高级别胶质瘤术后放疗联合替莫唑胺治疗临床分析

Clinical analysis of postoperative high-grade glioma treated with radiotherapy combined with temozolomide

目的高级别脑胶质瘤是原发性脑肿瘤发病率最高的恶性肿瘤,目前多采用手术后放疗和化疗结合的综合治疗。本研究回顾性分析高级别脑胶质瘤术后三维适形及调强放疗联合替莫唑胺治疗(temozolomide,TMZ)的疗效和安全性,探讨其影响预后的因素。方法选取安徽医科大学第一附属医院放疗科2009-06-01-2016-05-31治疗的78例高级别胶质瘤(high grada glioma,HGG)术后患者,回顾性分析其临床特点和生存率。所有患者均接受三维适形放疗(3dimensional conformal radiation therapy,3DCRT)或调强适形放疗(intensity modulated radiation therapy,IMRT)精确放疗期间同步给予TMZ化疗,其后行6个周期辅助化疗。采用Kaplan-Meier法计算生存率,Log-rank法进行单因素分析,多因素分析采用Cox比例风险模型。结果 78例患者1、2和3年总生存率(overall survival,OS)分别为86.2%、53.4%和36.1%,无进展生存率分别为68.2%、46.3%和32.3%。单因素分析显示,病理分级(χ~2=5.55,P=0.018)、手术切除程度(χ~2=12.82,P<0.001)是影响胶质瘤患者术后生存率的重要因素,同时手术完全切除(χ~2=11.687,P=0.001)和TMZ长周期化疗(χ~2=4.548,P=0.033)也是影响患者疾病无进展生存时间(progression-free survival,PFS)的有利临床因素。术后至放疗开始的时间间隔控制在6~8周较<6周组并未显示出生存影响的劣势,χ~2=1.853,P=0.173。多因素回归分析表明,PS评分、病理分级及手术切除程度是影响OS的独立预后因素。此外,手术切除程度和TMZ长周期化疗是影响PFS的预后因素。多数患者在治疗期间出现的血液学毒性、肝功能及胃肠道不良反应轻微,均可耐受。结论 HGG术后行精确放疗联合TMZ同步化疗及序贯化疗疗效确切,安全性较好。患者PS评分、病理分级和手术切除程度,可作为判断临床预后的独立因素。

OBJECTIVE High-grade glioma （HGG） is the most common tumor in primary malignant brain tumors, nowadays the treatment modality include radiation therapy combined with chemotherapy post surgical resection. This study aimed to retrospectively assess the efficacy and safety of three-dimensional conformal radiotherapy （3DCRT） or in- tensity-modulated radiotherapy （IMRT） combined with temozolomide （TMZ） for patients with HGG after operation, and to explore the clinical prognostic factors. METHODS Totally 78 patients with high-grade gliomas who were received treatment in the 1st affiliated hospital of Anhui Medical University between June 1,2009 and May 31,2016 were selected, and a retrospective analysis was performed based on clinical characteristics and survival rate. All patients received 3DCRT or intensity-modulated radiotherapy （IMRT）. Temozolomide was used for concurrent chemoradiotherapy, following 6 cy- cles of adjuvant chemotherapy. The survival rate was calculated by Kaplan-Meier method and analyzed by the Log-rank test, and Cox regression model applied in multivariate analysis. RESULTS The 1-, 2-, 3-year overall survival（OS） rates were 86. 2%, 53. 4% and 36. 1%, respectively, and the corresponding progression-free survival（PFS） rates were 68. 2%, 46.3% and 32. 3%. Univariate analysis showed that pathological grade （x2= 5. 55, P〉0. 018）, extent of resection（X2= 12.82,P〈0. 001） were important factors affecting the survival rates of patients, meanwhile gross total resection（X2 =11. 687, P^0. 001） and longer TMZ chemotherapy （X2 =4. 548, P=0. 033） were favorable factors for PFS. There was no evident reduction in survival in patients received radiotherapy within 6--8 weeks interval after surgery when com- pared with those received earlier radiotherapy （x2= 1. 853, P= 0. 173）. Multivariate regression analysis showed that PS score, pathological grade and extent of resection were independent prognostic factors for OS. Besides these, extent of re- section and the cycles of TMZ chemotherapy affected PFS independently. Most patients were tolerable to the slight ad- verse effects such as hematologic toxicity, liver dysfunction and gastrointestinal toxicity. CONCLUSIONS 3DCRT and IMRT combined with TMZ concurrent chemotherapy and sequential chemotherapy achieved good efficacy and safety for HGG patients. PS score, pathological grade and extent of resection are independent prognostic factors for patients with HGG.