本文選題：磁共振成像 + 放射性腦病　； 參考：《浙江大學(xué)》2015年博士論文

【摘要】：放射性腦病(radiation encephalopathy,REP)是頭頸部惡性腫瘤及腦腫瘤放射治療常見的并發(fā)癥之一。目前,晚期放射性腦病被普遍認(rèn)為是漸進(jìn)性、不可逆性的病理過程,臨床治療效果差,常導(dǎo)致患者神經(jīng)功能受損,影響患者的生活質(zhì)量,甚至致殘、致死。已有多項(xiàng)研究顯示,貝伐珠單抗治療放射性腦病(尤其是早期階段)療效較好,所以早期發(fā)現(xiàn)放射性腦病顯得尤為重要。目前,診斷放射性腦病金標(biāo)準(zhǔn)是病理診斷,但創(chuàng)傷較大,應(yīng)用較局限。臨床上主要通過磁共振成像(Magnetic Resonance Imaging,MRI)診斷放射性腦病,并有多項(xiàng)研究證實(shí)有效可靠。然而我們對(duì)放射性腦病的自然病程了解較少,我們需要掌握放射性腦病MRI特征及進(jìn)展規(guī)律,為放射性腦病的早期診斷及治療提供臨床參考價(jià)值,具有重要臨床意義。高級(jí)別膠質(zhì)瘤(High-grade glioma,HGG,WHO Ⅲ或Ⅳ級(jí))是成人腦腫瘤中最常見的惡性腫瘤。目前研究顯示,雖然高級(jí)別膠質(zhì)瘤經(jīng)歷手術(shù)、放療及化療的積極治療,但是預(yù)后較差,例如膠質(zhì)母細(xì)胞瘤(glioblastoma,GBM)的中位生存時(shí)間為14.6月,不可避免的會(huì)出現(xiàn)復(fù)發(fā)。然而,了解高級(jí)別膠質(zhì)瘤復(fù)發(fā)模式對(duì)我們制定放化療方案,尤其是確定放射治療靶區(qū)很有參考意義,尤其是在中國(guó)人群,對(duì)這一問題的探討較少。本研究通過MRI動(dòng)態(tài)隨訪評(píng)價(jià)分析鼻咽癌患者放療后放射性腦病的MRI特征及進(jìn)展規(guī)律,得出了一些具有臨床意義的結(jié)論。通過觀察貝伐珠單抗治療放射性腦病的臨床療效和MRI特征,分析貝伐珠單抗治療放射性腦病的療效。通過評(píng)價(jià)高級(jí)別膠質(zhì)瘤復(fù)發(fā)模式,為制定放化療方案,尤其是確定放射治療靶區(qū)提供一定的依據(jù)。具體如下:第一部分:68例鼻咽癌放療后患者在診斷為顳葉放射性腦病后,共行162次MRI隨訪檢查,回顧性分析這162次MRI隨訪檢查圖像及報(bào)告,通過MRI評(píng)價(jià)鼻咽癌放療后顳葉放射性腦病的自然進(jìn)展規(guī)律。研究結(jié)果:68例患者中初診時(shí)共發(fā)現(xiàn)105個(gè)病變顳葉:出現(xiàn)強(qiáng)化灶105個(gè)(100%)顳葉,出現(xiàn)白質(zhì)病灶98個(gè)(93.3%)顳葉,出現(xiàn)囊腫2個(gè)(1.7%)顳葉,出現(xiàn)含鐵血黃素沉積2個(gè)(1.7%)顳葉。在隨訪過程中出現(xiàn)12顳葉發(fā)生放射性腦病,其中4個(gè)顳葉發(fā)生放射性腦病時(shí)僅有實(shí)性結(jié)節(jié)狀強(qiáng)化病灶。值得關(guān)注的是,總共117個(gè)病變顳葉中,有11個(gè)(9.4%)顳葉發(fā)生放射性腦病時(shí)僅有實(shí)性結(jié)節(jié)狀強(qiáng)化病灶。所有大于2cm的結(jié)節(jié)狀強(qiáng)化灶均出現(xiàn)壞死。在隨訪結(jié)束時(shí),117個(gè)病變顳葉中均出現(xiàn)強(qiáng)化病灶和白質(zhì)病灶�；屹|(zhì)病灶、顳葉萎縮、囊腫及含鐵血黃素沉積發(fā)生的比例分別為 98.3%(115/117)、20.5%(24/117)、5.1%(6/117)和 5.1%(6/117)。研究結(jié)論:MRI隨訪能很好的了解鼻咽癌放療后放射性腦病的自然病程:本研究首次發(fā)現(xiàn)鼻咽癌放療后MRI隨訪首次出現(xiàn)的病灶是實(shí)性結(jié)節(jié)狀強(qiáng)化病灶。強(qiáng)化病灶是鼻咽癌放療后放射性腦病最常見的病灶,其次依次是白質(zhì)病灶、灰質(zhì)病灶、顳葉萎縮、囊腫及含鐵血黃素沉積。強(qiáng)化病灶大于8mm開始出現(xiàn)中央壞死,所有大于2cm的強(qiáng)化灶均發(fā)生壞死。第二部分:對(duì)8例接受貝伐珠單抗治療的放射性腦病患者進(jìn)行動(dòng)態(tài)MRI評(píng)價(jià),研究治療前治療過程中及治療后的臨床及MRI特征變化。分別測(cè)量治療前后增強(qiáng)T1WI強(qiáng)化灶和T2WI/FLAIR高信號(hào)病灶最大垂直徑乘積的變化。研究結(jié)果:貝伐珠單抗治療后增強(qiáng)T1WI強(qiáng)化灶兩個(gè)最大垂直徑的乘積比治療前降低的平均百分比為54%,治療后T2WI/FLAIR高信號(hào)病灶兩個(gè)最大垂直徑的乘積比治療前降低的平均百分比為40%。所有患者均有較明顯的臨床癥狀好轉(zhuǎn)。5例患者KPS評(píng)分均有不同程度上升,分別為:40分,40分,10分,10分,40分;另外3例患者治療前后KPS評(píng)分無(wú)明顯提高:2例患者治療前后均為90分,1例患者治療前后均為80分。有4例患者在貝伐珠單抗治療前及四次治療后均接受了簡(jiǎn)易精神狀態(tài)評(píng)分(mini-mental status examination,MMSE,滿分30分)測(cè)試,評(píng)分依次提高了 5分、7分、0分、8分。研究結(jié)論:放射性腦病接受貝伐珠單抗治療后臨床癥狀及神經(jīng)功能評(píng)分有明顯改善;MRI能反映出放射性腦病接受貝伐珠單抗治療后的反應(yīng),并能提供量化指標(biāo);貝伐珠單抗治療放射性腦病時(shí),增強(qiáng)T1WI強(qiáng)化灶的緩解快于T2WI/FLAIR高信號(hào)病灶。MRI影像改變與患者臨床癥狀改善具有良好的一致性。第三部分:通過MRI對(duì)54例高級(jí)別腦膠質(zhì)瘤術(shù)后接受過放療聯(lián)合替莫唑胺化療的患者復(fù)發(fā)模式進(jìn)行評(píng)價(jià)。提示腫瘤復(fù)發(fā)的MRI增強(qiáng)T1WI與放療定位CT融合,勾畫出復(fù)發(fā)腫瘤體積Vrecur,再通過評(píng)價(jià)V recur與60Gy等劑量曲線的關(guān)系來(lái)判斷復(fù)發(fā)模式。研究結(jié)果:54例腫瘤復(fù)發(fā)患者的中位生存時(shí)間為14個(gè)月,中位無(wú)進(jìn)展生存時(shí)間為10.5個(gè)月。34例患者發(fā)生中央型復(fù)發(fā);8例患者發(fā)生野內(nèi)復(fù)發(fā);2例患者發(fā)生邊緣型復(fù)發(fā);2例患者發(fā)生遠(yuǎn)處復(fù)發(fā);11例患者發(fā)生腦脊液播散,其中2例患者同時(shí)發(fā)生中央型復(fù)發(fā),1例患者同時(shí)發(fā)生邊緣型復(fù)發(fā)。在本研究的54例患者中,有20例患者在術(shù)前或放療前增強(qiáng)T1WI顯示腦室壁下區(qū)域(subventricular zone,SVZ)受累及,其中有9例發(fā)生腦脊液播散。研究結(jié)論:高級(jí)別膠質(zhì)瘤放化療后以局部復(fù)發(fā)為主(中央型復(fù)發(fā)與野內(nèi)復(fù)發(fā));說(shuō)明我們目前采用的較小的靶區(qū):不包全水腫區(qū),以MRIT1增強(qiáng)圖像顯示的術(shù)后殘留腫瘤和(或)術(shù)腔為GTV,GTV外擴(kuò)2 cm/1 cm為CTV1/CTV2的靶區(qū)勾畫標(biāo)準(zhǔn)是合適的。腦脊液播散是一種較為獨(dú)特的復(fù)發(fā)模式,需要特別關(guān)注。HGG術(shù)前和放療前MRI評(píng)價(jià)能在一定程度上預(yù)測(cè)腦脊液播散的發(fā)生:術(shù)前和放療前SVZ累及可能是發(fā)生腦脊液播散的一個(gè)影像學(xué)高危因素。SVZ受累及的HGG患者發(fā)生在側(cè)腦室(尤其是同側(cè)側(cè)腦室)腦脊液播散比例較高,SVZ受累及的HGG患者是否需要接受同側(cè)側(cè)腦室甚至是幕上腦室系統(tǒng)一定劑量預(yù)防照射或者鞘內(nèi)化療,需要進(jìn)一步的臨床觀察。
[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.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R739.41;R445.2

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