鼻咽癌腮腺淋巴结转移风险分析与放射性脑坏死发生的剂量学研究

发布时间：2018-01-13 11:00

本文关键词：鼻咽癌腮腺淋巴结转移风险分析与放射性脑坏死发生的剂量学研究　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：第一部分、鼻咽癌腮腺区淋巴结转移风险分析研究目的:在鼻咽癌放疗中,IMRT技术虽然降低了腮腺剂量、保护了腮腺功能,但是也会导致腮腺区域失败。对有腮腺淋巴结转移高危因素的患者,应该行腮腺区域预防照射。本研究拟探讨鼻咽癌腮腺淋巴结转移的高危因素。材料与方法:本研究为1:2病例对照研究,入组患者为我院2005年1月至2012年12月收治的鼻咽癌患者。20例患者发现腮腺淋巴结转移,排除1例N1患者。其中3例患者发生双侧腮腺淋巴结转移。研究组为22例含有腮腺淋巴结转移的一侧;从N2-3患者中随机选择44例无腮腺淋巴结转移的鼻咽癌患者,选择肿瘤中心同侧或者颈部淋巴结转移明显的一侧作为对照组。评价不同区域淋巴结转移、长径之和(SLD)、胞膜外侵、坏死的情况。结果:本研究中,初诊鼻咽癌发生腮腺淋巴结转移的概率为1.82%。研究组与对照组相比,Ⅱ区淋巴结长径之和较大(6.0 cm vs.3.6 cm,p = 0.0 03)。研究组中Ⅱ区淋巴结坏死、Va/b区淋巴结受累、少发区淋巴结受累的发生率均较对照组常见(p=0.016,p=0.034,p0.001)。咽后淋巴结、Ⅲ区、Ⅳ区淋巴结转移情况在两组之间的差别无统计学意义。Logistic回归分析提示,Ⅱ区淋巴结SLD≥5.0cm(OR=4.11,p=0.030)和少发淋巴结区受累(OR =3.95,p =0.045)与鼻咽癌腮腺淋巴结转移有关。结论:鼻咽癌发生腮腺淋巴结转移比较少见。Ⅱ区淋巴结长径之和(SLD)≥5.0cm和少发淋巴结区受累可能是腮腺淋巴结转移的高位因素。对存在腮腺淋巴结转移高危的患者,不再推荐应用保护腮腺的放射治疗。第二部分、鼻咽癌IMRT后腮腺淋巴结复发模式及原因分析研究目的:在鼻咽癌的放疗中,保护腮腺的IMRT已经普遍应用,在提高肿瘤剂量的同时尽量保护了腮腺功能,但是,近年来出现了腮腺区淋巴结失败的报道。因此,我们在第一部分的研究基础上,进一步探讨鼻咽癌IMRT后,腮腺区淋巴结复发的原因。材料与方法:回顾我院2005年1月至2012年12月鼻咽癌IMRT患者1096例,腮腺复发13例,可分析的腮腺复发12例。以腮腺复发侧为病例组,以腮腺未复发侧为对照组,进行病例对照研究。分析腮腺区淋巴结失败与肿瘤侵犯范围、IMRT剂量分布、局部复发等因素之间的关系。结果:11/12例患者的原发鼻咽癌为III-IV期;根治性IMRT后,9/12例有局部区域残留。腮腺复发的中位时间是16(8-43)个月。腮腺复发中,8例位于腮腺浅叶、1例位于深叶,另外3例累及腮腺深、浅叶。腮腺复发见于原发肿瘤中心同侧(p0.001)。腮腺复发侧颈部穿刺/手术史较对侧多见(p=0.025)。从腮腺受照情况看,复发侧腮腺的平均V30、V50、V60分别为60.5%、29.8%、17.5%,无复发侧腮腺受照剂量分别为58.4%、28.2%、15.2%。两组腮腺V30平均值均高于50%,而V50、V60平均值均明显低于95%。腮腺复发多合并同侧颈淋巴结复发(66.7%vs.8.3%,p=0.003);并有合并同侧原发灶复发(41.7%vs.8.3%,p=0.059)的趋势。单纯腮腺区淋巴结复发的患者,挽救性治疗效果较好。结论:鼻咽癌IMRT后腮腺复发率很低(1.2%)。腮腺复发可能与鼻咽癌局部晚期、治疗后残留、颈部穿刺/手术史,以及局部区域复发有关。IMRT导致腮腺区放疗低剂量可能是腮腺复发的重要原因。第三部分、鼻咽癌IMRT后放射性脑损伤发生的剂量学分析研究目的:在三维技术放疗中,对脑组织剂量限制的认识仍有很多不足。本研究拟探讨鼻咽癌IMRT治疗引起放射性脑损伤的剂量-体积因素。材料与方法:回顾性分析2006年1月至2013年12月就诊我院的鼻咽癌患者,共计1300例,发现放射性脑损伤患者58例。排除不符合和研究条件的10例患者。9例患者发生了双侧脑组织坏死。将含有坏死灶的一侧脑组织作为研究组,共计57例;将无坏死灶的一侧脑组织作为对照组,共计39例,进行病例对照研究。定义“颞叶”、“部分脑组织(PB)”、“脑损伤区域”三个评价脑组织受照剂量的危及器官(OAR)。收集的剂量参数包括 Dmax,D0.5cc,D1.0cc,D2.0cc,D3.0cc,D5.0cc。结果:鼻咽癌IMRT后发生放射性脑损伤的潜伏期平均为33.7(95%CI,30.0-37.5)个月。发生放射性脑损伤的潜伏期与“部分脑”受照剂量呈负相关。“颞叶”作为OAR不足以覆盖受到照射的脑组织。“部分脑组织”作为OAR,其高剂量区比“脑损伤区域”高0.7-2.5Gy。PB与脑损伤区的高剂量区受照剂量密切相关,相关系数在0.896-0.986之间,p值均小于0.001。以“部分脑组织”作为的OAR,研究组的Dmax、D0.5cc、D1.0cc、D2.0cc、D3.0cc、和 D5.0cc 均明显高于对照组,p值均小于0.001。将“部分脑组织”的剂量学参数进行ROC曲线分析,曲线下面积均大于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分别作为判断发生放射性脑损伤的剂量-体积拐点,敏感性、特异度、阳性预测值、阴性预测值均在80%以上。结论:在三维技术放疗年代,小体积脑组织受到照射时,耐受剂量明显提高。在鼻咽癌的IMRT治疗中,采用“部分脑(PB)”对脑组织剂量覆盖进行评价可能更合理。当受照剂量超过 Dmax75Gy,D0.5cc71Gy,D1.0cc68Gy,D2.0cc65Gy,D3.0cc 63Gy,D5.0cc59Gy时,放射性脑损伤的发生风险明显提高。第四部分、放射性脑损伤的转归及疗效分析研究目的:放射性脑损伤是脑组织受到照射后引起的严重并发症。本研究拟探讨放射性脑损伤的发展过程以及影响疗效的因素。材料与方法:回顾性分析2006年1月至2013年12月就诊我院的1300例鼻咽癌患者,有58例患者治疗后发生放射性脑损伤。排除12例没有影像随访信息的患者,共有46例患者纳入分析。其中,应用神经节苷脂治疗的患者20例,无神经节苷脂治疗的患者26例。收集发生放射性脑损伤以后3-24个月的MRI随访资料,分别记录MR T2WI,T1WI+C的信息。参考RECIST标准对放射性脑损伤的疗效进行评价。将达到完全缓解(CR)和部分缓解(PR)的患者称为有效或缓解的患者。结果:将随访信息分为3-6个月、10-12个月、18-24个月3个阶段进行整理。在3-6个月评价时,以进展和稳定期为主,其中好转的患者21.9%,进展期患者占43.8%;到10-12个月评价时,以好转和稳定的患者占了绝大多数,其中好转的患者占36.1%,进展期患者19.4%;到18-24个月评价时,好转的患者占45.2%,进展期患者占12.9%,进一步减小。将患者分为缓解组(CR+PR)、未达缓解组,分别分析10-12个月、18-24个月时对患者缓解率有影响的因素。性别、年龄、病理分型、吸烟史、T分期、高治疗强度、受照剂量等因素对两个时间段的客观缓解率没有明显影响。但是,应用神经节苷脂治疗的患者,客观缓解率明显增高。10-12个月评价时,缓解率达68.8%(p0.001),18-24个月评价时缓解率达81.8%(p=0.008)。多因素分析显示:以10-12个月、18-24个月两个时间段MRT1WI+C影像作为评价终点,应用神经节苷脂均为放射性脑病缓解的有利因素(p=0.001、p=0.005)。结论:鼻咽癌IMRT引起的脑损伤通常经历活动期和稳定期两个过程,很少出现持续进展的、致死性损伤。早期应用神经节苷脂可能是治疗放射性脑损伤的有效措施。
[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.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R739.63

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