磁共振成像评价放射性脑病及高级别胶质瘤复发模式

发布时间：2018-05-13 08:33

本文选题：磁共振成像 + 放射性脑病　；参考：《浙江大学》2015年博士论文

【摘要】：放射性脑病(radiation encephalopathy,REP)是头颈部恶性肿瘤及脑肿瘤放射治疗常见的并发症之一。目前,晚期放射性脑病被普遍认为是渐进性、不可逆性的病理过程,临床治疗效果差,常导致患者神经功能受损,影响患者的生活质量,甚至致残、致死。已有多项研究显示,贝伐珠单抗治疗放射性脑病(尤其是早期阶段)疗效较好,所以早期发现放射性脑病显得尤为重要。目前,诊断放射性脑病金标准是病理诊断,但创伤较大,应用较局限。临床上主要通过磁共振成像(Magnetic Resonance Imaging,MRI)诊断放射性脑病,并有多项研究证实有效可靠。然而我们对放射性脑病的自然病程了解较少,我们需要掌握放射性脑病MRI特征及进展规律,为放射性脑病的早期诊断及治疗提供临床参考价值,具有重要临床意义。高级别胶质瘤(High-grade glioma,HGG,WHO Ⅲ或Ⅳ级)是成人脑肿瘤中最常见的恶性肿瘤。目前研究显示,虽然高级别胶质瘤经历手术、放疗及化疗的积极治疗,但是预后较差,例如胶质母细胞瘤(glioblastoma,GBM)的中位生存时间为14.6月,不可避免的会出现复发。然而,了解高级别胶质瘤复发模式对我们制定放化疗方案,尤其是确定放射治疗靶区很有参考意义,尤其是在中国人群,对这一问题的探讨较少。本研究通过MRI动态随访评价分析鼻咽癌患者放疗后放射性脑病的MRI特征及进展规律,得出了一些具有临床意义的结论。通过观察贝伐珠单抗治疗放射性脑病的临床疗效和MRI特征,分析贝伐珠单抗治疗放射性脑病的疗效。通过评价高级别胶质瘤复发模式,为制定放化疗方案,尤其是确定放射治疗靶区提供一定的依据。具体如下:第一部分:68例鼻咽癌放疗后患者在诊断为颞叶放射性脑病后,共行162次MRI随访检查,回顾性分析这162次MRI随访检查图像及报告,通过MRI评价鼻咽癌放疗后颞叶放射性脑病的自然进展规律。研究结果:68例患者中初诊时共发现105个病变颞叶:出现强化灶105个(100%)颞叶,出现白质病灶98个(93.3%)颞叶,出现囊肿2个(1.7%)颞叶,出现含铁血黄素沉积2个(1.7%)颞叶。在随访过程中出现12颞叶发生放射性脑病,其中4个颞叶发生放射性脑病时仅有实性结节状强化病灶。值得关注的是,总共117个病变颞叶中,有11个(9.4%)颞叶发生放射性脑病时仅有实性结节状强化病灶。所有大于2cm的结节状强化灶均出现坏死。在随访结束时,117个病变颞叶中均出现强化病灶和白质病灶。灰质病灶、颞叶萎缩、囊肿及含铁血黄素沉积发生的比例分别为 98.3%(115/117)、20.5%(24/117)、5.1%(6/117)和 5.1%(6/117)。研究结论:MRI随访能很好的了解鼻咽癌放疗后放射性脑病的自然病程:本研究首次发现鼻咽癌放疗后MRI随访首次出现的病灶是实性结节状强化病灶。强化病灶是鼻咽癌放疗后放射性脑病最常见的病灶,其次依次是白质病灶、灰质病灶、颞叶萎缩、囊肿及含铁血黄素沉积。强化病灶大于8mm开始出现中央坏死,所有大于2cm的强化灶均发生坏死。第二部分:对8例接受贝伐珠单抗治疗的放射性脑病患者进行动态MRI评价,研究治疗前治疗过程中及治疗后的临床及MRI特征变化。分别测量治疗前后增强T1WI强化灶和T2WI/FLAIR高信号病灶最大垂直径乘积的变化。研究结果:贝伐珠单抗治疗后增强T1WI强化灶两个最大垂直径的乘积比治疗前降低的平均百分比为54%,治疗后T2WI/FLAIR高信号病灶两个最大垂直径的乘积比治疗前降低的平均百分比为40%。所有患者均有较明显的临床症状好转。5例患者KPS评分均有不同程度上升,分别为:40分,40分,10分,10分,40分;另外3例患者治疗前后KPS评分无明显提高:2例患者治疗前后均为90分,1例患者治疗前后均为80分。有4例患者在贝伐珠单抗治疗前及四次治疗后均接受了简易精神状态评分(mini-mental status examination,MMSE,满分30分)测试,评分依次提高了 5分、7分、0分、8分。研究结论:放射性脑病接受贝伐珠单抗治疗后临床症状及神经功能评分有明显改善;MRI能反映出放射性脑病接受贝伐珠单抗治疗后的反应,并能提供量化指标;贝伐珠单抗治疗放射性脑病时,增强T1WI强化灶的缓解快于T2WI/FLAIR高信号病灶。MRI影像改变与患者临床症状改善具有良好的一致性。第三部分:通过MRI对54例高级别脑胶质瘤术后接受过放疗联合替莫唑胺化疗的患者复发模式进行评价。提示肿瘤复发的MRI增强T1WI与放疗定位CT融合,勾画出复发肿瘤体积Vrecur,再通过评价V recur与60Gy等剂量曲线的关系来判断复发模式。研究结果:54例肿瘤复发患者的中位生存时间为14个月,中位无进展生存时间为10.5个月。34例患者发生中央型复发;8例患者发生野内复发;2例患者发生边缘型复发;2例患者发生远处复发;11例患者发生脑脊液播散,其中2例患者同时发生中央型复发,1例患者同时发生边缘型复发。在本研究的54例患者中,有20例患者在术前或放疗前增强T1WI显示脑室壁下区域(subventricular zone,SVZ)受累及,其中有9例发生脑脊液播散。研究结论:高级别胶质瘤放化疗后以局部复发为主(中央型复发与野内复发);说明我们目前采用的较小的靶区:不包全水肿区,以MRIT1增强图像显示的术后残留肿瘤和(或)术腔为GTV,GTV外扩2 cm/1 cm为CTV1/CTV2的靶区勾画标准是合适的。脑脊液播散是一种较为独特的复发模式,需要特别关注。HGG术前和放疗前MRI评价能在一定程度上预测脑脊液播散的发生:术前和放疗前SVZ累及可能是发生脑脊液播散的一个影像学高危因素。SVZ受累及的HGG患者发生在侧脑室(尤其是同侧侧脑室)脑脊液播散比例较高,SVZ受累及的HGG患者是否需要接受同侧侧脑室甚至是幕上脑室系统一定剂量预防照射或者鞘内化疗,需要进一步的临床观察。
[Abstract]:Radiation encephalopathy (REP) is one of the common complications of radiotherapy for head and neck malignant tumor and brain tumor. At present, advanced radiation-encephalopathy is generally considered to be progressive, irreversible pathological process and poor clinical treatment, which often leads to impaired neurologic function, and affects the quality of life and even disability of the patients. Many studies have shown that bevacizumab has a good effect in the treatment of radioactive encephalopathy (especially early stage), so it is very important to find radioactive encephalopathy early. At present, the diagnosis of gold encephalopathy is a pathological diagnosis, but the trauma is larger and the application is limited. Magnetic Resonance Im is mainly through magnetic resonance imaging (MRI). Aging, MRI) diagnosis of radionuclide encephalopathy, and many studies have proved effective and reliable. However, we know less about the natural course of radiation-encephalopathy. We need to master the MRI characteristics and progress of radiation-encephalopathy and provide clinical reference for the early diagnosis and treatment of radiation-encephalopathy. It is of important clinical significance. High grade glioma (Hig H-grade glioma, HGG, WHO III, and IV) are the most common malignant tumors in adult brain tumors. The present study shows that although high grade gliomas undergo surgery, radiotherapy and chemotherapy, the prognosis is poor, such as the median survival time of the glioblastoma (glioblastoma, GBM) for 14.6 months, but the recurrence is inevitable. In order to understand the recurrence pattern of high grade glioma, it is very useful for us to formulate the chemotherapy regimen, especially to determine the target area of radiation therapy, especially in Chinese people. The study of this problem is less. This study analyzed the MRI characteristics and progress of radiation encephalopathy after radiotherapy in patients with nasopharyngeal carcinoma by MRI dynamic follow-up. By observing the clinical efficacy and MRI characteristics of bevac monoclonal antibody in the treatment of radioactive encephalopathy, the efficacy of bevacizumab in the treatment of radionuclide encephalopathy was analyzed. By evaluating the recurrence pattern of high grade glioma, a certain basis for the formulation and chemotherapy, especially for the target area of radiation therapy, was provided. One part: 68 cases of nasopharyngeal carcinoma after radiotherapy were diagnosed as temporal lobe radioactive encephalopathy, 162 MRI follow-up examinations were performed. The 162 MRI follow-up examination images and reports were reviewed, and the natural progression of temporal lobe radionuclide encephalopathy after radiotherapy of nasopharyngeal carcinoma was evaluated by MRI. Results: 105 lesions of temporal lobe were found in 68 patients at first diagnosis. There were 105 (100%) temporal lobes, 98 (93.3%) temporal lobes of white matter, 2 (1.7%) temporal lobes, 2 (1.7%) temporal lobes with iron hemoflavin, 12 temporal lobe occurred in the follow-up process, and 4 temporal lobe occurred only solid nodular enhanced lesions in 4 temporal lobes. It is worth paying attention to 11 in total. In the 7 temporal lobes, 11 (9.4%) temporal lobe occurred radiation-encephalopathy only with solid nodular enhancement. All of the nodular fortified foci greater than 2cm were necrotic. At the end of the follow-up, the lesions and white matter focus in the temporal lobes of 117 lesions, gray matter, temporal lobe atrophy, cysts, and the proportion of hemoflavin deposition 98.3% (115/117), 20.5% (24/117), 5.1% (6/117) and 5.1% (6/117). Conclusions: MRI follow-up can well understand the natural course of radionuclide encephalopathy after radiotherapy of nasopharyngeal carcinoma: This study first found that the first occurrence of nasopharyngeal carcinoma after radiotherapy in MRI follow-up is the solid nodular enhancement focus. The enhanced focus is the radioradioactivity after radiotherapy for nasopharyngeal carcinoma. The most common focus of encephalopathy, followed by white matter focus, gray matter, temporal lobe atrophy, cysts and hemoflavin deposition. Intensification focus more than 8mm began to appear central necrosis, all of the intensification foci greater than 2cm were necrotic. Second part: the dynamic MRI evaluation of 8 cases of radiation-encephalopathy treated by bevacizumab treatment Changes in the clinical and MRI characteristics of pre treatment and after treatment. The changes in the maximum vertical diameter product of the enhanced T1WI focus and the T2WI/FLAIR high signal focus before and after treatment were measured. Results: the average percentage of the two maximum vertical diameters of enhanced T1WI foci after bevac monoclonal antibody treatment was 54%. The average percentage of the two maximum vertical diameters of the T2WI/FLAIR high signal lesion after treatment was higher than that before the treatment. All the patients had obvious clinical symptoms in 40%.. The KPS scores of.5 patients increased in different degrees, respectively: 40 points, 40 points, 10 points, 10 points, and 40 points; the other 3 patients had no significant improvement in the KPS score before and after treatment: 2 patients. All were 90 points before and after treatment, and all 1 patients were 80 points before and after treatment. 4 patients received a simple mental state score (mini-mental status examination, MMSE, full score 30) before and after bevacizumab treatment. The score increased by 5, 7, 0 and 8. Research conclusions: radiation-encephalopathy received bevaco. The clinical symptoms and neurological function scores were obviously improved after anti treatment; MRI could reflect the reaction of radiation encephalopathy after bevacizumab treatment and provide quantitative indicators. When bevacizumab was used to treat radioactive encephalopathy, the enhancement of T1WI enhancement was faster than the.MRI image change of the T2WI/FLAIR high trust lesion and the improvement of the patient's clinical symptoms. Good consistency. Third: the third part: To evaluate the recurrence pattern of 54 patients with high grade glioma after radiotherapy combined with temozolomide chemotherapy. It suggests that the MRI enhanced T1WI of the tumor recurrence and the radiotherapy of CT fusion, draw the Vrecur of the recurrent tumor volume, and then evaluate the relationship between the dose of V recur and 60Gy. The median survival time of 54 patients with tumor recurrence was 14 months, and the median survival time of 54 patients with tumor recurrence was 14 months. The median progression free survival time was 10.5 months in the central recurrence; 8 patients had a wild recurrence; 2 patients had marginal recurrence; 2 cases had a distant recurrence; 11 patients had cerebrospinal fluid dissemination, 2 of which had cerebrospinal fluid dissemination. A central recurrence occurred at the same time, and 1 patients had marginal recurrence at the same time. Of the 54 patients in this study, 20 patients were enhanced by T1WI before or before radiotherapy (subventricular zone, SVZ), including 9 cases of cerebrospinal fluid dissemination. Conclusions: high grade glioma after radiotherapy and chemotherapy was localized. Hair mainly (central recurrences and intracerebral recurrences); the smaller target areas we currently use: no oedema area, MRIT1 enhanced images of postoperative residual tumors and (or) cavity as GTV, GTV external expansion of 2 cm/1 cm for CTV1/CTV2 target delineation standard is appropriate. Cerebrospinal fluid dissemination is a more unique recurrence mode, need special. Do not pay attention to the occurrence of cerebrospinal fluid dissemination to a certain extent before and before.HGG MRI evaluation: preoperative and preoperative SVZ involvement may be an imaging high risk factor for cerebrospinal fluid dissemination..SVZ affected HGG patients in the lateral ventricle (especially the ipsilateral ventricle) have a higher proportion of cerebrospinal fluid dissemination and SVZ affected HGG patients. Whether a person needs to receive a dose of radiation or intrathecal chemotherapy in the ipsilateral ventricle or even supratentorial ventricular system needs further clinical observation.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R739.41;R445.2

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