiotherapy.

RESULTS

Eighty-six patients (median age, 56 years; 60% male) were included. Most of them (> 80%) were of performance status (PS) 0-1 at the beginning of chemoradiotherapy. Total macroscopic resection was performed in 20% of the patients, subtotal in 65%, partial in 9%, and just biopsy in 6%. Median PFS was 7.0 months (2.0-35.5), median OS was 13.0 months (2.5-70). Postoperative performance status (PS), the extent of resection, and administration of planned treatment without reduction had statistically significant influences on PFS and OS. Median PFS and OS were 22.0, 7.0 and 6.0 months for PFS (p = 0.0018) in patients with PS O, 1 and 2 respectively and 32.0, 13.0 and 9.0 months for OS (p = 0.0023). Patients with total removal of tumor had longer PFS (14.0 vs 6.0 months, HR = 0.5688; p = 0.0301) and OS (23.0 vs 12.0 months, HR 0.4977; p = 0.0093), as did patients without dose reduction of radiotherapy and/or chemotherapy. Patients with radiotherapy dose of over 54 Gy had PFS 8.0 vs 3.0 months (HR = 0.3313; p = 0.0001) and OS 15.0 vs 5.0 months (HR = 0.1730; p < 0.0001). Similarly, treatment with concurrent chemotherapy for more than 40 days was also important: PFS 8.0 vs 5.0 months (HR = 0.5300; p = 0.0023) and OS 17.0 vs 9.5 months (HR = 0.5943; p = 0.0175). Age, gender and position of tumor had no significant influence. Treatment-related hematology toxicity grades 3 and 4 occurred relatively often: thrombocytopenia (9%), leukopenia (6%), neutropenia (6%) and lymphopenia (25%). Thrombo-embolic events were dominant in non-hematology toxicity. Serious toxicity occurred mainly in the subgroup of patients with PS 2. Treatment of progression was useful in selected patients. Second surgery was of the most benefit (OS 24.0 vs 12.5 months, HR = 0.5325; p = 0.0111).

CONCLUSION

Postoperative performance status, extent of resection, successful administration of the majority of planned concurrent chemoradiotherapy and possibility of surgical treatment at the time of recurrence correlate with better prognosis for our patients with glioblastoma. Our experience indicates that performance status should be the main factor in decisions about treatment intensity. Treatment of malignant glioma requires a multidisciplinary team.

摘要

背景

多形性胶质母细胞瘤是成人最常见的原发性脑恶性肿瘤。标准治疗包括最大程度的手术切除、辅助同步放化疗以及替莫唑胺辅助治疗。与单纯术后放疗相比,这种方法可提高生存率。

患者与方法

对2003年1月至2009年12月期间组织学确诊为多形性胶质母细胞瘤的连续患者进行回顾性分析,这些患者术后接受放疗(1.8 - 2.0 Gy/天,共60 Gy)加每日同步化疗(替莫唑胺75 mg/m²/天),随后进行6个周期的替莫唑胺治疗(150至200 mg/m²,连用5天,每28天重复)。主要终点是描述已知临床因素、治疗与无进展生存期(PFS)和总生存期(OS)之间的相关性。我们评估了放化疗的毒性和安全性。

结果

纳入86例患者(中位年龄56岁;60%为男性)。大多数患者(> 80%)在放化疗开始时的体能状态(PS)为0 - 1。20%的患者进行了全宏观切除,65%为次全切除,9%为部分切除,6%仅做了活检。中位PFS为7.0个月(2.0 - 35.5),中位OS为13.0个月(2.5 - 70)。术后体能状态(PS)、切除范围以及未减少剂量的计划治疗实施情况对PFS和OS有统计学显著影响。PS为0、1和2的患者,PFS的中位值分别为22.0、7.0和6.0个月(p = 0.0018),OS的中位值分别为32.0、13.0和9.0个月(p = 0.0023)。肿瘤完全切除的患者PFS更长(14.0 vs 6.0个月,HR = 0.5688;p = 0.0301),OS也更长(23.0 vs 12.0个月,HR 0.4977;p = 0.0093),放疗和/或化疗未减少剂量的患者情况相同。放疗剂量超过54 Gy的患者PFS为8.0 vs 3.0个月(HR = 0.3313;p = 0.0001),OS为15.0 vs 5.0个月(HR = 0.1730;p < 0.0001)。同样,同步化疗超过40天的治疗也很重要:PFS为8.0 vs 5.0个月(HR = 0.5300;p = 0.0023),OS为17.0 vs 9.5个月(HR = 0.5943;p = 0.0175)。年龄、性别和肿瘤位置无显著影响。与治疗相关的血液学3级和4级毒性相对常见:血小板减少(9%)、白细胞减少(6%)、中性粒细胞减少(6%)和淋巴细胞减少(25%)。血栓栓塞事件在非血液学毒性中占主导。严重毒性主要发生在PS为2的患者亚组中。进展期治疗对部分患者有用。二次手术获益最大(OS为24.0 vs 12.5个月,HR = 0.5325;p = 0.0111)。

结论

术后体能状态、切除范围、成功实施大部分计划的同步放化疗以及复发时手术治疗的可能性与我们多形性胶质母细胞瘤患者的较好预后相关。我们的经验表明,体能状态应是治疗强度决策的主要因素。恶性胶质瘤的治疗需要多学科团队。

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