Antitumor effect and peritumoral brain edema formation in relation to MX2, ACNU, and doxorubicin therapy: a comparative analysis using rodent models of gliomas

The potential antitumor effect of MX2, a new lipophilic morpholino anthracycline, was compared with those of ACNU or doxorubicin (DOX) using two different rodent glioma models. A mouse subcutaneous glioma model (203 glioma) was used to measure the effect of each drug on reducing the glioma size and a rat 9L intracerebral glioma model (9L glioma) was used to assess the antitumor effect on survival rate in a clinically similar fashion. Treatment with ACNU inhibited tumor growth by 94.6% (p < 0.0001) and complete regression of the tumor was observed in 3 of 25 (12.0%) of the ACNU-treated cases. Tumor growth was inhibited by 32.4% with DOX despite a tendency (p < 0.16) and by 59.4% with MX-2 (p < 0.001); neither of these drugs resulted in complete tumor regression. In the intracerebral glioma rats, only ACNU tended to ameliorate survival rate, but there was no statistical significance. These results suggest that ACNU has the most potent effect but MX2 can be an option for chemotherapy of malignant gliomas. Interestingly, all three drugs significantly elevated the brain water content on both the ipsilateral and contralateral sides of the tumor, although they did not induce brain edema in the normal rat brains. Careful management of brain edema might be required regardless of the drug used during chemotherapy to maximize the prognosis of glioma patients.     

Antitumour effect of MX2, a new morpholino anthracycline against C6 glioma cells and its cytotoxic effect in combination with photodynamic therapy.

MX2, a novel lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to Adriamycin (ADM) against murine and human tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0-3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at high concentrations of MX2 illuminated with white light but not red light (> 630 nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of whether the cells were treated with MX2 either immediately after red light illumination following incubation with HpD, or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.     

纳米纤维介导的紫杉醇/阿霉素序贯联合治疗SHg-44胶质瘤

摘要 背景：纳米纤维技术可同时担载多种药物，避开血脑屏障限制实现脑胶质瘤的序贯联合化疗。 目的：用乳液电纺法制备同时担载紫杉醇和阿霉素的聚乙二醇-聚乳酸共聚物纳米纤维并实现两种药物的序贯释放，探讨纳米纤维介导的紫杉醇和阿霉素序贯联合治疗SHg-44胶质瘤的效果及机制。 方法:实验分为4组，1640培养液对照组，1%阿霉素组，1%紫杉醇组，5%(阿霉素+紫杉醇)组。采用高效液相色谱法测定紫杉醇和阿霉素的体外释放情况。四甲基偶氮唑盐法检测纳米纤维介导的紫杉醇和阿霉素序贯治疗对SHg-44胶质瘤细胞的增殖抑制率；流式细胞仪检测法检测紫杉醇和阿霉素序贯治疗对SHg-44胶质瘤细胞的凋亡诱导作用。 结果与结论：纳米纤维介导的紫杉醇和阿霉素序贯治疗对SHg-44胶质瘤细胞具有明显的生长抑制及促凋亡作用,且作用效果好于单独药物应用。提示聚乙二醇-聚乳酸纳米纤维作为一种药物载体能提高紫杉醇和阿霉素对SHg-44胶质瘤细胞增殖抑制和诱导凋亡作用。 关键词：胶质瘤；紫杉醇；阿霉素；序贯化疗；细胞凋亡 doi:10.3969/j.issn.1673-8225.2011.12.022     

恶性脑肿瘤的超选择性脑动脉灌注治疗

目的:对恶性脑胶质细胞瘤术后残留的肿瘤组织,用化疗方法将其杀灭和抑制生长,以延长病人的生存期和改善生存质量;并比较嘧啶亚硝脲(ACNU)加氨甲喋呤(MTX)(A组)以及三尖杉酯碱加MTX(B组)的疗效。方法:将ACNU2～3mg/kg,三尖杉酯碱0.1～0.5mg/kg,MTX0.1～0.2mg/kg按A、B两组方案,采用超选择性脑动脉内联合灌注化疗,每例1～5次不等。结果:A组12例中CR1例,PR3例,NC7例,PD1例;B组12例中CR1例,PR2例,NC7例,PD2例。A组和B组对恶性脑胶质瘤的有效率分别为33.33％和25％,化疗后肿瘤体积缩小率分别为48.32％和46.21％,各组治疗前后肿瘤体积变化均有显著性差异,但两组疗效对比无明显差异。结论:恶性脑胶质细胞瘤术后辅以超选择性脑血管内化疗,能抑制肿瘤生长,ACNU加MTX与三尖杉酯碱加MTX的联合化疗方案合理,毒副作用小。     

脑胶质瘤经颈内动脉灌注ACNU的疗效观察

目的比较盐酸尼莫司汀（ACNU）经动脉灌注与经静脉灌注的疗效，并了解不同剂量的疗效。方法培养大鼠C6胶质瘤细胞株．建立大鼠C6胶质瘤模型。分为对照组及动、静脉灌注组，将ACNu按15、30、45mg／kg分别通过颈内动脉和股静脉注入荷瘤大鼠体内。10d后处死大鼠，取脑标本，行苏木精-伊红染色，测量肿瘤体积，比较不同给药方式和剂量对肿瘤生长的影响。结果ACNU治疗大鼠颅内肿瘤体积均小于对照组（P≤0．01）；ACNU颈内动脉灌注组肿瘤体积缩小较静脉灌注组更明显（P≤0．05）。结论单次经颈内动脉灌注ACNU较单次经静脉灌注能更有效地抑制脑胶质瘤的生长。     

Possibility of overcoming of ACNU resistance in an ACNU-resistant subline of C6 rat glioma

Membrane-modifying agents such as reserpine, calcium antagonists (nicardipine, verapamil) and calmodulin inhibitor (trifluoperazine) were found to enhance the cytotoxicity of ACNU in vitro and in vivo in ACNU-resistant C 6 (C 6/ACNU) glioma. In in vitro experiments, uptake and retention studies with [14C] ACNU revealed that intracellular uptake and retention of ACNU in C 6 cells were larger than those in C 6/ACNU cells, and that these membrane-modifying agents increased the cellular uptake and retention of ACNU in C 6, especially in C 6/ACNU cells. The amount of ACNU in C 6/ACNU cells reached the same level as that detected in C 6/ACNU cells. When these drugs were added along with ACNU at the concentration of 10 to 20 microM to the culture in vitro, ACNU resistance was completely overcome. In in vivo experiment, reserpine, nicardipine, verapamil and trifluoperazine in doses 250 to 500 micrograms/kg intrathecally administered with 1 mg/kg ACNU 1 day after the tumor inoculation significantly enhanced the chemotherapeutic effect of ACNU in C 6/ACNU bearing (C 6/ACNU-MG) rats. It might be concluded that the mechanism of enhancement of ACNU cytotoxicity presented in in vitro and in vivo is explained by the enhanced accumulation of ACNU by these membrane-modifying agents in C 6, especially in ACNU-resistant (C 6/ACNU) cells, and, furthermore, that combination chemotherapy with ACNU and such membrane interacting drugs as reserpine, calcium antagonists (nicardipine, verapamil) and calmodulin inhibitor (trifluoperazine) could lead to the capability of overcoming resistance to ACNU in glioma.     

Evaluation of ACNU alone and combined with tegafur as additions to radiotherapy of the treatment of malignant gliomas--a cooperative clinical trial

Controlled, prospective, randomized studies were performed to evaluate the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and ACNU plus tegafur as additions to radiotherapy for the treatment of malignant gliomas. In the first trial, 105 patients with glioblastoma or anaplastic astrocytoma were randomly divided into two groups after surgery and received radiotherapy (RT, 40 to 60 Gy to the whole brain), or radiotherapy plus concomitant chemotherapy with ACNU (100 mg/m2 on day 1 and 42). Effects of the treatment were compared in 82 evaluable patients from results of CT scans taken before and one month after the completion of radiotherapy. The regression rates more than 50% of the tumor size were observed in 15.0% of patients treated with RT alone and in 47.6% of patients treated with RT plus ACNU. The difference was statistically significant (p less than 0.005). In the second trial, 87 patients were randomly divided into two groups and received RT plus ACNU, or RT plus combined chemotherapy with ACNU and tegafur (400 mg/m2, daily for 8 weeks). Sixty-nine patients were within the valid study group. The regression rates more than 50% of the tumor size were observed in 34.2% of patients treated with RT plus ACNU: and in 41.2% treated with RT, ACNU plus tegafur. No statistical difference was noted in the response rate between the groups. These results indicate that ACNU is an effective agent in conjunction with radiotherapy for patients with malignant gliomas, and that tegafur does not enhance the effectiveness of ACNU.     

5-FU多聚缓释体植入技术治疗脑胶质瘤

目的观察5-氟尿嘧啶(5-FU)多聚缓释体植入胶质瘤内化疗的临床效果,探索化疗药物的新剂型和新途径。方法在60例胶质瘤病人在开颅术中或以立体定向方式植入5-FU多聚缓释体,5-FU含量100～150mg。随访5～24周,通过影像学检查,计算肿瘤平均径。比较手术前及各随访时间段肿瘤平均径的变化,并观察瘤周水肿情况。结果38例病人术后病情稳定。无化疗不良反应。肿瘤平均径在术后5、12和24周以上均有显著缩小。其中第12周随访病例肿瘤平均径缩小最显著。肿瘤周边水肿带在开颅手术的病人比较宽,而在立体定向手术病人无明显加重表现。结论低剂量5-FU瘤内缓释体植入术治疗脑胶质瘤安全有效,无明显不良反应。     

In vitro damage of isolated DNA from two brain tumor cell lines induced by a water-soluble antitumor nitrosourea

We report the DNA sites damaged by the antitumor drug, nimustine hydrochloride (ACNU), in highly reiterated DNA sequences of rat glioma cells. A reiterated fragment of 370 base pairs (bp), obtained after Hind III restriction endonuclease digestion of rat glioma C6 or 9L cells DNA, was divided into 167 and 203 bp by subsequent Hae III enzyme reaction. The reaction of end-labelled 167 and 203 bp fragments with ACNU resulted in scission breaks corresponding to the locations of guanine. Moreover, ACNU and subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at the guanine positions, thus forming alkali-labile sites. These results indicate that the preferred site of DNA strand scission induced by ACNU is at guanine positions.     

黑色素瘤抗原-1,-3基因在脑胶质瘤中的表达及意义

目的 探讨肿瘤特异性黑色素瘤抗原（MAGE）-1、-3基因作为胶质瘤的免疫检测和治疗、基因治疗分子标志物的可行性。方法 采用逆转录-聚合酶链反应（RT-PCR）检测52例胶质瘤、6例正常脑组织、5例脑脓肿、10例脑膜瘤组移标本中MAGE-1、MAGE-3mRNA的表达。结果 脑胶质瘤中MAGE-1、MAGE-3mRNA阳性表达率分别为64．5％、55．8％，MAGE-1及MAGE-3mRNA同时表达22例（42.3％）。正常脑组织、脑脓肿和脑膜瘤均不表达MAGE-1和MAGE-3mRNA。在胶质瘤组织中MAGE-1、MAGE-3mRNA的表达均与病理级别和病人生存时间有关（P＜0．05），而与性别、年龄、肿瘤部位及肿瘤直径无关（P＞0．05）MAGE-1的表达与MAGE-3的表达有关（P＜0．05）。结论 基于MAGE-1和MAGE-3在胶质瘤中的高表达率，可利用这两种蛋白作为靶分子进行免疫治疗，同时也可作为一种临床有用的随访指标。     

脑胶质瘤组织培养化疗药物敏感性的研究

目的建立脑胶质瘤的组织培养药敏检测法，用于筛选化疗药物及指导临床个体化化疗。方法应用组织培养药敏检测法对69例人脑胶质瘤标本进行化疗药物敏感性测定，所测药物为脑肿瘤常用化疗药物顺铂（DDP）、长春新碱（VCR）、替尼泊甙（VM26）、尼莫司汀（ACNU）、替莫唑胺（TMZ）及DDP＋VM26组合。比较6组化疗药物体外抗肿瘤作用的差异，并分析药物敏感性与病人临床资料之间的相关性。结果DDP＋VM26组合用药的敏感性与VM26单独用药比较，差异无统计学意义．但明显优于其他4种单药。病人性别、年龄、肿瘤初发或复发均对药物敏感性无显著性影响；除组合用药DDP＋VM26外，其他药物的敏感性与病理分级无显著相关性。结论胶质瘤标本不同个体对同一药物及同一个体对不同药物的敏感性差异很大，脑胶质瘤化疗应优先选择以VM26为主的联合用药。     

脑肿瘤超选择性脑动脉灌注化疗的临床分析

目的:研究超选择性脑动脉插管灌注嘧啶亚硝脲(ACNU)或卡氮芥(BCNU)治疗恶性脑肿瘤的近期疗效及其并发症的防治。方法:对67例经组织学确诊的恶性脑肿瘤采用超选择性脑动脉插管灌注嘧啶亚硝脲或卡氮芥化疗,并对照化疗前后的影像学表现,评价该化疗对恶性脑肿瘤的疗效。结果:本组67例病人治疗后完全缓解10例(14.9％),部分缓解43例(64.2％),稳定11例(16.4％),恶化3例(4.5％)。对部分病例行免疫组化和神经病理研究,证实超选择性脑动脉灌注化疗可诱导肿瘤的凋亡。超选择性脑动脉插管灌注化疗可明显降低常规化疗的并发症和毒性反应,并发症和毒性反应的发生率明显低于文献报道。结论:超选择性脑动脉插管灌注化疗治疗恶性脑肿瘤可明显降低药物毒性,近期疗效良好。     

Quantitative analysis of brain edema in patients with malignant glioma treated with BCNU wafers

BCNU wafers are a form of interstitial chemotherapy that is expected to improve the survival of patients with malignant glioma. However, their adverse events, especially brain edema, sometimes cause significant clinical symptoms. In this study, we performed a volumetric analysis of brain edema after the implantation of BCNU wafers and reported on the clinical course, and exacerbation factors of brain edema. Twelve patients who underwent surgical resection of supratentorial malignant glioma and BCNU wafer implantation, were enrolled. Radiographic quantitative analysis was conducted and compared with a historical control. The volume change in brain edema was divided into three groups and correlation with clinical symptoms was then evaluated. Compared with the control group, the brain edema in the BCNU wafer implantation group was significantly prolonged after surgery. Radiographic volumetric analysis revealed an increase of more than 25% at any time after surgery in four patients (33%) and a reduction of less than 25%, 1 month after surgery in three patients (25%). Grade 3 clinical deterioration related to brain edema occurred in two patients and Grade 2 in one patient. Univariate analysis revealed that the radiographic deterioration of brain edema had no correlation with age, sex, diagnosis, tumor grade, preoperative volume of brain edema and tumor, residual tumor volume, or number of BCNU wafers. Radiographic quantitative analysis of brain edema indicated that BCNU wafer implantation may induce the prolongation and enlargement of brain edema with or without neurological deterioration. Brain edema may be controlled by intensive perioperative treatment with diuretics and corticosteroids.     

Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions

Over the past 25 years, we have treated 17 patients with chiasmo-hypothalamic astrocytomas. Before 1988, the initial treatments consisted of surgery and/or radiotherapy, while since 1989, 4 children (1 male, 3 females, aged 3–8 years) were treated primarily with chemotherapy. None of them was associated with neurofibromatosis. After a biopsy of the tumor, the intraveneous administration of ranimustine (MCNU; 30–86 mg/m²) and/or nimustine (ACNU; 30.3–64.1 mg/m²) was given without radiation therapy. Chemotherapy was usually given as an out-patient, with a total of 5–13 courses. The total doses of MCNU and ACNU administered ranged from 150 to 570 mg and from 64.8 mg to 100 mg, respectively. After chemotherapy 2 patients showed clinical improvement and tumor regression on neuro-imaging, while one patient showed clinical improvement and tumor size stabilization on neuro-imaging. The remaining one child, however, showed a clinical worsening and tumor progression on neuro-imaging studies. He was thus treated with a second chemotherapy regimen with carboplatin and etoposide, which brought about tumor regression. The acute and subacute toxicity of chemotherapy was mild. All patients are now leading almost normal lives with a median of 43 months after diagnosis. Although a longer and more careful clinical observation is required, the quthors conclude that chemotherapy with MCNU and/or ACNU may benefit patients with unresectable pilocytic astrocytoma requiring treatment. The advantages of this therapy include its mild side effects and the lack of any hospitalization in most patients. It may also delay the need for radiation therapy, which can have a deleterious effect on the young developing brain.     

大鼠C6脑胶质瘤模型的病理特征与MRI的观察

目的建立SD大鼠C6胶质瘤模型并对其病理特征及MRI进行观察。方法50只SD大鼠随机分成5组，每组10只，c6胶质瘤细胞悬液立体定向接种于大鼠的右侧尾状核，接种后观察大鼠的生活状态、生存期；分别于接种后不同时段进行MRI观察肿瘤生长特性及肿瘤体积的测量；取不同时段组大鼠脑标本行脑组织HE染色、透射电镜(transmission electron microscope，TEM)、脑组织含水量测量(与10只正常大鼠对照)、胶质纤维酸性蛋白(GFAP)免疫组化检查。结果立体定向颅内接种成功率97．5％，未见远处及颅外转移，肿瘤在一定时期内牛长较快，脑水肿随肿瘤的生长明显加重，生存期观察组中7只荷瘤鼠死亡，3只肿瘤自发部分消退。结论立体定向建立大鼠C6胶质瘤模型成功率高，接种后颅内肿瘤呈浸润性生长，与人脑胶质瘤具有相似性，由于生存期观察组中有部分荷瘤鼠出现肿瘤自发部分消退，故应用该模型评价治疗效果时应慎重；TIWI增强扫描可清晰显示肿瘤影像，且能更早发现肿瘤；MRI联合病理可较好反映肿瘤生长方式及发展过程。     

The 9LLUC/Wistar rat glioma model is not suitable for immunotherapy

The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9LLUC glioma cells syngenic to Fischer 344 (F344) rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9LLUC/F344 rats, and tumor regression was found in some 9LLUC/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9LLUC/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9LLUC/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.     

The anti-tumor effect of ACNU and X-irradiation on mouse glioma (author's transl)

Anti-tumor activities of ACNU and X-irradiation on methylcholanthrene induced glioma in C57BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and X-irradiation in M phase. As to the combined therapy of ACNU and X-irradiation, the anti-tumor effect was most remarkable when the cells were treated by X-irradiation in the G2, M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and X-irradiation on the cells in G1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and X-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local X-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or X-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of X-ray was remarkably effective. Evidence obtained indicates that the combination therapy of ACNU and X-irradiation have synnergistic anti-tumor effect on experimental mouse glioma.     

The changes of cerebral blood flow and metabolism of normal brain tissue after surgery, radiation, and chemotherapy in brain tumor patients: evaluated by position emission tomography

The changes of cerebral blood flow (CBF) and metabolism of normal brain tissue after surgery, radiation, and chemotherapy in brain tumor patients were measured by positron emission tomography (PET). The subjects consisted of 6 men and 3 women, and were from 11 to 62 years old. Those were four patients with glioblastomas, one patient with malignant oligodendroglioma, one patient with astrocytoma grade II, one patient with astrocytoma grade III, one patient with pontine glioma, one patient with pineal germinoma. Seven patients were operated and pathohistologically diagnosed. Two patients with pineal germinoma and pontine glioma were not operated and radiologically diagnosed. Of 7 operated patients, first PET was performed before operation in 3 patients, and from 10 to 16 days after operation in 4 patients. Following first PET, the patients were treated with irradiation (1 case), or with both irradiation and chemotherapy (8 cases). The total radiation dose for tumor was from 59 to 61 Gy distributed in a period of 6-8 weeks. Whole brain irradiation was performed up to 30 or 40 Gy, with a remaining dosimetry (20-30 Gy focused on the tumor field. Chemotherapy consisted of intravenous administration of ACNU and oral administration of FT-207. Second PET was performed 1 month after therapy (9 cases), and third PET was performed from 4 to 24 months after therapy (6 cases). Fourth PET was performed in 2 patients (22 and 35 months after therapy), and fifth PET was performed in one patient (35 months after therapy).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced antitumor effect of combined-modality treatment using convection-enhanced delivery of hydrophilic nitrosourea with irradiation or systemic administration of temozolomide in intracranial brain tumor xenografts

Abstract

Objective: Convection-enhanced delivery (CED) is a local infusion technique that delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood–brain barrier and reducing systemic side effects. We previously reported the safety and efficacy of CED of ACNU (nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride), a hydrophilic nitrosourea, in rat brain tumor models. This study evaluated the efficacy of combined-modality treatments using CED of ACNU with irradiation or systemic administration of temozolomide.

Methods: Antitumor efficacy and toxicity of the treatment were evaluated using rat 9L intracranial brain tumor models.

Results: Combined treatment using CED of ACNU with irradiation produced significantly longer survival time than each treatment alone (versus CED: p<0.001, versus irradiation: p<0.05, log-rank test) or systemic administration of ACNU with irradiation (p<0.001). Long-term survival (120 days) and eradication of tumor occurred only in this combined-treatment group. We also showed that CED of ACNU plus systemic administration of temozolomide significantly enhanced survival rate compared with each treatment alone (versus CED: p<0.001, versus systemic temozolomide: p<0.05).

Discussion: Multimodality treatment using CED of ACNU, radiotherapy and systemic chemotherapy with temozolomide is a promising strategy for treatment of brain tumors.     

原发性人脑胶质瘤的预后影响因素:基于SEER数据库的分析

目的 探讨原发性人脑胶质瘤病人预后影响因素。方法 通过SEER*Stat（8.3.8版本）软件搜集SEER数据库2004~2015年原发性人脑胶质瘤病人的临床资料,采用R（4.0.2版本）软件进行单因素与多因素Cox回归分析,通过Kaplan-Meier生存曲线分析不同治疗方式和婚姻状态与病人预后的关系。结果 共纳入符合标准的原发性人脑胶质瘤18 523例。多因素Cox回归分析结果显示,年龄≥30岁、肿瘤直径≥2 cm、病理级别高、肿瘤位于额叶以外部位、离婚、丧偶为原发性胶质瘤预后不良的独立危险因素（P<0.05）,手术治疗、术后放疗、化疗是原发性胶质瘤预后的独立保护因素（P<0.05）。生存曲线分析结果显示,手术治疗（全切除或部分切除肿瘤）、术后放疗、化疗均明显延长原发性胶质瘤病人的生存期（P<0.05）,婚姻状态为结婚的病人预后明显好于丧偶的病人（P<0.05）。结论 对原发性人脑胶质瘤,尽可能手术全切除肿瘤,同时术后辅助放化疗,能够延长病人的生存时间。同时,临床应加强病人心理干预。