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  本文關(guān)鍵詞：鼻咽癌腮腺淋巴結(jié)轉(zhuǎn)移風(fēng)險(xiǎn)分析與放射性腦壞死發(fā)生的劑量學(xué)研究　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 鼻咽癌 腮腺淋巴結(jié)轉(zhuǎn)移 高危因素 病例對照研究鼻咽癌 IMRT 腮腺失敗 病因分析 病例對照放射性腦損傷 劑量體積效應(yīng) 劑量耐受 鼻咽癌 IMRT放射性腦損傷 療效 神經(jīng)節(jié)苷脂 鼻咽癌 IMRT

【摘要】：第一部分、鼻咽癌腮腺區(qū)淋巴結(jié)轉(zhuǎn)移風(fēng)險(xiǎn)分析研究目的:在鼻咽癌放療中,IMRT技術(shù)雖然降低了腮腺劑量、保護(hù)了腮腺功能,但是也會導(dǎo)致腮腺區(qū)域失敗。對有腮腺淋巴結(jié)轉(zhuǎn)移高危因素的患者,應(yīng)該行腮腺區(qū)域預(yù)防照射。本研究擬探討鼻咽癌腮腺淋巴結(jié)轉(zhuǎn)移的高危因素。材料與方法:本研究為1:2病例對照研究,入組患者為我院2005年1月至2012年12月收治的鼻咽癌患者。20例患者發(fā)現(xiàn)腮腺淋巴結(jié)轉(zhuǎn)移,排除1例N1患者。其中3例患者發(fā)生雙側(cè)腮腺淋巴結(jié)轉(zhuǎn)移。研究組為22例含有腮腺淋巴結(jié)轉(zhuǎn)移的一側(cè);從N2-3患者中隨機(jī)選擇44例無腮腺淋巴結(jié)轉(zhuǎn)移的鼻咽癌患者,選擇腫瘤中心同側(cè)或者頸部淋巴結(jié)轉(zhuǎn)移明顯的一側(cè)作為對照組。評價不同區(qū)域淋巴結(jié)轉(zhuǎn)移、長徑之和(SLD)、胞膜外侵、壞死的情況。結(jié)果:本研究中,初診鼻咽癌發(fā)生腮腺淋巴結(jié)轉(zhuǎn)移的概率為1.82%。研究組與對照組相比,Ⅱ區(qū)淋巴結(jié)長徑之和較大(6.0 cm vs.3.6 cm,p = 0.0 03)。研究組中Ⅱ區(qū)淋巴結(jié)壞死、Va/b區(qū)淋巴結(jié)受累、少發(fā)區(qū)淋巴結(jié)受累的發(fā)生率均較對照組常見(p=0.016,p=0.034,p0.001)。咽后淋巴結(jié)、Ⅲ區(qū)、Ⅳ區(qū)淋巴結(jié)轉(zhuǎn)移情況在兩組之間的差別無統(tǒng)計(jì)學(xué)意義。Logistic回歸分析提示,Ⅱ區(qū)淋巴結(jié)SLD≥5.0cm(OR=4.11,p=0.030)和少發(fā)淋巴結(jié)區(qū)受累(OR =3.95,p =0.045)與鼻咽癌腮腺淋巴結(jié)轉(zhuǎn)移有關(guān)。結(jié)論:鼻咽癌發(fā)生腮腺淋巴結(jié)轉(zhuǎn)移比較少見。Ⅱ區(qū)淋巴結(jié)長徑之和(SLD)≥5.0cm和少發(fā)淋巴結(jié)區(qū)受累可能是腮腺淋巴結(jié)轉(zhuǎn)移的高位因素。對存在腮腺淋巴結(jié)轉(zhuǎn)移高危的患者,不再推薦應(yīng)用保護(hù)腮腺的放射治療。第二部分、鼻咽癌IMRT后腮腺淋巴結(jié)復(fù)發(fā)模式及原因分析研究目的:在鼻咽癌的放療中,保護(hù)腮腺的IMRT已經(jīng)普遍應(yīng)用,在提高腫瘤劑量的同時盡量保護(hù)了腮腺功能,但是,近年來出現(xiàn)了腮腺區(qū)淋巴結(jié)失敗的報(bào)道。因此,我們在第一部分的研究基礎(chǔ)上,進(jìn)一步探討鼻咽癌IMRT后,腮腺區(qū)淋巴結(jié)復(fù)發(fā)的原因。材料與方法:回顧我院2005年1月至2012年12月鼻咽癌IMRT患者1096例,腮腺復(fù)發(fā)13例,可分析的腮腺復(fù)發(fā)12例。以腮腺復(fù)發(fā)側(cè)為病例組,以腮腺未復(fù)發(fā)側(cè)為對照組,進(jìn)行病例對照研究。分析腮腺區(qū)淋巴結(jié)失敗與腫瘤侵犯范圍、IMRT劑量分布、局部復(fù)發(fā)等因素之間的關(guān)系。結(jié)果:11/12例患者的原發(fā)鼻咽癌為III-IV期;根治性IMRT后,9/12例有局部區(qū)域殘留。腮腺復(fù)發(fā)的中位時間是16(8-43)個月。腮腺復(fù)發(fā)中,8例位于腮腺淺葉、1例位于深葉,另外3例累及腮腺深、淺葉。腮腺復(fù)發(fā)見于原發(fā)腫瘤中心同側(cè)(p0.001)。腮腺復(fù)發(fā)側(cè)頸部穿刺/手術(shù)史較對側(cè)多見(p=0.025)。從腮腺受照情況看,復(fù)發(fā)側(cè)腮腺的平均V30、V50、V60分別為60.5%、29.8%、17.5%,無復(fù)發(fā)側(cè)腮腺受照劑量分別為58.4%、28.2%、15.2%。兩組腮腺V30平均值均高于50%,而V50、V60平均值均明顯低于95%。腮腺復(fù)發(fā)多合并同側(cè)頸淋巴結(jié)復(fù)發(fā)(66.7%vs.8.3%,p=0.003);并有合并同側(cè)原發(fā)灶復(fù)發(fā)(41.7%vs.8.3%,p=0.059)的趨勢。單純?nèi)�腺區(qū)淋巴結(jié)復(fù)發(fā)的患者,挽救性治療效果較好。結(jié)論:鼻咽癌IMRT后腮腺復(fù)發(fā)率很低(1.2%)。腮腺復(fù)發(fā)可能與鼻咽癌局部晚期、治療后殘留、頸部穿刺/手術(shù)史,以及局部區(qū)域復(fù)發(fā)有關(guān)。IMRT導(dǎo)致腮腺區(qū)放療低劑量可能是腮腺復(fù)發(fā)的重要原因。第三部分、鼻咽癌IMRT后放射性腦損傷發(fā)生的劑量學(xué)分析研究目的:在三維技術(shù)放療中,對腦組織劑量限制的認(rèn)識仍有很多不足。本研究擬探討鼻咽癌IMRT治療引起放射性腦損傷的劑量-體積因素。材料與方法:回顧性分析2006年1月至2013年12月就診我院的鼻咽癌患者,共計(jì)1300例,發(fā)現(xiàn)放射性腦損傷患者58例。排除不符合和研究條件的10例患者。9例患者發(fā)生了雙側(cè)腦組織壞死。將含有壞死灶的一側(cè)腦組織作為研究組,共計(jì)57例;將無壞死灶的一側(cè)腦組織作為對照組,共計(jì)39例,進(jìn)行病例對照研究。定義“顳葉”、“部分腦組織(PB)”、“腦損傷區(qū)域”三個評價腦組織受照劑量的危及器官(OAR)。收集的劑量參數(shù)包括 Dmax,D0.5cc,D1.0cc,D2.0cc,D3.0cc,D5.0cc。結(jié)果:鼻咽癌IMRT后發(fā)生放射性腦損傷的潛伏期平均為33.7(95%CI,30.0-37.5)個月。發(fā)生放射性腦損傷的潛伏期與“部分腦”受照劑量呈負(fù)相關(guān)。“顳葉”作為OAR不足以覆蓋受到照射的腦組織�！安糠帜X組織”作為OAR,其高劑量區(qū)比“腦損傷區(qū)域”高0.7-2.5Gy。PB與腦損傷區(qū)的高劑量區(qū)受照劑量密切相關(guān),相關(guān)系數(shù)在0.896-0.986之間,p值均小于0.001。以“部分腦組織”作為的OAR,研究組的Dmax、D0.5cc、D1.0cc、D2.0cc、D3.0cc、和 D5.0cc 均明顯高于對照組,p值均小于0.001。將“部分腦組織”的劑量學(xué)參數(shù)進(jìn)行ROC曲線分析,曲線下面積均大于0.85,p值均小于 0.001。其中 Dmax ≥75Gy,D0.5cc ≥71Gy,D1.0cc ≥68Gy,D2.0cc≥65Gy,D3.0cc≥63Gy,D5.0cc≥59Gy分別作為判斷發(fā)生放射性腦損傷的劑量-體積拐點(diǎn),敏感性、特異度、陽性預(yù)測值、陰性預(yù)測值均在80%以上。結(jié)論:在三維技術(shù)放療年代,小體積腦組織受到照射時,耐受劑量明顯提高。在鼻咽癌的IMRT治療中,采用“部分腦(PB)”對腦組織劑量覆蓋進(jìn)行評價可能更合理。當(dāng)受照劑量超過 Dmax75Gy,D0.5cc71Gy,D1.0cc68Gy,D2.0cc65Gy,D3.0cc 63Gy,D5.0cc59Gy時,放射性腦損傷的發(fā)生風(fēng)險(xiǎn)明顯提高。第四部分、放射性腦損傷的轉(zhuǎn)歸及療效分析研究目的:放射性腦損傷是腦組織受到照射后引起的嚴(yán)重并發(fā)癥。本研究擬探討放射性腦損傷的發(fā)展過程以及影響療效的因素。材料與方法:回顧性分析2006年1月至2013年12月就診我院的1300例鼻咽癌患者,有58例患者治療后發(fā)生放射性腦損傷。排除12例沒有影像隨訪信息的患者,共有46例患者納入分析。其中,應(yīng)用神經(jīng)節(jié)苷脂治療的患者20例,無神經(jīng)節(jié)苷脂治療的患者26例。收集發(fā)生放射性腦損傷以后3-24個月的MRI隨訪資料,分別記錄MR T2WI,T1WI+C的信息。參考RECIST標(biāo)準(zhǔn)對放射性腦損傷的療效進(jìn)行評價。將達(dá)到完全緩解(CR)和部分緩解(PR)的患者稱為有效或緩解的患者。結(jié)果:將隨訪信息分為3-6個月、10-12個月、18-24個月3個階段進(jìn)行整理。在3-6個月評價時,以進(jìn)展和穩(wěn)定期為主,其中好轉(zhuǎn)的患者21.9%,進(jìn)展期患者占43.8%;到10-12個月評價時,以好轉(zhuǎn)和穩(wěn)定的患者占了絕大多數(shù),其中好轉(zhuǎn)的患者占36.1%,進(jìn)展期患者19.4%;到18-24個月評價時,好轉(zhuǎn)的患者占45.2%,進(jìn)展期患者占12.9%,進(jìn)一步減小。將患者分為緩解組(CR+PR)、未達(dá)緩解組,分別分析10-12個月、18-24個月時對患者緩解率有影響的因素。性別、年齡、病理分型、吸煙史、T分期、高治療強(qiáng)度、受照劑量等因素對兩個時間段的客觀緩解率沒有明顯影響。但是,應(yīng)用神經(jīng)節(jié)苷脂治療的患者,客觀緩解率明顯增高。10-12個月評價時,緩解率達(dá)68.8%(p0.001),18-24個月評價時緩解率達(dá)81.8%(p=0.008)。多因素分析顯示:以10-12個月、18-24個月兩個時間段MRT1WI+C影像作為評價終點(diǎn),應(yīng)用神經(jīng)節(jié)苷脂均為放射性腦病緩解的有利因素(p=0.001、p=0.005)。結(jié)論:鼻咽癌IMRT引起的腦損傷通常經(jīng)歷活動期和穩(wěn)定期兩個過程,很少出現(xiàn)持續(xù)進(jìn)展的、致死性損傷。早期應(yīng)用神經(jīng)節(jié)苷脂可能是治療放射性腦損傷的有效措施。
[Abstract]:The first part, the transfer of risk analysis to parotid lymph nodes in nasopharyngeal carcinoma: in the radiotherapy of nasopharyngeal carcinoma, although the IMRT technology reduces the parotid gland dose, protect parotid function, but also can lead to failure. The parotid gland region of parotid lymph node metastasis in the patients with high risk factors should be the prevention of parotid gland region. This study intends to explore the high risk exposure the factors of parotid lymph node metastasis in nasopharyngeal carcinoma. Materials and methods: This was a 1:2 case-control study, who enrolled in our hospital from January 2005 to December 2012 were found in patients with nasopharyngeal carcinoma.20 patients with parotid lymph node metastasis, 1 cases of N1 patients were excluded. 3 patients had bilateral parotid lymph node metastasis. The study group is 22 with parotid lymph node metastasis; randomly selected from N2-3 patients in 44 cases of parotid lymph node metastasis in patients with nasopharyngeal carcinoma, tumor center or ipsilateral cervical lymph node metastasis The obvious side as control group. The evaluation of different regional lymph node metastasis, and the long diameter (SLD), cell membrane invasion, necrosis. Results: in this study, the probability of occurrence of nasopharyngeal carcinoma of parotid lymph node metastasis compared to 1.82%. study group and control group II lymph node diameter and larger (6 cm vs.3.6 cm, P = 0.003). The study area in group II lymph node necrosis, Va/b lymph node involvement, the incidence of lymph node involvement less than that of the control group (p=0.016, p=0.034, common p0.001). Retropharyngeal lymph node, area III, IV region of lymph node metastasis in different conditions between the two groups was not statistically significant.Logistic regression analysis showed that SLD II lymph nodes than 5.0cm (OR=4.11, p=0.030) and less lymph nodes involvement (OR =3.95, P =0.045) and nasopharyngeal carcinoma of parotid lymph node metastasis of nasopharyngeal carcinoma. Conclusion: parotid lymph node metastasis is rare. 2 lymph node size And (SLD) more than 5.0cm and less lymph nodes involvement may be high risk factors of parotid lymph node metastasis. The existence of parotid lymph node metastasis patients at high risk, is no longer recommended application of protection of parotid gland radiotherapy. In the second part, after parotid lymph node recurrence of nasopharyngeal carcinoma IMRT mode and cause analysis objective: in nasopharyngeal carcinoma radiotherapy, protection of parotid IMRT has been widely applied in improving the tumor dose at the same time, try to protect the parotid gland function, but in recent years there have been reports of parotid lymph node failure. Therefore, we in the first part of the basic research, to further explore the cause of nasopharyngeal carcinoma IMRT after parotid lymph node recurrence. Methods: review of 1096 cases of nasopharyngeal carcinoma patients with IMRT in our hospital from January 2005 to December 2012, 13 cases of recurrence in parotid gland, 12 cases of parotid gland recurrence analysis in the parotid gland. The recurrence side as the case group, the side of parotid gland without recurrence According to the group, a case-control study was performed. Analysis of parotid lymph node failure and tumor invasion, IMRT dose distribution, the relationship between the factors of local recurrence. Results: 11/12 patients with primary nasopharyngeal carcinoma stage III-IV; radical IMRT, 9/12 cases with local regional residue. The median time to relapse of 16 parotid gland (8-43) months. Recurrence in 8 cases of parotid gland, located in the superficial lobe of parotid gland, 1 cases were located in the deep lobe, the other 3 cases involving the deep parotid superficial lobe of parotid gland, recurrent patients. Primary ipsilateral tumor center (p0.001). The recurrence of lateral cervical puncture / parotid surgery compared to contralateral (see p= 0.025). According to the situation from the parotid gland, average V30, recurrent side of parotid gland V50, V60 were 60.5%, 29.8%, 17.5%, no recurrence of parotid gland dose were 58.4%, 28.2%, two 15.2%. group of parotid V30 average value was higher than 50%, and V50, the average value of V60 was significantly lower than that of 95%. with recurrent parotid gland lateral cervical lymph node recurrence (6 6.7%vs.8.3%, p=0.003); and the same side with local recurrence (41.7%vs.8.3%, p=0.059). The trend of pure parotid lymph node recurrence patients, salvage therapy has a good effect. Conclusion: IMRT of nasopharyngeal carcinoma after parotid gland, the recurrence rate is very low (1.2%). With locally advanced nasopharyngeal carcinoma of parotid gland may recur after treatment, residual neck. Puncture / surgery, and local recurrence of.IMRT resulted in low dose of parotid gland radiotherapy may be an important cause of recurrence of parotid gland. In the third part, radiation brain injury of nasopharyngeal carcinoma after IMRT dosimetric analysis objective: in three dimensional radiotherapy technology, there are still a lot of insufficient knowledge on brain tissue dose limitation. This paper intends to discuss the nasopharyngeal carcinoma induced by IMRT treatment of radiation brain injury dose volume factors. Materials and methods: nasopharyngeal carcinoma were retrospectively analyzed from January 2006 to December 2013, a total of 1300 cases, found that radiation Brain injury in 58 cases. Exclude nonconformance bilateral brain tissue necrosis and the conditions on the 10 cases of.9 patients with focal necrosis. One side of the brain as the study group, a total of 57 cases of brain tissue; one side without necrosis as the control group, a total of 39 cases, a case-control study was conducted. The definition of "temporal", "parts of the brain (PB)", "brain injury area" three evaluation of brain tissue dose of the organs at risk (OAR). The dose parameters collected include Dmax, D0.5cc, D1.0cc, D2.0cc, D3.0cc, D5.0cc. results: the occurrence of radiation-induced brain injury of nasopharyngeal carcinoma after IMRT average latency 33.7 (95%CI, 30.0-37.5) months. Incidence of radiation-induced brain injury and latency "part of the brain" dose was negatively correlated. "Temporal lobe" as OAR not enough to cover the exposure of the brain. "The parts of the brain" as OAR, the high dose area than the "brain damage zone The high dose region of high 0.7-2.5Gy.PB and brain injury area dose is closely related to the correlation coefficient between 0.896-0.986, P values were less than 0.001. in the parts of the brain "as the study group OAR, Dmax, D0.5cc, D1.0cc, D2.0cc, D3.0cc, and D5.0cc were significantly higher than those in control group, ROC curve analysis of dosimetric parameters of P values were less than 0.001. will be" parts of the brain ", the area under the curve were greater than 0.85, P values were less than 0.001. where Dmax = 75Gy, D0.5cc = 71Gy, D1.0cc = 68Gy, D2.0cc = 65Gy, D3.0cc = 63Gy, D5.0cc = 59Gy respectively as to determine the occurrence of radiation-induced brain injury dose volume inflection point the sensitivity, specificity, positive predictive value, negative predictive value was above 80%. Conclusion: in 3D radiotherapy technology in small volume of brain tissue irradiated, tolerated dose increased. IMRT in the treatment of nasopharyngeal carcinoma, the part of the brain (PB)" Cover on the brain tissue dose evaluation may be more reasonable. When the dose of more than Dmax75Gy, D0.5cc71Gy, D1.0cc68Gy, D2.0cc65Gy, D3.0cc, 63Gy, D5.0cc59Gy, radioactive brain injury risk increased significantly. In the fourth part, the prognosis of radiation-induced brain injury research objective: radiation brain injury is a serious complication caused by brain tissue after irradiation. This paper intends to discuss the development process of radiation brain injury and the factors affecting the efficacy. Materials and methods: 1300 cases of nasopharyngeal carcinoma were analyzed retrospectively from January 2006 to December 2013 in our hospital, radioactive brain injury in 58 patients after the treatment. 12 patients with no radiographic follow-up information were excluded, into the analysis of 46 cases of patients. Among them, 20 patients treated with ganglioside treatment, 26 patients without ganglioside treatment. Collected radioactive brain injury after 3- MRI 24 months follow up, record MR T2WI, T1WI+C information were evaluated according to the criteria of RECIST on radiation-induced brain injury. The complete remission (CR) and partial remission (PR) patients referred to as effective or remission patients. Results: the follow-up information is divided into 3-6 months, 10-12 month, 18-24 months in 3 stages, finishing. In 3-6 months of evaluation, to progress and stable, the patients improved 21.9%, advanced patients accounted for 43.8%; 10-12 months of evaluation, to better and stable patients in the majority, which improved patients accounted for 36.1%, progress 19.4% patients; to 18-24 months of evaluation, improvement in 45.2% of the patients, advanced stage patients accounted for 12.9%, further reduced. The patients were divided into remission group (CR+PR), non remission group, were analyzed for 10-12 months, 18-24 months for patients with the remission rate of influential factors. Gender, age pathological. Type, smoking history, T staging, treatment of high intensity, dose and other factors on the two time the objective remission rate had no obvious effect. However, the application of ganglioside in the treatment of patients, the objective response rate was significantly higher in.10-12 months, the response rate was 68.8% (p0.001), 18-24 months of evaluation the remission rate was 81.8% (p=0.008). Multivariate analysis showed that in 10-12 months, 18-24 months the two time MRT1WI+C image as the end point of evaluation, application of ganglioside are favorable factors for the mitigation of radiation encephalopathy (p=0.001, p=0.005). Conclusion: IMRT induced brain injury of nasopharyngeal carcinoma is usually experienced active and stable two, rarely appear progressive, fatal injury. Early application of gangliosides may be the effective measures of treatment of radiation-induced brain injury.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R739.63

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